Twenty-Second Meeting of the European Neurological Society 9–12 June, 2012 Prague, Czech Republic

J Neurol (2012) 259 (Suppl 1):S1–S236 DOI 10.1007/s00415-012-6524-4 ABSTRACTS

Twenty-second Meeting of the European Neurological Society 9–12 June, 2012 Prague, Czech Republic

Symposia and Free Communications

The abstracts have been reviewed by: O. Abramsky, C. Angelini, P. Annunziata, F. Antonaci, Z. Argov, A. Arzimanoglou, T. Back, O. Bajenaru, E. Bartels, J. Bednarˇik, P.D. Berlit, K. Bhatia, P. Boon, T. Brandt, B. Brochet, M.J. Brodie, C. Caltagirone, P. Canhaõ, H. Cock, C. Colosimo, G. Comi, L. Cunha, M. de Carvalho, J. de Keyser, J.L. De Reuck, M. de Visser, L. Deecke, R. Dengler, S. Di Donato, M. Dieterich, V. Dietz, C. Elger, M. Eraksoy, F. Fazekas, J. Ferro, M. Filippi, D. Galimberti, T. Gasser, A. Grau, W. Grisold, U. Gschwandtner, O. Hardiman, H.P. Hartung, W. Heide, C. Helmchen, G. Ickenstein, R. Jech, P. Kanˇovsky´, P. Kalvach, L. Kappos, A. Keyser, B. Kieseier, T. Klopstock, C. Krarup, G. Lammers, S. Laureys, G. Mayer, S.I. Mellgren, G. Meola, R. Milo, I. Milonas, X. Montalban, O. Nascimento, E. Nobile-Orazio, L. Nobili, W.H. Oertel, M. Onofrj, A. Palla, S.G. Papageorgiou, D. Pareyson, Y. Parman, M. Partinen, H.W. Pfister, W. Poewe, D. Pohl, P. Portegies, H. Reichmann, P.F. Reyes, M.A. Rocca, A. Rossetti, P.M. Rossini, J. Roth, E. Ru˚zˇicˇka, G. Said, M. Sandberg-Wollheim, J. Santamaria, E. Scarpini, N. Schaeren-Wiemers, B. Schalke, P. Schestatsky, E. Schmutzhard, J. Schoenen, A. Sena, V. Silani, A. Siva, P. Soelberg-Sørensen, R. Soffietti, C. Sommer, K. Sˇonka, A. Steck, G. Stoll, A. Sumner, E. Tolosa, A. Toscano, K.V. Toyka, H. Tumani, J. Valls-Sole´, M. Veloso, A. Vendelho, P. Vermersch, M.J. Viana Baptista, R.D. Voltz, J. Vymazal, M. Weller We would like to thank the reviewers for their precious help and assistance.

123 S2 J Neurol (2012) 259 (Suppl 1):S1–S236

Presidential Symposium POSTER SESSIONS

Parkinson Syndrome: an everlasting challenge 45–47 Poster session 1 Symposia Multiple sclerosis: disease modifying treatment I P336–P360 Joint ENS-CNS Symposium—Audio & video media in evaluation of Cerebrovascular disorders I P361–P380 movement disorders 100–104 Neuro-imaging P381–P406 Symposium—Stem cells ready for clinical practice 106–109 Movement disorders P407–P424 Symposium—Neuro-imaging and early diagnosis of General neurology P425–P451 neurological diseases 110–113 Preclinical biology P452–P456 Symposium—MS and acquired demyelinating disorders 143–146 Symposium—Neurology and sleep-wake disorders 147–150 Poster session 2 Symposium—Knowledge exchange programme in neurology between European and Indian Clinicians 158–161 Multiple sclerosis: disease modifying treatment II P457–P482 Cerebrovascular disorders II P483–P498 Peripheral neuropathy P499–P524 FREE COMMUNICATIONS Dementia I P525–P541 Motor neuron disease P542–P555 General neurology II P556–P570 Oral sessions Child neurology P571–P578

Session 1: Multiple sclerosis: Poster session 3 Imaging/neurophysiology O192–O197 Session 2: Epilepsy I O198–O203 Multiple sclerosis: variants and symptomatic treatment P579–P602 Session 3: Movement disorders I O204–O209 Cerebrovascular disorders III P603–P619 Session 4: Neuro-ophthalmology O210–O215 Pain and headache P620–P644 Session 5: Multiple sclerosis II O216–O221 Dementia II P645–P661 Session 6: Epilepsy II O222–O227 Epilepsy P662–P677 Session 7: Movement disorders II O228–O233 Neurogenetics P678–P692 Session 8: Imaging O234–O239 Clinical neurophysiology P693–P700 Session 9: Movement disorders III O240–O245 Session 10: Sleep disorders O246–O251 Poster session 4 Session 11: General neurology O252–O256 Session 12: Multiple sclerosis III O258–O263 Multiple sclerosis: miscellaneous P701–P729 Session 13: Cerebrovascular disorders I O264–O269 Cerebrovascular disorders IV P730–P752 Session 14: Neuromuscular disorders O270–O275 Muscle disorders P753–P768 Session 15: Child neurology O276–O281 Neurorehabilitation P769–P780 Session 16: Neuro-oncology O282–O287 Neuro-oncology P781–P790 Session 17: Multiple sclerosis IV O288–O293 Infection P791–P799 Session 18: Cerebrovascular disorders II O294–O299 Neuro-ophthalmology P800–P805 Session 19: Motor neuron disease O300–O305 Session 20: Infection O306–O311 Session 21: Neurorehabilitation O312–O317 Session 22: Clinical neurophysiology O318–O323 Session 23: Dementia O324–O329 Session 24: Pain and headache O330–O335

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S3

Presidential Symposium short half-life drug L-Dopa is now seen as the main factor for the development of motor response oscillations and drug-induced dyskinesias associated with this type of treatment. Improving the Parkinson Syndrome: an everlasting challenge pharmacokinetics and mode of delivery of dopaminergic agents is therefore a key element of managing motor response oscillations. Standard approaches include adjunct COMT-inhibition and/or MAO- 45 B-inhibition with L-Dopa as well as the use of longer half-life non- Does early diagnosis lead to early treatment ergolinic dopamine agonists and their extended release formulations. of Parkinson’s disease? Continuous drug delivery using subcutaneous apomorphine infusions H. Reichmann or intrajejunal infusions of duodopa not only smooth out motor University of Dresden (Dresden, DE) fluctuations but also lead to reductions in pre-existing dyskinesias. Future developments of novel dopaminergic approaches to PD ther- We don’t know how long it takes from the onset of first clinical apy may also include intrapulmonary delivery with inhaler systems as symptoms of Parkinson’s disease (PD) to medical diagnosis. Until well as gene-therapeutic enhancement of local DA-production in the recently, no major interest has focused in these early stages, because it striatum. Currently amantadine is the only drug with proven efficacy is classically recommended to wait for prescribing treatments until to reduce levodopa dyskinesias, but several non-dopaminergic drugs disability occurs. Such views are changing, with novel concepts in the targeting glutamatergic receptors are being developed to broaden the natural history of early PD and new attempts to diagnose and treat the spectrum of antidyskinetic agents of PD. In addition, drugs targeting patients earlier than previously. glutamatergic, serotonergic, alphaadrenergic as well as adenosine- We know for many years that PD begins years before patients and A2a receptors are being developed and may be a promising approach doctors notice the first motor signs. There is increasing evidence that a to control levodopa-induced dyskinesias or motor fluctuations. variety of non-motor symptoms are common in PD patients before the Deep brain stimulation (DBS) targeting the STN or GPi are an onset of any motor sign. Such non-motor symptoms include hyposmia, established modality for the management of motor complications in REM sleep behaviour disorder, constipation, depression, problems in drug refractory patients. colour discrimination and sensory signs. It is now proposed that these Recent randomized trials have shown similar effects of STN and symptoms may characterize a ‘‘pre-motor’’ phase of PD. GPi stimulation and also that DBS improves quality-of-life of patients There is a growing debate to decide whether we should continue or with advanced PD. not to wait for ‘‘sufficient’’ disability before treating patients. The UK PD-LIFE study showed that immediate anti-Parkinsonian treatment maintained quality of life scores (PDQ-39) stable in early PD patients over 18 months, while scores deteriorated in those remaining 47 untreated. Moreover, the recent ADAGIO placebo-controlled study, Treatment of non-motor symptoms using the delayed-start design, showed that patients with early PD (5 months from diagnosis) randomized to receive rasagiline (1mg/day) P. Barone immediately (early-start group) had less worsening in UPDRS scores University of Salerno (Salerno, IT) after 18 months of follow-up than those receiving the same treatment Non-motor symptoms (NMSs) are common in Parkinson’s disease 9 months later (delayed-start group). Unfortunately, the PROUD (PD) and have recently gained relevance for their impact on prospective placebo-controlled delayed-start study with the dopamine patients’ quality of life (QoL) and their contribution to institution- agonist pramipexole did fail and showed no superiority for patients alization. Despite their impact, NMSs in PD are under-recognized in who were treated immediately after diagnosis. clinical practice and, consequently, undertreated. NMSs can present To avoid dyskinesia it is common practice to start with a dopamine at any stage of disease, including early and pre-motor phase of PD. agonist and due to the results of ADAGIO and previously TEMPO it The pathophysiology of NMSs is still poorly understood, and a may be well taken to add a MAO-B-inhibitor. dysfunction of both dopaminergic and non-dopaminergic systems A practical way would therefore be to start mildly impaired de contributes to their development. Recently the PRIAMO study novo patients with a MAO-B-inhibitor and those who are more described the prevalence of NMSs, their relevance for cognitive impaired with a dopamine agonist to add the other substance later. impairment and their overall impact on QoL in a large cohort of During the course of the disease levo-Dopa will be needed which Italian patients with PD. Most frequently reported NMSs were should be initiated in biologically old patients at the beginning of psychiatric, sleep, gastrointestinal, pain, fatigue and urinary. More- their PD disease. over patients who reported apathy, attention/memory deficit and Professor Reichmann was acting on Advisory Boards and gave psychiatric symptoms had lower scores on cognitive scales and lectures and received research grants from Abbott, Bayer Health Care, lower QoL. The non-motor symptom complex of PD includes Boehringer/Ingelheim, Cephalon, Desitin, GSK, Merck-Serono, neuropsychiatric symptoms, sleep disorders, autonomic symptoms, Novartis, Orion, Pfizer, TEVA/Lundbeck, UCB Pharma, and Valeant. gastrointestinal symptoms and other symptoms as fatigue and olfactory loss. Recently, the Movement Disorder Society (MDS) Task Force on 46 Evidence-Based Medicine (EBM) Review of Treatments for Parkin- Treatment of motor complications son’s Disease (PD) has reviewed the treatments that are efficacious W. Poewe for the management of the different non-motor symptoms. The results indicate as useful the following drugs: pramipexole for the treatment Medical University of Innsbruck (Innsbruck, AT) of depressive symptoms, clozapine for the treatment of psychosis, After more than 40 years after its first introduction oral levodopa rivastigmine for the treatment of dementia, and botulinum toxin A substitution has remained the gold standard of symptomatic drug (BTX-A) and BTX-B for the treatment of sialorrhea. Possibly useful therapy for the motor symptoms of Parkinson’s disease. The superior treatments include: the tricyclic antidepressants for the treatment of efficacy of levodopa, however, is to some extent offset by the depression and macrogol for the treatment of constipation. Many development of motor complications. Discontinuous and pulsatile reports and open studies suggest possible efficacy of a variety of dopamine receptor stimulation through intermittent oral dosing of the treatments on different non-motor symptoms. 123 S4 J Neurol (2012) 259 (Suppl 1):S1–S236

Symposia Introduction: Hypokinetic dysarthria (HD) in Parkinson’s disease (PD) is characterized by monotony of pitch and loudness, reduced stress, variable rate, imprecise consonants, and a breathy and harsh Joint ENS-CNS Symposium—Audio & video voice. Pharmacotherapy and surgery have only partial effects on HD. media in evaluation of movement disorders rTMS is a non-invasive tool used to modulate cortical plasticity and function of various cortical regions and circuitries. Objective: Based on results of fMRI studies, we explored 100 effects of high-frequency repetitive transcranial magnetic stimula- Acoustic analysis of speech progression in Parkinson’s tion (rTMS) of the primary orofacial sensorimotor area (SM1) and disease dorsolateral prefrontal cortex (DLPFC) on paraclinical aspects of voiced speech in PD using voice signal analysis. Effects of J. Rusz, R. Cmejla, H. Ruzickova, J. Klempir, V. Majerova, dopaminergic treatment on HD have also been assessed using the J. Picmausova, J. Roth, E. Ruzicka same voice analysis and fMRI. Czech Technical University in Prague (Prague, CZ); Charles Methods: Non-depressed and non-demented subjects with PD (mean University in Prague (Prague, CZ) age 65.7 ± 7.45 SD, mean PD duration 8.6 ± 3.41 SD) have participated in this ongoing study. Participants underwent 3 sessions of 10 Hz rTMS Background: Hypokinetic dysarthria in Parkinson’s disease (PD) is a over the dominant hemisphere with 2250 stimuli/day applied in a ran- multidimensional impairment of phonation, respiration, articulation, dom order over the: SM1 (an active stimulation site, 90 % of the motor and prosody. While the beneficial effect of dopaminergic therapy on threshold [MT] intensity), DLPFC (an active stimulation site, 110 % of the principal motor symptoms in PD has been well-documented over MT), and occipital cortex (a control stimulation site, 90 % of MT). decades, its effect on speech remains unclear. The aim of this study Detailed speech evaluation and audio-recordings were performed prior was to investigate the feasibility of acoustic measures in analyzing the to and after each rTMS session. Voice intensity, clarity, prosody, effect of treatment initiation on the progression of speech impairment articulation and intelligibility of speech was assessed using physical in PD. parameters, such as mean fundamental frequency and its variability, Methods: 19 de novo patients with PD were tested and re-tested jitter, short-time energy of the signal, shimmer, speech rate, VOT after 13-24 months after the introduction of antiparkinsonian ther- (Voice Onset Time), and Vowel Articulation Index. Wilcoxon matched- apy. As a control group, 19 age-matched healthy persons were pairs test and ANOVA were performed for data analyses. Effects of a recorded. Speech data included sustained phonation, fast syllable single levodopa dose on HD have also been evaluated using the same repetition, reading text, and monologue. Unified PD Rating Scale speech analysis and fMRI data analysis. motor subscore (UPDRS III) was rated in both evaluations. Voice Results: rTMS of the left SM1 was associated with significant parameters were obtained using quantitative acoustic analyses of the enhancement of the tongue movements velocity and changes of key aspects of speech. Subsequently, the evaluation criteria based fundamental voice frequency. This is an interim analysis and the upon Gaussian kernel distributions, statistical decision-making the- studies are ongoing. ory, and minimal detectable change of healthy speech was designed Conclusions: Results of fMRI studies will be discussed with to assess individual changes of parkinsonian speech in the course of respect to pathophysiological mechanisms of HD and effects of treatment. dopaminergic therapy. An interim analysis of our data revealed an Results: A trend for speech performances to improve was dem- improvement of some articulatory and voice parameters of speech onstrated after treatment mainly in quality of voice, loudness and induced by rTMS applied over the SM1 of the dominant hemisphere. pitch variability, and articulation. The treatment-related changes The abstract has received an institutional support from the Central differed individually across various aspects of speech. Improvements European Institute of Technology, Masaryk University, Brno, Czech in vowel articulation correlated with treatment-related changes in Republic. bradykinesia (r = 0.45, p \ 0.05) and rigidity (r = 0.52, p \ 0.05). In addition, there was a significant correlation between changes in rigidity and pitch variability (r = 0.45, p \ 0.05). Voice quality and loudness variability were improved with dopaminergic medication 102 independently of changes in motor performances. Conclusions: Acoustic analysis and advanced statistics revealed Video-oculography in the Movement Disorders Clinic improvements in speech parameters after the introduction of anti- C. Bonnet parkinsonian therapy in PD patients. Moreover, changes in vowel Charles University in Prague, 1st Faculty of Medicine and General articulation and pitch variability appear to be related with dopami- University Hospital (Prague, CZ) nergic responsiveness of bradykinesia and rigidity. Therefore, speech Eye movements can be measured with extreme precision, are usually can be considered as a marker of disease progression. Acoustic rich in terms of derivable parameters, have been well documented in analysis appears as a helpful tool for monitoring the severity of healthy adults and in patients with brain lesions. Video-based infrared speech impairment and the effects of therapy in PD. oculography (VOG), or infrared eye tracking, is the most frequently used method to record eye movements in clinical practice. A light source is reflected on the surface of the eye to track horizontal and 101 vertical eye movements. In clinical practice, VOG provides insights into patients with movement disorders due to underlying genetic, Evaluation of hypokinetic dysarthria in Parkinson’s degenerative or metabolic disorders. Eye movements are often dis- disease and effects of repetitive transcranial magnetic turbed early in the course of Progressive Supranuclear Palsy (PSP) stimulation and dopaminergic treatment by means and VOG may be helpful in distinguishing it from Parkinson disease. of voice signal analysis and fMRI PSP patients show slow vertical saccades, especially downward, with preserved range of movement, slow and hypometric horizontal sac- I. Rektorova, I. Eliasova, M. Mrackova, M. Kostalova, cades, disruption of steady gaze, impaired smooth pursuit, loss of J. Mekyska, Z. Smekal convergence and preservation of the vestibulo-ocular reflex. How- Masaryk University (Brno, CZ) ever, patients with Parkinson disease show hypometric horizontal and 123 J Neurol (2012) 259 (Suppl 1):S1–S236 S5 vertical self-paced saccades, normal saccadic velocity, impaired domain, which may be helpful in the differential diagnosis of parkin- convergence, impaired smooth pursuit, and normal vestibular eye sonism and in the study of bradykinesia mechanisms. movements. VOG may also be of use in the clinical evaluation of Supported by the Czech Ministry of Education, MSM0021620849. other diseases, such as Whipple disease of the central nervous system where involvement of the rostral mesencephalon results in abnormal vertical gaze, as well as in Huntington disease as oculomotor impairment is one of the first manifestations of disease and correlates 104 with advancing motor signs and disease severity. Furthermore, VOG Beware of YouTube: movement disorders on internet can be used as a model to test the functional integrity of different K. Bhatia neuronal circuits involved in the pathogenesis of movement disorders, FRCP, Institute of Neurology (London, UK) serving as an interesting, accessible and low cost tool for clinical research. This lecture provides a detailed description of the VOG Background: Patient-to-patient exchange of medical information on technique and an update on the clinical and scientific application of the internet is popular, and YouTube has provided an accessible and this technique in the movement disorders clinic. convenient vehicle for patient interaction. We observed that people in Cecilia Bonnet is supported by the Czech Ministry of Education, YouTube videos indicating that they suffered from a neurological research project MSM0021620849, Grantove agentury UK 441611 movement disorder often appeared to have features more typical of Charles University in Prague and IGA MZCR NT/12288-5/2011. conversion disorder (‘‘psychogenic movement disorders’’). Methods: We asked 7 neurologists specialized in movement disorders to evaluate 30 of the most popular patient-uploaded movement disorders videos on YouTube. The interrater agreement was determined with the 103 interrater reliability coefficient using the intraclass correlation coefficient. Results: In the majority of the videos (66 %) the movement dis- Video as a tool for quantitative analysis of tremor order was assessed as psychogenic with an excellent interrater and bradykinesia agreement and high certainty. Videos judged to be psychogenic E. Ruzicka, Z. Sturcova, R. Krupicka, M. Hoskovcova, movement disorders more often suggested treatment than those O. Ulmanova, Z. Szabo, V. Hlavac judged to be organic movement disorders. Conclusion: A large proportion of the most widely viewed Charles University (Prague, CZ); Czech Technical University movement disorder videos on YouTube are psychogenic in nature. (Prague, CZ) This is not only misleading for the general public and patients but also Video recordings have become part of routine procedures in move- risks causing harm to patients with psychogenic and ‘‘organic’’ ment disorders practice, allowing to register abnormal movement movement disorders alike. patterns for diagnostic and educational purposes, as well as to monitor the progression in time. By simple observation of a patient, experienced clinicians are able to precisely classify hypokinetic and hyperkinetic movement disorders. However, the severity of symptoms Symposium—Stem cells ready for clinical is usually estimated only using ordinal rating scales that have a practice number of limitations including inter and intra-individual variability of the ratings. We thus aimed to employ advanced methods of video 106 analysis to more accurately quantify the parameters of abnormal movements in time and space. Somatic cell reprogramming into dopaminergic We have recently developed TremAn - a tool for automatic neurons for Parkinson’s disease therapy detection of tremor and measurement of its frequency from conven- V. Broccoli, M. Caiazzo, M.T. Dell’ Anno, D. Leo, tional videos. TremAn validity was assessed in a study combining R. Gainetdinov, G. Pezzoli, A. Dityatev tremor assessment from video with accelerometry and Fahn–Tolosa– San Raffaele Scientific Institute (Milan, IT); Italian Institute Marin tremor scale in 26 patients with essential tremor and 5 healthy of Technology (Genoa, IT); Parkinson Institute (Milan, IT) volunteers. Results showed that the frequencies of tremor measured by TremAn and by accelerometry are closely related, attaining Having access to human neurons for regenerative therapies and agreement with less than 0.5 Hz in 94 % of measured samples. The understanding diseases has been prohibited for long time. However, reproducibility of frequency measurements was comparable, with the genetic technologies of cell reprogramming have widen this possi- mean TremAn/accelerometry ratio of measurement error standard bility by in vitro differentiation of fibroblast-derived iPS cells. deviations equal to 0.99. However, a new method of cell reprogramming has become available The ease of TremAn use allowing to analyze any archived video which convert fibroblasts directly into functional neurons without sequence compensates for the fact that it cannot measure the ampli- passing through a pluripotent stem cell stage (iPSCS). This technol- tudes. To overcome this weak point, we have designed BradykAn, a ogy has some relevant advantages since it is very fast and efficient three-dimensional motion capture system with two static cameras for and can be employed with human adult fibroblasts. Recently, we rhythmic repetitive fingers movement analysis in real time. Pilot found a minimal set of three transcription factors (Mash1, Nurr1 and results show that BradykAn allows to precisely measure the finger Lmx1a) able to efficiently convert mouse and human fibroblasts into distance (amplitude) and tapping frequency. The validation study will functional dopaminergic neuronal (iDAN) cells. Molecular and tran- follow to confirm the ability of BradykAn to quantify bradykinesia. scriptome studies showed iDAN cells to recapitulate gene expression In summary, the video based technique for tremor frequency mea- of their brain homolog neurons to large extent while lacking surement proved a good reproducibility and a high concordance with expression of other monoaminergic neuronal subtypes markers. accelerometry. TremAn thus appears suitable for routine clinical use by Transgene expression is necessary for at least 6 days to achieve a virtue of its ease of application, adequate frequency range and sensi- stable cell conversion sustained by activation of the endogenous tivity of tremor detection. The new BradykAn system automatically genes of the three reprogramming factors. Strikingly, iDAN cells processes three-dimensional movement data and computes amplitude, showed spontaneous electrical activity organized in regular spikes speed and other parameters of finger movements in the space and time consistent with the pacemaker activity featured by brain DA neurons.

123 S6 J Neurol (2012) 259 (Suppl 1):S1–S236

Furthermore, iDAN cells express D2 autoreceptors and their activity 108 is regulated by the D2/3R agonist quinperole. The three factors were Stem cell gene therapy in adrenoleukodystrophy able to elicit DA neuronal conversion in prenatal or adult fibroblasts from healthy donors and Parkinson’s disease patients. Mouse iDAN P. Aubourg cells integrated in orthotopic brain side after transplantation in the Inserm UMR745, University Paris Descartes (Paris, FR) forebrain structures and matured into functional neurons. Importantly, X-linked adrenoleukodystrophy (ALD), the most common inherited when transplanted in rats unilaterally lesioned with 6-OHDA, iDAN peroxisomal disorder, is caused by mutations in the ABCD1 gene that cells were able to rescue drug-induced locomotor impairment over encodes a transmembrane transporter (ALDP) that imports very-long- long time. In order to strength and expand iDAN cell therapeutic chain fatty acids (VLCFA; [ C22) in peroxisomes where those fatty potential, we devised a remote control system to modulate activity of acids are degraded. A defect in ALDP results in elevated levels of the transplanted IDAN cells. This method relays on a ligand mole- VLCFA in plasma and tissues. The most severe form of ALD is cule, which crosses efficiently the blood-brain barrier and is safe and characterized by rapidly progressive and lethal cerebral demyelina- inert for the entire living organism. With this system, we foresee to tion in childhood (3–12 years). The progression of cerebral modulate iDAN cell activity in vivo to regulate their therapeutic demyelination of ALD can be arrested by allogeneic hematopoietic effects depending by the patient’s needs. stem cell (HSC) transplantation (HCT), provided the procedure is iDAN cell technology and its future developments might have performed at an early stage of the disease. The long term beneficial significant implications in studies of neural development, disease in effects of HCT in ALD are likely due to the progressive turn-over of vitro modeling and cell replacement therapies. brain microglia that are derived from myeloid progenitors in the bone- marrow. Despite the increased availability of cord blood, not all boys with cerebral ALD who are candidate for HCT have a suitable HLA- 107 matched donor. In addition, allogeneic HCT remains associated with significant mortality risk. Targeting the ALD gene into HSCs of ALD Stem cells in multiple sclerosis: where we are patients followed by reinfusion of modified cells would circumvent and where we go most of the problems associated allogeneic HCT. The source of HSC G. Martino would be the CD34-positive fraction purified from bone marrow or San Raffaele Scientific Institute (Milan, IT) from cytokine-mobilized peripheral blood cells. Normal cells have no selective advantage over ALD cells and transduction of HSC with Although the central nervous system (CNS) has been considered for murine retrovirus vectors would result in the loss of ABCD1 gene years as a ‘perennial’ tissue, it is now becoming clear that reparative expression in long term because murine retrovirus vectors transduce regeneration occurs in inflammatory and degenerative disorders of the poorly non-dividing such as HSCs. In contrast, human immunodefi- CNS, including multiple sclerosis (MS). However, this process is not ciency virus (HIV)-based lentiviral vectors are able to transduce robust enough to promote a functional and stable recovery of the CNS nondividing cells. In late 2009, we reported that HSC gene therapy architecture. To overcome this regenerative impotence, since early with lentiviral vector was able to arrest the progression of cerebral seventies, cell-based transplantation therapies have been envisaged as ALD in two boys who have no HLA-matched donor to perform HCT. a promising tool for restoring the structure of the myelin sheath within Long-term (5 years) follow-up of these two first treated patients has CNS demyelinated areas. Initially, different types of myelin-forming confirmed the definitive stabilization of their cerebral demyelinating cells have been transplanted into rodents affected by genetic, chem- disease. Data will be presented on two other patients treated more ical or autoimmune experimental CNS demyelination. However, these recently. In the four patients, ALD protein expression in myeloid and approaches have shown serious limitations. In particular, lineage- lymphoid lineages as well as the identification of identical lentiviral restricted myelinogenic cells show limited growth and expansion insertion sites in myeloid and lymphoid lineages strongly suggested characteristics in vitro and, once transplanted (in vivo), induce re- that HSCs were transduced. HIV1-based lentiviral vectors are inte- myelination, only within restricted CNS areas close to the grative vectors that potentially could result in the integration of transplantation site. More recently, stem and progenitor cells of neural transgene in or close to oncogenes, with the risk of leukemia, as it and mesenchymal origin have been considered as a cell-based ther- happened in several patients with inherited immunodeficiency disor- apeutic tool owing to their intrinsic unlimited self-renewal and ders treated with HSC gene therapy using murine retrovirus vectors. migratory capacities as well as their ability to differentiate into dif- In the four treated ALD patients, hematopoiesis has remained poly- ferent cell lineages. The results, mainly obtained in experimental clonal up to now. If those promising results are extended to a larger autoimmune model of MS, consistently challenge the sole and limited number of patients with cerebral ALD, autologous HSC gene therapy view that such cells may therapeutically work exclusively throughout may replace in a near future allogeneic HCT. These data also high- cell replacement. As a matter of fact, undifferentiated stem cells can light that the recruitment of lentivirally modified bone marrow– also promote CNS repair via the release—at the site of tissue damage derived cells to the CNS macrophages/microglia may provide a cell- but also in immune-relevant bodily organs (e.g. lymph nodes)—of a based gene therapy to treat other CNS diseases. milieu of neuroprotective molecules (e.g. immunomodulatory sub- stances, neurotrophic growth factors, stem cell regulators) whose release is temporally and spatially orchestrated by environmental needs. Thus, the concept of stem cell therapeutic plasticity is now 109 emerging and refers to the capacity of somatic stem cells to adapt Neural stem cells in ischaemic stroke: their fate and function(s) to specific environmental needs, including from bench-to-bedside those occurring in the CNS as a result of different pathological K.W. Muir conditions. The exact knowledge and the potential impact of non- University of Glasgow (Glasgow, UK) conventional stem cell-mediated therapeutic mechanisms might result, in certain circumstances, in more efficacious curative alterna- Human neural stem cells show evidence of improved behavioural tives. However, we need to confront with still unsolved and function in animal models of stroke. The CTX0E03 human neural challenging questions regarding the best way to tightly control and stem cell line is a genetically modified, conditionally immortalised, regulate in vivo the different/articulated, but also potentially diver- human foetal cell line currently undergoing phase I clinical evaluation gent, therapeutic stem cell-mediated functions. for safety in chronic stroke patients on the basis of evidence of

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S7 recovery of sensorimotor function in rodent focal ischaemia models. detected in all the main clinical phenotypes of the disease, including The cell line was clonally derived from expansion of foetal cortical patients at presentation with CIS. A model for DIS which includes the neural stem cells after insertion of a c-mycERTAM fusion gene that presence of at least one intracortical lesion, in addition to the presence permits controlled expansion in the presence of growth factors and of at least one infratentorial and one spinal cord or gadolinium- 4-hydroxytamoxifen. Preclinical studies have used CTX cells manu- enhancing lesion, showed to have a higher specificity and accuracy factured to Good Manufacturing Practice (GMP) standards, identical than the available sets of criteria while maintaining a relatively high to the product used in clinical trials. Several weeks after middle sensitivity. Another key requirement in the diagnostic work-up of cerebral artery occlusion stroke in rats, cell implantation in the stri- patients suspected of having MS is the exclusion of alternative neu- atum was associated with dose-related behavioral recovery in rological conditions that can mimic MS. A series of MRI ‘‘red flags’’, sensorimotor function. There is evidence of cell survival, limited derived from evidence-based findings and educated guesses, have migration, angiogenesis and enhanced endogenous neurogenesis. It is been identified in the setting of clinically suspected MS, which should a general observation in preclinical studies of stem cells that func- alert the clinicians to prompt the performance of ‘‘non-routine’’ tests tional recovery does not depend solely on the survival and integration and to reconsider differential diagnosis more extensively. Finally, of exogenous cells, and it is assumed that trophic effects of cell high-field and ultra-high field MRI scanners are becoming progres- implantation on endogenous recovery processes may underlie the sively available and they are contributing to detect a greater number recovery process. and a higher volume of T2 and enhancing brain lesions. This new The Pilot Investigation of Stem Cells in Stroke (PISCES) trial generation of scanners is also likely to provide a better definition of is an ongoing phase I open label, ascending dose study whose lesion location in the brain WM and GM, their morphology and their primary endpoint is safety, with exploratory secondary efficacy association with vasculature at a resolution which resembles that of endpoints. The PISCES trial is being undertaken in men over 60 pathological assessment. years of age with ischaemic stroke involving the basal ganglia or subcortical white matter that occurred between 6 months and 5 years earlier. Cells are implanted by stereotaxic neurosurgery in the putamen near the site of infarction. Four groups of 3 subjects will receive 2, 5, 10 and 2 million cells. Follow-up will be for 10 years, 111 with clinical and imaging assessments. Up to March 2012, five Alzheimer’s disease and associated conditions subjects had undergone implantation as planned, with no adverse effects attributable to cells. Secondary end-points exploring neu- O. Colliot rological function, activities of daily living, disability, and brain CNRS, ICM (Brain and Spine Institute), Pitie´-Salpeˆtrie`re Hospital imaging indices (structural and functional MRI) are collected pre- (Paris, FR) and post-implantation. Early and accurate diagnosis of Alzheimer’s disease (AD) is partic- After completion of the phase I PISCES trial, design of explor- ularly important in the perspective of possible future disease- atory efficacy trials will require to consider optimal patient selection, modifying treatments. Recently, new criteria for the early diagnosis of including anatomical location of stroke, interval since stroke onset, AD were proposed by Dubois et al. These criteria include a core and age range, appropriate clinical end-points, and the potential role feature of episodic memory impairment and additional biomarkers for biomarkers of activity such as brain imaging. Further trials will derived from magnetic resonance imaging (MRI), positron emission require to achieve the greatest likelihood of establishing evidence of tomography (PET) and cerebrospinal fluid biomarkers (CSF). Neu- biological activity with the smallest number of patients. roimaging is likely to play a pivotal role in the design of new biomarkers for the early diagnosis of AD, as well as for prognosis and tracking disease progression. In particular, automated computational Symposium—Neuro-imaging and early analyses and mathematical models are becoming increasingly important because they provide quantitative, objective and repro- diagnosis of neurological diseases ducible assessment of brain alterations that can be overlooked by conventional visual assessment. In this talk, I will present recent advances in the computerized 110 analysis of neuroimaging date for deriving biomarkers of AD. First, I will present computational anatomy approaches (including automatic Multiple sclerosis hippocampal morphometry, cortical thickness measures, white matter M. Filippi tractography) that provide a comprehensive assessment of structural Vita-Salute San Raffaele University (Milan, IT) alterations in AD. I will then briefly review some recent results in functional imaging including resting-state fMRI, magnetoencepha- Magnetic resonance imaging (MRI) has a high sensitivity in revealing lography and PET. I will emphasize the role of statistical learning macroscopic tissue abnormalities in patients with multiple sclerosis approaches such as support vector machines, which allow mining data (MS). This, combined with its availability, repeatability and capa- for new markers. Relationships between neuroimaging, biological and bility of providing objective measures of overall disease activity and cognitive markers will also be discussed. I will conclude my talk by burden, has led to the extensive use of MRI for diagnosing MS and discussing the potential of ultra-high field MRI (7 Tesla) in neuro- monitoring its evolution. In patients at presentation with clinically degenerative disorders. isolated syndromes (CIS) suggestive of MS, MRI has been formally included in their diagnostic work up through the definition of ad hoc sets of criteria to show disease dissemination in space (DIS) and time. Several proposals have been made to simplify further such criteria and to make them easier to be implemented in clinical and research settings. One aspect that has not been considered yet in the available 112 sets of MRI diagnostic criteria is the presence of lesion in the brain Stroke gray matter (GM). The introduction of double-inversion recovery F. Fazekas sequences has contributed to imaging GM lesions, which have been Medical University of Graz (Graz, AT)

123 S8 J Neurol (2012) 259 (Suppl 1):S1–S236

The ability to identify intracerebral hemorrhage from infarction with Symposium—MS and acquired demyelinating CT has been and still is a cornerstone in the management of acute disorders stroke. However, neuroimaging nowadays has much more to offer than that. Diffusion-weighted MRI (DWI) allows to detect ischemic lesions within 30–60 min after the acute event which gives an almost 143 immediate morphology based diagnosis of ischemic stroke. Toge- Diagnostic criteria for multiple sclerosis: 2010 revisions ther with conventional MRI this fact may also help in the timing of to the McDonald criteria the attack such as in wake up stroke. DWI frequently shows acute ischemic lesions even in patients with transient ischemic attacks X. Montalban (TIA). Beyond thus indicating a need to change the current defini- University Hospital and Research Institute Vall d’Hebron (Barcelona, tion of TIA this also conveys prognostic information in terms of a ES) high risk for subsequent stroke. CT or MR angiography provide According to the 1983 Poser Multiple Sclerosis diagnostic criteria, a complementary information regarding vessel patency which has diagnosis of (clinically definite) Multiple Sclerosis (MS) could only both prognostic and management implications. Additional insights be made after two clinical episodes of the kind seen in MS, which come from perfusion imaging which serves to indicate threatened were mandatory to demonstrate dissemination in time and space. but potentially salvageable brain tissue (mismatch concept). Finally Changes introduced in the 2001 McDonald Criteria improved our iron sensitive MR sequences help in identifying acute hemorrhage ability to diagnose MS, as magnetic resonance imaging (MRI) find- with MRI as safely as with CT but also indicate clinically silent old ings could be considered as a formal proof of dissemination in time bleeds (microbleeds) and thus provide important etiologic clues. and space after a single episode of neurological dysfunction typical of Given all these possibilities of neuroimaging in stroke we are MS. Further changes introduced in the 2005 Revisions to the challenged to individually tailor the use of these imaging tools McDonald Criteria allowed us to perform even earlier diagnoses of according to the maximum benefit and least burden / cost for our MS by reducing the timing for a new lesion to be considered as a patients. demonstration of dissemination in time. Thus, whereas according to the 2001 criteria new lesions needed to appear at least three months after a Clinically Isolated Syndrome (CIS) to qualify for dissemination in time, in accordance with the 2005 revisions to the criteria, the 113 demonstration of new lesions that had appeared from the first month - Parkinson’s disease and parkinsonisms after the CIS- onwards were already indicative of dissemination in time. D.J. Brooks Well along these lines, the latest revision of the diagnostic criteria Imperial College (London, UK) (the 2010 Revisions to the McDonald Criteria, Ann. Neurol. 2011) In established PD the Queen Square Brain Bank criteria applied by has enabled us to produce even earlier diagnoses of MS, as con- experts show around 90 % sensitivity and specificity for the presence comitant presence of enhancing and non-enhancing lesions suffices to of midbrain Lewy bodies at subsequent autopsy. However, in early demonstrate dissemination in time. Thus, for the first time, a diagnosis disease clinical diagnosis is less straightforward and diagnosis of PD of MS after a CIS could be made, in some patients, with a single MRI made in the community by non-experts has been reported to be scan. Besides, should this concomitance of lesions at different evo- associated with a 25 % error rate. Imaging biomarkers can potentially lutionary stages not be observed, the demonstration of new or help support clinical diagnosis. Nigral abnormalities can now be enhancing lesions at any time after a CIS would equally be indicative detected in vivo in PD with 7 teslan MRI and at 3 tesla with diffusion of dissemination in time. Requirements for dissemination in space tensor MRI. Magnetisation transfer can demonstrate melanin loss in have also been simplified in the 2010 criteria. As per them, the the substantia nigra. Transcranial sonography (TCS) detects midbrain presence of at least one lesion in at least two of four locations hyperechogenicity in both sporadic and genetic PD and in at-risk gene characteristic for MS, i.e. periventricular, juxtacortical, infratentorial carriers and subjects with late onset hyposmia or REM sleep behav- or spinal cord, already qualifies for dissemination in space. Besides, iour disorder. PET and SPECT ligands can demonstrate the presence differently from previous versions of the diagnostic criteria, the of dopamine terminal dysfunction in early and preclinical disease and presence of positive cerebrospinal fluid findings (two or more oli- FDG PET reveals an abnormal covariance pattern between levels of goclonal bands or elevated IgG index), although admittedly crucial to resting brain blood flow metabolism in cortical and subcortical evaluate the risk of conversion to clinically definite MS and rule out regions. alternative diagnoses, has not been taken into account for defining In the atypical parkinsonian syndrome multiple system atrophy dissemination in space after a CIS -although it continues to be one of (MSA) T2-weighted MRI can reveal characteristic changes including the mainstays for the diagnosis of primary progressive MS. reduced putmen signal due to iron deposition and the pontine ’hot Whereas the increasing sensitivity of the 2010 revisions to the cross bun sign’ as transverse fibres become visible. Progressive diagnostic criteria has undeniable advantages, it may involve persis- supranuclear palsy (PSP) is associated with midbrain atrophy and 3rd tence of risk of misdiagnosis. Thus, the expertise of the clinician, who ventricular widening. In both these conditions diffusion weighted should detect clinical and radiological red flags, becomes an indis- MRI shows increased striatal water diffusivity but they can be dis- pensable tool to avoid diagnostic mistakes, which may lead to criminated as the middle cerebellar peduncle is targeted in MSA erroneous therapeutic choices. while the superior peduncle is targeted in PSP. Functional imaging reveals characteristic patterns of subcortical hypometabolism in MSA and PSP and a loss of lentiform nucleus dopamine receptor 144 binding. In this lecture the role of structural and functional imaging for The new players in the basic treatment of MS supporting the differential diagnosis of the various degenerative L. Kappos parkinsonian syndromes will be discussed. University Hospital Basel (Basel, CH)

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S9

Nearly 20 years after the first approval of IFNB as treatment of 146 relapsing MS, a new generation of disease modifying drugs is Update in the pathogenesis, clinical aspects entering daily practice. In addition to Natalizumab some cell depleting and/or immu- and treatment of NMO noregulatory monoclonal antibodies (MABs) have shown efficacy R. Gold in reducing inflammatory activity in relapsing MS in the range of Ruhr University (Bochum, DE) [50 - 90 %. Whilst Natalizumab may celebrate a come back to a Neuroimmunology always tries to understand the pathogenesis of a broader first line indication in patients negative for JC Virus disease, starting from the antigen until the full evaluation of clinical antibodies if the still increasing body of evidence confirms their symptoms and treatment. This has been achieved early on in myas- value as risk stratification criterion, most neurologists would hesi- thenia gravis, and since almost a decade also neuromyelitis optica tate to use Alemtuzumab as a first line treatment and - pending the (NMO, Devic disease) reached this level. In up to 80 % of NMO results of recently initiated Phase III trials - also the B-Cell patients antibodies against the water channel aquaporin-4 are detec- depleting humanized monoclonal antibody Ocrelizumab. As a first ted. They initiate a B-cell mediated, perivascular destruction of immunoregulatory MAB IL-2 Receptor targeting Dac-HYP has astrocytes and associated demyelination, which was confirmed in created high expectations also by the possible availability of a animal experimentation by passive transfer of patients’ sera. The treatment effect predicting test. resulting histopathology of lesions is resembling a B cell mediated The first oral drug, Fingolimod has now been approved in most type of multiple sclerosis (MS). countries of the world for the treatment of relapsing MS. Further The radiological features are unique, in that more than 90 % of clinical observations and an ongoing study in primary progressive MS NMO patients have normal cranial MRI except mild periventricular will show if in addition to its strong anti-inflammatory effects this abnormalities in the brainstem where aquaporin-expression is very new therapeutic principle can also address the unmet need of effective high. Yet spinal cord pathology has long-stretching lesions extending treatments against the more neurodegenerative features of the disease for more than 3 vertebral bodies. Therapeutic approaches have greatly that accompany its steadily progressive phase. improved. For acute therapy glucocorticosteroids, combined with More therapeutic options are to come, including antimetabolites plasma exchange in severe cases should be used. Long-term therapy like Teriflunomide and new immunomodulatory or even potentially uses azathioprine, glatiramer in mild cases and in highly active dis- directly neuroprotective oral compounds like BG12 and Laquini- ease anti-CD20 (rituxan). Mitoxantrone can serve as another rescue mod with innovative modes of action that have shown statistically therapy. Importantly, IFN-ß has no therapeutic activity and may be significant effects on relapse rates and progression of impairment/ even harmful in NMO, and much more so natalizumab which should disability as well as on MRI measures of inflammation and be avoided. The presentation will cover all these aspects of NMO. degeneration in recently presented or announced Phase II and III trials. Neurologists are challenged with deciding which of these numerous options and when in the course of the disease to select for Symposium—Neurology and sleep-wake the individual patient. Evidence to support these decisions is emerging but is still scarce. The different efficacy and adverse event disorders profile of the available compounds as well as accompanying studies of biomarkers in controlled trials provide first hints towards differential indications that allow to better balance risks and benefits. To 147 inform future treatment choices and to better define the individual profiles of the available and emerging treatments controlled studies Narcolepsy: a disease model of the brain have to be complemented by well-designed systematic and compre- C. Bassetti hensive observational cohort studies. University Hospital (Berne/Lugano, CH) Human narcolepsy is a rare brain disorder which manifests itself with a complex clinical phenotype including sleep-wake, motor, vegetative, psychiatric and cognitive disturbances. The leading symptom is 145 an excessive, overwhelming daytime sleepiness. The only patho- The new players in the symptomatic treatment of MS gnomonic symptom is cataplexy (sudden, short-lasting loss of muscle A. Thompson tone triggered by sudden emotions). Sleep disturbances are frequent and include insomnia, periodic limb movements, REM sleep behavior UCL (London, UK) disorder, other parasomnias, and sleep disordered breathing. Management of symptoms in multiple sclerosis (MS) has received Animal and human studies have shown that narcolepsy is usually little attention compared with disease-modifying treatments. How- linked to a reduction of hypocretin (orexin) neurons in the lateral ever, the effect of these symptoms on quality of life can be profound. hypothalamus, which results from the interaction between a genetic Clinical trials of pharmacological drugs to treat symptoms of MS predisposition (HLA DQB1*0602) and non specific (infectious?) have often been underpowered and have used inappropriate measures environmental factors. The immune system is implicated in a of outcome. Therefore, the evidence base on which to make clinical molecular cascade of events eventually leading to the hypocretin decisions has been less than adequate. Interest in pharmacological deficiency. Neurochemically narcolepsy is linked to multiple signal- treatment of symptoms in MS has increased in the last decade. Sev- ling deficits including not only the hypocretinergic systems. eral large randomised controlled trials have been reported focussing Neurophysiologically narcolepsy is best explained by a dyscontrol of particularly on motor symptoms including weakness and spasticity state boundaries, the consequence of which are a disinhibition of and including agents such as long acting aminopyridenes and can- REM sleep mechanisms and the occurrence of dissociated states. nabinoids. It is important to build on these successes and encourage Neuroimaging studies have expanded our knowledge of narcolepsy as more definitive trials with scientifically sound clinical outcomes a brain disorder arising from the dysfunction of multiple brain areas evaluating interventions which address some of the other disabling including the hypothalamus, amygdala, and dorsal mesencephalo- symptoms affecting those with MS. pontine junction.

123 S10 J Neurol (2012) 259 (Suppl 1):S1–S236

The diagnosis of narcolepsy is made on clinical grounds. Neuro- 149 physiological tests (MSLT, polysomnography), HLA-typing and the Insomnia/hypersomnia and neurological assessment of hypocretin-1 levels in the cerebrospinal fluid may be used to confirm the diagnosis. disorders Management of narcolepsy is symptomatic but nevertheless often P. Jennum satisfactory. Non pharmacological and pharmacological interventions Glostrup Hospital, University of Copenhagen are needed in most cases. Excessive daytime sleepiness is improved (Copenhagen, DK) by drugs influencing the dopaminergic, and cataplexy by those Objective: to highlight the impact of insomnia in central neurological modulating the noradrenergic transmission. Sodium oxybate is disorders by providing information on its prevalence and give rec- effective in improving both wake and sleep disturbances of ommendations for diagnosis and treatment. narcolepsy. Methods: literature review and own data. Results: Insomnia in neurological psychiatric disorders is frequent, but underestimated symptom. Its occurrence may be a direct 148 consequence of the disease itself or may be secondary to pain, REM sleep behaviour disorder and parkinsonism depression, other sleep disorders or the effects of medications. Insomnia can have a significant impact on the patient’s cognitive J. Santamaria and physical function and may be associated with psychological Hospital Clıńic of Barcelona, University of Barcelona distress and depression. Diagnosis of insomnia should be based on (Barcelona, ES) adequate medical history, including other sleep complaint, and the REM sleep behaviour disorder (RBD), initially considered a rare use of actigraphy and a sleep full polysomnography should be sleep problem, has gained a well justified interest among neurolo- performed to further evaluate sleep disorders, which may present as gists given its association with neurodegenerative disorders. Two chronic sleep complaints. Secondary causes to insomnia should be essential findings characterize RBD: the presence of recurrent identified. First line treatment aims at the underlying neurologic periods during sleep of abnormally vigorous limb/body movements disease. The few high quality treatment studies show that short term with or without vocalizations and the report of vivid, typically treatment with hypnotics may be recommended in most disorders aggressive dreams where the subjects reacts against a threat by a after having ruled out high risk for adverse effects. Sedating anti- person or animal. This combination gives the bed partner the depressants may have some potential for managing insomnia in impression that the patient is dreaming and acting out their dreams stroke and Parkinson’s disease (PD) patients/other neurodegenera- (2). tive disorders, but side effects limits its use and the evidence for its There are three clinical contexts where RBD may appear: a) in use is low. Melatonin, light treatment physical activity can stabilize patients without any discernible neurological disorder -the idiopathic the sleep-wake circadian rhythm and shorten sleep latency in form of the disorder, b) in patients with a known neurological dis- dementias and PD. Cognitive behavioural therapy are an important order, essentially neurodegenerative disorders with parkinsonism such treatment for primary insomnia, and may show potential in neuro- as Parkinson’s disease (PD), dementia with Lewy bodies (DLB) or logical and psychiatric diseases. Multiple System Atrophy (MSA); and c) associated with drug treat- Conclusion: Insomnia is prevalent in neurological and psychiatric ment or withdrawal such as antidepressants or alcohol withdrawal. diseases which may reflect the underlying disease process with the The clinical characteristics of the parasomnia in these 3 contexts do involvement of the sleep-wake and diurnal regulating system. There is not differ very much. an unmet need to a) better understand the underlying pathophysio- Schenck et al. first reported in 1996 that 38 % of their idiopathic logical processes and disease involved in sleep disorders in brain RBD patients developed parkinsonism in the ensuing years, a finding disorders, and b) to develop and improve specific evidence-based confirmed later by two other studies. Approximately half the patients treatment strategies. with idiopathic RBD will develop PD, DLB or MSA in the ensuing 10 years. The fact that a sleep disorder might be the first manifestation of a neurodegenerative disease is one of the most important discoveries 150 in sleep medicine. Epilepsy and sleep A different situation is when a patient with an already known neurodegenerative disorder, such as PD, develops RBD. What is the P. Jennum relevance of that finding? We can help the patient trying to reduce the Glostrup Hospital, University of Copenhagen (Copenhagen, DK) risk of injuring himself/herself or the bed partner during the episodes During sleep a number of motor and behavioural phenomena may of RBD and using pharmacological treatment if necessary. For occur. A main issues is to which extend these episodes may be epi- example, protection with pillows, putting objects in the nightstand leptic or non-epileptic. Some epileptic seizures especially occurs in table far from the patient, sleeping in different mattresses, etc. may be sleep; frontal and temporal lope seizure and epileptic syndromes with of help. Clinical experience reveals that drugs such as clonazepam or continued epileptic activity in sleep wave sleep (CSWS). melatonin are helpful to decrease the severity of the movements, in a Nocturnal frontal lobe epilepsy (NFLE) is characterized by sei- similar way than in idiopathic RBD. Although there are studies zures with complex, often bizarre, violent behaviour arising only or suggesting that idiopathic RBD improves with pramipexol and a few mainly during sleep. These unusual seizures and their occurrence anecdotal reports of improvement of RBD in patients with early PD during sleep are often accompanied by normal EEG tracings and when starting L-dopa, others suggest that dopaminergic treatment neuroradiological findings, making it difficult to distinguish NFLE does not improve RBD in PD. In patients with PD related RBD seizures from other non-epileptic nocturnal paroxysmal: parasomnias improvement of parkinsonism with subthalamic deep brain stimula- and sleep related movement disorders. Despite several aspects of tion does not modify RBD and antidopaminergic treatment does not parasomnias and NFLE and other epileptic events have been evalu- induce RBD. Finally a relevant point of diagnosing RBD in PD, ated in the last years, a problem to clinicians is still: differential especially in patient without dementia, is that it RBD appears to diagnoses and management. Despite these conditions have been predict the development of cognitive impairment in the subsequent known for more than 25 years, there is still limited data available years. regarding the morbidity, consequences and evidence for treatment.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S11

This paper discusses some controversial points still under debate: Imbalance or type 3 dizziness is essentially a balance disorder, the difficulties in distinguishing nocturnal epileptic seizures from which may occur from various neurological disorders, right from NREM and REM parasomnias, pathophysiological mechanism and Binswanger’s disease and Parkinsonism to cerebellar disorders, management aspects. myelopathies, neuropathies and bilateral vestibular failure. Psychogenic or type 4 dizziness is often due to psychogenic factors, eg stress or depression. But one should always keep in mind the other forms of dizziness. A patient may describe numbness in his Symposium—Knowledge exchange programme head, but if it is triggered by rolling over in bed, one would think of in neurology between European and Indian BPPV. Clinicians Many patients, especially older patients may well have more than one kind of dizziness. Also it is generally useful to ask about the first episode of dizzi- 158 ness and understand it first. Approach to a dizzy patient Examination must include apart from standing and supine blood S. Kothari pressure, checking for spontaneous nystagmus with and without fix- ation, looking for pursuit and saccadic eye movements, doing the Poona Hospital (Pune, IN) head impulse test and the Dix-Hallpike test, the Romberg test and Dizziness and Vertigo are very common but very frustrating com- observing gait. In patients with balance disorders, we need a much plaints that a doctor faces. This is because patients use these words in more complete Neurological examination. a very loose way to describe a number of similar but pathophysio- We shall see with case illustrations, typical nystagmus patterns of logically different sensations, like spinning, faintness, unsteadiness of vestibular neuritis, stroke presenting as vestibular pseudoneuritis, gait or non-specific heaviness or lightness or numbness in the head. acoustic neuromas, Arnold Chiari malformation, Multiple sclerosis, Very often dizziness is due to a relatively benign inner ear problem. etc. We shall touch upon the increasingly recognized entity of One can therefore get dulled into complacence and easily miss dan- Migraine associated vertigo and finally we shall highlight the very gerous causes of dizziniess. common, but misdiagnosed and mistreated entity of BPPV and all its Doctors need to have a clear strategy to approach such patients to variants, including approaches to repositioning, manually and with avoid getting similarly confused. Relying on lab tests or diagnostic the use of Videonystagmometry and repositioning chairs. measures can confound the situation further. Fortunately a good history and a targeted Neuro-otological examination can help us find our way in this maze. We outline here an essentially bedside clinical approach to dizziness, essentially using 160 our ears to get a good history and looking closely at the eyes of the Causes and treatments of neuroleptic malignant patient. syndrome Our aim is first to identify true vertigo and narrow down the possibilities from nonvertiginous dizziness. Sometimes patients may R. Balakrishnan mislead by not being able to describe the symptom clearly. (Thrissur, IN) But, in general, if we use the quality of the dizziness along with Neuroleptic malignant syndrome is a potentially fatal complication of the circumstances or precipitating or aggravating factors as well as the neuroleptic treatment. duration of each individual spell of dizziness, we can usually get a It is characterized by a variety of signs and symptoms associated working hypothesis on which to base the further examination. Trig- with autonomic instability, and hypothalamic and extrapyramidal gers, aggravating and relieving factors are major points in history and dysfunction. Since other medical disorders may mimic its clinical sometimes may be more important than the description of the presentation, the accurate recognition of this syndrome in the medical dizziness. setting is often a diagnostic dilemma. One medically ill patient with a True vertigo or type 1 dizziness is a clear spinning or rotatory clinical presentation suggestive of neuroleptic malignant syndrome is sensation, precipitated or aggravated by head movement. This usually presented here. The complexity of making the diagnosis, and a brief means one is dealing with the vestibular system, either peripheral or review of the literature is discussed. of its central connections. Rarely cardiogenic disorders can present with true vertigo though. Once we identify true vertigo, we learn to distinguish peripheral causes from central ones and use the duration of individual attacks to 161 diagnose causes like BPPV, Vestibular neuritis, Meniere’s, stroke, Presurgical evaluation in a developing country scenario posterior fossa lesions, etc. M. Tripathi There are some general pointers, eg more vertigo and less ataxia. All India Institute of Medical Sciences (Delhi, IN) Similarly vomiting or ataxia out of proportion to vertigo may indicate a central cause. Significant headache usually implies a central cause, Trends and standards of care for persons with drug refractory epilepsy maybe Migraine but may be more sinister causes, like dissection of (DRE) have been set in developed countries. However the developing the vertebral artery. Central vertigo can be deceptively less distressing countries have not trailed behind in performing surgery for persons and may have more variable symptoms. with surgically remediable DRE. Most are able to perform the It is usually easy to diagnose peripheral vertigo when the patient lesional resective procedures and palliative procedures with good has some aural symptoms. But aural symptoms can happen in central presurgical localisation and outcomes similar to the developed world. disorders just as central disorders may present with pure vertigo or However fewer centers in the developing world perform phase II or dizziness without any other central symptoms. complex surgeries. Apart from mesial temporal sclerosis, cortical Faintness or type 2 dizziness is essentially presyncope, due to dysplasias, DNETS etc, some of the pathologies encountred in the reduced blood flow to the brain. The causes are esssentially cardio- developing world are complex (post- infectious), perinatal insult vascular or vasovagal attacks. Simply checking standing and supine (hypoxic ischemic encephalopathy), multiple calcifications and nor- BP may often give a clue. mal brain MRI. One of the main reasons complex pathologies still

123 S12 J Neurol (2012) 259 (Suppl 1):S1–S236 continue to be difficult to operate in these regions is the difficulty O193 faced in localising the source (ictal onset zone) in a comprehensive Resting state functional connectivity abnormalities are non invasive way. My preesentation will deal with the role of Non Invasive investigations in the evaluation of a possible surgical cure associated with cognitive impairment in patients for epilespy. Role of VEEG, SPECT, PET and MEG and MSI which with paediatric multiple sclerosis are noninvasive tools for the same. These have added advantage in M. Filippi, M.A. Rocca, P. Valsasina, M.P. Amato, such nations as individual patient costs can be kept low with the state M. Absinta, A. Ghezzi, L. Moiola, A. Fiorino, P. Veggiotti, managing these systems in there health care and research models. The number of investigations in resource limited and under served pop- A. Falini, G. Comi and the MS and Neuroimaging Study ulations specially by policy makers will help in further reducing the Groups of the Italian Neurological Society huge treatment gap of epilepsy surgery in these countries. Objective: Aim of this study was to explore abnormalities of functional connectivity (FC) and functional interaction among cognitive networks (RSNs) in patients with pediatric multiple sclerosis (MS), as well as their correlation with cognitive impairment and T2 focal lesions. ______Methods: Brain dual-echo and RS fMRI scans were acquired from FREE COMMUNICATIONS 34 pediatric MS patients, and 18 age-matched controls. T2 lesion volume (T2LV) was assessed on dual-echo images. Independent component analysis (ICA) and a template-matching procedure were Oral sessions used to identify the default mode network (DMN), the executive control network (ECN), the salience network (SN) and the attention network. Within-group and between-group FC comparisons were Oral session 1 performed with SPM8. The functional network connectivity (FNC) toolbox was used to assess changes of interactions among RSNs. In MS patients, correlations between network abnormalities, cognitive Multiple sclerosis: Imaging/Neurophysiology impairment and structural damage were also assessed. Results: Significant RS FC changes were detected in all RSNs of pediatric MS patients vs. controls. A decreased FC was found in regions of the posterior lobes, as well as in the cerebellum of the O192 attention, SN and ECN. Conversely, an increased FC was found in A cohort of patients with Neuromyelitis optica in South frontal regions of the SN and DMN. FC decrease in the PCC was Wales and the South West of England higher in cognitively impaired vs. cognitively preserved patients S. Luppe, K. Harding, M. Cossburn, G. Ingram, (p=0.01), whereas FC increase in the R SFG and R IFG were higher in cognitively preserved than in cognitively impaired patients (p=0.01 T. Pickersgill, N.P. Robertson and 0.02, respectively). Patients with lower T2LV had a higher FC Cardiff University (Cardiff, UK) increase in the IFG (r=-0.36, p=0.04). The DMN and the attention Objectives: The discovery of a disease specific auto-antibody against network were significantly anticorrelated in healthy controls (r=-0.12, the astrocyte water channel aquaporin-4 (AQP4) in 2004 has allowed p=0.03), but they were disconnected in pediatric MS patients (r=- earlier and more accurate diagnosis and has led to the Wingerchuk 0.02, p=0.72). 2006 revised diagnostic criteria for Neuromyelitis optica (NMO). Conclusion: Significant RS FC abnormalities occur in cognitive Using these criteria we studied the clinical disease course, relapse rate, RS networks of pediatric MS. A decreased FC is associated with and the treatment strategies used, in a Northern European case series. cognitive impairment, whereas increased FC seems to be related with Methods: The study is a retrospective case series with longitudinal a preserved functional reserve. follow up. Patients were recruited from 7 neurology departments in This work has been partially supported by a grant from Italian South Wales and the South West of England. Multiple ascertainment Ministry of Health (GR-2009-1529671). strategies were used (hospital files and databases, physician referrals and a registry for anti-AQP4 antibody test results). The patients underwent a detailed neurological examination including disability O194 assessment. Results: 36 patients fulfilled the established criteria for NMO Microstructural MR imaging of cortical lesions and NMO spectrum disorders, 31 (86 %) of these were anti-AQP4 in multiple sclerosis phenotypes positive, 92 % were Caucasian. The female:male ratio was 9:1, P. Preziosa, M.A. Rocca, E. Pagani, M. Copetti, median age at onset 38.1 years (range 4-77), mean disease duration S. Mesaros, B. Colombo, M.A. Horsfield, A. Falini, 9 years (SD=9.2), and a mean annual relapse rate 0.84 (SD=0.62). The clinical presentation was heterogeneous including optic neuritis, G. Comi, H. Lassman, M. Filippi transverse myelitis and brainstem syndromes. Median delay from Vita-Salute San Raffaele University (Milan, IT); IRCCS Casa onset to EDSS 4 was 7 years. 79 % were receiving long-term immu- Sollievo della Sofferenza (San Giovanni Rotondo, IT); University of nosuppressive therapy, with the treatment strategies varying between Belgrade (Belgrade, RS); University of Leicester (Leicester, UK); 10 different drugs (azathioprine, beta-interferon, cyclophosphamide, Medical University Vienna (Vienna, AT) intravenous immunoglobulins, methotrexate, mitoxantrone, myco- Objectives: Double inversion recovery (DIR) sequences allow the phenolate, plasma exchange, prednisolone and rituximab). in vivo visualization of a proportion of cortical lesions (CLs) in Conclusion: This study provides new data on the disease course, multiple sclerosis (MS), and their application has demonstrated that relapse rate and disability accrual in NMO in a UK cohort of 36 CLs occur in all the major disease clinical phenotypes. We used patients. These data suggest a high variability of treatment regimes. DIR and diffusion tensor (DT) MRI to quantify tissue damage in After analysis and consultation with other UK groups we propose a CLs and the apparently normal cortical gray matter (GM) treatment algorithm. in patients with relapse-onset MS at different stages of the disease.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S13

Methods: Brain DIR, DT MRI and 3D T1-weighted scans were O196 acquired from 35 relapsing remitting (RR), 23 secondary progressive Methylprednisolone-regulated genes affecting multiple (SP), 12 benign (B) MS patients and 41 healthy controls (HC). Dif- fusivity values in CLs, skeletonised cortical GM, white matter (WM) sclerosis pathogenesis lesions and normal-appearing (NA) WM were assessed. F. Hahn, H. Faber, P. Weber, B. Pu¨tz, M. Knop, S. Results: Compared to HC, MS patients had a significantly lower Nischwitz, F. Weber fractional anisotropy (FA) and higher axial (AD), radial (RD) and mean Max Planck Institute of Psychiatry (Munich, DE) diffusivity (MD) in the skeletonized cortical GM and NAWM. CLs had higher FA (p=0.02), AD (p=0.01) and MD (p=0.05) vs. HC skeletonized Objectives: Methylprednisolone (MP) constitutes a common treat- cortical GM, as well as higher FA (p=0.00002) and lower RD (p=0.01) vs. ment for multiple sclerosis (MS) relapses using high-dose, short-term patients’ skeletonized cortical GM. Compared to RRMS, SPMS patients (3-5 days) intravenous (i.v.) application. Despite frequent use, the had higher WM lesion volume and more severe damage to the skele- mechanisms responsible for the therapeutic effect are largely tonized cortical GM, NAWM and WM lesions. Damage in the other unknown. compartments was similar between SPMS and BMS patients. Compared Methods: Genome wide expression profiling was performed in to SPMS, BMS patients had lower MD, AD and FA of CLs. Damage in blood of six MS patients before, during and after i.v. therapy with the CLs had a high power to discriminate BMS from SPMS (area under 2000 mg MP using the Illumina HumanHT-12 v4.0 Expression BeadChip. Significantly regulated genes were detected via limma, the curve: 77-80 %), with high specificity (93 %), sensitivity (89 %) and accuracy (87 %). Conclusions. Microstructural diffusivity features of BioConductor. Candidates were selected using Pathway Studio CLs, quantified using DT MRI, differ from those of WM lesions and are (Ariadne Genomics) and validated by quantitative Real-Time-PCR in likely to reflect neuronal damage and microglial activation. Their quan- whole blood of six further patients as well as in peripheral blood tification may help in the early identification of RRMS patients at risk of mononuclear cells (PBMC) and neutrophil cells (NC) stimulated with developing a progressive form of the disease. MP for 12 h in vitro. Serum levels were quantified in relapsing Acknowledgments. The study was partially supported by a grant remitting MS patients before, during and after MP therapy by com- from FISM/2008/R/13. mercially-available ELISAs. Results: 1908 MP-regulated genes (p \ 0.05) were detected. Pathway Studio showed an interaction of three genes: oncostatin M (OSM, 2.82-fold change during MP treatment versus before treat- O195 ment), secretory leukocyte peptidase inhibitor (SLPI, 8.97-fold Deficits in memory and spatial cognition correlate change) and matrix-metallo-proteinase-9 (MMP-9, 2.52-fold change). with regional hippocampal atrophy in multiple sclerosis We validated these results in six additional patients and furthermore G. Longoni, M.A. Rocca, E. Pagani, G. Riccitelli, demonstrated that MP increased the expression of SLPI, OSM and MMP-9 in PBMC as well as in NC in vitro. In addition, SLPI and B. Colombo, M. Rodegher, A. Falini, G. Comi, M. Filippi MMP-9 serum levels were elevated during MP treatment in com- Vita-Salute San Raffaele University (Milan, IT) parison with blood samples before/after therapy and healthy controls. Objective: The hippocampus has a critical role in episodic memory Beyond that, MS patients in relapse exhibit higher serum levels than and visuospatial abilities, which are frequently affected in MS. Aim healthy controls. of our study is to assess the patterns of whole and regional hippo- Conclusion: MP treatment upregulates expression of SLPI, OSM campal atrophy in a large group of multiple sclerosis (MS) patients, and MMP-9 and serum levels of SLPI and MMP-9 in MS. MMP-9 and their correlations with neuropsychological impairment. promotes the breakdown of the blood–brain-barrier. OSM, however, Methods: From 103 MS patients (22 relapsing remitting [RR], 33 was reported to inhibit inflammation and disease progress in experi- secondary progressive [SP], 23 primary progressive [PP], and 25 mental allergic encephalomyelitis (EAE). The upregulation of SLPI benign [B] MS) and 28 healthy controls (HC), brain dual-echo and 3D in active EAE induces proliferation of neuronal stem cells and T1-weighted images were acquired using a 3.0 Tesla scanner. All differentiation towards oligodendrocytes, which implicates neurore- subjects underwent neuropsychological evaluation, including word- generative functions. Thus, OSM and SLPI may mediate some of the list (WL), short-story (SS), delayed recall of Rey-Osterrieth Complex beneficial effects of MP treatment. Therefore, our results indicate that Figure (ROCF-recall) and ROCF-copy. The hippocampi were man- corticosteroids induce genes that are protective against MS on the one ually segmented and volumes derived. From contours, radial atrophy hand and genes having disease-promoting attributes on the other was calculated for assessment of regional atrophy distribution. Cor- hand. relations between regional hippocampal atrophy and clinical, neuropsychological and T2 lesion metrics were assessed. Results: Right and left hippocampal volumes differed significantly between MS patients and HC (p\0.001 for the right and p=0.002 for the O197 left hippocampus). In MS patients, radial atrophy was detected in the lateral portion of the body and tail (CA1 subfield) and the subiculum, Exploring the relationship between regional grey- bilaterally. The ventral surface of the subiculum was also affected. Sig- matter atrophy and cognitive impairment in paediatric nificant correlations (p\0.01) were found between performance at: 1) multiple sclerosis WL vs. tail (CA1 subfield) of the left hippocampus atrophy; 2) ROCF- M.A. Rocca, M. Absinta, M.P. Amato, A. Ghezzi, L. Moiola, recall vs. tail (CA1 subfield) of the right hippocampus atrophy; and 3) ROCF-copy vs. body of the left hippocampus atrophy. Regional hippo- A. Fiorino, P. Veggiotti, A. Falini, G. Comi, M. Filippi campal atrophy correlated with brain T2 lesion volumes, while no and the MS and Neuroimaging Study Groups of the Italian correlation was found with clinical disability. Neurological Society Conclusion: Hippocampal subregions have a different vulnera- bility to MS-related damage, with a relative sparing of the head. The Objective: To assess the patterns of regional abnormalities in the assessment of hippocampal atrophy at a regional level may contribute brain gray matter (GM) and white matter (WM) in pediatric multiple explaining deficits in specific cognitive functions, including memory sclerosis (MS) patients according to their cognitive profile, using and spatial cognition. voxel-based morphometry (VBM).

123 S14 J Neurol (2012) 259 (Suppl 1):S1–S236

Methods: Using a 3.0 Tesla scanner, brain dual-echo and 3D in community studies. They experienced more seizures, had lower T1-weighted scan were acquired from 35 pediatric MS patients (22 girls, knowledge of epilepsy and its management, and reported greater mean age=15.3 years, median EDSS=1.5, mean disease duration=2.1 perceived epilepsy-related stigma. However in the previous 12 years) and 16 gender- and age-matched controls. All patients underwent months, most had received epilepsy care which was consistent with a neuropsychological assessment and patients with at least two abnor- national guidelines. Using regression, knowledge, stigma, medication mal tests were considered as cognitively impaired (CI). T2 and T1 lesion management, and seizure frequency (in descending order) predicted loads (LL) were calculated using Jim5 software. VBM was performed emergency use. using SPM8 and DARTEL (p\0.001, cluster extent 10 voxels). Conclusion: People presenting to EDs due to epilepsy re-attend Results: Sixteen pediatric MS patients were CI. Compared to controls, more frequently than people with other chronic conditions. Inter- pediatric MS patients had a significant atrophy of the left (L) thalamus, L ventions aiming to reduce attendances need to address the lower lingual gyrus, several regions in the frontal lobes, right (R) caudate epilepsy knowledge, sense of stigma, suboptimal self-management nucleus, L postcentral gyrus (PcG), R inferior temporal gyrus and L and frequent seizures reported by this group of people. People with superior temporal gyrus. Compared to controls and to cognitively pre- other long-term conditions, like asthma and diabetes, who have high served patients, CI patients had more severe atrophy of the bilateral service use are already being offered proactive self-help interventions, precuneus, L lingual gyrus, L inferior frontal operculum, L insula, L targeted to their specific needs. Our findings can be used to develop middle temporal gyrus, and L PcG. In pediatric MS patients, thalamic and test specific interventions for people with poorly controlled atrophy was significantly related to T2-LL (r=-0.52, p\0.001) and T1-LL epilepsy. (r=-0.58, p\0.001), while R precuneus atrophy correlated with the This study was totally supported funding from the National Health number of abnormal neuropsychological tests (r=-0.57, p\0.001). Service, National Institute for Health Research, Service Delivery Conclusions: In pediatric MS, GM atrophy is not limited to the Organization. No other disclosures of interest. thalamus (whose damage is strongly related to focal lesion burden), but also involves several cortical and subcortical regions. The assessment of the regional distribution of GM atrophy contributes explaining cognitive deficits in these patients. O199 This work has been partially supported by a grant from Italian Does adequate delivery of anti-epileptic drugs change Ministry of Health (GR-2009-1529671). the prognostic of status epilepticus? V. Alvarez, J.-M. Januel, B. Burnand, A.O. Rossetti ______Centre Hospitalier Universitaire Vaudois (Lausanne, CH) Objective: Because of high mortality and morbidity rate, SE repre- Oral session 2 sents a medical emergency and prompt treatment institution is important. Several robust predictors for status epilepticus (SE) prognosis are known, especially etiology, de novo presentation, severe consciousness impairment, and age. International and national Epilepsy I treatment guidelines are available, but the specific role of anti-epileptic treatment quality, has received little attention to date in SE outcome prediction. O198 Methods: A prospective cohort of adults with incident SE (excluding postanoxic cases) was analyzed. SE treatment adequacy What are the characteristics of people who attend was defined according to the current guidelines of our country. We emergency departments with epilepsy? assessed dosages of drugs (allowing a ±30 % deviation as compared L. Ridsdale, A. Noble, L. Goldstein, P. McCrone, P. Seed to the Swiss SE treatment protocol), and medication sequence. The King’s College London (London, UK) prognostic impact of SE treatment for mortality and likelihood to return to baseline clinical conditions was assessed through uni- and Objectives: People with established epilepsy frequently attend hos- multivariable tests, adjusting for the most important predictors in this pital emergency departments (ED) and are in the UK 50 % are setting; SE severity was assessed through the validated ‘‘Status epi- admitted. These attendances are frequent in inner city areas. Persons lepticus severity score’’ (STESS). attending ED have low levels of well-being, and often do not require Results: Of the studied 225 patients, treatment was considered or benefit from expensive emergency medical care. Unplanned hos- inadequate in 37 %. Mortality occurred in 12 %, and 36 % were pitalizations are costly and reducing them is a common target around discharged with a new handicap. In univariate assessments, age, eti- the world. The development of new pro-active interventions for ology, SE severity and medical comorbidities were significantly such patients is challenging. Policy-makers lack information about related to outcome, but not treatment adequacy. Logistic regression their characteristics, pattern of ED use, needs and the factors asso- for mortality identified only etiology (OR 18.8, 95 % CI 4.3-82.8) and ciated with ED frequent use. This study aimed to provide this STESS (OR 1.7, 95 % CI 1.2–2.4) as independent predictors; similar information. results were found for lack of return to baseline: etiology (OR 7.4, Methods: We prospectively recruited adults attending three Lon- 95 % CI 3.9–14.0), STESS (OR 1.7, 95 % CI 1.4–2.2). ROC curves don EDs for seizures (diagnosed for [=1 year). Participants for the two outcomes showed that consideration of treatment ade- completed questionnaires on their service use, their knowledge of quacy did not improve outcome prediction. epilepsy, their self-management and their psychosocial state. Conclusions: This analysis on a large cohort of SE patients sug- Results: 85 patients were recruited. The mean age was 41 and 53 % gests that SE treatment plays a relatively negligible prognostic role. were male. Their average number of ED attendances in the prior year Obviously, treatment protocols according to current guidelines remain (mean=3.2; median =2) exceeded that of other ED attenders, and that of important in daily practice; however, awaiting treatment trials in SE, attenders for other chronic conditions. Frequency of ED use was not it appears questionable to apply important resources in refining cur- homogenous amongst patients, with the some attending much more rent treatment protocols; rather, new therapeutic approaches should be frequently. Attenders were distinguishable from the people with epilepsy identified.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S15

O200 Conclusions: While CAM use approaches 42 % in the US, lack of Determination of the efficacy of phenytoin awareness and availability due to expense is a potential barrier to its use in an indigent, urban county hospital population. However, due to on prevention of late post-traumatic seizure the safety net function of US county hospitals, medically refractory P. Dolati, M.S. Akhtar Shomar, S.M. Ziabary epilepsy patients (who tend to be underinsured) are over-represented University of Calgary (Calgary, CA); University of Kerman (Kerman, in these settings. This survey suggests in a refractory epilepsy pop- IR); University of Tehran (Tehran, IR) ulation CAM use may surpass that of a general medical population, Background: Phenytoin is commonly used for prevention of late post- and may reflect the problems associated with inadequate control of a traumatic seizure worldwide. However, there is a lack of high-quality chronic disease. Better understanding of the actual impact of a variety evidence demonstrating benefit. of CAM therapies on refractory epilepsy is greatly needed. Methods: This study was a prospective, quasi-randomized clinical Denver Health and Hospitals offers statistical support staff for trial in 1160 Traumatic Brain Injury (TBI) patients. The inclusion investigator initiated studies; in conjunction with the University of criteria were: 1-All Patients with TBI and GCS\8 and 2-All TBI Colorado, the REDCap database management application was also patients who had GCS[8 but they had a cortical lesions on Brain CT used for data collection and manipulation for statistical analysis. Scan. The intervention group was treated with phenytoin for a full year. Serum levels of phenytoin were maintained in the high therapeutic range (3 to 6 lmol of free phenytoin per liter). The control O202 group received placebo. Patients were followed for five years. The Skin autonomic seizures primary outcome was new or recurrent seizure. ´ Results: The two groups were equal in distribution of age, sex and S. Rocha, J. Pinho, F. Sousa, A. Machado the type of treatments, medical versus surgical. Twenty four out of Hospital de Braga (Braga, PT) 580 patients (4.1 %) had a late seizure in the phenytoin group com- Introduction: Autonomic symptoms often occur during seizures, pared to 5/580 (0.86 %) in the placebo group. Phenytoin treatment accompanying other symptoms or as its main manifestation. These was associated with a greater risk of seizures (p=0.0005; RR=4.8; seem not to result from simple reactions to other clinical features, but 95 % CI, 1.8-12.5). from central autonomic network activation. We report two cases of Conclusion: This study showed that prophylactic administration of skin autonomic seizures. phenytoin was associated with a greater risk of late post-traumatic Clinical reports: 1 – A 51 years-old man, seen for herpes simplex 1 seizure. encephalitis with left temporo-insular lesion, resulting in a mild residual aphasia. One month later he reported having several episodes per day of a strange feeling in his left body, which he described as a O201 «cold sensation» or «goose bumps». These had a typical Jacksonian Use of complementary and alternative medicine march (sequentially affecting face, arm and leg) over a period of about in an urban county hospital epilepsy clinic 2-3 min, with paramount piloerection at close inspection. Interictal E. Maa EEG was normal. Treated with carbamazepine (400mg) he became free of these paroxysmal episodes 2 days later. 2 – A 51 years-old man, Denver Health and Hospital (Denver, US) with hypertension and alcohol abuse, seen for acute right parieto- Objective: To better understand the use of Complementary and occipital ischemic stroke. Four months later he noticed transient epi- Alternative Medicine (CAM) in epilepsy patients in an urban county sodes, occurring twice weekly, lasting for about 60 min, of a hospital setting, a survey was conducted to examine the general «shivering sensation» over his left body, which was simultaneously acceptance and usage patterns of CAM in our epilepsy clinic. pale, sweaty and with piloerection. Interictal EEG was normal. Methods: We provided a self-administered CAM survey to all Gabapentine (600mg) led to complete remission of these episodes. consecutive patients seen at the Denver Health Epilepsy Clinic Conclusions: Autonomic manifestations as the sole symptoms of between September–October 2011. Information collected included epilepsy are rather rare. Nevertheless, it is very important to recognize demographic information as well as experience with a list of potential its occurrence, as proper treatment with antiepileptic drugs seems to CAM therapies. have excellent results. Although a generator of these autonomic Results: 85 of a total of 121 patients with epilepsy seen between manifestations probably exists, its exact location remains largely September–October 2011, responded to the survey. Ethnic and racial unknown. Both the insula and the amygdale seem to be the strongest composition included 37.6 % Hispanic or Latino, 35.3 % White, candidates, although several structures of the central autonomic net- 22.4 % Black or African American, and 3.5 % Native American. work could also be involved, as the hypothalamus, the limbic system There were 42 men, mean age 39.5 with STD 11.4; and 37 women and the frontal lobe (orbital cortex and premotor area). mean age of 39.6 with STD 13.7. These patients were taking 2.12 AEDs with only 19 % being seizure free, and only 25.6 % being employed. Overall 68 % of patients used some form of CAM. The O203 most frequently used CAMs were medical marijuana (31.8 %), Migralepsy: confirming the real existence of this prayer/spirituality (27.1 %), meditation (20 %), stress management nosologic entity as a true migraine complication techniques (17.6 %), vitamins (16.5 %), diet modification (12.9 %), massage (12.9 %), yoga (11.8 %), aromatherapy (9.4 %), chiropractic and proposing therapy (9.4 %), and acupuncture (8.2 %). In addition to their medications, B. Colombo, D. Dalla Libera, M.A. Volonte`, F. Spagnolo, employed patients were likely to use meditation (33 %), stress man- G. Dalla Costa, V. Martinelli, G. Comi agement (33 %), prayer/spirituality (29 %), and medical marijuana INSPE, Scientific Institute San Raffaele (Milan, IT) (24 %) for relief of seizures. Self-identified non-epileptic seizure patients made up only 7 % of respondents and were equally likely to Objectives: Migralepsy is a rare entity included among the compli- use medical marijuana (33 %), meditation (33 %), massage (33 %), cations of migraine according to IHS criteria. By definition it is a prayer/spirituality (33 %), stress management (33 %), and vitamins migraine triggered-seizure that must fulfil two diagnostic criteria: (33 %), to treat their events. (a) migraine fulfilling the criteria for 1.2 migraine with aura and (b) a

123 S16 J Neurol (2012) 259 (Suppl 1):S1–S236 seizure fulfilling the diagnostic criteria for one type of epileptic attack heterozygous for N370S (six cases), D409H (six cases), D380V (one that occurs within one hour of a migraine aura. case), E388K (one case) and L444P (one case) GBA mutations, were Most of the so far reported cases have been criticized by several enrolled in this study. Twenty PD patients without GBA mutations authors particularly because of inadequate migraine-epilepsy (mean age 63 years, mean age at onset 56 years, median HY stage sequence. Revision of diagnostic terminology is still under debate. score 3.0) and 16 healthy controls (mean age 64 years) were also We report a case with a definite diagnosis of migralepsy according to studied. DTI scans were obtained from all subjects. Tract-based IHS criteria, confirming the real existence of this nosologic entity as a spatial statistics was used to perform a brain voxel-wise analysis of true migraine complication. mean diffusivity (MD) and fractional anisotropy (FA). Methods and Results: single case-report of a 43-years old, right- Results: Compared to controls, GBA mutation PD carriers showed handed woman. She was born with a normal delivery and had normal an increased MD of the genu of the corpus callosum and a decreased developmental milestones. At age 9 years she developed migraine with FA of the corpus callosum, cingulum, external capsule, anterior tha- visual and sensitive aura. Aura consisted of flickering flashing lights, lamic radiations, bilaterally, and right superior longitudinal fasciculus developing gradually in 15 min with a total duration of 45 min, followed (p\0.05, Family-wise error corrected). PD patients without GBA by sensitive symptoms (paresthesia of hand and face) and headache with mutations did not show significant DT MRI abnormalities when migraine features (frequency of 1 attack/month). In September 2011 she compared with healthy controls. had a typical visual aura lasted about 15 min, then she lost conscious- Conclusions: PD patients carrying GBA mutations show WM ness, felt to the ground and had a generalised tonic seizure. This lasted abnormalities involving the interhemispheric, limbic and associations about 5 min, after which she remained unresponsive and confuse until tracts. Future research will clarify whether WM damage in these the admission at the Hospital. EEG demonstrated epileptiform dis- patients may have an impact on the clinical phenotype, in particular charges in right temporal hemisphere. Brain CT scan was normal. The on the development of cognitive impairment. event was followed by a severe migraine attack, localised in left parietal and temporal side. Physical and neurologic examinations were normal. She underwent brain MRI (normal), basal EEG and sleep-deprived EEG (normalization of previous epileptiform features, residual theta slowing O205 over the left hemisphere). She was discharged with a diagnosis of mi- Diffusion tensor imaging contributes to differentiate gralepsy and therapy with Topiramate 100 mg/day. In a subsequent Richardson’s syndrome from progressive supranuclear follow-up visit she reported a cessation of migraine with aura attacks and no further seizures. Her last EEG was normal. palsy-parkinsonism Conclusion: Our case of defined migralepsy support this nosologic F. Agosta, M. Pievani, M. Svetel, M. Jecmenica Lukic, M. entity as a migraine with aura complication. Therapeutical approach Copetti, A. Tomic, A. Scarale, G. Longoni, G. Comi, V.S. with Topiramate was able both to reduce the frequency of migraine Kostic, M. Filippi and stop seizures. Further studies are required to consider Topiramate Vita-Salute San Raffaele University (Milan, IT); University of as a specific pharmacological approach for patients with migralepsy. Belgrade (Belgrade, RS); IRCCS Casa Sollievo della Sofferenza (San Giovanni Rotondo, IT) Objective: Abnormal diffusion tensor imaging (DTI) measures of the ______superior cerebellar peduncles were reported in patients with Rich- Oral session 3 ardson’s syndrome (PSP-RS). A few studies showed that PSP-RS patients had DTI alterations also in the corpus callosum, internal capsulae, and long-range white matter (WM) tracts. However, most of Movement disorders I the previous studies did not include the atypical clinical presentations of PSP. The aims of this study were to investigate the regional distribution of WM damage in patients with PSP-RS and progressive O204 supranuclear palsy-parkinsonism (PSP-P) using DTI, and quantify the White-matter damage in Parkinson’s disease patients DTI classificatory ability in diagnosing PSP syndromes, when used in combination with infratentorial volumetry. with glucocerebrosidase gene mutations: a study using Methods: In 37 PSP (21 PSP-RS, 16 PSP-P) and 42 controls, tract- diffusion tensor imaging based spatial statistics was applied. DTI metrics were derived from L. Sarro, F. Agosta, K. Davidovic, N. Kresojevic, M. Svetel, supratentorial, thalamic, and infratentorial tracts. Brain atrophy was I. Stankovic, G. Comi, V.S. Kostic, M. Filippi investigated using voxel-based morphometry. The MR parkinsonism index (MRPI), a combined conventional MRI measurement taking Vita-Salute San Raffaele University (Milan, IT); University of into account the midbrain and pons areas and the SCP and middle Belgrade (Belgrade, RS) cerebellar peduncle widths, was calculated. Objective: Mutations in the gene encoding glucocerebrosidase (GBA) Results: In PSP, grey matter (GM) atrophy involved fronto-tem- represent a significant risk factor for the development of Parkinson’s poral lobes and basal ganglia, and was greater in PSP-RS than PSP-P. disease (PD) and other Lewy body disorders. The mechanisms under- PSP-RS had a more severe and distributed WM loss, including the lying the association between GBA mutations and PD are still not known. midbrain, SCP, and prefrontal and motor/premotor regions. All PSP GBA mutation carriers with PD frequently have an earlier age of onset harboured diffusivity abnormalities in the corpus callosum, fronto- and increased likelihood to present cognitive symptoms compared with parietal and fronto-temporo-occipital tracts. Infratentorial WM and non-carriers. Diffusion tensor imaging (DTI) allows an in vivo assess- thalamic radiations were severely affected in PSP-RS and relatively ment of WM damage. This study investigated brain white matter (WM) spared in PSP-P. When MRPI and DTI measures were combined, the damage in patients with PD carrying GBA gene mutations. discriminatory power increased from 0.92 to 0.98 for PSP-RS vs. Methods: Among 360 PD patients screened for mutations of the controls, from 0.70 to 0.82 for PSP-P vs. controls, and from 0.77 to GBA gene, 19 (5.3 %) heterozygous mutation carriers were identified. 0.84 for PSP-RS vs. PSP-P. Fifteen of them (mean age 64 years, mean age at onset 57 years, Conclusions: Distinct patterns of GM and WM alterations occur in median Hoehn and Yahr [HY] stage score 3.0), found to be PSP-RS and PSP-P. Adding DTI measures to MRPI improves the

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S17 diagnostic accuracy in differentiating each PSP syndrome from pathophysiology remains uncertain, there is support for the hypothesis healthy individuals and each other. that it is a functional movement disorder (FMD). Diagnosis and differentiation from other causes of (fixed) postures is recognised to be difficult, and here we present preliminary data exploring the possible utility of EMG and reaction time measurements in diagnosis. O206 Objective: To compare the pattern of voluntary muscle contraction A loud auditory stimulus overcomes voluntary in the affected and normal limbs of patients with fixed dystonia using movement limitation in cervical dystonia surface EMG. T. Serranova´, M.J. Marti, R. Modreanu, F. Valldeoriola, Methods: We prospectively recruited patients with a clinical diagnosis of fixed dystonia. Muscle activity was recorded using T. Sieger, R. Jech, E. Ruzicka, J. Valls-Sole´ sEMG in agonist and antagonist muscles of dystonic movement in the Charles University (Prague, CZ); Hospital Clıńic (Barcelona, ES) affected and normal limbs. We used a simple reaction time paradigm Objectives: Dystonia is characterized by defective inhibition of with auditory ’preparation’ and ’go’ signal. The maximum peak to unwanted muscle activity as part of an abnormal programming peak amplitude, area under the rectified curve and reaction time (RT) of motor actions. In simple reaction time tasks, subjects are able to were measured and compared between the two limbs. prepare their motor programmes well in advance of their execution. In Results: Seven female participants with a mean age of such a state of preparation, motor programmes can be released faster 42.17(SD=13.32) years were included. The area under the rectified if a startling auditory stimulus (SAS) is delivered at the time of the EMG in the affected limb was significantly lesser [mean=246.50 mvs imperative signal (IS). Our aim was to investigate whether such form SD=183.70] than the normal limb [mean=619.68mvs SD=381.37 of preparation was normal or not in patients with cervical dystonia (p=0.03)]. Mean RT of the affected side [mean 186.7 ms (SD=128)] (CD). and normal limb [mean= 210.3 ms (SD=95)] did not differ signifi- Methods: We examined 16 CD patients (mean age 47.1 (22-66) cantly (p=0.27). Both were prolonged and more variable compared years, TWSTRS 31 (15-56)) and 15 controls (46.3 (24-66) years). with historical data from healthy subjects and patients with primary Subjects were asked to perform a neck rotational movement (RM) to dystonia. There was no significant difference in the maximum peak to either side as quick as possible immediately after the IS perception (a peak amplitudes of the affected limb [1.29±0.05 mv] and normal low intensity electric stimulus to the II finger). In randomly interlimb [2.31±0.06 mv (p=0.18)]. spersed test trials (25 %) a 130 dB SAS was delivered simultaneously Conclusion: Motor recruitment seems to be impaired in the fixed with the IS. RMs were recorded in horizontal plane with a high speed dystonic limb. There was a prolonged reaction time on the affected video camera (2.38 ms per frame) in synchronization with the IS. The and unaffected sides compared to values reported in historical RM kinematic-parameters (latency, velocity, duration and amplitude) cohorts of health subjects and primary dystonia. This is compatible and the range of RM were analyzed using video-editing software and with a difficulty for patients with FD in producing voluntary screen protractor. Patients were asked to rate the difficulty of their movement in an explicit RT setting, comparable perhaps with the RMs in a numerical rating scale. difficulties that patients with other FMD have with production of Results: The CD group differed from the controls in all kine- movement when explicitly asked to do so, compared with more matics parameters (MANOVA, p\0.001). RMs of CD patients had normal performance when movement is accessed in an implicit lower velocity (ANOVA, p\0.05) and amplitude (p\0.001), espe- manner. We are currently extending this study to include patients cially when rotating towards the direction of dystonia, while they with organic dystonia to further assess the clinical usefulness of this had a longer duration (p\0.05) and restricted range of RM (p\ procedure. 0.001) mainly when rotating against the direction of dystonia. In the test trials, the SAS improved all RM measures in both groups (p\0.001). For RM duration, this effect was larger in CD than in controls (p\0.01). In addition, patients were more likely to reach O208 beyond their baseline maximal range of RM than controls (chi2, Dopamine D2 receptor gene polymorphisms in Wilson’s p\0.001) and rated their performance better (t-test, p\0.01) in trials disease: impact on clinical presentation with SAS. A. Czlonkowska, T. Litwin, G. Gromadzka, Conclusions: Patients with CD are able to effectively prepare their subcortical motor structures for task execution. SAS activation of J. Samochowiec, A. Grzywacz such structures improved the kinematic parameters and the subjective Institute of Psychiatry and Neurology (Warsaw, PL); Pomeranian perception of motor performance. Our results may be relevant for Medical University, Poland (Szczecin, PL) better understanding the pathophysiology of dystonia and might have Objectives: Dopamine receptor D2 (DRD2) polymorphisms are pro- potential clinical applicability. posed to be important factors in the presentation of symptoms in the The project was supported by the ENS and by the grant IGA MZ movement disorders. The aim of the present work was to investigate ČR NT12282-5/2011. the possible association between DRD2 gene polymorphisms and clinical manifestation of Wilson’s disease (WD. Methods: We analyzed data from 97 symptomatic WD patients, O207 investigating the ANKK TaqIA (rs1800497), DRD2 PROM -141C Ins/Del (rs1799732), and DRD2 Ex8 (rs12364283) polymor- Impaired initiation of voluntary contraction phisms. We assessed the polymorphisms’ impact on the phenotypic on a reaction time task may support the clinical presentation of WD in all patients, as well as the effect of WD diagnosis in fixed dystonia genotype. A. Batla, P. Kassavetis, I. Parees, K. Bhatia, M.J. Edwards Results: ANNK TaqIA A1 allele carriers presented earlier onset of WD neuropsychiatric symptoms by about 4 years compared with non- UCL (London, UK) A1 allele carriers (25.0 vs. 29.0 years; p\0.098). Additionally, -141C Introduction: Fixed dystonia (FD) is a disabling, often devastating Ins/Del deletion (Del+) allele carriers tended to present earlier onset condition that typically affects young women. Although its of WD neuropsychiatric symptoms compared with patients without

123 S18 J Neurol (2012) 259 (Suppl 1):S1–S236 this allele (22.7 vs. 28.4 years; p\0.069). The effect of the -141C Ins/ Oral session 4 Del polymorphism was more pronounced in adenosine triphosphatase 7B gene (ATP7B) p.H1069Q homozygous patients, where Del+ allele carriers presented earlier onset of WD symptoms by 9 years (20.1 vs. Neuro-ophthalmology 29.4 years; p\0.019) and neuropsychiatric symptoms by about 13 years earlier (18.3 vs. 31.6 years; p\0.007). DRD2 gene polymorphisms had no impact on predominant hepatic or neuropsychiatric O210 WD presentation. Conclusions: Changes in dopamine receptor density due to Differentiation of cortical processing of visual stimuli genetic variation in DRD2 gene may produce an earlier clinical in patients with phobic postural vertigo and healthy presentation of neuropsychiatric WD signs in the course of dopa- controls minergic system impairment due to copper accumulation in the R. Feuerecker, R. Schniepp, T. Stephan, M. Dieterich brain. Großhadern University Hospital (Munich, DE) Objectives: Phobic postural vertigo (PPV) is one of the most common diagnoses (16%) in specialized centres for dizziness. Most of the O209 patients describe a pronounced sensitivity for visual stimuli like A breath test for personalising carbidopa therapy waves or moving objects which can trigger dizziness in those patients. In fMRI studies with visual stimulation, healthy controls (HC) show in Parkinson’s disease brain activations in visual cortical network areas like the occipital A. Modak, R. Durso, E. Josephs, D. Rosen cortex and in motion sensitive areas like MT/MST. Otherwise, there Cambridge Isotope Laboratories Inc (Andover, US); VA Healthcare are deactivations in the other sensory systems like Insula, the medial/ System (Boston, US); Physical Sciences Inc (Andover, US) superior temporal gyrus, and in the postcentral gyrus in terms of a reciprocal inhibition. Objective: To examine a dose response curve with respect to carbi- Methods: Until now, 7 patients with PPV and 6 sex- and age- dopa using exhaled 13CO2 as a tool to measure optimal inhibition of matched HC took part in an fMRI-study (GE, 3 Tesla) using hori- peripheral LD decarboxylation in PD patients after administrating zontal (right and left) and rotational (clockwise, counter clockwise) 4 varying doses of carbidopa with 200 mg of stable isotope labeled moving dots in order to cause optokinetic nystagmus (OKN). The LD-1-13C. stimuli were demonstrated in a pseudo randomized order. The par- Background: The primary pathology of Parkinson’s disease (PD) ticipants were urged to press a button with their right index-finger is destruction of cells within the substantia nigra of brain, which after the moving dots have stopped and their subjective feeling that results in a loss of striatal dopamine (DA)1. Pharmacologic therapy is the dots are moving on was over. designed to replace diminished levels of brain DA within the striatum Results: The study is still in progress. We want to investigate by giving levodopa (LD), the immediate precursor of DA. Sinemet a whether there’s a difference in the cortical activation-deactivation combination of Levodopa and Carbidopa is the treatment of choice pattern of visual stimuli in patients with PPV and HC. for PD patients. However, variable interindividual dopa decarboxyl- Conclusion: A different activation-deactivation pattern would lead ase (DDC) activity makes it difficult to optimize the dose of us to the assumption that patients with PPV have a different cortical Carbidopa a DDC inhibitor to prevent the peripheral conversion of processing of visual stimuli which yields to an over—interpretation of Levodopa to dopamine. visual stimuli and thus causes dizziness. A different processing of Methods: A single center feasibility study was carried out at sensory stimuli in patients with PPV would be an explanation for the VA Healthcare system in Boston recruiting patients 5 PD patients described dizziness and could be named as visual evoked vertigo. already on LD/CD and 1 treatment naı¨ve PD patient using stable isotope labeled LD-1-13C as a substrate for a non invasive breath test for evaluating each patient’s DDC enzyme activity using varying doses of carbidopa. Each patient received 200 mg LD- 13C at each visit and were blinded to receive one of the Carbidopa O211 doses from 0, 25, 50, 100 and 200 mg. The metabolite 13CO2 in breath was measured using a commercially available IR spec- Association of retinal nerve fibre and ganglion cell layer trometer for evaluating DDC enzyme activity and plasma measures with grey- and white-matter atrophy metabolite levels for LD-13C and HVA were measured at multi- in multiple sclerosis ple time points for 4 h. H. Zimmermann, A. Freing, T. Oberwahrenbrock, Results: Homovanillic acid in plasma and 13CO2 in breath are degradation products of LD, We found a good direct correlation of G. Gaede, F. Kaufhold, S. Schippling, J. Wuerfel, J. Doerr, the 13CO2 DOB AUC with serum HVA AUC for both 0-120 min F. Paul, A.U. Brandt and 0-240 min following oral dose of LD-1-13C for all 5 doses of NeuroCure Clinical Research Center, Charite´ - University Medicine CD (r2 = 0.9378). With increasing inhibition of DDC enzyme Berlin (Berlin, DE); Department of Neuroimmunology and Clinical activity with CD we observed an increase in the plasma concen- Multiple Sclerosis Research, Neurology Clinic, University Medical tration of LD. We found an inverse correlation of the 13CO2 DOB Center Zurich (Zurich, CH); Institute of Neuroradiology, University AUC with serum LD-13C AUC. The optimal dose of CD for max- Lu¨beck, (Lu¨beck, DE) imal suppression of DDC enzyme activity can, therefore, be Objective: Retinal nerve fibre layer (RNFL) thickness is related to determined for each individual from the breath curves of 13CO2 brain parenchymal fraction in multiple sclerosis (MS). However, generation from the LD-BT. existing data are based on non-normalised grey and white matter Conclusions: The LD-BT can be a useful non invasive diagnostic volumes and time-domain optical coherence tomography (OCT). This tool for evaluation of DDC enzyme activity using 13CO2 as a bio- study investigates the relationship between RNFL and retinal gan- marker thereby personalizing Carbidopa dose. glion cell layer thinning as determined by spectral-domain OCT and SBIR phase I grant

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S19 normalised grey and white matter volumes as determined by magnetic Conclusions: In DOA patients carrying OPA1 mutations, struc- resonance imaging (MRI) in MS patients. tural abnormalities are present in the central nervous system. Such a Methods: 123 eyes of 63 patients with relapsing-remitting MS damage is not limited to the anterior and posterior visual pathways, were included in a cross-sectional, prospective study. Retinal peri- possibly due to trans-synaptic degeneration phenomena, but also papillary and macular volume scans were obtained using spectral involves the auditory and the motor cortices, probably due to local domain OCT. Total brain, grey and white matter volumes were mitochondrial dysfunction. assessed using 1.5T MRI with FSL SIENAX. Associations between MRI and OCT were analysed using generalized estimating equations. Results: Peripapillary RNFL thickness (regression coefficient (B) = 0.053, standard error (SE) = 0.015, p \ 0.001) and macular O213 volume (B = 0.003, SE = 0.001, p \ 0.001) are predicted by brain Post-vaccination optic neuritis in postpartum caucasian volume. Peripapillary RNFL thickness is significantly associated with female patients white matter volume both in eyes with (B = 0.140, SE = 0.042, S. Iyadurai, P. Anprasertporn p = 0.001) or without (B = 0.093, SE = 0.027, p = 0.001) history Saint Louis University (St. Louis, US) of optic neuritis. Only in eyes without history of optic neuritis RNFL thickness is significantly predicted by grey matter volume Objective: To report a series of 2 postpartum female patients with (B = 0.092, SE = 0.029, p = 0.001). In eyes with history of optic bilateral Optic Neuritis (ON) after receiving routine vaccines. neuritis the association is lost (p = 0.170). Method: Case series. Conclusions: This study supports the hypothesis that changes in Background: Patients with ON usually complain of visual loss, RNFL in MS patients are associated with changes in brain paren- and pain with eye movements. While ON is usually associated chyma, mainly in the white matter. A previous optic neuritis is an with multiple sclerosis, several other etiologies may also underlie important factor for the dispartment of data between retinal measures ON. However, ON in the setting of multiple sclerosis is usually and grey matter. Data on retinal ganglion cell layer will be included unilateral. Bilateral ON (occurring at the same time), is rather by date of presentation. unusual, but can be seen in neurosarcoidosis, neuroborreliosis, This study was supported by DFG grant Exc. 257, BMWi grant tuberculosis, neuromyelitis optica, neurosyphilis, optic gliomas, ZIM KF2286101FO9 and Teva Pharmaceuticals. neurofibramatosis, and other inflammatory disorders. Here we describe 2 post-partum females with bilateral ON following routine vaccinations. Results: Patient 1: A 40-year old caucasian woman Gravida 7 para 7, received DTaP vaccine, 1 day after delivery. 24 days later she O212 complained of bilateral visual loss and pain upon eye movement. White- and grey-matter damage extends beyond Neurological exam revealed visual perception only to hand motion the visual pathways in patients with autosomal (OD) and to counting fingers at 2 feet (OS), and RAPD on the right. Fundoscopic exam revealed bilateral disc edema without hemorrhage dominant optic atrophy and OPA1 mutations or exudates. Rest of the neurological examination was normal. Lab- R. Messina, M.A. Rocca, S. Bianchi-Marzoli, J. Milesi, oratory and CSF evaluations were normal. MRI of the orbits showed M. Petrolini, A. Falini, G. Comi, M. Filippi gadolinium enhancement of bilateral optic nerves. The MRI of brain San Raffaele Scientific Institute, Vita-Salute San Raffaele University and cervico-thoraco-lumbar spines was normal. Treatment with (Milan, IT) intravenous methylprednisolone (IVMP) 1 gram/day for 5 days significant improvement in visual acuity was noted. Patient 2: A 24-year Objective: Patients with autosomal dominant optic atrophy (DOA) old caucasian woman Gravida 1 para 1, received Influenza vaccine, 2 typically present a slowly progressive, painless, bilateral visual loss, days after delivery. 14 days later she complained of bilateral visual in the first two decades of life. Extra-ocular neurological complica- loss and pain upon eye movement. Neurological examination, labo- tions affect up to 20 % of all mutational carriers and may include ratory, CSF, and MRI evaluations showed results similar to that of sensorineural deafness, ataxia, myopathy, peripheral neuropathy, patient 1. Treatment with IVMP, resulted in significant improvement, external ophthalmoplegia, spastic paraparesis and a multiple sclero- as noted with patient 1. sis-like illness. Aim of this study was to assess the patterns of regional Conclusion: Here we describe 2 cases of bilateral ON in post- atrophy in the brain gray matter (GM) and white matter (WM) in partum caucasian female patients who received routine vaccines. patients affected by DOA linked to OPA1 gene mutations, using Post-partum presentation of neuromyelitis optica has been reported. A voxel-based morphometry (VBM). rare case of post-vaccination bilateral ON has been reported with Methods: We studied eight patients with DOA and 20 healthy Rabies vaccine. To our knowledge, this is the first report of bilateral controls. A complete neuro-ophthalmologic examination, including ON associated with DTaP and Influenza vaccines. While the exact average retinal nerve fiber layer thickness (RNFL) and ganglion cell etiology is unknown, we favor the concept of an immune-mediated complex (GCC) measurements, was obtained in all patients. VBM process underlying this process. was performed on the 3D T1-weighted images using SPM8 and DARTEL. Results: Average GCC and RNFL thicknesses were decreased significantly in DOA patients. Focal lesions in the brain WM were O214 identified in two patients. Optic nerve and chiasm atrophy were Post-traumatic ophthalmic artery pseudoaneurysm detected in four patients. Compared with controls, DOA patients showed a significant WM loss in the optic tracts. They also had GM presenting as epistaxis: case report and review loss in several regions located in the occipital lobes (including the of the literature lingual gyrus and superior occipital gyrus), the temporal lobes P. Dolati, W. Morrish, J. Wong (including the auditory cortex), and the left precentral gyrus. University of Calgary (Calgary, CA)

123 S20 J Neurol (2012) 259 (Suppl 1):S1–S236

Background: Traumatic brain aneurysms represent about 1 % of the Oral session 5 brain aneurysms. Most frequently, these aneurysms are associated with skull base fractures. Traumatic pseudoaneurysms (PsA) of the ophthalmic artery (OphA) are extremely rare after severe head injury. Multiple sclerosis II We report an unusual example presenting as persistent post traumatic epistaxis, with review of the literature. Case report: The patient was a 48 year old female presented in a O216 comatose state to the emergency room after 7 meter fall. Her right eye had proptosis and an unreactive 6 mm dilated pupil. Brain CT Endovascular treatment of CCSVI in patients scan revealed contusions of the fronto-temporal lobes and fracture with multiple sclerosis: clinical outcome of an italian of the anterior cranial base and tri-wall fracture of the orbits. She cohort of 251 cases had persistent epistaxis. Cerebral digital subtraction angiography A. Ghezzi, P. Annovazzi, M.P. Amato, R. Balgera, (DSA)showeda6x3mmPsAarisingfromtheintraorbitalseg- ment of the right OphA. Attempted endovascular embolization R. Bergamaschi, A. Bianchi, A. Bosco, E. Capello, resulted in unsuccessful access into the PsA but unexpected ther- M. Capobianco, G. Coarelli, M. De Riz, N. De Rossi, apeutic occlusion of the proximal OphA and in turn the PsA. M.T. Ferro, L. La Mantia, G. Lus, S. Malucchi, L. Moiola, Cerebral DSA 10 days later confirmed persistent occlusion of the B. Palmeri, F. Patti, L. Provinciali, A. Protti, M. Rodegher, aneurysm. Extensive review of the medical literature including Medline, Pub Med, and Google Scholar and major neurosurgery G. Salemi, P. Sola, M. Troiano, G. Comi and the MS Study and trauma journals yielded only 9 previously reported post trau- Group of the Italian Society of Neurology matic PsAs of the OphA, which are reviewed and summarized in Background and objectives Although the relationship between MS table 1. and CCSVI is not defined and there is no proven demonstration that Conclusion: Posttraumatic pseudoaneurysms of the ophthalmic endovascular treatment of CCSVI is effective to improve MS evo- artery are very rare; however, it should be suspected in the setting of lution, many patients decide to undergo such a treatment. anterior skull base or orbital wall fractures and persistent or delayed The Italian Multiple Sclerosis Study Group-Italian Society of epistaxis. Neurology has promoted a multicentric study to collect clinical information on MS subjects who have spontaneously decided to be submitted to endovascular treatment. Results. 19 Italian MS centres have participated to this study. A O215 form has been standardized to collect complete demographic, clinical, Idiopathic intracranial hypertension is characterised MRI and safety data. All consecutive MS patients who have declared (spontaneously or asked by physicians) to have been submitted to by impaired cerebrovascular autoregulation endovascular treatment of CCSVI have been included in the database. J. A. Sharpe, B. Hui, J. Poublanc, A. Chmielewski, Up to now complete data are available of 251 patients (mean age J. Fierstra, D. M. Mandell, D. J. Mikulis 43,7 ± 10 years), 43 % with RR-MS, 57 % with SP/PP-SM. The mean University of Toronto (Toronto, CA) EDSS score before the intervention was 5,0 ± 2.0. After a mean follow up of 23,6 ± 20,1 weeks, the mean EDSS was 5,15 ± 2.0 and 51 patients Objective: To analyse cerebrovascular reactivity (CVR) in idiopathic developed a relapse. MRI data are available of 91 patients, after a follow intracranial hypertension (IIH) before and during treatment with up of 21 ± 19 weeks, showing the appearance of new T2 lesions or acetazolamide. gadolinium enhancing lesions in 27 patients. A subjective clinical Background: IIH is confirmed by raised intracranial pressure improvement was reported by 52 % of patients, 33 % reported to be (ICP), detected by high opening cerebrospinal fluid (CSF) pressure, unchanged and 15 % to be worsened. In subjectively improved patients normal CSF content, and absence of mass lesion or other cause on the mean pre-intervention EDSS was 4,8 ± 2.0; it was 4,9 ± 2.0 after MRI/MRV. Its pathophysiology is unknown. Impaired cerebrovas- the surgical procedure. Serious adverse events have been observed in 6 cular autoregulation might be the primary trigger. Measuring the cases: inguinal haematoma in 3, jugular venous thrombosis in 3. blood oxygen level-dependent (BOLD) MRI response during hyper- Conclusions. The results of our study, with the known limitation of capnea quantifies cerebrovascular autoregulatory reserve and may be the observational design, do not show any clear beneficial effect of a useful diagnostic test in IIH. endovascular treatment for CCSVI in MS. The subjective positive Methods: Five patients were studied. Three patients who pre- effects reported by about 50 % of patients can be largely due to the sented with new onset IIH, confirmed by papilledema, high opening high expectation of patients for an intervention called ‘‘liberation’’. pressure, benign CSF content, and normal MRI/MRV, underwent The intervention is not totally free from serious adverse events, that MRI CVR mapping by BOLD in response to transient hypercapnia. occurred in 6/251 cases. Two other patients with IIH improving on acetazolamide were scanned using the same protocol. CVR maps were individually compared to a group of 29 normal control subjects. Results: In patients with new onset, untreated IIH, CVR was O217 globally reduced throughout the parenchyma, with greatest reductions MRI endpoints and relapse rates in the double-blind, in the lenticular nuclei bilaterally. Six days following initiation of placebo-controlled, Phase 2, 26-week DreaMS trial acetazolamide treatment in one patient, CVR remained globally impaired. After 7 weeks of acetazolamide in a different patient, there of a selective S1P receptor agonist ONO 4641 in patients was resolution of symptoms and normalization of CVR. with relapsing-remitting multiple sclerosis Conclusions: Impaired cerebrovascular autoregulation is a feature K.W. Selmaj, T.L. Vollmer, A. Bar-Or, F. Zipp, B.R. Due of IIH. MRI measurement of CVR may be a method of identifying on behalf of the DREAMS Study Group patients with IIH and monitoring their response to therapy. Whether the reduction in CVR reflects a primary failure of autoregulation in Objectives: The Drug Research EvaluAtion for Multiple Sclerosis IIH or is the result of elevated ICP is uncertain. (DreaMS; NCT01081782) study investigated the efficacy and safety

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S21 of ONO-4641, a potent and selective sphingosine-1-phosphate Methods: Patients treated with fingolimod (0.5mg/1.25mg) in the receptor -1 and -5 agonist, following multiple oral doses in patients Core phase (M0-12) continued the same dose (continuous-group) in with Relapsing Remitting Multiple Sclerosis (RRMS). the Extension phase, while those on interferon beta-1a (IFN b-1a) Methods: 407 RRMS patients (aged 18-55 years; Expanded Dis- were re-randomised (1:1) to fingolimod (switch group; IFN-0.5mg/ ability Status Scale score \= 5.5, and [= 2 relapses during the 2 IFN-1.25mg). This dose assignment was double-blinded until the lock previous years or [= 1 within the previous year or [= 1 Gd- of the Core phase and was dose-blinded until implementation of an enhancing lesion within 3 months) were randomized (1:1:1:1) to amendment to drop the 1.25mg dose. All patients then received open- ONO-4641 at a dose of 0.05, 0.10, or 0.15 mg or placebo once daily label fingolimod 0.5mg until the end of study (EOS [up to 4.5 yrs]). for 26 weeks. Primary endpoint was cumulative number of T1- Efficacy parameters included annualised relapse rate (ARR), dis- weighted gadolinium (Gd)-enhancing lesions on MRI, performed 4 ability progression and MRI outcomes. weekly from Weeks 10- 26; secondary endpoints included the Results: Of the 1292 patients enrolled in the Core phase, 1030 cumulative number of new/enlarged T2 lesions and annualized (79.7 %) entered the Extension and 772 (75.2 %) patients completed relapse rate (ARR). the study. The mean (median) duration of exposure was 1217 (1305) Results: The cumulative number of Gd-enhancing lesions from and 1169 (1282) days for the 0.5mg and 1.25mg continuous-groups Week 10 to 26 was significantly reduced in all three active groups and 810 (921) and 787 (916) days for the IFN-0.5mg and IFN-1.25mg vs placebo, with a relative reduction in mean cumulative lesions of switch groups, respectively. 82 %, 92 %, and 77 % at 0.05, 0.10, and 0.15 mg, respectively The low aggregate ARR observed at the end of core phase, M0- (mean±SD: 1.5±3.8, 0.7±1.5, 1.9±8.5 vs. 8.3±11.5 in placebo, M12 (0.5mg: 0.16; 1.25mg: 0.20) vs. IFN b-1a (0.33) was main- p\0.0001 for all groups). The cumulative number of new or tained from M12 till EOS in continuous-groups (0.5mg: 0.16; enlarged T2 lesions was significantly reduced with ONO-4641 1.25mg: 0.16) and reduced in the switch group (0.20 from 0.33). At versus placebo, with reductions of 73 %, 82 %, 71 % with 0.05, EOS, the percentage of patients free of confirmed MS relapse was 0.10, and 0.15 mg doses, respectively (p\0.001 for all groups). ARR higher in continuous-groups (0.5mg: 58.6 %; 1.25mg: 61.1 %) vs. was 0.56 with placebo, 0.42 with 0.05 mg (p=0.5146), 0.17 with switch group (52.5 %). Both continuous-groups demonstrated low 0.10 mg (p=0.0069), 0.34 with 0.15 mg (p=0.2991); relative MRI lesion activity and reduced brain atrophy rate throughout the reduction vs placebo: 25 %, 70 %, and 39 %, respectively. Inci- study. The percentage of patients free of MRI disease activity (M12- dences of adverse events (AEs) appeared dose related. EOS) was comparable in all groups (Gd enhanced T1 lesions: Asymptomatic atrioventricular block and bradycardia occurred 77.4 % in switch group vs. 74.7 % [0.5mg] and 72.1 % [1.25mg]; transiently at treatment initiation and did not require ONO-4641 new/newly enlarged T2 lesions: 45.0 % in switch group vs. 42.0 % discontinuation. Lymphopenia was more common in the ONO-4641- [0.5mg] and 36.9 % [1.25mg]) as was the rate of brain volume loss treated groups; grade 4 lymphopenia occurred in 4 patients (4 %) at (-1.01 % [0.5mg], -1.06 % [1.25mg] and -0.96 % [switch group]). 0.15 mg and in 1 patient (1 %) at 0.10 mg. Infections were similar Patients in the switch group displayed a slowing of atrophy fol- with ONO-4641 and placebo, but the incidence of non-disseminated lowing the switch to fingolimod. The continuous and switch groups herpes was higher in the ONO-4641 0.05 and 0.1 mg groups. Most did not significantly differ with respect to disability progression at serious AEs were related to MS. EOS. Conclusion: Treatment with ONO-4641 conferred significantly Conclusions: The efficacy of fingolimod in reducing disease greater benefits over placebo in terms of cumulative numbers of Gd- activity and rate of brain volume loss was maintained over long-term enhancing lesions and new or enlarged T2 lesions at all three doses. In treatment (up to 4.5 yrs). Switching from IFN-b 1a to fingolimod led addition, a statistically significant reduction in ARR in the 0.10 mg to enhanced efficacy. group vs placebo was observed. ONO-4641 was well tolerated in The study was supported by Novartis Pharma AG, Basel, patients with RRMS. Switzerland. Study supported by Ono Pharmaceutical Co., Ltd. – Osaka, Japan.

O219 O218 Fingolimod significantly reduced brain volume loss Long-term efficacy data from the extension of the phase in patients with relapsing-remitting multiple sclerosis: III TRANSFORMS study of fingolimod 4-year data from FREEDOMS extension study versus interferon beta-1a in relapsing-remitting E. Radue, L. Kappos, P. O’Connor, C. Polman, multiple sclerosis: 4.5 year follow-up R. Hohlfeld, P. Calabresi, K. Selmaj, A. de Vera, N. Sfikas, B. Khatri, F. Barkhof, G. Comi, H. Hartung, L. Kappos, L. Zhang-Auberson, G. Francis X. Montalban, J. Pelletier, T. Stites, E. Kornyeyeva, University Hospital Basel (Basel, CH); St. Michael’s Hospital F. Holdbrook, P. von Rosenstiel, J. Cohen (Toronto, CA); VU University Medical Center (Amsterdam, NL); Regional MS Center, Center for Neurological Disorders (Milwaukee, Ludwig-Maximilians University of Munich (Munich, DE); Johns US); Vrije Universiteit Medical Centre (Amsterdam, NL); University Hopkins Multiple Sclerosis Center (Baltimore, US); Medical Vita e Salute (Milan, IT); Heinrich-Heine-University (Du¨sseldorf, Academy of Lodz (Lodz, PL); Novartis Pharma AG (Basel, CH); DE); University Hospital Basel (Basel, CH); Hospital Universitari Novartis Pharmaceuticals Corporation (East Hanover, US) Vall d’Hebron (Barcelona, ES); CHU Timone (Marseille, FR); Objectives: Brain atrophy, measured by magnetic resonance Novartis Pharmaceuticals Corporation (East Hanover, US); Novartis imaging (MRI), is considered one of the best methods for quan- Pharma AG (Basel, CH); Cleveland Clinic Foundation (Cleveland, tifying neurodegeneration and tissue integrity and has predictive US) value for future disability. We evaluated the effect of fingolimod Objective: To report long-term (up to 4.5 yrs) efficacy results from on the rate of brain volume loss in patients with relapsing-remitting the extension of the phase III, TRANSFORMS study of oral, MS. once-daily fingolimod in relapsing-remitting multiple sclerosis Methods: Patients on fingolimod (1.25 or 0.5mg/day) in the core (RRMS). phase continued the same regimen (continuous-fingolimod) in the

123 S22 J Neurol (2012) 259 (Suppl 1):S1–S236 extension phase while those on placebo (PBO) were re-randomised Methods: In REFLEX, patients were randomized to sc IFN beta- (1:1) to one of the two doses of fingolimod (PBO-fingolimod). The 1a, tiw or qw, or placebo, for 24 months or CDMS diagnosis. At percentage change in brain volume (PCBV) was obtained using the CDMS diagnosis, all patients switched to open-label sc IFN beta-1a Structural Image Evaluation of Normalized Atrophy (SIENA). 44 mcg tiw. At month 24 all patients were eligible for the extension PCBV was analysed between-groups (continuous-fingolimod and study. Initial placebo patients without CDMS were switched to sc IFN PBO-fingolimod) as well as within-group for M0-M24 and M24- beta-1a tiw (delayed treatment); those still receiving qw treatment M48. continued on this regimen until CDMS. Patients receiving tiw treat- Results: Of the 1272 patients enrolled in FREEDOMS, 920 ment also continued. Original blinding was maintained. Primary entered the extension phase of whom 773 (84 %) completed the endpoint: time to CDMS conversion up to month 36; secondary extension study. At M48, mean PCBV from core baseline was sig- endpoints included McDonald MS and annualised relapse rates nificantly less for both continuous-fingolimod groups (1.25mg: - (ARRs). 1.83 % [p=0.023]; 0.5mg: -1.76 % [p=0.016] vs. -2.43 % for the Results: 402/517 (77.8 %) patients entered the extension study. PBO-fingolimod group). Switching to fingolimod treatment from Integrated data from REFLEX and REFLEXION (delayed treatment, placebo in the extension phase (M24-M48) led to a significant n=171; qw, n=175; tiw, n=171) were analysed by original REFLEX reduction in mean PCBV of 0.515, p=0.008 (-1.42 % from M0-M24 treatment group. Month 36 cumulative probability of CDMS was: vs. -0.90 % from M24-M48 for PBO-fingolimod 0.5 mg). The delayed treatment, 41.3 %; IFN beta-1a qw, 27.6 % (p=0.006 vs reduction in the rate of brain volume loss was observed as early as the delayed treatment); IFN beta-1a tiw, 27.1 % (p=0.002 vs delayed first 6 months after fingolimod treatment. In continuously treated treatment; p=0.941 vs qw). Month 36 cumulative probability of patients, improvement in PCBV in the core phase was sustained in McDonald MS was: delayed treatment, 86.5 %; IFN beta-1a qw, extension for the 1.25mg and 0.5mg doses respectively (-1.01 % and - 79.1 % (p=0.009 vs delayed treatment); IFN beta-1a tiw, 66.8 % 0.98 % from M0-M24; -0.87 % and -0.78 % from M24-M48). In the (p\0.001 vs delayed treatment; p=0.024 vs qw). ARRs were: delayed extension phase there were no statistically significant differences in treatment, 0.19; IFN beta-1a qw, 0.11 (p=0.010 vs delayed treatment); PCBV between continuously treated patients and those switching IFN beta-1a tiw, 0.12 (p=0.021 vs delayed treatment; p=0.813 vs qw). from placebo for all measured time intervals. No new or unexpected drug reactions were reported. Conclusions: Continuous fingolimod treatment was associated Conclusion: Following a FCDE, early IFN beta-1a treatment (44 with sustained efficacy in terms of decreased PCBV and significantly mcg tiw or qw) significantly delayed CDMS compared with delayed less brain volume loss over 4 years compared to PBO-fingolimod treatment over 36 months. The effect on McDonald MS, but not on group. Patients switched from placebo to fingolimod experienced a CDMS, was significantly more pronounced in the tiw group than in significant and immediate reduction in the rate of brain atrophy, the qw group. comparable to that observed in the continuous-fingolimod treatment Study supported by Merck Serono S.A. – Geneva, Switzerland (a group during M24-M48. These data confirm that the benefit of fin- branch of Merck Serono SA, Coinsins, Switzerland, an affiliate of golimod on reducing brain atrophy as measured by MRI occurs early Merck KGaA, Darmstadt, Germany). and demonstrates persistence during long-term treatment. The study was supported by Novartis Pharma AG, Basel, Switzerland. O221 Deep rTMS with H-coil enhances improvement O220 of walking abilities in patients with progressive multiple Efficacy of two dosing frequencies of subcutaneous sclerosis undergoing rehabilitation: a randomised, interferon beta-1a on the risk of conversion from a first placebo-controlled, double-blind study demyelinating event to multiple sclerosis: 3-year results L. Leocani, A. Nuara, A. Formenti, P. Rossi, A. Zangen, of a phase III, double-blind, multicentre trial M. Comola, G. Comi (REFLEXION) Univ.Hosp. San Raffaele (Milan, IT); Ben Gurion University (Beer G. Comi, N. De Stefano, M. Freedman, F. Barkhof, Sheva, IL) C.H. Polman, B.M.J. Uitdehaag, E. Verdun di Cantogno, Objective: To investigate whether repeated sessions of transcranial L. Lehr, D. Issard, S. Haller, B. Hennessy, L. Kappos repetitive magnetic stimulation (rTMS) with H-coil could enhance the benefit of rehabilitation on walking abilities in patients with spasticity Ospedale San Raffaele (Milan, IT); University of Siena (Siena, IT); associated with multiple sclerosis (MS). The Ottawa Hospital (Ottawa, CA); VU University Medical Center Background: Impaired walking has a strong impact on disability (Amsterdam, NL); Merck Serono S.A., (Geneva, CH); Merck Serono associated with MS and its treatments options are limited. Preliminary S.A. (Geneva, CH); University Hospital Basel (Basel, CH) findings showed that repeated sessions of focal repetitive transcranial Objectives: Subcutaneous (sc) interferon (IFN) beta-1a, 44 mcg three stimulation improved spasticity associated with MS but no data are times weekly (tiw), is effective in patients with relapsing multiple available on the impact on walking ability. Recently, the development sclerosis (MS). The results of the double-blind, placebo-controlled of H-coils has been proved to allow reaching deeper brain regions as REFLEX study (NCT00404352) showed that initiation of treatment compared with focal stimulation. with sc IFN beta-1a, 44 tiw or once weekly (qw), at the time of a first Design/Methods: Twenty-three progressive MS patients with clinical demyelinating event (FCDE) delayed diagnosis of McDonald lower limb spasticity, undergoing inpatients rehabilitation, were MS (2005) and clinically definite MS (CDMS) over 24 months. Here randomized to receive real (11 pts) or sham (11 pts; one patient we report clinical data from the double-blind extension of REFLEX refused to participate after randomization) 10-min sessions of high- (REFLEXION; NCT00813709), which investigated whether sc IFN frequency rTMS for 3 weeks following their rehabilitation sessions. beta-1a treatment initiated immediately after the FCDE versus Primary outcome was percent change at the 10-meter walk test. delayed treatment delayed CDMS conversion up to 36 months after Secondary outcomes were: walking-endurance (6-min walking test), randomization in REFLEX. Modified Ashworth Scale (MAS) and Visual Analogue Scale (VAS)

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S23 for spasticity, Fatigue Severity Scale (FSS), EDSS, PASAT and Nine- 9 %), lamotrigine (n=3, 4 %), and levetiracetam (n=1, 1 %). Eight Hole Peg Test (9HPT). patients (12 %) received AED polytherapy. Nine patients (13 %) Results: At the end of treatment, both groups showed improve- needed hospitalisation due to recurrent seizures, although most of ment in all outcome parameters, although significant improvement in them were seizure-free after treatment. walking tests (10-mt-WT and 6-min-WT) was significant in the real Conclusions: Seizures in elderly patients were more common in rTMS group only. The latter group, compared with the sham group, those with cognitive impairment and brain atrophy. Epileptiform had significantly better improvement of the primary outcome (10-mt- discharges were less and slow activities were more frequent on EEG WT; p\0.05) and of 6-min-WT (p=0.002) and MAS score (p=0.037). compared with adolescents. Further studies are needed of non-con- No serious adverse effects were reported and no patient discontinued vulsive seizures. the study due to adverse effects. Conclusions: These findings demonstrate that deep brain stimulation with H-Coil increases the effects of rehabilitation in improving walking ability, in terms of both speed and endurance. The treatment O223 is safe and feasible. These encouraging results need validation with High-frequency oscillations in a cortical microdomain – phase-3 studies. a modelling study J. Pyrzowski, A. Zakrzewska, A. Ossowska, M. Sawicka, M. Sieminski ______Medical University of Gdansk (Gdansk, PL) Oral session 6 Objectives: Despite over a century of epilepsy research, the basic mechanisms of seizure generation are still poorly understood. High frequency oscillations (HFO) recorded from cortical microdomains Epilepsy II during interictal periods and at seizure onset have been proposed to be a highly specific electrophysiological marker of epileptic tissue. We present a biophysically realistic neuronal network model that gener- O222 ates spontaneous bursts of oscillations in the HFO band with a range Clinical characteristics of newly developed epileptic of realistic features. Methods: We simulate a network of 1000 cortical spiking neurons seizures in elderly Japanese with realistic electrophysiological features, random connectivity and T. Mitsueda-Ono, M. Hagiwara, M. Daifu, K. Kobayashi, distributed synaptic delays. The strength of individual synapses K. Watanabe, Y. Nakaya, Y. Miyazaki, M. Matsui evolves continuously through spike timing-dependent plasticity. We Otsu Red Cross Hospital (Otsu, JP); NHO Utano Hospital (Kyoto, explore the parameter dependence of stationary behavior of our model JP); Kyoto University Graduate School of Medicine (Kyoto, JP); Eisei with particular focus on the oscillatory profile of steady-state neuronal Clinic (Hachioji, JP) activity. Results: We demonstrate that, for an appropriate choice of Objectives: Elderly people aged 65 years or older frequently suffer parameters, the model generates spontaneous bursts of oscillations in from newly developed symptomatic seizures provoked by underlying the HFO band (80-200Hz). The mean durations of bursts and inter- diseases, such as cerebrovascular disorder or Alzheimer’s disease. burst intervals are similar to those observed experimentally. We show Their seizures often recur unless proper treatment is provided, and, that the intra-burst frequency is closely related to the average synaptic thus, may have different clinical characteristics compared with ado- delay which suggests that these oscillations arise from recurrent lescents. We aimed to clarify the clinical features of such newly excitatory feedback. Within selected parameter ranges we also developed seizures of elderly patients in Japan. observe infrequent spontaneous large-amplitude fluctuations in aver- Methods: Sixty-eight patients aged 65 years or older, who had age neuronal activity that suggestively resemble epileptic seizures. been admitted to our hospital due to seizure disorders from March These events are preceded by a gradual buildup of HFO suggesting 2008 to April 2011, were retrospectively reviewed. We examined that these dynamical phenomena may be interrelated. seizure types, past histories, neuroimaging studies, EEG findings, Conclusion: We present a mathematical network model capable of treatment outcomes, and other clinical information. reproducing some important characteristics of experimentally recor- Results: Of the total of 68 patients, men numbered more (40 ded HFO including their relationship to seizure-like events. Our work patients, 59 %) than women. On the other hand, in much older suggests a potential mechanism of HFO generation ready for exper- patients of 85 or older (n=14), women were predominant (n=9, 64 %). imental verification. Forty-seven patients (69 %) had their first seizure, and 21 (31 %) had recurrent seizures. The main comorbidities were advanced dementia (n=20, 29 %), cortical infarction (n=20, 29 %), and intracranial haemorrhage (n=10, 15 %). Only 2 patients (3 %) have had seizures O224 since their adolescence. Types of seizure semiology were unilateral tonic–clonic seizures with secondary generalisation (n=34, 50 %), Automatic onset localisation of rhythmic EEG generalised tonic–clonic seizures (n=27, 40 %), complex partial sei- patterns – A proof of concept zures (n=5, 7 %), and simple partial seizures (n=2, 3 %). Head MRI G. Gritsch, F. Fu¨rbass, H. Perko, Ch. Baumgartner, studies revealed marked brain atrophy, old cortical infarction (n=20, M. Hartmann, T. Kluge 29 % for each), and other chronic structural lesions (n=15, 21 %). AIT Austrian Institute of Technology GmbH (Vienna, AT); General Diffusion-weighted MRI indicated transient high-intensity areas in 4 Hospital Hietzing (Vienna, AT) patients (6 %). Nine patients (13 %) showed no particular abnormalities. In an EEG study, 23 patients (34 %) showed regional slow Objectives: Identification of the onset of epileptic activity is essential waves as a non-paroxysmal abnormality; however, only 8 patients in pre-surgical evaluation of epilepsy patients. Today, seizure detec- (12 %) showed spikes. They were medically treated with valproic tion systems are available to assist with the detection of seizures. acid (n=30, 44 %), carbamazepine (n=7, 10 %), phenytoin (n=6, However, the systems provide alarms with significant time delay from

123 S24 J Neurol (2012) 259 (Suppl 1):S1–S236 the true onset and cannot help identifying seizure onsets. Our aim is to Results: Our method was evaluated on uncut, unselected retro- localize the true onset of ictal rhythmic EEG patterns in time auto- spective data from 264 patients with 22,463 h of EEG including 623 matically by correcting the detection time of our seizure detection seizures of all types of epilepsy. The average sensitivity for all system EpiScan. This information might also improve the localization patients with recorded seizures (N=96) was 70 %, where half of the of the seizure onset zone by combining this approach with an patients had 100 % sensitivity (N=47) and only 12 patients had sen- appropriate source localization method. Furthermore, it may enable a sitivity of 0 % because of only minor or no visible EEG correlates in computer aided analyze of temporal seizure evolution. the seizure. For the subgroup of patients with temporal lobe epilepsy Methods: The approach is an extension of our automatic seizure (N=61) the average sensitivity was 84 %. The average false alarm rate detection system EpiScan. One of the information reported by Epi- for all patients (N=264) was 0.32 false alarms per hour (FA/h). Scan is the strength of rhythmic activity observed in the EEG signal. Conclusion: Our method proves its high sensitivity and robustness Since EpiScan is designed for a high specificity and low false alarm against detection artifacts on the huge EEG-database of the AIT rate, the system will report alarms only when the rhythmicity is sig- providing a reliable tool for online seizure detection. The improved nificantly high, leading to a delay of several seconds compared to the patient adaptation reacts at an early stage to slow EEG changes true seizure onset. The aim of our new approach is to estimate the true avoiding false alarms. Compared to [1], the overall sensitivity raised onset based on the alarm reported by EpiScan. The method is inspired from 59 % to 70 % while reducing the false alarm rate by 0.04 FA/h. by the clinical EEG review procedure. Starting at the reported alarm [1] F. Fu¨rbaß et al. ‘‘Detection of Epileptic Seizures During Pre- the algorithm traces back in time as long as the time course of the Surgical Evaluation using Rhytmic EEG Patterns’’; 15th EFNS fundamental frequency of the corresponding rhythmic activity is Congress 2011, Budapest. smooth. The time point when the fundamental frequency starts jit- tering is defined as onset. Results: Applying our new method to 13 patients, we found a significant reduction of the delay between the true seizure onset time O226 and the time reported by our system. On average the improvement is Increased fronto-temporal cortical thickness in juvenile approximately 8 s, resulting in a time delay of around 1 s compared to the true onset. myoclonic epilepsy: evidence from quantitative MRI Conclusion: With this proof of concept we show that it is possible S. Alhusaini, L. Ronan, C. Scanlon, C. Whelan, C. Doherty, to significantly improve the estimation of the onset time of rhythmic N. Delanty, M. Fitzsimons EEG pattern automatically. Such an estimated onset might provide an Royal College of Surgeons in Ireland (Dublin, IE); Beaumont additional objective measure for the beginning of epileptic activity. Hospital (Dublin, IE); James’s Hospital (Dublin, IE) This might especially be interesting where visual interpretation is difficult due to small amplitudes or artefacts. The estimated onset may Objectives: Previous volume-based MRI studies of the cerebral cortex also be valuable for systems trying to automatically determine the in juvenile myoclonic epilepsy (JME) have provided inconsistent seizure onset zone and for automatically analyzing the temporal findings. Cortical thickness has been proposed as a viable alternative evolution of seizures. to volumetric measurements for the assessment of subtle cortical pathological changes. In this study, we aimed to characterize cortical thickness alterations as well as volumetric changes of subcortical structures in patients with JME. O225 Methods: Twenty four patients with JME and 40 healthy controls underwent T1-weighted MRI. An automated brain reconstruction Improved online seizure detection system for epilepsy method (FreeSurfer) was applied to process the MR images. Cortical monitoring units thickness (covariates: age, and gender) across the entire cortex as well F. Fu¨rbaß, M. Hartmann, H. Perko, C. Baumgartner, as the volume of the subcortical structures (covariates: intracranial A. Skupch, P. Dollfuß, T. Kluge volume, age, and gender) were compared between patients and controls using linear regression models. AIT Austrian Institute of Technology GmbH (Vienna, AT); General Results: Bilateral increase in cortical thickness was revealed Hospital Hietzing with Neurological Center Rosenhuegel (Vienna, within frontobasal regions, inferior temporal/fusiform gyri, and AT) inferior parietal cortex in JME patients. Further, increased cortical Objectives: The evaluation of long-term electroencephalography thickness was detected in right medial frontal regions. In addition, (EEG) recordings during pre-surgical evaluation is a difficult and bilateral thalamic volume reduction was revealed. time-consuming task. Medical experts are required not only to analyse Conclusion: This is the first study to report increased cortical seizures and inter-ictal events but also to continuously monitor the thickness in frontotemporal regions of the cerebral cortex in JME and brain activity of patients with a reduced anti epileptic drug dose. We explain previous volume-based findings. The increase in grey matter propose a novel method that reliably marks seizures during recording thickness may reflect abnormal frontotemporal corticothalamic net- and alerts medical stuff immediately. The method will extend the works or malformations of cortical development. seizure-detection system EpiScan [1] with an improved EEG baseline This study was funded by a Health Research Board fellowship adaptation. The method is currently under clinical evaluation at the (HSR/2006/7). Neurological Department Rosenhu¨gel. Methods: One of the most common patterns in epileptic seizures is rhythmic activity arising from epileptogenic zones in sub-cortical areas like e.g. the hippocampus. EpiScan is able to detect rhythmic epile- O227 ptoform EEG activity in real time using the digital EEG data-stream Cytokine and neurotransmitter data in patients only. Because of high inter- and intrapatient diversity of the EEG such a with drug-resistant epilepsy system needs a continuous tuning to the EEG baseline. Our proposed method builds a chronological and spatial model of all rhythmic patterns Y. Lekomtseva, G. Cubina, T. Gorbach in order to distinguish normal from ictal epochs. This model is able to Institute of Neurology, Psychiatry and Narcology (Kharkiv, UA); predict changes in the baseline like e.g. the sleep-wake cycle. Kharkiv National Medical University (Kharkiv, UA)

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S25

Object: Role of glial cells in mechanisms of seizure precipitation is neuropsychological assessment including tests of episodic memory, important as seizures can activate microglia and astrocytes to release language, visuospatial/constructional praxis, attention and executive a number of proinflammatory mediators initiating cascade of functions, as well as quantitative ratings of motor symptom severity inflammatory processes in brain tissue. Mediators and molecular and functional status. MCI was diagnosed in nondemented patients mechanisms involved in glio-neuronal interactions may explain how who had cognitive impairment based on neuropsychological testing brain inflammation can contribute to neuronal hyperexcitability in and no functional impairment. epilepsy. The aim of work was to determine proinflammatory cyto- Results: Relative to controls, MSA-MCI group showed significant kine and neurotransmitter levels in patients with severe epilepsy. deficits in immediate recall (p=0.001) of the Free and Cued Selective Materials and Methods: Patients with long-standing intractable Reminding Test, digit span backward (p\0.001), verbal fluency drug-resistant epilepsy (n=24; 26-48 years) with high seizure fre- (p\0.001), WCST (p\0.001) and Stroop test (p\0.001). However, quency, psychiatric complications were included and compared to this group was unimpaired in recognition memory, long-term for- controls (HC, n=16; 21-35 years). Serum interleukin (IL) IL-6 and IL- getting, naming, visuospatial abilities and constructional praxis. 8 were measured at baseline condition by standard immunoenzyme Conclusion: The most prominent features in cognitive profile assays using Vector Best reagents (Russia); neurotransmitters: glu- of our MSA-MCI patients are the deficits in different aspects of tamate (Glu), aspartate (Asp), GABA were measured in sera by ion- executive functions, such as short term/working memory, conceptu- exchange chromatography method. alization, initiation, executive control and response inhibition. The Results: As compared to HC, epilepsy showed an elevated per- possible relationship between MCI and incipient dementia in indi- centage of IL-6 serum concentration suggesting that increased IL-6 viduals with MSA remains to be investigated in follow-up studies. (Mean: 16.7 pg/ml; range 10.2 – 18.5 pg/ml vs. Mean: 4.1 pg/ml; range: 0.9 – 4.5 pg/ml) might be generated from activation of cytokine astrocytes network (P\0.05). IL-6 is an important interleukin O229 that acts as both pro-inflammatory and anti-inflammatory cytokine secreted by T-cells and macrophages to stimulate immune response. Diffusion tensor imaging reveals widespread white- IL-6 was quantified as a marker of humeral immune response. Drug- matter changes in multiple system atrophy resistant epilepsy showed no differences in interictal IL-8 concen- A.M. Rulseh, J. Keller, H. Brozova, R. Rusina, R. Jech, tration compare to HC: Mean 27.8; range was between 19.4 and 32.6 J. Vymazal pg/ml vs Mean 5.9 pg/ml, range: 4.0 – 9.5 (P[0.05). Microglia- Na Homolce Hospital (Prague, CZ); Charles University in Prague, astrocyte activation could be pronounced as a potential cause of high 1st Faculty of Medicine (Prague, CZ); Faculty Thomayer Hospital proinflammatory cytokines data. Glu level was 144.3±12.4 mkmol/l (Prague, CZ) vs 124.5±11.07 in HC, mkmol/l; Asp level was 11.6±1.4 vs 8.022±0.7, mkmol/l and GABA, respectively, 2.67±1.01 vs Objectives: To investigate white matter changes in Multiple System 5.97±0.9, mkmol/l (P\0.05), so serum GABA level was below nor- Atrophy (MSA), a neurodegenerative disease characterized by auto- mal values in each occasions; Glu level was moderately elevated. nomic dysfunction with parkinsonian (MSA-P) and/or cerebellar Conclusion Drug-resistant epilepsy revealed high interictal pro- (MSA-C) features. inflammatory IL-6 cytokine level with low serum GABA which could Methods: Ten patients diagnosed with probable MSA-P (4M, 6F, be influenced by long antiepileptic drug treatment. Inflammatory mean age 62.0 Y ±9 SD),tenwith probable MSA-C(6M, 4F, mean59.9 Y processes are the importance of clinical understanding of chronic ±4 SD) and twenty healthy volunteers (9M, 11F, mean 61.3 Y ±7SD) epilepsy outcome and might have predictive character for pharmaco- were included. All subjects provided informed consent. DWI was per- resistance course or development of epilepsy with psychiatric formed at 1.5T (b=1100; 12 dir; 2.2 mm isotropic). Fractional anisotropy complications. (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) maps were processed in TBSS (FA threshold[0.3, 50k permuta- tions). Results were thresholded at p\.05. Additionally, specific JHU- White Matter-label-masks were skeletonized and projected based on ______TBSS results in template space. Considering the frequent overlap between Oral session 7 MSA-P/C, both diagnosis (MSA-P/C) as well as the clinical presence of parkinson/cerebellar signs (cMSA– cMSA-p/pc/c) were considered. Results: TBSS did not reveal differences between MSA-P and Movement disorders II MSA-C in any diffusion metric. In examining all MSA versus controls, RD increase (RDi) was most conspicuous. RDi, FA reduction (FAr) and MD increase (MDi) were present in the superior (SCP), O228 middle (MCP) and inferior cerebellar peduncles (ICP) bilaterally, with AD increase (ADi) in the bilateral MCP only. Supratentorially, Mild cognitive impairment in patients with multiple RDi was observed throughout the corona radiata, in the anterior system atrophy commissural fibers bilaterally and body/genu of the corpus callosum, S. Skelina, R. Pavlova, M. Petrova, O. Grigorova, the internal capsule (IC) and external capsule (EC) bilaterally, the M. Raycheva, L. Traykov bilateral corticospinal tract and in many subcortical regions. FAr and MDr followed a similar pattern but in fewer voxels. ADi was present Medical University Sofia (Sofia, BG) in the bilateral EC. In group-wise comparison of ROI data, we Background: Cognitive deficit is often associated with Multiple sys- observed [2SD separation between cMSA-c and cMSA-p in a tem atrophy (MSA) and it can occur even in the early stages of the number of regions and metrics. MD and RD can differentiate cMSA-c disease. However, the exact pattern of MCI in patients with MSA and cMSA-p infratentorially, and FA in the bilateral posterior limb of (MSA-MCI) is still unclear and subject of considerable controversy. the IC supratentorially. cMSA-pc values were generally intermediate Objective: To determine the pattern of mild cognitive impairment between cMSA-p and cMSA-c. in patients with Multiple system atrophy. Conclusion: White matter changes in both MSA-P and MSA-C are Methods: We investigated 21 patients with MSA-MCI and 25 widespread and not limited to discrete regions. Dramatic changes in normal controls. All subjects underwent a comprehensive RD with nearly unaltered AD support previous studies that

123 S26 J Neurol (2012) 259 (Suppl 1):S1–S236 oligodendrocytes are primarily affected in MSA. Grouping MSA Objective: To determine and compare the accuracy of the Nexframe patients by clinical findings rather than diagnosis more accurately and the Leksell stereotactic frame in deep brain stimulation (DBS) reflects the underlying pathology and may improve the results of procedures. future MSA studies. Background: The ‘‘frameless’’ Nexframe uses bone fiducials rather Supported by IGA grants NS9654-4/2008 and NT11328-4/2010. than a head mounted frame and is therefore considered more com- fortable for patients undergoing DBS. The accuracy of lead implantation is of crucial importance but has not been extensively studied for the frameless system nor have the factors that potentially O230 affect the accuracy. Clinical and cognitive correlates of white-matter tract Design/Methods: The location of 97 (Leksell frame n=47, Nex- damage in progressive supranuclear palsy frame n=50) DBS leads was determined on postoperative MRI and CT imaging. The obtained stereotactic coordinates were compared S. Galantucci, F. Agosta, K. Davidovic, M. Svetel, with the expected intra-operative target coordinates. The resulting M. Copetti, M. Jecmenica Lukic, A. Tomic, G. Comi, absolute errors in X (medial–lateral), Y (anterior-posterior) and Z V.S. Kostic, M. Filippi (dorsal–ventral) coordinates (DeltaX, DeltaY and DeltaZ) were then used to calculate the vector error (VE): VE = square root((Del- Vita-Salute San Raffaele University (Milan, IT); University of Turin 2 2 2 (Turin, IT; Universita` degli Studi di Milano–IRCCS Istituto taZ) +(DeltaY) +(DeltaZ) ). The vector error describes the total error Auxologico Italiano (Milan, IT) in 3D space and represents our main outcome measure. Additionally, principal component analysis (PCA) were used to show the degree of Objective: Progressive supranuclear palsy (PSP) is characterized by similarity between each of the absolute X, Y and Z coordinates in an extensive white matter (WM) pathology. Diffusion tensor imaging Euclidean space. (DTI) provides information on the organization and integrity of brain Results: The (mean ± SD) vector error was 2.8 ± 1.3 for the WM tracts. DTI-derived measures might be useful as markers of Nexframe and 2.5 ± 1.2 for the Leksell frame (p = 0.43). For the disease severity and clinical symptoms in PSP. The aim of this study Nexframe the absolute X, Y, and Z errors were 1.4 ± 1.3 mm, 1.7 ± was to use DTI tractography to assess WM tract damage in PSP 1.2 mm, 1.0 ± 0.9 mm. For the Leksell frame the absolute X, Y and Z patients and to investigate correlations between tract integrity and errors were 1.4 ± 1.0 mm, 1.2 ± 1.0 mm, 1.3 ± 0.9 mm. In the clinical and cognitive measures. anterior-posterior plane (Y coordinate), the Leksell frame was more Methods: Thirty-seven PSP patients and 42 healthy controls accurate than the Nexframe (p=0.04). In contrast, the Nexframe was underwent clinical and cognitive testing and DTI scans. Probabilistic more accurate in the dorsal–ventral plane (Z coordinate) (p=0.04). tractography was used to identify bilateral superior (SCP) and middle There was no difference in accuracy between the two methods in the cerebellar peduncles, corpus callosum, corticospinal tracts (CST), medial–lateral plane (X coordinate). PCA showed high similarity for inferior (ILF) and superior (SLF) longitudinal fasciculi, and uncinate both Nexframe (R-square 9.99 x 10-1) and Leksell frame (R-square fasciculi. Tract mean fractional anisotropy, axial, radial and mean 9.98 x 10-1). diffusivities were compared between groups, adjusting for age. Cor- Conclusion: This comparison of Nexframe and Leksell frame relations between DTI metrics and disease severity (Hoehn and Yahr shows that both techniques have equivalent overall 3D accuracy. We score, PSP Rating Scale), motor dysfunction (Unified Parkinson’s are currently expanding the study to confirm the present results and Disease Rating Scale part III), cognition (Mini-Mental State Exami- evaluate factors that may affect the accuracy of lead placement. nation, Addenbrooke’s Cognitive Examination-revised), and Authors gratefully acknowledges support from the Parkinson’s behavioral changes (Frontal Assessment Battery) were estimated Disease Foundation Parkinson’s Research Center and Dutch Parkin- using the Spearman coefficient. son Foundation. Results: Patients showed a severe intrinsic damage to the SCP and corpus callosum. Abnormal DTI measures were also found in the cingulum, ILF, uncinate fasciculus, bilaterally. DTI metrics of the O232 SCP, corpus callosum, uncinate, bilaterally, and right cingulum correlated with disease severity. Corpus callosum mean diffusivity Effect of levodopa on vowel articulation correlated with motor dysfunction. DTI measures of the corpus cal- in parkinsonian dysarthria losum, left SLF, and bilateral uncinate were related to cognitive Y. Okada, T. Toda, M. Murata deficits. DTI alterations of the left cingulum, uncinate, and SLF, and Kobe University Graduate School of Medicine (Kobe, JP); National bilateral ILF were correlated with the severity of behavioral changes. Center Hospital of Neurology and Psychiatry (Tokyo, JP) Conclusions: PSP is associated with degeneration of the SCP, interhemispheric, and major association WM tracts. The intrinsic Objectives: The aim of this study is to investigate the effect of damage to WM tracts likely plays a central role in clinical, cognitive levodopa on vowel articulation in individual patients with Parkinson’s and behavioral disturbances in PSP patients. disease (PD). In most types of dysarthria, the limitations of articulator movements lead to inadequate vowel formation by restriction of formant production, which is characterized by lowering of normally high frequency formants and elevation of normally low frequency O231 formants. These changes in turn result in reduction of vowel space Analysis of stereotactic accuracy in patients undergoing area (VSA), namely formant centralization (Sapir et al., 2007, Roy deep brain stimulation using Nexframe and Leksell et al., 2009). To analyze the first (f1) and second (f2) formants of each frame vowel and the VSA before and after levodopa treatment should be a good indicator for clarifying the effect of the drug on parkinsonian M. Bot, P. van den Munckhof, R.A.E. Bakay, D. Sierens, dysarthria. G.T. Stebbins, L. Verhagen Metman Methods: Twelve patients (7 males and 5 females, Hoehn and Rush University Medical Center (Chicago, US); Academic Medical Yahr score 3-5) with idiopathic PD were required to phonate 5 Jap- Center (Amsterdam, NL); Rockford Memorial Hospital (Rockford, anese vowels (/a/,/i/,/u/,/e/, and/o/) 20 times and tested motor US) performances (finger tapping counts and Unified Parkinson’s Disease

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S27

Rating Scale part III) before and after levodopa treatment. Five Oral session 8 vowels were selected because they are the basic phonemes in Japa- nese syllabary. The f1 and f2 formants of each vowel were determined using computer speech lab software (Fujitsu-Animo). The plotting of Imaging f1 frequency as a function of f2 for 5 vowels provides a graphic display of a pentagonal vowel space area (pVSA). We compared the pVSA before and after levodopa treatment. In 4 patients, sequential O234 changes in plasma levodopa concentrations after treatment were determined and correlated with those of pVSA and motor Correlation between cortical beta-amyloid plaque performance. deposition and glycolysis in preclinical Alzheimer’s Results: In 7 patients, pVSA was significantly expanded after disease treatment together with the improvement of motor performances. In A.G. Vlassenko, L. Couture, T.M. Blazey, Y. Su, J.C. all patients, there was a significant difference in pVSA before and after levodopa treatment. A time course of increase of plasma levo- Morris, T.L.S. Benzinger, M.A. Mintun, M.E. Raichle dopa concentrations after treatment agreed quite well with that of Washington University School of Medicine (St. Louis, US); Avid expansion of pVSA and improvement of motor disturbances. Levo- Radiopharmaceuticals (Philadelphia, US) dopa commonly and most significantly changed f1 frequency of Objectives: We have previously identified using brain positron vowel/a/among the f1 and f2 formants of the 5 vowels. emission tomography (PET) that the pattern of glucose metabo- Conclusion: Expansion of pVSA after treatment indicates clearly lism outside of oxidative phosphorylation (hereinafter simply that levodopa is effective for the improvement of vowel articulation in referred to as glycolysis), in healthy young adults has a high PD patients. To measure simply the f1 frequency of vowel/a/could be a spatial correlation with the pattern of beta-amyloid plaque good indicator of testing the effect of levodopa on parkinsonian deposition in patients with dementia of Alzheimer type. A clue to dysarthria. the relative specificity for beta-amyloid deposition may be the fact that most of beta-amyloid-prone regions have high levels of baseline synaptic activity and that beta-amyloid levels are regulated by synaptic activity. In this study, we evaluated the O233 relationship between brain metabolism and beta-amyloid deposi- Relaxation guided imagery as a new therapeutic tool tion in cognitively normal (CN) older adults in the preclinical for the treatment of motor fluctuations in Parkinson’s stage of Alzheimer’s disease (AD). Methods: Beta-amyloid deposition as measured with disease [11C]Pittsburgh Compound B (PIB) binding potentials (BP) and I. Schlesinger, O. Benyakov, I. Erikh, E. Sprecher metabolic PET images were acquired in 21 CN individuals (mean Rambam Medical Center (Haifa, IL) age 74 years). Mean cortical binding potential (MCBP) from precuneus, gyrus rectus, prefrontal and lateral temporal cortex was Objective: We aimed to assess the short term efficacy and safety of used to define PIB positivity (preclinical AD, MCBP [ 0.18). The relaxation guided imagery (RGI) and relaxing music in patients with relative (i.e., local to global ratio) metabolic rate of oxygen Parkinson’s disease (PD) and motor fluctuations who were receiving (CMRO2) was computed based on the acquisition of three PET levodopa and other antiparkinsonian medications. Background: Motor scans using [15O] tracers (CO, O2 and H2O) and relative metabolic fluctuations in PD patients are currently treated with medication and rate of glucose (CMRGlu) was estimated using [18F]FDG PET. surgery which are limited by their efficacy, side effects and safety. Images of glycolysis were generated by calculating the pixel-by- Methods: In this pilot study patients came for 4 sessions; a base- pixel residual after regression of CMRGlu on CMRO2. PET line visit, a visit where they heard relaxing music and received a CD parameters were evaluated in 34 cortical gray matter regions with relaxing music to listen to at home, a visit with RGI after which defined using FreeSurfer software. they received a CD with RGI to listen to at home and an end of study Results: In preclinical AD participants (n=10, MCBP = 0.45 ± visit. The primary outcome was change in daily off time from base- 0.20), regional PIB BP demonstrated strong correlation with glycol- line. Secondary outcome was change in Unified PD Rating Scale after ysis (r2 = 0.49, p \ 0.0001, Pearson correlation); lower correlation vs. before the relaxation sessions. with CMRGlu (r2 = 0.27, p = 0.0017); and weakest correlation with Results: Twenty PD patients experiencing severe motor fluctua- CMRO2 (r2 = 0.11, p = 0.0515). There were no significant regional tions were enrolled. One subject withdrew due to an ankle fracture. differences in glycolysis, CMRGlu and CMRO2 between PIB-posi- Daily off time at baseline (9h, inter-quartile range [IQR] 6.5 - 11h) tive (preclinical AD) and PIB-negative (n=11, MCBP = 0.00 ± 0.03) was reduced at end of study after RGI (median 6h, IQR 5 - 9h; individuals. P=0.0001), but not after relaxing music (median 9 h, IQR 7 - 10h; Conclusion: Our results suggest that in preclinical AD, brain NS). Unified PD Rating Scale after vs. before the RGI was improved glycolysis and synaptic activity may be preserved and regions with (median before 23, IQR 16 - 33; median after 20, IQR 6 - 38; high glycolytic activity accumulate most of beta-amyloid plaques. P\0.0001) mainly due to reduced rigidity (median before 2, IQR 2 - Longitudinal PET studies are needed to determine whether an 3, median after 1, IQR 1-2 p=0.0005); music also resulted in UPDRS impairment of synaptic activity destroys this relationship and results improvement (median before 21, IQR 15 - 33; median after 21, IQR in a decrease in beta-amyloid accumulation, which is often observed 11 - 32; p=0.0001), without any change in rigidity. RGI was superior at later stages of AD. to music in improving UPDRS, P=0.022. This work was supported by National Institute on Aging grants Conclusion: RGI may be clinically useful in reducing off time in P50 AG05681, PO1 AG026276, PO1 AG03991, National Institute of PD patients with motor fluctuations. Larger studies are necessary to Neurological Disorders and Stroke grants p50 NS006833 and P30 determine the long term efficacy of RGI. NS048056.

123 S28 J Neurol (2012) 259 (Suppl 1):S1–S236

O235 consciousness. We replicated the sedation protocol previously Multi-tracer PET early frames as a functional marker published by Boveroux et al., 2010. The ON of the participants as well as a familiar name (FN) were used as auditory stimuli and were in Alzheimer’s disease presented in blocks of 25 s with the same name repeated every 2 s V.H. Abreu, S. Carter, A. Nordberg within the block. There were 8 blocks of each name, presented in a Akershus Universitetssykehus (Oslo, NO); Karolinska Institutet randomized order. fMRI images were acquired on a 3 Tesla Siemens (Stockholm, SE) Allegra scanner (TR=2460ms). Simultaneous EEG recordings were Objectives: Reduced blood perfusion is linked to the onset of astro- performed using a 64-electrodes Brain Amp MRI compatible cytosis, a known neuroinflammatory trigger of early Alzheimer’s acquisition setup. fMRI and EEG data were preprocessed and ana- disease (AD). It is therefore of great interest to develop multi-tracer lyzed using SPM8 toolbox or software (www.fil.ion.ucl.ac.uk/spm). PET studies with (11)C-Pittsburgh compound B (PIB) and (11)C-L- Results: In wakefulness, both names activated superior and middle deprenyl (DEP) for visualizing astrocytes in vivo, enabling the study temporal as well as inferior and middle frontal gyri. In contrast to of its dynamic regional distribution in early PET frames. Our study FN, presentation of ON during wakefulness additionally activated aims to assess whether both tracers distribution is flow-dependent, as medial prefrontal (MPFC – self-related) brain area. These self- well as its clinical value as an estimate of early cerebral blood flow related brain activations disappeared during deep sedation, while a and inflammation. residual brain activity on the primary auditory cortices and superior Methods: Dual-tracer PET scans were performed in a group of 7 temporal gyri for both stimuli was still observed. Finally, we iden- patients with clinical diagnosis of ‘‘probable AD’’ (mean age ± SD, tified a significant correlation between MPFC activation (in response 64.1±6.1y; mean Mini-Mental State Examination [MMSE] score ± to ON versus FN) and the level of consciousness. The differential SD, 22.2±6.0) and a group of 7 age-matched controls (mean age ± fMRI activation in response to ON during wakefulness was mirrored SD, 60.3±9.3y; mean MMSE score ± SD, 28.7±1.0), both in the ERP by a differential synchronization in the beta band at recruited from Karolinska University Hospital. Quantitative data 150 ms. This difference in stimulus-induced oscillatory activity was was obtained by summing all early PIB and DEP frames and an also correlated with the level of consciousness across sedation iterative algorithm generated normalized perfusion images with stages. standard uptake values for selected regions of interest (frontal, Conclusion: Our results suggest that when level of consciousness parietal, temporal and posterior cingulate cortex). We calculated decreases, discrimination between self versus non-self stimuli simulta- Pearson’s correlation coefficient for the combined frames in all neously diminished. We stress the importance of functional specialization brain tissue voxels and group differences were analyzed with two- of brain activity – in particular the integrity of external versus internal tailed t-tests. awareness systems in the generation of normal conscious perception. Results: PET frames between minutes 1-3 produced the only voxelwise correlation found (R=0.78±0.05) in both groups. In this 3-min window were the lowest PIB and DEP uptake values mea- O237 sured, but the binding/flow ratio was significantly higher (p\0.05) in Functional network connectivity in the behavioural most AD patients (n=6) than in the control group, suggesting that tracer distribution may be flow-dependent. No correlation was found variant of frontotemporal dementia in the other frames studied (minutes 4-10). Brain regions of interest M. Filippi, F. Agosta, E. Scola, E. Canu, G. Magnani, identified as significant discriminators (p\0.05) of AD disease were A. Marcone, P. Valsasina, F. Caso, M. Copetti, G. Comi, posterior cingulate cortex and temporal cortex. S.F. Cappa, A. Falini Conclusion: The distribution of PET tracers in the very early frames is likely flow-dependent, which may be useful to derive Vita-Salute San Raffaele University (Milan, IT); IRCCS Casa clinical estimates of cerebral blood flow and neuroinflammation from Sollievo della Sofferenza (San Giovanni Rotondo, IT) a single multi-tracer PET scan. Objective: The most consistent resting state (RS) functional magnetic resonance imaging (fMRI) feature in patients with the behavioral variant of frontotemporal dementia (bvFTD) is a reduced connectivity within the salience network. The functional connectivity patterns of O236 the default mode network (DMN) in these patients have been less Does self-referential stimuli perception decrease consistent. Furthermore, whether RS networks (RSN) other than the with diminished level of consciousness? salience network and DMN are affected by bvFTD, and whether these A. Vanhaudenhuyse, P. Boveroux, M. Bruno, O. Gosseries, abnormalities differ from those seen in probable Alzheimer’s disease (AD) have not been investigated yet. This study investigated, using Q. Noirhomme, A. Soddu, F. Gomez, M. Bahri, RS fMRI, the functional connectivity within and among brain net- M. Babo-Rebelo, S. Lauwick, C. Degueldre, A. Plenevaux, works in patients with bvFTD, compared with healthy controls and M. Schabus, D. Ledoux, V. Bonhomme, J. Brichant, patients with pAD. M. Boly, S. Laureys Methods: In 12 bvFTD patients, 18 pAD patients and 30 controls, University of Lie`ge (Lie`ge, BE); University of Salzburg (Salzburg, functional connectivity within the salience, DMN, executive, atten- AT); CHR Citadellef Lie`ge (Lie`ge, BE) tion/working memory, and dorsal attentional networks was assessed using independent component analysis. The temporal associations Objectives: We hypothesized that the perception of a self-referential among RSN were explored using the functional network connectivity auditory stimulus (the own name-ON) would be related to the level toolbox. of consciousness. We expected a particularly strong link between Results: A decreased dorsal salience network mean connectivity, the level of consciousness and the activation of self related brain mainly involving the anterior cingulate cortex, was observed in areas activation (Northoff et al., 2006). Methods: 12 healthy vol- bvFTD compared with both controls and pAD. BvFTD was also unteers (mean age 24±4SD) were scanned in 4 clinical states: characterized by a decreased ventral salience network connectivity normal wakefulness, mild sedation, deep sedation, and recovery of of the basal ganglia, and divergent connectivity effects vs. controls

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S29 in the dorsolateral prefrontal cortex (decreased) and precuneus august 2011, just a few days before submission of her virtually (enhanced) within the right attention/working memory network. In completed manuscript to our Medical Faculty, she died in a tragic car addition, the dorsal attentional network had a decreased connectivity accident. Since a posthumous submission of her dissertation is not with the DMN and executive network in bvFTD vs. controls, and a allowed, this contribution to the ENS-meeting is meant to com- decreased connectivity with the dorsal salience network vs. pAD memorate and honour her work. patients. Conclusion: RSN abnormalities occur in bvFTD, involving not only the salience network, but also the DMN and fronto-parietal networks associated with attention and working memory modulation. Regional connectivity changes differ from those seen in pAD. O239 The altered interactions among RSN observed in bvFTD and pAD Interaction between spontaneous fluctuation may provide a new venue to explore the functional correlates of and auditory evoked activity during wakefulness cognitive abnormalities in neurodegenerative and psychiatric disorders. and loss of consciousness O. Gosseries, V. Charland-Verville, M. Boly, A. Vanhaudenhuyse, MA. Bruno, R. Phan-Ba, C. Phillips, P. Boveroux, V. Bonhomme, D. Ledoux, JF. Brichant, O238 S. Lauwick, M. Schabus, E. Balteau, C. Delgueldre, Evaluation of the cortical localisation of language A. Luxen, P. Maquet, S. Laureys in patients with gliomas – a longitudinal fMRI- University and University Hospital of Liege (Liege, BE); University Hospital of Liege (Liege, BE); University of Salzburg (Salzburg, AT) investigation D. Kopp, J. Nickel, R.J. Seitz Objectives: Functional MRI studies have identified spontaneous fluctuations in neural activity within auditory cortices during both University Hospital Du¨sseldorf (Du¨sseldorf, DE) wakefulness and unconsciousness. The functional significance of the Objectives: Functional imaging of language in patients with gliomas preserved ongoing fluctuations during loss of consciousness remains enables to characterize the spatial relation between the mass lesion however poorly understood. We here investigated the influence of and eloquent cortex. This helps to plan a surgical resection, to spontaneous fluctuation in the auditory resting-state network on estimate a potential deficit caused by resection or growth and stimulus-evoked auditory responses under propofol anesthesia, as delineates alterations in the structure to function-relationship in compared to wakefulness. these patients. Methods: Simultaneous functional MRI and EEG data were Methods: We present fMRI investigations of language processing acquired in 13 healthy volunteers (6 females, mean age 23±5 SD). in a clinical cohort of patients with left-hemispheric low and high All subjects underwent four sessions (wakefulness, mild sedation, loss grade gliomas (11 patients, mean age 36±13 years, one up to four of consciousness, and recovery of consciousness) where pure tones consecutive measurements, time span 3 to 39 months), both in cross were presented with a randomized jitter. After obtaining an auditory sectional and longitudinal analysis of imaging data and neuropsy- network template from awake states, we identified a spontaneous chological tests. auditory brain activity spatial map in each condition for each subject. Results: Sounds were then classified into two classes: ’up’ if the tone onset 1. Mechanisms of spatial language reorganisation predominantly occurred within the upper half spontaneous auditory activity, and used intrahemispheric shifting of language activation to regions ’down’ otherwise. Data were analyzed with SPM8 and FMRIB adjacent to the mass lesion. Additionally, a right-hemispheric Software Library. co-activation of homologous areas was observed frequently. Results: During wakefulness, ’up’ tones induced stronger cere- 2. Activation patterns remained pretty much stable over time with bral activation than the ’down’ tones, in a set of areas encompassing a predominance for the frontal lobe. The amount of variation across temporal, parietal, frontal and limbic cortices. During deep sedation, patients was relatively large. Major changes in the activation pattern the effect of spontaneous activity was restricted to primary auditory of individual patients were associated with (partial) resection or cortices only. A correlation between the influence of spontaneous excessive growth of the glioma. fluctuations on the responses to sounds and the level of conscious- 3. The neuropsychological tests for language processing/compre- ness was found in parietal, frontal and occipital cortices. A hension and other language based cognitive functions remained consciousness-dependent effect of spontaneous activity on the pro- relatively stable over time in the individual patients. Again, a wide cessing of stimuli was also found for stimulus-induced beta band variation of individual performance existed across patients. synchronisation at a latency of 200 ms after the presentation of 4. Most patients showed a good functional compensation of lan- sounds. guage performance. Dysfunction was restricted to single aspects of Conclusion: During wakefulness, spontaneous auditory corti- language in most cases. ces fluctuations elicits large differences in activation Conclusion: This series demonstrates a wide variety of language (encompassing frontoparietal cortices) and beta synchronization re-organization in patients with gliomas. The data demonstrates the in late latencies. In contrast, the localized effect of spontaneous impressive potential for sufficient functional reorganization (’cortical activity in primary auditory cortices during loss of consciousness plasticity’) of the adult human brain in the face of a progressive mass is unlikely to lead to changes in awareness of auditory stimuli. lesion. Our data suggest a graded correlation between the level of con- Acknowledgements: sciousness and the interaction between spontaneous and stimulus Most of the work contributing to this investigation was done as evoked activity. They shed light on the lack of functional sig- part of her doctoral thesis by Mrs. Daniela Kopp, neé Will, who was a nificance of fluctuations observed during loss of consciousness for diligent and really likeable M.D. student in our Neuroimage-Lab. In the processing of auditory stimuli.

123 S30 J Neurol (2012) 259 (Suppl 1):S1–S236

Oral session 9 O241 Dopa responsive dystonia, associated with early-onset Movement disorders III parkinsonism and restless legs syndrome in a family with GCH1 deletion M. Vila-Real, M. Sampaio, R. Rocha, S. Franca, M. Leao, O240 D. Alves Myoclonus dystonia syndrome: SGCE mutations Hospital Sao Joao (Porto, PT) and psychiatric disease K. Peall, A. Waite, M. Kurian, M. Wardle, Introduction: GTP cyclohydrolase 1-deficient dopa-responsive dystonia (GTPCH1-deficient DRD) is characterized by childhood- T. Hedderly, J.P. Lin, M. Smith, H. Pall, M. King, onset dystonia and a dramatic and sustained response to low doses of T. Lynch, C. White, P. Chinnery, T. Warner, oral levodopa. This disorder typically presents by the age of six years D. Blake, M. Owen, H. Morris with gait disturbance caused by foot dystonia, later development of Cardiff University (Cardiff, UK); UCL (London, UK); Evelina parkinsonism, and diurnal fluctuation of symptoms. Initial symptoms Children’s Hospital (London, UK); Birmingham Children’s Hospital are often gait difficulties attributable to flexion-inversion (equino- (Birmingham, UK); Children’s University Hospital (Dublin, IE); varus posture) of the foot. Gradual progression to generalized Mater Hospital (Dublin, IE); Singleton Hospital (Swansea, UK); dystonia is often observed. The disorder is mostly inherited as an Newcastle University (Newcastle, UK) autosomal dominant trait with reduced penetrance, mainly in male sex. Most mutations described in GHC1 are single base changes. Background: Myoclonus Dystonia Syndrome (MDS) is a childhood Routine molecular diagnosis is usually restricted to the sequencing of onset movement disorder involving trunk and upper limb myoclonus the six exons of GCH1. As mutations mostly occur in the heterozy- and dystonia of the neck and hands. Motor symptoms are typically gous state, deletions are not detected by sequencing. Deletion alcohol responsive. Mutations in the epsilon-sarcoglycan gene detection requires special methods such as quantitative real-time PCR (SGCE) are seen in 30-80 % of cases and co-morbid psychiatric (qPCR) or multiple ligation-dependent probe amplification (MLPA). disease described in a number of cohorts. Case report: Eleven years old girl that by the age of eight devel- Aims: We aimed to establish a cohort of MDS cases and sys- oped a paretic gait with left foot dystonia, that worsened by the end of tematically assess the rates and type of psychiatric disease using the day and showing a dramatic response to levodopa. MLPA analysis standardised protocols. was performed revealing the presence of a heterozygous deletion of Methods: MDS cases with SGCE mutations (described as man- exon 2 and exon 3 of the GCH1 gene. ifesting carriers, MC) were systematically assessed, collecting She had a paternal grandmother diagnosed with early onset par- information with regard to age at onset of the movement disorder, kinsonism with more than 20 years of evolution and with response to distribution of symptoms and family history. Psychiatric features low doses of levodopa. Her grandmother, a paternal uncle and a were assessed using standardised tools including the MINI Inter- paternal aunt fulfil criteria of restless legs syndrome. All three showed national Psychiatric Assessment (MINI), Patient Health the same heterozygous deletion. His father, two paternal uncles and Questionnaire-9 (PHQ-9), Alcohol Use Disorders Questionnaire one paternal aunt were asymptomatic although sharing the same (AUDIT), Yale-Brown Obsessive Compulsive Score (YBOCS), deletion. In addition she had a cousin with the same symptoms and Montgomery-Asberg Depression Rating Scale (MADRS) and SCID- response to treatment. II, Axis-II to assess personality disorders. Additional family mem- Conclusion: GCH1 deletions should be included into the routine bers were recruited to undertake the same standardised interview molecular diagnosis of all patients with DRD, restless legs syndrome being classified as non-manifesting carriers (NMC) or non-carriers and, eventually, early onset parkinsonism with good response to low (NC) based upon the presence or absence of a SGCE mutation doses of levodopa. respectively. Results: 27 MC, 7 NMC and 14 NC cases were identified within the study. There was no significant difference in ages between the groups at time of data collection. Overall there was a higher rate of O242 psychiatric disease amongst MC when compared to the other two Prevalence of neurodegenerative parkinsonism groups. Specifically there was a higher rate of Obsessive–Compul- sive disorder (OCD), alcohol abuse/dependence and to a lesser in the isolated population of south-eastern Moravia, degree social phobia and recurrent depression. There was no sta- Czech Republic tistically significant difference between the NMC and NC groups K. Farnikova, P. Kanovsky, M. Kaiserova, L. Mikulicova, overall, although recurrent depression was higher amongst the NMC M. Vastik, P. Jugas, J. Ovecka group. Palacky University Medical School, Faculty Hospital (Olomouc, CZ); Conclusion: Psychiatric disease, specifically OCD and alcohol Neurological Outpatient Clinic (Veselı´ nad Moravou, CZ); General dependence are elevated within the MC group. Excess alcohol use is Practitioner (Lipov, CZ) likely a secondary effect due to its suppressive effects upon the movement disorder, however OCD most likely forms part of the MDS Objective: To assess the prevalence of neurodegenerative parkin- phenotype. There was no excess psychiatric disease or OCD symp- sonism in the small, isolated, rural population of far South-Eastern toms when comparing NMC and NC groups however, this does not Moravia. exclude a gene effect in causing psychopathology as SGCE is Background: It has been recently described that the prevalence believed to be imprinted and therefore non-functioning within this of neurodegenerative diseases in a small, isolated European com- group. munities might be higher than in the general population. We have

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S31 observed this phenomenon also in the small village (population 1500) O244 in the far south-east Moravia. Richardson’s syndrome presenting as atypical MSA: Methods: To assess precisely this increased prevalence, we have used the three-stage ascertainment method. All villagers received a clinico-pathologic case report validated screening mail questionnaire for parkinsonism. In the sec- M. Vastik, K. Mensikova, L. Tuckova, R. Matej, ond stage of the ascertainment method, trained primary care P. Kanovsky neurologists identified all persons with positive signs of parkinsonism Palacky University Medical School (Olomouc, CZ); Thomayer0s among those screened positive. In the third stage, all identified per- Hospital (Prague, CZ) sons were admitted to the tertiary movement disorders center to exclude or confirm the diagnosis of parkinsonism. Objective: To report the clinical and neuropathological features of a Results: The response rate was 42 %. There were 56 per- patient with Richardsons syndrome presenting as a atypical MSA sons screened positive, and 19 of them were identified as manifesting Background: We will document the case of a female patient who signs of parkinsonism; the diagnosis has been confirmed in 16 of manifested first signs of postural instability with feeling of pull in them. all directions at the age of 67. During next 5 years progression of Conclusions: The prevalence rate of 1 % is surprisingly high; it postural instability, hypokinesia, rigidity, quadruhyperreflexia, gait substantially differs from the estimated prevalence in the common initiation difficulties, walk with short shuffling steps and reduced Central-European population. The next research will focus on the synkinesis, dystonic contractures, impaired articulation, increased genetic background of the families in which has been parkinsonism urination frequency, feeling of stiffness in the extremities, frequent identified. falls and later immobility developed. The patient died at the age of 74. Methods: Clinical examination, paraclinical investigations : brain MRI, CSF examination, US examination of substantia nigra, Head– up tilt test, bedside Thompson test, psychological and genetic O243 examination, response to L–dopa therapy suggested the diagnosis of Voluntary, spontaneous and reflex blinking in multiple MSA–P. Post mortem pathological and histopathological examina- system atrophy tions, 20 paraffin blocks of temporal, frontal, parietal and occipital M. Bologna, L. Marsili, N. Kahn, A. Khandker Parvez, cortex, hippocampal areas, basal ganglia, brain stem, substantia nigra, vermis and cerebellar hemispheres were examined by using N. Modugno, C. Colosimo, G. Fabbrini, A. Berardelli H-E, Luxol blue, impregnation of silver salts, immunohistochemistry Sapienza, University of Rome (Rome, IT) with monoclonal antibodies - alpha- synuclein, amyloid – beta- Objectives: Recent studies disclosed a variety of voluntary, sponta- peptide, hyperphosphorylated form of tau protein and isoform of tau neous and reflex blinking abnormalities in Parkinson’s disease, protein. Progressive Supranuclear Palsy and other parkinsonian syndromes. Results: The findings of clinical and paraclinical examinations By contrast data on blinking in MSA are limited in literature. The aim suggested the diagnosis of MSA–P. The pathological and histopa- of the present study is to investigate the kinematic features of vol- thological examinations confirmed neurodegenerative disease that untary, spontaneous and reflex blinking in patients with clinically meets diagnostic criteria of PSP/PSP tau score 6-7 by Williams/. In probable multiple system atrophy (MSA) and healthy control this case we present an example of phenotypic overlap of two neu- subjects. rodegenerative diseases – Richardson´s syndrome presenting as Methods: Ten MSA patients and 10 healthy age- and gender- atypical MSA. matched controls participated in the study. Participants were asked to blink voluntarily as fast as possible; spontaneous blinking was recorded during two 60 s rest periods during which the subjects just O245 relaxed; reflex blinking was evoked by electrical stimulation of the supraorbital nerve using standard techniques. Eyelid movements were Clinical, biochemical and radiological profile recorded with the SMART analyzer motion system (BTS, Milan, of Wilson’s disease and effect of treatment Italy). Data analysis was performed using a dedicated software N. Kumar, D. Joshi (Analyzer software, BTS, Milan, ltaly). Differences between MSA Indira Gandhi Institute of Medical Sciences (Patna, IN); Institute of and healthy controls in blinking parameters were evaluated using Medical Sciences, BHU (Varanasi, IN) multivariate analysis of variance. Results: During voluntary blinking, the opening phase duration Objectives: To study clinical, biochemical and radiological profile of lasted longer and the peak velocity was lower in MSA patients than in Wilson’s disease(WD)and effect of treatment. healthy controls. There was a trend toward prolongation of duration Methods: This study was carried on 31 patients who were subjected and reduction of peak velocity of the closing phase of voluntary to a detailed clinical history, physical and neurological examination. blinking in MSA. The spontaneous blinking rate was lower in Slit lamp examination of cornea for Kayser-Fleischer (KF) ring, bio- patients. During spontaneous blinking MSA patients had reduced chemical studies (including serum ceruloplasmin, copper and urinary peak velocity and amplitude, for both the closing and opening phases. copper) and neuroimaging was done in all patients. In addition, during reflex blinking MSA patients had longer duration Results: The mean age of onset was 12.41 years and the mean and a lower peak velocity of the opening blink phase comparing to delay in diagnosis was 16.96 months. 24 (77.4 %) patients were healthy controls. Finally in MSA, the inter-phase pause duration, a juveniles (age below 18 years) and 7 (22.6 %) were adults (age more neurophysiological marker of the switching processes between the than 18 years). Dystonia was the commonest initial neurologic feature closing and opening phases, was prolonged during voluntary but not (64.5 %) followed by dysarthria (41.9 %), drooling of saliva (38.7 %) during spontaneous and reflex blinking. and parkinsonism (38.7 %).Among the main neurologic features, the Conclusions: Abnormal voluntary, spontaneous and reflex blink- dystonic group (83.9 %) predominated followed by the parkinsonian ing in MSA patients reflects the widespread cortical, subcortical and group (64.5 %), cerebellar group (22.6 %) and the choreoathetoid brainstem degeneration related to this disease. The results of the group (9.7 %).While parkinsonism predominated in the juvenile present study have several pathophysiological implications. group, cerebellar features predominated in the adults. Psychiatric

123 S32 J Neurol (2012) 259 (Suppl 1):S1–S236 complaints (41.9 %), seizures (19.4 %) and headache (22.5 %) were Statistical evaluation showed an increasing age-related trend of sleep also observed. Bilateral KF ring was seen in all patients. Non-neu- comorbidities: REM behavior disorder (RBD) (p\0.01), obstructive ropsychiatric features(bleeding, hepatosplenomegaly and joint pains) sleep apnea (p\0.001), periodic limb movements (p\0.05) and were seen predominantly in juveniles. Serum ceruloplasmin was low restless leg syndrome (p\0.001). The peak of all evaluated sleep (\20 mg/dl) in 93.54 % patients, 24 h urinary copper ([100 micro- comorbidities was between 40-59 years with the exception of RBD gram/day) was increased in all patients and serum copper was low signs predominating in patients over 60 years. However, no clinical (\75 microgram/dl) in 64.5 % patients. MRI brain was done in 27 feature of Parkinson´s disease or other synucleinopathies were found patients with basal ganglia signal changes being the commonest in any of the patients under study. finding (85.2 %). 4 patients had CT scan brain done with basal gan- Conclusion: The main difference between childhood and adult- glia hypodensity being the commonest finding (75 %).All patients hood narcolepsy is in the absence of cataplexy suggesting its possible were treated with zinc and penicillamine. 23 (74.2 %) patients took development later in life. Sleep comorbidities increased with age regular treatment with neurological worsening occurring in 16 reaching the peak in older adults, with exception of RBD predomi- (51.6 %) patients. 13 (41.9 %) patients improved completely; 12 nating in seniors. Narcolepsy seems to have a protective factor against (38.7 %) patients showed incomplete improvement with sequelae; 4 development of alpha-synucleinopathies. (12.9 %) patients remained status quo and were lost in follow up and Supported by MSM 0021620849. 2(6.45 %) patients deteriorated and died. Conclusions: This series of WD from Eastern India highlights that the disease is not that rare in India and has varied clinical presentations. Dystonia and parkinsonian features predominated in juvenile patients, O247 while cerebellar features predominated in the adult group. Screening of Normative EMG values during REM for the diagnosis all asymptomatic siblings for WD must be carried out. Early diagnosis of RBD and proper treatment can prevent devastating consequences. B. Frauscher, A. Iranzo, C. Gaig, V. Gschliesser, M. Guaita, V. Raffelseder, L. Ehrmann, N. Sola, M. Salamero, E. Tolosa, W. Poewe, J. Santamaria, B. Ho¨gl ______Innsbruck Medical University (Innsbruck, AT); Hospital Clıńic of Oral session 10 Barcelona (Barcelona, ES)

Objective: Correct diagnosis of REM sleep behavior disorder Sleep disorders (RBD) is important since it can be the first manifestation of a neurodegenerative disease, it may lead to serious injury, and it is a well treatable disorder. Our aim in this study was to obtain normative O246 values for the correct diagnosis of RBD for clinical practice. Methods: We evaluated the electromyographic (EMG) activity in Narcolepsy—clinical differences and sleep co- the SINBAR montage (mentalis, flexor digitorum superficialis, morbidities in different age groups extensor digitorum brevis) and other muscles during REM sleep in S. Nevsimalova, J. Buskova, D. Kemlink, I. Prihodova, thirty RBD patients (15 idiopathic -iRBD-, 15 with Parkinson’s dis- J. Pisko, J. Skibova, K. Sonka ease -PD-) and 30 matched controls recruited from patients with effectively treated sleep-related breathing disorders. Charles University (Prague, CZ); Institute of Experimental Medicine Results: Participants underwent video-polysomnography including (Prague, CZ) registration of 11 body muscles. Tonic, phasic and ‘‘any’’ (either tonic Objectives: Narcolepsy-cataplexy (N–C) is a focal neurodegenerative or phasic) EMG activity was blindly quantified for each muscle. disease with a predisposed genetic and autoimmune etiology, patho- When choosing a specificity of 100 %, the 3-second mini-epoch cut- genesis of narcolepsy without cataplexy (Nw/oC) is less clear. We off for a diagnosis of RBD was 18 % for ‘‘any’’ EMG activity in the aimed to evaluate clinical differences and particularly sleep comor- mentalis (AUC 0.990). Discriminative power was higher in upper bidities over the life span of narcoleptic patients. limbs (100 % specificity, AUC 0.987–9.997) than in lower limb Methods: A cohort of 148 patients (66 men, 82 women, mean age muscles (100 % specificity, AUC 0.813-0.852). We combined ‘‘any’’ 40.9±20.3 years, age range 7-85 years) underwent clinical face-to EMG activity in the mentalis with both phasic flexor digitorum face interview, HLA-DQB1*0602 typing, nocturnal polysomno- superficialis muscles and found a cut-off of 32 % (AUC 0.998) for graphic (PSG) examination followed by multiple sleep latency test both subjects with iRBD and PD-RBD. (MSLT) and Epworth Sleepiness Scale rating (ESS). The cohort was Conclusion: For the diagnosis of idiopathic RBD and RBD asso- divided into 4 age groups: children and adolescents under 19 years ciated with PD, we recommend a polysomnographic montage (n=31), adults aged 20-39 years (n=51), 40-59 years (n=28) and over quantifying ‘‘any’’ (either tonic or phasic) EMG activity in the 60 years (n=38). 108 patients were classified as N–C, 39 as Nw/oC. mentalis and phasic EMG activity in the right and left flexor digito- For statistics we used the Chi-square, Fisher´s, two sample t-tests and rum superficialis in the upper limbs with a cut-off of 32 %, when the linear trend test in a frequency table. using 3-second mini-epochs. Results: Comparisons between childhood and adulthood cases found N–C in 92 adult patients (79.5 %) and in 16 children (51.6 %), p\0.01. No difference was found in the presence of hypnagogic/hypnopompic hallucinations and sleep paralysis, in sleep O248 latency and the number of SOREMs in the MSLT, or in the ESS, Periodic limb movement disorder presenting either. While the N–C group showed equal results in HLA- DQB1*0602 positive cases (93.7 versus 92.6 %), Nw/oC had a high as a parasomnia increase of positive childhood cases (78.6 versus 52.9 %), p\0.001, C. Gaig, A. Iranzo, J. Santamaria suggesting a possible later appearance of cataplexy in children. Hospital Clıńic (Barcelona, ES)

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S33

Objective: Periodic limb movement disorder (PLMD) is characterized frequent in RLS patients (7/40 vs. 1/39; p=0.03). RLS pregnant by repetitive limb movements during sleep (PLMS) causing sleep women had a higher ESS score than pregnant controls (10.6 ± 3.1 vs. disturbances, most often insomnia, excessive daytime sleepiness 7.6. ± 3.6; p\0.001). (EDS) and fatigue, in absence of other primary sleep disorder. Our Discussion: In our study, RLS is frequent in pregnant women. RLS aim is to report a series of patients presenting with a complaint of patients describe more daytime sleepiness. These results are in line with abnormal behaviors during sleep that were found to be caused by previous studies. Surprisingly, preeclampsia was much more frequent in PLMS involving the whole body. RLS patients. Preeclampsia is known to be more common in women who Methods: We reviewed the clinical records and video-polysom- have preexisting hypertension, diabetes, autoimmune diseases such as nography (V-PSG) of eight patients (7 males and 1 female; Mean age lupus, or women with a family history of preeclampsia. This is the first ± standard deviation (SD): 66.7 ± 7.5 years, range: 53-76) presenting study indicating a possible association between RLS and preeclampsia. abnormal sleep behaviors due to PLMS. PLMD was diagnosed according to ICSD-2 criteria. Results: Abnormal sleep behaviors reported consisted of vocalizations such as talking, crying, shouting or laughing, and movements O250 included knocking the bed partner, kicking, punching or gesticulating. Anxiety and its role in different types of sleep disorders Two patients had fallen out of the bed and two suffered injuries. Mean A. Howe, Y. Levin, K. Strygin, M. Poluektov duration of abnormal behaviors was 11.5 ± 9.7 years (range: 2.5-30). Somnological center of the I.M. Sechenov First State Moscow Seven patients had been referred to the sleep lab because of suspected Medical University (Moscow, RU) REM sleep behavior disorder (RBD). Nightmares such as arguing or being attacked or chased by people or animals occurred in 5 patients. Objective: To explore the level of anxiety and its influence on sleep in Six patients had mild sleep onset and maintaining insomnia. Mild different types of sleep disorders (insomnias - I, sleep-related EDS occurred in 5 patients and daytime fatigue in 3. Mild Restless leg breathing disorders - SA, parasomnias -P). syndrome (RLS) symptoms were present in 5 patients. None of these Methods: 190 patients with different sleep disorders (83 women additional symptoms were the main complaints. V-PSG recorded and 107 men, age from 12 to 83 (mean 43.56 ± 14.22), I – 96, SA – frequent and prominent PLMS, involving the lower and upper limbs 77, P – 17) were examined in the somnological center with the help of and trunk (mean PLMS index: 80.1 ± 38.3, range: 32.6-148). V-PSG polysomnography – PSG, measurement of nasal airflow, respiratory ruled out other sleep disorders such as RBD, sleep apnea or epilep- effort and oxygen saturation during sleep, scale of subjective sleep tiform activity. Two patients had low serum ferritin levels. Treatment quality measurement (SQ), hospital anxiety and depression scale with dopaminergic agonists in all 8 patients and iron supplements in 2 (HADS), day sleepiness scale Epworth (E). patients, improved markedly abnormal sleep behaviors, as well as To measure the anxiety level screening scale HADS was used, we other additional symptoms such as nightmares, insomnia, EDS and considered high anxiety level (HAL) as greater than 11 score using RLS, in all patients. HADS (low anxiety level - LAL). Statistically significant difference Conclusion: PLMS can involve the whole body and may mimic a was considered as t[2, p\0.05. parasomnia. Exclusion of traditional NREM and REM parasomnias Results: Patients with different sleep disorders commonly expe- and demonstration of abnormal body movements associated to PLMS rience HAL in 26.3 % of cases and in this group there are more should be made with Video-PSG. Abnormal behaviors during sleep women, more complaints on stress in the past, lower SQ level (15.96 linked to PLMS improve with dopaminergic agents. ± 3.85 versus 18.29 ± 4.01 points), higher depression scores (8.42±4.68 versus 5.21± 3.23 points), lower latent period of stage 4 on PSG (37.59±35.35 versus 68.72±72.4 min). O249 In different sleep disorders anxiety incidence and level were dif- Restless legs syndrome and pregnancy: frequency ferent: I with HAL – 57.4 %, SA with HAL – 15.6 %, P with HAL – and characteristics in a Peruvian population 22.2 %, comparing I and SA level of anxiety is higher in I: 8.6±4.2 versus 6.28±3.51 points. J.O. Ramirez, S.A.S. Cabrera, H. Hidalgo, S.G. Cabrera, On PSG different sleep disorders with anxiety had different changes: M. Linnebank, C. Bassetti, U. Kallweit in I - lower latent period of stage 4 (HAL 32.15±27.8 versus LAL Hospital Nacional Docente Madre Ninõ San Bartolome (Lima, PE); 60.9±60.12 min), in SA - decreased length of delta-sleep (HAL Kamillus-Klinik (Asbach, DE); University Hospital Zurich (Zurich, 6.83±5.6 versus LAL 13.84±5.01 %), higher level of central apnea CH); University Hospital (Berne/Lugano, CH) index (HAL 4.61±2.17 versus LAL 0.8±11.5), in P - higher latent Background/Objectives: Restless legs syndrome (RLS) is a common period of stage 1 (HAL 54.07±34.26 versus in LAL 20.42±18.78 min). neurological disorder. Secondary RLS forms include pregnancy and Conclusion: Presence of high level of anxiety has its impact on iron deficiency. In western countries, prevalence of RLS in pregnancy different sleep disorders. On PSG of patients with high anxiety level ranges between 12-26 %. Pregnancy or delivery complications due to there are different changes within different types of sleep disorders, RLS are not described. We aimed at assessing frequency and char- however they all could be found during non-REM sleep. As for sleep- acteristics of RLS in pregnancy in a Peruvian population. related breathing disorders – high anxiety was associated with higher Methods: We assessed 218 consecutive expectant mothers at the level of central apnea index. in- and outpatient clinic of the Hospital Nacional Docente Madre Ninõ San Bartolome, Lima, Peru. Assessment was performed by using the standard diagnostic criteria for RLS and by a face to face medical interview. Questionnaires for RLS severity (IRLS) and O251 excessive daytime sleepiness (EDS) by Epworth Sleepiness Scale Effect of transdermal methylphenidate wear times (ESS) were used. Blood examination was performed for hemoglobin on sleep in children with ADHD and/or hematocrit. For comparison, RLS patients were matched for A. Ashkenasi age- and BMI with pregnant women without RLS. Pediatric neurology of the ozarks (Springfield, US) Results: Out of 218 patients, 40 (18.4 %) fulfilled diagnostic criteria for RLS. In RLS patients, iron supplementation therapy during Sleep disturbances are common among children and adolescents with pregnancy was taken less frequently (p=0.02). Preeclampsia was more attention deficit hyperactivity disorder. This study sought to evaluate 123 S34 J Neurol (2012) 259 (Suppl 1):S1–S236 the effects of individualizing wear times of the methylphenidate Conclusion: In TBI patients showing GHD, substitutive treatment transdermal system on sleep parameters. In this open-label, random- can contribute to better improvement in cognitive performance and ized trial, 26 children with attention deficit hyperactivity disorder and QoL. This benefit is more evident for those with more severe diffi- sleep disturbances were randomized (after dose optimization) to one culties before treatment. of four groups with different sequences of patch wear times (i.e., 9, 10, 11, and 12 h per day wear times each for week in different sequences). The primary endpoint comprised sleep latency. Second- ary endpoints included total sleep time, sleep quality, and attention O253 deficit hyperactivity disorder and related signs (assessed with Atten- Assessment of localisation to auditory stimulation tion Deficit Hyperactivity Disorder Rating Scale-IV and Connor’s in post-comatose states: use the patient’s own name Global Impression-Parent). A mixed-effects regression model evalu- O. Gosseries, L. Cheng, V. Charland-Verville, L. Ying, ated the effects of patch wear time on sleep and symptom measures. Patch wear time exerted no significant effect on sleep latency or total X. Hu, D. Yu, H. Gao, M. He, C. Schnakers, H. Di, sleep time, although a trend toward improved sleep quality was evi- S. Laureys dent (P 0.059) with longer patch wear times. Sleep parameters were University and University Hospital of Lie`ge (Lie`ge, BE); Hangzhou not adversely affected by longer methylphenidate transdermal system Normal University (Hangzhou, CN); (Lie`ge, BE); Wujing Hospital of patch wear times. Thus, if replicated in larger samples, the individ- Hangzhou City (Hangzhou, CN) ualization of patch wear times should be considered according to the Objectives: At present, there is no consensus on what auditory needs and responses of patients. stimulus should be employed for the assessment of localization to Sponsored by shire pharma and noven pharma. sound in patients recovering from coma. The aim of this study was to investigate behavioral responses to auditory localisation using the patient’s own name as compared to a meaningless sound (i.e. ringing ______bell) in patients with disorders of consciousness. Methods: Eighty-six post-comatose patients (67 men; mean age Oral session 11 46±17 SD) diagnosed with a vegetative state/unresponsive wakefulness syndrome (n=47) or a minimally conscious state (n=39) from General neurology traumatic (n=52) and non-traumatic (n=34) etiology were prospectively included in the study. Median time between injury and assessment was 5 months (IQR: 3 – 13 months). Localisation of auditory stimulation (i.e., head or eyes orientation toward the sound) O252 was assessed using the patient’s own name as compared to a ringing Substitutive treatment for GH deficit in patients bell. Statistical analyses used binomial testing (at p\0.05, corrected with traumatic brain injury for multiple comparisons). Results:. 37 (43 %) out of the 86 studied patients showed locali- O. Kozlowski, J. Paquereau, E. Merlen, C. Cortet Rudelli, sation to auditory stimulation. More patients (n=34, 40 %) oriented M. Rousseaux the head or eyes to their own name as compared to sound (n=20, CHRU de Lille, Hopital Swynghedauw (Lille, FR); CHRU de Lille, 23 %). Localisation preference was different according to the diag- Hopital Huriez (Lille, FR) nosis (i.e. minimally conscious patients showed more responses to their own name as compared to vegetative/unresponsive patients) but Objectives: Pituitary deficits are frequent in patients with severe it was not different depending on etiology or time since injury. traumatic brain injury (TBI) and could contribute to explain the late Conclusion: When assessing auditory function in disorders of cognitive sequelae and reduction of quality of life (QoL). A recent consciousness, using the patient’s own name is here shown to be more study has suggested that treatment of growth hormone deficit (GHD) suitable to elicit a response as compared to neutral sound. Our find- can improve cognitive disorders. However, we have no idea about the ings emphasize the clinical importance of using the patient’s own possible effects on participation to daily living activities and quality name when performing bedside testing of localisation to sound, of life (QoL) and about factors which could contribute to this adding to previous studies stressing the importance of using auto- improvement. Here, we analyzed the effectiveness of GHD substi- referential stimuli in disorders of consciousness (i.e., the use of a tutive treatment and factors contributing to this effect. mirror in the assessment of visual tracking). Methods: We included patients complaining of fatigue and cognitive disorders at least one year after TBI. They were assessed for i) pituitary functions (with stimulation tests), and ii) cognitive disorders (attention, memory, executive functions), participation in daily living activities and O254 QoL (QOLIBRI scale). Hormonal deficits were supplemented and GHD Pseudobulbar affect as a transient sports concussion treatment was provided in 23 cases (treated group) and was not given in symptom: the first case report 27 cases (non treated group). Control of cognitive assessment, partici- D. Kantor pation in daily living activities and QoL was performed one year later. Neurologique Foundation (Ponte Vedra, US) We performed ANOVAs of factors Group and Session (p\=0.05). Results: Most cognitive parameters improved, but without Objective: The objective of this study is to describe a case of transient between-group differences. More definite effect of GH treatment pseudobulbar affect (PBA) as a transient symptom of a sports (group x session interaction) was found for vigilance, recall of the concussion. Rey complex figure, and 2 out of 6 subtests of the QoL questionnaire: Background: PBA is a recognized symptoms of multiple neuro- personal and functional factors assessed by the patient. Tendencies logical conditions, and a growing body of literature suggests that it (p\=0.08) were also found for spatial orientation, and immediate may be much more common than previously thought. While traumatic recall in the verbal memory test (Buschke). Patients who most brain injury (TBI) is a known underlying condition associated with improved in QoL subtests were those with lower performance in PBA, transient PBA as a result of a sports concussion has not pre- cognitive tests and especially with lower QoL before GHD treatment. viously been described.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S35

Design/Methods: Case report of a single patient. nine patients the functional diagnosis had changed (11 % out of 84). Results: A 29-year-old previously healthy man sustained a con- Two patients were diagnosed with multiple sclerosis, two Parkinson’s cussion while catching a football at an American arena football game disease, one cerebellar ataxia, one hereditary sensorimotor neuropathy by falling over a 1.25 meters wall and hitting the back of his head. He type II, one idiopathic non-familial dystonia, one manganese-ephed- continued to play the rest of the game but after the conclusion of the rone related encephalopathy, one rheumatoidarthritis. Thirteen people game, instead of celebrating the win, he was found holding his head were dead (mean age 56.4 ± 14.2 years). and complaining of excessive emotionality (crying without a feeling Conclusion: Motor symptoms unexplained by organic disease, of sadness). He also developed dull occipital headaches exacerbated usually referred to as FMD, is not a rare problem. After follow-up by loud noises, but without other associated migrainous features. The period of 8–12 years around half of the patients symptoms have not PBA resolved over less than 24 h and the headaches improved over 5 improved. In nine cases the diagnosis of FMD proved to be incorrect. days. His neurological examination was normal and computerized and formal neuropsychological testing were both normal (on ImPACT computerized testing his cognitive efficiency index actually improved from a baseline of 0.31 to 0.4 post concussion – this is most likely effort related). O256 Conclusions: PBA can be a serious socially disabling symptom Accuracy of the prehospital diagnosis of acute associated with multiple underlying neurologic conditions. While cerebrovascular events PBA is seen commonly in patients suffering from TBI, it has not previously been described as a transient symptom of a concussion. M. A. Karlinski, M. Gluszkiewicz, A. Czlonkowska The social isolation and embarrassment felt by this otherwise healthy Institute of Psychiatry and Neurology (Warsaw, PL) man, would have been magnified had he suffered a TBI as opposed to Objectives: All patients suspected of an acute cerebrovascular event a mild TBI of sports related concussion. It is incumbent upon neu- (ACE) require immediate neurological assessment to initiate proper rologists to screen their patients for PBA; further research into the early management. The role of emergency health services is to pathophysiology of PBA in relation to the underlying neurological identify those patients and transfer them to the nearest stroke center. conditions (multiple sclerosis, amyotrophic lateral sclerosis, Alzhei- However, there are many conditions may be misdiagnosed as stroke, mer’s dementia, stroke, Parkinson’s disease and TBI) is warranted. and not all cases of stroke are correctly diagnosed in the prehospital setting. The aim of our study was to evaluate the accuracy of ACE diagnosis made by healthcare professionals in patients referred to a neurological emergency department (ED) and identify the conditions O255 misdiagnosed as ACE. Prognosis of the patients with functional motor Methods: We analyzed consecutive patients referred to a single neurological ED with a suspicion of ACE (defined as acute stroke, disorders TIA or descriptive diagnosis of unilateral weakness/aphasia) and also L. Leht, U¨. Krikmann, S.-M. Luü¨s, S. Haldre those discharged with a final diagnosis of stroke or TIA during a Tartu University Hospital (Tartu, EE) 12-month period. The referrals were considered correct if both prehospital and the discharge diagnosis were classified as ACE. Data Objectives: Functional motor disorders (FMD) include paralysis, were prospectively collected using a structured questionnaire. bradykinesia, dystonia, tremor, aphonia and motor tics, whereas the Results: The prehospital diagnosis of ACE was correct in 360 of symptoms are unexplained by organic disease or inconsistent with 570 patients suspected of ACE. Additionally 21 patients referred an medical condition of the patient. The main purpose of the study was non-ACE (mostly vertigo or headache) proved to suffer from ACE. to verify the diagnosis of FMD 8–12 years after initial diagnosis. The prehospital diagnosis was made with 95 % (95 % CI 92–96) Methods: The patients diagnosed with FMD in Neurology Clinic sensitivity, 37 % (95 % CI 49–58) specificity, 63 % (95 % CI 59–67) of Tartu University Hospital from 1998 to 2002 were included in the positive predictive value (PPV) and 92 % (95 % CI 88–95) negative study. The selection was based on the information from the case predictive value. The highest PPV was for descriptive syndrome- reports. Questionnaires about the course of the disease and new based diagnoses (100 %) and the lowest for TIA referrals (34 %). The neurological diagnoses with an invitation to specialist consultation conditions most frequently misdiagnosed as ACE were vertigo were sent to the patients. (18.3 %), electrolyte and metabolic disturbances (11.7 %), seizures Results: Eight-four patients were diagnosed with FMD, of them 55 (11.3 %), cardiovascular disorders (9.9 %), hypertension (8.0 %) and (65 %) women and 29 (35 %) men, mean age 41.1 ± 13.6 years. brain tumor (5.2 %). The ratio of misdiagnosis was significantly in Seventy-one patients had paresis, 17 hyperkinetic syndrome, 4 patients referred by general practitioners or other outpatient special- patients were diagnosed to have both. The most prevalent hyperki- ists than by emergency physicians (48.2 vs 31.8 %, p \ 0.001). nesis was tremor, followed by dystonia, ataxia, parkinsonian Conclusion: According to our findings, Polish emergency physi- syndrome, motor tics and unspecified jerks. 36 % of the patients had cians are sufficiently sensitive in identifying patients with ACE but acute onset of the disease. Precipitating factors were chronic stress in they tend to overuse the prehospital diagnosis of TIA. It emphasizes 31 %, burdened life anamnesis in 22 %, psychological trauma 18 %, the necessity to refer all patients suspected of ACE to the ED with a depression in 17 %, physical trauma in 12 % and using alcohol in direct access to proper neurological assessment. 10 %. Gait disorders were seen in 44 %. Fifty-five percent had additionally sensory disturbancies, 30 % had problems with balance, 20 % had speech disorders, 19 % problems with vision. Fifty-six people were contacted by questionnaire or by telephone O257 interview, data about two patients were found on medical databases, Clinical presentations of Vogt-Koyanagi-Harada 13 people (16 %) were not possible to contact with and no informa- disease tion about their medical condition was found. From 37 patients 22 % had fully recovered from the disease, in 19 % symptoms were J. Morgado, C. Nobrega, R. Relvas, A. Calado, improved, 27 % have got worse and for 22 % of the patients the I. Henriques disease had intermittent course. During follow-up of 8–12 years for Hospital Central of Lisbon (Lisbon, PT)

123 S36 J Neurol (2012) 259 (Suppl 1):S1–S236

Objectives: Vogt-Koyanagi-Harada disease (VKH) is an idiopathic (RRMS) over 2 years. Here we describe the clinical efficacy of BG-12 granulomatous inflammatory disorder. Diagnosis is based on the in RRMS in the Phase 3 CONFIRM study. Revised Diagnostic Criteria defined in 2001, which includes oph- Methods: Patients (18–55 years) with a diagnosis of RRMS thalmic, neurologic and dermatologic criteria. Generally, it is (McDonald criteria) and an Expanded Disability Status Scale (EDSS) characterized by neurological involvement (meningism, CSF pleo- score of 0.0–5.0 were randomized 1:1:1:1 to receive oral BG-12 240 cytosis) in an acute phase, followed by ophthalmic (uveitis, retinal mg twice (BID) or three times daily (TID), or matching placebo; or detachment and papilledema) and dermatologic manifestations. We subcutaneous glatiramer acetate (GA) 20 mg/day, an active reference report two presentation forms of VKH disease. comparator arm. The primary endpoint was ARR at 2 years. Sec- Methods: We reviewed the clinical history, brain CT and MRI, ondary clinical endpoints included the proportion of patients who blood and CSF analysis, optical coherence tomography (OCT) and relapsed and disability progression as measured by EDSS at 2 years. fluorescein angiography. Results: A total of 1,417 patients received placebo (n=363), Results: A 34-year-old woman presented a frontal headache, 8/10 BG-12 BID (n=359), BG-12 TID (n=345) or GA (n=350); and of intensity, with bilateral periorbital irradiation for 14 days. On baseline demographic and clinical characteristics were similar across examination, only a bilateral decreased of visual acuity was all groups. ARR (and 95 % confidence interval [CI]) at 2 years was observed. Brain MRI was normal and the CSF analysis showed a 0.401 (0.329, 0.488) for placebo versus 0.224 (0.179, 0.282) for BG- 3 pressure of 280 mmH2O, 400 mononucleated cells/mm and 68 mg/ 12 BID, 0.198 (0.156, 0.252) for BG-12 TID, and 0.286 (0.232, dl of protein. Initially we suspected of an infectious cause, but one 0.353) for GA, representing significant relative reductions versus week later a bilateral anterior uveitis and a retinal detachment were placebo of 44 % for BG-12 BID and 51 % for BG-12 TID (both observed and confirmed by OCT and fluorescein angiography. p\0.0001), and 29 % for GA (p=0.0128). Compared with placebo, Infectious serologies and viral PCR on CSF came negative. It was BG-12 BID, TID, and GA significantly reduced the risk of relapse diagnosed an incomplete VKH disease according to the diagnostic over 2 years by 34 % (p=0.0020), 45 % (p\0.0001), and 29 % criteria. She started corticotherapy, presenting a clinical and oph- (p=0.0097), respectively. At 2 years, the risk of 12-week confirmed thalmic improvement and CSF values normalization. A 22-year-old disability progression was reduced, although not significantly, by woman presented a progressive decrease of visual acuity for 14 days 21 % for BG-12 BID, 24 % for TID, and 7 % for GA versus placebo and a bilateral panuveitis with retinal detachment, other physical (p[0.05 for all comparisons). The incidence of adverse events and examination was normal. Brain CT was normal and CSF analysis serious adverse events was similar across all groups. showed 59 mononucleated cells/mm3 and a normal glucose and Conclusion: Clinical efficacy results from CONFIRM are consistent protein level. Criteria for incomplete VKH disease were also filled, with and further support those from DEFINE. Together with the so she started corticotherapy and then cyclosporine presenting a acceptable safety profile, these results suggest that BG-12 has the good clinical response. potential to be a valuable treatment option for patients with relapsing MS. Conclusions: VKH disease is an uncommon systemic inflamma- Study Supported by: Biogen Idec Inc. tory disorder with neurological involvement. We report two clinical presentations of this disease, both with a good response, which can be due to an early diagnosis. O259 Effects of BG-12 on magnetic resonance imaging outcomes in CONFIRM (Comparator and an Oral ______Fumarate in Relapsing-Remitting Multiple Sclerosis), Oral session 12 a randomized, placebo-controlled, phase 3 study D. Miller, R.J. Fox, J.T. Phillips, M. Kita, M. Hutchinson, Multiple sclerosis III E. Havrdova, D. MacManus, T. Yousry, R. Zhang, V. Viglietta, K.T. Dawson University College London’s Institute of Neurology (London, UK); O258 Cleveland Clinic (Cleveland, US); Baylor Institute for Immunology Clinical outcomes with BG-12 treatment in CONFIRM Research (Dallas, US); Virginia Mason Medical Center (Seattle, US); St. Vincent’s University Hospital (Dublin, IE); Charles University in (Comparator and an Oral Fumarate in Relapsing- Prague (Prague, CZ); (London, UK); Biogen Idec Inc. (Cambridge, Remitting Multiple Sclerosis), a multicentre, US) randomised, placebo-controlled, phase 3 study Objectives: In DEFINE, the first of two Phase 3 studies, oral BG-12 E. Havrdova, R.J. Fox, D. Miller, J.T. Phillips, M. Kita, (dimethyl fumarate) demonstrated significant reductions in clinical M. Hutchinson, M. Yang, R. Zhang, M. Novas, V. Viglietta, relapses, accumulation of disability progression, and magnetic reso- K.T. Dawson nance imaging (MRI) measures of disease activity versus placebo. Charles University (Prague, CZ); Cleveland Clinic (Cleveland, US); Here we describe the efficacy of BG-12 on MRI endpoints in patients University College London’s Institute of Neurology (London, UK); with relapsing-remitting multiple sclerosis (RRMS) from the Phase 3 Baylor Institute for Immunology Research (Dallas, US); Virginia CONFIRM study. Mason Medical Center (Seattle, US); St. Vincent’s University Methods: Patients aged 18–55 years with a diagnosis of RRMS Hospital (Dublin, IE); Biogen Idec Inc. (Cambridge, US) (McDonald criteria) and an Expanded Disability Status Scale score of 0.0–5.0, were randomized 1:1:1:1 to receive oral BG-12 240 mg twice Objectives: In DEFINE, the first of two Phase 3 studies, oral BG-12 (BID) or three times daily (TID), matching placebo, or subcutaneous (dimethyl fumarate) significantly reduced the proportion of patients glatiramer acetate (GA) 20 mg/day, an active reference comparator relapsed, annualized relapse rate (ARR), and disability progression arm. MRI evaluations were performed in a subset of intent-to-treat versus placebo in patients with relapsing–remitting multiple sclerosis patients; MRI endpoints included the number of new or newly

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S37 enlarging T2 hyperintense lesions, new T1 hypointense lesions, and presence or absence of risk factors. Studies are ongoing to fur- gadolinium-enhancing (Gd+) lesions at 2 years. ther characterize the PML risk in the subgroups identified in this Results: The MRI cohort included 681 patients. Baseline demo- analysis. graphic and clinical characteristics were similar across treatment This study was supported by Biogen Idec Inc. and Elan Pharma- groups and were representative of the overall intent-to-treat study ceuticals, Inc. population. BG-12 BID and TID groups had significantly reduced numbers of lesions at 2 years, with relative mean reductions versus placebo of 71 % and 73 % for new or newly enlarging T2 hyperintense (both p\0.0001) and 57 % and 65 % for new non-enhancing T1 O261 hypointense lesions (both p\0.0001), respectively. Relative odds Ò reductions for Gd+ lesions were 74 % and 65 % (p\0.0001 and Tysabri Observational Program (TOP) results: p=0.0001), respectively. In the GA group, relative mean reductions long-term safety and efficacy and association versus placebo at 2 years were 54 % for new or newly enlarging T2 between baseline treatment history and postbaseline hyperintense lesions (p\0.0001) and 41 % (p=0.0021) for new non- relapses in multiple sclerosis patients treated enhancing T1 lesions, and the relative odds reduction for Gd+ lesions was 61 % (p=0.0003). with natalizumab Conclusion: The MRI efficacy results with BG-12 from the L. Kappos, S. Belachew, H. Butzkueven, F. Pellegrini, CONFIRM study demonstrate significant effects on brain lesion M. Trojano, H. Wiendl, A. Zhang, R. Arnold activity as measured by T2, T1 and Gd+ lesions and provide further University Hospital Basel (Basel, CH); University Hospital of Sart- support for the potential role of BG-12 in the treatment of relapsing Tilman (Lie`ge, BE); The Royal Melbourne Hospital (Victoria, AU); MS. Consorzio Mario Negri Sud (Chieti, IT); University of Bari Study Supported by: Biogen Idec Inc. (Bari, IT); University of Mu¨nster (Mu¨nster, DE); Biogen Idec Inc. (Weston, US) Objectives: Evaluate long-term safety, efficacy, and associations O260 between baseline treatment history and postbaseline annualised Updated analysis of progressive multifocal relapse rate (ARR) in multiple sclerosis (MS) patients treated with leukoencephalopathy risk factors in natalizumab- natalizumab. Methods: The natalizumab (TYSABRI) Observational Pro- treated multiple sclerosis patients gram (TOP) study is an ongoing, open-label, multinational, G. Bloomgren, S. Richman, R. Arnold, M. Subramanyam, observational study of long-term outcomes in relapsing-remitting A. Natarajan, S. Lee, T. Plavina, J. Scanlon, A. Sandrock, MS patients in the postmarketing setting in Europe, Australia, and C. Bozic Canada. Incidence of serious adverse events (SAEs) was analysed. Biogen Idec Inc. (Weston, US) ARR and Expanded Disability Status Scale (EDSS) scores were assessed. Associations between baseline therapy and postbaseline Objectives: To update PML risk estimates in multiple sclerosis (MS) ARR were analysed using negative binomial regression for 5 patients considering or receiving natalizumab using three risk factors: baseline groups: therapy naı¨ve (n=337), interferon (IFN) only anti-JCV antibody positive serostatus, prior immunosuppressant use, (n=1626), glatiramer acetate (GA) only (n=288), switched between and natalizumab treatment duration. GA and IFN in either order (n=595), or immunosuppressant (IS) Methods: Data from postmarketing sources, clinical studies, and use (n=487). an independent Swedish registry were used to estimate PML inci- Results: As of June 2011, 3484 patients from 15 countries were dence in natalizumab-treated MS patients according to anti-JCV enroled. Patients received a mean of 14.6±11.2 (median 13 [range antibody status (positive or negative), prior immunosuppressant use 1-53]) natalizumab infusions. Overall, 5.1 % of patients experienced (yes or no), and natalizumab treatment duration (1-24 or 25-48 [=1 SAE; infections (1.1 %) and hypersensitivity reactions (0.7 %) months). Blood samples were available for anti-JCV antibody testing were most frequent. Seven cases of progressive multifocal leuko- from 5896 MS patients and from 37 natalizumab-treated MS patients encephalopathy occurred after 35, 29, 28, 26, 24, 24, and 12 who later developed PML. natalizumab infusions; 3 were previously exposed to mitoxantrone. Results: As of September 2011, 159 PML cases were confirmed Overall, the mean EDSS score was 3.5 at baseline and 3.4 after 3 among 92,105 natalizumab-treated patients (1.73 cases per 1000 years. ARR decreased significantly regardless of baseline treatment patients). All PML patients with samples available prior to diagnosis history; mean ARR decreased (n=3458) from baseline (1.98) to (n=37) tested anti-JCV antibody positive, and no PML patients testing postbaseline (0.28; P\0.0001), overall. Across groups, mean base- anti-JCV antibody negative were identified. When PML risk was line ARRs were similar (range 1.91-2.03; P=0.731), but stratified by anti-JCV antibody status, prior immunosuppressant use, postbaseline ARRs differed significantly (P\0.0001): therapy and natalizumab treatment duration, PML risk was lowest in anti-JCV naı¨ve=0.16; prior IFN=0.20; prior GA=0.23; prior IFN/GA or GA/ antibody negative patients (estimated at \=0.10 per 1000 [95 % IFN=0.25; prior IS=0.34. Lower mean on-therapy ARRs were confidence interval {CI}: 0-0.56] or\=0.17 per 1000 [95 % CI: 0.00- associated with fewer relapses in the year prior to starting natal- 0.94] patients, assuming one hypothetical PML case testing anti-JCV izumab (\=1 relapse: ARR=0.17 vs [1 relapse: ARR=0.27; antibody negative prior to diagnosis, and exposures [=1 natalizumab P\0.0001). Greater mean on-therapy ARRs were associated with dose or[=18 natalizumab doses, respectively). Patients with positive higher EDSS scores at baseline (EDSS score 0.0-2.0: ARR=0.18; anti-JCV antibody status, prior immunosuppressant use, and 25-48 EDSS score 2.5-4.0: ARR=0.22; EDSS score 4.5-9.5: ARR=0.24; months of natalizumab treatment had the highest estimated risk (10.6 P=0.001). per 1000 [95 % CI: 7.7-14.2] patients). Conclusion: The overall incidence and types of SAEs reported in Conclusion: The algorithm in this analysis can identify discrete TOP are consistent with natalizumab’s known safety profile. EDSS cohorts of patients at lesser or greater PML risk based upon the scores were stable. ARR was significantly reduced after 3 years of

123 S38 J Neurol (2012) 259 (Suppl 1):S1–S236 natalizumab. ARRs were lowest in therapy-naı¨ve patients, highest in O263 patients with prior IS. Updated data will be presented. Evaluation of patient satisfaction from the TENERE This study was supported by Biogen Idec Inc. and Elan Pharma- ceuticals, Inc. study: a comparison of teriflunomide and subcutaneous interferon beta-1a in patients with relapsing multiple sclerosis P. Vermersch, A. Czlonkowska, L. Grimaldi, O262 C. Confavreux, G. Comi, L. Kappos, T. Olsson, S. Jodl, Effects of a 24-week natalizumab treatment D. Bauer, P. Truffinet, A. Miller, J. Wolinsky, interruption on clinical and radiologic parameters M. Freedman, P. O’Connor for the TENERE Trial Group of multiple sclerosis disease activity: the RESTORE Objective: Teriflunomide is a new oral disease-modifying therapy in study development for relapsing forms of multiple sclerosis (RMS). This M. Kaufman, B. Cree, J. De Se`ze, R. Fox, R. Gold, study evaluated the effectiveness and safety of teriflunomide compared with subcutaneous interferon beta-1a (IFN) in patients with H. Hartung, D. Jeffery, L. Kappos, X. Montalban, RMS. Here we report secondary endpoints from TENERE B. Weinstock-Guttman, A. Natarajan, A. Pace, (NCT00883337), including patient satisfaction scores. D. Campagnolo, B. Ticho, P. Duda Methods: In this multicentre, parallel-group, rater-blinded study, Carolinas Health Care System (Charlotte, US); University of 324 patients were randomised to receive once-daily teriflunomide 7 California San Francisco Multiple Sclerosis Center (San Francisco, mg or 14 mg, or IFN (albumin-free formulation, three-times weekly). US); Hopital Civil (Strasbourg, FR); Cleveland Clinic (Cleveland, The study had variable individual duration and a fixed common end, US); St. Josef Hospital, Ruhr University (Bochum, DE); Heinrich- with treatment duration, for patients completing treatment, ranging Heine-University (Du¨sseldorf, DE); The MS Center at Advance from approximately 48 to 114 weeks. The primary endpoint was time Neurology at Cornerstone Health Care (Advance, US); University to failure, defined as the first occurrence of confirmed relapse or Hospital Basel (Basel, CH); Vall d0Hebron University Hospital permanent treatment discontinuation for any reason, whichever came (Barcelona, ES); Jacobs Neurological Institute (Buffalo, US); Biogen first. Secondary endpoints included annualised relapse rate (ARR), Idec Inc. (Weston, US) Fatigue Impact Scale (FIS) and Treatment Satisfaction Questionnaire for Medication (TSQM), an assessment of effectiveness, side effects, Objectives: RESTORE was a randomized, partially placebo (Pbo)- convenience and global satisfaction. controlled exploratory study evaluating effects of a 24-week natal- Results: There was no statistical superiority in any group for time to izumab treatment interruption on multiple sclerosis (MS) disease failure. No difference was detected in adjusted ARRs between the ter- activity; it compared continued natalizumab treatment with Pbo or iflunomide 14 mg and IFN groups (0.259 and 0.216, respectively); the with switching to an alternative immunomodulatory therapy (AIT) of rate was higher in the teriflunomide 7 mg group (0.410). The least- interferon beta-1a (IFNB-1a), glatiramer acetate (GA), or methyl- square (LS) mean changes from baseline in FIS total score at Week 48 prednisolone (MP). AIT drug was chosen by participants and/or their (positive change indicating a worsening), were 0.969 (p=0.0276 vs neurologists. IFN), 4.096 (p=0.1789 vs IFN) and 9.099 for teriflunomide 7 mg, 14 mg Methods: Eligible patients were relapse free during natal- and IFN. Patients receiving both doses of teriflunomide reported higher izumab treatment for [=12 preceding months and had no TSQM scores (higher score indicating greater satisfaction) for effec- gadolinium-enhancing (Gd+) lesions on screening brain MRI. tiveness (7 mg, p=0.0229 and 14 mg, p=0.2759 vs IFN), side effects Patients were randomized 1:1:2 to continue natalizumab or to (p\0.0001 for both teriflunomide doses vs IFN) and convenience switch to Pbo or to open-label AIT. If protocol-defined MS dis- (p\0.0001 for both teriflunomide doses vs IFN) at Week 48. The LS 3 ease activity (clinical relapse and/or 1 new Gd+ lesion [0.8 cm mean TSQM global satisfaction score at Week 48 was 68.292 in volume or [=2 Gd+ lesions) occurred, rescue treatment with (p=0.0239 vs IFN), 68.818 (p=0.0162 vs IFN) and 60.975 for teriflun- high-dose corticosteroids and/or natalizumab could be given. omide 7 mg, 14 mg and IFN, respectively. Both doses of teriflunomide After the 24-week randomized period, open-label natalizumab were well tolerated, with no new/unexpected safety signal identified. was reintroduced for 24 weeks. Conclusions: No significant difference was observed between the Results: Patients (n=175) were randomized to natalizumab 26 %, treatment groups on the risk of failure. Teriflunomide patients expressed Pbo24%,orAIT50%(IFNB-1a19%,GA19%,MP61%).Pre- greater satisfaction with treatment than did IFN patients at Week 48. natalizumab activity was balanced, except for lower activity in the Study supported by: Genzyme, a sanofi company. IFNB-1a group; 167 patients were evaluable for efficacy. Overall, 50 of 167 (30 %) patients, all in Pbo or AIT groups, were rescued with natalizumab during the randomized period because of MRI or ______clinical disease activity; the first rescue was at week 10. Of 167 patients, 48 (29 %) met MRI rescue criteria: 0/45 (0 %) natal- Oral session 13 izumab; 18/41 (44 %) Pbo; 1/14 (7 %) IFNB-1a; 8/15 (53 %) GA; 21/52 (40 %) MP. MRI activity during natalizumab interruption did not exceed pretreatment levels. Four percent of natalizumab patients Cerebrovascular disorders I and 15 %–29 % of patients in the other arms were diagnosed with relapse. Conclusion: RESTORE data confirm a high rate of MRI and O264 clinical MS disease activity recurrence after natalizumab cessation. Does thrombolysis enhance seizures in the acute MRI scans helped identify patients with recurring disease activity during natalizumab interruption; the majority of activity was seen at ischaemic stroke setting? 16–20 weeks. V. Alvarez, A. O. Rossetti, P. Michel Supported by Biogen Idec Inc. and Elan Pharmaceuticals, Inc. Centre Hospitalier Universitaire Vaudois (Lausanne, CH)

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S39

Background: Seizures are related to stroke in various ways. They can and Eastern European countries between February 2003 and February appear at stroke presentation, in the acute phase (commonly defined 2010. All included patients had a complete 3-month follow-up. as the first 7 days) or as a late complication. The incidence of seizures The frequency of sICH was 2.1 % for SITS definition, 7.0 % for in acute phase varies between 1.2 % to 6.3 % in different studies ECASS II and 9.9 % for NINDS. The positive predictive value (PPV) depending mainly of inclusions criteria and methods. Several pre- for 3-month mortality was 0.81, 0.78 and 0.65, respectively. The PPV dictors have been described and confirmed but thrombolysis has not for death or disability was 1.00, 0.97, and 0.94. The OR for death at 3 been investigated as a risk factor despite its potential neurotoxic month follow-up comparing the SITS and ECASS II definition was effect. The aim of our study was to identify risk factors for seizures 1.20 (95 %CI: 0.66-2.17), p=0.554, SITS and NINDS 2.26 (95 %CI: during the acute phase of ischemic stroke in a large consecutive series 1.28-3.98), p=0.004 and ECASS and NINDS 1.89(1.34-2.66), of patients that includes thrombolysed patients. p\0.001. The differences in 3-month death or disability rate were Methods: We performed a case–control study at our tertiary care significantly worse for the SITS defined sICH comparing with center using data from the Acute Stroke Registry and Analyse of NINDS, (p=0.005). Lausanne (ASTRAL) containing acute ischemic strokes prospectively Our findings show, that although all types of sICH are associ- assessed. Patients with a seizure occurring during the first 7 days ated with poor outcome, the SITS defined sICH has the highest following stroke were retrospectively indentified. Uni- and multi- PPV for poor outcome after 3 months in ischaemic stroke patients variable statistical analyses were applied to compare cases and treated with intravenous thrombolysis. Considering the time point randomly selected controls. for the occurrence of sICH, it also seems to have the strongest Results: We identified acute 28 seizures in 2327 acute ischemic relation to the treatment itself. Therefore, it would be rational to strokes (1.2 %). All seizures occurred during the three first days and prefer this classification for stroke research and everyday clinical mostly within the first 24 h. Demographics, premorbid treatment, practice. prevalence of previous clinical stroke and previous seizures were globally comparable. Cortical involvement, recanalisation, thrombolysis and higher NIHSS were statistically associated with seizures in univariated analysis. Stepwise logistic regression including cortical O266 involvement, NIHSS on admission, thrombolysis and blood glucose Morphologic findings in young adults with ischaemic on admission identified cortical involvement (OR 7.48, CI: 2.09 - cerebrovascular disease: the Stroke in Young Fabry 26.73, p=0.002) and thrombolysis (OR 2.82, CI: 1.08 – 7.37, p=0.034) Patients (sifap1) study as independently associated with seizure occurrence. Conclusions: Acute seizures in ischemic stroke seem relatively F. Fazekas, C. Enzinger, R. Schmidt, M. Dichgans, infrequent and cortical involvement is the principal risk factor. Our B. Ga¨rtner, G.J. Jungehu¨lsing, M. Hennerici, results also show that thrombolysis with rt-PA increase the likelihood P. Heuschmann, M. Holzhausen, M. Kaps, C. Kessler, of seizures in acute phase independently from recanalisation or P. Martus, J. Putaala, S. Ropele, C. Tanislav, symptomatic intracerebral hemorrhage. This does not seem to eliminate the overall beneficial effects of rt-PA. If our findings are T. Tatlisumak, B. Norrving, A. Rolfs on behalf of the sifap1 confirmed in other studies, the use of other, less ‘‘neurotoxic’’ agents Investigators for acute recanalisation may show more benefits than intravenous rt- Objectives: Information on cerebral morphologic findings in young PA. patients with stroke is limited and may give pathophysiologic insights. We wanted to extend this knowledge by central collection and interpretation of imaging data in a prospective multinational O265 study on the frequency of Fabry disease in young adults (18-55 years) with an acute cerebrovascular event (sifap1). Reliability of different symptomatic intracranial Methods: We here analyzed the MRI scans of patients enrolled haemorrhage definitions in predicting 3-month outcome into the SIFAP1 project with a clinical evidence for ischemic stroke after intravenous thrombolysis for ischaemic stroke (IS) or a transient ischemic attack (TIA) and in whom MRI including A. Kobayashi, M. Karlinski, A. Czlonkowska, R. Mikulik, DWI was obtained\10 days of the cerebrovascular event (CVE). Age was categorized according to the WHO: 18 to 24, 25 to 34, 35 to 44, M. Brozman, V. Svigelj, L. Csiba, K. Fekete, J. Korv, and 45 to 55 years and we compared age- and gender-specific pro- V. Demarin, A. Vilionskis, D. Jatuzis, Y. Krespi, N. Ahmed, portions of various infarct features, white matter hyperintensities N.-G. Wahlgren on behalf of the SITS-EAST Collaborative (WMH) and of microbleeds (MB). Group Results: There were 2278 patients with IS and 724 patients with TIA. In both groups the proportions of patients with acute ischemic Three different classification of sICH are frequently used: SITS (Safe abnormalities were similar across all age categories (IS: 84 %; TIA: Implementation of Thrombolysis for Stroke) – parenchymal type 2 14 %). The relative percentage of acute infarcts in the posterior cir- haemorrhage (PH2) within 24 h of treatment and deterioration by culation decreased continuously with advancing age (particularly in [=4 points NIHSS or leading to death, ECASS II (European Coop- men). In the highest age decade there was a rather stepwise increase erative Acute Stroke Study) – any new haemorrhage and clinical in the frequency of lacunar infarcts (\45 yrs: 16 %,[=45 yrs: 25 %) deterioration or neurological decline by [=4 points NIHSS and and of early confluent to confluent deep WMH (\45 yrs: 6 %,[=45 NINDS (National Institute of Neurological Disorders and Stroke) - yrs: 15 %). We also noted a high prevalence of old infarcts (24.5 %) any new haemorrhage and any neurological worsening. All of them which remained high (18.8 %) even when excluding patients with an are associated with poor clinical outcome. However, it is not estab- earlier symptomatic CVE. The prevalence of old infarcts in first ever lished which one carries the highest predictive value for the long term CVE patients increased with age (from 7.8 % in those aged \=24 to outcome. Our aim is to compare those classifications in terms of 25 % in those aged [45 yrs). Old MB were rare (6 %). 3-month outcome. Conclusion: Our findings show a high rate of silent old infarcts in We analyzed 4199 acute stroke patients treated with intravenous young adults with a first ischemic CVE and a preference for posterior thrombolysis that were contributed to the SITS registry by 9 Central circulation ischemia in the very young. Findings associated with

123 S40 J Neurol (2012) 259 (Suppl 1):S1–S236 small-vessel related stroke become apparent especially in patients aim is to assess if lesions of these nuclei worsen post-stroke glycae- aged [=45 years. mic control. We compared pre and post-stroke glycaemic control The sifap1 study (Stroke In Young Fabry Patients, www.sifap.eu; between patients with LMS and controls with other acute stroke ClinicalTrials.gov: NCT00414583) has been supported partially by an locations. unrestricted scientific grant from Shire Human Genetic Therapies. Methods: We identified 33 patients admitted to our hospital from 2000 to 2010 with a first ever stroke confirmed by MRI as LMS; 26 fulfilled the inclusion criteria: a) alive at the end of the first 24 h, b) had no simultaneous infarct of other brain region, and c) admitted in O267 the first 24h after stroke onset. Glycaemic values and clinical data Risk reduction of brain infarction during carotid were retrieved from a hospital-based prospective stroke registry and clinical records. Random sampling was used to select a control group endarterectomy or stenting using sonolysis. of patients with strokes not affecting the insula or brainstem, matched A prospective randomised pilot study for age and gender. We used HbA1c at admission to estimate pre- M. Kuliha, D. Sˇkoloudı´k, M. Roubec, V. Procha´zka, stroke glycaemic control. T. Jonszta, J. Krajca, D. Czerny, T. Hrbać, R. Herzig, Results: The average serum glucose (ASG) of LMS patients was 168,6 mg/dl (Sigma=58,1) from stroke onset to 24h and 137,1 mg/dl K. Langova´, D. Ota´hal (Sigma=51,2) from 24h to 72h. In the control group the ASG were University Hospital Ostrava (Ostrava, CZ); Palacky University and 133mg/dl (Sigma=50,9) and 127,2 mg/dl (Sigma=47,9) respectively. University Hospital Olomouc (Ostrava, CZ) A linear regression model, adjusted for previous diabetic state and Background: Sonolysis is a new therapeutic option for the infections, showed that ASG in LMS patients was significantly acceleration of artery recanalization. The aim was to confirm the higher than in controls (p=0,001; R2=55,6 %) in the 24 h after risk reduction of brain infarction during carotid endarterectomy stroke, with no significant differences for the 24-72 h period. As (CEA) and carotid stenting (CAS) using sonolysis with continu- compared to pre-stroke glycaemic levels, glycaemia in LMS patients ous transcranial Doppler (TCD) monitoring by diagnostic 2 MHz raised significantly more than in controls during the 24h after stroke probe. (p=0,01). There were no significant differences in the 24-72 h Methods: All consecutive patients 1/presenting with [70 % ste- period. nosis of the internal carotid artery, 2/indicated to CEA or CAS, 3/who Conclusion: This study supports the hypothesis that vascular signed informed consent were enrolled to the study since September lesions of the vagus nerve nuclei worsen post-stroke glycaemic 2010 to January 2012. Patients were randomized into 2 groups: Group control. This hypothesis and the long-term effects of these lesions 1 with sonolysis performed during the intervention using continuous justify further studies. TCD monitoring with diagnostic 2 MHz probe and, Group 2 without continuous TCD monitoring. Neurological examination and brain magnetic resonance imaging (MRI) were performed in all patients O269 before and 24 h after intervention. The number of symptomatic and Very small cerebral aneurysms: do they rupture? asymptomatic new brain ischemic lesions was assessed, including statistical evaluation using T-test. P. Dolati, M. Tso, W. Morrish, J. Wong, G. Sutherland Results: Eighty-six patients (54 males, mean age 65.3±8.5 years) University of Calgary (Calgary, CA) were included in the study. Out of the 41 patients randomized to Background: The risk of bleeding from a cerebral saccular aneurysm Group 1 (29 males, mean age 65.5±8.3 years), 22 underwent CEA has been estimated at about 1-2 % per year. A current belief amongst (Group 1a) and 19 CAS (Group 1b). Out of the 45 patients random- neurosurgeons is that the larger the aneurysm, the higher the chance ized to Group 2 (25 males, mean age 65.0±8.6 years), 19 underwent of rupture. This implies that small unruptured aneurysms may be CEA (Group 2a) and 26 CAS (Group 2b). New brain infarctions on considered benign. We conducted a local analysis of aneurysmal follow up MRI were found in 12 (29.3 %) patients in Group 1; 4 subarachnoid hemorrhage, with an emphasis on those ruptured lesions (18.2 %) in Group 1a and 8 (42.1 %) in Group 1b. In Group 2, new of small size. brain infarctions were found in 16 (35.6 %) patients; 4 (21.1 %) in Methods: We retrospectively reviewed hospital records and Group 2a and 12 (46.2 %) in Group 2b (p[0.05 in all cases). radiological tests of all patients who presented to our tertiary care Conclusion: The pilot study demonstrated an apparent trend for center with a ruptured saccular aneurysm from January 2008 to the reduction of the risk of brain infarctions during CEA and CAS September 2011. The size of the dome and neck (in millimeters), using sonolysis. aspect ratio (AR), and location of the aneurysms was determined Supported by grants IGA MH CR NT/11386-5/2010 and NT/ using preoperative computed tomography angiography (CTA) and 11046-6/2010. digital subtraction angiography (DSA). Result: We identified 123 patients with a ruptured saccular aneurysm. Of these, 44 patients were treated by clipping and 79 patients via coiling. The average size of the dome, neck, and AR was O268 6.6±4.1 mm (range 5-26 mm), 3.1 mm, and 2.6±0.9, respectively. Lateral medullar infarction and hyperglycaemia: study Forty-five patients (37 %) had a ruptured aneurysm measuring less in 26 patients with control group than 5 mm. For these small aneurysms (range 1.5-4.9 mm), the L. Ruano, I. Alves, R. Barreto, C. Veira, V. Tedim Cruz average size of the dome, neck, and AR was 3.9±1.1 mm, 1.6 mm, and 2.1±0.6, respectively. The anterior communicating artery was the Centro Hospitalar de Entre Douro e Vouga (Santa Maria da Feira, PT) most common location regardless of size. Objectives: Post-stroke hyperglycaemic peaks are common. The Conclusion: Small aneurysms (\5 mm) are a substantial cause of insular infarct is associated with higher glucose levels than infarcts in aneurysmal subarachnoid hemorrhage in our center and should be other cortical areas. Animal models showed that the ambiguous and considered lesions with potential for rupture. We suggest that size dorsal nuclei of the vagus nerve modulate insulin secretion. These alone should not be the main characteristic in determining appropri- nuclei are affected in the lateral-medullar ischemic stroke (LMS). Our ateness of prophylactic aneurysm repair.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S41

Oral session 14 performance is superior to placebo and equals the effect of intravenous infusion (IVIG). Methods: Subjects with motor involvement in maintenance ther- Neuromuscular disorders apy with IVIG fulfilling the EFNS/PNS criteria for CIDP, aged 18 – 80 years were considered for participation. Exclusion criteria were pregnancy, malignancies, dementia, severe medical disorders and psychiatric disturbances. Thirty patients characterized as IVIG- O270 responders by their treating physicians were included in the study. Peripheral autonomic neuropathy: a morphological Participants were randomised to receive either subcutaneous IgG and functional study of sympathetic innervation (1.6 g/10 cc) or subcutaneous saline in a double-blinded fashion. Infusions were given twice or thrice weekly for 12 weeks at home. R. Liguori, A. Incensi, M. Giannoccaro, V. Di Stasi, The amount of immunoglobulin given corresponded to the clinical F. Pizza, A. Baruzzi, V. Donadio predetermined dose divided by the interval. The first subcutaneous University of Bologna (Bologna, IT) infusion was delivered two weeks after the last IVIG treatment at the usual dosage. Objectives: The diagnosis of peripheral autonomic neuropathy (PAN) Participants were evaluated at four time intervals: - 2 weeks, 0, 10 has recently been improved even though autonomic tests directly and 12 weeks after treatment with subcutaneous infusions. Muscle exploring peripheral sympathetic fibre morphology and function are strength was determined at isokinetic dynamometry at four prede- lacking in this condition. The aim of this study was to report the first termined and weakened muscle groups. Moreover, an Overall morphological and functional evaluation of muscle and skin sympa- Disability Sum Score (ODSS), a 40 meter walking test, a nine hole thetic innervation in PAN. peg test, a Neurological Impairment Score (NIS), a Medical Research Methods: We studied 28 patients (mean age 51±20 years) with Council (MRC) score and a grip strength test were included. Stan- PAN signs and/or symptoms. Among them 7 patients showed dardized electrophysiological recordings from three nerves and diabetes mellitus, 4 Sjogren disease, 7 immune-mediated disorder, plasma IgG levels were obtained, also. 1 paraneoplastic disorder, 2 primary amyloidosis, 2 hepatitis C, and The primary end-point was the change of strength at isokinetic in 5 the aetiology was undetermined. Patients underwent micro- dynamometry in the two study groups. Secondary end-points were the neurographic record of muscle and skin sympathetic nerve treatment response of SCIG vs IVIG and the variation of the treatment activities from peroneal nerve and punch skin biopsy from thigh response during SCIG vs IVIG. and leg to evaluate skin autonomic innervation analyzed by a Results: The study ran during the period April 2010 – October quantitative method showing a high intervariability and intravari- 2011. Results will be presented. ability correlation. Thirty-two age-matched healthy subjects served J. Jakobsen has received research grants from Baxter A/S. as controls. Results: Skin autonomic innervation density was reduced in the distal site (i.e. leg) of 24 patients (96 %) whereas the proximal site (i.e. thigh) was less affected (60 %) indicating length-dependent O272 damage. Autonomic innervation dysfunctions usually included a Prediabetes/early diabetes-associated polyneuropathy is deranged pattern of innervation and morphological nerve fibre abnormalities such as fragmentation. Microneurographic failure to predominantly preclinical and involves sensory small record sympathetic activity characterized 61 % of patients and was fibres frequent in patients with orthostatic hypotension. S. Bursova, J. Bednarik, E. Vlckova, M. Hnojcikova, Conclusion: Autonomic innervation study of skin annexes is a M. Nemec, P. Dubovy, J. Beloradkova, L. Dusek, sensitive method aid in diagnosing PAN. Microneurography although showing less sensitivity could be an useful neurophysiological J. Jarkovsky approach for PAN diagnosis particularly in patients with orthostatic Masaryk University (Brno, CZ); Faculty Hospital (Brno, CZ) hypotension. Aim: A prospective case–control study in a group of patients with prediabetes (preDM) and early (\3 years) diabetes mellitus type 2 (eDM2) and normoglycemic controls was performed to investigate the prevalence and anatomical profile of preDM/eDM2-associated O271 neuropathy and the value of the most frequently used diagnostic tests, A randomised, double-blinded, placebo-controlled trial bedside and laboratory. of the effect of subcuta-neous immunoglobulin Methods: A group of 48 consecutive patients with eDM2, 17 patients with impaired glucose tolerance or impaired fasting glucose on muscular performance in chronic inflammatory and 40 age- and sex-matched normoglycemic controls were exten- de-myelinating polyneuropathy sively evaluated for neuropathy. T. Harbo, L.H. Markvardsen, S. Sindrup, H. Andersen, Results: Both clinical and laboratory signs of prediabetes/early I. Christiansen, N.K. Olsen, L. Lassen, J. Jakobsen DM2-associated polyneuropathy were detected in 30.8 % and 13.8 % of pooled preDM/eDM2 patients using two alternative criteria for Aarhus University Hospital (Aarhus, DK); Odense University neuropathy: at least one clinical sign and one laboratory abnormality Hospital (Odense, DK); National Hospital (Copenhagen, DK); or at least two clinical and two laboratory abnormalities, in com- Aalborg University Hospital (Aalborg, DK); Glostrup University parison with 7.5 % and 0.0 % of abnormalities in the control subjects Hospital (Copenhagen, DK) (p = 0.007 and p = 0.012). The differences in intraepidermal nerve Objectives: Subcutaneous treatment with large amounts of immuno- fibre density values in distal calf represented the most significant globulins is feasible and effective in multifocal motor neuropathy and difference between pooled preDM/eDM2 patients and controls (4.54 has been reported in a few cases in chronic inflammatory demyelin- vs. 9.99/mm; p \0.0001). Patients with possible peripheral neuro- ating polyneuropathy (CIDP). We hypothesized that the effect of pathic pain (23.1 % of preDM/eDM2 patients) had a significantly subcutaneous treatment with immunoglobulins (SCIG) on muscular higher prevalence of abnormalities of tactile, pressure and thermal

123 S42 J Neurol (2012) 259 (Suppl 1):S1–S236 sensation, vibration and thermal perception threshold, nerve con- levels (reduced or absent) deficiency due to mutations in CAPN-3 duction studies, and intraepidermal nerve fiber density distally gene. compared to painless preDM/eDM2 patients. The aim of this study is to present a series of 31 cases of A/P Conclusions: PreDM and eDM2 are significantly associated with hyperCKemia showing calpain-3 deficiency in muscle biopsy polyneuropathy that predominantly involves sensory small fibres and Patients and Methods: Patients referred with serum CK levels is mostly preclinical. The presence of neuropathic pain in preDM/ above 300 IU/L in which primary causes had been ruled and patho- eDM2 is a strong predictor for neuropathy. logical calpain-3 levels were detected by western blot. We performed Supported by a project of the Internal Grant Agency of the Min- a review, of clinical features, histological evaluation, protein analysis istry of Health of the Czech Republic (grant No. NS9667-4). with immunohistochemical and western blot methods, and sequencing the gene CAPN-3. Results: The series included 24 male and 7 female; Three out of them were children, 14 teenagers and 14 adults. Seven patients were O273 asymptomatic and 24 paucisymptomatic. Histology was normal The pure sensory form of Lewis-Sumner syndrome (3 %), non-specific (42 %) or with specific features (55 %) that were M. de Freitas, O. Nascimento, F. Cardoso, C. Pupe grouped into dystrophic (16 %), mitochondrial (23 %), inflammatory University Federal Fluminense (Niteroí, BR) (10 %) and glycogenosis (6 %). In addition to calpain-3 deficiency, some patients showed other protein abnormalities: dysferlin (1), lamin Lewis–Sumner syndrome (LSS) is a dysimmune peripheral nerve dis- A/C (1) and caveolin-3 (2). Genetic sequencing of CAPN-3 gene was order, characterized by a predominantly distal, asymmetric weakness normal in 20 patients, 5 with polymorphisms (T32T, A236T, and mostly affecting the upper limbs. LSS represents the asymmetric variant c.606T P26P \C), 3 carriers of LGMD 2A (R748Q, R572W and of chronic inflammatory demyelinating polyneuropathy (CIDP) with M262L) and 3 with LGMD 2A. multifocal pattern of motor and sensory loss. Nerve conduction studies Conclusions: The deficit of calpain-3 in muscle of patients with show conduction block and other features of demyelination. There is A/P hyperCKemia is relatively frequent (16 %), but it is mostly few reports of a pure sensory presentation of LSS, without weakness and secondary. Exceptionally hyperCKemia expression may be hetero- atrophy. We report two patients with these features. zygous carriers or presymptomatic stages of a LGMD 2A. The first one, a 45 year old man, in a period of six months had pain, paresthesia and superficial hypoesthesia in left ulnar and in both superficial peroneal nerves territories. The second one, a 53 year old man presented sensory complains in the territories of right femuro- O275 cutaneous, left ulnar and left posterior tibial nerves during a period of 18 months. Ankle jerks were absent in both patients. CSF examina- CUGBP1 in myotonic dystrophies: new diagnostic tion revealed increased protein level in the first case and was normal histopathological marker and player in pathomolecular in the second patient. The nerve conduction revealed increased sen- mechanism sory latencies in both ulnar and sural nerves with prolonged latency G. Meola, E. Bugiardini, L. Renna, F. Rizzo, R. Cardani and reduced motor conduction velocity (MCV) in the right peroneal University of Milan (San Donato, IT); Fondazione Malattie nerve in the first case. In the second one there were increased motor Miotoniche - IRCCS Policlinico S. Donato (San Donato, IT) latencies, conduction block and low MCV in ulnar nerves, temporal dispersion in median nerves, no SNAP in sural nerves and the F wave Objectives: Myotonic dystrophies (DM) are multisystemic neuro- latency were prolonged in the upper limbs nerves. The sural nerve muscular disorders caused by non-coding mutations. Two loci are biopsy was preformed and showed features of demyelination. Clinical associated with DM diseases, DM type 1 (DM1) caused by the improvement was obtained with IVIg treatment, in both patients. expansion of an unstable CTG repeat in the 3’UTR of DMPK gene and Although LS syndrome is defined as a multifocal acquired DM type 2 (DM2) caused by the expansion of an unstable CCTG demyelinating sensory and motor neuropathy, there are few reports of expansion in the first intron of the ZNF9 gene. Mutant RNA transcripts cases of only sensory symptoms. Our cases present electrophysio- accumulate in multiple ribonuclear inclusions interfering with the logical and pathological criteria for an acquired asymmetric activity, localization or expression levels of specific RNA-binding demyelinating neuropathy. Both patients became better with IVIg. In proteins such as MBNL1 and CUGBP1. MBNL1 is sequestered in the conclusion we believe that CIDP spectrum is broad and a pure sen- nucleus by ribonuclear inclusions and the cytochemical detection of sory presentation of LSS could be included. nuclear foci containing expanded RNAs or MBNL1 is accepted Lewis-Sumner syndrome may presents in a pure sensory form. diagnostic marker for DM (Cardani et al., 2004; 2006). On the other hand, it has been demonstrated that CUGBP1 is upregulated in DM1 muscle cells. A combined effect of decreased MBNL1 and increased CUGBP1 activity deregulate the splicing program of a subset of genes O274 resulting in DM multisystemic phenotypes. However the role of CU- Calpain-3 deficiency in paucisymptomatic GBP1 in DM2 is particularly intriguing since contradictory results on its expression have been reported. Thus additional studies are required or asymptomatic hyperCKemia to clarify the role of CUGBP1 in DM2 molecular pathogenesis. P. Martı´, N. Muelas, O. Jaka, M. Zulaika, A. Saenz, Methods: The expression of CUGBP1 has been analyzed in DM F. Mayordomo, T. Sevilla, R. Vilchez, A. Lopez de Muniain, muscle biopsies by immunohistochemistry (I.H.) and western blot (W.B.) J. Vilchez assay. Total protein extracts have been obtained from biceps brachii of DM1 and DM2 patients and from healthy subjects used as control. University Hospital la Fe (Valencia, ES); BIODONOSTIA (San Results and Conclusions: I.H. and W.B. results obtained from 5 Sebastian, ES) DM1 and 5 control subjects indicate a clear increase of CUGBP1 The asymptomatic or paucisymptomatic (A/P) hyperCKemia are is a expression in DM1 muscle biopsies as compared to controls syndromes that may represent a muscle disease in a subclinical or (0.13±0.03 vs 0.08±0.02). On the contrary no differences in muscle preclinical stage, such as limb-girdle muscle dystrophies (LGMD). CUGBP1 expression have been found between DM2 (n=5) and Among these, LGMD 2A is characterized by pathological calpain-3 controls (0.08±0.02 vs 0.08±0.02). To further investigate the role of

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S43

CUGBP1 in DM muscle biopsies, the expression of this protein will O277 be analyzed on a larger number of samples and correlated to pre- Early infantile epileptic encephalopathy 4: case report senting phenotypes (congenital vs adult form in DM1 and PROMM vs PDM vs paucisymptomatic in DM2). Moreover CUGBP1 expression of two Portuguese patients with novel mutations will be related to the expression of other proteins involved in DM in the STXBP1 gene molecular pathology such as MBNL1, DMPK and ZNF9. M. Sampaio, D. Alves, S. França, R. Rocha, R. Sousa, M. Vila Real, S. Biskup, M. Leaõ Centro Hospitar de Saõ Joaõ (Porto, PT); Centro Hospitar de Vila ______Nova de Gaia (Porto, PT); CeGaT GmbH and Hertie Institute for Oral session 15 Clinical Brain Research (Tu¨bingen, DE) Introduction: Early infantile epileptic encephalopathy (EIEE) 4 with suppression-burst is caused by heterozygous mutations in the Child neurology gene encoding syntaxin binding protein 1 (STXBP1), which can be associated with other neurological phenotypes. We describe two Portuguese patients with EIEE and ‘‘de novo’’ heterozygous O276 mutations in the STXBP1 gene, not previously reported in the literature. New type-4 D-bifunctional protein deficiency caused Case report: Patient 1 is a 8 years old male, born after a normal by compound heterozygous mutation of hydroxysteroid pregnancy. At 6 weeks of age he started to have partial and gen- 17-beta dehydrogenase 4 (HSD17B4) eralized tonic–clonic seizures, followed, at 3 months old, by tonic H.J. McMillan, T. Worthylake, M. Geraghty, D. Bulman, spasms, with poor control. The EEG showed suppression-burst and brain MRI was normal. At 5 months of age, when there was a C. Gottlieb, S. Coupand, S. Lawrence, K.M. Boycott transition to West syndrome, he started vigabatrin and remained Children’s Hospital of Eastern Ontario (Ottawa, CA); Ottawa Eye seizure free from the age of 6 months. Sequencing of the STXBP1 Institute (Ottawa, CA) disclosed a ‘‘de novo’’ mutation c.1462-2A[T, a splice-site mutation D-bifunctional protein (DBP) catalyzes the peroxisomal B-oxidation of intron 16 probably resulting in a non-functional STXBP1 protein. of fatty acids & their derivatives. Abnormal function of DBP is typi- Presently the neurological examination shows absent language, cally associated with congenital life-limiting disease. DBP has 3 communication limited to elementary emotions, spastic diplegia, functional units: a dehydrogenase, a hydratase & a sterol carrier pro- generalized ataxia, tremor and dystonic movements of the upper tein. DBP deficiency can be divided into 3 types depending on the limbs. He remains seizure free, without antiepileptic therapy from deficiency:(1) type I is characterized by deficiency of both hydratase & the age of 6 years. dehydrogenase units; 2) type II by isolated deficiency of the hydratase Patient 2 is a 18 month old male, born after an uneventful unit;(3) type III by deficiency of the dehydrogenase unit. pregnancy, as well. At 2 weeks of age he started to have tonic We report 2 brothers with mid-childhood onset of this degenera- spasms, partial and myoclonic seizures followed by flexion spasms, tive disease. Exome analysis identified compound heterozygous all refractory to multiple antiepileptic drugs, until the age of 10 mutations in DBP; 1 each of the dehydrogenase and hydratase units. months when deflazacort was added. The EEG showed suppression- The older sibling, now 16yrs old, presented at 3 yrs old with burst during sleep and brain MRI was normal. Sequencing of the language delay from sensorineural hearing loss. All early motor STXBP1 revealed a ‘‘de novo’’ mutation c.444delC, p.D148DfsX17 development was normal. Around 11 yrs old, he developed insidious, (het.) that is predicted to truncate the domain-3 region of the progressive gait ataxia. Neurology evaluation (at 12yrs old) noted STXBP1 protein leading to haploinsufficiency. Currently he is sei- bilateral pes cavus. He had no weakness but diffuse areflexia with zure free, but showing severe hypotonia and no language or ocular flexor plantar responses were seen. Distal small-fiber sensory loss was contact. seen. Proprioception was normal. Romberg was negative. Nerve Conclusion: We present these 2 cases for its relevance in the conduction studies showed mild sensorimotor polyneuropathy with growing knowledge of clinical manifestations of STXBP1 gene demyelinating features (cond velocity 20-25 m/s). MRI brain showed mutations, since less than 30 cases have been reported so far. We also cerebellar atrophy. Extensive genetic testing was normal (PMP22, emphasize that although there are currently no targeted treatment for MPZ, GJB1, c10orf2, Friedrich & spinocerebellar ataxias, chromo- EIEE in general, molecular genetic testing must be included in the somal microarray). Vitamin E was normal. Muscle biopsy (15-yrs workup diagnosis of EEIE since it may establish a precise etiology, old) revealed mild neurogenic changes. Muscle electron transport eliminating the need for further diagnostic tests and providing the chain enzymes were normal. Ophthalmology exam noted retinitis possibility of genetic counselling. pigmentosa. The younger sibling, now 14 yrs old, possesses identical albeit milder symptoms. The older sibling is now unable to walk independently due to progressive ataxia. Exome sequencing of both siblings revealed two different muta- O278 tions, both previously reported to be associated with disease in Epidemiological and molecular diagnostic landscape HSD17B4; one inherited from each parent. Normal urinary bile acid of Pelizaeus-Merzbacher disease and associated secretion, plasma VLCFA & branched chain fatty acid levels, adrenal & testicular sex steroid levels were confirmed. Enzyme activity was disorders in Japan: a nation-wide survey also normal, consistent with hypomorphic (milder) dysfunction. K. Inoue, Y. Numata, A. Iwaki, K. Kurosawa, J. Takanashi, The diagnosis of DBP deficiency in these 2 siblings underscores K. Deguchi, T. Yamamoto, H. Osaka the value of exome analysis. Our findings also highlight a new type National Center of Neurol & Psychiat (Tokyo, JP); Kyushu University (IV) of DBP deficiency, one which cannot be detected using (Fukuoka, JP); Kanagawa Children’s Medical Center (Yokohama, sophisticated biochemical & enzyme studies thus, this disorder is JP); Kameda Medical Center (Kamogawa, JP); Tokyo Women’s likely under diagnosed. Medical University (Tokyo, JP)

123 S44 J Neurol (2012) 259 (Suppl 1):S1–S236

Objectives: Pelizaeus-Merzbacher disease (PMD) is the most com- errors of metabolism. In most cases, the diagnosis was much delayed mon form of congenital hypomyelinating disorders in the CNS, but at age of one month to 8 years and 5 months (mean 13 months). the exact frequency of this group of diseases is currently unknown. In MMACHC gene analyses were performed in 23 cases with combined this study, we conducted a nation-wide epidemiological study in methylmalonic aciduria. CblC defect were confirmed. Clinical Japan to determine the prevalence and incidence of congenital hyp- improvement was observed in 157 patients after treatment. But omyelinating disorders. unfortunately, 3 patients died in early infancy. Methods: We enrolled all hospitals with pediatric neurology Conclusions: The clinical manifestation in neonatal period of the division and institutes for severely retarded children in Japan, the total patients with methylmalonic aciduria is complex. Non-specific of 918 institutions. Two-step questionnaire survey was conducted. symptoms should be paid attention to. Early metabolic investigation is The first step was to determine the presence of the patients in the past very important to reach diagnosis. Combined methylmalonic aciduria 1 year, and the second step was to obtain detailed clinical information and homocysteinemia is the common type of methylmalonic aciduria. of the patients. This study was approved by IRB at National Institute Serum and urine total homocysteine determination is essential to the of Neurology and Psychiatry, Japan. correct diagnosis. Results: We identified 102 children (87 males and 15 females) The clinical manifestation in neonatal period of the patients with with congenital hypomyelinating disorders. The prevalence of con- methylmalonic aciduria is complex and non-specific. genital hypomyelinating disorders was 0.8 per in 100,000 (0*19 years old), and the incidence was 1.4 per 100,000 live births. The age of patients ranged from 0 to 48 years, with median age of 12.2 ± 0.9 years. Clinical diagnosis of PMD was given to 66 patients (65 %). O280 Molecular testing was performed on 75 % of the patients, in 60 % of Atypical presentation of subacute sclerosing which PLP1 gene abnormalities were detected. Estimated incidence panencephalitis of PMD was at least 1.44 per 100,000 male live births. The most common symptoms included nystagmus (74 %), hypotonia (71 %), T. Uyar, P. Topaloglu, Z. Yapici, M. Eraksoy and quadriplegia (56 %). Nystagmus and hypotonia tend to disappear Beijingl University (Istanbul, TR) later in the patients with PLP1 gene abnormalities, while this ten- Subacute sclerosing panencephalitis(SSPE) is a chronic and progres- dency was not observed in those without PLP1 gene abnormalities. sive fetal neurodegenerative disease caused by defective measles virus Conclusion: As far as we know, this is the first report to determine in the central nervous system. Initial presenting symptom is usually the prevalence and incidence of these disorders by a comprehensive insidious and cognitive degenerative symptoms are predominated. This nation-wide survey. About 20 % of the congenital hypomyelinating process is accompanied by myoclonic seizures, intellectual decline that disorders remain undiagnosed, suggesting the presence of other dis- evolves to vegetative state. However, the course and characteristics of ease-causing genes unveiled. the disease can be highly variable as poorly controlled generalized seizures, sudden vision loss and isolated extrapyramidal syndrome. Hemiparkinsonism and coma can be atypical presentations of SSPE. O279 Diagnosis of SSPE is based upon the typical clinical picture as the presence of characteristic periodic discharges in electroencephalog- Brain injury of 160 Chinese patients with neonatal- raphy (EEG) and high titers of measles antibodies in blood and onset methylmalonic aciduria cerebrospinal fluid. Magnetic resonance spectroscopy (MRS) is non- Y. Yang, Y. Liu, Y. Ma, X. Li, Y. Ding, Q. Wang invasive and clinically useful tool for identifying cerebral metabolite Beijing University First Hospital (Beijing, CN) concentrations in various pathologic conditions. All patients have reductions in N-acetyl aspartate (NAA) and increase in myoinositol Objectives: Methylmalonic aciduria is the most common disorder of (mI) levels. NAA and mI concentrations are correlated with diagnosis organic aciduria in Mainland China. It is also the one of treatable and clinical severity. This report describes a 11 year-old boy with metabolic disorders. The clinical spectrum of the patients varies from atypical initial symptom of hemiparkinsonism. 2 years ago he started to severe neonatal-onset forms to milder forms with adult-onset. The complain about gait difficulty. Movements of his left limbs were clinical manifestations of neonates with methylmalonic aciduria are slower than the right side, his facial expressions reduced and school non-specific. Early diagnosis and adequate treatment contribute a lot performance got worse. At first, presence of atypical extrapyramidal to improving the prognosis of the patients. In this study, the clinical symptoms make us to think of especially neurodegenerative diseases and laboratory profiles of 160 Chinese patients with neonatal-onset (Acute disseminated encephalomyelitis, Lafora disease, Juvenile methylmalonic aciduria were investigated. neuronal ceroid lipofuscinoses) other than SSPE. We want to empha- Methods: From 1996 to 2011, 398 patients with methylmalonic size that, SSPE may present with atypical neurological findings and aciduria were diagnosed in our hospital. Among them, 160 patients MRS may be a diagnostic tool for SSPE. presented symptoms in neonatal period. Their urine organic acids were analyzed by gas chromatography-mass spectrometry. Blood amino acids and acylcarnitine profiles were determined by tandem mass spectrometry. Serum and urine total homocysteine were mea- O281 sured using a fluorescence polarization immunoassay. In 23 patients, gene analysis was performed. Based on the disease types and general MRI predictors of efficacy of constraint-induced condition, individually dietary and medical interventions were started movement therapy in paediatric patients with brain soon after diagnosis. injury: a diffusion tensor and resting-state study Results: 131 (81.9 %) out of the 160 patients with neonate-onset M.A. Rocca, E. Beretta, M. Absinta, P. Valsasina, had combined methylmalonic aciduria and homocysteinemia. Isolated methylmalonic aciduria was found in 29 cases (18.1 %). The common S. Strazzer, A. Turconi, M. Cazzagon, A. Falini, G. Comi, presentations in neonate period were feeding difficulty, seizures and M. Filippi lethargy. The most common initial clinical diagnosis was hypoxic- Vita-Salute San Raffaele University (Milan, IT); IRCCS E. Medea, ischemic encephalopathy. Even in 36 cases with abnormal family La Nostra Famiglia (Bosisio Parini, IT); IRCCS E. Medea, La Nostra history, only three patients were admitted with suspected inborn Famiglia (Pasian di Prato, IT) 123 J Neurol (2012) 259 (Suppl 1):S1–S236 S45

Objective: Constraint-induced movement therapy (CIMT) has emerged within participants enrolled in a multicenter population-based epide- as a promising intervention for reducing impairment and improving the miology study. Sera from cases (n=349) and controls (n=349) were functional use of an affected upper limb in children with brain injury. In screened for reactivity to the proteins, ENO1, NKTR, and NUMA1. this study, we applied resting state (RS) functional MRI (fMRI) and Results: Case–control differences were not evident for ENO1; diffusion tensor (DT) MRI to evaluate the short-term structural and however, antibodies to NKTR and NUMA1 were more commonly functional brain changes following CIMT in pediatric patients with detected in cases compared to controls in men only (age, gender, chronic hemiplegia and the MRI predictors of clinical improvement at and allergy adjusted OR NKTR continuous = 3.2, 95 %CI: 1.2-15; and termination and six months after the cessation of the physiotherapy. adjusted OR NUMA1 continuous =3.6, 95 %CI: 1.1-11). Allergy and. Methods: From 16 children with acquired or congenital brain injury NUMA1 demonstrated evidence of statistical interaction, and and 10 sex- and age-matched healthy controls, brain dual-echo, DT MRI non-allergic men exhibited the largest case–control differences and RS fMRI sequences were acquired at baseline, at the end of CIMT (Non-allergic men, adjusted OR NUMA1 continuous = 9.2, 95 %CI: (10 weeks) and after 6 months. At each time points, QUEST and 1.5-55). BESTA clinical scale scores were obtained. From DT MRI, fractional Conclusions: Our results indicate that men with meningioma anisotropy (FA), mean diffusivity (MD) and tensor eigenvalues values commonly react with a serologic anti-meningioma response, which is were measures in the lesion responsible for the clinical symptomatol- suggestive of a distinctive etiology of the disease in men. This result ogy, in the affected and unaffected corticospinal tract (CST), and corpus may be also be exploitable for early detection or therapeutic callosum (CC). The sensorimotor RS network was identified using the modalities. independent component analysis and the GIFT software. Differences between groups in demographic, clinical variables and MRI variables were assessed using the Fisher exact test or the Mann–Whitney U test, for categorical and continuous variables. The ability of baseline MRI O283 variables to predict the clinical changes over time was assessed using New therapeutic targets for malignant gliomas: multivariate linear models with stepwise variables selection. role of Tie2-expressing monocytes in the failure Results: At baseline, patients had abnormal DT MRI metrics in the of antiangiogenesis therapies symptomatic lesion, the affected CST and the CC. Reduced functional connectivity (FC) at rest was found in the bilateral cerebellum, right K.R. Gabrusiewicz, J. Fueyo, D. Liu, N. Cortes-Santiago, precentral gyrus, and right secondary sensorimotor cortex (SII). At M.B. Hossain, C.A. Conrad, M. Gilbert, W.A. Yung, week-10, an improvement at QUEST and BESTA was observed, which G. Fuller, C. Gomez-Manzano remained stable after 6 months. The MRI predictors of clinical M.D. Anderson Cancer Center (Houston, US) improvement at week 10 were baseline average lesion fractional anisotropy (r2=0.50) and right SII FC (r2=0.10); and at month 6 they Objectives: The prognosis of patients with malignant gliomas remains were baseline CC axial diffusivity (r2=0.44) and right SII FC (r2=0.58). poor despite decades of basic and clinical research. Since high-grade Conclusions: DT MRI and RS fMRI offer promising and objective gliomas are highly angiogenic, there is a convincing rationale for markers to predict clinical outcomes following CIMT in pediatric targeting the tumor vasculature. Among the broad-spectrum of antian- patients with congenital or acquired hemiplegia. giogenic drugs bevacizumab (Avastin), a humanized anti-VEGF This study was partially supported by a grant from Italian Ministry monoclonal antibody, has been widely tested as a second line for of Health. treatment for malignant gliomas. Treatment with bevacizumab caused reductions in MRI contrast enhancement and vasogenic edema, and increase in the rate of patients alive and free of progression at six months. ______However, clinical results and preclinical data from our laboratory and others showed the presence of a heightened invasive phenotype after Oral session 16 treatment with anti-VEGF agents. We undertook this study to explore the responsible mechanisms for this recurrence to happen. Methods: Mice bearing intracranial human xenografts were treated Neuro-oncology with anti-VEGF therapies and analyzed for survival. The histopathology of the tumors was performed with special emphasis in invasion. Double immunofluorescence was used to identify myeloid O282 populations and Tie2-expressing subpopulations (TEMs). Both M2 Effect of gender on the production of autoantibodies polarized monocytes and monocytes isolated from blood donors were used to study tissue remodeling molecules and their effect in migra- to meningioma antigens tion/invasion of glioma cells. J. Wiemels, P. Bracchi, M. Wrensch, J. Schildkraut, Results: Here, we present evidence of the over-representation of a M. Bondy, J. Pfefferle, M. Zhou, J. Sison, L. Calvocoressi, subpopulation of myeloid cells, TEMs, in the brain of animals treated E.B. Claus with anti-VEGF agents co-existing with a tumoral invasive pattern. These cells accumulate in the tumor/normal interphase regions and University of California (San Francisco, US); Duke University their presence was significantly higher than in brains of animals (Durham, US); M.D. Anderson Cancer Center (Houston, US); Yale treated with other therapies, such as temozolomide. Approximately University (New Haven, US); Brigham and Women’s Hospital 50 % of Tie2+ cells co-localized with microglia/macrophages marker, (Boston, US) Iba1, after anti-VEGF therapy. Interestingly, the molecular profile Objective: Meningioma is an intracranial tumor with relatively few expression of TEMs is related to tumor remodeling (e.g. MMP2, confirmed risk factors apart from gender, age, and ionizing radiation. MMP9, CD44, and CXCR4), and Tie2 signaling is playing a direct Recent research points to an impact on meningioma risk from factors role in the regulation of MMP9, a major protease in gliomas. Of related to immune function and development, such as allergy, IGE, significance, our studies show that TEMs facilitate the development and Varicella infection status. of an invasive phenotype in glioma cells. Methods: To explore immune function further, we assessed indi- Conclusions: Together, our results suggest a mechanism of escape vidual seroreactivity to three meningioma tumor associated antigens of GBMs to anti-VEGF therapies, and persuade to modify regimens

123 S46 J Neurol (2012) 259 (Suppl 1):S1–S236 based on antiangiogenic therapies, by targeting Tie2-expressing primary brain tumors (PBT). Most high-grade and progressive PBT monocytes, to improve clinical outcome in malignant glioma patients. are known to demonstrate significant enhancement on neuro-imaging Support from NIH/NINDS R01, and Concern Foundation. studies, indicative of dense vascularity and an angiogenic phenotype. Vascular endothelial growth factor (VEGF) is the most important molecular mediator of this angiogenic phenotype, via VEGF receptors O284 on tumor endothelial cells. Bevacizumab is a humanized IgG1 monoclonal antibody that targets VEGF, and has shown activity in Phase I clinical trial in patients with recurrent gliomas: systemic solid tumors and high-grade gliomas, and is now FDA- delta-24-RGD oncolytic adenovirus induces an anti- approved. glioma immune-response Methods: Twenty-four patients (male – 18, female – 6) with newly J. Fueyo, C. Gomez-Manzano, C. Conrad, A. Heimberger, diagnosed (GBM – 2) or progressive (GBM – 12, anaplastic glioma – 4, grade II glioma – 4, vestibular schwannoma – 2) PBT were treated L. Vence, K. Aldape, W.A. Yung, R. Sawaya, G. Fuller, with intravenous BEV (5-10 mg/kg) every two weeks, alone (N=2) or F. Lang in combination with other chemotherapy (N=22; temozolomide, iri- M.D. Anderson Cancer Center (Houston, US) notecan). Twenty-two patients each had received prior irradiation and chemotherapy. Patients ranged in age from 24 to 72 years (median Objectives: Immunotherapy against gliomas is a promising thera- 56), with a median Karnofsky of 70. Results: After receiving a mean peutic strategy. In a Phase I clinical trial using Delta-24-RGD, a of 7.5 cycles of BEV (range 1-24), objective responses on MRI were tumor selective replication competent adenovirus, as experimental noted in 10 of 24 patients (41.6 %; PR – 3, MR – 7). The overall treatment for patients with recurrent malignant glioma, we aimed to mean TTP was 35.7 weeks; 38.75 weeks and 37.3 weeks in the GBM test the safety/toxicity of this biological agent, to examine to which and anaplastic glioma cohorts, respectively. Therapy was well toler- extent Delta-24-RGD infects, replicates and kills glioma cells, and to ated, with frequent fatigue (90 %) and occasional mild hypertension ascertain whether the adenovirus infection of tumors ignites an anti- (12.5 %). There were no episodes of significant intracranial or sys- tumor immune response with therapeutic benefit. temic hemorrhage, venous or arterial vascular events, GI perforation, Methods: In Group A, patients with unresectable gliomas received or proteinuria. an intratumoral injection of Delta-24-RGD and were followed for Conclusion: These results are consistent with other investigators, toxicity. In Group B, patients underwent a two-phase approach: first, a and demonstrate that BEV is active in patients with newly diagnosed single dose of Delta-24-RGD was administered intratumorally, and and progressive PBT. The drug can safely be used in combination two weeks later the tumor mass was resected. Surgical specimens with traditional chemotherapy, with a tolerable side effect and tox- were analyzed for viral replication and IHC and FACS were used to icity profile. identify lymphocyte populations and expression of cancer antigens in resected tumors. In 20 patients, a modified solid-phase ELISA was used to detect antibodies against cancer testis antigens (CTAs) in the sera before and after the injection of the adenovirus. O286 Results: Half of patients in Group A showed radiographic Combination of quadrigeminal cistern lipoma responses. 40 % of the patients survived longer than 1 year, and one of these patients showed a complete radiographic response by 17 and foramen magnum meningioma months after the treatment. Examination of tumors from group B, N. Dimitrov, E. Todorova-Dimitrova, K. Genov showed adenovirus replication and treatment-related tumor necrosis. Second City Hospital Sofia (Sofia, BG); Military Medical Academy IHC analyses showed that a subset of these tumors were positive for (Sofia, BG) the CTA MAGE E1. Importantly, we detected antibodies against Objective: to perform the paucity of signs in a patient with lipoma of CTAs before the treatment and some patients developed them after the quadrigeminal cistern and foramen magnum meningioma and the Delta-24-RGD injection. All four patients with titers of anti-NY- advantages of the magnetic resonance imaging (MRI) over the ESO-1 antibodies survived after treatment: 301 days (still alive), 281 computed tomography (CT) for the diagnose. days (deceased), 273 days (still alive), and 126 days (still alive). A case of 64 years old woman with pain in the occipital area of the Histological analyses of the post-treatment tumor from a patient with head and impaired balance after a cranial trauma is described. The high titers of anti-NY-ESO 1, showed vast areas of necrosis, massive clinical examination found discrete nystagmus to the left side and inflammatory reaction, and CD3+/CD8+ lymphocytic infiltration. positive Romberg test. According to neurosurgical examination the Analyses of data for antibodies against 12 CTAs are pending and will patient is liable to operative intervention. be presented in the meeting. The CT scan of the head showed well-turned, adipose density zone Conclusion: The favorable radiographic and clinical responses of in the ambient cistern, measured as 12/14 mm and groups of calcium the patients treated with Delta-24-RGD adenovirus may be the result density depositions caudal to the latter. of the combination of a direct oncolytic effect and the ‘‘unmasking’’ The MRI of the brain demonstrated a quadrigeminal lipoma and of cancer antigens followed by a potent anti-tumor immunity. foramen magnum meningioma visualized as 12/13 mm lesion in the Supported by NIH/NCI Brain Tumor SPORE grant to MDACC, left half of the quadrigeminal system, high intensive on T1-T2 and Will Power Foundation. weighted images and low intensive on fat suppressing images and ovoid 18/14/13mm formation at the level of the foramen magnum on the right side of the skull base compressing the intracranial part of O285 distal medulla oblongata. Bevacizumab chemotherapy for the treatment of newly This case confirms the difficulty of the diagnose due to the diagnosed and progressive primary brain tumours capricious anamnesis and peculiar findings on neurological exami- H.B. Newton, J. Lima, H.L. Cunningham nation and demonstrates the mainstay of MRI for revealing the Ohio State University Medical Center (Columbus, US) tumors. This is especially important in light of the fact that severe symptoms as spastic quadriparesis often develops with the progres- Objective: To investigate the activity and tolerability of intravenous sion of the disease and the earlier the diagnosis, the better the chance bevacizumab (BEV) in patients with newly diagnosed and progressive for preventing the complications.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S47

O287 Background/Objective: Alemtuzumab patients were significantly more Relationship between the degree of malignancy likely than interferon beta-1a (IFNB-1a) patients to be free of clinical disease activity, defined as no relapses and no sustained accumulation of of gliomas and the current value of the motor-evoked disability (SAD), in a previous 3-year phase 2 clinical trial. In CARE- potential during brain surgery MS I, a phase 3 clinical trial with treatment-naı¨ve relapsing-remitting S. Asano, I. Suzuki, A. Morita, N. Kawahara, T. Nakagomi, multiple sclerosis (RRMS) patients, alemtuzumab significantly reduced A. Matsuno, T. Toyoda, K. Furuya the relapse rate compared to IFNB-1a. Alemtuzumab is compared to Teikyo University School of Medicine (Tokyo, JP); Japanese Red IFNB-1a on the tertiary endpoint of MS disease activity-free (no clinical Cross Medical Centre (Tokyo, JP); NTT Medical Centre Tokyo disease activity and no MRI activity) in CARE-MS I. (Tokyo, JP); Yokohama City University Hospital (Yokohama, JP); Methods: CARE-MS I was a 2-year, randomized, rater-blinded ¨ Teikyo University Chiba Medical Centre (Ichihara, JP); Tokyo Kosei- trial comparing alemtuzumab to IFNB-1a in active, treatment-naıve Nenkin Hospital (Tokyo, JP) RRMS patients. Alemtuzumab treatment was administered intravenously 12mg/day on 5 days at study start and 3 days 12 months later. Objectives: During glioma removal brain surgery, we have had some IFNB-1a treatment was administered subcutaneously 44mcg 3-times relationship between the degree of malignancy and current value of weekly for 24 months. Expanded Disability Status Scale (EDSS) was the motor evoked potential (MEP) monitoring. assessed by a blinded rater at baseline, quarterly, and for suspected Methods: From 1999 to 2011, we performed MEP monitoring with relapses. 6-month SAD is defined as an increase of [=1 EDSS point anodal five-train stimulation of the brain surface of the primary motor ([=1.5 point if baseline EDSS=0) sustained for 6 months. Magnetic cortex and lead of contralateral muscle of the ball of the thumb during resonance imaging with and without gadolinium occurred annually. glioma removal. We retrospectively reviewed the histological results MS disease activity-free was defined as no relapse, no SAD, no new and current value of MEP, nitrous oxide, muscle relaxant. In all cases, gadolinium-enhancing lesions or new/enlarging T2 hyperintense we used intravenous anesthesia with propofol. lesions. Results: Twenty-nine cases were extracted. They were 17 females and Results: Through Year 1, alemtuzumab patients were signifi- 12 males, and mean age was 47±17 years. During their anesthesia, for 15 cantly more likely to be MS disease activity-free (50.1 %) than cases nitrous oxide was used, and for nine cases muscle relaxant was IFNB-1a patients (37.9 %) (odds ratio [OR]: 1.70 [95 % CI: 1.17, administered. Mean current value of the beginning MEP was 14.3±6.3mA, 2.47], p=0.0053). Through end of study, alemtuzumab patients and that of the last MEP was 18.5±7.6mA. In their histological results, the continued to be significantly more likely to be MS disease activity- number of grade II was 13 (astrocytoma: 7, oligodendroglioma: 5, oligo- free (38.6 %) than IFNB-1a patients (26.7 %) (OR: 1.75 [95 % CI: astrocytoma: 1 [B-group]), and that of grade III and IV was 16 (anaplastic 1.17, 2.61], p=0.0064). Among patients with disease activity, astrocytoma: 3, anaplastic oligodendroglioma: 4, gliobastoma: 9 [M- 42.1 % had relapsed, 13.3 % had SAD, 29.1 % had gadolinium- group]). In the univariate analysis, we had statistical significance between enhancing lesion activity, and 78.4 % had T2 lesion activity. the current value of the beginning MEP and with or without nitrous oxide Notable alemtuzumab-related adverse events included infusion (mean current value with nitrous oxide: 11.0±5.7mA, that without nitrous reactions, infections, autoimmune thyroid disorders and immune oxide: 17.8±4.9mA, p\0.01). We had also statistical significance between thrombocytopenia. the current value of the last MEP with or without nitrous oxide (mean current Conclusions: Alemtuzumab was more effective at reducing overall value with nitrous oxide: 14.4±6.8mA, that without nitrous oxide: MS disease activity than IFNB-1a in RRMS patients newly initiating 23.0±5.7mA, p\0.01). Although between B- and M-group and the current therapy. The superiority of alemtuzumab over IFNB-1a in disease activity value of MEP there were no statistical significances, we had the tendency was largely driven by suppression of relapses and MRI lesion activity. that the current value in B-group was higher than that in M-group. In the Funding provided by Genzyme (a Sanofi company)and Bayer multivariate analysis with logistic regression analysis with step-wise method Healthcare Pharmaceuticals. between B- and M-group, we yielded two significant variables: use of nitrous oxide (p=0.03), and the current value of the last MEP (p=0.02). This logistic analysis showed the tendency that the current value of the last MEP in B-group was higher than that in M-group. O289 Conclusion: Our results suggested that there was some relationship Disability outcomes for alemtuzumab in RRMS patients between the degree of malignancy of gliomas and electroconductance who relapsed on prior therapy: CARE-MS II of the brain with gliomas. We may think that electroconductance of H.P. Hartung, D.L. Arnold, J. Cohen, A.J. Coles, the malignant glioma brain was higher than that of benign glioma. C. Confavreux, E.J. Fox, E. Havrdova, K. Selmaj, H. Weiner, T. Miller, C.L. Twyman, S.L. Lake, D.H. ______Margolin, M. Panzara, A. Compston for the CARE-MS II Oral session 17 Investigators Objective/Background: Alemtuzumab was significantly more effec- Multiple sclerosis IV tive than subcutaneous interferon beta-1a (SC IFNB-1a) in reducing relapses in 2 clinical trials with treatment-naı¨ve, relapsing-remitting O288 multiple sclerosis (RRMS) patients (pts). Treatment options are lim- Disease activity-free status in comparison ited for RRMS pts experiencing disease activity during therapy, and few controlled studies have been conducted to determine appropriate of Alemtuzumab and RebifÒ efficacy in multiple management. Alemtuzumab and IFNB-1a were compared on dis- sclerosis I (CARE-MS I) phase 3 study ability outcomes in RRMS pts who relapsed on prior therapy. G. Giovannoni, D.L. Arnold, J. Cohen, A.J. Coles, Methods: Comparison of Alemtuzumab and Rebif Efficacy in C. Confavreux, E.J. Fox, H.P. Hartung, E. Havrdova, K. Selmaj, Multiple Sclerosis II (CARE-MS II) was a 2-year rater-blinded trial with RRMS pts who had relapsed during prior therapy after at least 6 H. Weiner, V. Brinar, S.L. Lake, D.H. Margolin, M. Panzara, M. months of treatment. Alemtuzumab treatment was administered IV 12 Rizzo, A. Compston for the CARE-MS I Investigators mg/day (or 24 mg/day in an exploratory cohort) on 5 days at study 123 S48 J Neurol (2012) 259 (Suppl 1):S1–S236 start and 3 days 12 months later. IFNB-1a treatment was administered hemispheres and in scattered white matter (WM) areas, indepen- 44mcg SC 3-times weekly throughout the study. Entry criteria dently from T2-lesion volume (LV). In contrast, patients with ON included 18-55 years old, MS symptom onset within 10 years, and and SC onset had low lesion frequency in scattered areas of the WM, Expanded Disability Status Scale (EDSS) score \=5. EDSS was but this disappeared after controlling for T2-LV. At 1 year, CDMS assessed at baseline and quarterly. The Multiple Sclerosis Functional developed in 26 % of patients. Baseline T2-LV was greater in Conv Composite (MSFC) was assessed at baseline and every 6 months. than in Non-Conv patients (7±8.1 cm3 versus 4.6±6.7 cm3, EDSS and MSFC were assessed by blinded evaluators. Primary p\0.001). In both groups, lesions were mostly distributed symmet- endpoints included relapse rate and time to 6-month sustained accu- rically across the WM and had the peak of lesion frequency in the mulation of disability (SAD) based on EDSS increase. Additional superior corona radiata (CR, 16 %) in the Conv group and in the disability endpoints included changes in EDSS and MSFC. body of the corpus callosum (10 %) in the Non-Conv group. At Results: 840 pts from 180 sites in 23 countries were randomized. voxelwise analysis, Conv group had higher lesion frequency than Baseline characteristics (mean) were: age 35 years; disease duration Non-Conv group in clusters of the anterior CR and cingulum, after 3.9 years; EDSS 2.7; with 1.6 and 2.7 relapses in 1 and 2 years prior correction for brain T2-LV. In the subgroups of patients with B/C to study entry, respectively. The most common prior MS therapies and SC onset, lesion frequency in the superior and posterior CR was were interferon-beta (78.6 %) or glatiramer acetate (32.5 %); less higher in Conv than in Non-Conv patients, independently from brain than 5 % of pts had received other prior MS therapy. Risk of 6-month T2-LV. SAD was reduced by 42 % (p=0.0084). Additional disability analyses Conclusion: Following a first demyelinating event suggestive of will be reported. Adverse events included infusion-associated reac- MS, the distribution and frequency of lesions in clinically ‘‘eloquent’’ tions and infections of predominantly mild to moderate severity; brain areas, in particular CR, may influence the short-term evolution 16 % of alemtuzumab pts developed an autoimmune thyroid-related of CIS to CDMS. This can be potentially important when planning adverse event; 1 % developed immune thrombocytopenia. treatments. Conclusions: Alemtuzumab more effectively reduced the accumulation of disability than IFNB-1a in a population of RRMS pts who relapsed on prior therapy. Additional analyses of changes in disability will explore the robustness of these results. The safety profile was O291 consistent with previous studies. Vitamin D levels and risk of developing multiple Funding provided by Genzyme (a Sanofi company) and Bayer Healthcare Pharmaceuticals. sclerosis V. Martinelli, G. Dalla Costa, B. Colombo, D. Dalla Libera, L. Leocani, R. Furlan, M. Filippi, G. Comi O290 San Raffaele Hospital (Milan, IT) Spatial mapping of brain lesions in clinically isolated Objectives: to evaluate the correlation between 25-hydroxyvitamin D syndrome with short-term conversion to multiple levels (25(OH)D) in patients with Clinically Isolated Syndromes (CIS) and the development of Clinically Defined Multiple Sclerosis sclerosis (CDMS). A. Giorgio, M. Battaglini, M.A. Rocca, A. De Leucio, Methods: This is a retrospective study on 107 CIS patients hos- M. Absinta, F. Barkhof, A. Rovira, M. Tintore´, D. Chard, pitalized from 2000 to 2009 at San Raffaele Hospital. We evaluated O. Ciccarelli, C. Enzinger, C. Gasperini, J. Frederiksen, baseline serum 25(OH)D level as well as clinical, magnetic resonance (MRI), multimodal evoked potential and cerebrospinal fluid (CSF) M. Filippi, N. De Stefano data. University of Siena (Siena, IT); Scientific Institute and University Results: 21 % patients developed CDMS at 12-month follow- ‘‘Vita-Salute’’ San Raffaele (Milan, IT); VU University Medical up, 36 % at 2-year follow-up and 44 % at 5 year follow-up. A Centre (Amsterdam, NL); Hospital Vall d’Hebron (Barcelona, ES); statistically significant inverse correlation between 25(OH)D levels University College London (UCL) Institute of Neurology (London, and an increased risk to develop CDMS (p = 0,0381) was observed. UK); Medical University of Graz (Graz, AT); San Camillo-Forlanini The difference between serum 25(OH)D levels in patients who Hospital (Rome, IT); Glostrup Hospital and University of subsequently developed CDMS and patients who did not, is sta- Copenhagen (Copenhagen, DK) tistically higher during summertime (p \ 0,05). Serum 25(OH)D Objectives: To assess in a large population of patients with clinically levels better stratify the risk of CDMS in patients with low lesion isolated syndrome (CIS) voxelwise differences in baseline lesion number and low Barkhof criteria (BC), and in patients without CSF distribution and frequency, measured on MRI-derived brain lesion oligoclonal bands (OB). Moreover, low 25(OH)D levels were probability map (LPM), between patients who clinically converted associated with a shorter interval between CIS and the occurrence (Conv) and those who did not convert (Non-Conv) to clinically def- of a second clinical attack (p \ 0,05) and with an increased inite (CD) multiple sclerosis (MS) within 1 year. annualized relapse rate, especially in summer (p \ 0,02). The Methods: MRI data and segmented T2-lesion masks of 1165 presence of CSF OB (p\ 0,05), the clinical type of onset (multi- patients with CIS (age: 31.2±7.6 years, 68 % female, disease dura- focal vs monofocal p \ 0.01), multimodal evoked potential tion: 60±43 days) with at least 1-year clinical follow-up were abnormalities (p\0.05) and the presence of periventricular lesions collected from MAGNIMS sites. T2-lesion masks were used to create at baseline MRI (p\0.01) have a predictive role on short-term risk LPM for different patient groups. Significance of voxelwise analyses, of developing CDMS. performed with FSL, was set at p\0.05, cluster-corrected for multiple Conclusions: Serum 25(OH)D level has an independent prognostic comparisons. value for CDMS in CIS patients. The seasonality in the observed Results: The type of onset was optic neuritis (ON, 30 %), multi- differences in serum 25(OH)D of patients who develop CDMS and focal (MF, 21 %), brainstem/cerebellum (B/C, 18.8 %), spinal cord patients who do not, highlights the stand-alone role of low vitamin D (SC, 18.8 %), and cerebral hemispheric (CH, 11.4 %). On LPM levels, regardless of acquired factors. The presence of at least 3 analysis, patients with B/C, CH and MF onset showed high lesion negative clinical/paraclinical prognostic factors highly predicts short frequency, respectively, in middle cerebellar peduncle, cerebral term conversion to CDMS (OR 5.39, p \ 0,005).

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S49

O292 CDMS. Our study examined differences in clinical and MRI param- Preferential expression of the mutant ABCD1 allele is eters between the patients with CIS and CDMS after 2 years of disease onset. common in adrenoleukodystrophy female carriers Methods: SET is an ongoing 4-year observational study of early but unrelated to clinical symptoms Interferon beta 1-a treatment in CIS. Of 220 patients, complete 2-year E. Salsano, S. Tabano, S. Sirchia, P. Colapietro, data (comprising 3-monthly clinical assessments and 6-monthly MRI B. Castellotti, C. Gellera, M. Rimoldi, V. Pensato, scans) from 217 patients were included in this analysis [females = 67 %, age = 29 (15-55) years, disease duration = 2.8 months, C. Mariotti, M. Miozzo, D. Pareyson, G. Uziel Expanded Disability Status Scale (EDSS) = 1.7 (0-3.5)]. Comparisons Istituto Neurologico ‘‘C. Besta’’ (Milan, IT); Universita` degli Studi di between the patients with CIS and those progressing into CDMS Milano (Milan, IT) within 2 years were done with mixed-effect and Cox models adjusted Objectives: Approximately 20 % of adrenoleukodystrophy (X-ALD) for gender, age and changes in treatment. female carriers may develop clinical manifestations. A skewing in X Results: Patients with CIS were older than those progressing into Chromosome Inactivation (XCI), leading to the preferential expres- CDMS (30 vs. 28 years, p = 0.01), while showing similar gender ratio. sion of the X chromosome carrying the mutant ABCD1 allele, has While EDSS remained stable in the CDMS group, it decreased in the -5 been proposed as a mechanism influencing X-linked adrenoleuko- CIS group (2-year median difference = 0.5, p = 10 ). However, this dystrophy (X-ALD) carrier phenotype, but reported data so far are was not seen in the Multiple Sclerosis Functional Composite score. conflicting. The aim of this work is to shed light into this topic. T2 and T1 lesion volumes were higher in the CDMS group by 1.6 and 3 Methods: We assessed the pattern of XCI and ABCD1 allele- 0.3 cm , respectively, and remained so throughout the study (p = specific expression in the peripheral blood mononuclear cells 0.003). While brain parenchymal fraction deteriorated faster in the (PBMCs) of 30 X-ALD female carriers and in the urinary sediment of CDMS group (by 0.6 in 2 years, p = 0.03), no similar statistically a small subgroup of them (n=8). Very long-chain fatty acid (VLCFA) significant effects were seen in brain volume. In contrast, a larger levels were also determined in the same patients using a standard atrophy of corpus callosum was seen in the CDMS patients (differ- 3 -4 procedure. In order to prevent a frequent problem with XCI studies, ence = 0.23 cm , i.e. 3 % over 2 years, p = 10 ). Neither grey nor i.e. the underestimation of the skewing due to the incomplete sample white matter differed between the CIS and CDMS patients when digestion by restriction enzymes, we developed a pyrosequencing analysed separately. When examining the baseline differences in T2 assay to identify the completely digested samples on which to per- lesion volume, we have seen that patients with initial T2 lesion vol- 3 form the XCI assay. Pyrosequencing was also used to quantify the ume exceeding 5 cm showed increased risk of progression into ABCD1 allele-specific expression. CDMS (66 % vs. 37 %, p = 0.003). Results: The clinical features of our cohort of symptomatic women Conclusion: Patients who reach CDMS within 2 years of CIS onset (n=9) were similar to those previously reported, mainly characterized show more sustained disability as indicated by EDSS, larger T2 lesions by spastic paraplegia, lower limb sensory disturbances, and neuro- and accelerated brain atrophy. Atrophy of the corpus callosum is more genic bladder. We found severely (more or equal to 90:10) or sensitive marker of these changes than that of the whole brain. Higher moderately (more or equal to 75:25) skewed XCI in 23 out of 30 initial T2 lesion volume indicates higher risk of progression to CDMS. (77 %) X-ALD carriers and proved that preferential XCI is mainly Supported by Biogen Idec and the Czech Ministry of Education associated with the preferential expression of the mutant ABCD1 MSM 0021620849. allele, irrespective of the manifestation of symptoms. The expression of the mutant ABCD1 allele also correlates with intracellular VLCFA ______concentrations, and the XCI pattern and/or the ABCD1 allele-specific expression data were comparable among blood and urinary sediment. Oral session 18 Conclusion: Our results indicate that the preferential XCI leads to the favored expression of the mutant ABCD1 allele. This emerges as a Cerebrovascular disorders II general phenomenon in X-ALD carriers not related to the presence of symptoms. Our data support the intriguing, postulated growth advantage of cells with the preferential expression of the mutant ABCD1 allele. In contrast, they argue against the use of the XCI O294 pattern and ABCD1 allele-specific expression data from accessible C1-inhibitor protects from ischaemic stroke in rodents tissues as biomarkers to predict the development of symptoms in by combined anti-inflammatory and anti-thrombotic X-ALD carriers. mechanisms N. Heydenreich, M.W. Nolte, F. Langhauser, G. Stoll, C. Kleinschnitz Uniklinikum Wu¨rzburg (Wu¨rzburg, DE); CSL Behring GmbH O293 (Marburg, DE) Higher T2 lesion volume in clinically isolated syndrome Background/Objectives: Inflammation and thrombosis are pathophysi- indicates higher risk of clinically definite multiple ological hallmarks of ischemic stroke still largely unamenable to sclerosis therapeutic interventions. The contact-kinin system represents an T. Kalincik, M. Vaneckova, J. Krasensky, Z. Seidl, interface between inflammatory and thrombotic circuits and is critically M. Tyblova, J. Volna, E. Havrdova, D. Horakova involved in stroke development. The serine protease inhibitor C1-inhibitor (C1-INH) counteracts activation of the contact-kinin sys- Charles University (Prague, CZ) tem at multiple levels for instance by blocking of activated coagulation Objectives: About 50 % of patients with clinically isolated syndrome factor FXII (FXIIa) and plasma kallikrein. We investigated the thera- (CIS) fulfil criteria of clinically definite multiple sclerosis (CDMS) peutic potential of C1-INH in different models of ischemic stroke. within 6 years of disease onset. Baseline T2 lesion volume and brain Methods: C57Bl/6 mice (n=353) were subjected to middle cerebral atrophy over the initial year were shown to predict conversion to artery occlusion (MCAO) and treated with C1-INH (Berinert P) after

123 S50 J Neurol (2012) 259 (Suppl 1):S1–S236

1h or 6h. Infarct volumes and functional outcomes were assessed Objectives: Lymphocytes such as T cells are critically involved in stroke between day 1 and day 7, and findings were validated by magnetic development (Kleinschnitz et al., 2010). The selective immunosup- resonance imaging (MRI). Blood–brain-barrier damage and edema pressor FTY720 is a sphingosine 1-phosphate receptor agonist that formation were determined using vascular tracers. Invasion of inflam- blocks lymphocyte egress from lymphoid organs into the blood stream. matory cells was visualized by immunohistochemistry and the extent of It has been shown that FTY720 reduces stroke size and improves thrombus formation was quantified by Western blot and histology. neurological outcome in rodent models of stroke but the underlying Results: Treatment with 15.0 U C1-INH, but not 7.5 U 1h after stroke mechanisms are only incompletely understood. We investigated the reduced infarct volumes by *50 % and improved clinical scores on day modes of fingolimod action in a mouse model of ischemic stroke. 1. This protective effect was preserved at later stages of infarction and Methods: 90 min transient middle cerebral artery occlusion persisted in old mice as well as in another species, i.e. rats (n=42). (tMCAO) was induced in Rag1-/- mice, that lack functional lympho- Delayed treatment still improved clinical outcome. Blood–brain-barrier cytes and are largely protected from ischemic stroke (Kleinschnitz damage, edema formation and inflammation were significantly lower et al., 2010), and C57Bl/6 mice (controls). The following treatment compared with controls. Moreover, C1-INH showed strong antithrom- groups were defined: a) Rag1-/- mice + vehicle, b) Rag1-/- mice + botic effects without increasing the risk of intracranial bleeding. FTY720, c) C57Bl/6 mice + vehicle, d) C57Bl/6 mice + FTY720. FTY Conclusion: In conclusion, C1-INH is a multifaceted anti-inflam- was given i.p. at a dosage of 1 lg/g bodyweight immediately after the matory and anti-thrombotic compound that safely protects from induction of stroke. On day 1 after tMCAO infarct volumes were ischemic neurodegeneration in clinically meaningful settings. calculated from TTC-stained brain sections and functional scores were This study was supported by the DFG/SFB 688 A13/B1, the Wil- assessed. Immune cell counts in the blood were determined before helm-Sander Stiftung and CSL Behring GmbH, Marburg, Germany. tMCAO, and again 3h and 24h after tMCAO. The invasion of immune cells into the ischemic brain was quantified by immunohistochemistry. To analyze the integrity of the blood–brain-barrier (BBB), the vascular tracer Evans Blue (EB) was used and the expression of tight junction O295 proteins (e.g. Occludin) was assessed by Western Blot. Results: FTY720 treatment caused a rapid and profound reduction in Aquaporin-4 as a therapeutic target peripheral lymphocyte counts (CD4+ T cells, CD8+ T cells) (p\0.01). for neuroprotection by piroxicam in rat model of focal In addition, FTY720 significantly reduced stroke size (p\0.01) and cerebral ischaemia improved neurological outcome (p=0.04) in C57Bl/6 mice compared P. Bhattacharya, A. Pandey, S. Paul, R. Patnaik with vehicle-treated controls. Importantly however, FTY720 was not Banaras Hindu University (Varanasi, IN) able to lower infarct volumes in the absence of lymphocytes, i.e. in Rag1-/- mice (p[0.05). Less T cells invaded the ischemic brains of mice Cerebral ischemia results into neuro-inflammation which is a nor- receiving FTY720 but markers of BBB disruption were similar between mal protective response to brain injury. The intracellular calcium FTY720-treated mice and untreated controls. overload resulting from glutamate excitotoxicity is considered as a Conclusion: FTY720 is effective in acute ischemic stroke in mice. major determinant for neuronal loss during cerebral ischemia. ‘‘Trapping’’ of lymphocytes leading to successive lymphopenia and According to present line of approach, treatment of focal cerebral reduced immune cell invasion rather than direct stabilization of the ischemia is suboptimal without considering the combination of BBB or neuroprotective effects appears to be the major underlying thrombolytics with a free radical scavenger and anti inflammatory mechanism. pharmacological molecule. Hence thinking in this direction we considered the effects of Piroxicam, a NSAID and an inhibitor of COX-2 activity, on brain damage inducedbyafocalischemic- reperfusion model of rats. Piroxicam treatment, thirty minutes prior O297 to ischemia and two hour post reperfusion, afforded significant Does the protective effect of oestrogen in the rat stroke neuroprotection from ischemic injury as evident by the reduction in model extend to old age? cerebral infarct volume and neurobehavioral assessment. Further an R. Sandu early calcium dependent rise in levels of nitrite and MDA was also found to be significantly (P\0.01) reduced in ischemic brain Neuropsychiatry Hospital Craiova (Craiova, RO) infarction following Piroxicam pretreatment. Moreover it also Background & Aim: Although estrogen is neuroprotective in younger improved the motor function coordination as well as the electrical animal models of stroke, clinical trials demonstrate that estrogen activity of the brain which was reduced due to ischemic insult. increases the incidence and severity of stroke in aged women. The Determination of the brain antioxidant status reveals potentiation goal of this project is to test the neuroprotective efficacy of estrogen of antioxidant redox system by Piroxicam administration. Further, in an aged rat model of stroke, a more valid animal model of human considering Aquaporin-4 as a target, we revealed that Piroxicam cerebral ischemia. modulates its activity and reduces brain swelling. These studies Methods: Following focal ischemia middle-aged (18 month) thus provide neuroprotective profile of Piroxicam in rat model of ovariectomized female rats were implanted with 17beta-estradiol focal cerebral ischemia. (E2), sub or placebo pellets. Histological and functional outcomes were measured at 14 days after MCAO and compared to intact female rats treated with placebo pellets. Results: Aged rats treated with E2 had significantly increased O296 ischemic brain injuries and worsened mortality compared to placebo- FTY720 protects mice from ischaemic stroke treated aged rats. Young adult rats treated with E2 had significantly by reducing lymphocyte trafficking decreased infarct volumes and functional outcome compared to but not by stabilising the blood-brain barrier ovariectomized young adult rats. Conclusions: Estrogen acts in an age-dependent manner in the P. Kraft, W. Pfeilschifter, G. Stoll, C. Kleinschnitz post-ischemic rat brain. In young adult rats, estrogen is neuropro- University of Wu¨rzburg (Wu¨rzburg, DE); University of Frankfurt tective; chronic estrogen treatment during aging leads to worsened (Frankfurt, DE) stroke outcome in aged female rats.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S51

O298 conventional angiography (50 % vs 33.3 %, P=0.288) did not differ The factor XIII Val134Leu polymorphism between HCB and LCB groups. The frequency of partial or full recanalization following IV thrombolytic therapy (25.0 % vs 47.8 %, and ischaemic stroke in children p=0.155) and good final reperfusion grade after IA treatment (TICI IIb I. Kopyta, I. Zak, T. Iwanicki, T. Nowak, E. Emich-Widera or III; 66.7 % vs 69.2 %, p=0.847) did not differ between HCB and Medical School of Silesia (Katowice, PL) LCB groups. The HCB group had higher incidence of SAH after Factor XIII (FXIII) is a transglutaminase consisting of 2 catalytic A-sub- recanalization therapy (21.4 % vs 3.1 %, p=0.011) than the LCB units and 2-carrier protein B –subunits. The G-[T polymorphism of the group. HCB group was significantly associated with higher NIHSS XIII factor gene, leading to a valine (Val) to leucine(Leu) substitution 3 scores at discharge (15.29±12.41 vs 6.89±6.62, p=0.027) and poor amino acids from the thrombin activation site is associated with the pro- outcomes at 3 months (mRS 5 or 6; 57.1 % vs 22.0 %, p=0.009). HCB tective effect against occlusive arterial disease and venous thrombosis. was proven to be an independent predictor for poor outcomes at 3 Some articles considering the role of the mutation in etiopatho- months when age, sex and initial NIHSS score were adjusted (odds genesis of ischemic and hemorrhagic stroke, myocardial infarction or ratio 4.045; 95 % confidential interval 1.027-15.928, p=0.046). venous thrombosis in adult patients, but very few in children. Conclusion: Intracranial calcification is independently associated The aim of the study was to investigate the association between with a poor prognosis in patients with acute MCA stem occlusion childhood ischemic stroke and the Val134Leu polymorphism of the followed by recanalization therapy. factor XIII. Material and method: Seventy two patients younger than 18 years (middle age 8,7; total amount of 42 boys, and 30 girl) with a history of ______ischemic stroke, their biological parents and one hundred and thirty – three Oral session 19 healthy children of the same group age were included to the study. All the children were diagnosed of ischemic stroke according to the interview, neurological examination and the result of the neuroimaging (computed Motor neuron disease tomography and/or magnetic resonance). Genomic DNA was extracted in patients, parents and controls from peripheral lymphocytes and the PCR- RFLP method was used to genotype FXIIIVal134Leu polymorphism. Statistical analysis did not show the significance in the case–control study. O300 Conclusions: Our findings do not support the hypothesis that Global epidemiology of amyotrophic lateral sclerosis: Val134leu polymorphism in FXIII gene has a protective effect against a systematic review of the published literature ischemic stroke in children. Further studies are needed in the larger groups of patients. A. Chio`, G. Logroscino, B. Traynor, J. Collins, J. Simeone, KNW-1-065/09. L. Nalysnyk, L.A. White University of Turin (Turin, IT); University of Bari (Bari, IT); National Institutes of Health (Bethesda, US); United Biosource Corporation (Lexington, US); Biogen Idec (Weston, US) O299 High intracranial calcification burden Objective: To review the epidemiology of amyotrophic lateral sclerosis (ALS) with a focus on incidence, prevalence, and mortality. as an independent risk factor of poor outcome Methods: A systematic review of English-language literature (1995 in patients with acute middle cerebral artery stem through October 2011) was performed by searching MEDLINE (Pub- occlusion and recanalization therapy Med) and EMBASE. Publications of interest included observational S.J. Lee, J.S. Lee, D.H. Shin, J.M. Hong, I.S. Joo studies reporting ALS incidence, prevalence, mortality, survival, or risk Ajou University School of Medicine (Suwon, KR) factors of mortality. All studies reporting quantitative data on incidence or prevalence of ALS were selected for further review. For mortality and Objectives: The significance of intracranial calcification has not been risk factors of mortality, studies were limited to those that provided the well defined with regard to outcomes following recanalization therapy best evidence, based on a sample size[=100, study design, and gener- for acute intracranial artery occlusion. In the current study, we sought alizable population. Information on study characteristics and estimates to identify its significance on outcomes of patients undergoing for incidence, prevalence, all-cause mortality, survival, and mortality risk intravenous (IV) thrombolysis and intra-arterial (IA) treatment due to factors were extracted for each country. acute middle cerebral artery (MCA) stem occlusion. Results: A total of 1,727 publications were identified through the Methods: Consecutive 80 patients with acute MCA stem occlusion search; of these, 86 met the inclusion criteria. Incidence or prevalence and NIHSS scores of 5 or higher, who underwent IV or IA treatment, was reported in 44 of 86 studies, 12 reported mortality, and 30 were enrolled. Intracranial artery calcification scores were calculated reported risk factors of mortality. Four studies were excluded after by counting the number of major intracranial arteries with calcifica- determining that case ascertainment methods likely resulted in large tion on simple head CT scan (ranging from 0 to 7; 2 distal internal overestimates or underestimates. Annual ALS incidence ranged from carotid, 2 middle cerebral, 2 vertebral and 1 basilar arteries). Patients 0.42 (Iran) to 3.7 (UK) per 100,000 population (with outlier 7.5 were divided into high calcification burden (HCB; score[=3) and low [Guam]). Prevalence ranged from 1.9 (Uruguay) to 11.3 (Japan) per calcification burden (LCB; score\3). The characteristic findings of 100,000. Most incidence estimates ranged from 1-3 per 100,000. CT and conventional angiography, responses of IV and IA treatment, Prevalence ranged more widely across studies, with a group of esti- and clinical outcomes were compared between the groups. mates clustering around 2-4 per 100,000. Annual mortality rates Results: Among 80 patients, 65 patients had LCB while 15 patients ranged from 0.67-2.54 per 100,000. Reported median survival from had HCB. Patients with HCB was older (72.47±9.69 vs 61.63±13.91, diagnosis in selected studies ranged from 1.5 yrs (UK) to 3.3 yrs (US). p=0.006), and more commonly had diabetes (42.9 % vs 12.5 %, Risk factors associated with higher mortality rates included male P=0.009) than those with LCB. Sex and initial NIHSS score did not gender, older age at disease onset, and bulbar onset of ALS. differ. The frequency of high ASPECTS score ([=8) on nonenhanced Conclusions: Although ALS is relatively rare, reported incidence CT (53.8 % vs 36.5 %, p=0.244) and full leptomeningeal collateral on and prevalence varies widely across geographies. This may be partly

123 S52 J Neurol (2012) 259 (Suppl 1):S1–S236 due to differences in population age distributions and case ascertainment and symptoms at an early stage. This will facilitate appropriate methods. Notably, few studies of incidence and prevalence have been referral, and may lead to earlier treatment and improved outcomes. conducted. Due to significant data gaps and broad methodological The ALS specialists meeting in June 2011 and this program were variation, estimating numbers of incident and prevalent ALS cases using funded by Biogen Idec. rates reported in the literature may not accurately reflect the global disease burden. There is a clear need for large-scale epidemiological studies of ALS that utilize sound case ascertainment approaches. O302 This research was funded by Biogen Idec. White-matter damage in amyotrophic lateral sclerosis and primary lateral sclerosis: a tract-based spatial O301 statistics study Development of a ‘‘red flags’’ symptom list to assist F. Agosta, S. Galantucci, E. Scola, A. Chio`, N. Riva, with early recognition and diagnosis of amyotrophic V. Silani, A. Calvo, S. Iannaccone, A. Falini, G. Comi, lateral sclerosis M. Filippi N. Atassi, I. Nakano, J.S. Mora, V. Drory, M. Cudkowicz, Ita-Salute San Raffaele University (Milan, IT); University of Turin J. Shefner, A. Chio`, H. Mitsumoto, V. Silani, L. Zinman, (Turin, IT); Universita` degli Studi di Milano–IRCCS Istituto Auxologico Italiano (Milan, IT) M. Weber, L.H. van den Berg, W. Robberecht, L-O Ronnevi, O. Hardiman, L. Bruijn, D. Kerr, J.R. Williams Objective: Primary lateral sclerosis (PLS) and amyotrophic lateral sclerosis (ALS) are two of the major clinical presentations in the Massachussetts General Hospital (Charlestown, US); Jichi Medical motor neuron disease (MND)-spectrum. PLS is associated with iso- University (Togichi, JP); Hospital Carlos III (Madrid, ES); Tel-Aviv lated upper motorneuron degeneration and ALS with both upper and Sourasky Medical Center (Tel-Aviv, IL); Upstate Medical University lower motorneuron involvement. Diffusion tensor imaging (DTI) may (Syracuse, US); University of Turin (Turin, IT); Columbia University help the understanding and differentiation of MND phenotypes in Medical Center (New York, US); University of Milan Medical School vivo. The aim of this study was to investigate white matter (WM) (Milan, IT); Sunnybrook Health Sciences Centre (Toronto, CA); damage in PLS and ALS using DTI. Kantonsspital St. Gallen (St. Gallen, CH); University Medical Centre Methods: We enrolled 27 PLS patients, 28 ALS patients, and 35 Utrecht (Utrecht, NL); University Hospital Leuven (Leuven, BE); matched healthy subjects. The two patient groups were matched for Karolinska Institute (Stockholm, SE); Trinity College and Beaumont the ALS-FRS-r score. Tract-based spatial statistics was used to per- Hospital (Dublin, IE); ALS Association (Florida, US); Biogen Idec form a brain voxel-wise analysis of fractional anisotropy (FA), axial, (Cambridge, US) radial (radD) and mean diffusivity, adjusted for age. Results: Compared to controls, PLS patients showed abnormalities Objectives: Amyotrophic lateral sclerosis (ALS) is characterised by of all the DTI metrics involving the corticospinal tracts (from the progressive motor neuron degeneration, muscle atrophy, and weak- cerebral peduncles to the posterior limbs of the internal capsule [PLIC] ness, and in some cases cognitive decline. ALS diagnosis is primarily to the WM adjacent to the motor, premotor and supplementary motor based on signs and symptoms observed by the physician. Currently, cortices) and the corpus callosum (CC). The frontal WM, cortico- there is a 10-22 month delay from symptom onset to diagnosis, mainly pontine fibers and thalami were also damaged in these patients. due to similarities between early symptoms of ALS and other com- Compared to controls, ALS patients showed a significant FA decrease mon, non-fatal, diseases. This initiative aimed to develop a shortlist of and a radD increase of the entire corticospinal tracts and body of the hallmark symptoms to assist with early recognition/diagnosis of ALS. CC. When compared with ALS, PLS patients showed a significant FA Methods: A shortlist of characteristic ALS signs and symptoms for decrease and diffusivity increases of the body of the CC. ALS diagnosis was developed at a meeting of ALS specialists (June Conclusions: Different degrees of WM involvement occur in PLS 2011). This shortlist, termed ‘‘ALS red flags,’’ was developed by the and ALS. The most extensive pattern of WM damage was observed in ALS specialists based on their clinical experience and a review of PLS patients. PLS was found to be associated with an involvement of their patient databases. The ALS red flags list is being validated using the inter-hemispheric fibers connecting the two primary motor corti- patient data from the General Practice Research Database (GPRD), ces. Voxel-wise DTI measures are valuable in the differentiation of which contains anonymised data from *630 primary care practices WM involvement in the different clinical phenotypes of MND. (over 11 million patients) in the United Kingdom. Published literature indicates that the computer-identified ALS incidence from the GPRD is comparable with rates in population-based registries in Scotland, O303 Ireland, and Italy; thus this is a reasonable database for validation of the red flags list. Red flags will be abstracted from the medical records Prospective memory tasks: a more sensitive method of a sample of patients referred to neurologists by general practitio- for screening cognitive impairment in early-phase ners (GPs). Latent class analyses will test if red flag clusters can amyotrophic lateral sclerosis? differentiate patients with ALS from other neurology referrals. Y. Ji, L. Wei, K. Wang, D. Fan Results: Characteristic signs and symptoms in considering an ALS Beijing University Third Hospital (Beijing, CN); Anhui Medical diagnosis, and modifying terms, were discussed and agreed upon. Modifiers University First Hospital (Hefei, CN) (e.g, progressive, excessive, or unusual location) were considered a key element to be used with each sign/symptom. Symptoms include clumsiness, Objective: To find a sensitive screening battery for detecting subtle speech change, dysarthria and dysphagia, cramps, fatigue, and gait changes; cognitive deficits in early-stage patients with amyotrophic lateral scle- signs include fasciculation, atrophy, and weakness. Examples of red flags rosis (ALS). that should prompt further investigation for ALS are ‘‘excessive fatigue’’, Methods: Eighty consecutive patients with ALS and 57 matched ‘‘excessive cramps’’, ‘‘progressive tongue fasciculation’’, or ‘‘progressive normal controls underwent a series of neuropsychological tests: the weakness’’. Further list/methodology details will be presented. Mini-Mental Status Examination (MMSE); the Neuropsychiatric Conclusions: It is expected that the ALS red flags list will enable Inventory (NPI); the Frontal Behaviour Inventory (FBI); the verbal clinicians, particularly GPs and neurologists, to recognise ALS signs fluency test (VFT); the Stroop Colour Word Interference Test (CWT);

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S53 and the prospective memory (PM) tests, including event-based pro- O305 spective memory (EBPM) and time-based prospective memory Age-related association of TDP-43 mislocalisation (TBPM). Furthermore, a subset of the patients underwent examinations involving picture and music emotional perception or decision- with reduced activity of ADAR2, an RNA editing making (Iowa Gambling Task and risk-taking task). enzyme, in normal mouse motor neurons suggests Results: The patients did not differ from the controls on the MMSE but a molecular basis for age-related acceleration of ALS significantly differed in the behavioral inventories, including the NPI T. Hideyama, S. Teramoto, T. Yamashita, S. Kwak (P\0.001) and FBI (P\0.001). Our patients did not differ from the controls University of Tokyo (Tokyo, JP) in the traditional neuropsychological tests (VFT and CWT). By contrast, statistically significant differences were found in the PM tests (EBPM: Objectives: Motor neurones of patients with sporadic amyotrophic P=0.043; TBPM: P\0.001) and the arousal from negative pictures lateral sclerosis (ALS) express GluA2, an AMPA receptor subunit, (P=0.015). More interestingly, TBPM was more sensitive than EBPM in with the Q/R site unedited due to the downregulation of an RNA the early-phase patients (possible + probable laboratory-supported ALS). editing enzyme called ADAR2. This is a disease-specific and death- We did not find that the ALS patients performed more poorly than the causing molecular abnormality. Down regulation of ADAR2 is closely controls on the valence and recognition of pictures, musical emotional associated with TDP-43 pathology, a neuropathological hallmark of perception, Iowa Gambling Task or risk-taking task instruments. sporadic ALS, has recently been shown to be closely associated with Conclusions: Prefrontal lobar dysfunction does exist among ALS the downregulation of ADAR2 in the motor neurones of patients with patients and may spread from the medial to the lateral region. The sporadic ALS (Aizawa et al., Acta Neuropathol 120:75-84, 2010). behavioural and PM tests used in this study are more sensitive for Because TDP-43 pathology is found more frequently in the brains of detecting behavioural and cognitive impairment in early-stage ALS elderly patients, we investigated the age-related changes in the patients than are the classical cognitive measures. localization of TDP-43 and ADAR2 activity in mouse motor neurones. Methods: Spinal cord of C57BL/6J mice with various ages (raging from 1 day to 104 weeks) were used. Immunohistochemistry for TDP- O304 43 and ADAR2 was performed on the spinal cord sections. Expres- Brown-Vialetto-Van Laere and Fazio Londe overlap sion level of ADAR2 mRNA in the spinal cord was investigated by motor neuron syndromes with bulbar involvement. means of quantitative RT-PCR. Extents of the editing efficiency at the A clinical, biochemical and genetic study ADAR2-specific RNA editing sites, including the Q/R site of GluA2 mRNA and the K/E site of cytoplasmic fragile X mental retardation M. Catteruccia, M. Ciccolella, S. Benedetti, I. Moroni, protein interacting protein 2 (CYFIP2) mRNA, were investigated by G. Uziel, C. Pantaleoni, L. Chiapparini, A. Bizzi, quantitative measurement of restriction enzyme-dependent fragments A. D’Amico, F. Fattori, M. Salzano, A. Pastore, of the RT-PCR products in the spinal anterior horn and laser-captured G. Tozzi, F. Piemonte, E. Bertini motor neurone tissues. Results: We found that the ADAR2 activity was developmentally Bambino Gesu’ Children’s Research Hospital (Rome, IT); IRCCS C. upregulated, and its mRNA expression level was progressively decreased Besta (Milan, IT) in the spinal cords of aged mice. Wild-type motor neurones exhibited Objectives: Brown-Vialetto-van Laere (BVVL) and Fazio-Londe nuclear ADAR2 and TDP-43 immunoreactivity, whereas fast fatigable (FL) are rare and clinically overlapping motor neuron syndromes with motor neurones in aged mice demonstrated a loss of ADAR2 and bulbar involvement. Recently BVVL has been associated with abnormal TDP-43 localization. Importantly, these motor neurones mutations in C20orf54/hRFT2 and defective riboflavin transport. We expressed significant amounts of the Q/R site-unedited GluA2 mRNA, compared clinical, laboratory and molecular genetic findings on six which is a lethality-causing molecular abnormality observed in the motor patients (age range 11-17 years) affected by BVVL&FL overlap neurones of sporadic ALS patients. motor neuron syndromes. Conclusion: These results suggest that age-related decreases in Methods: Blood levels of riboflavin and redox status, electro- ADAR2 activity play a mechanistic role in aging and serve as a risk physiological, neuroradiological and pulmonary studies, ALS factor for ALS. functional rating scale and molecular genetic analysis were performed. Results: Two patients manifested deafness at ages of 3 and 10 years, and developed later subacute progressive limb weakness and bulbar palsy. A third patient manifested subacute palsy of multiple ______cranial nerves; he completely recovered after intravenous immuno- Oral session 20 globulins (IVIG), but then relapsed remaining unresponsive; he was not deaf although had abnormal auditory evoked responses (BAERs). The remaining 3 patients had no deafness, although likewise mani- Infection fested subacute progressive ponto-bulbar palsy. No patient had reduced riboflavin blood levels. However, on riboflavin supplementation (10mg/kg/day) the most severely affected BVVL patient O306 stopped progression of symptoms following 8 months of treatment. Molecular genetic analysis disclosed compound heterozygous Hypothalamic proline-rich polypeptide PRP-1: mutations mutations in 3/6 patients manifesting deafness or abnormal new immunomodulator against methicillin-resistant BAERs. All the patients with mutations in C20orf54/hRFT2 corre- Staphylococcus aureus infection sponded to the BVVL phenotype while we did not find any mutation A. Durgaryan, M. Matevosyan, T. Seferyan, A. Galoyan in the remaining patients with a FL phenotype, and these patients had Institute of Biochemistry (Yerevan, AM) no mutations in the additional riboflavin transporter genes hRFT1 and hRFT3. Proline-rich polypeptides isolated from neurohypophyseal and Conclusion: BVVL and FL are severe progressive diseases with hypothalamic neurosecretory granules represent a new family of overlapping symptoms although only hRFT2 mutated patients mani- hypothalamic neuropeptides which are synthesized in the form of fest deafness and correspond to the BVVL phenotype. a common precursor protein minus neurophysin-vasopressin-

123 S54 J Neurol (2012) 259 (Suppl 1):S1–S236 associated glycoprotein (NVAG) by genetically determined mech- non-occurrence of vomiting with the platelet count. There are no anisms and released from the precursor by proteolysis during significant associations between the occurrence and non-occurrence axonal transport. One of these peptides, a 15 amino acids PRP-1 or of headache, restlessness or decreased sensorium with the platelet Galarmin (AGAPEPAEPAQPGVY) possess a broad-spectrum of count. biological activities including antibacterial, antitumor, immuno- Conclusion: Neurologic manifestations of dengue hemorrhagic modulatory and neuroprotective properties. PRP-1 is a regulator of fever consist of headache, vomiting, restlessness and decreased sen- humoral and cellular immunity, thymocyte differentiation, and sorium. However, its occurrence is rare in this tertiary hospital in the myelopoiesis. Systematic administration of PRP-1 can prevent Philippines. neurodegeneration in hippocampus induced by amyloid peptide There is an association between vomiting and platelet count. Abeta 25-35 and protects from aluminum neurotoxicity causing However, it is inconclusive to deduce its association since most of the Alzheimer-like disease. PRP-1 was shown to be also powerful cases of vomiting were not related to any neurologic symptom. antibacterial agents in vivo against such pathogens as Bacillus This study showed no association between hematocrit elevation anthracis, Clostridium perfringens and Mycobacterium tuberculosis. and headache, vomiting, restlessness, and decreased sensorium. There Our data indicates strong prophylactic activity of PRP-1 against are also no associations between platelet count and headache, rest- methicillin resistant S. aureus (MRSA). Recent increase of MRSA lessness, and decreased sensorium. strains at large hospitals as well as community settings (community associated) started to pose great difficulty in selecting antimicrobial agents. We have shown that PRP-1 could fully protect mice against O308 a lethal infection of MRSA injected 24h before infection and 1h post infection period at a concentration of 1 lg per mice, and its Expression profile of neuropeptide Y, its receptors higher concentrations (5 and 10 lg) protect animals against MRSA, and its role in seizures on mouse models even when injected simultaneously with the bacteria. It was dem- of toxoplasmosis and African trypanosomiasis onstrated that the protective activity of PRP-1 is not due to a direct Y.W. Woldeamanuel effect on bacteria, but rather on the host response to infection. We Addis Ababa University (Addis Ababa, ET) could show that PRP-1 significantly increased the level of proinflammatory cytokine IL-6, IL-8 and modulate the expression of Objectives: A. To compare expression of NPY and its receptors serum immunoglobulins IgA, IgM and IgG. The hematological NYPR1, NYPR2 and NYPR5 in hippocampi of: effect (complete blood count) under PRP-1 influence was revealed i) BALB/c mice infected with Toxoplasma versus Trypanosoma, as well. Received data demonstrate that PRP-1 plays regulatory against their controls. role in immune response modulating process during MRSA ii) Trypanosoma infected seizure resistant C57Bl/6 [B6] versus infection. seizure prone BALB/c mice, against their controls. iii) Trypanosoma infected inducible nitric oxide synthetase knock- out [iNOS-/-] B6 mice versus iNOS-/- B6 control. O307 B. To compare seizure with tail rotation in the above experiments Neurologic manifestations of dengue haemorrhagic Methods: Hippocampi were punched from 4 frozen BALB/c mice fever in a tertiary hospital in the Philippines, 2010 brain that were infected with Toxoplasma tachyzoites, and the tran- M.K. Garcia, R. Espiritu-Picar scripts for NPY and its receptors were measured using real-time RT PCR and compared to their controls. Twenty B6 and twenty BALB/c Makati Medical Center (Makati, PH) mice [8-12 weeks old] were infected with 2000 Trypanosoma brucei Objectives: The objectives of the study are to enumerate and describe brucei [T.b.b.] and 4 animals from each group were sacrificed. Their the neurologic signs and symptoms of patients with dengue hemor- hippocampi were dissected at 8, 21, 28, 33 days post-infection [dpi] rhagic fever (DHF) admitted in 2010 in a tertiary hospital in the for the B6 mice and at 10, 18, 26, 35 dpi for the BALB/c mice and Philippines, and to determine the association of platelet count and transcripts for NPY and its receptors were determined. In addition to hematocrit elevation with headache, vomiting, restlessness and RT PCR, comparison of expression of NPY and its receptors along decreased sensorium. the dorsal hippocampus in BALB/c mice was made by immunohis- Methods: 192 medical charts with a discharge diagnosis of tochemistry [IHC] using tyramide signal amplification [TSA] between aˆ€œdengue hemorrhagic feveraˆ€ admitted in 2010 in a tertiary hos- the T.b.b. infected and non-infected BALB/c mice. Similar expression pital were reviewed. was compared between 4 iNOS-/- T.b.b. infected B6 and non-infected Results: There were 49 adult patients and 143 pediatric patients. iNOS-/- B6 mice. Seizure susceptibility was serially checked by tail The mean age for pediatric cases is 11 years and 30 years for adult rotation in all mice. cases. The mean lowest platelet count among all patients is 63,126. Results: Increased expression of NPY, NPYR1, NPYR2 and Forty-two percent had elevations in hematocrit. NPYR5 is seen in the toxoplasmosis infected BALB/c. T.b.b. infected In this study, the 3 common symptoms were fever, rash and B6 mice had early increased expression of NPY and its receptors, headache, followed by abdominal pain, vomiting and malaise. Only however in late dpi levels decreased to control. T.b.b. infected BALB/ one patient presented with restlessness and decreased sensorium. c mice showed progressively increased expression of NPY, NPYR1 Thus, a neurological presentation occurred in 1 patient with DHF and NPYR5. The IHC showed increased NPY expression, comparable supporting the current view that encephalopathy is rare in DHF. NPYR1 and NPYR2 expression in the late dpi samples of the BALB/c Chi-square test was used to determine the association of hemat- T.b.b. infected mice. iNOS-/- B6 mice, the only ones to develop ocrit elevation with headache, vomiting, restlessness, and decreased seizures on tail-rotation, showed up-regulated NPY but down-regu- sensorium. There are no significant associations between the occur- lated receptors. rence of headache, vomiting, restlessness, and decreased sensorium Conclusion: Progressive increased expression of NPY receptors in with hematocrit elevation. the seizure-prone BALB/c mice t-test was used to determine the association of the mean lowest models of trypanosomiasis and in the seizure-prone toxoplasmosis platelet count with headache, vomiting, restlessness, and decreased mice models, supports the protective role of NPY against seizure in sensorium. There is a significant association of the occurrence and the neuroinflammation. iNOS maybe an important factor in the

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S55 expression of NPY receptors. This necessitates a full study on the role Objectives: To describe a case of locked-in syndrome caused by of NPY and iNOS during brain infections. Immune Reconstitution Inflammatory Syndrome (IRIS) in a patient with AIDS and brainstem Progressive Multifocal Leukoencephalop- athy (PML). Methods: Case report. O309 Results: A 37 year-old woman with history of AIDS, CD4 cell The two variants of HHV-6 in CNS disease count of 37, HIV viral load of 115,354 copies/mL presented with J. Pietilaïnen-Nickleń, O. Virtanen, L. Uotila, M. Fa¨rkkila¨, right hemiparesis involving the face, arm and leg. Magnetic reso- M. Koskiniemi nance imaging (MRI) revealed non-enhancing T2 hyperintense lesions in the right cerebellar hemisphere and middle cerebellar Haartman Institute (Helsinki, FI); National Institute of Neurological peduncle extending to the pons. JC virus DNA was detected in the Disorders and Stroke (Bethesda, US); HUSLAB (Helsinki, FI); cerebrospinal fluid (CSF) by PCR. In the absence of evidence of Department of Neurology (Helsinki, FI) other opportunistic infections (OI) and negative cytology, PML was Objectives: To evaluate the role of human herpes virus (HHV-6) in diagnosed. Highly active antiretroviral therapy (HAART) and central nervous system (CNS) diseases. mirtazapine were started. Methods: Serum and cerebrospinal fluid (CSF) samples were The patient was readmitted 2 weeks later, with fever, rapidly collected from MS study of 80 patients with positive oligoclonal band progressive generalized weakness and obtundation, dysphagia and (OCB) finding in their CSF. OCBs were detected by using isoelectric respiratory compromise requiring intubation. She maintained ade- focusing (IEF) and localized by immunofixation with peroxidase- quate oxygen saturation and defervesced without antibiotic therapy. conjugated IgG-antiserum and visualization with immunoperoxidase Initial blood, urine and sputum cultures were negative. CSF anal- staining. HHV-6 -specific IgG OCBs were studied by affinity driven ysis revealed a mild lymphocytic pleocytosis and the presence of immunoblotting using purified viral HHV-6A and HHV-6B lysates as JC virus DNA. Cytology and testing for other OIs, including antigens. HHV-6 infection was diagnosed serologically using Cryptococcus and Toxoplasma was negative. MRI revealed exten- immunofluorescence (IFA) and defined as acute primary infection or sion of the existing pontocerebellar lesion into the entire pons, with past infection, based on the avidity of IgG antibodies. new subtle enhancement. The CD 4 cell count had increased to Results: Acute primary infection was observed in 16 patients 114, HIV viral load decreased to 162 copies/mL. Neurologic exam (20 %), 5 with only HHV-6A, 6 with only HHV-6B and 5 with both revealed a locked-in state, with diffuse flaccid paralysis of all 6A and 6B infection. In 63 cases (79 %) high avidity IgG antibodies extremities and horizontal gaze, profound bulbar musculature were present indicating past HHV-6 infection, in 59 cases (94 %) for weakness and preservation of alertness and volitional vertical eye both variants. One patient had no HHV-6 IgG antibodies in serum. movements. HHV-6 specific OCBs were detected in 14 cases (22 %) of past PML-IRIS was diagnosed and treated with high-dose intravenous infections and in 3 cases (19 %) of acute primary infections. Up to steroids. HAART and mirtazapine were continued. Strength improved 56 % (minimum 5 %) of the total number of CSF specific OCBs were minimally for 2 days, with subsequent deterioration and complication specific to HHV-6, with highest numbers in patients with a serolog- by multiorgan failure. The patient expired 16 days after her second ically past HHV-6 infection. A and B variants were present in equal hospitalization. number of cases. Both variants also had same number of bands in Conclusion: PML is a known OI of the CNS, complicating patients total. In all cases of acute infection there were specific OCBs only for with compromised cellular immunity, commonly seen in AIDS one variant. 8 cases of 14 past infections (57 %) had specific OCBs patients. No known therapy exists, and it is accepted that initiation of for both variants. Patients with HHV-6 specific OCBs in CSF had HAART improves survival. higher leukocyte content (1 to 62, average 13 E6/l) and IgG index However, IRIS can complicate the treatment of PML with HA- (0,48 to 3,58, average 1,30) of CSF compared to patients with HHV-6 ART initiation in AIDS patients, with fatal consequences. Caution negative OCBs (0 to 62, average 8 and 0,50 to 3,14, average 1,05, should be exercised when initiating HAART in patients with PML respectively). lesions in critical brain regions, including the brainstem. Conclusion: HHV-6 infections might play a role in CNS diseases as suggested by HHV-6 specific OCBs. HHV-6 specific OCBs may be present even in acute primary HHV-6 infections both in 6A and 6B associated cases. However, the reaction appeared much more prom- O311 inent in patients with past infection. Many patients seemed to have a double infection of 6A and 6B or the other virus reactivates the latent Pro-inflammatory cytokines and cognitive deficit variant. It is also possible that there appears a cross reaction between in HIV dementia antibodies. The increasing number and specificity of the bands, as D. Labunskiy, T. Fedotova well as CSF leukocyte reaction, point out the possible activity in University of Northern California (Santa Rosa, US); Tver State CNS. Medical Academy (Tver, RU) Neurocognitive impairment following CNS opportunistic infections and HIV-dementia (HAD) were common clinical features of HIV O310 infection prior anti-retroviral associated therapy. The levels of proinflammatory cytokines (IL-6 and TLF-alpha) were detected in a Locked-in syndrome caused by immune reconstitution serum and CSL of 24 patients with HIV dementia. Pro-inflammatory inflammatory syndrome in a patient with AIDS cytokines (PIC) detection was performed by Western blot analysis and brainstem progressive multifocal and quantified a by enzyme-linked immunosorbent assay. The level of leukoencephalopathy cognitive deficiency was evaluated by the International HIV Dementia Scale (IHDS). Control group was comprised from 56 rel- V.A. Lioutas, A.M. Cervantes- Arslanian, D.M. Green, atively healthy donors. It was revealed a strong correlation between a J.D. Burns dementia level for one hand, and IL6 and TLF-alpha for other in 19 Boston Medical Center (Boston, US) patients with a clear symptoms of dementia caused by HIV infection.

123 S56 J Neurol (2012) 259 (Suppl 1):S1–S236

Antiviral therapy caused decrease the manifestation of dementia signs O313 in 17 patients alongside with a normalization of PIC in a biological The awareness in patients in coma or vegetative state is liquid of HIV dementia patients. not an ON-OFF process F. Villa, K. Colombo, V. Pastore, S. Galbiati, M. Recla, F. Locatelli, S. Galbiati, S. Strazzer ______IRCCS E. Medea - La Nostra Famiglia (Bosisio Parini, IT) Oral session 21 Objectives: A early rehabilitation for acquired brain injury has been shown to improve responsiveness in patients with altered conscious- Neurorehabilitation ness in the early post-acute stage. Besides physical rehabilitation and speech therapy, in our Institute these patients also receive cognitive- behavioral psychostimulation treatment. The goal of this protocol is to O312 stimulate and reinforce the patient’s responsiveness by optimizing his/her resources and skills and turning them into means of commu- Outcomes in severe disorders of consciousness - nication and interaction with the environment. The assessment of preliminary results of a prospective German registry these patients is made by Level of Cognitive Functioning Assessment (KOPF-R) Scale (LOCFAS). The present study aim to describe the progressive A. Bender, A.-M. Klein, U. Mansmann, A. Straube, improvement in cognitive-behavioral functioning level and responsiveness in patients, compared the LOCFAS score for each level J. Herzog, F. Mu¨ller, E. Koenig, D. Nowak, R. Jox, E. Grill reached by the patient in each evaluation. Therapiezentrum Burgau (Burgau, DE); University of Munich Methods: 40 patients, aged between 1 to 17 years, were recruited (Munich, DE); Schoen Klinik Mu¨nchen-Schwabing (Munich, DE); from a cohort of children with acquired brain injury and attending our Schoen Klinik Bad Aibling (Bad Aibling, DE); Neurologie Institute for a rehabilitation treatment in the post-acute stage. Two Kipfenberg (Kipfenberg, DE) groups of patients were formed consisting of 25 post-traumatic Objective: Disorders of consciousness (DOC) presenting as coma, a patients and 15 patients with vascular, infective or post-anoxic brain vegetative (VS), or minimally conscious state (MCS), are frequent lesions. All patients were evaluated with LOCFAS, the first one when consequences of severe brain injury, such as anoxic-ischemic patients arrived in the Institute, before starting the cognitive-behav- encephalopathy (AIE), traumatic brain injury (TBI), and subarachnoid ioral psychostimulation program. In this study we considered four hemorrhage (SAH). Prognostication of the long-term DOC outcome is evaluation for each patient, and included patients with an initial a challenge in the intensive care as well as in the neurological reha- LOCFAS level of I or II. bilitation setting. Current practice parameters for prognostication are Results: The most patients show an improvement in cognitive- partially based on outdated studies and carry the risk of too pessi- behavioral functioning level and responsiveness through different mistic assumptions and self-fulfilling prophecies. This novel registry evaluations, as demonstrated by the changing of the LOCFAS level. examines determinants of the long-term outcome and functioning of Even if some patients reach the fifth level, the most of them obtain the the most severely affected brain injured DOC patients. third level, because of the motor and language deficits. Furthermore, Methods: Prospective multicenter neurological rehabilitation reg- also patients who maintain the same level through subsequent eval- istry with currently five active neurological rehabilitation inclusion uations, show a score improvement in the LOCFAS. sites. Enrolled are patients in the VS or the MCS as defined by the Conclusions: Our study shows that awakening from coma is not an coma recovery scale-revised (CRS-R) following acute brain injury. ON–OFF process, but a gradual transition. Patients in coma or veg- Main Outcome Measures: CRS-R, Functional Independence Measure etative state improve their interaction with environment and their (FIM), quality of life (EuroQOL), caregiver burden (CSI) and atti- responsiveness thanks to an early intervention and such improvement tudes towards end-of-life decisions. Follow-up assessments are at 6 can be observed monitoring patients over time. This is a fundamental months and then annually. tool for operators who work with patients in coma or vegetative state, Results: At the time of abstract submission, 42 patients were because only observation and reinforcement of little improvement can included; mean age was 57 years (SD 16 years). Main diagnoses favorite bigger improvements. responsible for DOC were TBI (24 %), SAH (31 %), and AIE (45 %). This study was partially supported by a grant from Italian Ministry Mean CRS-R score at admission to rehabilitation was 5.9 (SD 3.3). 11 of Health -RICERCA FINALIZZATA BANDO 2008 patients died within the follow-up period (26 %). Among the 31 PROGETTO ORDINARIO. survivors, 9 patients emerged from MSC (29 %, 2 with TBI, 5 with SAH, 2 with AIE). 36 patients (86 %) had one or more of the established negative prognostic factors (i.e. absence of brainstem O314 reflexes, NSE levels [ 33 lg/L, bilateral loss of cortical N20, unreactive EEG), five of whom emerged from MCS. Regression analysis Summarising 16 years of research showed, that none of the typical prognostic markers were associated in neurorehabilitation and cell therapies for spinal cord to emergence from MCS. injury We will present at the ENS meeting all patients that will have been A. Bryukhovetskiy, I. Bryukhovetskiy, M. Zhukova enrolled until May 31st, 2012. Neurovita Clinic of Interventional and Restorative Neurology and Conclusions: Despite a strong negative selection bias in our reg- Therapy (Moscow, RU) istry, a significant proportion of patients emerged from MCS, suggesting that their rehabilitation potential may have previously Objectives: Evaluation of long-term effects of neurorehabilitation and been systematically underestimated. Our data highlight the actual cell therapies in spinal cord injury (SCI). danger of self-fulfilling prophecies in the setting of comatose brain Methods: First results of fetal neural cells (FNCs) therapy for injury survivors. combat mine-blast injury of spinal cord and brain were published in The project is partially funded by the Hannelore-Kohl-Stiftung and 1996. About 10-20•106 of allogeneic FNCs isolated from cerebral the Deutsche Stiftung Neurologie. vesicle of 2 or 3 embryos 8-12 weeks old were intrathecally

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S57 administered in 115 cases of combat SCI and brain injury (BI). The training, 25 % strength training, 4 % team sports, 9 % miscellaneous method was successfully used in 176 SCI cases of civilian population. types, frequently mentioned Yoga (no data = 27 %). Only 38 % of From 2002 till now we apply granulocyte colony-stimulating experts recommended physical exercise. However, concrete experts‘ factor mobilized autologous hematopoietic stem cells (AHSCs) information about type of sports, frequency, duration and intensity (CD34+, CD45-) isolated from peripheral blood and cryopreserved. were really rare. Furthermore, about two thirds of the experts never AHSCs in the dose of 5•106 were intrathecally administered to 578 mentioned sport as a therapy option. patients. Cells were administered every 3 months for 4 to 5 years, Conclusion: The results of this survey show that research findings totaling 3156 administrations. In 8 cases cell therapy lasted 9 years. concerning positive effects of physical exercise in MS still haven’t Patients received neurorehabilitation according to patented method of been transferred in everyday practice. MS patients show reduced activating lost motor functions. Patients regularly passed magnetic exercise behaviour, comorbidities as a result of enhanced immobility, resonant imaging, CSF and blood tests, urodynamic testing, repeated even nescience or fear in physical exercise. Patients, even if fit for evaluation with American Spinal Injury Association score and Spinal sports, do not receive evidence-based information to benefit from Cord Independence Measure. In most cases neurophysiological con- potential effects. Recommendations about training principles must be trol was done every three months. transferred by appropriate experts who are in constant contact with Results: Combat SCI and BI group that received FNCs therapy MS patients. It seems suitable that patients improve empowerment in reduced mortality rate from 7.2 % (1997) to 2.2 % (1999) and disorder to identify myths and wrong information concerning MS and ability rate from 48.8 % to 17 % as compared to control group of 120 training options. combat SCI and BI cases who received conventional therapy. This study was financially and organisationally supported by the Comparative analysis showed clinical and neurophysiologic German Multiples Sclerosis Society (department of Saarland). restoration in all types of cell therapies and their efficiency varies from 30.5 % to 65 % directly depending on cell type. Achieved improvement of life quality persisted after cell therapy was ceased. Follow up showed no cancer onset, prion, viral or bacterial con- O316 tamination. Specialized neurorehabilitation increased therapy Effect on functional brain plasticity of a motor dexterity efficiency rate by 10-12 %. Maximal restoration (65.1 %) was training carried out with and without musical cues: observed in intrathecal AHSCs administrations for moderate SCI a fMRI study of the mirror neuron system in healthy cases (involving\=50 % of spinal cord crosswise and\=1 segment longwise). FNCs therapy demonstrated apparent biostimulative individuals effect, though regenerative and restorative effect was rare and M.A. Rocca, L. Panicari, G. Riccitelli, E. Gobbetti, impossible to repeat. M.C. Di Fabio, R. Gatti, P. Valsasina, A. Falini, G. Comi, Conclusion: FNCs and AHSCs therapies are both safe, the latter M. Filippi demonstrated significant regenerative and restorative effect. Thera- Vita-Salute San Raffaele University (Milan, IT) peutic efficiency is higher if applied to the cases of moderate SCI and can be considerably enhanced by specialized rehabilitation. Objective: To assess, using functional magnetic resonance imaging (fMRI), the effect on the recruitment of the motor and mirror neurons system (MNS) of a motor dexterity training, carried out with and without musical cues in young healthy subjects. O315 Methods: Forty-five right-handed healthy subjects without any Exercise behaviour in multiple sclerosis patients musical experience performed a 2-week motor training, consisting of S. Kersten, M. Mahli, C. Mai, G. Wydra, C. Haas 10 daily sessions of 30 min each, where they executed with their right Saarland University (Saarbru¨cken, DE); Hochschule Fresenius hand a pre-defined ‘‘colours and fingers’’ sequence on a computer (Idstein, DE) modified keyboard, at a rhythm marked by a metronome. Subjects were randomized in 3 groups: ‘‘Metronome’’ group (MG) heard no Objectives: Several studies revealed that Multiple Sclerosis (MS) musical cue, ‘‘Rhythm’’ group (RG) heard a musical cue at the same patients benefit from physical exercise concerning their physical rhythm of the metronome, and ‘‘Over-rhythm’’ group (OG) heard a working capacity and MS symptoms. Due to this fact, one might musical cue having higher rhythm of the metronome. At baseline (T0- expect that MS patients participate in therapeutical training treatments before training) and after 2 weeks (W2-after the training), fMRI was or exercise self-regulated. This study aimed at evaluating the actual acquired during the performance of the 9HPT and an observation/ exercise behaviour in German MS patients and experts‘ (i.e. neurol- imitation task of a learned and a novel motor sequence. fMRI analysis ogists, physiotherapists) recommendations concerning physical was performed using SPM8. exercise in MS disease. Results: At W2, during the 9HTP, the MG and OG showed an Methods: Based on a cooperation of the German MS Society increased activation of the cerebellum and a decreased activation of (department of Saarland) and the Sports Science Institute Saarbru¨c- some regions in the right frontal and parietal lobes; the MG and RG ken, Germany, 1100 MS patients were invited to participate in this had an increased recruitment of the putamen. During the observation/ survey. 263 MS patients (age = 47.6 ± 9.8, disease duration = 13.5 ± imitation of a learned task, the MG and RG showed a reduced acti- 9.1 years) answered the self-report questionnaire (response rate: vation of the right hippocampus. Compared to the other two groups, 24 %) about their exercise behaviour before and after MS diagnosis, the MG had an increased activation of the right precentral gyrus, the general health, independence in daily living and experts’ RG had an increased activation of the left precentral gyrus, and the recommendations. OG an increased activation of the precuneus and the inferior frontal Results: The general health score (SF 36) averaged on 52.9 ± gyrus. During the observation of a novel task, compared with the 19.5, which is significantly lower compared to healthy controls (p \ learned one, all groups showed a reduction of the activation of the .0001). 46 % of MS patients currently exercise (59 % did sports MNS, whereas during imitation all groups had an increased recruit- before the MS diagnosis), whereas 52 % did no exercises (no data = ment of this neural network. 2 %). There is a significant reduction in exercise behaviour after the Conclusion: Motor training is associated with significant fMRI MS diagnosis concerning duration and intensity of physical exercise activity changes, and different training schemes are associated with (p \ .0001). 35 % of the currently exercising patients do endurance different patterns of activations.

123 S58 J Neurol (2012) 259 (Suppl 1):S1–S236

O317 University Scientific Institute Hospital San Raffaele (Milan, IT) Outpatient rather than inpatient: results of a new Objectives: Converging evidence indicates that intense musical housing project for people with severe neurological training is associated with plastic changes in the human nervous disabilities in Germany system. However, more studies are needed to further understand the mechanisms of musical training-induced plasticity. In the present K. Wolf-Ostermann, S. Naber, J. Gra¨ske study, we used electroencephalography (EEG) and transcranial Alice Salomon University of Applied Sciences (Berlin, DE) magnetic stimulation (TMS) to investigate the effects of piano key- Objectives: In 2009 the Fu¨rst Donnersmarck Foundation (FDST) board training on interhemispheric interactions and brain activity. launched a new housing project in Berlin, Germany for people with Methods: 12 right-handed, music-naı¨ve subjects underwent a (multiple) severe disabilities caused by acquired brain injuries (e.g. motor training consisting in ten 35-minute sessions (2 weeks), playing stroke, traumatic brain injury). People moved from a traditional an electronic piano keyboard. Before and after training, subjects long-term care arrangement (LTC) to a supported living accom- underwent hand motor function (finger tapping, pinch, Jamar grip, modation (SLA) to regain a more self-determined life. In SLA and nine hole peg-9HPT tests) and neurophysiological assessments residents can perceive a 24/7 individual support of nursing and using EEG and TMS. The 32 channel-EEG recording aimed at social pedagogic staff. The new life in the SLA is considered to evaluating task-related desynchronization (TRD) of mu rhythm dur- improve residents´ autonomy and quality of life (QoL) and will ing motor performance. TMS, targeting the abductor pollicis brevis enable residents to become more active members of society again. (APB) and abductor digiti minimi (ADM) of both hands, was per- The objective of this study is to evaluate the effect of SLA con- formed to obtain resting motor threshold (RMT), amplitude of motor cerning residents’ QoL, physical and psychosocial outcomes and evoked potentials at 120 % RMT, and ipsilateral silent period (ISP) social inclusion. duration during voluntary tonic co-contraction of APB and ADM. Methods: In a longitudinal design residents in two SLA and one Results: All subjects dramatically improved their motor perfor- LTC were surveyed for 18 months: at baseline and follow-up after 6, mance at keyboard playing. The 9HPT score for the left hand 12 and 18 months (t1-t4). Considered outcomes are social and as well significantly improved in every subject. Pre-training, ISP durations as health and psychosocial aspects: day to day functioning (WHO- were asymmetrical, left ISPs being significantly longer than right DAS II), ADL functioning (EBI), needs of assistance (Metzler ISPs. Post-training, right ISPAPB duration significantly increased, H.M.B.-W), QoL (WHOQoL-Bref, EQ-5D), anxiety and depression leading to symmetrical ISPAPB durations. Moreover, sensorimotor (HADS-D), life goals, social inclusion and additional social factors. rhythms activation during unilateral task execution became also more Results: We included 40 residents (65 % male, 35 % female) with symmetrical, since mu TRD amplitude decreased contralaterally and an average age of 46.2 years. Almost all residents (82.5 %) are in increased ipsilaterally to the movement’s side. need of assistance (H.M.B.-W.; level 4). The total score of the day to Conclusion: Our results showed that bimanual motor skill training, in day functioning at baseline indicated an intermediate level of func- right-handed subjects, was associated with significant improvement of tioning and achieved moderate levels. Significant differences between left hand dexterity, together with increased interhemispheric inhibition age, sex and need of assistance could not be observed at baseline from the right hemisphere towards the left. The rebalance of hand dex- between the three different groups. At t4 14 residents have moved into terity and interhemispheric interactions was accompanied by a reduced a SLA 18 months ago and 15 persons 12 months ago. 11 residents and more symmetrical cortical activation during skilled motor perfor- stayed in the LTC. First results did not show significant overall dif- mance, as shown by the desynchronization of sensorimotor EEG ferences in development over time concerning QoL, functioning and rhythms. These findings suggest that 10 days of skilled motor training anxiety or depression between the three groups. Residents of SLA may be sufficient to induce cortical plastic changes, sharing similarities reported improved social inclusion. Further results of the longitudinal with findings reported on professional musicians. analysis will be presented. Conclusion: For the first time in many years the new housing project offers residents of LTC with multiple severe disabilities the O319 chance of a more self-determined life and of active participation in new social networks. To reliably verify effects of special forms of Muscle sympathetic response to arousal predicts living facilities on residents’ QoL and social inclusion further studies neurovascular reactivity during mental stress and also evaluations over a longer period of time are necessary. V. Donadio, G. Wallin, M. Elam, T. Karlsson, We disclose any personal financial interests related to the spon- M. Giannoccaro, G. Pegenius, F. Giambattistelli, sored project. R. Liguori IRCSS Bologna, University of Bologna (Bologna, IT); University of Gothenburg (Gothenburg, SE); University ‘‘Campus Biomedico’’ ______(Rome, IT) Oral session 22 Objectives: Mental stress often begins with a sudden sensory (or internal) stimulus causing a brief arousal reaction, and is followed by a more long lasting stress phase. Both arousal and stress regularly Clinical neurophysiology induce blood pressure (BP) increases whereas effects on muscle sympathetic nerve activity (MSNA) are variable. The aim of the present study was to search for a link between MSNA responses induced by arousal and by mental stress. O318 Methods: We recorded 30 healthy males aged 33 ± 10 years. Plasticity of motor cortex after musical training: Firstly we studied the effect of a simple arousal (electrical) stimulus a neurophysiological study on MSNA. Subsequently we have compared responses of MSNA and E. Houdayer, S. Zanini, M. Cursi, A. Nuara, G. Comi, BP during arousal and mental stress evoked by a 3-min paced auditory serial arithmetic test (PASAT) in 30 healthy males aged 33 ± 10 R. Gatti, L. Leocani years. In addition, recordings were made of ECG, respiratory

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S59 movements, electrodermal activity and perceived stress. We also Objective: Marcus-Gunn phenomenon is known as a congenital monitored corresponding effects of a cold test (two minutes immer- condition characterized by unilateral blepharoptosis relieved by sion of a hand in ice water). mouth opening. The circuits responsible are not known, but they Results: The arousal stimulus evoked significant inhibition of one could involve reciprocal effects from trigeminal muscle afferents, or two MSNA bursts in 16 subjects, who were classified as which could be either facilitatory for the levator palpebrae (LP) or responders; the remaining 14 subjects were non responders. During inhibitory for the orbicularis oculi (OOc) muscle. Our aim was to mental stress responders showed a significant decrease of MSNA and assess brainstem circuits in a patient with history of pontine lesion, a lesser BP increase compared to non responders. In non responders blepharospasm and jaw-ocular synkinesis MSNA was unchanged or increased. Perceived stress was higher in Methods: The patient was a 64 y.o. man who presented with non responders (p = 0.056) but other measures were similar in the two involuntary eyelid closure relieved by mouth opening after a left groups. In non responders stress induced increases of MSNA and BP upper pontine infarct. He had history of chronic smoking and sleep lasted throughout the subsequent rest period. During the cold test apnea-hypopnea syndrome. He had no other neurological problems. MSNA and BP increased equally much in responders and non Conventional EMG and laboratory analysis ruled out a neuromuscular responders. In the whole group of subjects there was a significant junction disorder. correlation (r = 0.80, p\0.001) between MSNA responses induced by Apart from conventional electrodiagnostic brainstem examination, arousal and by mental stress but not between responses evoked by we performed a reaction time task paradigm in which the patient was arousal and the cold test (r \ 0.1, p[0.6). Additionally arousal- asked to open his eyes widely at the perception of a weak electrical induced MSNA change was positively correlated with blood pressure stimulus to the index finger (imperative signal) and, subsequently, he changes during MS (systolic BP: r=0.48; p\0.01; diastolic BP: was presented with the same stimulus together with a startling audi- r=0.42; p\0.05) but not with blood pressure changes during CT. tory stimulus at the same time. We monitored the EMG activity of the Conclusion: We conclude that in males the MSNA response to orbicularis oculi muscles with surface electrodes and recorded jaw arousal predicts the MSNA and BP responses to mental stress. movement with an accelerometer attached to the chin. Results: Blink reflex to electrical stimuli to the supraorbital nerve of either side showed signs suggesting blepharospasm, such as enhanced R2 responses, and reduced inhibition of the blink reflex O320 excitability recovery curve to pairs of stimuli. Jaw jerk and masseteric Brain CT scan compared to somatosensory-evoked inhibitory reflex were normal. Jaw tapping caused a reflex response in potential grade for predicting outcome in comatose the orbicularis oculi at a latency of about 30 ms. The reaction time patients with traumatic brain injury task paradigm showed that eye opening was accompanied by a slight decrease in the tonic EMG activity of the orbicularis oculi and a slight P. Dolati, M. Hill, R. Midha, M. Schwartz, D. Houlden movement of the jaw at about 130 ms. When a startling noise was University of Calgary (Calgary, CA); University of Toronto (Toronto, applied unexpectedly during preparation, reaction time shortened CA) significantly (65 ms), the movement of the jaw was significantly Background: Early SSEP grade is a strong predictor of final GOS in larger and the patient reported that the eyelid opening task was much comatose TBI patients. Unfortunately, SSEP testing is either not easier. However, the amount of inhibition in the orbicularis oculi available or difficult to obtain in many centres. The purpose of this activity did not change. study was to compare the predictive value of early brain CT scan to Conclusion: Masseteric muscle Ia afferent inputs do not produce that of SSEP grade. clear inhibition of the OOc. Therefore, eyelid opening with jaw Methods: Eighty-four comatose patients with TBI had brain CT movements is likely to be due to facilitation of activity in the LP Scans within 24 h after TBI (Day 1). The CT scans were graded muscle. according to the Trauma Coma Data Bank Classification system (Grade I = normal, II = diffuse injury, III = diffuse injury with swelling, IV = diffuse injury with shift, V = mass lesion surgically evacuated, and VI = O322 mass lesion not operated). In the same patients, Day 1 SSEPs were graded based on the combined results from left–right brain (Grade I = Cutaneous silent period in clinical practice absent–absent, II = absent-abnormal, III = absent-normal, IV = abnor- I. Stetkarova, M. Kofler, A.A. Leis mal–abnormal, V = abnormal-normal, VI-normal–normal). Glasgow Charles University, FNKV Hospital (Prague, CZ); Hochzirl Hospital Outcome Scale (GOS) was measured 1 year after injury. A receiver (Zirl, AT); Mississippi Methodist Rehabilitation Center (Jackson, US) operating characteristic (ROC) curve analysis was performed to com- Objectives: Cutaneous reflexes are useful tests to study sensorimotor pare Day 1 CT grade to Day 1 SSEP grade in predicting 1 year GOS. integration at spinal and supraspinal levels. One of the most robust Results: The ROC area-under-the-curve was 0.84 for SSEP grade cutaneous reflexes is designated the cutaneous silent period (CSP). and 0.79 for brain CT grade (P=0.5126; not statistically different). The CSP is a brief pause in the voluntary EMG activity which occurs Conclusion: Although Day 1 SSEP grade was marginally better in response to a painful stimulus applied to a cutaneous nerve. It is a than Day 1 brain CT grade in predicting GOS one year after TBI, the spinal inhibitory reflex mediated primarily by small-diameter A-delta two were not significantly different. Accordingly, Day 1 CT grade is a fibers, which enter the spinal dorsal horn and suppress activity in useful tool for predicting outcome in comatose patients with TBI. spinal motor nuclei in neighboring myotomes. CSP testing may be particularly useful in evaluation of certain segments of the nervous system and of certain components of sensory nerves that are not well O321 assessed by routine electrodiagnostic methods. Marcus-Gunn jaw-ocular synkinesis after a pontine Methods: The CSP can be obtained using standard EMG equipment. Digital or skin nerves are activated by painful stimuli which are infarct delivered while the subject maintains a moderately strong voluntary G. Barraza, C. Medici-Olaso, V. Martıńez-Quiterio, muscle contraction. The CSP is defined as clear reduction or absence M.J. Martı´, J. Valls-Sole´ of voluntary EMG activity following the stimulus at appropriate Hospital Clıńico de Barcelona (Barcelona, ES) latencies. For clinical purposes, the beginning, duration and end of the

123 S60 J Neurol (2012) 259 (Suppl 1):S1–S236

CSP can be measured in individual traces. For exact quantification, difference was also found in the definition of the waveforms between rectified averaged traces are necessary. the different stimulus polarities. Results: The CSP has been studied in peripheral nervous system Conclusion: Stimulus polarity does not make a significant differ- lesions, e.g. in different types of neuropathies, Friedreich’s ataxia, and ence to the cVEMP response either in terms of amplitude or latency. entrapment syndromes. The small afferent fibers appear to be rela- This may be due to one of two reasons, or to both: (1) cVEMP tively less affected and their dysfunction occurs often late in the amplitudes are large making any small change in recorded amplitude course of polyneuropathy. Preserved CSPs may serve to document negligible, or (2) the cVEMP pathway is not represented by separate residual nerve continuity in severe entrapment neuropathies as well as subpathways that may be sensitive to specific stimulus polarities. in cervical radiculopathies and suspected root avulsions. The CSP has been studied in a variety of disorders of the central nervous system, ______e.g. in syringomyelia, centromedullary spinal lesions, whiplash syndrome, and cervical spondylogenic myelopathy. CSPs were highly Oral session 23 associated with upper limb spinothalamic dysfunction. Abnormal CSPs have been reported in patients with pyramidal syndrome, dys- Dementia tonia, restless legs syndrome and Parkinson’s disease. Conclusion: CSP is a simple electrodiagnostic method suitable for measurement of small-diameter slowly conducting nerve fibers. The clinical interest in CSPs is to better understand and characterize O324 neural circuits which are involved in peripheral and central nervous Conversion to preclinical Alzheimer’s disease system disorders that affect sensorimotor processing. in cognitively normal adults: beta-amyloid imaging Supported by Grant Project of Czech Ministry of Health NT 12282-5. data A.G. Vlassenko, T.M. Blazey, Y. Su, C. Xiong, A.M. Goate, T.L.S. Benzinger, M.A. Mintun, J.C. Morris O323 Washington University School of Medicine (St. Louis, US); Avid Radiopharmaceuticals (Philadelphia, US) Cervical vestibular-evoked myogenic potentials: stimulus polarity (rarefaction, condensation Objectives: The concept of preclinical Alzheimer’s disease (AD) implies that beta-amyloid deposits may accumulate in the brain years or alternating) does not appear to make prior to the clinical manifestations. Cognitively normal (CN) indi- a significant difference viduals with preclinical AD as detected by increased uptake of [11C] E. Papathanasiou, M. Pantzaris, M. Vasiliades, Pittsburgh compound B (PIB) positron emission tomography (PET) S. Papacostas have a greater risk of progression to symptomatic AD. In our longi- Cyprus Institute of Neurology & Genetics (Nicosia, CY); University tudinal study of the development of preclinical AD in CN adults, we of Cyprus (Nicosia, CY) have recently characterized the rate of conversion to preclinical AD. In this project, the aim was to analyze the extent of beta-amyloid Objectives: Cervical vestibular evoked myogenic potentials deposition at this early stage of preclinical AD. (cVEMPs) is a recently discovered diagnostic examination that Methods: Seventy five CN adults (mean age 71 years) underwent evaluates the vestibular nervous system. The response is recorded two PIB PET scans about 2.6 years apart. PIB-positivity (preclinical against a background of tonic contraction of the sternocleidomastoid AD) was defined using the mean cortical binding potential from muscle (SCM). The stimulus can either be air- or bone-conducted precuneus, gyrus rectus, prefrontal and lateral temporal cortex. Of the sound. This phenomenon is thought to occur as the saccule is located 75 participants, 45 individuals were PIB-negative and 20 individuals close to the stapes footplate, and eddy currents elicited in the peri- were PIB-positive at both PIB scans. Ten individuals, who were PIB- lymphatic space are somehow transmitted to the vestibular negative at the first PIB scan, converted to PIB-positive state. We endolymph. Optimum recording and stimulus characteristics for used the data from the second PIB scan to evaluate the differences in recording a cVEMP have been investigated many times. However, the regional beta-amyloid deposition between groups. For all individuals, effect of stimulus polarity has not been examined to the same extent. PIB binding potentials were calculated in 41 cortical and subcortical Methods: Ten physiologically normal volunteers were recruited. regions defined using FreeSurfer software. Unilateral stimulation was performed using a 1 kHz tone burst air- Results: Compared to PIB-negative individuals, converters dem- conducted auditory stimulus, with a 7 ms duration, and an intensity of onstrated substantially greater beta-amyloid deposition in 27 of 34 120 dB pSPL, delivered at a frequency of 5 Hz, with contralateral cortical gray matter regions, caudate and putamen (two-tailed masking noise. The active electrode was placed over the midpoint of unpaired t-test, corrected for multiple comparisons, p\0.00125) with the SCM, the reference electrode over the midpoint of the clavicle, the highest difference in precuneus, posterior cingulate and prefrontal and the ground electrode on the forehead. EMG activity was moni- regions. These differences remained after partial volume correction tored and measured in parallel. Recordings obtained during a run of was applied. In PIB-positive individuals, regional beta-amyloid 250 stimulations were averaged. Two runs were averaged separately deposition was significantly greater in all regions compared to PIB- and superimposed. The results were obtained as a ratio of actual negative individuals, and in 18 of 34 cortical gray matter regions cVEMP amplitude over EMG amplitude. The order of stimulation compared to converters. After partial volume correction significant with each of the three polarities was randomized between subjects. differences between converters and PIB-positive individuals were Statistical analysis was performed using the Students t-test. observed in more regions including caudate and putamen. Results: Ten physiologically normal volunteers were examined Conclusion: Our findings suggest that conversion to preclinical (age range 20- 28 years, 6 female and 4 male). No significant dif- AD in CN adults is associated with widespread and continuous pro- ference was noted in the absolute amplitudes and P13 absolute gression in AD pathology, and demonstration of this pathological latencies, nor in the interside amplitude ratio difference and interside event with beta-amyloid imaging may be an important step in the P13 interside latency difference (p[0.05). Similar findings were longitudinal assessment of preclinical AD and planning the anti- found with the N23 absolute and interside latency difference. No amyloid treatment.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S61

This work was supported by National Institute of Aging grants p50 included and matched to the EOAD and LOAD patients based on age AG05681, P01 AG026276, and P01 AG03991, and National Institute and gender. Tract-based spatial statistics were used to perform a brain of Neurological Disorders and Stroke grant P30 NS048056. voxel-wise analysis of fractional anisotropy (FA) and mean diffusivity (MD). Gray matter (GM) atrophy was assessed using voxel- based morphometry. Results: Compared to HC, EOAD patients showed a decreased O325 FA and an increased MD of the corpus callosum (CC), whole cin- Microbleeds in post-mortem brains of patients gulate bundle, and major long associative WM tracts, bilaterally, with Alzheimer’s disease: a T2*-weighted gradient-echo and a distributed pattern of parieto-temporal and frontal GM atro- 7.0-T magnetic resonance imaging study phy. Compared to HC, LOAD patients showed a decreased FA of the CC and posterior cingulate bundle, bilaterally, and left medial J. De Reuck, C. Cordonnier, V. Deramecourt, F. Auger, temporal GM atrophy. Compared to LOAD, EOAD showed a more N. Durieux, R. Bordet, C.-A. Maurage, D. Leys, severe MD increase of the splenium of the CC bilaterally, left F. Pasquier posterior cingulate bundle, and left superior longitudinal fasciculus, University of Lille (Lille, FR) as well as a more severe GM atrophy in the posterior cingulate cortex. Objectives: This study aims to determine the distribution and to Conclusions: WM damage is more distributed and severe in quantify microbleeds (MBs) in post-mortem brains of patients with EOAD patients compared with typical LOAD, and is likely to Alzheimer’s disease (AD) on T2*-weighted gradient echo 7.0-T contribute to the more generalized cognitive deficits in these magnetic resonance imaging. patients. Patients and Methods: Twenty-eight AD brains were compared to 5 controls. The AD brains were subdivided in 18 without and 10 with additional severe cerebral amyloid angiopathy (AD-CAA). The distribution and the number of cortical focal signal intensity losses, O327 representing MBs, were assessed on coronal sections at the frontal, Frequency of the chromosome 9 hexanucleotide repeats the central and the occipital level of a cerebral hemisphere. Micro- in Italian patients with frontotemporal lobar scopic examination was also performed to evaluate the number of micro-infarcts and small bleeds, and the severity of the white matter degeneration changes. D. Galimberti, C. Fenoglio, M. Serpente, D. Roberto, Results: On MRI MBs prevailed in the central sections (P = 0.005) L. Benussi, R. Ghidoni, G. Binetti, B. Nacmias, S. Sorbi, of AD brains without CAA, while in AD-CAA brains they were more A. Marcone, S. Cappa, G. Magnani, M. Filippi, F. Agosta, frequent in all coronal sections (P \= 0.002). They prevailed in the deep cortical layers of the AD brains as well as of the controls G. Comi, M. Franceschi, I. Rainero, A. Confaloni, (P\= 0.03). They were significantly increased in all cortical layers of P. Piscopo, G. Bruno, A. Cagnin, F. Clerici, C. Mariani, the AD-CAA brains (P \= 0.04), compared to the controls, while G. Comi, N. Bresolin, E. Scarpini there was only a trend of more MBs in the deep cortical layers of the IRCCS Ospedale Policlinico (Milan, IT); IRCCS S.Giovanni di Dio AD brains without CAA (P = 0.08). On the neuropathologic sections Fatebenefratelli (Brescia, IT); University of Florence (Florence, IT); all types of cerebrovascular lesions prevailed in the AD-CAA brains Vita Salute University, S. Raffaele Hospital (Milan, IT); IRCCS (P \ 0.01). Multimedica (Milan, IT); University of Turin (Turin, IT); Istituto Conclusion: MBs prevalence in brains of AD patients had a dif- Superiore di Sanita` (Rome, IT); Istituto Superiore di Sanita` (Rome, ferent topographic distribution according to the absence or presence IT); University ‘‘Sapienza’’, (Rome, IT); Clinica Neurologica I of severe CAA. (Padua, IT); University of Milan, Ospedale Sacco (Milan, IT) Background: a hexanucleotide repeat expansion in the first intron of C9ORF72 has been shown to be responsible for a high O326 number of familial cases of amyotrophic lateral sclerosis or Patterns of microstructural white-matter damage Frontotemporal Lobar Degeneration (FTLD) with or without con- in early and late age of onset Alzheimer’s disease comitant Motor Neuron Disease (MND) phenotype and TDP-43 based pathology. patients Objectives: To analyze the frequency of the hexanucleotide E. Canu, F. Agosta, G. Magnani, E. Scola, A. Marcone, expansion in a population of patients with FTLD (with or without E. Spinelli, M. Falautano, S.F. Cappa, A. Falini, G. Comi, MND) M. Filippi Population and Methods: DNA from 924 patients with FTLD (27 with concomitant MND) were collected. Analysis was done by Vita-Salute San Raffaele University (Milan, IT) Repeat-Primed PCR and sequencing. Objective: Patients with early age of onset Alzheimer’s disease Results: At present, 590 samples have been screened. Twenty (EOAD, before the age of 65 years) show a more severe brain atrophy eight were carriers of the mutation (4.7 %). Twenty two of them were and hypometabolism compared to the typical late-onset patients diagnosed clinically with behavioural variant Frontotemporal (LOAD) at a similar disease stage. Diffusion tensor (DT) MRI allows Dementia (bvFTD), 5 with bvFTD-MND (diagnosed initially with an in vivo assessment of WM integrity to be obtained. The aim of the bvFTD and developing MND over time) and one with semantic study was to investigate patterns of brain WM integrity in AD patients dementia. with a different age of onset. Conclusions: the hexanucleotide expansion in chromosome 9 is Methods: Structural and DT MRI were obtained from 19 EOAD likely a common cause for FTLD, together with progranulin and tau and 19 LOAD patients. Patients were matched on an individual basis mutations. Patients’ follow up is ongoing to clarify whether the for age, gender and dementia severity as measured by the Clinical presence of this genetic defect is a prognostic biomarker predicting Dementia Rating scale. Thirty-eight healthy controls (HC) were the development of MND in patients diagnosed with bvFTD.

123 S62 J Neurol (2012) 259 (Suppl 1):S1–S236

O328 variant of frontotemporal dementia (bvFTD) using resting state Right temporal atrophy versus frontal atrophy functional MRI (RS fMRI) and graph theory. Methods: Eighteen bvFTD patients (mean age=61.9 years, in patients with frontotemporal lobar degeneration: SD=8.4, MMSE: 22+6), and 50 sex-matched healthy controls (mean cognitive and behavioural profiles age=61.1 years, SD=9.1) underwent RS fMRI examination. Whole- C. Koros, T. Kontaxis, C. Routsis, A. Tsapanos, S. Matsi, brain networks were constructed using graph theory methods. First, M. Psaltaki, A. Bonakis, N. Kalfakis, A. Kyrozis, the correlation coefficients between the fMRI time series extracted from the 90 cortical regions of the automated anatomical labeling S.G. Papageorgiou (AAL) atlas were computed, obtaining a correlation matrix repre- Eginition Hospital, University of Athens (Athens, GR); Attikon senting functional connectivity inside the brain for each subject. This Hospital, University of Athens (Athens, GR) matrix was subsequently binarized at different correlation thresholds Objective: Right temporal atrophy variant of frontotemporal lobar (between 0.05 and 0.20). The overall topology of functional brain degeneration (rtv-FTLD) presents with symptoms in many ways com- connectivity was examined at each threshold by computing the parable to these of the behavioral variant with marked frontal lobe commonest graph theoretical metrics, comprising the degree (i.e., the atrophy. The aim of the present study was to assess the distinct cognitive number of connections of a node), the clustering coefficient (i.e., and behavioral profile of patients of these FTLD subgroups. While in the the number of connections of a node with its neighbours), the char- literature there are studies comparing the symptomatology of right acteristic path length (i.e., the average number of minimum versus left temporal atrophy, this is the first study focusing on clinical connections that should be passed to join any two nodes in the net- features of right temporal versus frontal lobe atrophy patients. work), and the global efficiency (i.e., the inverse of the path length, Methods: From 105 patients with FTLD referred to our unit during representing how efficiently is the network to exchange information at a 6 year period, six patients with predominant right temporal lobe a global level). Between-group differences of network connectivity atrophy met the clinical criteria for rtv-FTLD. The clinical features of metrics were investigated with a two-sample t-test for non-paired data. these patients were compared with those observed in a group of 26 Results: Most of graph theoretical metrics were found to be sig- patients with predominant frontal lobe atrophy. Patients were desig- nificantly altered in bvFTD patients with respect to healthy controls. nated as having predominant right temporal or frontal atrophy In particular, the average degree and global network efficiency were according to their brain MRI scans (double blindly assessed by a significantly decreased in bvFTD patients vs. controls at all consid- neurologist and a neuroradiologist). ered correlation thresholds (p ranging from 0.015 to 0.045). On the Results: The prevalence of the majority of cognitive symptoms contrary, the average path length was significantly increased (p rang- (concerning episodic memory, executive functions, speech) was ing from 0.015 to 0.03). The average clustering coefficient was similar in both groups. Nevertheless, the most prominent cognitive significantly lower in bvFTD patients than in healthy controls at the symptom in rtv-FTLD was prosopagnosia and it was rarely encoun- correlation thresholds of 0.05 and 0.10 (p=0.02 and 0.04, respec- tered in frontal lobe atrophy patients (80 % vs 10 %). tively), and there was a trend towards significance at the other As far as behavioral symptoms are concerned, symptoms in the thresholds (p=0.06 and 0.09, respectively). spectrum of apathy (loss of initiative, loss of interests) were Conclusions: The large-scale functional network organization is more frequent in rtv-FTLD patients than in the frontal lobe group significantly altered in bvFTD patients vs. control subjects, suggesting (70 % vs 30 %). Symptoms related to loss of self control (disin- a loss of efficiency in information exchange between brain areas. hibition, inappropriate laughters, irritability, aggressiveness) were of equal predominance in both groups. Behavioral rigidity symptoms were more frequent in rtv-FTLD patients and the difference was significant for obsessive–compulsive behavior (70 % ______vs 20 %). Oral session 24 Depression and food related disorders were equally recorded in both groups. Interestingly, psychotic symptoms (delusions and hallucinations) were noted mainly in rtv-FTLD patients and the Pain and headache difference was significant for delusions (70 % vs 20 %). Conclusion: Although the cognitive-behavioral profiles of patients with right temporal or frontal lobe atrophy present substantial similarities, each subtype has a number of distinct characteristics O330 facilitating clinical diagnosis. It appears that difficulty in person Personality traits and migraine: a multicentre study identification, apathetic symptoms, obsessive behavior and delusions using Salamanca screening test are more prominent in rtv-FTLD patients. I. Munõz, E. Toribio, F.J. Carod-Artal, M.L. Penãs, L. Ruiz, L. Gallardo, M. Pedraza, P. Mulero, S. Herrero, E. Cortijo, A.L. Guerrero, F. Uribe O329 University Hospital (Valladolid, ES); Hospital del Henares (Madrid, Abnormalities of functional connectivity in patients ES); Hospital Virgen de la Luz (Cuenca, ES); Hospital Virgen de la with frontotemporal dementia: a network analysis using Concha (Zamora, ES); Hospital de Paraplejicos (Toledo, ES) resting state fMRI and graph theory Objectives: Comorbidity between migraine and clinical disorders M. Filippi, S. Sala, P. Valsasina, F. Agosta, G. Magnani, (Axis I) listed in Diagnostic and Statistical Manual of the American S.F. Cappa, E. Scola, A. Falini, G. Comi Psychiatric Association, 4th Edition (DSM-IV), as anxiety and depression, have been widely studied. Relationship between migraine San Raffaele Scientific Institute, Vita-Salute San Raffaele University and personality disorders (Axis II) of DSM-IV has been less fre- (Milan, IT) quently tested. We aim to evaluate personality traits in a population of Objective: Aim of this study was to investigate the functional orga- migraine patients using Salamanca screening test, which assess with nization of large-scale brain networks in patients with the behavioural 22 simple questions 11 personality disorders grouped in 3 clusters.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S63

Methods: We prospectively evaluated patients consecutively atten- adults. They are associated with negative impact on health-related ded due to migraine (according to International Classification of quality of life. We aim to analyze characteristics of young patients Headache Disorders, II Edition (ICHD-II) criteria) at 4 hospitals. We attended in an outpatient headache clinic in a tertiary hospital, and excluded those in which medical or psychological disorders could limit burden of different headaches codified according to International their ability to answer the questionnaire. In each patient we gathered Classification of Headache Disorders, II Edition (ICHD-II) demographic and nosological characteristics. Chronic migraine (CM) Methods: Due to our health system organization, only patients and medication overuse (MO) were diagnosed according ICHD-2 older than 14 years were referred to this office, most of them by revised. We administered six-item Headache Impact Test (HIT-6), general practitioners. We prospectively considered patients younger Salamanca test, Hospital Anxiety and Depression Scale (HADS) and than 25 years attended during a four-year period (January 2008 to EuroQol questionnaire. Relationship between the presence of each January 2012). We gathered in each patient gender, complementary personality trait and clinical and demographic variables was assessed. tests required, and symptomatic or prophylactic therapies previously Results: We included 139 patients (114 female, 25 male). Mean age used. When a patient fulfilled criteria for more than one type of of 37.1 ± 12.8 years (range 16-78). 23 (16.5 %) patients presented a headache, all of them were diagnosed and classified. We measured migraine with aura, 48 (34.5 %) CM and 31 (22.3 %) MO. Average adverse headache impact with six-item Headache Impact Test (HIT-6) HIT-6 score there was 63 ± 7.4 (range 42-78) and 112 (80.6 %) Results: 208 patients (55 males, 153 females) out of 1668 attended patients presented at least substantial (HIT-6[= 55) headache-related (12.5 %) during inclusion period were younger than 25 years. 201 impact. Most frequent personality traits were those included in cluster (96.6 %) had received at least one symptomatic treatment, but only 93 C, anxious (54.7 %), anancastic (46.8 %), and dependent (33.8 %). (44.7 %) had previously used a preventative. 141 (67.8 %) did not We found no relationship between the presence of different personality required ancillary tests. A total of 297 headaches were recorded in traits and demographic and clinical variables considered. these 208 patients. Only 19 (6.4 %) were secondary headaches, and Conclusion: According to Salamanca screening test, personality most of them were codified in Group 8 (Headache attributed to a traits are common among migraine patients in our population, mainly substance or its withdrawal). Regarding primary headaches, 215 those include in cluster C. Although we found no correlation between (72.4 % of all headaches) were in Group 1 (Migraine); among them them and the clinical status of migraine, larger studies are needed to 14 were classified as chronic migraine. 19 (6.4 %) headaches were determine whether personality disorders are related to MO or adaptive included in Group 2 (Tension-type), 3 (1 %) in Group 3 (Trigeminal patterns to pain. autonomic), and 16 (5.4 %) in Group 4 (Other primary headaches). One (0.3 %) was classified as Group 13 of ICHD-II (Cranial neu- ralgias) and only 2 (0.7 %) headaches corresponded to Group 14 O331 (Unspecified or not elsewhere classified headaches). In 114 patients Patients with migraine do not have MRI-visible cortical (54.8 %) HIT-6 score showed a severe impact ([59) Conclusion: Most headaches in young age can be codified lesions according to ICHD-II criteria. Migraine was the most frequent diag- R. Messina, M. Absinta, M.A: Rocca, B. Colombo, nosis. Chronic migraine and medication overuse headache are not M. Copetti, D. De Feo, A. Falini, G. Comi, M. Filippi infrequent diagnosis in our population. Though headache was com- Vita-Salute San Raffaele University (Milan, IT);IRCCS-Ospedale monly associated with negative impact among our patients, Casa Sollievo della Sofferenza (San Giovanni Rotondo, IT) preventatives were not widely used before referral. Objectives: Migraine patients with multiple brain white matter hyperintensities (WMHs) may represent a diagnostic challenge. Using double inversion recovery (DIR) imaging, we studied whether cortical O333 lesions (CLs) could be seen in these patients. Clinical picture of primary stabbing headache: results Methods: CLs and WM lesions were assessed on brain scans from in a series of 67cases 32 migraineurs with WMHs, and in two control groups, consisting of 15 relapsing-remitting multiple sclerosis (RRMS) patients and 20 M. Pedraza, A.L. Guerrero, S. Herrero, P. Mulero, healthy controls, matched for age and gender. I. Munõz, M. Ruiz, C. Cruz, V. Casado, J. Baroń, Results: By definition, brain WM lesions were detected in all N. Fernańdez-Buey, J. Marco, R. Fernańdez migraine and RRMS patients. The number and volume of WM lesions University Hospital (Valladolid, ES) were lower in migraine vs. RRMS patients (p\0.0001). No CLs were identified in migraine patients and healthy controls, while 20 CLs Objectives: Primary stabbing headache (PSH) is a short-lasting pain were seen in 9 (60 %) RRMS patients. disorder occurring as sharp stabs, predominantly felt in the first Conclusions: The application of DIR imaging to assess focal cortical division of trigeminal nerve. It is a common headache accordingly to involvement seems to be useful in the diagnostic work up of patients population studies, but most people suffer attacks of low frequency with WMHs of unknown aetiology, including those with migraine. and intensity and they do not seek for medical assistance. CPP is commonly associated with other headache and is considered an indomethacin-responsive disorder. We aim to analyze clinical char- O332 acteristics of PSH in a consecutive series of 67 cases. Headache in young age: clinical characteristics Methods: We prospectively reviewed patients with PSH attended in a headache outpatient clinic over a 4-year period (January 2008 to and adverse impact in a series of 208 cases January 2012). In every patient we considered demographic and M. Pedraza, A.L. Guerrero, B. Aylloń, P. Mulero, L. Sierra, clinical characteristics including sex, age at onset, temporal pattern, A. Sańchez, S. Herrero, E. Callejo, M. Abete, I. Munõz, location and pain intensity. We also analyzed if there were other L. Gallardo, R. Fernańdez concomitant headaches. Regarding therapy, we considered whether it was prescribed due to PSH or associated headaches, and its efficacy. University Hospital (Valladolid, ES) Results: 67 patients (51 females, 16 males) out of 1668 (4 %) Objectives: Headache disorders are common causes of somatic attended in mentioned clinic, were diagnosed of PSH. Mean age at complain and medical consultation among adolescents and young onset was 34.5 ± 16.7 years (range: 8-72). 38 (56.7 %) patients

123 S64 J Neurol (2012) 259 (Suppl 1):S1–S236 suffered more than one jab per day and only 11 (16.4 %) an average Objectives: Supraorbital neuralgia (SON) is an uncommon disorder over 10 jabs per day. Stabs were bilateral in 46 patients (68.7 %) and included in the II Edition of the International Classification of located in one fixed area in 34 (50.7 %). The duration of a single jab Headache Disorders (ICHD-II). Accordingly to diagnostic criteria, was less than 5 s in 48 (71.6 %) patients, and 11 (16.4 %) suffered SON is characterized by pain in the region of the supraorbital paroxysms longer than 10 s. Mean intensity of stabs was 6.8 ± 1.5 notch and medial aspect of the forehead, and tenderness over the according to a verbal analogical scale. 49 (73.1 %) patients fulfilled supraorbital nerve in the supraorbital notch. Prevalence of nontrauma criteria for other headaches, mainly migraine (32 cases). Regarding SON is only 0.15 % and few hospital-based series of this neuralgia therapy, 28 (41.8 %) patients required a preventative for an associated have been published. We aim to analyze clinical characteristics and headache and 16 (23.8 %) received indomethacin due to CPP. therapeutic results in a consecutive series of 13 cases. Remission rate (at least 50 % improvement in CPP) did not differ Methods: We prospectively analyzed patients with SON attended in between the two groups (78.5 % vs 75 %). a headache outpatient clinic in a tertiary hospital over a 4-year period Conclusion: PSH is not an uncommon diagnosis in our headache (January 2008 to January 2012). In every patient we gathered age at outpatient office but its clinical picture differs from that described in onset, sex, and clinical characteristics of background pain and exacer- population-based studies. Attacks intensity is at least moderate, and bations (temporal pattern, pain quality, intensity). We also considered frequency and duration of stabs may be higher and annoying. Pre- therapeutic results with anesthetic blockade or antineuralgic drugs. ventive therapy is frequently required due to either CPP or comorbid Results: 13 patients (11 females, 2 males) out of 1668 (0.8 %) headache disorder and it frequently leads to CPP remission, regardless attended in mentioned clinic, were diagnosed of SON. Mean age at of the cause of prescription. onset was 46.3 ± 18.2 years (range: 16-83). All patients presented tenderness on the supraorbital notch and none of them associated hypoesthesia or allodynia. Appropriate investigations ruled out other O334 headaches. Background pain was mostly dull and rated 5.3 ± 1.1 Discrepancy of laser types in stimulating AMH-1 (range: 4-8) on a verbal analogical scale (VAS). In addition 9 (69.2 %) patients reported sharp, burning or piercing exacerbations, and AMH-2 nociceptors lasting from 2 s to 15 min, and with an intensity of 8 ± 1.6 (range: B. Isak, A. Biasotta, A. Truini, G. Di Stefano, S. La Cesa, 5-10) on VAS. Temporal pattern was chronic in 6 (46.1 %) patients, A. Pepe, M. Gabriele, M. Inghilleri, G. Cruccu episodic with spontaneous remissions in 4 (30.8 %) and too recent to University Hospital (Aarhus, DK); Marmara University Hospital be determined in 3 (23.1 %). In 7 (53.8 %) cases an anesthetic (Istanbul, TR); University La Sapienza (Rome, IT) blockade was required with a complete relief beginning immediately after the procedure and lasting from 2 to 6 months. When blockade Objective: This study aims to evaluate cutaneous silent periods was repeated, time of relief increased in subsequent procedures. 3 (CSPs) and laser evoked potentials (LEPs) under carbon dioxide laser (23.1 %) patients had received Gabapentin before referral to our (CO2-laser) and neodymium:yttrium–aluminum–perovskite laser clinic with no or only slight improvement. (Nd:YAP-laser) in order to differentiate subtypes of A-delta me- Conclusion: Non-traumatic supraorbital neuralgia is an uncommon chanoheat (AMH) receptors in normal subjects. disorder in our headache outpatient office. In our series female pre- Methods: 10 healthy subjects (6 females and 4 males, age 29.1± ponderance and quality and intensity of pain, are comparable to those 5.3 years) were assessed based on CSPs obtained with electrical, previously published. Spontaneously remitting pattern is not uncom- CO2-laser and Nd:YAP-laser and LEPs with CO2-laser and Nd:YAP- mon and anesthetic blockade is not always required. laser after palmar stimulation of the right ulnar sensory nerve. Recordings were obtained from the right adductor digiti minimi muscle for CSP and the left temporoparietal cortex for LEPs. ______Results: CSP latencies were 80.61 ± 11.99 ms for electrical, 99.36±12.53 ms for CO2-laser and 134.86± 9.97 ms for Nd:YAP POSTER SESSIONS laser stimulations (P\0.0001, for all comparisons). Latencies of the CO2-LEPs were shorter than the latencies for Nd:YAP-LEPs (for N1, 121.2.±5.93 ms vs. 254.4±18.84 ms; for N2, 149.2±7.73 ms Poster session 1 vs.213±23.73 ms and for P2, 266±36.85 ms vs. 361.2±45.69 ms), (P\0.0001 for all comparisons). Conclusions: The short vs. long latencies in response to CO2- and Multiple sclerosis: disease modifying Nd:YAP- laser stimulations corresponded with conductions of AMH- treatment 1 and AMH-2 nociceptors, respectively. Detailed examination for the A-delta fibre subtypes in the nociceptive sensory system can be available by combined evaluation of the data coming from the laser evoked CSPs and LEPs. P336 The authors report the absence of conflicts of interest. The authors Safety and tolerability of fingolimod 0.5 mg alone are responsible for the content and writing of the article. during the first 4 months of administration in patients with relapsing forms of multiple sclerosis. Results O335 from the open-label, multicentre FIRST study Non-traumatic supraorbital neuralgia: a clinical study L. Kappos, G. Comi, J. Palace, A. Siever, M. Marrosu, of 13 cases M. Mehling, R. Gottschalk, M. Bijarnia, A. Keil, P. Mulero, A.L. Guerrero, M. Pedraza, S. Herrero, D. Tomic, P. von Rosenstiel, R. Gold University Hospital (Basel, CH); University of Milan (Milan, IT); C. de la Cruz, M. Ruiz, I. Munõz, J. Baroń, C. Atea, John Radcliffe Hospital, University of Oxford (Oxford, UK); M. Abete, L. Gallardo, R. Fernańdez Gemeinschaftspraxis (Oldenburg, DE); Centro Sclerosi Multipla, University Hospital (Valladolid, ES) Ospedale Binaghi (Calgiari, IT); Novartis Pharmaceuticals

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S65

Corporation (East Hanover, US); Novartis Healthcare Pvt. Ltd. at Wk 72. Safety was assessed throughout the study through regu- (Hyderabad, IN); Novartis Pharma AG (Basel, CH); University lar neurological and physical examinations, adverse events Hospital, Ruhr-University (Bochum, DE) (AEs) reporting and incidence of infections and infusion-related reactions. Objectives: To evaluate the safety and tolerability of fingolimod 0.5 mg Results: 183 pts (83 %) completed the 96-wk treatment period. during the first 4 months of administration in a broader relapsing multiple Incidence of serious AEs (SAEs) related to study treatment was sclerosis (MS) population than previously studied, including patients consistent across treatment groups up to Week 96 (wks 0–24: 2/54; with controlled diabetes, chronic asthma, certain cardiac conditions, with 1/55, 1/55 and 0/54 pts had SAEs related to treatment in groups A–D; extended age limit to 65 and expanded EDSS score up to 6.5. wks 24–48: 0 pts had SAEs related to treatment; wks 48–72: 1 pt in Methods: Safety and tolerability of fingolimod 0.5 mg/day was each group had a SAE related to treatment; wks 72–96: 0 pts had evaluated by adverse event (AE), laboratory studies, vital signs, SAEs related to treatment). As previously reported, one death ophthalmology and skin assessments data. occurred in group C, in Cycle 1 (wks 0–24). Over 96 wks, 3 AEs led Results: Of 2417 enrolled patients, 2282 (94.4 %) completed the to withdrawal in group B, with 1 AE in group C and 2 AEs in group D study. Adverse events (AEs) were recorded in 75.3 % of patients with leading to withdrawal (none in group A). Infection rates remained the most frequent being nasopharyngitis (14.8 %), headache (11.3 %), decreased over time up to Week 96 and were consistent across groups. lymphopenia (9.4 %) and fatigue (6.6 %). Serious adverse events were Risk of respiratory tract, urinary tract and herpes infections was noted in 4.1 % of patients. There was no case of systemic or dissemi- similar across treatment groups and remained low through 96 wks. nated opportunistic infection.. Herpes infections accounted for 4.9 % Serious infection rates were similar for the OCR 600 mg group (1.97 of any infections reported in the study (34.3 %), mostly due to occur- events/100 pt-years [95 % CI: 0.49–7.88 pt-years]) and the OCR 2000 rences of oral herpes (3.1 %). There were 16 (0.7 %) cases of macular mg group (1.93 events/100 pt-years [95 % CI: 0.48–7.71 pt-years]), oedema. Nine (0.4 %) malignancies were reported in the context of this and did not increase with time on OCR treatment. No opportunistic short-term, single arm study; mostly attributed to non-metastatic non- infections were reported. Infusion-related reactions were more com- melanoma skin cancers (0.3 %). Sixteen patients (0.6 %) discontinued mon after the 1st OCR infusion, but decreased to placebo levels in the study due to abnormal liver function test results. subsequent infusions. 120 wk safety data will be presented. Conclusions: The type and frequency of the most common adverse Conclusions: Over 96 wks, OCR was generally well tolerated with events recorded in this study are comparable to those reported in no imbalances in SAEs or types of infections, and no reports of previous clinical trials with fingolimod within the first six months of opportunistic infections. treatment. These study results and low patient discontinuation rate The study was sponsored by F. Hoffmann-La Roche Ltd. (5.6 %) indicate that fingolimod is well tolerated in a broad relapsing MS population. Furthermore these results confirm the favourable safety profile of fingolimod as observed in the large clinical development program in MS containing a cumulative exposure of P338 approximately 15000 patient-years at the end of 2011. Alemtuzumab improves patient-reported quality of life The study was supported by Novartis Pharma AG, Basel, Switzerland. in relapsing-remitting multiple sclerosis: CARE-MS I and II phase 3 trials P337 K. Selmaj, D.L. Arnold, J. Cohen, A.J. Coles, Long-term safety results from a phase II, randomised, C. Confavreux, E.J. Fox, H.P. Hartung, E. Havrdova, multicentre trial with ocrelizumab in relapsing- H. Weiner, V. Brinar, A. Boscoe, S.L. Lake, D.H. Margolin, remitting multiple sclerosis M. Panzara, M. Rizzo, A. Compston for the CARE-MS I L. Kappos, D. Li, P. Calabresi, P. O’Connor, A. Bar-Or, and II Investigators F. Barkhof, C. Wells, D. Leppert, R. Glanzman, Objective: In the phase 3 study Comparison of Alemtuzumab & J. Tinbergen, S. Hauser Rebif Efficacy in Multiple Sclerosis I (CARE-MS I), alemtuzumab University Hospital (Basel, CH); University of British Columbia demonstrated significant benefit over interferon beta-1a (IFNB) with (Vancouver, CA); Johns Hopkins University (Baltimore, US); 55 % reduction in relapses (p \0.0001). In CARE-MS II with University of Toronto (Toronto, CA); Montreal Neurological Institute relapsing-remitting MS (RRMS) patients (pts) who relapsed on prior and Hospital, McGill University (Montreal, CA); VU University therapy, relapse rate was reduced by 49 % in alemtuzumab pts Medical Center (Amsterdam, NL); Roche Products Ltd (Welwyn compared to IFNB pts (p\0.0001); risk of sustained accumulation of Garden City, UK); F. Hoffmann – La Roche Ltd (Basel, CH); disability (SAD) was reduced by 42 % (p=0.0084). Patient-reported Genentech Inc (Nutley, US); University of California San Francisco quality of life (QoL) was also assessed in CARE-MS I and II. (San Francisco, US) Methods: CARE-MS I & II were 2-yr, randomized, rater-blinded trials comparing alemtuzumab to IFNB in active, RRMS pts. CARE- Objectives: Ocrelizumab (OCR) is a recombinant humanised mono- MS I pts (n=581) were treatment-naı¨ve & CARE-MS II pts (n=840) clonal antibody that selectively targets CD20-expressing B cells. In a had relapsed on prior therapy. Alemtuzumab was administered IV 24 week (wk) phase II trial in relapsing-remitting multiple sclerosis 12mg/day on 5 days at study start & 3 days 12 months later. IFNB (RRMS), OCR reduced gadolinium (Gd+)-enhancing lesions (primary was administered 44mcg SC 3-times wkly for 24 months (M). The endpoint) by[=89 % versus placebo. Here, we present the long-term Medical Outcomes Study Short Form-36 (SF-36) has Physical & safety of OCR up to 96 wks. Mental Component Summaries (PCS & MCS) & was assessed at Methods: At baseline, 220 RRMS patients (pts) were randomised baseline, M12, & M24. The EuroQoL Visual Analogue Scale (EQ- 1:1:1:1 to placebo (A), intravenous OCR (days 1, 15) for a total dose VAS) was measured at baseline & every 6 months, capturing self- of 600 mg (B), 2000 mg (C), or open-label weekly intramuscular ratings of health status from 0-100. interferon (IFN) beta-1a 30 lg (D). At Wks 24, 48 and 72 all pts Results: In CARE-MS I, both treatment groups improved signifi- received open-label OCR: groups A, B and D received 600 mg/cycle; cantly from baseline on MCS at M12 and M24 (all p-values\0.001), group C received 1000 mg at Wks 24 and 48, and switched to 600 mg with no significant differences between groups. At M12, alemtuzumab

123 S66 J Neurol (2012) 259 (Suppl 1):S1–S236 pts improved significantly from baseline on the PCS (p\0.0001) & Conclusions: Monthly DAC HYP 150mg monotherapy demon- significantly more than IFNB pts (p=0.0002), who did not improve strated net improvements on measures of HRQoL over one year of from baseline. Both alemtuzumab (p\0.0001) & IFNB (p=0.023) treatment. The timing of these improvements suggests an early and pts improved from baseline on the PCS at M24, with no significant sustained impact of DAC HYP monotherapy on both physical and difference between treatment groups. Mean PCS scores at M24 psychological status in patients with RRMS. were 49.5 for alemtuzumab & 49.4 for IFNB. The normal value for This study was funded by Biogen Idec and Abbott Biotherapeu- PCS is 50. On the EQ-VAS, both treatment groups improved from tics; editorial assistance was provided by Alison Gagnon of UBC baseline at all time points (all p-values\0.01); alemtuzumab pts Scientific Solutions, which was supported by Biogen Idec. improved significantly more than IFNB pts at M6 & M12 (p-values\0.05), but not at M18 & M24. CARE-MS II data will also be reported. Conclusions: CARE-MS I pts reported improvement in MCS & PCS of QoL in a naı¨ve population initiating therapy. Alemtuzumab P340 demonstrated significant benefits on physical aspects of QoL above Thyroid autoimmunity in comparison of Alemtuzumab IFNB in the first yr of treatment. CARE-MS II will provide data on the impact of alemtuzumab on patient-reported QoL in a population and RebifÒ efficacy in multiple sclerosis studies I and II who experienced a significant reduction in SAD compared to IFNB. M. Habek, D.L. Arnold, J. Cohen, A.J. Coles, Rebif is a registered trademark of Ares Trading S.A. C. Confavreux, E.J. Fox, H.P. Hartung, E. Havrdova, Funding provided by Genzyme (a Sanofi company) and Bayer K. Selmaj, H. Weiner, V. Brinar, C. Twyman, P. Oyuela, Healthcare Pharmaceuticals. S.L. Lake, D.H. Margolin, M. Panzara, A. Compston for the CARE-MS I and II Investigators P339 Objective: Alemtuzumab showed significantly better effect on relapse Impact of daclizumab HYP monotherapy on health- rate than IFNB-1a in two 2-year phase 3 studies, CARE-MS I and II. related quality of life in relapsing-remitting multiple Because autoimmune thyroid abnormalities were previously seen after alemtuzumab, both studies included regular thyroid monitoring. sclerosis patients We describe thyroid autoimmunity with alemtuzumab treatment in K. Selmaj, E. Havrdova, R. Gold, S. Greenberg, CARE-MS I and II. G. Phillips, K. Umans, J. Elkins Methods: Alemtuzumab was administered 12mg/day IV on 5 days Medical University of Lodz (Lodz, PL); Charles University (Prague, at study start and 3 days 12 months later. IFNB-1a treatment was CZ); St. Josef-Hospital/Ruhr-University (Bochum, DE); Abbott 44mcg SC 3-times weekly. Baseline thyroid testing included serum Biotherapeutics (Redwood City, US); Biogen Idec (Cambridge, US) TSH, free T3 and T4, and anti-TSH receptor and anti-thyroid peroxidase (TPO) antibodies; thereafter, TSH was tested quarterly, and if Objectives: Daclizumab (DAC) HYP is a humanized monoclonal abnormal, T3 and T4 were also tested. antibody specific for the IL-2 receptor alpha subunit. SELECT was a Results: In CARE-MS I (n=376 alem, n=187 IFNB-1a, treated), randomized, double-blind, placebo-controlled study to evaluate the thyroid AEs occurred in 18.1 % of alemtuzumab patients vs. 6.4 % safety and efficacy of DAC HYP monotherapy in patients with of IFNB-1a patients at 2 years. Most common AEs with ale- relapsing-remitting multiple sclerosis (RRMS).The objective of the mtuzumab were hyperthyroidism (5.1 %), hypothyroidism (4.8 %), current analyses was to evaluate the efficacy of DAC HYP on health- Graves’ disease (2.9 %), autoimmune thyroiditis (1.6 %), and goiter related quality of life (HRQoL) outcomes in RRMS patients. (1.6 %); with IFNB-1a were hypothyroidism (2.1 %) and hyper- Methods: 621 patients were randomized to placebo or subcuta- thyroidism (1.6 %). Thyroid laboratory abnormalities were reported neous DAC HYP 150mg or 300mg monthly for 52 weeks. The as AEs in 5.6 % of alemtuzumab vs. 2.7 % of IFNB-1a patients. In primary study endpoint was the annualized relapse rate (ARR). Both the alemtuzumab group, 95.5 % of thyroid AEs were mild to general (12-Item Short-Form Health Survey [SF-12], EQ-5D Health moderate in severity; 4 patients had serious thyroid AEs. Two Survey [EQ-5D] and, EQ-Visual Analogue Scale [VAS]) and MS patients discontinued alemtuzumab due to thyroid AEs but com- disease-specific (Multiple Sclerosis Impact Scale [MSIS-29]) HRQoL pleted the study. Incidence of thyroid AEs in alemtuzumab patients measures were included. increased from Year 1 (6.9 %) to Year 2 (13.8 %). Thyroid AEs Results: DAC HYP 150mg administered subcutaneously every 4 occurred more frequently in patients with positive vs. negative weeks resulted in net improvements in HRQoL compared with baseline anti-TPO antibodies (32 % vs. 17.2 % of alemtuzumab declines in placebo-treated patients at Week 52 as measured by patients; 33 % vs. 4.6 % of IFNB-1a patients). In CARE-MS II MSIS-29 physical impact score (-1.0 vs. +3.0 points; P\0.001), SF-12 (n=426 alem, n=202 IFNB-1a, treated), approximately 16 % of physical component summary (+1.2 vs. -0.4 points; P=0.012), SF-12 alemtuzumab patients developed autoimmune thyroid disorders at 2 mental component summary (+0.7 vs. -1.4 points; P=0.012), EQ-VAS years; additional results will be presented. Follow-up of patients (+2.9 vs. -1.8 points; P\0.0001), and EQ-5D summary health index from both studies will continue as in previous studies the incidence (+0.01 vs. -0.04 points; P=0.009). There was also a trend favoring of thyroid AEs was highest between the second and third year DAC HYP 150mg over placebo on the MSIS-29 psychological impact following treatment initiation. score (-1.8 vs. +0.6, P=0.068). The improvements associated with Conclusions: Consistent with previous findings, autoimmune DAC HYP 150mg treatment on each of these outcome measures were thyroid disorders in CARE-MS I and II were more common among generally apparent by Week 24 and then persisted throughout the alemtuzumab patients than IFNB-1a patients. The safety monitoring treatment period. Although trends favored DAC HYP 300mg over program allowed for early detection and management with conven- placebo on these QoL measures, the effect was not statistically sig- tional therapies and good outcomes. nificant (P[0.1) with the exception of a positive impact compared Funding provided by Genzyme (a Sanofi company) and Bayer with placebo on the EQ-VAS (+1.0 vs. -1.8 points; P=0.015). Healthcare Pharmaceuticals.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S67

P341 Objective: Blockade of the high-affinity interleukin (IL)-2 receptor by Alemtuzumab pharmacokinetics daclizumab (DAC) results in increased intermediate-affinity IL-2 signaling and expansion of CD56bright natural killer (NK) cells. This and pharmacodynamics in comparison expansion of CD56bright NK cells has been correlated with better of Alemtuzumab and RebifÒ efficacy in multiple treatment response to DAC in small studies. The objective of the sclerosis current analysis was to evaluate CD56bright NK cell expansion and I. Kovarova, D.L. Arnold, J. Cohen, A.J. Coles, response to treatment with DAC in patients with relapsing-remitting multiple sclerosis (RRMS) enrolled in SELECT. C. Confavreux, E.J. Fox, H.P. Hartung, E. Havrdova, Methods: SELECT was a randomised, placebo-controlled, double- K. Selmaj, H. Weiner, V. Brinar, G. Giovannoni, M. Hard, blind study comparing monthly subcutaneous 150mg or 300mg DAC S.L. Lake, D.H. Margolin, M. Panzara, S. Richards, high yield process (HYP) with placebo in 621 patients with RRMS A. Compston for the CARE-MS I Investigators over 52 weeks. Serum IL-2, CD122, and CD56bright NK cell counts, were measured at multiple time points. CD56bright NK cells were Objective: In CARE-MS I, alemtuzumab showed significant benefit defined as CD3negative CD16dim CD56bright lymphocytes on a over IFNB-1a with a 55 % reduction in relapses (p\0.0001). validated FACS assay. Brain MRI was obtained at baseline and Percentage of patients (pts) with sustained accumulation of disability Weeks 24, 36, and 52 in all patients. by EDSS was lower with alemtuzumab (8 %) than IFNB-1a (11 %) Results: Treatment with DAC HYP increased serum IL-2 levels at but the difference was not statistically significant (p=0.22). We Week 8 versus baseline (median change: DAC HYP, 2.30 pg/mL vs. describe alemtuzumab’s pharmacodynamics and pharmacokinetics in placebo, -0.075 pg/mL; P\0.0001). CD122 was expressed at higher CARE-MS I. levels on CD56bright NK cells at baseline (mean Mean Equivalents Methods: CARE-MS I, a 2-yr, randomized, rater-blinded trial of Soluble Fluorescence [MESF]: 21400) versus CD56dim cells compared alemtuzumab to IFNB-1a in treatment-naı¨ve, relapsing- (mean MESF: 13700; P\0.0001) or other T-lymphocytes (mean remitting MS (RRMS) pts. Alemtuzumab was administered intrave- MESF: 960, P\0.0001). CD56bright NK cell expansion was observed nously 12mg/day on 5 days at study start and 3 days 12 months later. as early as Week 4 (first post-baseline visit) in both DAC HYP arms Blood counts were tested monthly. Circulating lymphocytes were versus placebo (P\0.0001), increasing from a median of 0.6 % of phenotyped by flow cytometry for all treated pts (n=563) quarterly lymphocytes at baseline to 3.6 % at Week 52. A higher number of and at months 1 and 13 for alemtuzumab pts. Serum concentrations of CD56bright NK cells at Week 4 and Week 8 predicted fewer new T2 alemtuzumab were tested by ELISA in 57 pts. lesions between Weeks 24-52 of treatment (P\0.0001 for both) in Results: During the 5 days of treatment at Month 0 and the 3 days DAC HYP-treated patients. DAC HYP-treated patients in the highest of treatment at Month 12, maximum alemtuzumab concentrations quartile of CD56bright NK expansion at Week 8 had 63 % fewer new (Cmax) increased with each daily administration. Mean Cmax was T2 lesions between Weeks 24-52 versus DAC HYP-treated patients in 3339 ng/mL on Day 5 of treatment at Month 0, and 2654 ng/mL on the lowest quartile of expansion (0.46 vs. 1.25 new T2 lesions; Day 3 of treatment at Month 12. Serum alemtuzumab concentrations P=0.004) and 86 % fewer lesions than in the placebo group (0.52 vs. decreased to low or undetectable levels within *30 days following 3.64; P\0.001). A similar but weaker association was observed each treatment. Alemtuzumab depleted circulating B and T lympho- between the Week 8 CD56bright NK cell count and the annualized cytes at each treatment period, with lowest values recorded at the first relapse rate among DAC HYP-treated patients (P=0.129). post-treatment time point, 1 month after the start of treatment (median Conclusion: Results from this prospectively defined analysis of a CD4 count 309106/L). Median CD4 count recovered to 2619106/L large, randomised trial of DAC HYP in patients with RRMS support (LLN=4909106/L) 1 yr after the first treatment and 2809106/L 1 yr the role of CD56bright NK cells in immunomodulation in RRMS and after the 2nd treatment; median CD8 counts were 2109106/L and as a potential DAC HYP efficacy biomarker. 2009106/L, respectively (LLN=1809106/L). Median CD19 counts This study was funded by Biogen Idec and Abbott Biotherapeu- returned to baseline values by 6 months and were approximately tics; editorial assistance was provided by Alison Gagnon of UBC 35 % above baseline 12 months following each treatment. Scientific Solutions, which was supported by Biogen Idec. Alemtuzumab had minimal effects on neutrophil, monocyte, and NK cell counts; mean and median counts remained within normal limits. Conclusions: Alemtuzumab concentrations following treatment in RRMS pts decreased to low or undetectable levels within 1 month P343 after dosing. The pharmacodynamic effect lasted much longer. Ale- Fingolimod reduces direct medical costs compared mtuzumab-induced lymphocyte depletion was consistently followed to natalizumab in patients with relapsing-remitting by lymphocyte repopulation, although CD4 T-cell levels remained multiple sclerosis in the Netherlands below LLN for at least 1 yr after treatment. Other leukocytes were minimally affected by alemtuzumab, suggesting important elements M. Heisen, M.J. Treur, W.S. van der Hel, M.T. Groot, of protective immunity are preserved during alemtuzumab treatment. B.G. Verheggen Funding provided by Genzyme (a Sanofi company) and Bayer Pharmerit Europe (Rotterdam, NL); Novartis Pharma B.V. Healthcare Pharmaceuticals. (Arnhem, NL) Objective: To assess the costs of oral treatment with fingolimod (Gilenya) compared to intravenous infusion of natalizumab (Tysa- P342 bri) in patients with relapse remitting multiple sclerosis (RRMS) in CD56bright natural killer cell expansion and response the Netherlands. Methods: In light of the EMA conclusion stating that fingolimod to daclizumab HYP treatment in relapsing-remitting and natalizumab show broadly similar efficacy and tolerability, a multiple sclerosis cost-minimization analysis (CMA) was used to compare both J. Elkins, J. Sheridan, L. Amaravadi, K. Riester, G. O’Neill treatments. In this CMA the following cost categories were distin- Biogen Idec (Cambridge, US); Abbott Biotherapeutics (Redwood guished: drug acquisition costs; administration costs; and monitoring City, US) costs; the latter consisting of costs for specialist visits, testing/

123 S68 J Neurol (2012) 259 (Suppl 1):S1–S236 imaging and safety monitoring. Costs were discounted at 4 %, and predicted to be 0.35 (0.27–0.46) in the modelled population using incremental model results were presented over a 1, 2, 5 and 10 year AFFIRM characteristics, consistent with the effect of natalizumab in time horizon. The robustness of the model results was determined AFFIRM (0.32 [0.24–0.41]). The ARR ratio (95 % CI) for fingolimod by means of a number of deterministic univariate sensitivity anal- 0.5 mg vs placebo in the modelled population using CLARITY yses. Additionally, a break-even analysis was carried out to characteristics was 0.46 (0.37–0.58), similar to the effects of fingo- determine at which natalizumab IV infusion costs a cost neutral limod 0.5 mg vs placebo in FREEDOMS and of cladribine vs placebo outcome would be obtained. in CLARITY (0.43 [0.34–0.54]). Disability progression HR (95 % Results: Comparing fingolimod to natalizumab, the model pre- CI) for fingolimod 0.5 mg vs placebo was 0.70 (0.52–0.96) in dicted discounted incremental costs of -€2,966 (95 %CI: -€4,209;- FREEDOMS and 0.64 (0.45–0.92) and 0.63 (0.45–0.90) in the pop- €1,801), -€6,240 (95 %CI: -€8,800;-€3,879), -€15,328 (95 %CI: - ulations modelled using AFFIRM and CLARITY characteristics, €21,539;-€9,692) and -€28,287 (95 %CI: -€39,661;-€17,955) over a respectively; the reported HR (95 % CI) for natalizumab vs placebo 1, 2, 5 and 10-year time horizon, respectively. Results of the sensi- in AFFIRM was 0.58 (0.43–0.77) and for cladribine vs placebo in tivity analyses showed that these predictions were most sensitive to CLARITY was 0.67 (0.48–0.93). changes in the costs for IV administration of natalizumab. Changing Conclusions: Differences in population characteristics may these costs of €255 within a range from €165 to €364 per IV infusion, explain some of the apparent differences in efficacy estimates resulted in cost savings varying from €4,031 to €8,923 after 2 years. between the FREEDOMS/CLARITY studies and AFFIRM. However, The additional break-even analysis showed that IV infusion costs – as with all indirectly adjusted comparisons, uncertainty in estimates including aseptic preparation of the natalizumab solution – needed to warrants care in the interpretation. be as low as the respective costs of €94 and €80 to obtain a cost Analyses were supported by Novartis Pharma AG, Basel, neutral result after 2 and 10 years. Switzerland. Conclusion: The present analysis showed that treatment with fingolimod resulted in considerable cost savings compared to natalizumab: starting at €2,966 in the first year, increasing to a total of €28,287 after 10 years per RRMS patient in the Netherlands. P345 The robustness of this estimate was confirmed by sensitivity Cost-effectiveness of fingolimod compared to interferon analyses. This study was sponsored by Novartis Pharma B.V. beta-1a based on patient transitions in TRANSFORMS N. Bergvall, R. Hettle, J. Murphy, M. Tambour, F. Henriksson, B. Eckert, S. Fredrikson P344 Novartis Pharma AG (Basel, CH); HERON Group (Luton, UK); Novartis Sverige AB (Taby, SE); Karolinska Institute Indirect comparisons of oral fingolimod (Stockholm, SE) versus natalizumab and cladribine for the treatment Objectives: To assess lifetime cost-effectiveness of fingolimod of relapsing–remitting multiple sclerosis based on data (FTY720; Gilenya, Novartis Pharma AG) compared to interferon- from FREEDOMS, AFFIRM and CLARITY beta-1a in patients diagnosed with relapsing-remitting multiple scle- R. Nixon, B. Eckert, G. Cutter, F. Mercier, G. Francis, rosis (RRMS), based on disability health state transitions and L. Kappos annualized relapse rates as observed in TRANSFORMS (Trial Assessing Injectable Interferon versus FTY720 Oral in Relapsing– Novartis Pharma AG (Basel, CH); Novartis Pharmaceuticals Remitting Multiple Sclerosis). Corporation (East Hanover, US); University of Alabama Methods: A Markov model was developed with patients transi- (Birmingham, US); Former employee of Novartis Institutes for tioning through health states based on the Kurtzke Expanded Biomedical Research Inc (Cambridge, US); University Hospital Disability Status Scale (EDSS). The effectiveness of fingolimod and (Basel, CH) interferon beta-1a on sustained progression of disability was included Objectives: Comparisons of efficacy between fingolimod and natal- by using patient level transitions between defined health states as izumab and cladribine are limited by a lack of head-to-head trials and observed in the pivotal 1-year trial in 1 292 patients (TRANS- differences in population characteristics between studies. We conduct FORMS). Annualized relapses rates for the two treatments were the indirect comparisons of the efficacy of fingolimod, natalizumab and same as those observed in TRANSFORMS. Withdrawal rates in the cladribine by modelling population characteristic effects in FREE- model were the same as those observed in TRANSFORMS, and DOMS (FTY720 Research Evaluating Effects of Daily Oral therapy patients withdrawing were assumed to follow the disease course in in MS), AFFIRM (natalizumab safety and efficacy in relapsing– placebo treated patients in FREEDOMS (for missing information, remitting MS) and CLARITY (cladribine tablets treating MS orally). transition probabilities were imputed from the Ontario natural history Methods: Cox proportional hazards and negative binomial cohort). Mean patient age at baseline was 37 years. Costs and utilities regression models were used to analyze disability progression (based are based on a Swedish observational study in 1339 patients. Drug on Expanded Disability Status Scale scores) and annualized relapse costs were 204 022 SEK and 119 106 SEK for fingolimod and rate (ARR), respectively, at 24 months. Initial models were con- interferon-beta-1a, respectively. Monitoring and follow-up of treat- structed with eight baseline characteristic covariates as main and ment in the model are the same as those recommended by the Swedish treatment-interaction effects; refined models were then selected by a MS-Association. The primary outcomes of the model were societal stepwise algorithm using Akaike information criterion, and were used lifetime costs, including medical and non-medical costs, patient costs, to predict the hazard ratio (HR) for disability progression and ARR informal care and production losses, and quality-adjusted life years ratio, relative to placebo, at 24 months for the average patient from (QALYs). Costs (2010 SEK) and outcomes were discounted at 3 % both the AFFIRM and CLARITY populations if treated with fingo- annually. limod 0.5 mg. Results: In the base case analysis, treatment with fingolimod was Results: The ARR ratio (95 % confidence intervals [CI]) for fin- less costly (-47,443 SEK) and more effective (0,42 QALYS) than golimod 0.5 mg vs placebo was 0.46 (0.37–0.57) in FREEDOMS and treatment with interferon-beta-1a. When only healthcare costs were

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S69 included, the cost per quality-adjusted life year gained with fingoli- P347 mod was 279,547 SEK. Results are sensitive only to the time horizon Cardiac safety of fingolimod 0.5 mg during the first- of the analyses and assumptions about effectiveness of fingolimod beyond the trial. dose observation in a 4-month, open-label, multicentre Conclusions: Fingolimod is cost-effective, and even cost-saving FIRST study in relapsing multiple sclerosis patients from a societal perspective, compared to interferon-beta-1a based on R. Gold, L. Kappos, J. Palace, A. Siever, M. Marrosu, patient transitions between disability health states and relapse rates as R. Gottschalk, M. Bijarnia, A. Keil, D. Tomic, observed in TRANSFORMS. Analyses were supported by Novartis Pharma AG, Basel, P. von Rosenstiel, G. Comi Switzerland Universitatsklinikum der Ruhr-Universitat (Bochum, DE); University Hospital (Basel, CH); John Radcliffe Hospital, University of Oxford (Oxford, UK); Gemeinschaftspraxis (Oldenburg, DE); Ospedale Binaghi (Calgiari, IT); Novartis Pharmaceuticals Corporation (East P346 Hanover, US); Novartis Healthcare Pvt. Ltd. (Hyderabad, IN); Fingolimod is cost-saving compared with natalizumab Novartis Pharma AG (Basel, CH); University of Milan (Milan, IT) for the treatment of relapsing–remitting multiple Objectives: To report the first-dose cardiac monitoring results of sclerosis: a cost-minimisation analysis in Sweden fingolimod 0.5 mg in relapsing multiple sclerosis patient population N. Bergvall, M. Tambour, F. Henriksson, S. Fredrikson including patients with certain cardiac risk factors. Novartis Pharma AG (Basel, CH); Novartis Sweden AB (Stockholm, Methods: 2417 patients were enrolled in this study. Unless patients SE); Karolinska Institute (Stockholm, SE) met pre-defined cardiac risk criteria, the first dose of fingolimod was taken at home. The cardiac risk factors included past or current his- Objectives: Fingolimod is the first oral agent licensed in the EU for tory of recurrent symptomatic bradycardia, resting pulse rate at treating relapsing–remitting multiple sclerosis (MS) in patients with baseline of 45-54 beats per minute (bpm), patients with a history of high disease activity despite treatment with interferon beta, or rapidly positive tilt test from workup for vasovagal syncope, patients under evolving severe disease. The EU Committee for Medicinal Products concomitant treatment with beta-blockers and patients with history or for Human Use (CHMP) considers fingolimod to have broadly similar presence of Mobitz I 2nd degree AV-block (AVB). Heart rate and efficacy to natalizumab, which has the same EU licensed indication. ECG abnormalities were assessed by Holter–ECG for 24 h at We report results of a cost-minimization analysis (CMA) of fingoli- screening and for 6 h after administration of the first-dose. Herewith mod vs natalizumab, which formed part of a reimbursement we present a comparison of the first 6 h of Holter-ECG data recorded submission to the Dental & Pharmaceutical Benefits Board (TLV) in at screening and 6 h of Holter-ECG data recorded after the first dose. Sweden. Results: 2282 patients completed the study. The study included 295 Methods: A CMA was performed from a societal perspective patients who met the cardiac risk criteria (12.2 %). At pre-dose, 4.6 % according to TLV guidelines, including costs associated with ini- patients had a pulse\55 and 0.3 % had a pulse values\45. During the tiating and following treatment (physician visits, monitoring and 6 h post-first dose, 14.9 % patients exhibited a sitting pulse of\55 bpm tests), continuing therapy (drugs and administration), and lost and 1.3 % had a pulse of\45. During the first 6 h of screening Holter- patient productivity and leisure time over 10 years. Costs assumed ECG recording, the incidences of 2nd degree Mobitz I AVB and 2:1 treatment follow-up recommendations by the Swedish MS society AVB were 0.5 % and 0.1 %, while during the 6 h of Holter-ECG and product SmPCs. Unit costs were based on Swedish regional recording post-first dose the incidences of 2nd degree Mobitz I AVB and data, including median prices for physician visits and monitoring 2:1 AVB were 1.3 % and 0.5 %. One case of high-grade AVB occurred sessions. Costs in Swedish kronor (SEK) were discounted at 3 % at screening while there was none post-first dose. There was no annually. Natalizumab infusion costs were based on the occurrence of marked sinus bradycardia (HR \ 30). One patient had weighted mean cost of intravenous drug delivery in patients with [3 s pauses in both screening and post-dose Holter-ECG readings. MS (3750 SEK/visit) in hospitals included in the national cost-per- Conclusions: First-dose monitoring data did not reveal increased patient database. Drug costs for both therapies were 15 651 SEK/ risk of clinically notable cardiac events in this study population. The 28 days. Differences in adverse event costs were calculated to be results are similar to those observed in previous controlled fingolimod negligible. An annual withdrawal rate of 8.4 % was used for both trials where transient cardiac effects on treatment initiation were therapies. generally benign. Results: After 3 years, fingolimod was associated with savings of The study was supported by Novartis Pharma AG, Basel, 149 200 SEK/patient vs natalizumab (total cost/patient: 543 571 Switzerland. SEK vs 692 772 SEK). Cost savings with fingolimod after 1 year were 56 153 SEK/patient and after 10 years were 344 181 SEK/ patient. Over 3 years, natalizumab therapy was 27 % more expensive than fingolimod therapy. Costs associated with infusions, P348 magnetic resonance imaging (MRI) and lost patient time accounted Long-term ([7-year) efficacy and safety data for 84 %, 9 % and 7 %, respectively, of the additional natalizumab from a phase II extension study of fingolimod costs over 3 years. Sensitivity analyses varying the costs of infusions, monitoring and MRI showed that fingolimod was cost-saving in relapsing multiple sclerosis in all scenarios. X. Montalban, G. Comi, J. Antel, P. O’Connor, Conclusion: Fingolimod is associated with savings of over 50 000 A. de Vera, M. Cremer, N. Sfikas, G. Francis, L. Kappos SEK/patient/year vs natalizumab for the treatment of MS in Sweden. Hospital Universitari Vall d’Hebron (Barcelona, ES);Universita Vita- Based on these results, the Dental & Pharmaceutical Benefits Board Salute San Raffaele (Milan, IT); Montreal Neurological Institute (TLV) concluded that fingolimod is cost-effective and granted (Montreal, CA); St. Michael’s Hospital (Toronto, CA); Novartis reimbursement. Pharma AG (Basel, CH); Novartis Pharmaceuticals Corporation (East This abstract was supported by Novartis Sweden AB, Stockholm, Hanover, US); University Hospital of the University of Basel (Basel, Sweden. CH)

123 S70 J Neurol (2012) 259 (Suppl 1):S1–S236

Objectives: To report the long-term ([7 years) results at close out of a Methods: Patients treated with fingolimod (0.5mg/1.25mg) in the Phase II, open-label extension study of fingolimod in relapsing mul- Core phase (M0-12) continued the same dose (continuous-group) in tiple sclerosis. the Extension phase, while those on interferon beta-1a (IFN b-1a) Methods: In the 6-month (M), Core phase, patients were ran- were re-randomised (1:1) to fingolimod (switch group; IFN-0.5mg/ domised equally to fingolimod (1.25 mg/5 mg) or placebo. In the IFN-1.25mg). This dose assignment was double-blinded until the lock Extension phase, placebo patients were randomized to fingolimod of the Core phase and was dose-blinded until implementation of an 1.25 mg/5 mg (switch group); and the rest continued with their amendment to drop the 1.25mg dose. All patients then received open- assigned dose (fingolimod group). Between M15-24 all the 5 mg label fingolimod 0.5mg until the end of study (up to 4.5 yrs). Safety patients received open-label, fingolimod 1.25 mg and later all the parameters included monitoring and recording of adverse events patients received 0.5 mg until the end of study (EOS). Clinical disease (AEs), serious AEs (SAEs), laboratory abnormalities, ECG, oph- activity and MRI were measured at different time points. thalmology and dermatology assessments. Results: Of the 281 patients randomised in the Core study, 122 Results: Of 1027 (safety population), 772 (75.2 %) completed the patients (43.4 %) completed [7 years with an overall mean and study. Overall exposure in patient-years (PY) was: continuous group median exposure to fingolimod of 4.4 and 5.1 years respectively. By (0.5mg: n=356, 1185.7 PY; 1.25mg: n=330, 1056.5 PY), switch group EOS, annualised relapse rate in the fingolimod group was maintained (IFN-0.5mg: n=167, 370.5 PY; IFN-1.25mg: n=174, 375 PY). The most low at 0.16, while in the switch group it was reduced as compared to frequently reported AEs included nasopharyngitis, headache, and upper Core (0.21 vs. 0.77). By EOS, 55-66 % of patients in the fingolimod respiratory tract infection which were comparable across all groups. Both group and 44 % in the switch group were relapse-free. The proportion lymphopenia (0.5mg [14.6 %], 1.25mg [21.5 %], IFN-0.5mg [15.6 %], of patients free from 6M-confirmed disability progression ranged IFN-1.25mg [22.4 %]), and liver enzyme elevations (0.5mg [11.2 %], from 53 % (5 mg) to 70 % (1.25 mg). Overall 76 % of patients at the 1.25mg [16.7 %], IFN-0.5mg [15.6 %], IFN-1.25mg [21.3 %]) were EOS were free of any MRI inflammatory activity. The most frequent more frequent in both 1.25mg dose groups. The SAE incidence ( %) was reasons for study discontinuation overall were adverse events (AEs) higher in the IFN-1.25mg group (21.3) compared to the other treatment and withdrawal of consent (both 18.5 %). Other reasons included groups (0.5mg [15.4], 1.25mg [12.1], IFN-0.5mg [12.6]). On treatment unsatisfactory therapeutic effect (6.4 %), and abnormal laboratory initiation, asymptomatic transient bradycardia was observed in the switch value (2.5 %). Majority of patients (97.5 %) reported at least one AE, groups (IFN-0.5 mg [0.6 %], IFN-1.25 mg [1.7 %]) which resolved the most common ([=10 %) being nasopharyngitis (40.9 %), head- without treatment. In the IFN-1.25mg group, post first dose, 1 patient had ache (31.3 %), fatigue and influenza (each 21.7 %), and back pain transient 3rd-degree, narrow-complex AV block and 2 patients had (20.3 %). Serious AEs (n=76) were reported, the majority (n=32) in transient 2nd-degree AV block (Mobitz type I). Overall cardiac events the 5.0 mg group. No chronic effects of fingolimod on heart rate, were similar across all groups. One confirmed macular oedema case each cardiac function or AV conduction were observed and no case of was reported in both 1.25mg groups. The incidence of herpes viral confirmed macular oedema was reported. Alanine aminotransferase infections was comparable across all groups (10.1 %-15.0 %). One death ([=3ULN) increased in overall 16.7 % of patients and no case of liver due to suicide was reported in the IFN-0.5mg group. failure was reported. An initially observed increase in blood pressure Conclusion: Fingolimod 0.5mg long-term treatment was well remained stable up to EOS. Infections (serious: 2.1 %, severe: 4.3 %) tolerated and in line with previously reported data. Patients switching occurred infrequently. Herpes zoster (n=16) infections were reported from IFN b-1a to fingolimod reported expected transient fingolimod including a serious AE (otic zoster). Malignancies (n=14) were treatment initiation effects. reported (skin: 10, others: 4). ‘‘The study was supported by Novartis Pharma AG, Basel, Conclusions: Long-term ([7 years) fingolimod treatment was Switzerland’’. associated with low MRI and clinical disease activity and was well tolerated with no new safety concerns. The study was supported by Novartis Pharma AG, Basel, P350 Switzerland. Fingolimod leads to early clinical and MRI benefits in relapsing-remitting multiple sclerosis P. Chin, P. von Rosenstiel, D. Haering, G. Francis, P349 L. Kappos Long-term safety data from the extension Novartis Pharmaceuticals Corporation (East Hanover, US); Novartis Pharma AG (Basel, CH); University Hospital (Basel, CH) of the phase III TRANSFORMS study of fingolimod versus interferon beta-1a in relapsing-remitting Objectives: Rapid onset of treatment efficacy can avoid unnecessary morbidity in multiple sclerosis (MS). We evaluated early benefits multiple sclerosis: 4.5 year follow-up of fingolimod at the approved 0.5 mg dose in a Phase 3 randomised H. Hartung, F. Barkhof, G. Comi, X. Montalban, controlled trial. J. Pelletier, B. Khatri, T. Stites, E. Kornyeyeva, Methods: Data from the FREEDOMS study were analysed for F. Holdbrook, P. von Rosensteil, W. Collins, treatment differences between 0.5 mg of fingolimod and placebo on relapse and MRI endpoints within the first 6 months. Analyses were L. Kappos, J. Cohen conducted on the intent-to-treat (ITT) population without multiplicity Heinrich-Heine-University (Du¨sseldorf, DE); VU University Medical adjustments. Centre (Amsterdam, NL); University of Milan (Milan, IT); Hospital Results: A significant (p\0.05) time to first relapse treatment Universitari Vall d’Hebron (Barcelona, ES); Department of effect was established within the first 3 months. The proportions free Neurology (Marseille, FR); St Luke’s Medical Center (Milwaukee, of confirmed relapse on fingolimod vs. placebo, respectively, were US); Novartis Pharmaceuticals Corporation (East Hanover, US); 91.5 % vs. 86.8 % at 3 months, and 87.1 % vs. 78.2 % at 6 months. Novartis Pharma AG (Basel, CH); University Hospital (Basel, CH); At 6 months fingolimod was associated with relative reductions of Cleveland Clinic Foundation (Cleveland, US) 84.6 % in mean number of T1-enhancing lesions and 72.2 % in new/ Objectives: To report the long-term safety of fingolimod in patients with newly enlarged T2 lesions on brain MRI compared to placebo (both relapsing-remitting multiple sclerosis (RRMS) treated for up to 4.5 years. p\0.001). The proportions free of T1-enhancing lesions (89.6 % vs.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S71

62.2 %), new/newly enlarged T2 lesions (64.7 % vs. 38.1 %), and by training is not shown consistently in the literature. Therefore the both T1-enhancing and new/newly enlarged T2 lesions (65.0 % vs. effect of an individualized e-training combining endurance and 39.4 %) were higher with fingolimod compared to placebo, respec- strength training on fatigue is investigated in fingolimod treated MS tively (all p\0.001). Mean percent brain volume change after 6 patients. months was -0.224 for fingolimod compared to -0.344 for placebo Design: In the PACE study (Physical ACtivity in Gilenya treated (p=0.006). MS patiEnts) 226 patients with relapsing remitting MS and a fatigue Conclusion: Treatment with 0.5 mg fingolimod significantly score higher than 14 assessed by mFIS, will be included. After a reduced the risk of relapse within 3 months and reduced new MRI baseline assessment of neurologic, aerobic and muscular capabilities, lesion activity by the first study scan at 6 months. Fingolimod also patients will be randomized 1:1 in a training group and a waiting reduced whole brain volume loss by approximately 35 % over the first group which will start the training six months later. The training 6 months of treatment. Anti-inflammatory and neuroprotective ben- consists of individualized strength and endurance home based exer- efits of fingolimod are evident after a short treatment duration. cises. Patients are supervised by a sports therapist via internet who The study was supported by Novartis Pharma AG, Basel, Switzerland. adapts the training according to the individual physical limitations. After 6 and 12 months, the effect of exercise will be assessed. Objectives: The primary objective is to evaluate the effect of individualized physical e-training vs. no training on fatigue in fin- P351 golimod-treated MS patients (expanded disability status scale (EDSS) Fingolimod may be safe in patients with baseline 0–3.5) assessed by mFIS fatigue scale. In addition, the effect of bradycardia: a case report exercise on muscular strength and aerobic capacity, quality of life, D. Kantor depression as well as MS disease activity will be assessed. Conclusion: This study will provide first-time data on the efficacy Neurologique Foundation (Ponte Vedra, US) of an individualized e-training on fatigue in a large cohort of fingo- Objectives: To report the cardiovascular effects of fingolimod in a limod-treated MS patients. single MS (multiple sclerosis) patient with a baseline heart rate of 41 Study sponsored by Novartis Pharma GmbH bpm (beats per minute). Fingolimod, an oral sphingosine 1-phosphate receptor modulator used to treat relapsing MS has been associated with a dose-dependent decrease in heart rate that reaches its nadir approximately 5 h post- P353 dose. In Phase 3 trials (TRANSFORMS and FREEDOMS) fingolimod Fingolimod (GilenyaÒ) in combination with an SSRI was not studied in subjects with baseline heart rates beneath 55 bpm. Methods: Case report. or SNRI antidepressant in multiple sclerosis patients Results: A 32-year-old white man with relapsing-remitting mul- with mild to moderate depression: design of a phase tiples sclerosis was switched from weekly intramuscular interferon IIIb study (REGAIN) beta-1a to oral fingolimod due to two breakthrough relapses, new K. Schuh, A. Bayas demyelinating lesions on brain magnetic resonance imaging (MRI) Novartis Pharma GmbH (Nuremberg, DE); Klinikum Augsburg and persistent flu-like injection side effects. He presented to an MS (Augsburg, DE) Center for first dose administration of fingolimod and minimum of six hour monitoring. His baseline heart rate was 41 bpm and blood Background: Almost half of all patients with multiple sclerosis (MS) pressure of 130/61 mm Hg. The decision was made to proceed with are affected by concomitant psychological diseases, depression being dosing after discussions with the patient and treating neurologist; most frequent (46 %). The 12-month prevalence of depression in MS it was felt that the athletic patient’s excellent vagal tone may mitigate patients is 26 %, which is three times higher than in the general against a significant drop in heart rate. Throughout monitoring, his population. Although some studies have shown a positive effect of heart rate ranged from 40 - 49 bpm, with the nadir of 40 bpm at hour selective serotonin/noradrenaline or serotonin re-uptake inhibitors 4. Throughout the monitoring, the patient remained asymptomatic. (SNRIs or SSRIs, respectively), there is currently no established drug Conclusions: Fingolimod may be safe for use in MS patients with treatment of depression in MS patients. Therefore, in this open-label lower heart rates than 55 bpm. Further use in clinical practice may study, the safety and tolerability of the combination of fingolimod and help neurologists make informed decisions regarding weighing the an SSRI or SNRI antidepressant will be investigated in MS patients potential for side effects vs. efficacy in the treatment of relapsing MS. with mild to moderate depression. Study design: In the REGAIN study (Reduce dEpression with Gilenya And SNRI/SSRI antIdepressant in MS-patieNts) 500 patients P352 with relapsing remitting MS and a mild to moderate depression, will be included. Patients will be pre-treated for 2 weeks with fingolimod, Impact of individualised physical training on fatigue followed by a 16-week concomitant antidepressant treatment phase, in multiple sclerosis patients treated with fingolimod with either an SSRI or an SNRI (Citalopram, Fluoxetine or Venla- (GilenyaÒ) design of a phase IV study (PACE) faxine), at the discretion of the investigator, while maintaining on K. Schuh, C. Hentschke, M. Maeurer fingolimod therapy. Novartis Pharma GmbH (Nuremberg, DE); University of Erlangen After 8 and 16 weeks, the safety and tolerability of the combi- (Erlangen, DE); Caritas Hospital (Bad Mergentheim, DE) nation therapy will be assessed. Objectives: The primary endpoint is the safety and tolerability Background: Fatigue is one of the most common and disabling profile of the combination of an SSRI or SNRI antidepressant with symptoms of multiple sclerosis and it is reported by up to 80 % of all fingolimod in MS patients (expanded disability status scale (EDSS) MS patients. Up to 40 % of patients with MS report fatigue as the 0–6.5) who are suffering mild to moderate depression (BDI-II 14-28). most disabling problem, severely affecting daily activities and thus In addition, the efficacy of the combination therapy on quality of life, reducing quality of life. Several studies have shown a positive effect treatment satisfaction and other MS related sequelae will be explo- of exercise on muscle force and aerobic capacity and to some extent ratively assessed. Furthermore, in terms of health economics, the MS- on walking ability and fatigue. However, the improvement of fatigue specific and depression-specific use of resources will be evaluated.

123 S72 J Neurol (2012) 259 (Suppl 1):S1–S236

Summary: This study will provide first-time data on the safety and Objectives: Fingolimod (FTY720; Gilenya) is a sphingosine-1-phos- tolerability of a combination therapy of fingolimod and an SSRI or phate (S1P) modulator that has been approved as an oral treatment for SNRI antidepressant in MS patients with mild to moderate multiple sclerosis (MS) in the United States, Europe and several other depression. countries. Fingolimod inhibits recirculation of autoreactive CD4+ T Study sponsored by Novartis Pharma GmbH. cells to the CNS, thereby reducing inflammation in animal models of MS. Methods: Here we utilized lymphocytic choriomeningitis virus (LCMV) infection in mice as a model to investigate how fingolimod P354 treatment influences anti-viral immune responses and virus loads. Study design and first results of a non-interventional Control mice were also infected, but either not treated with drug or given depleting anti-CD8 antibody. Results: We found that anti-CD8 registry study to establish long-term safety treatment increased viral loads by approximately 100-fold. In fingo- and pharmaco-economic data on fingolimod (GilenyaÒ) limod-treated mice, the induction and expansion of antiviral effector in multiple sclerosis patients in Germany (PANGAEA) CD8+ T cells were unaffected as evident from normal frequencies of T. Ziemssen, T. van Lokven, R. Kempcke, M. Meergans viral epitope-specific CD8+ T cells, but cells were reduced in circulation. Still, LCMV loads were unaltered when mice were treated with Carl Gustav Carus University Hospital (Dresden, DE); Novartis fingolimod. Pharma GmbH (Nuremberg, DE) Conclusions: These findings confirm that fingolimod allows Objective: Fingolimod is licensed in Germany since April 2011 as induction and expansion of anti-viral effector CD8+ T cells and does escalation treatment for patients with relapsing-remitting multiple not detectably affect virus control. In contrast, treatment with the sclerosis (RRMS). Fingolimod is orally available and the first repre- depleting anti-CD8 antibody was associated with massive virus sentative of a new substance class, the sphingosine-1-phosphate expansion. Intact virus control in fingolimod-treated mice suggests receptor modulators. In order to investigate the safety and efficacy of that a critical number of effector CD8+ T cells is generated to fingolimod (Gilenya) in everyday clinical practice, a 4000-patient guarantee infectious immune surveillance. national safety study is being conducted, in which pharmaco-eco- This work has been supported by Novartis Pharma AG. nomic data will also be collected (PANGAEA = Post-Authorization Non-interventional German sAfety study of GilEnyA in RRMS patients). Methods: The Multiple Sclerosis Documentation System (MSDS) P356 Project Development Group in Dresden adapted the patient man- Prevalence of chronic cerebrospinal venous agement software, ‘‘MSDS 3D’’ to the use of fingolimod. In addition insufficiency in MS and its correlations with clinical to the documentation of safety parameters, PANGAEA also fulfils a features quality assurance function. RMP-measures such as monitoring of the first dose, ophthalmological examination and regular laboratory tests, R. Lanzillo, M. Mancini, R. Liuzzi, E. Salvatore, V. Magli, are represented in PANGAEA and integrated into MSDS 3D. O. Di Donato, G. Vacca, L. Amato, G. Orefice, A. Brunetti, Results: The Study Design of this non-interventional registry study V. Brescia Morra will be presented. The study consists of a 5-year observation period Federico II University (Naples, IT); NRC (Naples, IT) including pharmaco-economic data over 2 years from a sub-sample of 800 patients. It is planned to recruit 4,000 RRMS patients from Background: Multiple Sclerosis (MS) has a multi-factorial patho- neurological clinics and practices until end of 2012. In addition to genesis and, recently, an association with a condition defined as compliance and a resources questionnaire, the following instruments chronic cerebrospinal venous insufficiency (CCSVI) was non-unani- will be used: UK NDS, PRIMUS, EQ5-D and TSQM-9. MSFC and mously reported. SDMT questionnaires, as well as lipid-values will be monitored in Objective: to further investigate the prevalence of CCSVI by another sub-population of 1000 patients. rigorous intra and extra cranial Echo-Color-Doppler (ECD) methods Until October 2011, more than 750 patients have been enrolled. A in MS patients and in healthy controls and to point out whether its summary safety profile of patients documented until April 2012 will presence might be related to specific MS clinical subsets. be presented. The presented interims analysis will additionally Patients and methods: we included consecutive voluntary MS include the following data: percentage of patients who are referred to patients belonging to Relapsing Remitting (RR), Secondary Progres- a clinic for first-dosing, MRI imaging data and frequency of varicella sive (SP), Primary Progressive (PP) forms of disease and Clinically zoster antibody analysis. Isolated Syndromes (CIS), and matched controls, after signing an Conclusion: First results regarding safety and other parameters of informed consent. We performed neck and transcranial ECD, as pre- the register study PANGAEA will be presented and are intended to viously described, to define CCSVI condition. Clinical and deliver continuous information and transparency with regard to the demographic data were collected, EDSS was evaluated and MSSS safety profile of fingolimod in patients with RRMS under real-life measured. Prevalence, sensitivity and specificity and Odds ratios were conditions. calculated for CCSVI and single venous hemodynamic criteria. ECD The study was sponsored by Novartis Pharma GmbH. results were correlated with clinical data. Results: The 171 enrolled patients belonged to 4 clinical subtypes (62 RR, 71 SP, 22 PP and 16 CIS). Prevalence of CCSVI was 75,4 % in MS patients and 22 % in controls (table 2) (p\0,001). Sensitivity P355 and specificity of CCSVI status for MS were 75,4 % (67,4-81) and Anti-CD8 treatment but not fingolimod impairs control 78 % (63,8- 88,6) respectively, with an Odds Ratio of 10,9 (CI 4,8- of LCMV infection in mice 24,7). Age was related to CCSVI in the whole sample (p=0,004) and in the MS group (p=0,028), but not in control group (p=0,174). No S. Johnson, M. Kreutzfeldt, K. Steinbach, M. Fernandez, correlations were found between CCSVI status and gender or clinical D. Merkler, D. Pinschewer parameters. CCSVI was equally distributed in the different MS sub- University of Geneva (Geneva, CH) types (X2= 0,445, p=0,931), while VH criterion 4 was significantly

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S73 related to the PP MS subtype (50 % in PP vs 33 % in SP, 18 % in RR Objectives: Multiple sclerosis (MS) is an immune-mediated disorder and 14 % in CIS patients and 29 % in total MS patients) (p=0,024). of the central nervous system, featuring demyelination and axonal Conclusions: CCSVI seems to be an age dependent epiphenome- damage. Recent evidence suggests that altered ion channel homeo- non, without clinical correlations in MS. Its higher prevalence in MS stasis may be substantially involved in the neurodegenerative process might dependent on some still not well studied cerebral venous leading to axonal damage. The observation that voltage-gated Ca2+ hemodynamic alterations, that could be associated with different channels (VGCCs) are expressed on axons and that damaging pro- clinical MS phenotypes. cesses involve augmented Ca2+-dependent protease activity led to the hypothesis that compounds selectively interfering with the intracellular calcium influx could exert a potential therapeutic effect in MS. In this study, we assessed whether nimodipine, a dihydropyridine P357 selectively blocking the L-type VGCCs, could modify the clinical Nogo-A expression kinetics in experimental course of murine experimental autoimmune encephalomyelitis autoimmune encephalomyelitis in C57BL/6 mice (EAE), an animal model of MS. P. Theotokis, A. Lourbopoulos, O. Touloumi, R. Lagoudaki, Methods: We induced EAE in SJL/J mice (n=20) by active immunization with proteolipid protein peptide 139-151 (PLP139-151) E. Kofidou, E. Nousiopoulou, E. Spandou, N. Tascos, in complete Freund’s adjuvant (CFA) to mimic a relapsing-remitting N. Grigoriadis type of MS. Mice were randomized to receive daily intraperitoneal AHEPA University Hospital (Thessaloniki, GR) injections of nimodipine (10 mg/kg) or vehicle starting from the day of immunization. The extent of demyelination and axonal damage Objectives: Nogo-A is a myelin inhibitor of axonal regrowth within was assessed in brains as well as spinal cords by fluorescence the central nervous system (CNS). Although Nogo-A inhibition is microscopy and the following primary antibodies: anti-myelin basic considered beneficial in experimental autoimmune encephalomyelitis protein (MBP), anti-neurofilament M (NF-M), anti-amyloid precursor (EAE), the corresponding changes of Nogo-A have not been sys- protein (APP). Antigen-dependent T cell activation was studied in ex tematically studied, so far. vivo cultures by assessing proliferation and expression of the fol- Methods: Chronic MOG35-55 EAE was induced in C57BL/6 mice lowing markers by flow cytometry: CD25, CD44, CD54, CD62L, (n=35). Animals were sacrificed on day 0 (naive animals), preclinical CD69. (day 10), acute (day 18-22) and chronic (day 50) phase of the disease. Results: In SJL/J mice, nimodipine treatment determined a sig- Nogo-A mRNA expression (using a specific Nogo-A region within nificant clinical improvement in the remission phase after relapses the 3rd exon of Reticulon 4 gene) was studied using in situ hybrid- compared to vehicle-treated mice (p\0.05). We found significantly ization (ISH) and real-time PCR while Nogo-A protein was assessed reduced demyelination (p\0.05) and axonal loss (p\0.0001) in using immunohistochemistry (IHC). lesions from brains of nimodipine-treated mice as well as milder Results: Nogo-A mRNA was ubiquitously expressed in neurons and axonal damage (p\0.0001) in spinal cord lesions from nimodipine- oligodendrocytes in brain and spinal cord of naive animals. ISH and real- treated compared to vehicle-treated mice. No significant differences time PCR revealed significant reduction of Nogo-A expression in T cell proliferation and activation from nimodipine- and vehicle- (p\0.0001) at preclinical and acute phases while chronic phase highly treated mice were observed. increased Nogo-A mRNA (p\0.0001) in all CNS structures indepen- Conclusion: Nimodipine exerts neuroprotective effects without dently of their coherence to inflammation or glial scar. Moreover, Nogo- showing immunosuppressive properties in EAE. Further studies A protein expression was similar among naive, preclinical and acute aimed at clarifying the molecular pathways involved in its neuro- phase EAE animals, and significantly increased (p\0.001) during chronic protective effect are needed. phase. Within inflammatory foci, Nogo-A protein was initially reduced This study was supported by Bayer. during acute phase and was later increased during chronic phase; this L.D.S received financial support from the EFNS for this study expression was inversely correlated with axonal regeneration (indicated (EFNS scientific fellowship program 2011). by the Growth Associated Protein 43, GAP-43+ axons) and axonal injury (indicated by Amyloid Precursor Protein, APP+ axons). Confocal microscopy revealed that APP+ axons were always in contact with Nogo- A processes irrespectively of the disease phase (possibly as a myelin remnant through the axonal degeneration indicated by the APP+ signal), P359 while the GAP-43+ axons were 60 % Nogo-A free (presumably not Cortical activation changes following botulinum-toxin inhibited by Nogo-A, thus allowing for axonal regeneration as indicated treatment of leg spasticity in multiple sclerosis: pilot by GAP-43+ signal) during acute phase and almost 0 % in chronic phase. study Conclusion: Our data indicate that early preclinical conditions in EAE downregulate Nogo-A mRNA expression while inflammatory invasion J Klosova´, P. Hlusˇtı´k, P. Hok of acute phase potentates a consequent upregulation therafter. Nogo-A is Faculty Hospital (Olomouc, CZ) actively regulated by inflammatory conditions, allowing for an acute- Background: Botulinum neurotoxin (BoNT) treatment affects multi- phase, localized time-window for axonal regeneration in EAE. ple levels of the sensorimotor system and can relieve spasticity of lower limbs caused by multiple sclerosis. The aim of our functional magnetic resonance study was to evaluate cortical activation changes P358 following botulinum-toxin treatment of leg spasticity in multiple Clinical amelioration and reduced axonal damage sclerosis. in nimodipine-treatedEAE Methodology: Four patients (1 man, 3 women, mean age 46.5, SD L. De Santi, J. Ingwersen, B. Wingerath, J. Graf, 9.3 years) with multiple sclerosis affected with leg spasticity were studied. Patients performed repeated knee extension-flexion move- F. Schro¨ter, T. Prozorovski, H-P. Hartung, P. Annunziata, ments during brain functional MRI which was acquired in three O. Aktas sessions: before and 4 and 12 weeks after BoNT treatment into the University of Siena (Siena, IT); Heinrich-Heine-University spastic muscles. The change of leg spasticity was assessed using the (Du¨sseldorf, DE) Snow scale.

123 S74 J Neurol (2012) 259 (Suppl 1):S1–S236

Results: BoNT treatment decreased leg spasticity across the group. Cerebrovascular disorders I fMRI pre-BoNT treatment showed extensive bilateral task-related activation of frontoparietal sensorimotor cortical areas, whereas post- BoNT treatment caused retraction to midline and contralateral sensorimotor cortex. Third examination after 12 weeks of BoNT P361 treatment showed re-expansion to a similar extent as seen in the pre- Factors contributing to delirium in subarachnoid BoNT session. haemorrhage patients Conclusions/Relevance: This pilot study suggests that relief of B. Maia, R. Roque, A. Paiva-Nunes, A. Amaral-Silva, leg spasticity may be associated with temporary partial normalization of activation in primary and association sensorimotor cortical T. Mesquita, J. Alcaˆntara areas. Spasticity may be contributing to the documented compen- Centro Hospitalar de Lisboa Central (Lisbon, PT) satory overactivation of the sensorimotor system in multiple Background: Delirium is a well recognized complication during the sclerosis. management of patients with subarachnoid hemorrhage (SAH). Alterations in global cerebral metabolism, global or local cerebral blood flow may contribute to delirium. Other SAH complications such as vasospasm, hyponatremia, hydrocephalus or seizures may P360 increase even further the incidence of delirium in SAH patients. We Assessing the level of MMP-9, TIMP-1 and MMP-9 aimed to identify which complications of SAH may contribute to the occurrence of delirium during the acute management of SAH. TIMP-1 ratio in relapsing-remitting multiple sclerosis Methods: Retrospective analysis of all SAH patients admitted to patients during relapse and remission periods our unit during 1 year. Exclusion criteria included intubated patients A. Sanli Turk, M. Ozturk, A. Soysal, Y. Doventas, and a Glasgow Score\14. Delirious patients were identified according S. Baybas to the DSM-IV criteria. Age, sex, Fisher score, delirium as initial Bakirkoÿ Neurological and Psychiatric Research Hospital presentation, vasospasm, delayed cerebral ischemia, hyponatremia, (Istanbul, TR); Haseki Research Hospital Biochemistry infection, seizures and hydrocephalus were identified and correlation (Istanbul, TR) with delirium was assessed using the Chi-square and Fisher’s Exact tests. Odds Ratio were calculated for each of them. Objective: Matrix Metalloproteinases (MMPs) are capable of prote- Results: 30 patients were identified. All were submitted to aneu- olytic activity for extracellular matrix proteins. They are known to rism embolization during the first 48 h of onset. 12 were men and play a role in the pathogenesis of Multiple Sclerosis (MS) by growing mean age was 58,8. 16 (53,3 %) exhibited delirium during the first 15 and differentiating the cells and connecting them. A member of this days of SAH. No significant correlations were achieved for a p value enzyme family, MMP-9; is significant due to degrading the compo- of 0,05. Infection as a risk factor and delirium (as the initial mani- nents of basal membrane, collagene type 4,5 and fibronectin, allowing festation of SAH) as a protection factor showed values closer to T lymphocytes to enter brain parenchyma by damaging blood–brain statistical significance, indicating a weak tendency for a correlation barrier. The aim of this study is to measure the level of MMP-9, (infection p=0,063 with OR=4,17[CI 95 %=0,9:9,4] and delirium as TIMP-1(tissue inhibitors of matrix metalloproteinases) and MMP-9/ initial presentation p=0,21 with OR=0,36[CI 95 %=0,28:0,66]). TIMP-1 ratio and to evaluate the role of these enzymes in determining Patients in whom delirium was the initial manifestation were treated, the stage of the disease. from the beginning with psychotropic medication. Materials and method: 25 Relapsing-Remitting MS(RR-MS) Conclusion: Among all factors studied that relate to the occurrence patients (16 female, 9 male) with EDSS score 0-5.5 from our out- of delirium in SAH patients, infection seems to have a higher ten- patient MS clinic and 25 healthy controls(18 female, 7 male) are dency to increase the likelihood of delirium, and initial onset delirium participated in our study. The patients were diagnosed as definite MS seems to protect from late onset delirium,. Further studies with larger according to Mc Donald criteria and none of them had received any samples are needed to achieve statistical significance. immunosuppressive and immunomodulatory therapy. Peripheral blood samples were collected once from healthy controls and two times from RR-MS patients to detect the levels of MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio. These parameters have been detected by P362 competitive ELISA. NCSS 2007 & PASS 2008 Statistical Software Endovascular treatment of ugly aneurysms using programme was used for statistical analyses. Student t test and Chi- sandwich technique square test were used to compare mean values among the various groups. B.H. Lee, M.S. Kim, M.S. Park Results: In RR-MS patients, a significant elevation in the levels of Eulji University Hospital (Daejeon, KR) MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio were detected during Objectives: To report preliminary results of endovascular treatment relapse and remission period when compared with healthy con- for ugly aneurysms with sandwich technique trols(p\0.01). MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio were Methods: Between Dec 2009 and Nov 2011, endovascular treat- higher in relapse periods compared to remission periods nevertheless ment with sandwich technique(stent/coils/stent/coils/stent…) was changes did not reach the threshold for statistical signifi- performed in 6 patients (M:F=2:4, mean age: 59.7years) with aneu- cance(p[0.05). Positive correlation was found between MMP-9/ rysm surgically difficult or difficult with conventional endovascular TIMP-1 ratio and duration of disease. treatment. Lesion characteristics were as follows: unruptured aneu- Conclusions: MMP-9 has a role in etiopathogenesis of MS by rysm in five and ruptured in one 4 saccular dissecting aneurysms: 3 in facilitating proteolytic activity in BBB which is going on in both supraclinoid ICA and one in P1 segment 1 fusiform dissecting relapse and remission periods. As a result, we suggest that serum aneurysm in intracranial vertebral artery levels MMP-9 could be a biomarker of determining disease activity. 1 P-com aneurysm (rupture during stent-assisted coiling) We also think that MMP inhibitors are promising compounds for the Results: Technical success was achieved in all patients (total future treatment of MS. occlusion in five and subtotal occlusion in one). There was no

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S75 procedure-related morbidity or mortality. Serial angiographic follow- been defined so far. We tested a pragmatic step-wise diagnostic up was available in four patients (mean: 9.3months, range: 2-15 algorithm including CT/CTA, MRI/MRA, and digital subtraction month). One patient with sub-total occlusion showed near-total angiography (DSA) and its effect on the detection of acutely treat- occlusion on 2 month follow-up angiogram and there was no recan- ment-relevant underlying pathologies. alization or regrowth of aneurysm in remaining three patients. Subjects and Methods: We analyzed a prospective cohort of 82 Conclusion: Endovascular treatment with Sandwich technique was consecutive patients (51 % women, mean age 64 years ±12) who technically feasible and safe for treatment of ugly aneurysm which were hospitalized after acute non traumatic ICH. All patients under- was surgically difficult or difficult with conventional endovascular went initial CT with or without CTA. Patients without evident treatment. It could be another treatment option if pipeline stent system underlying etiology and no contraindication underwent MRI/MRA. cannot be used. Eventually, diagnostic DSA was performed in cases without evident ICH etiology on prior imaging. Results: Of the 82 ICH patients, 3 (4 %) showed deep ICH with CT evidence of severe small vessel disease. In one case (1 %), CTA P363 revealed cerebral venous thrombosis. The remaining 77 (94 %) patients Multiple intracranial aneurysms by syphilitic infection without contraindication (n=1 had a pacemaker) underwent subsequent MRI/MRA studies allowing diagnosis of an underlying pathology in 51 in a patient with acute ischaemic stroke (64 %), including 6 (7 %) with acutely treatment-relevant underlying M.-J. Wang, B.-S. Kim, Y.-M. Shon, A.-H. Cho, S.-J. Han pathologies: one patient had acute cerebral venous thrombosis, two had Catholic University of Korea (Seoul, KR) secondary hemorrhagic infarcts, two showed cavernous malformations, and one an underlying glioblastoma. Twenty-six patients (32 %) Objective: Syphilitic infection can be one of the causes of multiple remained without diagnosis of an underlying pathology and underwent intracranial aneurysms. However, multiple intracranial aneurysms DSA revealing another 3 (4 %) acutely treatment-relevant underlying from syphilitic infection have been rarely reported, whereas the pathologies: Two (2 %) patients had an underlying dural arteriovenous thoracic aortic aneurysm from thoracic syphilitic aortitis has been fistula, and one (1 %) bled in the context of reversible acute cerebral reported. In this context, we aimed to report a case of multiple vasoconstriction syndrome. intracranial aneurysms incidentally found in a patient with confirmed Conclusion: Our findings suggest the diagnostic sensitivity of syphilis and acute ischemic stroke. brain CT alone is insufficient for the diagnostic work-up in ICH Methods: We reported a case by retrospective review of medical patients. A pragmatic, stepwise imaging algorithm based on addi- record. tional CTA, MRI/MRA and DSA lead to the diagnosis of an Results: A 62-year-old woman presented with right side weak- underlying pathology in 64 %, including the detection of acutely ness and dysarthria. She had previous medical history of 5 times of treatment-relevant underlying pathologies in 12 % (10 of 81 patients). spontaneous abortion at more than 10 weeks of gestational age. The MRI and CT angiography revealed acute left middle cerebral arterial territory infarction and incidental multiple intracranial aneurysms. On coronary CTangiography, minimal aneurysmal dilatation of proximal right coronary artery was observed. Blood tests showed P365 that anti-cardiolipin antibody Ig G, anti-phospholipid antibody Ig G, Profile of neuronal damage markers release in course M, anti-beta2-glycoprotein I antibody, lupus anticoagulant antibody of spontaneous intracerebral haemorrhage and anti nuclear antibody were positive. In addition, blood tests M. Florczak-Rzepka, A. Rocco, A. Kaminska, T. Steiner were positive for rapid plasma reasin (RPR) test and FTA-ABS Ig Medical University of Warsaw (Warsaw, PL); University of M. The cerebrospinal fluid tests for syphilis were negative for RPR Heidelberg (Heidelberg, DE) and FTA-ABS without significant leukocytosis nor high protein level. She was diagnosed with anti-phospholipid antibody syndrome Objectives: SICH is a massive, abrupt vascular event leading to direct and latent syphilis. The confirmation of syphilis through serologic and immediate brain tissue damage at least at hematoma site. tests, the exclusion of other cause for multiple intracranial aneu- Extravasated blood promotes activation of many different pathways rysms and the coexistence of coronary arterial aneurysm suggested causing e.g. neuronal death and hematoma expansion. S100 B (cal- that the multiple intracranial aneurysms might be caused by syphilic cium binding protein) and NSE (neuron specific enolase) were shown infection. to be upregulated after ischemic stroke but also in SICH. Conclusions: This report shows a rare case of CNS manifestation We aimed to investigate the sequence of changes in blood con- from syphilitic infection, presented as multiple intracranial aneu- centration of S100B and NSE within one week after SICH. rysms which are incidentally found in a patient with acute ischemic Methods: A total of 49 consecutive patients diagnosed with SICH stroke. were included into the study. Serum for S100B and NSE was collected on admission, within 24, 48, 72 h and on day 7 after SICH onset. Blood concentration of these biomarkers was also tested in 33 age and gender matched healthy controls. P364 Results: S100B peaked within 24 h from SICH onset and A diagnostic algorithm for patients with spontaneous decreased afterwards. However, during whole observational period S100B remained significantly higher in patients than in controls. intracerebral haemorrhage Blood concentration of NSE was relative stable and insignificantly C. Stapf, P. Reiner, J.-P. Guichard, D. Bresson, higher in patients than in controls. H. Chabriat, H.-M. Schneble Conclusion: SICH causes elevation of neuronal brain damage Hoˆpital Lariboisie`re (Paris, FR) markers level in serum. S100 seems to reflect the course of disease more accurately than NSE as its time profile seems to cover the Background: Acute intracerebral hemorrhage (ICH) is one of the natural sequence of hematoma alteration. Further studies are needed deadliest forms of stroke, but no standardized diagnostic work-up has to elucidate this phenomenon.

123 S76 J Neurol (2012) 259 (Suppl 1):S1–S236

P366 in prompt clinical and radiological regression in a few days in all Functional outcome after spontaneous intracerebral patients. Conclusion: To our knowledge, this is the first study that reports haemorrhage is related to biomarkers of inflammation steroid responsive symptomatic late perihematomal edema in cases of and neuronal damage blood concentration ICH. In our database the incidence of this type of perihematomal M. Florczak-Rzepka, A. Rocco, A. Kaminska, T. Steiner edema is 3.03 %. Dramatic responses to steroid in our patients sug- Medical University of Warsaw (Warsaw, PL); University of gest a late developing vasogenic edema. Heidelberg (Heidelberg, DE) Objectives: SICH is a devastating condition with an early mortality rate of 30-52 %. Numerous clinical and radiological features were P368 shown to be associated with prognosis in SICH patients. Recently the Relationship between inflammation and the early phase role of neuroinflammation is frequently raised as regards the SICH of cerebral venous thrombosis course. In stroke patients common inflammatory agents and cytokines were proved to be elevated and so were markers of neuronal damage. S. Kamisli, O. Kamisli, S. Gonullu¨, C. Ozcan, Y. Kaplan We aimed to establish the relationship between these biomarkers Inonu University (Malatya, TR) and the functional outcome within one week from SICH onset. Objective: Venous stasis, genetic and acquired factors, and inflam- Methods: Forty nine consecutive SICH patients were included in mation are important in the formation and re-canalization of cerebral the study. Serum was collected on admission, within 24, 48, 72 h and venous thrombosis (CVST). In this study, we investigated important on day 7 after SICH onset. CRP, WBC, Fibrinogen, IL-6 and S100B inflammation indicators such as total white blood cell, neutrophil, concentration was measured. Functional outcome was evaluated by and lymphocyte counts and the neutrophil and lymphocyte ratio means of modified Rankin Score (mRS) at one and three months from during the early phase of CVST. We also determined whether there admission. was a relationship between these parameters and intraparenchymal Results: WBC and S100B during the first 3 days, CRP and lesions Fibrinogen during the whole week excluding day of admission as well Methods: Thirty-five patients with a diagnosis of CVST during the as IL-6 during the whole observational period were significantly early phase were included. The patients were divided into two sub- related to mRS score at one and three months. groups based on the presence or absence of parenchymal lesions. Conclusion: Both markers of inflammation and neuronal damage Twenty patients without parenchymal lesions were classified into are associated with the functional outcome after SICH. This relation group 1, and 15 patients with parenchymal lesions were classified into is preserved at least over the week after disease onset. This implicates group 2. The control group consisted of 27 healthy subjects. All that neuroinflammation may be involved in the secondary brain injury groups and subgroups were compared for complete blood cell counts. during the course of SICH. Since this could be a potential target for Results: Leukocyte and neutrophil counts were similar, whereas SICH therapy further studies are vital to strengthen this observation. lymphocyte counts were significantly lower and the neutrophil/lymphocyte ratio was significantly higher in all groups, as compared to those in the control group. Lymphocyte counts were significantly P367 lower and leukocyte and neutrophil counts and the neutrophil/lymphocyte ratio were significantly higher in group 1 than those in the Steroid-responsive late symptomatic perihematomal control. oedema in intracerebral haemorrhages Conclusions: A relationship may exist between inflammation and E. Altindag, O.G. Tuncer, B.A. Koyuncu, S.T. Ozkan, the level of illness severity in patients with CVST on admission. This R. Tolun, Y. Krespi relationship may guide the treatment and prognosis of CVST. Florence Nightingale Hospitale (Istanbul, TR); Istanbul Bilim University (Istanbul, TR) Objectives: Intracerebral hemorrhage (ICH) is the most devastating subtype of stroke, causing high mortality, morbidity and disability. P369 While the evolution of mass effect after cerebral infarction is rela- Cerebral venous sinus thrombosis: a follow-up study tively well characterized, there is only limited knowledge about M. Krommyda, J. Rudolf, A. Mastrokosta, D. Kiourtidis, perihematomal edema in ICH which develops at 2 distinct time T. Tsironis, G. Xiromerisiou, P. Petrou, C. Zakestidis, points: within 2 days, associated with hematoma enlargement and in the second or third weeks, simultaneously with hematoma resorption. I. Tsiptsios The clinical significance and treatment of later developing edema in Papageorgiou General Hospital (Thessaloniki, GR) ICH is unclear. Objectives: Cerebral venous and sinus thrombosis (CVST) is a rare Cases and results: Out of 99 consecutive ICH patients prospec- condition, which accounts for\1 % of all strokes. It may present with tively registered to Florence Nightingale Stroke Database between a wide spectrum of clinical symptoms and may lead to severe mor- March 2005 and December 2011, we present 3 patients (3.03 %) with bidity and mortality, in case of delayed diagnosis and treatment. The clinical deterioration due to late perihematomal edema. They were aim of this study is to investigate the clinical, etiological, diagnostic aged 55 to 76 years, and showed a slow and progressive decline of features and risk of recurrence of CVST in a cohort of patients consciousness and initial focal neurological deficits that was detected diagnosed at our hospital. 12 to 20 days later after onset. Their diagnoses were hypertensive left Methods: The retrospective and prospective data of patients with putaminal hematomas in 2 patients and right frontal lobar hematoma radiologically confirmed CVST during the years 2002-1012 were due to cerebral amyloid angiopathy in the other. All patients showed collected from the clinical records and the electronic database of remarkably large perihematomal edema in cerebral tomography and/ Papageorgiou General Hospital in northern Greece. or magnetic resonance imaging compared to baseline neuroimaging Results: 29 patients (18 females), median age of 38.5 years studies. Late edema developed despite reduction in hematoma volume (range: 16-62), were studied. In most cases (25) the primary clinical either spontaneously or surgically. Initiating steroid therapy resulted symptom was acute cephalalgia. The first neurological exam 123 J Neurol (2012) 259 (Suppl 1):S1–S236 S77 revealed pathological findings in 17 cases. Epileptic seizures P371 occurred in 17.2 %. The most common predisposing factors were Corticosteroid-induced cerebral venous sinus postpartum condition (17.2 %) and treatment with prothrombotic drugs - including substitutive hormones and oral contraceptives thrombosis in a patient with clinically isolated (10.3 %). Superior sagittal sinus (72.4 %) was most commonly syndrome and mild hyperhomocysteinaemia involved. Concomitant complications were observed in 27.6 % (e.g. E. Andreadou, A. Papathanasiou, emergency admission to the intensive care unit, persistent epileptical M.-E. Evangelopoulos, P. Davaki seizures, chronic cephalalgia). Mortality rate was 3.5 % (1 patient National and Kapodistrian University of Athens (Athens, GR) with congestive heart failure, dysregulated diabetes mellitus and arterial hypertension). Until today, two CVST have recurred during Introduction: Cerebral venous sinus thrombosis (CVT) is an uncom- the follow-up period. mon type of stroke, usually affecting young individuals. CVT Conclusion: CVST can be a life-threatening condition with various represents 0.5-1 % of all strokes. Several drugs-among them steroids- complications. Diagnosis is still frequently overlooked or delayed as a have been considered as predisposing factors for CVT. Moreover, result of the variety of initial neurologic symptoms and the often hyperhomocysteinaemia is a risk factor for CVT, being present in subacute onset. Clinical awareness of this multi-factorial condition is 27–43 % of patients. very important, in order to suspect and recognize it before major Case presentation: A 39-year-old female was admitted to our stroke symptoms. The follow-up of these patients is mandatory in hospital for evaluation of a three-day history of lower limbs numb- order to determine the duration of anticoagulation treatment after ness. Neurological examination revealed dysesthesias extending from CVST and prevent recurrence. L3 to T5 level, bilaterally. Brain MRI revealed few hyperintense lesions in periventricular white matter and thoracic spine MRI an intramedullary lesion at T3 vertebral level, all without gadolinium enhancement. Cervical spine MRI and CSF were normal. The patient P370 was treated with intravenous corticosteroids for five days and was discharged with the diagnosis of Clinically Isolated Syndrome (CIS). A challenging case of pseudotumour cerebri Few hours later, she developed right hemiparesis and was re-hospi- F. Correia, C. Cruto, I. Rego, J.P. Pereira, talized. Brain MRI revealed a venous infarct in left frontal lobe due to L. Paris, N. Vila-Cha˜ superior sagittal sinus thrombosis that was confirmed with MRV. The Hospital Pedro Hispano (Matosinhos, PT); Centro Hospitalar do Porto patient was treated with anticoagulants that resulted in complete (Porto, PT) resolution of her hemiparesis within a week. Thorough rheumatologic evaluation, CT of chest-abdomen and mammography were normal. Introduction: Intracranial dural arteriovenous fistulas are rare lesions Laboratory evaluation for disorders of haemostasis revealed mild that can occur anywhere within the dura mater and patients may be hyperhomocysteinemia with homozygous methylenetetrahydrofolate clinically asymptomatic or may experience symptoms ranging from reductase (MTHFR) polymorphism. During 7 months of follow up, mild symptoms to fatal hemorrhage, according to the location and the the patient remains symptom-free. Brain MRI revealed recanalisation type of venous drainage. The syndrome of pseudotumor cerebri might of the occluded sinus, whereas the periventricular hyperintense be a form of presentation, and the diagnosis of these lesions will lesions remained unchanged. Thoracic spine MRI did not reveal any become a clinical challenge. change. Her autoimmune profile remains negative. Clinical case: We reported a 69 years old man referred to the Conclusion: CVT is typically multifactorial. In a large multicentre emergency room with a history of headache and progressive loss of prospective cohort study, about half of the patients had more than one vision, with 4 months of evolution. The neurological examination cause or predisposing factor. Herein we report superior sagittal sinus revealed bilateral papilledema and diminished visual acuity, thrombosis during treatment with corticosteroids in a patient with remaining normal the rest of the examination. The Head CT and CIS. It could be hypothesized that the mild hyperhomocysteinemia cerebral angiography showed suggestive images of superior longi- associated with homozygous MTHFR polymorphism in combination tudinal sinus thrombosis in the process of recanalization. On lumbar with the use of steroids might have predisposed our patient to CVT. puncture an increase in the CSF opening pressure was documented ([ 50 cmH20) with a normal cytochemical study. With the suspicion of intracranial hypertension secondary to venous thrombosis the patient started the oral hypocoagulation and the symptomatic treat- P372 ment with oral acetazolamide. As he still had headache and Soluble thrombomodulin and endothelial cell protein C deterioration of visual acuity he was proposed to place the lumbo- receptor levels in patients with cerebral venous sinus peritoneal shunt. Two days after placement of lumbar intrathecal drain he got into a convulsive status epilepticus. After reviewing the thrombosis angiography it was hypothesized a dural arteriovenous fistula. After M. Saadatnia, T. Shahsavarzadeh, S. Haghjoo, making a classical angiogram, which confirmed the diagnosis of left M. Tajmirriahi sigmoid sinus fistula of high speed, the partial embolization was Isfahan University of Medical Science (Isfahan, IR) implemented. At the end of the procedure, the evolution was favorable, without registering new crises, and verifying improve- Introduction: Cerebral venous and sinus thrombosis (CVST) is a ment of headache and visual acuity. potentially serious disorder. In search for underlying coagulopathy in Conclusions: We intend to emphasize that in cases of intracranial CVST patients, the plasma levels of soluble thrombomodulin (sTM) hypertension due to dural fistula it is necessary to conduct a detailed and soluble endothelial protein C receptor (sEPCR) in patients with vascular study using a classic angiography considering that CT CVST has been measured as candidate biomarkers of thrombosis. angiography and MRI brain may be normal or suggest another Materials and Methods: The concentrations of sTM and sEPCR in diagnosis, such as the presented case. The normality of the imaging 19 CVST patients without protein C (PC) and protein S (PS) defi- study might suggest a false benignity of the clinical picture and ciency has been measured by ELISA and compared with 53 healthy leading to the realization of contraindicated procedures and delaying controls. We also examined the association between those plasma the etiological diagnosis. markers and the risk of CVST.

123 S78 J Neurol (2012) 259 (Suppl 1):S1–S236

Results: Significant difference was identified in plasma sTM level Background: Atrial fibrillation (AF) is the most common cause of between CVST patients and controls [0.95 ± 0. 09 vs. 1.26± 0.12 cardioemboligenic ischemic stroke (IS). Patients with cardioem- (ng/ml) respectively; p = 0.038]. The plasma level of sEPCR was not boligenic IS and AF often present with more severe neurological different between groups and no significant quantitative association deficit associated with the occlusion of the large cerebral artery, was identified between the risk of CVST and the levels of sEPCR. worse clinical outcome and higher mortality. Especially paroxysmal The adjusted Odds Ratio for CVST associated with low (\10th perform of AF is high risky, because it is usually not being regis- centile) levels of sTM was 2.3(95 % CI, 1.29 to 20.08, p = 0.012) tered during a routine electrocardiogram (ECG) examination. The after adjustment with age and sex. aim was to assess the benefit of the early 24-hour Holter-ECG Conclusion: Decreased plasma sTM concentration may be asso- monitoring in patients with ischemic stroke and a negative history ciated with an increased risk of CVST. of AF. Methods: In the prospective study, the set consisted of 114 consecutive IS patients (57 males, average age 75.4 ± 9.8 years) with a negative history of AF and without the presence of AF on the P373 admission ECG exam. A standard 24-hour Holter-ECG was performed in all patients. Neuropsychiatric symptoms and quality of life of people Results: Thirty-three (28.9 %) patients had concurrent ischemic with dementia in shared-housing arrangements heart disease, 14 (12.3 %) had a positive history of myocardial J. Gra¨ske, A. Worch, S. Meyer, K. Wolf-Ostermann infarction and, 25 (22 %) a history of previous IS. Holter-ECG was Alice Salomon University of Applied Sciences (Berlin, DE) performed on average 4.1 ± 2.5 days after the IS onset. Newly detected AF was found in 10 (8.8 %) patients (paroxysmal form of Objectives: During the last years new living arrangements for people AF in 90.0 % out of these patients). No acute ischemic changes were with dementia (PwD) evolved in Germany. Shared-housing arrange- recorded on admission ECG in all patients. ments (SHA) are small-scale care arrangements completely Conclusion: Holter-ECG monitoring is a noninvasive and inex- disconnected from traditional residential facilities. On average 6-8 pensive method used for the early detection of AF, particularly of its PwD live together in one flat assisted by community care services paroxysmal form. The risk of recurrent stroke can significantly providing care in a home-like environment. SHA are considered to be reduced in IS patients with diagnosed AF using the anticoagulant beneficial in terms of residents‘ neuropsychiatric symptoms as well as therapy. their quality of life (QoL). The specific aim of the presentation is to Acknowledgement: Supported by the IGA MH CR grant number provide an overview on residents´ characteristics, as well as to analyse NT/11046-6/2010. changes in residents´ neuropsychiatric symptoms and QoL when especially focusing on quality of neurological health-care provision. Method: A cluster-randomized longitudinal study (2009-2012), performing face-to-face interviews with residents and staff in SHA P375 was conducted. Besides socio-demographic characteristics, residents´ neuropsychiatric symptoms (NPI) and QoL (QUALIDEM) were Head-up tilt test and r-r interval variation assessed in an intervention (improved neurological service) and a in the assessment of the autonomic nervous system control group (service as usual) for a one-year follow-up. in leprosy patients Results: 55 women and 16 men (mean age 79.0 years) participated R. Yiðiter, H. Ulvi in the study. 85.5 % of the participants are with dementia. Addi- Gaziantep University (Gaziantep, TR); Atatu¨rk University tionally about 20 % were suffering from other diseases of the nervous (Erzurum, TR) system, e.g. Morbus Parkinson. The cognitive screening at baseline (mean MMSE 11.5) indicated severe impairments. On average, the Backgound: The aim of this study was to compared being more residents show 1.5 neuropsychiatric symptoms at baseline and follow- effective in evaluating possible autonomic nervous system (ANS) up. The QoL remains nearly unchanged over time, reaching a mod- dysfunction in leprosy patients with head-up tilt test, the R–R (heart erate level and correlating weakly to moderate with cognitive rate) interval variation (RRIV) measurements during at rest and deep functioning. The overall QoL is significantly confounded by anxiety, breathing which are easy and reliable methods for evaluation of depression, and appetite (ANCOVA, p \ 0.001, R2 0.538). The use autonomic functions. of neurological services increased in the intervention group and Materials and methods: We studied 28 affected people (mean age: decreased in the control group. No impact on residents’ neuropsy- 35, 13 female and 15 male) and 35 age-matched healthy subjects chiatric symptoms and QoL could be established (all ANOVA (mean age: 34, 20 female and 17 male). Non-invasive head-up tilt p [ 0.05). test, the RRIV recordings on precordial region during at rest and deep Conclusion: Residents in the new setting SHA have various neu- breathing, and nerve conduction parameters were studied using an rological deficits and impairments. Further research may help to electromyogram (EMG) equipment in all the subjects. implement better structures of care for residents with neuropsychiatric Results: The mean values of ‘’30/15’’ head-up tilt test (in patients, symptoms to address their needs and improve their QoL. 0,97±0,46 vs controls, 1,12 ± 0,30 [p\0.05]) was significantly lower compared with the controls. The mean values of RRIV in leprosy patients during at rest (mean RRIV in patients, 18.41 %±7.63 % vs controls, 23.70 % ± 3.74 % [p\0.05]) and during deep breathing P374 (mean RRIV in patients, 22.65 % ± 8.07 % vs controls, 31.73 % ± The benefit of early Holter-ECG monitoring 6.97 % [p\0.005]) was significantly lower compared with the con- for the detection of paroxysmal atrial fibrillation trols. Out of 28 leprosy patients, 19 (67,85 %) showed abnormalities in patients with acute ischaemic stroke – pilot study head-up tilt test and 11 (47,6 %) abnormal RRIV during normal breathing and 20 (95,2 %) abnormal RRIV during deep breathing. M. Kral, D. Sanak, M. Hutyra, T. Veverka, A. Bartkova, Abnormal head-up tilt test were more pronounced in leprosy patients R. Herzig, D. Skoloudik, M. Taborsky, P. Kanovsky with clinical orthostatic functional abnormalities than those without University Hospital Olomouc (Olomouc, CZ) orthostatic functional abnormalities.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S79

Conclusions: RRIV and head-up tilt test which can be easily and Targeting the vicious oxidative stress-inflammation cycle may be an rapidly performed in an EMG laboratory can provide useful, objective effective strategy to reduce cell damage after ischemia. 4-hydroxy- information. RRIV during deep breathing are more sensitive than benzyl alcohol (4-HBA), one of the phenolic constituents widely head-up tilt test, but combined use of these three tests are more distributed in various kinds of plants, including Gastridua elata Blame effective (Orchidaceae) (Tian ma in Chinese), has been shown to exhibit a protective effects against cerebral injury. In the present study, we evaluated the molecular mechanisms involved in this effect. Methods: We used an in vivo ischemic model of middle cerebral P376 artery occlusion (MCAO) and an in vitro ischemic model of oxygen– Neuroprotective effect of Tanshinone IIA against glucose deprivation followed by reperfusion (OGD/R) to mimic cerebral ischaemia/reperfusion injury through cerebral ischemia. Post-assessment included cell viability, neurobe- inhibition of macrophage migration inhibitory factor havioral testing, brain edema measurement, and quantification of neutrophil infiltration and microglia/macrophage activation. Anti- in rats oxidative and anti-inflammation mechanisms were studied by Y. Chen, S. Yu, J. Zhao immunochemistry, western blotting and electrophoretic mobility shift Chongqing Medical University (Chongqing, CN) assay (EMSA). Results: 4-HBA administration markedly reduced superoxide Objectives: Ischemia/reperfusion (I/R) injury is associated with sys- generation and inhibition of nitric oxide (NO) and inducible nitric temic inflammatory response. Macrophage migration inhibitory factor oxide synthase (iNOS) in the ischemic brain and decreased the (MIF) has been implicated in many inflammatory processes. Tan- intracellular oxidative stress caused by OGD/R. After treatment, shinone IIA (TSA) is one of the active ingredients in danshen. Recent 4-HBA decreased neutrophil infiltration and microglia/macrophage studies have demonstrated that TSA has protective effects against activation in parallel with nuclear factor-erythroid 2-related factor 2 focal cerebral I/R injury. However, little is known regarding the (Nrf2) expressions. 4-HBA also enhanced the expression of genes underlying mechanisms. Herein, we put forward the hypothesis that involved in the Nrf2-regulated stress pathway (NAD(P)H:quinine the effect of TSA through inhibit MIF expression on focal cerebral oxidoreductase 1(NQO1), heme oxygenase-1(HO-1), peroxiredoxin I/R injury in rats. 6), leading to increased antioxidant capacity in the plasma. Further- Methods: Rats were subjected to middle cerebral artery occlusion more, this correlated with the suppression of nuclear factor-kappaB (MCAO) for 2 h followed by reperfusion. We measured neurological (NF-kappaB), cyclooxygenase-2(COX-2) and pro-inflammatory deficits, brain water content, infarct volume and myeloperoxidase cytokines, including interleukin-1 (IL-1) and tumor necrosis factor - (MPO) activity by appropriate methods. We measured MIF, tumor alpha (TNF-alpha). necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) expres- Conclusion: Our study indicates that 4-HBA could be useful for sion in the brain using enzyme linked immunosorbent assay (ELISA) the treatment of cerebral ischemia/reperfusion injury. 4-HBA may 1 h, 3 h, 6 h, and 24 h after reperfusion. We also measured the play an important role in defense against oxidative stress possibly by expression and location of MIF using Western blot analysis and activation of cellular antioxidant machinery as well as suppression of immunofluorescence staining and measured the expression and acti- pro-inflammatory signaling pathways. vation of nuclear factor kappaB (NF-kappaB) using Western blot and electrophoretic mobility shift assay (EMSA) analysis 24 h after reperfusion. Results: Neurological dysfunction, brain edema, and brain infarction were significantly attenuated by TSA 6 h after reperfusion. P378 At 6 and 24 h, neutrophil infiltration was significantly higher in the Effects of simvastatin on the expression of bradykinin vehicle group than in the TSA group. ELISA demonstrated that TSA receptors in penumbra after focal cerebral ischaemia- could inhibit MIF expression and the release of TNF-alpha and IL-6 reperfusion in rats induced by I/R injury. Western blot analysis and immunofluorescence staining showed that MIF expression was significantly decreased in Y.D. Zhang TSA group compared to vehicle group. MIF was found almost all Nanjing First Hospital (Nanjing, CN) located in neurons and hardly any located in astrocytes in the cerebral Aim: To determine the effects of simvastatin on the expression of cortex. Western blot analysis and EMSA demonstrated that NF-kap- bradykinin receptors in penumbra after focal cerebral ischemia - paB expression and activity were significantly increased in the vehicle reperfusion in rats. group. However, these changes were attenuated by TSA. Methods: Seventy-two male SD rats were randomly divided into Conclusion: We here conclude that TSA helps alleviate the pro- three groups, sham-operation group, cerebral ischemia–reperfusion inflammatory responses associated with I/R-induced injury and that group (0.9 % saline), simvastatin preconditioning group (10mg/kg.d), this neuroprotective effect may occur through downregulation of MIF which received pretreatment 14 days, respectively. The model of expression. middle cerebral artery occlusion (MCAO) was established according to the method reported by Longa except sham-operation group. Each group was further divided into three sub-groups at 3 h, 24 h and 48 h P377 after reperfusion, and each subgroup consisted of eight rats. At 3 h, 24 h and 48 h after reperfusion, the animals were observed for neuro- 4-hydroxybenzyl alcohol ameliorates cerebral logical deficits and the brain tissue morphology by neurological ischaemic injury by suppression of oxidative stress function score and HE staining, the levers of mRNA of BK-1Rs and and inflammation BK-2Rs were detected by fluorescent quantitative RT-PCR. S. Yu, Y. Zhao, J. Zhao, Y. Chen, L. Li Results: Compared with that in the ischemia–reperfusion group, the neurological function was significantly improved, the neurological Chongqing Medical University (Chongqing, CN) function scores (P\0.05, P\0.05, P\0.01) were reduced in 3 h, 24 h, Objective: Two important pathophysiological mechanisms involved 48 h simvastatin preconditioning group, and the pathological damages during ischemic stroke are oxidative stress and inflammation. were reduced in simvastatin preconditioning group. Compared with

123 S80 J Neurol (2012) 259 (Suppl 1):S1–S236 those in the sham-operation group, fluorescent quantitative RT-PCR ischemic cerebral tissue, as well as its effect on electroencephalog- analysis showed that the mRNA levers of BK-1Rs and BK-2Rs in raphy, an indicator of neuronal activity, in rats with experimentally ischemia penumbra significantly decreased in 3h ischemia–reperfu- induced cerebral ischemia–reperfusion. sion group (P\0.05, P\0.01). Compared with those in the ischemia– Material and Method: The study included 21 Wistar albino type reperfusion group, the mRNA levers of BK-1Rs and BK-2Rs in female rats, weighing about 300 to 350 gr. The rats were divided into ischemia penumbra significantly increased in 3h preconditioning 3 groups with 7 rats in each. EEGs of all rats were recorded for group (P\0.01, P\0.05). Compared with those in the sham-operation 10 min. Then, the first group was administered 30 mg/kg bosentan in group, the mRNA levers of BK-1Rs in ischemia penumbra signifi- 2 cc serum physiologic and second and third groups were injected cantly decreased in 24h, 48h ischemia–reperfusion group (P\0.01, with 2 cc serum physiologic through the intraperitoneal route. After P\0.01). Compared with those in the ischemia–reperfusion group, the the administration, right carotid communis of the animals in groups 2 mRNA levers of BK-1Rs in ischemia penumbra significantly and 3 were clipped for 10 min using aneurysm clippings. The rats in increased in 24h, 48h preconditioning group (P\0.01, P\0.01). the third group received only a subcutaneous incision. Ten minutes Conclusion: Pretreatment with simvastatin before cerebral ische- after the clips were removed in the first and second groups and after mia/reperfusion injury in rats reduced the neurological deficits and the incision in the third group, EEG recording was repeated for improved brain tissue pathomorphology, the beneficial effects of 10 min. Then all the rats were decapitated and malondialdehyde acid simvastatin may be partly mediated by an increased expression of values in the brain tissue were compared. BK-1Rs and BK-2Rs in the ischemia penumbra. Results: EEG showed minimal slowing in the left hemisphere of the rats in group 1 relative to pre-procedure values and generalized diffuse slowing all across the left hemisphere in the rats in group 2 in comparison to pre-procedure values. No difference was observed in P379 the pre- and post-procedure EEGs of the rats in group 3. The com- Curcumin inhibits oxidative stress after focal cerebral parison between malondialdehyde acid levels in the cerebral tissues of the rats in groups 1 and 2 did not reveal a statistical difference ischaemia/reperfusion injury in rats via PI3K/Akt (p [=0.05).However, when the values in these two groups were pathway compared to those in group 3, the former was found higher (p\0.05). J. Zhao, S. Yu, J. Wu, Y. Zhao Conclusion: It is speculated that bosentan molecule may reduce Chongqing Medical University (Chongqing, CN) the damage induced by ischemia on neuronal physiology probably through its vasodilating effect on cerebral vessels in rats with induced Objective: Curcumin, a member of the curcuminoid family of com- ischemia–reperfusion. pounds, is a yellow colored phenolic pigment obtained from the powdered rhizome of C. longa Linn. Recent studies have demonstrated that curcumin has protective effects against cerebral ischemia/ reperfusion injury. However, little is known about its mechanism. In Neuro-imaging the present study, we investigated whether curcumin protects brain and reduced oxidative damages via phosphatidylinositol 3-kinase(- PI3K)/Akt pathway in a rat model of focal cerebral ischemia/ reperfusion. P381 Methods: Adult male Sprague–Dawley rats were pretreated with Cervical cord atrophy in hereditary spastic paraparesis curcumin (300mg/kg, i.p.) or combined with LY294002 1h before F. Agosta, M. Scarlato, G. Longoni, P. Valsasina, MCA occlusion. Physiological parameters and infarct volume were assessed at 24h of reperfusion after 1h of occlusion. Oxidative stress M. Sessa, M.T. Bassi, M. Ferrari, A. Falini, G. Comi, was evaluated by malondialdehyde and superoxide dismutase assays. M. Filippi Anti-oxidative mechanisms were studied by immunohistochemistry Vita-Salute San Raffaele University (Milan, IT); E. Medea Scientific and Western blotting. Institute (Bosisio Parini, IT) Results: Curcumin treatment significantly reduced infarct volume Objective: Hereditary spastic paraplegia (HSP) is a genetically het- and oxidative stress levels compared with the I/R group. Curcumin erogeneous group of neurodegenerative disorders characterized by increased phospho-Akt, nuclear factor-erythroid 2-related factor progressive lower limb weakness and spasticity. Neuropathological 2(Nrf2) and NAD(P)H:quinone oxidoreductase1(NQO1) expression, studies of HSP described axonal loss involving corticospinal and hence, these effects were all suppressed by LY294002. somatosensory tracts in the spinal cord. In HSP, the in vivo investi- Conclusions: These findings indicate that curcumin inhibits oxi- gations of the spinal cord using magnetic resonance imaging are rare dative stress after focal cerebral I/R injury. This neuroprotective and almost limited to single cases. In this study, a new semiautomatic effect is likely achieved by activation of PI3K/Akt pathway. method for segmenting the cervical cord from C2 to C5 was used to investigate the cervical cord atrophy in patients with HSP. Methods: T2 and 3-dimensional T1-weighted cervical cord scans P380 were acquired from 42 patients with HSP (20 pure HSP and 22 Effect of bosentan on lipid peroxidation complicated HSP), and 20 sex- and age-matched healthy controls. Normalized cervical cord cross-sectional area (CSAn) was measured and electroencephalography in rats with induced by an active surface cord model. Between-group comparisons were cerebral ischaemia-reperfusion performed using linear mixed-effect models adjusted for subject’s age. M.S. Berilgen, M. Kaplan, B. Akgun, A. Sari, H. Ozdemir, Results: The mean CSAn was 89.8 mm2 (standard deviation [SD] 2 C.F. Demir 6.8) in healthy controls, 74.9 mm (SD 8.9) in pure HSP patients, and 73.1 mm2 (SD 8.2) in complicated HSP patients. Cord CSAn was Firat University (Elazig, TR) lower in both pure and complicated HSP patient groups compared Objective: In the present study we aimed to examine the effect of with healthy controls (p\0.001). No difference was found between bosentan, an ETA-ETB antagonist, on lipid peroxidation in the the two patient groups.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S81

Conclusions: This study indicates that spinal cord atrophy is a number of CT scans performed; would save millions of dollars in common finding in pure and complicated HSP. Cervical cord atrophy unnecessary scans and reduce emergency and radiology department provides a relevant and useful marker for the characterization of overcrowding. There are a few decision rules proposed in developed patients with HSP. countries. We have already developed a decision rule for CT scanning of MHI patients of developing countries and rural regions, in the year 2009. The aim of this study was to update the decision rule using a P382 larger sample size. Neural plasticity of brain motor networks Methods: Six hundred patients with history of blunt head trauma and Glasgow Coma Score (GCS)[13 presented within 12 h of trauma in professional fencers studied with functional MRI were studied. They all underwent non enhanced brain CT scanning. L. Parisi, M.A. Rocca, L. Leocani, R. Gatti, C. Castellani, Those findings which necessitate neurosurgical care (either M. Rossi, A. Falini, G. Comi, M. Filippi observation or intervention) were selected as positive finding. Vita-Salute San Raffaele University (Milan, IT) Logistic Regression method was utilized to develop the decision rule. Objective: Bilateral, symmetrical movements of limbs with respect Results: A normal GCS did not guarantee the absence of signifi- to the longitudinal axis of the body are performed more accurately cant neurological injury. Presence of any of the following symptoms than asymmetrical ones. Ipsilateral coordination of wrist and foot is or signs was indicator of a neurological finding in CT: GCS score \ easier if limb segments move in the same (in-phase) than in the 14, a sign of base skull fracture, failure to remember the impact, age[ opposite (anti-phase) direction. Fencing requires an optimal level of 65 years, vomiting after impact. Moreover presence of both of the interlimb coordination and asymmetrical motor skills. Using func- following signs was associated with intracranial lesion: scalp wound, tional magnetic resonance imaging (fMRI), we investigated the GCS score \ 15. brain areas involved in interlimb coordination in young high-level Conclusion: This decision rule needs less clinical expertise and is professional fencers in comparison to matched young, untrained useful for general practitioners in rural areas and developing subjects. We hypothesized that an intensive and continuous motor countries. This version of criteria, while in agreement with the training in fencers could optimize the recruitment of their neural previously published version, resulted in better specificity after a networks. minor modification. However, this decision rule is only useful to Methods: fMRI during the performance of bimanual anti-phase, detect the MHI patients who SHOULD be examined by CT scan. It right hand-foot in-phase and right hand-foot anti-phase movements needs to be validated in much larger populations to be suitable to was acquired from 14 high-level professional fencers (mean age=21.5 exclude MHI patients from being studied, despite of a clinical years; mean age at starting professional activity=8.9 years; mean judgment. weekly training=11 h) and 15 controls (mean age=21.7 years), who This study was supported by Sina Trauma Research Center, did not practice any continuous physical activity. affiliated to Tehran University of Medical Sciences, Tehran, Iran. Results: During bimanual movements, controls vs. fencers had an increased recruitment of areas known to be involved in bimanual tasks. Fencers vs. controls had an increased activation of the right (R) pallidum and left (L) postcentral gyrus. During R hand-foot in- phase movements, controls vs. fencers had an increased activation of P384 the R cerebellum, while fencers had higher recruitment of several Pseudotumoural cerebral lesion in a young female frontal areas. During R hand-foot anti-phase movements, controls vs. patient fencers had an increased activation of the R cuneus. During the three D. Popescu, A. Mergeani, C. Laza, O. Bajenaru, F. Antochi motor tasks, the motor cortex (left and right hand and left foot areas) Bucharest University Emergency Hospital (Bucharest, RO) had an increased functional connectivity with bilateral fronto-temporal areas and thalami in fencers, and with bilateral cerebellum and Objective: Pseudotumoral lesions of the central nervous system pose a temporo-parietal areas in controls. difficult problem in terms of differential diagnostic. Antibodies Conclusions: Specific intensive motor training can modulate against neural surface antigens are associated with different central neural plasticity of cerebro-cerebellar-basal ganglia loops involved in nervous syndromes but their presence doesn’t necessarily mean a interlimb coordination and their functional connectivities. paraneoplastic etiology. A pathogenic role of the antibodies is suggested by the response of symptoms to immunotherapy and the correlation between antibodies titer and neurological outcome. Anti- bodies to voltage-gated potassium channels (VGKC) have been P383 associated with non-paraneoplastic limbic encephalitis and case A decision rule to order CT scanning in minor head reports of Morvan syndrome or isolated epilepsy. injury Methods: We present a case of a young female who was referred S. Saadat, S.M. Ghodsi, M. Shakouri to our clinic for further investigation of a left side hemiparesis due to a cerebral mass located in the right cerebral hemisphere. The Sina Trauma Research Center, Sina Hospital, Tehran University of MRI of the brain revealed a cerebral mass located in the right Medical Sciences (Tehran, IR) hemisphere with hyperintensity on T2/FLAIR not confined to a Objectives: It is estimated that about 2 million blunt head trauma vascular territory, with diffusion restriction and mass effect, sub- occur in the United States (US), annually. The majority of them are cortical hemorrhage and a small lesion in T2 in the left hemisphere. classified as Minor Head Injury (MHI). Prevalence of significant Due to this mass the patient needed an urgent craniotomy to intracranial lesion in brain Computerized Tomography (CT) scan of decompress the swollen brain. MHI patients ranges from 0.7 % to 20 %. Since most of these patients Results: The patient had elevated titres of antibodies directed have insignificant injuries which require no specific therapy, the against voltage-gated potassium channel and respond well to intra- indications of CT scanning in MHI patients is still under debate. venous immunoglobulins. After the lumbar puncture the patient Using decision rules which help physicians to identify patients developed paradoxical intracranial hypotension which resolved after a with clinically important lesion on CT scan while reducing the few days.

123 S82 J Neurol (2012) 259 (Suppl 1):S1–S236

Conclusion: Our choice to present this case is due to unusual Lateral meningocele Syndrome is a rare disorder, described by presentation of a central nervous system voltage-gated potassium Lehamn et al. and subsequently reported in less than ten patients. channel autoimmunity as a life-threatening pseudotumoral cerebral These patients present some distinctive craniofacial features and lesion. The spectrum of neurologic manifestations and neoplasms skeletal abnormalities in addition to the multiple lateral meningoce- associated with voltage-gated potassium channel (VGKC) autoim- les, suggesting a connective tissue disorder. Autosomal dominant munity is broad. Evaluation for VGKC antibodies is recommended in inheritance was suggested in one single family. the comprehensive autoimmune serologic testing of subacute idio- We present a case of a 5 year old male, born from healthy parents. pathic neurologic disorders. This is a rare case of pseudotumoral The pregnancy was complicated by a cystic hygroma diagnosed at 12 lesion of the central nervous system associated with voltage gated weeks of gestation. He was delivered at full term by elective cesarean potassium channels antibodies. section, and Apgar scores were 8 at the first minute and 10 at the fifth minute. Anthropometric measures were adequate for gestational age. He was admitted to the Neonatal Intensive Care Unit for presenting general hypotonia and feeding difficulties. Additionally he had P385 bilateral ptosis, microretrognathia, low-set hears and an empty scro- Unusual localisation of central nervous system tum. Cardiologic observation showed a bicuspid aortic valve. At two toxoplasmosis in an HIV-negative immunocompetent years of age he was diagnosed with severe upper airway obstruction, sleep apnea and conductive hearing loss due to adenoid and tonsil male patient – case presentation hypertrophy. He underwent adenoidectomy as well as surgical cor- C. Laza, A.C. Mergeani, D. Popescu, O. Bajenaru, rection of retrognathia. Ophthalmologic observation showed a F. Antochi bilateral restriction in upward gaze. At the age of five, he had several University Emergency Hospital (Bucharest, RO) dysmorphic features such as hypertelorism, telecanthus, downslanting palpebral fissures and bilateral ptosis, low-set hears, micrognathia Objectives: to present the case of a 51 year-old male patient admitted with a high and narrow palate and dental crowding. Skin keloid to the hospital for diffuse intermittent headaches for the past month scarring from surgical interventions and joint laxity were also and facial asymmetry, dysarthria and slight decrease in muscle apparent. The patient height was 107.5cm (P25) and weight was strength of the right limbs, gradually occurring over the last three 20.8 kg (P50). He had a mild mental retardation and a history of gross days prior to hospital admission. motor delay. He had no features of neurofibromatosis, Marfan or Methods: the patient has a history of left lower limb deep vein Hajdu-Cheney syndromes. Cerebral and spine magnetic resonance thrombosis – ten years ago – and no other significant comorbidities. showed scalopping of vertebrae and multiple thoracic, lumbar and He denies smoking, alcohol/drug abuse. On admission the patient was sacral bilateral meningoceles. No hypoplasia of C1 or any patholog- stable, regular blood work was normal. HIV testing was negative. The ical cerebral anomalies were observed. Abdominal and renal neurological examination revealed mild right side central facial ultrasound exams showed no abnormalities. Electromyography and paresis, mild right ataxic hemiparesis, dysarthria and bilateral Ba- muscle biopsy were normal. Routine chromosome analyses were binski reflex. The cerebral computed tomography (CT) showed a performed and had normal results. discreet central pontine hypodensity without contrast enhancement. The findings of a bicuspid aortic valve in association with joint The cerebral magnetic resonance imaging (MRI) showed a focal laxity and keloid scarring support the hypothesis of a connective bulbo-pontine lesion with moderate internal hemorrhagic trasnfor- tissue basis for this disorder and further expand the phenotype. mation and mild perilesional edema – suggestive of an inflammatory process. A lombar puncture was performed with normal cell count, chemistry and flow cytometry, negative for oligoclonal bands and with a normal serum/cerebrospinal fluid (CSF) albumin/immuno- P387 globulin G (IgG) index. The parasitological tests showed elevated No face in PHACE syndrome values of the Toxoplasma gondii IgG and IgM antibodies both in D. Alves, M. Sampaio, M. L. Ribeiro da Silva, M. Leaõ serum and CSF but with negative polymerase chain reaction (PCR) Centro Hospitalar de S. Joaõ (Porto, PT) for Toxoplasma gondii DNA in the CSF. Results: the evolution was favorable. After five days of intrave- PHACE syndrome is a neurocutaneous syndrome which encompasses nous steroidal anti inflammatory drugs and osmotic diuretics the a large hemangioma associated with one or more extracutaneous symptoms resolved and the dimensions of the pontine lesion and anomalies including posterior fossa malformations, arterial cerebro- perilesional edema decreased. After the CSF results antiparasitic vascular anomalies, cardiac defects, eye anomalies and sternal medication was initiated and the steroidal anti inflammatory treatment defects. Diagnostic major and minor criteria were recently published. was continued orally in progressively decreasing doses. Six months Definite PHACE syndrome is diagnosed in patients with a facial after the completion of the treatment the patient is free of symptoms hemangioma greater than 5cm in diameter plus one major or two and the cerebral MRI showed a sequellar vertical linear left para- minor criteria. Possible PHACE syndrome is considered as a diag- median PD/T2 hypersignal pontine lesion, without diffusion nosis if additional criteria regarding the extracutaneous restriction or contrast enhancement. manifestations are met, in a patient without hemangioma or with an Conclusion: we present this case because of the unusual locali- hemangioma of the neck or upper torso. In a recent prospective study zation of the central nervous system toxoplasmosis in a HIV-negative conducted in infants with large facial hemangiomas the incidence of immunocompetent patient. PHACE was 31 %. The incidence of PHACE in infants with small facial hemangiomas and of possible PHACE remains unknown. The most common extracutaneous manifestations of PHACE association are the cerebrovascular anomalies, which are also the P386 major contributors for the associated morbidity. The patients with Lateral meningocele syndrome: case report cerebral anomalous vasculature are at a higher risk for arterial ischemic stroke. D. Alves, M. Sampaio, R. Figueiredo, M. Leaõ We report a case of a patient with Possible PHACE presenting Centro Hospitalar de S. Joaõ (Porto, PT) with cerebral vascular anomalies, cardiac defect, anterior and

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S83 posterior segment ocular abnormality and sternal depression, without General University Hospital Camilo Cienfuegos (Sancti Spiritus, CU) any cutaneous anomalies. Unlike patients presenting with large facial Introduction: The cranioencephalics traumas are the third leading hemangiomas, in whom neuroimaging and detailed cardiac imaging cause of death in our country, motor vehicle accidents remain the are recommended for being at-risk for PHACE, patients without the leading cause of admission to the health units. Major complications in cutaneous manifestations are much more prone to under recognition the first few months are the bruises and post-traumatic epilepsies. of the serious extracutaneous anomalies, putting them at an even Objectives: Evaluation of quantitative EEG brain mapping in the higher risk of undiagnosed potentially life-threatening complications. first two weeks of trauma, with the aim of locating statisticians pre- Therefore, we suggest that a brain magnetic resonance angiogram dictive variables of these complications and to establish an effective should be performed in infants with cardiac defects associated with treatment for them in the initial stage. Methods. We scanned 52 ocular anomalies of the posterior segment, and no other recognised patients admitted to the Intensive Care Unit, 34 men and 18 women, syndromic association. This would not only contribute to the growing including at the ages of 18 to 65 years, with montage 10-20 in knowledge of PHACE’s natural history, but it would also aid in MEDICID 4. establishing imaging and screening protocols based on appropriate Results: The analysis by quantitative methods CROSS and risk stratification. BCROSS indicated the presence of delta activity focal polymorphic frontoparietals regions in 39 patients, with areas of low density and frequency of signs of moderate cortical dysfunction being operated on 34 patients by the presence of haematoma located these levels, 11 P388 patients showed paroxysmal activity focal centre-parietal, well AQP4 expression and diffusion tensor imaging in rat defined in the analysis of maps frequently by Mahalanobis, of whom brainstem after acute alcoholism 10 patients had partial seizures in the third week of trauma. The study H.M. Liu, W.B. Zheng, L.M. Kong, H.D. Zhang, R.W. Chen of evolution at the two and six months under treatment, we note only in 3 patients with delta activity and the persistence of paroxysmal Second Affiliated Hospital, Shantou University (Shantou, CN) activity in 15 patients, the intensity of cortical dysfunction very Objectives: The aim of the present study was to detect whether the lightly. changes of AQP4 expression consistent with DTI parameters Conclusions: The EEG quantitative are very important to estab- (Apparent diffusion coefficient and Fractional anisotropy) of rats lished a rapid and effective medical treatment in the first two weeks of brainstem in a model of experimental acute alcohol consumption. severe cranial trauma and to prevent late complications. Methods: Thirty male SD rats (weight ranged from 200g to 250g)were divided randomly into the control group (n=5) and acute ethanol intoxication group(A group, n=25). The alcohol group randomized into 5 subgroups(1h, 3h, 6h, 12h, 24h) (n=5). Each rat was imaged before P390 administration of ethanol and imaged at 1h, 3h, 6h, 12h, 24h post alco- The signal intensity changes of cervical spinal cord holism by conventional MR imaging and DTI. Brains were extracted fMRI with electrical stimulation after MR examination, histopathological examination was performed. Z. Shen, Y. Chen, W. Yang, Y. Xiao Histological examination including HE, silver staining, and immuno- Shantou University (Shantou, CN) histochemistry of AQP4. The results of conventional MRI and DTI were compared with the changes of histopathology found. Object: To investigate the signal intensity changes in functional Results: Histological examination showed cytotoxic edema of the magnetic resonance imaging (fMRI) activity in the cervical spinal brain in rats of acute alcoholism groups exhibiting the glials swelling. cord with electrical stimulation. In the alcohol group, AQP4 expression and ADC value were Method: The cervical spinal cord fMRI, using electrical simulation decreased in the brain stem of rats and reached the minimum value at (5-10 mA, 5Hz) at the right palm of the hand, were acquired form 8 3h compared to control group and pre-alcohol. Significant differences healthy volunteer at 1.5 T with a single-shot fast spin-echo imaging was found for AQP4 expression in 3h and 6h subgroups compared to sequence. The fMRI data was analyzed with SPM2 and the signal control group(p\0.01, p\0.05),but there was no significant difference intensity changes were performed with Marsbar. in 1h, 12h and 24h subgroups. FA value in each subgroup was Results: All subjects had activation localized at C5-C7 vertebral decreased, but no significant difference was detected compared to pre- level. Signal increases were measured in all subjects; however one alcohol. subject was ejected for the extreme high signal gain. The rest of Conclusion: ADC values may be a valuable biomarker in detecting average fractional signal change was 4.34±0.28 % at C5 (n=2), the cytotoxic edema of the brain in the early phase of acute alco- 10.33±5.81 % at C5/C6 (n=3), 1.51±3.01 % at C6 (n=6), 5.85 at C6/ holism. The decreased expression of AQP4 may reFLect an C7 and 9.92±4.77 % at C7 (n=4). endogenous protective mechanism against acute brain edema in acute Conclusion: The results of this study indicate that fMRI can be alcoholism. The changes of ADC measurements can indirectly reflect used to assess activity in the cervical spinal cord and have the the alterations in the expression of the AQP4. potential clinical value to evaluate electrical stimulation treatment Science and Technology Planning Project of Guangdong Province, effect, although the accuracy this method and the repeatability of the China (Grant No. 2010B031600129). results would be further improved.

P389 P391 Correlatives variables in brain mapping and digital The surface ﬁtting approach for correction EEG in patients with severe craneoencephalic trauma of magnetisation transfer imaging bias ﬁeld in early states G. Xiao, M. Wei, Z. Dai, R. Wu T. Montes de Oca Dominguez, J. Rojas de Dios, G. Maya Hanshan Normal University (Chaozhou, CN); Shantou University Morales, I. Padron Lopez, O. Gonzalez Perez (Shantou, CN)

123 S84 J Neurol (2012) 259 (Suppl 1):S1–S236

Objectives: Bias field signal is a low-frequency and very smooth amplitude, latency and dispersion were analyzed. Additionally, we signal that corrupts MRI image especially magnetization transfer tested for age-related change of BOLD signal variability and grey imaging (MTI) produced by 1.5 Tesla machines. A pre-processing matter reduction. step is needed to correct for the bias field signal before corrupted MRI Results: No significant correlation was found between subjects’ images to quantitative MTI. In this report we discuss a surface fitting age and their performance. Significant age-correlated increase of the approach to deal with bias field corrupted MTI at 1.5 T. latency of the positive BOLD response was found in areas of the Methods: A common practice for magnetization transfer imagings visual cortex (calcarine gyrus, lingual gyrus, V2, V4), and geniculate that are unevenly illuminated is to divide the corrupted image by a body. The amplitude and dispersion of the positive and the negative background image represents an estimate of the variation in the BOLD response showed no significant correlation with age. Several illumination across the image. To improve the quality of the back- areas showing significant age-correlated increase of signal variability ground image, a two-dimensional surface equation is fitted to data (posterior insula, middle and superior temporal gyrus, inferior parietal points selected from the background image and then the fitted equa- lobule) overlapped with areas showing negative BOLD responses tion is used to generate the bias field signal. The steps of the algorithm during OKN. are: (1) Extract a background image from the corrupted MTI with a Conclusion: Age seems to have the biggest impact on the latency Gaussian low-pass filtering. (2) Select few data points from the of the BOLD response in visual areas activated during OKN. These background image and save their coordinates and gray level values findings could primarily reflect age-related changes in neurovascular into a matrix D. (3) Select a as low order polynomial surfaces coupling. Changes in the neural function (neural compensation or equation for the Fitted surface. (4) Estimate the parameters of the de-specialization) could additionally contribute to the results of surface that best fits the data in matrix D by the method of nonlinear increased signal variability in areas overlapping with areas of nega- least-squares. (5) Use the fitted equation to generate an image of the tive BOLD responses. Further research, however, is necessary to bias field signal. (6) Divide the corrupted MRI image by the estimated elucidate the exact mechanism behind the observed BOLD signal bias Field image in step (5). changes. Results: We tested the resulting algorithm named surface Fitting Supported by Deutsche Forschungsgemeinschaft, Grant number approach on MTI. The agar gels for these experiments were prepared. GRK 1091, 2 Orientation and Motion in Space. The phantom was scanned with a GE 1.5T MRI scanner using a head- neck coil for radiofrequency (RF) transmission and an eight-channel sensitivity-encoding coil for reception. MTI experiments consisted of a gradient echo sequence with TE=4 ms and TR= 50 ms. Magneti- P393 zation transfer sequence was applied before image readout, with an A winner shoe in the motor cortex offset frequency at -112 Hz. This technique works well for most M.S. Al-Rawi, J.P. Silva Cunha biased MRI images; however, it is better to fit low order polynomial IEETA - University of Aveiro (Aveiro, PT) surfaces. Conclusion: The method presented in this article is based on the Objectives: Using multivoxel pattern analysis MVPA [1] on func- assumption that magnetization transfer imaging bias field is multi- tional magnetic resonance images acquired via MRI, to investigate plicative, smooth, and slow-varying. We can summarize that the how the human brain would respond to stimuli represented as shoe surface fitting approach provides stable and efficient automatic images in the primary motor cortex (PMC). There have been great technique for fast correction of slow-varying nonuniformity in MTI. interests, mainly, in studying how to decode brain states related to This study was supported in part by the key program of National faces, houses, and few other subjects, which were originally sup- Natural Science Foundation of China (NSFC 30930027). ported and/or debated by the fusiform face area [2] and the parahippocampal place area [3]. Our intention was to take the MVPA to diverse regions in the brain and study how well, or how bad, the decoding is at these areas. Among the various brain regions we P392 investigated was the PMC, where the patterns of response are Age-related variability of BOLD signal in healthy expected to be weak with respect to visual stimulation. subjects during optokinetic stimulation Methods: The dataset that we used (pub. available [2]) contained I. Stefanova, T. Stephan, T. Dera, T. Brandt, M. Dieterich neural responses, as reflected in hemodynamic changes, that were measured in six subjects while they performed a one-back repetition Ludwig-Maximilians University (Munich, DE) detection task using gray-scale images of face, house, cat, bottle, Objectives: The visual-vestibular interaction is an example of reci- scissor, shoe, chair, and scrambled picture. We used SPM8 for pre- procal inhibitory interaction, which enables shifting of the sensorial processing steps on the fMRI data of each subject; e.g. motion weight to the more reliable sensory modality. Previous imaging correction, co-registration, normalize to MNI, temporal detrending, studies showed that visual optokinetic stimulation (OKN) elicits a and temporal z-scoring. Our MVPA implemented L2 regularized typical Blood-Oxygenation-Level-Dependent (BOLD) signal pattern logistic regression classifier, in a leave one run out cross validation consisting of signal increases within the visual cortex and signal manner, and we used permutation tests to find the classification decreases within multisensory vestibular areas of the temporo-parietal significance. cortex bilaterally. The aim of the current study was to address the Results: Faces and houses were the winners in many cortical effects of age on this pattern during OKN stimulation in healthy regions, e.g. the visual cortex. The shoe stimulus gave weak responses subjects, and thereby acquire new insights into physiological age- in those other regions, ranked the fifth among the eight stimuli. The related changes of the visual-vestibular interaction. shoe stimulus, gave the highest response compared to other stimuli for Methods: Forty-five healthy volunteers, aged 20 to 76 years, were brain signals extracted from the right hemisphere PMC. We also included in this functional magnetic resonance imaging (fMRI) study. found higher responses to the shoe stimulus for brain signals extracted Eye movements of horizontal OKN were recorded by video-oculog- from a region that combines the right hemisphere PMC and the left raphy (VOG). In order to compare age-related changes in the visual- supplementary motor area, which is higher than the PMC alone. vestibular interaction with those in other cortical functions, we used Conclusions: The results we obtained reveal an important clue that control stimuli for the motor cortex and visual cortex. Correlation associates the shoe stimulus (as a gray-scale image) to the right- between the age of the subjects and their performance, BOLD signal hemisphere PMC. Further analysis dedicated on motion-related

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S85 stimuli should be implemented in order to further investigate our demonstrate longitudinal increases in PIB, although remaining below findings. the threshold for PIB+. [1] K. A. Norman et al., Trends in Cog. Sciences, 10 (2006) Methods: Fifty five cognitively normal adults (CDR 0, mean age 63 424-430. years) underwent PIB PET scans *2.6 years apart. Mean cortical [2] J.V. Haxby et al., Science 293 (2001) 2425-2430. binding potential (MCBP) was calculated from precuneus, gyrus rectus, [3] Z. Kourtzi and N. Kanwisher, J. of Neuroscience, 20 (2000) prefrontal and lateral temporal cortex. PIB+ was defined as a MCBP 3310-3318. greater than 0.18. Volumetric MRI was obtained at the time of the 2nd ‘‘Fundaçaõ para a Cieˆncia e a Tecnologia (FCT)’’, PTDC/PSI/ PIB scan. The MPRAGE was processed using FreeSurfer to generate 67381/2006, GRID/GRI/81833/2006, C2007-UA/IEETA/SP/02. grey matter volumes. Mixed models were utilized to test whether volumetric measurements are related to change in PIB level or overall PIB level, while adjusting for age, ApoE4, gender and time between scans. Results: All participants were PIB- and cognitively normal (CDR 0) P394 throughout the study. Regional increases in PIB uptake were associated Quantititave analysis of brain metabolites in patients with decreases in cortical volume predominantly in the temporal lobe, with vascular cognitive impairment no dementia and also in the posterior frontal and occipital cortex. Z. Yang, Y. Liu, Z. Cao, Z. Shen, W. Chen, R. Wu Conclusion: Our findings suggest that increases in beta-amyloid deposition, even when below established thresholds for ‘‘PIB posi- Shantou University (Shantou, CN) tivity’’, may be not benign as they are associated with cortical volume Objective: To investigate metabolite changes in the brain of patients decreases in a pattern suggestive of early AD. Longitudinal data is with vascular cognitive impairment no dementia (VCIND) using needed to determine whether these participants have higher risk of magnetic resonance spectroscopy (MRS). dementia of Alzheimer’s type. Methods: Twenty-five patients with vascular cognitive impairment no dementia (VCIND) and thirty normal controls (NC) were participated in this experiment. The absolute concentrations of N-acetyl aspartate (NAA), choline (Cho), myo-inositol (MI), creatine (Cr) and P396 the metabolite ratios of NAA/Cr, Cho/Cr, MI/Cr, NAA/MI and NAA/ Lateralisation of activation during unilateral Cho were measured bilaterally in the posterior cingulate gyrus (PCG), and bilateral galvanic stimulation – an fMRI study white matter of the occipital lobe (OLWM), dorsal thalamus (DT), C.A.M. Cyran, R. Boegle, T. Stephan, R. Schmidt, and white matter of the frontal lobe (FLWM) by multivoxel MRS. The metabolite concentrations were quantified and post-processed S. Becker-Bense, M. Dieterich using SAGE 7.0 and LCModel software. Ludwig-Maximilians-University (Munich, DE) Results: Compared with the NC group, VCIND patients displayed Objectives: Previous PET- and fMRI-studies using warm caloric higher Cho level in the left FLWM (P\0.05). The NAA/Cr ratio in the vestibular stimulation and vestibular evoked myogenic potentials, bilateral DT and bilateral FLWM with VCIND patients showed lower respectively, detected activations in the multisensory vestibular net- than NC subjects (P\0.05). The patients with VCIND also displayed work predominantly ipsilateral to the stimulated ear and in the non- lower NAA/Cho ratio in the bilateral FLWM and left OLWM and dominant hemisphere (1, 2). Left-sided cold CVS in fMRI, however, right DT than NC subjects (P\0.05), while it displayed a significantly induced contralateral activations (3). In animal experiments galvanic lower NAA/Cho ratio in the bilateral FLWM than NC subjects stimulation of the peripheral vestibular nerve (GVS) increases the (P\0.01). spontaneous firing rate of vestibular neurons at the cathode and Conclusions: VCIND patients may be related to metabolite dys- decreases it at the anode (4). Aim of the current study was to examine functions in different regions of the brain. It may provide efficient the lateralisation effects during unilateral and bilateral GVS (uni-GVS information for clinical diagnosis, preventing and treating in the early and bi-GVS). stages of dementia. Methods: 19 healthy right-handers (10 male, 19-27 years) were studied alternately using uni-GVS and bi-GVS with direct current (block-design alternating stimulated ear and polarity, intermittent rest P395 condition, randomized block lengths). Electrodes were placed on the right/left mastoid bone and right/left paravertebrally of C7. The Increased beta-amyloid deposition in cognitively amplitude (1.25-3.25mA) was determined according to subjects normal adults is associated with decreased cortical reporting a sensation of being tilted. Switching the current on or off volume and block effects were modelled separately in the analysis (SPM5) T.L.S. Benzinger, G. D’Angelo, T.M. Blazey, G. Zhou, (results FDR-corrected) (5). Results: Only for uni-GVS with the cathode on the left mastoid B.M. Ances, A.G. Vlassenko, J.C. Morris and uni-GVS with the anode on the right mastoid significant clusters Washington University (St. Louis, US) were detected bilaterally in the vestibular cortex. Cerebellar, insular Objectives: Although beta-amyloid deposits may accumulate in the and parietal activations induced by bi-GVS of both polarities pre- brain years prior to the clinical manifestations, preclinical (predominated significantly in the hemisphere ipsilateral to the anode. symptomatic) stage of Alzheimer’s disease (AD) is not benign but Conclusions: Thus, uni- and bi-GVS induce bilateral activations in demonstrates progressive structural and functional deterioration. the multisensory vestibular network. Uni-GVS with the cathode on Cognitively normal adults with preclinical AD pathology as detected the left or with the anode on the right mastoid bone seem to have a by elevated uptake of [11C] Pittsburgh compound B (PIB) positron stronger effect than the inverse conditions. emission tomography (PET) have a greater risk of progression to The activation pattern during bi-GVS predominating in the symptomatic AD. We have recently characterized the conversion hemisphere contralateral to the cathode differs from the activations from PIB-negative (PIB-) to PIB-positive (PIB+) state (preclinical induced by warm CVS predominating in the ipsilateral hemisphere AD). Our current aim was to analyze whether early volumetric MR (1), raising questions whether the increase or decrease of the firing changes can be identified in cognitively normal individuals, who rate of vestibular neurons induces stronger activations and if the

123 S86 J Neurol (2012) 259 (Suppl 1):S1–S236 otolith fibers connect predominately to the contralateral hemisphere, and extrastriatal dopamine D2-receptor availability in patients with in contrast to those of the horizontal canals. BVF by using the high affinity D2-ligand [18F] fallypride. 1 Dieterich M et al. Cereb Cortex 2003 2 Schlindwein P et al. Methods: 12 BVF-patients (median age 64.5 years, 9 right handed, NeuroImage 2008 3 Marcelli V et al. Eur J Radiol 2009 4 Fitzpatrick 2 left handed and 1 both handed) and 13 age- and sex matched healthy RC et al. J Appl Physiol 2004 5 Stephan T et al. Ann N Y Acad Sci controls were included in this study. Parametric voxel-wise binding 2009 potentials (BPND) to the D2-receptors were estimated by means of This work was supported by DSN (Deutsche Stiftung fu¨r Neu- Logan’s graphical analysis. Parametric BPND images were coregis- rologie) and IFBLMU (BMBF). tered on individual MRI and afterwards normalised to the ICBM- template. Statistical analysis was performed using SPM8. Findings were compared with corresponding analyses in the age matched healthy control (HC) group. P397 Results: Patients with BVF presented with significantly decreased Detecting movement volition in disorders D2-receptor availability in the temporo-parieto-occipital cortex of consciousness including both motion sensitive areas (MT/V5), the inferior parietal F. Wang, X. Hu, D. Yu, M. He, H. Di, S. Laureys lobule (IPL), the insula bilaterally including the parieto-insular-vestibular cortex (PIVC), and the cingulate. In addition decreased D2- Hangzhou Normal University (Hangzhou, CN); Wujing Hospital of receptor availability was found in the striatum and the thalamus. Hangzhou (Hangzhou, CN); Coma Science Group (Lie`ge, BE) Shorter duration of illness (short term:\2 years; long term:[2 years) Objectives: The accurate assessment of patients with disorder of was associated with higher D2-receptor availability in the right consciousness (DOC) is a challenge to the most experienced clinician. inferior parietal lobe and the right temporal cortex. As a potential neuroimaging tool, fMRI could detect the internal Conclusion: Lower D2-receptor availability in the multisensory awareness of the DOC patients without the need of any real motor vestibular cortical network in patients with BVF might be interpreted responses. However, the sensitivity of this tool is limited. In order to as a down-regulation of D2-receptors due to the lack of peripheral increase the sensitivity of this method, we choose a simple motor vestibular input. Furthermore, the availability of D2-receptors in paradigm (hand raising) to exhibit residual awareness in these important vestibular cortical areas depends on the duration of illness: patients. patients with a short term duration have a relatively higher avail- Methods: A total of 30 patients, who met diagnostic criteria for the ability of D2-receptors in the IPL and in the temporal cortex when MCS (n=8), VS (n =21), emerged from MCS (EMCS) (n=1), par- compared to patients with longer disease duration. ticipated in this observational ‘active’ fMRI study. Before the ‘hand raising’ session, Patients were exposed to 2 sounds, one is patients’ own name by familiar voice (SON-FV), the other is a command which instruct the patients to ‘‘raise your hand’’. P399 Results: Of the 30 patients enrolled in the data analysis, 5(1EMCS, Superficial central nervous system siderosis of unknown 2MCS, 2VS) were able to modulate their brain activity to our ‘hand raising’ task. They showed activation in motor related region in their origin brain which couldn’t be discovered in own-name task. And the longitu- A.C. Ribeiro, J. Nunes, R. Veiga, A. Morgadinho dinal behavioral assessments tell us, among 5 patients, 2 patients escape Coimbra0s University and General Hospital Center (Coimbra, PT) VS to MCS, the CRS-R total score became higher in 1 MCS patients. Introduction: Superficial siderosis (SS) of the central nervous system Conclusion: This study supports the view that fMRI during ‘hand (CNS) is an uncommon and often unrecognized disorder in which raising’ task can elicit brain activations in patients with DOC similar cytotoxic hemosiderin is deposited in the leptomeninges, subpial layer to those observed in healthy subjects. These results also suggest that and ependymal surface of the CNS through chronic, slow or repeated activity of the motor related network may serve as an indicator of bleeding into the subarachnoid space. This leads to progressive and high-level cognition that cannot be discerned through conventional irreversible neurological dysfunction characterized by a classic triad behavioral assessment. of sensorineural hearing loss, cerebellar ataxia, and myelopathy. In Supported by the National Science Foundation of China. about 50 % of cases the cause is unknown. Case report: Female patient, 46 years old, complains of progressive gait imbalance and hearing loss with 8 month evolution. P398 Neurological examination disclosed cerebellar dysarthria, right hori- Assessment of extrastriatal dopamine D2-receptors zontal end-gaze nystagmus, bilateral sensorineural hearing loss, dysmetria and intention tremor in finger-to-nose and heel-to-knee test in patients with bilateral vestibular failure as well as gait ataxia. The CSF was xanthochromic after centrifuga- R. Feuerecker, N. Jansen, S. Bense-Becker, G. Xiong, tion with no other abnormalities. Brain MRI revealed extensive A. Rominger, B. Wa¨ngler, P. Cumming, P. Bartenstein, superficial siderosis of the CNS, predominantly in the posterior fossa M. Dieterich with cortical and cerebellar atrophy. The imaging study with spinal MRI and CT scan, CT myelography and classical spinal cord and Großhadern University Hospital (Munich, DE) brain angiography failed to localize the bleeding source. Objective: Chronic absence of bilateral peripheral vestibular input in Conclusion: Superficial siderosis of the CNS not only stands out bilateral vestibular failure (BVF) is suggested to induce a plastic for its rarity but also for the lack of a true therapeutic options since cortical reorganization at various sites in the brain and in various both steroids and iron or copper chelators have provided limited transmitter systems especially in the visual and vestibular cortex. evidence in terms of preventing or halting the progressive neurolog- Dopamine is known to be involved in processes leading to cortico- ical decline. The neurological deficit made by hemosiderin is striatal synaptic plasticity. To date, it is unclear whether the dopamine irreversible, and the only way to minimize poor outcomes is the early system is involved in vestibular neurotransmission of humans. The diagnosis of the disease with accurate identification and ablation of aim of the present study was therefore to analyse changes in striatal the bleeding source.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S87

P400 between the principal diffusion direction and the cortical surface in Regional hippocampal involvement differs the cortex in MS patients and HC. Methods: T2-weighted, 3D T1-weighted and DT MRI brain scans across multiple sclerosis clinical phenotypes: evidences were acquired from 113 MS patients (21 benign [B], 57 relapsing- from a radial mapping MR-based study remitting [RR] and 35 secondary progressive [SP]) and 35 HC. G. Longoni, M.A. Rocca, E. Pagani, B. Colombo, Expanded disability status scale (EDSS) score was assessed in all the M. Rodegher, A. Falini, G. Comi, M. Filippi patients. The DT was estimated by linear regression and the primary Vita-Salute San Raffaele University (Milan, IT) eigenvector derived. GM was segmented from the 3D T1-weighted scans using SPM8. GM maps were then skeletonized, the 3D vector Objective: Emerging data support the evidence of hippocampal field of normals to the cortical surface derived and smoothed. Finally, demyelination and neurodegeneration early and throughout the course the angles (alpha) between the primary eigenvectors and the vectors of multiple sclerosis (MS). Aim of the present work is to localize and normal to the cortical surface were calculated. Alpha ranges from 0 to compare the patterns of regional hippocampal atrophy associated to 90 degrees, where 0 degree means that the dominant structures pass the main MS clinical phenotypes. through the cortex perpendicularly and 90 degrees mean that they run Methods: 3D T1-weighted scans were acquired from 115 MS parallel to the cortex. patients (28 relapsing remitting [RR], 34 secondary progressive [SP], Results: Average histograms of the alpha angles for the patient 27 primary progressive [PP], and 26 benign [B] MS) and 28 healthy groups showed different behaviours, indicating that MS phenotypes in controls (HC). Hippocampal segmentation was performed manually the more advanced phase of the disease have an increased number of according to a standardized procedure, and global volumes derived. voxels in the cortex with alpha close to 90 degrees. The plot of the From contours, radial atrophy distribution was assessed using three- fitted polynomial curves for each patient showed a spread of behav- dimensional parametric surface mesh models. iours. The derivative at 10 degrees correlated (r=-0.42 for RRMS and Results: Right and left hippocampal volumes differed signifi- r=-0.29 for all patients) with EDSS score. cantly between groups (p\0.001, adjusted for age and gender). Conclusions: In MS patients, modifications in diffusion anisotropy Significant differences were found, for the right and left hippocam- seem to be driven by a degeneration of the ‘radial’ component pus respectively, in: RRMS vs. HC (p=0.001, p=0.004), SPMS vs. (towards the cortical surface) in the GM, resulting in a predominance PPMS (p=0.005, 0.02), BMS vs. RRMS (ns, p=0.06). Compared to of the parallel component. HC, RRMS patients had radial atrophy (p\0.001) involving the Acknowledgments. The study was partially supported by a grant medial and lateral parts of CA1 subfield and subiculum of the left from FISM/2008/R/13. hippocampal body and tail. Right hippocampus showed also additional involvement of the head (CA1 subfield). Compared to HC, PPMS patients had volume loss of lateral CA1 subfield, bilaterally, and right tail subicular region, with mild involvement of right hip- P402 pocampal head. Compared to the RRMS and PPMS, SPMS patients had atrophy of the left hippocampal head. Compared to RRMS, BMS Functional connectivity abnormalities and cognitive patients had focal decrease of radial distance in the medial aspect of impairment in relapse-onset MS patients: a whole-brain left hippocampal body, anteriorly. In RRMS and SPMS, brain T1 and functional network connectivity analysis T2 lesion loads were correlated (p\0.001) with volume loss in M. Filippi, P. Valsasina, P. Preziosa, G. Riccitelli, subicular and CA1 subregions of left hippocampus s well as with atrophy of CA1 subfield of right hippocampal head. In all MS V. Martinelli, A. Falini, G. Comi, M.A. Rocca phenotypes, regional hippocampal atrophy correlated with global Vita-Salute San Raffaele University (Milan, IT) brain and gray matter atrophy, while poor correlation was found with Objectives: To explore abnormalities of functional connectivity (FC) EDSS score. and of functional interaction among cognitive resting state networks Conclusions: Regional hippocampal atrophy differs among the (RSNs) in patients with relapsing remitting (RR) and secondary major MS disease clinical phenotypes, possibly reflecting differential progressive (SP) multiple sclerosis (MS), and their correlation with susceptibility to inflammatory insults and neurodegenerative pro- cognitive impairment and damage to selected white matter (WM) cesses of the hippocampal subfields. These results support the tracts. feasibility of MR-based radial mapping methods for the development Methods: RS fMRI and diffusion tensor (DT) MRI were acquired of reliable markers of disease progression in MS. from 30 RRMS, 30 SPMS patients and 30 matched controls. Maps of the corpus callosum (CC) and cingulum were produced using DT tractography. Independent component analysis (ICA) and a template- matching procedure were used to identify the DMN, the executive P401 control network (ECN) and the salience network (SN). Within-group Principal diffusion direction in relation to the geometry and between-group RS FC comparisons were performed with SPM8. The Functional network connectivity (FNC) toolbox was used to of the cortical surface in multiple sclerosis assess changes of interactions among RSNs. In MS patients, corre- M. Filippi, E. Pagani, P. Preziosa, S. Mesaros, lations between network abnormalities, cognitive impairment and B. Colombo, M.A. Horsfield, A. Falini, G. Comi, structural damage were also assessed. M.A. Rocca Results: Significant RS FC abnormalities, which were more pro- Vita-Salute San Raffaele University (Milan, IT); University of nounced in SPMS vs. RRMS, were detected in all RSNs, and were Belgrade (Belgrade, RS) characterized by a decreased FC in frontal, temporal, parahippocampal and cerebellar regions, as well as an increased FC in the Objective: Multiple sclerosis (MS) patients have increased diffusion anterior cingulate cortex. FC abnormalities were more severe in anisotropy within cortical lesions in comparison with healthy con- cognitively impaired vs. cognitively preserved patients (p ranging trols’ (HC) gray matter (GM), suggesting the existence of a from 0.02 to 0.04), and were correlated moderately with DT MRI preferential directionality of the GM structure, which is usually not indexes of damage to the CC and cingulum (r ranging from -0.40 to present in the normal GM. In this study, we evaluated the angle 0.48). FNC analysis detected a decreased connection between the

123 S88 J Neurol (2012) 259 (Suppl 1):S1–S236

DMN and ECN, and an increased connection between the SN and Faculty Hospital Motol (Prague, CZ); Vidia,s.r.o. (Prague, CZ) ECN in RRMS and SPMS patients. SPMS also showed an increased Objective: The role of asymmetrical pathology of basal ganglia/ FC between the SN and DMN. Altered connectivity among RSNs was including nuclei caudati and especially their damage by ferum moderately correlated with cognitive and structural MRI variables (r deposits and their relationship to disease progression in multiple ranging from -0.36 to 0.34). sclerosis/MS/are investigated, but not in relationship to blood perfu- Conclusions: Intra-network and inter-network dysfunction at rest sion. Furthermore, there are no studies investigating a relationship of is associated to more severe clinical disability and cognitive deficits in asymmetry of ncl.caudati´ hypoperfusion to axonal damage and MS patients. depression in depressive MS patients. These patients seems to have Acknowledgments. The study was partially supported by a grant basal ganglia´ hypoperfusion in previous studies and, for hypothesized from FISM/2008/R/13. effect of depression to MS worse course, be in higher risk of disease progression. Patients and methods: 12 patients fulfilling the McDonald´s criteria P403 for MS and depression recently or in anamnesis (9 with RR-MS and 3 Brain axonal damage in radiologically isolated SP-MS), to EDSS 4,5 and 7 years of disease progression, clinically stable on medication free of drugs provoking the depression were syndrome examined by BDI II, BAI II, SCL-90, fatigue MS scale, Hamilton M. Stromillo, A. Giorgio, F. Rossi, M. Battaglini, scales, psychiatric and psychologic examination, SPECT of and MRI B. Hakiki, E. Portaccio, G. Malentacchi, C. Gasperini, of thalami and ncl.caudati and serum IgM antibody to heavy neuro- M. Santangelo, M. Bartolozzi, M. Sormani, M. Amato, filamental protein/antiHNfl/. Symmetricity of hypoperfusion of nuclei caudati and thalami were compared by Wilcoxon test and correlation N. De Stefano of perfusion of left and right ncl.caudatus to antiHNfl and BDI score University of Siena (Siena, IT); University of Florence (Florence, IT); were correlated. Potenza Hospital (Potenza, IT); San Camillo Forlanini Hospital Results: No asymmetry was found in blood perfusion between (Rome, IT); Carpi Hospital (Carpi, IT); Empoli Hospital (Empoli, IT); thalami, contrary to higher than 0,05 statistical significant hypoper- University of Genoa (Genoa, IT) fusion in right ncl.caudatus, there are no correlation to BDI score, Objectives: We used brain proton magnetic resonance (MR) spec- which was in relationship to both ncl.caudati hypoperfusion in our troscopy (1H-MRSI) to assess metabolic changes in subjects with previous study. No correlation were found between hypoperfusion of radiologically isolated syndrome (RIS). This condition refers to each ncl.caudatus and IgM antiHNfl, but level of this antibody cor- subjects who show unanticipated brain spatial dissemination of MR related with hypoperfusion of both ncl.caudati on significancy more imaging lesions highly suggestive of multiple sclerosis (MS) in the than 0.01. absence of neurological signs or symptoms. Conclusion: Significant asymmetrical hypoperfusion of nuclei Methods: Nineteen subjects (male/female: 5/14; mean±SD age: caudati in depressive MS patients was confirmed, but without 36.9±9 years, range 19-52 years), who were previously classified as RIS clear relationship of depression to hypoperfusion of left or right according with the Okuda Criteria (Okuda DT. et al. Incidental MRI side and this asymmetry seems to be performed without hemisp- anomalies suggestive of multiple sclerosis: the radiologically isolated heral dysconnection. Furthermore, relationship of asymmetrical syndrome. Neurology 2009 72: 800–805), underwent 1H-MRSI exam- hypoperfusion, depression and axonal damage, either without inations. In each subject central brain levels of N-acetylaspartate (NAA, relationship to side preference of these structures, may be marker of neuro-axonal integrity) and choline (Cho) normalized to cre- possible. atine (Cr) ratios were measured. The 1H-MRSI data were compared to those of 20 demographically matched healthy controls (HC). Results: Central brain NAA/Cr levels were significantly lower in RIS subjects than in HC (2.9±0.3 vs 3.1±0.2; p=0.006). In contrast, P405 no between-group difference was found for Cho/Cr levels (1.4±0.2 vs Cerebellar peduncles intrinsic damage in multiple 1.4±0.2, p=0.6). A single-subject analysis of the NAA/Cr values sclerosis: association with clinical disabilty showed that 6 out of 19 RIS subjects (32 %, range of NAA/Cr: 2.4- 2.6) were at least two standard deviations below the corresponding P. Preziosa, M.A. Rocca, S. Mesaros, E. Pagani, mean of the HC. Interestingly, all these subjects were classified in a T. Stosic-Opincal, J. Drulovic, G. Comi, M. Filippi recent study (De Stefano N et al. Improving the characterization of Vita-Salute San Raffaele University (Milan, IT); University of radiologically isolated syndrome suggestive of multiple sclerosis. Belgrade (Belgrade, RS) PLoS One 2011;6: e19452) as having a very high probability (range: Objectives: The cerebellum and cerebellar peduncles (CP) are regions 70-90 %) of being affected by MS on a logistic regression analysis frequently affected by demyelinating and neurodegenerative pro- based on several quantitative MRI metrics. cesses in multiple sclerosis (MS). Aim of this study was to apply Conclusion: The results of this study indicate that brain axonal a voxel-wise analysis to metrics from diffusion tensor (DT) MRI damage, as shown by the reduced NAA/Cr values, can be significant tractography and T2 lesions of the middle (M) and superior (S) CP to in subjects with RIS. This could help in characterizing asymptomatic quantify their structural damage in MS patients, and to assess the subjects with this condition as having a pre-clinical form of MS. relationship between CP damage vs. global clinical disability, impairment in cerebellar (C) and brainstem (B) functional systems (FS) and ambulation. P404 Methods: Brain dual-echo and DT MRI sequences were collected Asymmetrical hypoperfusion of nuclei caudati in MS from 172 MS patients and 46 matched healthy controls (HC). The EDSS score, the degree of impairment in the different EDSS FS and patients is in relationship to depression and axonal loss Ambulation Index (AI) were rated. Patients were dichotomized using S. Cihelkova, Z. Baranı´kova´, M. Jung, P. Jinoch, CFS and BFS (impaired: FS[=1, unimpaired: FS=0), EDSS (ambu- K. Taborska´, M. Bojar latory impaired: EDSS[=4.0, fully ambulatory: EDSS\4.0) and AI

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S89

(impaired: AI[=1, unimpaired: AI=0). Using DT MRI tractography, Movement disorders probability maps of the SCP and MCP were produced. Voxel-wise analysis was used to assess the topographical distribution of damage along these tracts. Results: Compared to HC, MS patients showed widespread P407 increase of mean (MD), axial (AD), radial (RD) diffusivity and Public smelling test: a new way to detect hyposmia decreased fractional anisotropy (FA) in both tracts. Diffusivity as an early indicator of Parkinson’s disease abnormalities were more pronounced in patients with EDSS[=4.0, U. Liebetrau, S. Peuckert, O. Hackmann, S. Maune, CFS[=1, BFS[=1 and AI[=1. Patients with EDSS[=4.0 had a higher probability of having T2 lesions in the MCP bilaterally, par- V. Limmroth tially overlapping with diffusivity abnormalities, patients with Hospital Cologne-Merheim (Cologne, DE); Hospital of Ear-Nose- BFS[=1 showed a higher probability of having T2 lesions in one Throat-Diseases (Cologne, DE) small cluster in the left SCP, while no differences were found for the Hyposmia is an early non-motor sign of Parkinson´s disease. other comparisons. According to PONSEN (2004) 10 % of subjects with idiopathic Conclusions: The assessment of MCP and SCP damage, in terms hyposmia are likely to develop parkinsonism in the following years. of local inflammation (T2 focal lesions) and diffuse normal appearing Since the ADAGIO study it is well-established, that agents such as white matter tract injury (Wallerian degeneration), might contribute RASAGILIN have a positive influence on the course of Parkinson´s to explain global clinical impairment as well as impairment at single disease, in particular when treatment is started early. FS in MS. In order to reach as many people with hyposmia as possible we offered free public examination to detect subjects with possible hyposmia. 187 subjects were examined on a Saturday in the pedes- trian zone of the City of Cologne, supported by the oldest Eau de Cologne factory, FARINA. We detected 46 patients with mostly P406 unknown hyposmia. All of them got the opportunity for a follow up A voxel-based assessment of cervical cord damage examination in the out-patient clinic of the Cologne City hospital at in MS patients the departments of Neurology and Ear-Nose-Throat ENT. As a result M.A. Rocca, P. Valsasina, D. Damjanovic, S. Mesaros, 3 patients with so far unknown Parkinson‘s disease were discovered. Conclusion: By public smelling tests early Parkinson‘s disease can M.A. Horsfield, T. Stosic-Opincal, J. Drulovic, G. Comi, be discovered. In our investigation the incidence was 1.6 %. M. Filippi Moreover, the information about hyposmia as an early Parkinson´s Vita-Salute San Raffaele University (Milan, IT); University of disease indicator should receive broader attention in the public to Leicester (Leicester, UK); University of Belgrade (Belgrade, RS) facilitate early diagnosis. Objective: To apply a voxel-based method to assess the regional distribution of cord atrophy and cervical cord lesions of multiple sclerosis (MS) patients with different clinical phenotypes. P408 Methods: Brain dual echo (DE) scans, cervical cord 3D T1- Reproducibility of automatic measurement weighted and DE scans were acquired from 31 healthy controls (HC) and 89 MS patients (16 clinically isolated syndrome [CIS], 17 of substantia nigra from transcranial sonographic relapsing remitting [RR], 19 benign [B], 18 primary progressive images [PP] and 19 secondary progressive [SP] MS). 3D-T1 cervical cord M. Jelıńkova´, J. Blahuta, P. Cerma´k, T. Soukup, images were analyzed by using a semi-automatic active surface P. Ba´rtova´, R. Herzig, D. Skoloudı´k (AS) method. Unfolded cervical cord images were co-registered into City Hospital (Havirov, CZ); Silesian University (Opava, CZ); a common standard space, and smoothed cord binary masks, pro- Palacky University and University Hospital Olomouc (Olomouc, CZ); duced using the cord outlines estimated by the AS approach, were University Hospital Ostrava (Ostrava, CZ) used as input images for spatial statistics. Normalized cervical cord lesion masks were produced from the DE cord scans. Between- Background: Recent studies reported increased echogenicity of subgroup comparisons of regional cervical cord atrophy and correla- stantia nigra (SN) in 91 – 100 % PD patients using transcranial tions with clinical and structural MRI variables were assessed with sonography (TCS). However, the main limitation of TCS evaluation SPM8. of SN features is the dependency on the sonographer’s experience and Results: Compared to HC, CIS patients showed no cord atrophy, the quality of tissue imaging limited by quality of bone window. The while PPMS had diffuse cord atrophy. Several clusters of cord atro- experimental software for measurement of area in SN was developed phy were found in BMS vs. RRMS, SPMS vs. RRMS, BMS and for quantitative evaluation in patients with Parkinson’s syndromes. PPMS patients. Atrophy mainly involved the posterior and lateral The aim of study was to test the reproducibility of measured data cord segments at different levels. Fifty-five (62 %) MS patients had using developed software. focal cervical cord lesions. Lesions occurred more frequently in the Methods: The SN was imaged from right temporal bone window posterior vs. the anterior cord portion, and they were more frequently in mesencephalic plane using TCS. DICOM images of SN were saved localized between C1 and C4. In PPMS, regional cord atrophy was and encoded. All images were subsequently converted into JPEG correlated (p\0.001) with disability (r values ranging from -0.76 to format, which were processed. The mean values, variance and stan- -0.86) and brain T2LV (r values ranging from -0.78 to -0.90), while dard deviation between all 6 measurements of each patient were in the remaining MS phenotypes, taken separately, no correlations counted. Subsequently, a coefficient of variability was calculated were found. from results of all measurements. The 95th percentile of healthy Conclusions: Voxel-based assessment of cervical cord atrophy and volunteers was used as a border-line value for a differentiation lesions allows a precise localization of regional cord tissue damage between normal and pathological results to obtain a ROC curve. The and may contribute to a better characterization of the clinical heter- average value of all 3 measurements of each observer was used for a ogeneity of MS patients. computing of Cohen’s kappa coefficient to determine an inter-

123 S90 J Neurol (2012) 259 (Suppl 1):S1–S236 observer correlation. Cohen’s kappa coefficient as an intra-observer Objective: To determine which specific clinical and electrophysio- coefficient was counted from the first 2 measurements of both logical features enable to suspect a SWEDD when the neurologist is observers. Finally two intra-observer correlations were obtained for faced with a patient presenting parkinsonism with tremor suggesting observer 1 and observer 2. IPD. Results: Totally 100 images were evaluated using this software. Background: 4 to 15 % of the patients fulfilling the current Mean of standard deviation of measurement was 3.87; Cohen’s kappa diagnostic criteria for Idiopathic Parkinson’s Disease (IPD) have for intra-observer agreement of two observers were 0.947, and 0.943, normal dopamine transporter (DaT) functional imaging. These resp.; Cohen’s kappa for inter-observers agreement was 0.880. patients, named Scans Without Evidence of Dopaminergic Deficit Conclusions: The results of the presented study show a very good (SWEDDs), have a neurological disorder, different from IPD, but the repeatability and reproducibility of measurement of SN features using etiology remains unknown. designed application with ‘‘almost perfect’’ inter-observer and also Methods: This is a retrospective case–control study of 16 patients intra-observer agreements. presenting parkinsonism with tremor associated with a SWEDD followed-up in the Amiens University Hospital. We studied demographics, clinical features, the disease history and course, the alcohol and treat- P409 ment responsiveness, the family history of tremor, the presence of Determinants of delayed diagnosis in Parkinson’s psychiatric comorbidities and the tremor electrophysiological analysis disease data. All the DaTSCANs were analysed by the same operator. Results: A focal, task-specific tremor, with irregular frequency and D. Breen, J. Evans, K. Farrell, C. Brayne, R. Barker amplitude, and static or fluctuating parkinsonism, spontaneously University of Cambridge (Cambridge, UK) remittent, with mild severity were characteristic of tremulous Objectives: Early diagnosis of Parkinson’s disease (PD) allows doc- SWEDDs. Furthermore, clinical features such as asymmetric resting tors to advise patients about their likely prognosis and initiate tremor, rigidity, chin tremor appear to be less specific of IPD than it is treatment where appropriate. Timely diagnosis also has implications commonly accepted. Most of tremulous SWEDDs patients had dys- on recruitment to disease modifying drug trials where the goal is tonic tremor, psychogenic tremor and less frequently, essential increasingly to intervene at the earliest stages of the disease. The aim tremor. The electrophysiological analysis of tremor could not help for of this study was to uncover the major determinants of delayed the diagnosis of tremulous SWEDDs. diagnosis in a large cohort of patients with incident PD. Conclusions: Patients presenting parkinsonism with tremor asso- Methods: We studied 239 newly diagnosed PD patients. 76 % of ciated with a SWEDD have specific clinical features which allow to patients were referred to the study by a specialist – usually consultant distinguish them from IPD before the completion of the DaTSCAN. neurologist – whilst 24 % were referred directly by their general practitioner (GP). 62 % of patients were male. Mean age at diagnosis was 68 years (SD 9). UPDRS score was 32 (SD 12) and Hoehn and Yahr score was 1.8 (SD 0.8). Demographic information was collected P411 and all patients underwent a comprehensive battery of clinical and Relationship between nigro-striatal dopaminergic neuropsychological tests to investigate the factors determining diag- dysfunction and affective symptoms in de novo nostic delay. Results: Mean time from motor symptom onset to GP presentation Parkinson’s disease was 14.0 months (SD 13.2, range 0-100), whereas mean time from GP D. Frosini, L. Kiferle, E. Del Prete, F. Vanelli, presentation to PD diagnosis was 4.3 months (SD 7.5, range 0-53). D. Volterrani, U. Bonuccelli, R. Ceravolo Factors associated with delay between symptom onset and GP presen- University of Pisa (Pisa, IT) tation were male sex, presenting motor symptom (gait dysfunction had the longest delay) and increased UPDRS part 2 score (reflecting impaired Objective: to investigate the relationship between affective symptoms motor activities of daily living). Delay between GP presentation and PD and presynaptic dopaminergic function in a group of de novo PD diagnosis was associated with presenting motor symptom (axial rigidity patients. had the longest delay), apathy (reported by patient or carer), behavioural Background: The investigation of the relationship between affec- symptoms (particularly poor motivation and self-care) and communi- tive symptoms and dopamine transporter (DAT) density provided cation problems. Other factors such as age, co-morbidities, family conflicting data in both PD and non PD patients, resulting in both an history, retirement status, cognition and depression were found to have no increase and a decrease of DAT density. Also the potential interfer- significant influence on diagnostic delay. ence of psychoactive as well as anti-parkinsonian drugs on DAT Conclusions: There was significant variation in diagnostic delay in density should be taken into account, and so far no studies were our large incident PD cohort. The length of time between symptom carried out in drug-naı¨ve PD patients. onset and GP presentation was the major determinant of delayed diag- Methods: A sample of 44 de novo PD consecutive outpatients nosis – particularly in men who presented with gait dysfunction rather (mean age: 66,7 ys; mean disease duration: 10,5 mts, mean UPDRS than other symptoms such as rest tremor – and this has implications for II-III: 4,8-16,9) were recruited, the severity of anxious symptoms was strategies designed to aid early identification of PD patients. evaluated with the Hamilton Anxiety Rating Scale (HAM-A), and the severity of depressive symptoms with the Hamilton depression scale (HAM-D) and the Beck Depression Inventory (BDI). Six patients had P410 a formal diagnosis of depression. All patients performed 123I-FP-CIT SPECT according to a standardized acquisition protocol and semi- Clinical features of parkinsonism with tremor quantitative striatal indices were calculated. associated with Scans Without Evidence Results: As expected UPDRS III was inversely correlated with of Dopaminergic Deficit (SWEDDs) bilateral striatal, caudal and putaminal indices. Correlation analysis A. Sacko, V. Moullart, C. Duru, P.E. Merle, O. Godefroy, between scores in the rating scales for affective symptoms and SPECT measures showed a significant direct correlation between P. Krystkowiak bilateral caudate and putamen with HAM-D (r.326; r.300 respec- Amiens University Hospital (Amiens, FR) tively), BDI (r.353; r.293 respectively) and HAM-A (r.511; r.425

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S91 respectively). After controlling for UPDRS III, age, disease duration correlated significantly with disease duration (rS = 0.36, p =\0.001), and MMSE no significant reduction in r value was observed. mUPDRS score (rS = 0.52, p \ 0.001), H&Y stage (rS = 0.38, p \ Conclusion: Our data support the existence of a relationship 0.001), HAMD score (rS = 0.77, p\0.001) and PDQ-39 SI score (rS = between depressive and anxious symptoms and the striatal 123-FP- 0.76, p\0.001). The individual NMSS item scores for the symptoms CIT uptake. The finding of an association between increased DAT of fatigue, restless legs, drooling saliva, difficulty swallowing, con- density and mild affective symptoms could be due to the lack of stipation, nocturia and change in ability to taste or smell were found to compensatory mechanism usually present in early PD and/or it might be significant in discriminating between PD patients and controls. have a pathogenic role in affective symptoms by reducing the dopa- Conclusion: Non-motor symptoms as a whole are more severe and minergic tone in the synaptic cleft. frequent in PD patients than in controls, and should be assessed and managed in clinical practice.

P412 Frontal white-matter change underlies cognitive decline P414 in patients with de novo Parkinson’s disease Mechanisms of psychomotor slowing in Parkinson’s J. Ding, W. Fan disease Fudan University Zhongshan Hospital (Shanghai, CN) C. Duru, T. Lelard, M. Roussel, Y. Yerro, O. Godefroy, Objectives: Impaired frontal cognitive decline is common in early P. Krystkowiak stage Parkinson disease (PD). We aimed to investigate the underlying University Hospital of Amiens (Amiens, FR) mechanism using diffusion tensor imaging (DTI). Methods: Twenty de novo Parkinson patients and 20 age-sex- Objective: (1) to highlight psychomotor slowing in PD patients, (2) to education matched controls were enrolled. All participants underwent determine the underlying mechanisms and (3) to determine whether DTI on 3T MRI. Voxel-based diffusion tensor analysis was performed levodopa medication influences reaction time. to examine fractional anisotropy (FA) values. The Stroop test, word Methods: We recruited 20 patients with Parkinson’s disease (PD) fluency test and event-related evoked potential P300 were used to and 20 controls matched for education and age. First of all, we assess cognitive function in PD patients. Spearman correlation was examined the performance of both groups on psychomotor speed with performed to determine the correlation between cognitive assessment simple reaction time (SRT) (simple and dual task), digital tapping, and FA values. choice reaction time (CRT)and visual inspection time (VIT) tasks. Results: Patients with de novo PD exhibited decreased FA values Afterwards, we compared the effects of dopaminergic medication on in both frontal lobe and substantia nigra compared to normal controls. reaction time performance: PD patients were tested both in ‘‘worst FA values in bilateral frontal lobe significantly associated with pro- OFF’’ and in ‘‘best ON’’ conditions when an acute dopaminergic longed stroop reaction time and P300 latency in Parkinson patients. challenge. Between-group comparisons were performed with a one- Conclusion: Frontal white matter integrity impairment underlies way analysis of variance (ANOVA) using the group (PD and controls) the frontal cognitive decline in Patients with de novo Parkinson as a between-subjects factor. When necessary, ANOVA for repeated disease. measures on the condition factor was performed. Results: PD patients were not different from controls. Decision time (p=0.013) and tapping (p=0.026) were impaired in PD patients as P413 compared to controls. VIT, SRT (simple and dual task) and CRT were similar to controls. No significant improvement in reaction time The burden of non-motor symptoms in Parkinson’s performance was seen after administration of dopaminergic medica- disease tion. Only tapping frequency became increasingly impaired in OFF K.M. Prakash, M.H Yong, J.C Allen, E.K. Tan condition as compared to On condition (p=0.037). National Neuroscience Institute (Singapore, SG); Duke NUS Conclusions: Psychomotor slowing of PD is due to slower motor (Singapore, SG) and decision processes. This psychomotor slowing profile could constitute a diagnostic marker in PD. Objective: Non-motor symptoms (NMS) are common in Parkinson’s disease (PD), and have an impact on PD patients’ health-related quality of life. We conducted a case–control study to compare the NMS burden between PD patients and controls, and to determine the P415 NMS that best discriminate between these two groups. Method: Non-demented idiopathic PD patients from the special- From Parkinson’s disease to Alzheimer dementia ized movement disorder clinics in Singapore and controls which were H. Prikrylova Vranova, E. Henykova, M. Kaiserova, frequency-matched for age and sex were recruited for this study. All M. Vastik, K. Mensikova, J. Mares, P. Hlustik, M. Strnad, subjects were evaluated for non-motor symptoms using the Non- P. Kanovsky Motor Symptoms Scale (NMSS). PD patients were additionally Palacky University, University Hospital (Olomouc, CZ) assessed for motor symptoms using Part 3 (motor section) of the Unified Parkinson’s Disease Rating Scale (mUPDRS) and for disease Introduction: Both Parkinson’s disease (PD) and Lewy Body severity using the modified Hoehn and Yahr (H & Y) staging scale. Dementia (DLB) are synucleinopathies. PD patients often suffer from Depressive symptoms were measured using the Hamilton Depression dementia and then are classified as Parkinson disease with dementia Rating Scale (HAMD), and health-related quality of life with the (PDD). The main difference between PDD and DLB is the temporal Parkinson’s Disease Questionnaire-39 (PDQ-39). ordering of extrapyramidal symptoms and dementia onset. Some Results: The mean NMSS total score was significantly higher in PD authors even believe that both diagnoses represent different courses of patients than controls (37.9 vs. 11.2, p\0.001). Except for the sexual the same disorder. DLB is also sometimes considered a transition function domain, the mean scores for each domain were also higher in between PD and Alzheimer dementia (AD). The definite diagnosis of the PD patient group (p \ 0.001 in all cases). The NMSS total score these diseases is made during autopsy, therefore, efforts are under

123 S92 J Neurol (2012) 259 (Suppl 1):S1–S236 way to identify in vivo markers that could help in differential diag- present between the groups in left caudate and putaminal uptake nosis of these neurodegenerative (ND) diseases. The aim of this study values. was to assess cerebrospinal fluid (CSF) levels of ND markers tau Conclusions: The frontal impairment reported in PD patients with protein and beta-amyloid 1-42 and compare these levels among WH may be due to a right caudate dysfunction, as it is connected to patients with probable PD, PDD, DLB and AD. the frontal brain areas via neuronal loops. If confirmed in larger Methods: CSF levels of ND markers were assessed in 72 patients studies, our data could suggest early caudate dysfunction as a (32 men, 40 female; aged 44-82 years, mean 67.18±14.76). The potential predictive marker of development of VH during the course studied group included 32 patients with PD, 14 with PDD, 9 with of PD. DLB and 18 with AD. CSF levels of ND markers were assessed using ELISA, Kruskal–Wallis test, t-test and Mann–Whitney test were used for statistical analysis of the results. Results: Across the patient groups, levels of tau protein and the P417 index tau protein/beta-amyloid 1-42 were increasing in the order PD Orthopaedic complications of patients with Parkinson’s \ PDD \ DLB \ AD, whereas beta-amyloid 1-42 levels were disease in Japanese agricultural district decreasing in the same order. In pairwise group comparisons, the H. Takada, Y. Oyama, S. Kon following differences were statistically significant: higher levels of Aomori Hospital (Aomori, JP) tau protein and the index tau protein/beta-amyloid 1-42; and lower levels of beta-amyloid 1-42 were found in AD patients compared to Objectives: Orthopaedic complications often effectuate motor dis- all other patient groups. Levels of index tau protein/beta-amyloid 1-42 ability in Parkinson’s disease (PD). Aging and physical labor relate to were higher in PDD patients compared to PD patients (p=0.006) and some orthopedic impairments. Graying and hard manual work are levels of beta-amyloid1-42 were found lower in DLB patients than in pointed in Japanese agricultural villages. The aim of this study was PD patients (p=0.02). to clear medical conditions of orthopaedic complications in PD, Conclusion: The presented study shows that CSF of PDD and particularly in a Japanese agricultural district. DLB patients manifests similar changes as that in AD patients, but Methods: Orthopedic complications in PD were retrospectively some of these changes did not reach statistical significance. The investigated from medical records in series of outcome patients with results also suggest that PDD and DLB may represent gradual tran- PD in our hospital, situated in a Japanese agricultural district, from sition from PD to AD. 2008 to 2010. Complaints of pain for the spine or limbs including Supported by grant IGA MHCR NT12221-5/2010. joints, and existence of cervical or lumbar canal stenosis, osteoarthritis, osteoporosis, and fracture were surveyed. Results: One hundred and six patients (62 females and 44 males, 72.3 ± 8.3 years) were recruited (Hoen and Yahr scale, HY; 3.6 ± P416 0.6). Lumber pain was observed in 89 of 106 patients (84 %). Thirty Visual hallucinations in Parkinson’s disease: possible nine of 89 patients also complained pains for other parts of the spine or limbs. Knee joint pain was recognized in 26 % of patients. All role of FP patients with knee joint pain complained similarly other part pains. L. Kiferle, D. Frosini, D. Volterrani, S. Mazzucchi, The mean age was older and HY was higher significantly in patients U. Bonuccelli, R. Ceravolo with pains compared to those in patients without. Lumbar canal ste- University of Pisa (Pisa, IT) nosis was described 56 of 106 patients (53 %). Osteoporosis was observed in 34 %, and fracture of spine in 8 %. All patients with Objective: To unveil whether a worse nigrostriatal dysfunction osteoporosis or fracture complained lumber pain. Osteoarthritis of at baseline may predict the development of VH in the course of PD. knee was shown in 21 % of patients. All patients with osteoarthritis of Background: The pathogenesis of visual hallucinations (VH) knee complained knee joint or lumber pain. The mean age was older in Parkinson’s disease (PD) has been considered multifactorial. and HY was higher significantly in patients with orthopedic compli- Generally considered as an adverse effect of dopaminergic cations than those in patients without. Seventy three percents of treatment, they are at least partially caused by the disease itself. In patients with lumber pain had orthopaedic complication (lumber canal the pathophysiology of VH a combination of impaired visual stenosis; 63 %, osteoporosis; 30 %, fracture; 10 %). Seventy nine processing and attention has been reported. Imaging studies evi- percents of patients with knee joint pain diagnosed as osteoarthritis of denced a role of the primary visual system and visual association knee. areas as well as a dysfunctional activation of frontal areas in the Conclusion: Not a small number of patients were suffered from occurrence of VH. Moreover, longitudinal neuropsychological pains for the spine or limbs and had organic orthopaedic complica- studies showed an association of VH with baseline frontal dys- tions adding to motor disability according to PD, in a Japanese function, suggesting verbal fluency as a potential predictor of VH agricultural district. We should pay more attention to orthopaedic development within 2 years. Due to the functional connections complications in patients with PD. between basal ganglia and frontal areas, a role of basal ganglia and of the fronto-striatal circuits in the pathogenesis of VH may be postulated. P418 Methods: 16 non demented PD patients with VH and 14 PD non demented patients without WH, matched for age of onset of disease, Changes in extracellular noradrenaline levels disease duration and severity, levodopa equivalent dose, performed a after amantadine administration in the normal rat 123I-FP CIT SPECT at the onset of the disease. The striatal uptake cerebral cortex values in the two groups were investigated, in order to evaluate K. Kannari, E. Ishizawa nigrostriatal differences between the two groups with different Aomori University of Health and Welfare (Aomori, JP) behavioral phenotype. Results: The group of WH patients had a significant reduction Objectives: To determine whether administration of amantadine (p\0.05) of right caudate uptake values at baseline when com- affects extracellular noradrenaline (NA) levels in the rat cerebral pared with patients without WH. No significant differences were cortex.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S93

Background: Although NA is one of the major monoamines in the Objectives: The corticobasal syndrome is a neurodegenerative dis- central nervous system, the role of NA in the brain of Parkinson’s order that has core features consisting of asymmetric parkinsonism, disease remains to be determined. Previously we demonstrated that other movement disorders such as dystonia and myoclonus, cortical L-DOPA administration increased extracellular NA levels in the rat features as apraxia, disexecutive cognitive impairment and other cerebral cortex and the stratum. We hypothesize that amantadine, one clinical traits less prevalent. The diagnosis criteria include the of the drugs used for mild Parkinson’s disease, would exert its anti- exclusion of identifiable cause, but cases with previous brain lesion parkinsonian effect by increasing NA levels in the cerebral cortex. before development of the syndrome has been described and it may Methods: Using in vivo microdialysis method, we measured influence in the clinical progression of the disease. The objective of extracellular NA levels in the cerebral cortex (medial prefrontal our study was to assess of the clinical features, structural and func- cortex) of normal adult male Wistar rats. Dialysates collected for tional neuroimaging in four patients with corticobasal syndrome every 20 min were automatically injected onto the column for high developed after a stroke. performance liquid chromatography (HPLC). NA was detected by Methods: Four patients were evaluated (2 men and 2 women), aged electrochemical detection system. We observed changes in NA levels 71±1.63years (69-73 years). All patients had a previous stroke, 2 with following intraperitoneal injection of amantadine (0 mg/kg = vehicle, sequelaes and 2 without them. All patients developed a corticobasal 50 mg/kg, 100 mg/kg) for 4 h. syndrome. Neuroimaging studies including magnetic resonance Results: Although extracellular NA levels in the cerebral cortex imaging and functional 123I-FP-CIT SPECT were performed. did not show any change following vehicle administration, they were Results: All patients showed chronic ischemic lesions in structural increased to 195 % of basal levels by 50 mg/kg amantadine admin- neuroimaging besides a more severe atrophy ipsilateral to the ische- istration, and also increased to 223 % of basal levels by 100 mg/kg mic lesion and contralateral to the more affected hemibody. The amantadine administration. The AUCs of extracellular NA levels interval between the stroke and the development of the corticobasal during 260 min following amantadine administration were 1363 ± syndrome was 7.75±6.24 years. A presinaptic dopaminergic defi- 143 %•min, 2207 ± 184 %•min (p\0.05), and 2732 ± 98 %•min ciency in 123I-FP-CIT SPECT was demonstrated in all patients. (p\0.01) in 0 mg/kg, 50 mg/kg, and 100 mg/kg amantadine admin- Conclusion: Patients with preexisting to develop the corticobasal istration, respectively. syndrome, the initial clinical manifestations and the more severe Conclusion: The present results suggest that amantadine has an affected side are usually contralateral to them. This may suggest the ability to increase extracellular NA levels in the cerebral cortex. At possible susceptibility of brain areas previously damaged to develop a least some part of antiparkinsonian effect of amantadine may derive corticobasal syndrome. from its NA-increasing effect in the cerebral cortex.

P421 P419 Consequences of non-compliance in clinically Inspiratory stridor as an initial symptom of multiple asymptomatic Wilson’s disease patients diagnosed system atrophy by family screening M. Kaiserova, K. Mensikova, L. Tuckova, P. Kanovsky, K. Dziezyc, A. Czlonkowska M. Vastik Institute of Psychiatry and Neurology (Warsaw, PL) Palacky University (Olomouc, CZ) Objectives: Wilson’s disease (WD) is an autosomal recessive Background: Respiratory symptoms including stridor, sleep-disor- inherited disorder of copper metabolism. Familial screening should dered breathing and respiratory insufficiency are known to be part of be performed after WD was diagnosed in the proband, because the clinical spectrum of multiple system atrophy (MSA), often early diagnosis and treatment can prevent symptoms development. occurring late in the disease. Here we present a patient who developed The aim of study was compliance assessment in WD patients stridor caused by bilateral vocal cord paresis requiring urgent tra- diagnosed by family screening who had no previous history of any cheostomy, when only mild parkinsonian and autonomic symptoms symptoms. were present. Typical clinical features of MSA-P developed later in Methods: We have retrospectively analyzed data of 82 clinically the disease course. asymptomatic WD patients diagnosed by family screening in our Methods: Regular visits with physical examination supported by center between 1964 and 2008. We gained information about medical paraclinical tests (brain MRI, psychological examination, head-up tilt history, physical examination, laboratory tests, at the time of diag- table test, external sphincter electromyography) suggested diagnosis nosis and during control visits. Clinically asymptomatic patients were of MSA-P. Definitive diagnosis of MSA was confirmed neuropatho- defined as having any history of neurological or hepatic symptoms. logically post mortem, 5 years after the first symptoms occurred. Compliance on anti-copper treatment has been assessed by interviews Vocal cord paresis was caused by specific oligodendroglial inclusions during follow-up visits. Non-compliance was defined as irregular in the medulla oblongata. anti-copper treatment for at least one month. Results: In patients with only mild motor and autonomic symp- Results: We have assessed 70 of 82 WD clinically asymptomatic toms but who develop unexplained stridor, diagnosis of multiple patients after follow-up period (median follow-up period: 15 years). system atrophy should be always considered. 12 patients were lost in follow-up. 29 (41 %) of 70 patients were non- compliant. After the follow-up period: 20 (69 %) of 29 non-compliant patients developed clinical symptoms: 9 (45 %) hepatic failure, 7 (35 %) neuropsychiatric symptoms and 4 (20 %) patients died from P420 liver failure. Of 41 compliant patients 39 (95 %) remained without Corticobasal syndrome in patients with previous stroke: clinical symptoms, 2 died because of cancer (leukemia and bladder description of four cases cancer). Conclusions: Compliance is essential for successful WD treat- S. Jesus, M. Caceres, A. Sua´rez, E. Franco, E. Gil-Neciga, ment. Our observations indicate that anti-copper treatment prevent P. Mir WD symptoms development in patients without clinical symptoms, University Hospital Virgen del Rocio (Sevilla, ES) provided that there was adherence to drug therapy.

123 S94 J Neurol (2012) 259 (Suppl 1):S1–S236

P422 Results: A 59-year old Caucasian woman developed new-onset Case report: paroxysmal movement disorder in acute generalized seizures. EEG monitoring showed bilateral focal temporal and occipital spikes with secondary generalization. Initial neurolog- pontine infarct ical examination, metabolic profile, brain MRI, lumbar puncture, A.M. Lascano, N. Wassilew, A. Coeytaux, P. Pollak, were normal except for high anti-thyroglobulin antibodies (444 IU) I. Momjian-Mayor with normal anti-thyroperoxidase antibodies. Despite treatment with University Hospital (Geneva, CH) daily Prednisone (60 mg) and sequential addition of multiple antiepileptic drugs (levetiracetam, topiramate, phenytoin, lacosamide and Objective: Paroxysmal movement disorders (PMD) are rare invol- gabapentin), she had recurrent seizures and multiple admissions for untary and episodic phenomena which are currently underestimated in status epilepticus. She received IV methylprednisone for five days vascular disease; mainly due to briefness of symptom presentation without benefit. IVIg 2 gm/Kg was given twice at 1-month intervals and prompt clinical recovery. We report a case of rapid onset lower with some improvement in the seizures for about one week. However, limb PMD precipitated by an acute pontine infarct. In addition, we she relapsed and became confused, disoriented, agitated with visual discuss possible underlying physio-pathological mechanisms. hallucinations, appendicular rigidity and myoclonus and tested posi- Methods: A 84-year-old woman with a history of treated hyper- tive for anti-GAD antibody at 3.4 U/ml (normal 0-1.5U/ml). At this tension and ischaemic heart disease, was transferred to our centre on stage she was given IV Rituximab, 375 mg/m2, twice at 1-week account of a left motor hemisyndrome. On neurological examination, interval. There was marked improvement in cognition, rigidity and we found mild-to-moderate paresis of the left arm and leg, left-sided myoclonus and she was seizure-free after two cycles of Rituximab hyperreflexia and pathological plantar reflex. Every 10 s, we observed therapy. The anti-GAD antibody became undetectable. There were no an abrupt movement of the left leg at a rate of 4-6 times per minute, in immediate adverse effects from the therapy. resting position only, and lasting 48-72 h. While in supine position, Conclusion: Rituximab is a safe and effective treatment for HE muscles of the left lower limb contracted with quadriceps flexion and and PERM associated with anti-GAD antibody when refractory to plantar and toe extension. No impairment of the patient’s level of other immunomodulatory therapies. consciousness or mental status during the episodic movements was observed. Results: Diffusion-weighted brain magnetic resonance imaging showed an acute large right pontine ischaemic lesion without haemorrhagic transformation. No significant carotid atherosclerosis P424 was seen at carotid ultrasound Doppler. A transthoracic echocardi- Dispersion of ventricular repolarisation as diagnostic ography showed mild left auricular dilatation and moderate tool in the assessment of autonomic function concentric left ventricular hypertrophy. Due to the large lesion size, the stroke was suspected to be of cardioembolic origin. Patient was in Parkinson’s disease treated with acetylsalicylic-acid 300mg q.d. To control the move- H. Ulvi, L. O¨zel, R. Demir, G. O¨zdemir, A. Ertekin, ment disorder we introduced levetiracetam 500mg b.i.d. on R. Aygu¨l admission and we assessed a movement frequency reduction after Atatu¨rk University (Erzurum, TR) 72 h. The latter was diminished to 250mg b.i.d. and stopped 20 days after symptom onset. Purpose: The aim of our study was to evaluate possible autonomic Conclusion: Acute large brainstem lesions can be associated with nervous system (ANS) dysfunction in patients with Parkinson dis- focal PMD, sharing striking clinical similarities with the so-called ease (PD), and its correlation with score of Hoehn and Yahr Scale ‘‘tonic-seizures’’ (i.e. Matthews’ phenomena) experienced in multiple (SHYS). sclerosis. In our patient PMD could result of corticospinal tract Methods and results: We studied 21 patients with PD; the mean damage; provoking a disturbance of the sensory afferent input into the age was 63.56±17.92 years (yrs) (range 30 yrs to 70 yrs; 8 female and basal ganglia, thus, leading to cortical disinhibition. In order to val- 13 male) and 59 age-matched healthy subjects (control), the mean age idate this hypothesis, molecular medicine techniques should be was 61.64±11.21 years (yrs) (range 33 yrs to 87yrs; 31 female and 28 applied to assess basal ganglia function during brainstem lesions. In male). In all persons resting 12-lead electrocardiograms were recor- conclusion, PMD should be considered as a manifestation of brain- ded with paper speed of 50 mm per second and standardizations of 0.5 stem stroke. mV per centimeter for measurement of QT dispersion (QTd), corrected QTd (QTcd), JT dispersion (JTd) and corrected JT dispersion (JTcd). The QT and JT intervals were measured from beginning and P423 from the end of the QRS complex, respectively, to the end of T. If U Rituximab therapy in a patient with recurrent waves were present, QT interval was measured to the nadir of the curve between the T and U waves. None of the patients were taking Hashimoto’s encephalitis, anti-GAD antibodies any antiarrhythmics or drugs which may alter results of QT and JT and progressive encephalomyelitis with rigidity analysis. We excluded concurrent risk factors for other autonomic and myoclonus nervous system disorder. In the analyses of the QT and JT intervals, D. Kassar, S. Damodaram, P. Chand, S. Iyadurai the values of the maximum QT and JT interval were used and Bazett’s formula (QTc=QT/RR) was applied for heart rate correction (QTc, Saint Louis University (St. Louis, US) JTc). The QT and JT dispersion were defined as the difference Objective: To report the results of therapy with Rituximab in a patient between the maximum and the minimum QT and JT intervals, with recurrent HE, anti-GAD antibodies and PERM. respectively, in any of the 12 leads. Background: HE is a rare autoimmune disease with recurrent Differences between the means of groups were determined using neurologic and psychiatric features. PERM is a rare disorder char- the unpaired t-test. The correlation of two parameters was tested using acterized by muscular rigidity, painful spasms, myoclonus associated a linear regression analysis. Values of p\0.05 were accepted as sta- with autoantibodies to glutamic acid decarboxylase (GAD), glycine tistically significant and NMDA receptors. Mean QT-d, QTc-d, JTd, JTc-d in PD were significantly longer Method: Case report. than that of the normal subjects (p\0.05) (table 3). No correlation

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S95 was observed between SHYS and ventricu¨ler repolarization disper- investigate the possible role of sleep rebound in modulating neuro- sion parameters. protection observed in the prestroke SD paradigm. Conclusion: The autonomic nervous system effects the QT inter- Methods: Sprague–Dawley rats were used in the study. They were val, and QT prolongation is observed in patients with autonomic subjected to continuous polygraphic recordings for baseline, during SD, dysfunction. Dispersion of repolarization, the difference in repolari- and 24 h after ischemia. SD for 6h was performed by gentle handling zation duration among several electrocardiographic leads, has been before ischemia. Focal cerebral ischemia was induced by permanent proposed measure of repolarization heterogeneity, and increased occlusion of distal branches of the middle cerebral artery. Brains were dispersion has been found to be associated with ANS. We conclude collected 3 or 7 days after surgery. Control experiments included ische- that ventricular repolarization dispersion parameters evaluation are mia without SD (nSD), sham surgery with SD or nSD. Each experiment helpful and cheap method in the assessment of autonomic function in group included 6 rats. Nissl staining was used for assessing the infarct PD. volume and quantitative PCR (Taqman assay) for gene expression. Results: The total sleep time during the first 12 h (dark phase) after surgery increased significantly (p\0.05) in both SD groups (ischemia and sham), by 30 % when compared to the baseline (paired General neurology t-test) and by 20 % when compared with the nSD/ischemia group (One way ANOVA: F2, 15 =10.4, p=0.001, followed by post hoc comparison). Further analysis indicated a significant (p\0.05) increase in both NREM (One way ANOVA: F 2, 15 =5.88, p=0.013, P425 followed by post hoc comparison) and REM sleep (One-way Intravenous immunoglobulin treatment in post H1N1 ANOVA: F 2, 15 =12.3, p=0.001, followed by post hoc comparison). vaccination narcolepsy –cataplexy The infarct volume decreased significantly by 50 % in the SD/ H. Hidalgo, V. Uhl, C. Bassetti, U. Kallweit ischemia compared to nSD group (Mann–Whitney test: 28.8+10.4 vs. 57.4+16.2 mm3, p=0.0047) on poststroke day 7. Rats that were sub- Kamillus-Klinik (Asbach, DE); University Hospital Zurich (Zurich, jected to SD/ischemia but allowed to sleep for 24 h before ischemia Berne/Lugano, CH) showed no change in the infarct volume to the nSD group (48.5 vs. Background: An autoimmune basis for narcolepsy-cataplexy (NC) 57.4+16.2 mm3, p=0.211). The Taqman assay showed a massive has long been suspected and recent results have strengthened this increase (p\0.05) in expression of inflammatory genes TNFa (on day hypothesis. Infections or vaccinations might be precipitants for the 3), IL-1b and IL-10 in the SD/ischemia compared to nSD group. disease. Recent data indicate a possible association between H1N1 Conclusion: SD prior stroke resulted in a sleep increase (sleep vaccine and the onset of NC. Results of intravenous immunoglobulin rebound) in the acute phase of stroke and a decrease in the infarct (IvIg) therapy on NC patients are controversial. size. Removal of sleep rebound eliminated the reduction of infarction. Case report: We report on a 15-year-old girl who reported the These results suggest the sleep rebound may play a role in mediating onset of excessive daytime sleepiness (EDS), cataplexies and sleep neuroprotection pathways, such as neuroinflammation. paralysis about two to four months after H1N1 flu-vaccination on November 8th, 2009 with Pandemrix. In video-polysomnography immediate onset of REM sleep (5 min), a fragmented sleep pattern, REM sleep behavior disorder and P427 periodic leg movements (index 23/h) were found. On Multiple Sleep Comparison of transplantation of bone marrow stromal Latency Test, mean sleep latency was 2.5 min and 4 sleep onset REM cells and stem cell mobilisation by granulocyte colony- periods (SOREMP) occurred. She is HLA DQB1 9 0602 positive. stimulating factor after traumatic brain injury in rat Modafinil therapy (100-300mg/d) had a moderate effect on EDS. In October 2011, 19 months after disease onset, approximately, M. Marzban, M. Bakhtiary, S. Samavati IvIg therapy was initiated. She received IVIG 1 g/kg/day in 1 day/ Tehran University of Medical Science (Tehran, IR) month, 3 times. IvIg treatment was well tolerated. Background: Recent clinical studies of treating traumatic brain injury After three IvIg infusions, she did not describe any improvement. (TBI) with autologous adult stem cells led us to compare effect of Within the last six months, severity and frequency of cataplexies had intravenous injection of bone marrow mesenchymal stem cells deteriorated, EDS did not change. Due to lack of improvement, IvIg (BMSC) and bone marrow hematopoietic stem cell mobilization, treatment was stopped. induced by granulocyte colony stimulating factor (G-CSF), in rats Discussion: Our case does not support a favorable effect of IvIg in with a cortical compact device. the treatment of post H1N1 NC. The late start of IvIg therapy after Methods: Forty adult male Wistar rats were injured with con- disease onset may account for the lack of efficiency in our patient. trolled cortical impact device and divided randomly into four groups. The treatment groups were injected with 2 9 106 intravenous bone marrow stromal stem cell (n = 10) and also with subcutaneous G-CSF (n = 10) and sham-operation group (n = 10) received PBS and ‘‘bromodeoxyuridine (Brdu)’’ alone, i.p. All injections were per- P426 formed 1 day after injury into the tail veins of rats. All cells were Sleep rebound and neuroprotection in a rat model labeled with Brdu before injection into the tail veins of rats. Func- of focal cerebral ischaemia tional neurological evaluation of animals was performed before and B. Gao, A. Hodor, C. Bassetti after injury using modified neurological severity scores (mNSS). Animals were sacrificed 42 days after TBI and brain sections were Inselspital (Berne/Lugano, CH) stained by Brdu immunohistochemistry. Introduction: Sleep-wake disturbances are frequent in stroke patients Results: Statistically, significant improvement in functional out- and linked with a poorer functional outcome. Sleep deprivation (SD) come was observed in treatment groups compared with control group prior to stroke was reported to be neuroprotective and beneficial for (P\0.01). mNSS showed no significant difference between the BMSC functional recovery in rodents. The aim of this study was to and G-CSF-treated groups during the study period (end of the trial).

123 S96 J Neurol (2012) 259 (Suppl 1):S1–S236

Histological analyses showed that Brdu-labeled (MSC) were present Objective: X-linked adrenoleukodystrophy (XALD) is a rare neuro- in the lesion boundary zone at 42nd day in all injected animals. metabolic peroxisomal disorder due to mutations in ABCD1 gene on Conclusion: In our study, we found that administration of a bone Xq28 with excessive very-long-chain fatty acids accumulation, ner- marrow stimulating factor (G-CSF) and BMSC in a TBI model pro- vous system demyelination and impaired adrenocortical and testicular vides functional benefits. function. Often is being misdiagnosed as multiple sclerosis in adults. For the X-linked recessive mode of inheritance, XALD primarily affects males at different ages. However, heterozygous females carrying ABCD1 mutations may manifest XALD symptoms in P428 adulthood, exceedingly rare already in childhood. Our aim was to Clinical course and prognosis of paraplegia due evaluate XALD clinical presentations in adult female disease carriers. to metastatic spinal cord compression Methods: The study comprised 50 female XALD carriers, aged 20- 72 years, selected for the positive family history (female relatives of M. Hara, M. Yamamoto, T. Isaji, R. Kayamori XALD affected boys and men) and genetic confirmation of the het- Saitama Prefectural University (Saitama, JP); Teikyo University erozygous status for ABCD1 gene mutation. Neurological, Hospital (Tokyo, JP) psychiatric, neuroophthalmologic and endocrine examinations, brain Objectives: To clarify the clinical course and prognosis of paraplegia and spine magnetic resonance imaging (MRI) and magnetic reso- due to metastatic spinal cord compression (MSCC). nance spectroscopy (MRS) along with electromyoneurography Methods: Subjects were metastatic paraplegia patients who were (EMNG), electroencephalography (EEG), evoked potentials (EPs) admitted and consulted at the rehabilitation center of a university and cerebrospinal fluid (CSF) analyses were performed in the studied hospital from April 2009 to March 2011. Their neurological syn- XALD carriers. Results: Seven women (14 % of the studied), mean dromes and initial impairment levels were evaluated according to the age 47 years were diagnosed as XALD symptomatic carriers: five International Standards for neurological and functional classification exhibited slowly progressive lower limbs weakness with spastic of spinal cord injury and the American Spinal Injury Association paraparetic features and had sensory and sphincter disturbance due to Impairment Scale (AIS). Their daily living abilities were assessed by adrenomyeloneuropathy only; one had AMN accompanied by vom- Eastern Cooperative Oncology Group Performance Status at the time iting episodes, prominent intolerance to infections and increased of onset of paraplegia and after radiotherapy for MSCC. pigmentation referring to the associated Addison’s disease; one was Results: There were 14 patients (12 men and 2 women, mean age with AMN and clinically inapparent cerebral demyelination of the 63.8 years). The main primary malignancies causing MSCC were cerebral XALD pattern as assessed by brain MRI and MRS. The most lung cancer (5/14: 36 %), malignant lymphoma, cholangiocellular frequent disease presentation was AMN proved in all the symptomatic carcinoma and prostate cancer (2/14: 14 % respectively). Nine carriers. Majority (71.4 %) of the affected had AMN as an isolated patients (64 %) were diagnosed their main primary malignancies after disorder. AMN accompanied by Addison’s disease and AMN with the onset of paraplegia. All patients showed the preceding symptoms cerebral demyelination had rare and equal occurence (2 % of the as back pain (57 %), weakness of legs (29 %) and fall (14 %) studied). Polyneuropathy was the missing AMN feature in 57.1 % of between 4 and 180 days prior to the onset of paraplegia. As to the affected, while none of the studied carriers had either isolated impairment of paraplegia of onset, their AIS grades were classified cerebral XALD or isolated Addison’s disease. Conclusion: XALD into A (3/14: 21 %), B (8/14: 57 %), C (2/14: 14 %) and D (1/14: should be sought for also in females suffering from spastic parapa- 7 %). All patients showed that motor and sensory neurological resis, Addison’s disease or demyelinating encephalopathy as diverse involvements were thoracic level which were confirmed by MR/CT cell X-inactivation ways may cause various XALD clinical expres- imaging: Th 1-6 (64 %) and Th 7-12 (36 %). All patients were sions in XALD female carriers. classified into grade 4 as to disabilities of onset on the performance status. All patients were unable to walk and required catheterization due to neurogenic bladder. Local irradiation (21 to 48 Gy) and cor- P430 ticosteroid for the medical therapeutics of MSCC were provided for all patients, supportive or palliative physical therapies were provided The role of mitochondrial dysfunction for 12 patients and a spinal surgery was performed for 1 patient. No in the pathogenesis of Friedreich’s taxia one improved in the performance status grade even though providing W. Fadel, W. Fadel, H. Nassar, W. Ibrahim, W. Bahnasy comprehensive medical therapies and 10 patients (71 %) passed away Tanta University Hospital (Tanta, EG) within 18 months after onset of paraplegia. There were no statistical differences between the numbers of life and death comparing the Friedreich’s ataxia is a neurodegenerative disease caused by GAA thoracic lesion of MSCC and presence of visceral metastasis (Chi- expansion in a gene coding for a mitochondrial protein; frataxin. square test). Objectives: To study the role of mitochondrial complexes dys- Conclusion: Prognosis of the patients with MSCC were not sat- functions and increased oxidative stress in the pathogenesis of FRDA isfactory both in life expectancies and daily living abilities despite and their relation to disease severity. providing any necessary medical treatments and rehabilitative care. Methods: Blood samples were obtained from 20 Friedreich’s ataxia patients and 10 ages matched healthy control subjects. Mito- chondrial complexes activities were calibrated spectrophotometrically and the levels of each of serum and lymphocyte glutathione were examined by reverse phase liquid chromatography. P429 Results: There are decreased activities of all mitochondrial com- X-linked adrenoleukodystrophy clinical manifestations plexes (I, II, III & IV) in FRDA patients if compared with normal in adult female disease carriers control. Also, there are decreased level of each of serum and lymphocyte glutathione in FRDA patients. A. Potic, D. Momcilovic-Kostadinovic, A. Rovelli, P. Corti, Conclusions: FRDA is a mitochondrial disorder as evidenced by H. R. Waterham, T. Smiljkovic, J. Potic the decrease in activities of mitochondrial complexes in FRDA University of Belgrade (Belgrade, RS); University of Milan Bicocca patients. There is increased oxidative stress in FRDA patients both (Monza, IT); University of Amsterdam (Amsterdam, NL) intra- and extra cellular.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S97

P431 limbs weakness. The examination revealed dysarthria with sponta- Neurological complications after cardiac surgery neous myoclonus, proximal weakness of left lower limb, global areflexia with no pathologic plantar reflexes, mild thermalgesic and in octogenarians. is age a limiting factor? severe proprioceptive hypoesthesia in lower limbs, dysmetria on Y. Carrascal, A.L. Guerrero, H. Valenzuela, G. Laguna, P. finger-nose testing, wide-based gait and Romberg sign. Pareja, M. Fernańdez, J.R. Echevarrıá, N. Arce, S. Flores Results: Laboratory blood and CSF screening was normal. Cranial University Hospital (Valladolid, ES) MRI and toracoabdominal tomography were normal. The electrophysiologic testing reflected an axonal sensory neuropathy. Several Objectives: Neurological complications lead to significant morbidity months after admission, the neurologic features suffered a progressive and mortality related to cardiac surgery. Demographics of cardiac deterioration along the years. A genetic study was negative but, after surgery patients are changing, with a progressive increase in number 6 years of evolution, and due to high suspicion, a repeated study of patients aged 80 years and more. We aim to identify incremental showed homozygosis for FA with repeat range over 500. risk factor for major neurological complications in octogenarians Conclusion: FA primarily affects spinal cord and dorsal root following cardiopulmonary bypass. ganglia, leading to mixed ataxia. Initially the differential diagnosis in Methods: All patients 80 years of age or older who underwent our case included acute polyneuropathies such as ataxic Guillain- cardiac surgery with extracorporeal circulation in our department in a Barre´, and acute cerebellar ataxias, mainly described following tertiary hospital from January 2000 to January 2012 were identified infectious diseases. Metabolic and neurodegenerative disorders typi- (group A). They were matched with a contemporaneous population of cally manifest with gradual onset of ataxia. In FA the full patients in our institution younger than 80, with similar gender, type constellation of symptoms is not usually seen until several years after of surgery (including ascending aorta procedures in both groups) and presentation; however, in this case almost all the features were comorbidity (group B). We retrospectively evaluated risk factors for present since the beginning. There are reports of cases with delayed major neurological complications (stroke, transient ischemic attack age of onset, no affected relatives and retained lower limb reflexes, (TIA), seizures, coma and acute confusional syndrome) after cardiac but we have not found any case of FA with acute/subacute onset in the surgery. literature. This fact joined to the absence of familiar history, made Results: 375 patients were included in Group A and 165 in Group diagnosis difficult. FA must be part of the differential diagnosis of an B. Major neurological complications were slightly more frequent in acute ataxia, though it is not its common presentation. The finding of octogenarians (6.7 % vs 5.8 %). When analyzing the different neu- an axonal sensory neuropathy may support the suspicion. rological complications we found no significant difference between both groups regarding stroke, TIA, seizures or coma but we recorded more incidence of postoperative acute confusional syndrome in Group A (1.3 % vs 0.4 %). In multivariate analysis, preoperative anaemia (according with World Health Organization criteria) (p: 0.0037); RR P433 0.21, IC 95 % (0.07-0.6) and mitral valve surgery (p: 0.0305); RR Bilateral papilloedema in patient with rhinorrhoea 0.36 IC 95 % (0.14-0.91), were identified as risk factors for postop- C. Valencia, M.J. Gallardo, M.J. Corrales, J. Domıńguez, erative major neurological complications in group A. In group B, the B. Miguel, A. Lo´pez, M.J. A´lvarez, S. Carrasco only risk factor identified was peripheral vascular disease (p: 0.0068); Hospital General Universitario (Ciudad Real, ES) RR 3.72 (1.43-9.64). Conclusions: Major neurological complications after cardiopul- Objectives: Cerebrospinal fluid (CSF) leaks cause neurological monary bypass are not significantly higher in our octogenarian symptoms as well as spontaneous intracranial hypotension. The most population. Although in younger than 80 years peripheral vascular common CSF leak symptom is an orthostatic headache. Other disease is the most significant risk factor, it seems that intraoperative symptoms include dizziness, diplopia, nausea, vomiting, rhinorrhea or inadequate brain oxygenation (secondary to preoperative anaemia) is otorrhea. CSF leak diagnosis includes a lumbar puncture and a the most critical determinant of neurological complications in patients cisternography. older than 80 years. Methods: A 55 years old man presents, for eight days, rhinorrhea, headache (which gets worse at decubitus position), diminished visual field (mainly peripheral) and bilateral papilledema. Neither computed tomography or magnetic resonance imaging (MRI) show any space- P432 occupying lesion. MRI shows empty sella syndrome and suggests left cribriform plate defect. At lumbar puncture, opening fluid pressure is Acute onset of Friedreich’s ataxia mimicking ataxic normal. Cisternography shows abnormal deposit located in left nos- polyneuropathy tril. Cisternography confirms cranial CSF leak, and repairing surgery B. Miguel, A. Hernańdez, J. Domıńguez, C. Valencia, is programmed. During the procedure, neurosurgeon observes bilat- A. Lo´pez, M.A. Del Real eral cribriform plate defect, which was repaired. General Hospital (Ciudad Real, ES) Results: Four months after surgery, patient still presents headache and bilateral papilledema, although rhinorrhea is no longer present. Objectives: Friedreich Ataxia (FA) is a degenerative disorder with Headache has different characteristics now; it doesn’t change autosomal recessive inheritance, due to an expanded trinucleotide according to positions, and it increases with Valsalva maneuver. (GAA) repeat of the frataxin gene (pathologic number from 66 to Opening fluid pressure at control lumbar puncture is 33 cmH2O. 1700). The main manifestations are neurologic dysfunction, cardio- Conclusion: Idiopatic intracranial hypertension refers to patients myopathy and diabetes mellitus. FA usually begins before age 25 with with elevated pressure without any space-occupying lesion. It is progressive ataxia and gait disturbance. We describe a case of FA characterized by headache and papilledema, but other possible presenting with acute onset of cerebellar and sensory ataxia. symptoms are vomiting, pulsatile tinnitus, diplopia or visual blurring. Methods: We present a 21 years old man with action tremor and Headache increases with changing position and standing up. CSF leak myoclonus from several years ago and familiar history of tremor. He has been described as a rare but possible complication of idiopathic referred a clinical picture of fifteen days of evolution of mild gait intracranial hypertension. The cribriform plate and the sella region are instability and paresthesias in both knees and feet, with slight lower the most common sites for the development of a high pressure CSF

123 S98 J Neurol (2012) 259 (Suppl 1):S1–S236 leak. In our patient, rhinorrhea seems to be due to the cribriform plate Case 1. A 45 year old woman developed headaches and diplopia defect, but our patient also had an empty sella syndrome, which over 4 weeks. Examination was normal apart from an oculomotor could, aswell, contribute to develop the CSF leak. nerve palsy. MRI brain was unremarkable but cerebrospinal fluid (CSF) showed a mixed pleocytosis and low glucose. Extensive CSF tests failed to confirm an infective or malignant cause. Her condition did not respond to antibiotics, antituberculous drugs, and steroids. P434 Eight weeks later she developed radicular pain in one arm. Spinal Influence of volitional load on the Bereitschaftspotential cord MRI revealed dural based lesions, and biopsy demonstrated (readiness potential) poorly differentiated adenocarcinoma. No primary tumour was A. Rutschmann, L. Deecke found. Case 2. A 39 year old man developed back pain and bilateral sciatica. His symptoms resolved rapidly and he did not present until University of Vienna (Vienna, AT); Medical University of Vienna 2 weeks later with worsening headaches with diplopia. On exami- (Vienna, AT) nation there was an abducent nerve palsy and bilateral papilloedema. Objective: In voluntary movement cerebral processing, the frontal MRI brain was normal, CSF analysis showed mixed pleocytosis with lobe is, according to our data, the earliest station of planning. We raised protein and low glucose. He was treated for bacterial men- have reported that the frontal SMA (supplementary motor area ingitis although no infective cause was confirmed, and his symptoms [Brodmann’s area 6a alpha] including pre-SMA [6a beta] and cin- resolved over 2 weeks. Spinal MRI demonstrated an intrinsic conus gulate motor area, CMA [area 24]) generate the first recordable abnormality with the appearances of an ependymoma, subsequently movement-related cerebral activity. Other than previous belief the confirmed histologically. Case 3. A 35 year old man developed SMA activity is not travelling directly to motor cortex (MI [area 4]) worsening headaches over 5 weeks, with symptoms of raised but via the motor loop (cortico-basal ganglio-thalamo-cortical loop). intracranial pressure. On examination there was neck stiffness and The loop concept explains how the huge program storages of the basal bilateral papilloedema. MRI brain was normal, CSF opening pres- ganglia for skilled movements can be used by the MI. The basal sure raised and there was a mixed pleocytosis with high protein and ganglia establish subroutines for well-learned movements, which we very low glucose. No infective cause was found, and CSF cytology can perform automatically. The Bereitschaftspotential (BP or readi- identified no malignant cells. He deteriorated over three weeks in ness potential) is the EEG correlate of the planning and preparation of spite of sequential empirical treatment. Although there were no lo- volitionally intended movements. The BP has two components, an calising signs, MRI of the cord identified a lesion at the conus, early one, BP1, generated by SMA, and a late one, BP2, generated by which proved to have the histological feature of malignant mela- MI, accompanying final movement execution. During BP1 we do not noma. Discussion. In these 3 cases of chronic meningitis the yet consciously perceive our own motor planning, but during BP2 we diagnosis was made due to abnormalities on spinal MRI, when do. From this observation, Libet (1983) inferred that we do not have repeated brain imaging had been normal. In Case 1, radicular free will in the initiation of action (BP1), while in the control of it we symptoms developed after eight weeks. In Case 2, initial symptoms have (BP2). We think we have free will in initiation as well. Whether of bilateral sciatica had resolved completely prior to the onset of we have freedom or not (the latter would be total determinism) is meningitis. In Case 3 there were no clinical indicators to spinal cord inherent in the brain regardless of brain states (un-conscious or pathology whatsoever. These cases emphasise the role of spinal conscious). imaging in undiagnosed chronic meningitis, even in the absence of Methods: Using the EEG, we investigated the influence of dif- localising symptoms or signs. ferent volitional loads on the BP (28 leads, 10 Ss., 105 sequential flexions [right digits 2-4] per task). sLORETA (Low resolution brain electromagnetic tomography) was also employed. Results: With high volitional load, BP1 starts earlier in SMA and P436 MI than it does with low volitional load (p\0.001; SMA=260 ms Fatal suspected progressive multifocal earlier, MI=252 ms earlier). Activations were stronger with high leukoencephalopathy following rituximab treatment volitional load in SMA, MI and parietally in the last 100 ms of BP2 for rheumatoid arthritis: a case report (p\0.05; mean differences: Cz=-1.3, C1=-1.1, Pz=-1.4 lV). Conclusions: Earlier onset and stronger activation in high volition F. Karalis, A. Triantafyllou, N. Tascos, I. Milonas actions is in line with the concept that more wilfulness is needed to 2nd Neurologic Dept (Thessaloniki, GR) plan and prepare them. In view of the initiating and controlling role of Progressive multifocal leukoencephalopathy (PML) is a rare and the SMA as part of a commanding and supervising pre-motor system, often fatal infection caused by the JC polyomavirus and character- our findings indicate a volitional, wilful access to movement initiation ized by progressive inflammation and demyelination of the white which, in the beginning, is not yet conscious; nevertheless it is free. matter of the brain at multiple locations. It is mostly observed in Supported by the University of Vienna – Research Fellowship patients with HIV infection, lymphoid malignancies, after organ and (FSIB) to A. Rutschmann. stem cell transplantations and more recently in the context of new therapies with monoclonal antibodies like natalizumab, rituximab, infliximab and efalizumab. PML occurs at an estimated incidence of P435 0.2/100,000 patients with autoimmune diseases who do not have HIV or malignancy. PML occurs at a very low incidence among Chronic meningitis with a diagnosis made patients with rheumatic diseases. PML has been described until only after spinal cord imaging: a series of three cases today in about 50 patients treated with rituximab, all of whom had E. Theochari, K. Wardle, D. McKee received other immunosuppressive drugs. Herein we report a case of Salford Royal Hospitals Foundation Trust (Manchester, UK); PML in a male patient with rheumatoid arthritis treated with ritux- Manchester Royal Infirmary (Manchester, UK) imab combined with methotrexate. Neurological impairment started as early as 1 month after the last (sixth) course of rituximab with We present 3 cases of chronic meningitis where a diagnosis was made rapid deterioration of vision and subsequently cognitive decline. after magnetic resonance imaging (MRI) of the spinal cord. Neurological examination upon admittance revealed vision loss (\1/

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S99

20), major memory impairment, bilateral pyramidal signs without P438 functional deficit and brisk primitive reflexes. Magnetic resonance Concomitant neuromyelitis optica and sarcoidosis imaging (MRI) of the brain, which showed demyelinating subcortical white matter lesions in the parietal and occipital lobes P. Depireux, P. Laloux, E. Mormont, Y. Vandermeeren bilaterally, raised the suspicion of PML. The PCR analysis of the CHU Mont Godinne (Yvoir, BE) cerebrospinal fluid (CSF) was negative for JC virus DNA. Treatment Background: Sarcoidosis is a chronic multisystem inflammatory dis- with steroids, plasma exchange and mefloquine was ineffective and ease of unknown cause. Neurosarcoidosis accounts for approximately the patient died 8 months after the onset of the symptoms. This case 5-15 % of cases of systemic sarcoidosis; it rarely presents as longi- of suspected PML denotes the importance of the alertness for the tudinal extensive transverse myelitis (LETM) or recurrent optic possible diagnosis of PML in immunocompromised patients with neuritis (rON). new or progressive neurological symptoms who have been treated Anti-aquaporin-4 antibodies are considered to be the main bio- with immunosuppressant drugs. marker of neuromyelitis optica (NMO) with a high sensitivity and a very high specificity. However, NMO-IgG can be present in other auto-immune diseases especially in systemic lupus (SL) and Sjo¨gren’s syndrome (SS).We report on a case of neurosarcoidosis associated P437 with the presence of antiaquaporine-4 antibodies. Case report: A 57-year-old women was diagnosed with a LETM Behçet’s disease presenting as idiopathic intracranial in 2003. The cerebral magnetic resonance imaging (MRI) did not hypertension show demyelinating lesion. The cerebrospinal fluid (CSF) analysis R. Manso-Calderoń, P. Cacabelos, C. Torres, showed normal cell count (3,2 elements/mm3), normal proteins level M. Corteguera (32mg/dl) and no oligoclonal bands. A chest computerized tomography (CT) scan revealed lymphadenomegaly; the transbronchic Hospital Universitario (Salamanca, ES); Hospital Nuestra Senõra de biopsy showed a non caseating granuloma characteristic of sar- Sonsoles (A´ vila, ES) coidosis. A diagnostic of systemic sarcoidosis with LETM was thus Objectives: The diagnosis of Behçet disease (BD) is straightforward considered despite a normal rate of angiotensin converting enzyme when it presents classically with recurrent oral and genital ulceration (22U/L). The patient was treated with corticosteroids pulse treat- and ocular lesions. However, many cases present atypically with ment. Nine months later, the patient presented an unilateral optic uncommon neurological manifestations with none or only some of neuritis and recovered after corticosteroids pulse treatment. In 2005, the classical triad. Neurological involvement occurs in 5-49 % of a relapse of LETM occurred; a treatment with azathioprine was patients with BD and is a major cause of morbidity and mortality. initiated and maintained during 6 years at a dose of 150mg a day. In We report a patient who presented with idiopathic intracranial 2011, four months after discontinuation of azathioprine, she pre- hypertension (IIH) when the only other manifestation of BD was sented a second relapse of LETM. Azathioprine was resumed at the oral ulceration. same dose. Methods: A 22-year-old non-obese woman presented with a his- Anti-aquaporin-4 antibodies were tested and found positive. tory of horizontal diplopia for 1 week. It was accompanied by Finally, she presented a fourth LETM episode two months later. High intermittent headache and pulse-synchronous tinnitus. After 3 days, dose of intravenous corticosteroids and plasma exchanges provide a she also noticed blurred vision affecting her right eye. Closer ques- moderate improvement. tioning was negative apart from one year of recurrent oral aphthous Discussion: This case raises the question of the coexistence of ulceration. The neurologic examination revealed bilateral stage 2 both systemic sarcoidosis and neuromyelitis optica in the same patient papilledema and left cranial nerve VI palsy. Her pupils were 3.5 mm, versus the possibility of false positive anti-aquaporin-4 antibodies in round and reactive to light without relative afferent pupillary defect. neurosarcoidosis. As far as we know, anti-aquaporin-4 antibodies Her visual acuity was 20/100 in the right eye and 20/25 in the left eye. have never been detected in neurosarcoidosis, in contrasts to SL and Automated perimetry showed loss of inferonasal portions of the visual SS. Cross reactivity of antibodies, overlap of pathogenesis or coex- field. On general examination, several painful mouth ulcerations were istence of two rare diseases are discussed. visible. Results: The erythrocyte sedimentation rate and C-reactive protein were elevated, laboratory tests for collagen vascular disorders and tuberculosis were negative. A computed tomographic (CT) scan P439 excluded a space occupying lesion and demonstrated normal size ventricles. A lumbar puncture was carried out. Cerebrospinal fluid A 58-year-old female with encephalopathy and acute (CSF) pressure was 350 mm, with normal protein and glucose axonal and severe autonomic neuropathy values and no cells. MRI scan showed an empty sella and no venous of undetermined cause developing ovarian carcinoma sinus thrombosis. HLA B51 phenotype was demonstrated. Meta- and NMDA-receptor antibodies 33 months later bolic, toxic or hormonal causes of intracranial hypertension were ruled out. With a diagnosis of IIH as a neuro-Behçet manifestation, A. Ko¨hler, U. Hofstadt-van Oy, U. Po¨tzl, K.-P. Wandinger, the patient was treated with acetazolamide 1.5 g/day and dexa- J. Weis, P. Oschmann methasone. One month later, glucocorticoids were changed for Klinikum Bayreuth (Bayreuth, DE); Institut fu¨r experimentelle azathioprine first and, because of hair loss, colchicine finally. He Immunologie, affiliated at Euroimmun (Lu¨beck, DE); Institut fu¨r was asymptomatic at his outpatient visits 3 and 6 months later. Her Neuropathologie (Aachen, DE) visual field examinations were near normal, and her papilledema had Introduction: N-methyl-D-aspartate receptor antibodies (NMDAR- resolved. Ab) are associated with ovarian teratoma and can cause encephalitis Conclusion: A careful history and examination for evidence of BD presenting with psychiatric symptoms, seizures, decreased level of should be conducted in all patients presenting with IIH as treatment consciousness and movement disorders. directed at controlling the underlying disease may avoid the need for Case report: A previously healthy 58 year old female was admitted surgical procedures. due to progressive somnolence, tetraparesis, ptosis and external

123 S100 J Neurol (2012) 259 (Suppl 1):S1–S236 ophthalmoplegia developing over two months. Her husband reported P441 subtle changes of mood and behaviour since six months. The spinal An autopsy case of neuronal intermediate filament fluid displayed a normal cell count and protein, no significant viral antibody titers but oligoclonal bands. Motor and sensory neurogra- inclusion disease phies and electromyography indicated an acute motor axonal K. Inoue, H. Fujimura, K. Ueda, T. Matsumura, S. Sakoda, neuropathy, i.v. immunoglobulins were given. Cerebral MRI showed M. Yoshida small white matter lesions compatible with cerebral microangiopathy, Toneyama National Hospital (Osaka, JP); Aichi Medical University spinal MRI was normal. Tetraparesis and loss of consciousness pro- (Aichi, JP) gressed and several episodes of cardiac and ventilatory arrest required resuscitation. The patient was artificially ventilated and a cardiac Objective: Neuronal intermediate filament inclusion disease (NIFID) pacemaker was implanted. Anti-neuronal antibodies and NMDAB-Ab is a distinctive neurological disorder that clinically presents as were negative, CA 12-5 and CA 19-9 titers were elevated. An dementia with a pyramidal and/or extrapyramidal dysfunction, and is extensive tumor search was negative. A muscle-nerve biopsy revealed pathologically characterized by deposition of intermediate neurofila- vacuolar myopathy of undetermined cause and progressive axonal ments containing alpha-internexin. We report an autopsy case of neuropathy. High dose steroids were added. The condition of the NIFID who presented some different clinicopathological features, patient improved, cognitive function and ophthalmoplegia resolved comparing to previous cases. and she regained limited walking ability and selfcare. Muscle biopsy Method: We describe the clinical and pathological features of a nine months later confirmed vacuolar myopathy. In the following two case of NIFID. years she was stabilised with low dose oral steroids, a minor relapse A 41-year-old man first noticed his right lower limb stumbled with paraparesis was successfully treated with increasing dosage. 33 easily. One year later, he developed gait disturbance, weakness of months later a deep venous thrombosis developed. An ovarian pap- upper extremities, dysarthria and dysphasia. On hospital admission, 3 illary carcinoma with peritoneal carcinosis was found, a tumor- years after disease onset, the neurological examination disclosed reductive operation and polychemotherapy was performed. High-titre spastic quadriparesis, saccadic eye movement, generalized hyperre- serum NMDAR-Ab were detected by indirect immunofluorescence flexia, bulbar palsy and neurogenic bladder. He also suffered from using NR1 transfected HEK cells. mood disturbance and change of personality. 6 years later from first Discussion: In retrospect we hypothesize, that the steroid-respon- symptom, his consciousness became drowsy, and cognitive impair- sive encephalo-neuropathy at presentation was of paraneoplastic ment was evident. Brain MRI/CT images showed progressive atrophy origin even though NMDAR-Ab were detected not until the clinical of bilateral frontotemporal lobes. He had repeated pneumonia and diagnosis of the ovarian carcinoma 33 months later. Necrotizing died at the age of 57 years. myopathy associated with malignoma has been described previously, Results: The brain weight was 816g. Macroscopically it showed the distinct vacuolar component of the patients’ myopathy remained severe bilateral cortical atrophy with enlargement of ventricles and causally unclear. Follow-up for occult neoplasms is advisable in degeneration of pyramidal tracts. The microscopic examination patients with (sub-) acute neurologic syndromes of unknown cause. revealed severe neuronal loss with gliosis in frontotemporal cortices, caudate nucleus and putamen. There were also moderate degeneration in the thalamus, substantia nigra and the gray matter of the spinal cord. Hyalinized intracytoplasmic inclusions were observed in the P440 remaining neurons in the cortices which were negative for Bodian Neuralgic amyotrophy of the tongue: Parsonage- stain, alpha-synuclein, phosphorylated tau protein, while positive for Turner-like hypoglossal nerve palsy? ubiquitin and neurofilaments. These were most immunoreactive for alpha-internexin, while negative for fused in sarcoma protein (FUS). S. Fernańdez-Meneńdez, A. Galiana-Ivars, B. Cabezas- We also found some intranuclear inclusions in the neuron of the Delamare, L. Redondo-Robles, A. Are´s-Luque, R. Garcia- hippocampus, which were positive for Uq and negative for TDP43 or Santiago polyglutamin. Complejo Asistencial de Leoń (Leon, ES) Conclusion: It may be prudent to determine whether or not NIFID is included in the range of FTLD-FUS, because NIFID shows some Objectives: Isolated hypoglossal nerve lesions are often due to com- pathological heterogeneity, such as different involvement pattern and pressive, infiltrative or inflammatory lesions in the skull base or in the immunoreactivity for FUS. More number of NIFID cases should be neck region and they are seldom reversible. Neuralgic amyotrophy is carefully investigated. usually a benign condition with a good recovery, characterized by acute, severe pain followed by weakness and atrophy, with minimal sensory disturbances. Although it is usually thought to be a plexopathy, its diverse presentation can include isolated sensory nerves or even cranial nerves. P442 Methods: A 47 years old male, with an unremarkable past medical Charles Bonnet syndrome: a case report and review history, presented with an acute onset, disabling painful sensation of the literature around the left part of his mouth and neck. On the next days, as pain started to improve, the patient developed dysarthria and progressive A. Lerario, A. Altieri, A. Ciammola, V. Silani left hemitongue weakness and atrophy. The patient was evaluated IRCCS, S.Luca Hospital, (Milan, IT); University of Milan (Milan, IT) four months after the beginning of the disease. Clinical examination Objectives: Visual hallucinations (VHs) can be associated with a showed isolated left hypoglossal nerve palsy with marked left variety of settings: psychiatric disease, delirium, neurodegenerative hemitongue atrophy. A complete diagnostic workup, including head diseases, cerebral vasculopathy, epilepsy, drug ingestion, metabolic and skull base imaging, was negative. No therapy was indicated, but and endocrine disorders. VHs are also experienced when there is the patient showed marked improvement over the following months. inadequate stimulus to the sensory system as frequently occurs in Results and conclusion: Neuralgic amyotrophy of the tongue can older patients with impaired vision due to a ophthalmic disease. The be an oligosymptomatic variant of Parsonage-Turner syndrome and clinician should be aware that a significant proportion of visually should be included in the differential diagnosis of reversible, painful, impaired patients experience complex VHs, which are sometimes isolated hypoglossal nerve palsy. distressing. This condition is known as the Charles Bonnet Syndrome

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S101

(CBS). We present an exemplar case of CBS and review of the P444 literature. Hirayama disease associated with inversion Methods: we present the case of a 87 year old woman with age related macular degeneration in both eyes presenting with a 15 years of physiological cervical lordosis: a rare differential history of intermittent VHs. She reported that the symptoms occurred diagnosis of motor neuron degeneration mostly in the evening, when she saw people and animals around her. A. Merlini, S. Gerevini, M. Rodegher, M.J. Messina, Over the years she has never taken any treatment for VHs because U. Del Carro, V. Martinelli, G. Comi they didn’t bother her much, and she was reluctant to admit VHs due San Raffaele Scientific Institute (Milan, IT) to fear of being labeled with a psychiatric disease. At the age of 82 she developed hyposmia, resting tremor of the upper limbs and mild Objective: We describe a rare case of Hirayama disease (HD) asso- bradykinesia. DaTSCAN revealed reduced uptake of dopamine ciated to an inversion of the physiological lordosis at C5-C6 that was transporter bilaterally in the basal ganglia and she considerably revealed by dynamic MRI study. improved after levodopa treatment (125 mg three times a day). Methods: Observational case report. Results: Blood analysis were normal. EEG showed unremarkable Results: A 19-year-old man without relevant medical or family abnormalities. MRI showed cortical atrophy and diffuse white matter history lamented a 5-year history of progressive hyposthenia, pos- ischemic lesions. A workup for other pathological causes of VHs was tural tremor and fasciculations of the upper limbs. Neurological negative. The patient was diagnosed as having CBS. examination confirmed bilateral hyposthenia and hypotrophy of the Conclusion: Age associated microvascular changes may lead to triceps, pectoralis major and interossei muscles, more pronounced on subclinical deficits of the visual cortex, and to the appearance of CBS. the left side. Deep tendon reflexes were reduced at the upper limbs, In older patients the diagnosis of CBS needs a multidisciplinary while at the lower limbs bilateral hyperreflexia, ankle clonus and approach, and treatments with drugs remain unsatisfactory. No Babinski were detected. Accordingly, electromyography showed pharmacological interventions, such as increasing the lighting at bilateral reduction of the ulnar motor action potential and neurogenic home and reassurance that the syndrome is not related to mental motor unit potentials corresponding to C7-T1 and, to a lesser extent, illness is in itself a major relief to affected patients. C5-C6 myotomes. On the other hand, cervical non-flexion MRI showed a severe asymmetric cord atrophy with focal T2 hyperintensity at C5-C6 level. Altogether the clinical, neurophysiological and MRI findings were suggestive of HD. Thus, in flexion MR P443 studies, we detected the striking and pathognomonic picture of anterior shifting of posterior dura at the lower cervical spinal canal Effects of idebenone on colour vision in patients and prominent epidural venous plexus extended from C3 to D2. with Leber’s hereditary optic neuropathy Moreover, an inversion of the physiological lordosis was noted at G. Rudolph, K. Dimitriadis, B. Bu¨chner, S. Heck, C5-C6. Eventually, a diagnosis of HD was made and the patient was J. Al-Tamami, F. Seidensticker, C. Rummey, M. Leinonen, referred to orthopedic and neurosurgery departments for corrective surgery of the spine abnormality. T. Meier, T. Klopstock Discussion: HD is attributed to shifting of posterior dura at the Ludwig-Maximilians-University (Munich, DE); Santhera lower cervical spine when the neck is in flexion, which causes flat- Pharmaceuticals (Liestal, CH); 4Pharma (Stockholm, SE) tening of the cervical cord and subsequent ischemic degeneration of Aims: We investigated the correlation of Protan and Tritan color the anterior horns. HD is frequently associated with other spinal vision with disease characteristics in Leber’s Hereditary Optic Neu- abnormalities, such as cervical disc herniations and dural ligamentous ropathy (LHON). We also characterized the therapeutic potential of laxity. Indeed, our case also presented an inversion of the cervical idebenone in protecting from dyschromatopsia in LHON. lordosis that likely exacerbated the ischemic myelopathy. HD diag- Methods: Color contrast data of 39 LHON patients participating in nosis requires dedicated MRI techniques and an experienced a randomized, doubleblind placebo-controlled intervention study neuroradiologist to unveil its telling signs. On that note, our hospital were evaluated. Patients reported disease onset \5 years prior to has become a referring center for HD with the diagnosis of 3 other enrolment and were genetically confirmed. Protan and Tritan color cases. Since differential diagnosis of amyotrophy in young patients contrast sensitivity was measured using a computer graphics method includes heredodegenerative conditions and sporadic motor neuron in patients receiving idebenone (Catena, 900 mg/day; N=28) or disorders with less favourable prognosis, awareness of HD may ease a placebo (N=11) for six months. complex diagnosis, avoid unavailing investigations and prompt early Results: Mean age of patients was 28.1 years, 87.2 % were male, treatment. 76.9 % carried the m11778G[A mutation and mean duration since onset was 2 years. Assessing Protan and Tritan color vision at baseline revealed a high degree of color confusion even in young patients (\25 years) and with a short history of disease (\1 year). Treatment P445 with idebenone improved Tritan color vision compared to placebo (p=0.008 at week 24); a similar trend was seen for Protan. The effect Psychiatric and cognitive symptoms in a patient of idebenone was most prominent in patients with discordant visual with adrenal insufficiency acuity (inter-ocular difference of logMAR[0.2). In this subgroup the J. Morgado, A.P. Sousa, J. Pena, R. Pedrosa treatment effect at week 24 was 20.4 % (p=0.005) in favor of ideb- Centro Hospitalar de Lisboa Central (Lisbon, PT) enone for the Tritan color domain and 13.5 % (p=0.067) for the Protan domain. Objectives: X-linked adrenoleukodystrophy (ALD) is an inherited Conclusions: This study confirms that Protan and Tritan color neurodegenerative disorder associated to an accumulation of saturated confusion are early symptoms in LHON. Treatment with idebenone very long chain fatty acids (VLCFA) in the central and peripheral can protect from loss of color vision, particularly in nervous system, adrenal glands and gonads. As a result it is charac- patients who are at imminent risk of further vision loss. terized by leukoencephalomyeloneuropathy, adrenal insufficiency and This work was supported by the German ministry for Education hypogonadism. Clinical phenotypes vary widely. Adrenomyeloneu- and Research (BMBF) and by Santhera Pharmaceuticals. ropathy is the commonest presentation in an adult while the adult

123 S102 J Neurol (2012) 259 (Suppl 1):S1–S236 cerebral form occurs rarely. We present an uncommon disease phe- focal symptoms involving mainly the lower extremities without notype in an adult characterized by psychiatric and cognitive truncal or upper extremity involvement. She was treated with symptoms. gabapentin, oxycontin, valium and baclofen. However her disease Methods: Case retrieved from the Neurology´ files with review of still progressed despite polypharmacy, physical therapy and 3 rounds clinical aspects and diagnostic workup. of IVIG. Results: A 48-year-old man with a history of psychiatric symp- Results: Previous case reports and review articles on SLS have tomatology for 2 years and a cognitive decline for 2 months was failed to provide guidelines on diagnosis therefore delaying appro- referred to our hospital with a brain MRI showing an extensive priate management. On reviewing prior cases and this current case, periventricular white matter lesion, hyperintense on T2, localized in the diagnostic criteria that can be derived includes mostly female the atrium and occipital horn of the lateral ventricles bilaterally. patients with features of increased tone involving mainly the lower Careful clinical history revealed adrenal insufficiency for 20 years extremities (proximal or distal) with sparing of axial muscles and and no family history. Neurologic examination revealed a temporal good response to valium with characteristic EMG findings. Concur- disorientation, amnesic and frontal dysfunction, bilateral decreased rent presence of an autoimmune condition and presence of anti-GAD visual acuity, spastic gait without paraparesia, global hyperreflexia of antibodies is not characteristic of SLS. osteotendinous reflexes and bilateral Babinski sign, without pain or Conclusion: It is mandatory to report every case of SLS in order to postural sensibility abnormalities. Spine MRI was normal. The delineate a diagnostic criterion. plasma VLCFA analysis was pathognomonic of ALD and genetic test is in course. Four months later the patient was readmitted with recrudescence of cognitive and behavior changes. The examination was similar to the previous except for a spatial disorientation, prim- P447 itive reflexes and hypopallesthesia on lower limbs and hands. Brain Tetraparesis after electric shock MRI revealed an extension of the lesions to temporal and parietal lobes. Electroneuromyography showed an incipient polyneuropathy F. Sousa, M. Rodrigues, S. Rocha, R. Mare´, P. Beleza and somatosensory evoked potentials revealed a latency delay. Hospital de Braga (Braga, PT) Conclusions: We report a rare adult form of ALD characterized Introduction: Electric shocks can affect the central or peripheral predominantly by a cerebral involvement. This case illustrates the nervous system, causing transient or permanent disability. This effect importance for physicians to maintain a high index of suspicion for can be immediate or delayed for months or years later. psychiatric and cognitive symptoms in patients with adrenal insuffi- Case report: An healthy 28-year old female patient, medicated ciency even without family history. with oral contraceptives, suffered an electric shock when plugging the 2200 W electric vacuum cleaner in a 220 V outlet, with the right hand. Three minutes later, she started complaining of decreased muscle strength in lower limbs, that unable her to walk, and later P446 affecting the upper limbs. The neurological examination on admission showed a flaccid tetraparesis with hyperreflexia, indifferent Stiff limb syndrome: a case report and diagnostic cutaneous plantar reflexes, and a level of hyposthesia through L1 criteria with no proprioceptive or sphincter abnormalities. Cerebral and S. Syed medullar MRI only revealed a small dilation of the ependymal canal Boston University Medical Center (Brookline, US) from C4 to D10 compatible with syringomyelia. Lumbar puncture was performed in the next day with no cytochemical changes. Objectives: To discuss a case of Stiff Limb Syndrome(SLS)in order to Electromyography was normal. High doses of intravenous methyl- outline diagnostic criteria. prednisolone was given during 5 days. MRI repeated at the end of Methods: 65year old female presented with 18 months of hospitalization (day 6 revealed no other changes. The patient was worsening lower extremity spasms, which predominantly involved discharged 7 days after admission with normal neurological the thighs and caused her to rely on crutches and a walker to examination. ambulate. These spasms were precipitated by touch, stress and Conclusions: Only few cases of myelopathy after electric shock are voluntary activity. She also had associated weight loss and an described in literature. The mechanism of spinal cord injury remains anxious demeanor. On exam she had increased tone in her lower unknown but may be mediated by electrical or thermal action. Findings extremities, proximal more than distal, but intact strength and of spinal cord anoxia and edema, perivascular infiltration, intravascular hyperesthesia over the soles of her feet. Her reflexes were retained thrombosis and arteritis are reported in these patients. In this case, as in upper extremities and absent in lower extremities due to inability well in literature, no imaging, electromyographic or CSF changes were to relax. She had an extensive workup and responded well to a trial detected. It is hypothesized that, because of the low voltage and of valium. However she was readmitted 3 times over the next 4 exposure time, irreversible spinal cord cellular damage didn’t occurred, months for the same symptoms and had additional testing done. allowing a complete and fast recovery. Abnormalities included increased rheumatoid factor at 46, mildly elevated CPK 364 and CRP 5.7. Other serum tests were negative including HIV antibody, lyme titer, anti-GAD antibodies and a heavy metal screen. Her CSF studies were also negative for oli- P449 goclonal bands, myelin basic protein and VDRL. Her MRI brain Neuromyotonia: clinical, electrophysiological was unremarkable and MRI cervical and lumbar spine did not show and immunological findings of 4 cases any cord compression. She had an electromyogram (EMG) that revealed continuously firing motor unit action potentials in the lower P.J. Lorenzoni, R.H. Scola, C.S.K. Kay, A.P.P. Miranda, extremities that were not readily inhibited by the activation of the L. Filla, L.C. Werneck, A. Vicent antagonistic muscles. The needle EMG examination showed findings Universidade Federal do Parana´ (Curitiba, BR); University of Oxford, consistent with stiff person syndrome. The patient however had John Radcliffe Hospital (Oxford, UK)

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S103

Objectives: Neuromyotonia is a rare disease characterized by sponta- P451 neous and continuous muscle activity due to a disorder of the peripheral Amyloid beta neurotoxicity and neuroprotective role nerve hyperexcitability. Patients develop persistent muscle contraction, classically worsening after exercise. Electromyography is characterized of 17beta estradiol in aging rat brain synaptosomes by neuromyotonic discharges and about 40 % of patients have detect- P. Kumar, R. Kale, N. Baquer able voltage-gated potassium-channel (VGKC) antibodies. To analyze a Jawaharlal Nehru University (New Delhi, IN) series of patients with neuromyotonia from neuromuscular disorders Alzheimer’s disease (AD) is the most common form of dementia in ´ ´ unit, Hospital de Clınicas da Universidade Federal do Parana. the elderly. AD is characterized by the presence of amyloid plaques Methods: We studied four patients with neuromyotonia, regarding which are formed from deposits of b-amyloid protein (Ab). Accu- the clinical, electrophysiological and immunological findings. mulation of oligomeric Ab in the brain contributes to neuronal Results: The average age of onset of symptoms was 17.5 (7-35) dysfunction and ultimately leads to neurodegeneration. During aging years and there was no gender predilection. The average time between the brain experiences structural, molecular, and functional alterations. onset of symptoms and diagnosis was 9.5 (1-29) years. All patients These changes increase during menopausal condition in females when had muscle twitching, muscle hypertrophy and hyperhidrosis, 75 % the level of estradiol is decreased. had muscle cramps and stiffness, 25 % pseudomyotonia, 75 % The aim of the present study was to determine the effect of neu- weakness, 25 % paresthesias, 25 % dysphonia, dysphagia and dysp- ropeptide, neurokinin B (NKB) and amyloid beta fragment Abeta (25- nea and 25 % central nervous system symptoms. Family history and 35) on 17beta estradiol (E2) treated aging female rat brain of 3 exogenous intoxication were negative. All patients had the dosage of months (young), 12 months (adult) and 24 months (old) age groups. anti-VGKC negative. Electrophysiological findings: myokymia and Methods: The aged rats (12 and 24 months old) (n= 8 for each neuromyotonic discharges were found in all patients, douplets and group) were given subcutaneous injection of 17b-estradiol (0.1 lg/g multiplets at 100 % and triplets in 50 % of cases. The maximum body weight) daily for one month. After 30 days of hormone treat- intraburst frequency ranged from 70 to 200 Hz.3 patients were treated ment, experimental animals of all the groups were sacrificed and with carbamazepine and gabapentin with a good response to treat- brains were isolated for further study. Aging brain function were ment. 3 used phenytoin, and of these, 2 had a partial response and 1 assayed by measuring the activities of antioxidant enzymes, mono- had intolerance to the drug. 1 patient had epilepsy, 1 patient devel- amine oxidase (MAO), membrane bound ATPases, intracellular oped ulcerative colitis idiopathic, glomerulonephritis and eczema on calcium levels and lipid peroxidation in presence of neuropeptides. the face and another one hypothyroidism, arthralgia and myalgia. The results obtained in the present work revealed that increased Conclusion: The diagnosis of neuromyotonia is accomplished activities of antioxidant enzymes, membrane bound ATPases and primarily through clinical and electrophysiological findings. Elec- decrease in level of calcium levels, MAO activity and lipid peroxi- tromyography often confirms diagnosis by the presence of dation in presence of NKB and combined NKB and Abeta in vivo neuromyotonic discharges. The association with autoimmune diseases estradiol (E2) treated ageing rat brain. NKB treatment reversed the can be observed, as described in this series. beneficial in preventing some of the age related changes in the brain. An in vitro incubation of E2 treated synaptosomes with Abeta showed toxic effects on all the parameters, while NKB showed stimulating P450 effects and the combined NKB and Abeta showed a partial effects as Ethnic differences in syringomyelia in Bashkortostan compared to Abeta (25-35) and NKB alone. region of Russian Federation Present study elucidates an antioxidant, neuromodulatory and neu- T. Mirsaev, N. Borisova, R. Magzhanov roprotective role of tachykinin peptide NKB against the beta amyloid induced toxicity in E2 treated female rats. NKB treatment reversed the Bashkir State Medical University (Ufa, RU) beneficial in preventing some of the age related changes in the brain. Syringomyelia is a disorder in which a cyst develops within the spinal cord. It usually has a progressive course and leads to early disability and shortens the lifespan. Bashkortostan(Republic of) is a federal Preclinical biology subject of Russia characterized by abnormally high prevalence of syringomyelia. The aim of our study was to measure the prevalence of syringomyelia in three major ethnic groups(Bashkirs, Tatars and Russians) living in this region. P452 Patients and methods: We retrospectively studied all cases of syrin- Impact of the anticancer agent cytosine arabinoside gomyelia diagnosed in Bashkortostan from 1970 to 2011. Only patients administration on neuronal cytoskeleton proteins with MRI confirmation of cavity in the spinal cord were included in the of the developing rat cerebellum. A sexual dimorphism study. Ethnicity was established on patients self-identification. Results: The population in Bashkortostan nowadays is 4.1 million: C. Koros, E. Kitraki 36.1 % Russians, 29.5 % Bashkirs and 25.4 % Tatars. Totally 2117 Eginition Hospital, University of Athens (Athens, GR) cases were analyzed and 1415 matched inclusion criteria. 55.8 %(789) Objectives: The resistance of neuronal cytoskeleton to drug toxicity of patients clearly identified themselves as Tatars, 16.7 %(236) - as varies with age. In the adult cerebellum, neurofilament (NF) levels Bashkirs, 13.1 %(186) – as Russians. Prevalence of syringomyelia in and isoform analogy are severely affected by the anticancer agent total for the region was evaluated as 34.5/100000 although varying cytosine arabinoside (AraC) administration. The aim of the present significantly from 3.5 to 129 cases per 100 000 of population in different study was to assess the impact of AraC treatment and gender on NF administrative districts of Bashkortostan. Prevalence of syringomyelia proteins of the developing rat cerebellum. among Tatars was evaluated as 75.8/1000000, among Bashkirs as 19.5/ Methods: AraC (200mg/kg bw) was administered in male and 100000 and among Russians as 12.6/100000 respectively. female Wistar rats from postnatal day (PND) 14 to 16. Neurofilament Conclusion: Ethnic differences in the prevalence of syringomyelia susceptibility to treatment was assessed by means of western blot and have been identified, with a higher prevalence in Tatar people than in immunohistochemistry. Russians or Bashkirs. The cause of these ethnic differences is Results: The cerebellum of AraC treated 16-day-old pups of both unknown and warrants further investigation. sexes exhibited a decrease in external granular layer width. AraC did

123 S104 J Neurol (2012) 259 (Suppl 1):S1–S236 not affect neurofilament (NF) phosphorylation in either sex and non - crises, which are precipitated by infectious processes during an age- phosphorylated isoforms in male pups, but increased the medium- and dependent susceptibility period. low-MW-isoform levels in females. Androgenization of females on Methods: In the present work, we investigated whether chronic PND 3 by testosterone propionate (1.25 mg/rat) prevented the AraC - exposure of GA (5 lmol g of body weight minus 1, twice per day), in induced increase in NF isoforms. The levels of estrogen receptor beta the absence and presence of LPS during early development (from the (ER-beta), known to mediate neuroprotective actions of estrogens in 5th to the 28th day of life), could alter the cognitive performance of the brain, were significantly higher in the developing female cere- rats in the Barnes maze and evaluate if the alterations can be related to bellum, as compared to males and androgenized females. The levels structural or functional changes in the hippocampus. of brain derived neurotrophic factor (BDNF), involved in neuro- Results: We showed that GA-chronic treatment caused a deficit of plasticity, were not modified by AraC treatment in pups of either sex. spatial learning in pups rats, and that the presence of an inflammatory Conclusion: We conclude that neurofilament proteins of the rat process induced by LPS increase the spatial memory impairment induced cerebellum appear more resistant to neurotoxic effects of AraC during by GA. How none of the treatments affected the weight or locomotor the third week of life, comparing to adulthood. A sexually dimorphic activity of the animals, the effect of treatments on impairment of spatial pattern was detected in AraC - induced NF modifications, that was learning is not due the these alterations, but the increase in pro-inflam- reversed by early androgenization of females. matory cytokines, the reduction of hippocampal volume and the decreased in alpha1 subunit activity of Na+, K+-ATPase enzyme as observed. Besides, we found that the worsening in spatial memory observed in GA-LPS group, as compared with other groups, was alpha2/3 P453 isoform specific of enzyme, since only this group showed no a com- The role of ammonia in the methylmalonic acid-induced pensatory response in this subunits, and consequently presented a neurotoxicity in mice decreased in total activity of Na+, K+-ATPase enzyme. L.R. Ribeiro, L.M. Rambo, I.D. Della-Pace, R.S. Scalco, Conclusion: The results provide evidence that early chronic GA treatment induces long-lasting spatial behavioral deficit, and that a pres- F. Dobrachinski, L.F.F. Royes, M.R. Fighera ence the inflammatory process potentiates the deficit in spatial learning. Universidade Federal de Santa Maria (Santa Maria, BR); Pontificia Universidade Cato´lica do Rio Grande do Sul (PUCRS) (Porto Alegre, BR) P455 Objectives: Methylmalonic acidemia consists of a group of inherited neurometabolic disorders caused by deficiency of methylmalonyl- Pharmacokinetics and bio-distribution of new CoA mutase activity and characterized by accumulation of methyl- Gd-complexes of DTPA-bis (amide) (L3) in a rat model malonic acid (MMA) and seizures. Considering that seizures may be G. Yan, Y. Xuan, R. Wu, D.S. Kang precipitated by encephalophatic crises and hyperammonemia in Shantou University (Shantou, CN); Kyungpook National University children with methylmalonic acidemia, we investigated whether (Daegu, KR) ammonia (NH4Cl) modifies MMA-induced electrographic and neu- rochemical alterations in mice. Objectives. To investigate the blood pharmacokinetics and bio-distri- Methods: The effect of NH4Cl on convulsive behavior and elec- bution of DTPA-bis-amide(L3) Gd(III) complexes. Materials and troencephalographic (EEG) alterations induced by MMA (0.3; 0.66; Methods. The pharmacokinetics and bio-distribution of 1.0 lmol/striatum) was determined in freely moving mice. After EEG Gd(L3)(H2O).nH2O were investigated in Sprague–Dawley rats after recordings, we evaluated mitochondrial integrity, the levels of reac- intravenous administration at a dose of 0.1 mmol Gd/kg. The Gd content tive species production, succinate dehydrogenase (SDH, EC 1.3.5.1) in the blood, various tissues, and organs was determined by ICP-AES. and Na+,K+-ATPase activities in MMA-injected mice. Blood pharmacokinetic parameters were calculated using a two-com- Results: The co-administration of ammonia (6 mg/kg) and methyl- partment model. Results. The half-lives of alpha phase and beta phase malonate (0,66 lmol/2 lL) did not potentiate the seizures, but causes Gd(L3)(H2O).nH2O were 2.286±0.11 min and 146.1±7.5 min, motor abnormalities. In addition, NH4Cl and MMA administration respectively. The bio-distribution properties reveal that the complex is mainly excreted by the renal pathway, and possibly excreted by the increased NOx (NO2 plus NO3 content), free radical production levels and Na+, K+-ATPase activity, and decreased mitochondrial membrane hepatobiliary route. The concentration ratio of Gd(III) was significantly potential and SDH activity in cerebral cortex of mice. higher in the liver and spleen than in other organs, and small amounts of Conclusion: This date suggest that ammonia and MMA may act Gd(III) ion were detected in the blood or other tissues of rats only after 7 mutually damaging the central nervous system. days of intravenous administration. Conclusion. The MRI contrast agent Gd(L3)(H2O).nH2O provides prolonged blood pool retention in the circulation and then clears rapidly with minimal accumulation of Gd(III) ions. The synthesis of gadolinium complexes with well-balanced lipo- P454 philicity and hydrophilicity shows promise for their further development Lipopolysaccharide enhances the spatial memory as blood pool MRI contrast agents. impairment induced by chronic early postnatal glutaric acid in rats F. Rodrigues, M.A. Souza, B.C. Mota, A.P.O. Ferreira, P456 R.S. Scalco, L.F.F. Royes, M.R. Fighera Dynamics in fronto-parietal cortical motor network Universidade Federal de Santa Maria (Santa Maria, BR); Pontificia during preparation for reaching Universidade Cato´lica do Rio Grande do Sul (PUCRS) (Porto Alegre, BR) M. Rakusa, I. Zidar, J. Zidar, P.P. Battaglini, A. Belic Objectives: Glutaric aciduria type I, an inherited deficiency of glut- University Medical Centre Maribor (Maribor, SI); aryl-coenzyme A dehydrogenase characterized by accumulation of University Medical Centre Ljubljana (Ljubljana, SI); glutaric acid and neurological symptoms. It has been reported that University of Trieste (Trieste, IT); University of Ljubljana patients with GA-I have cognitive impairment after encephalopathic (Ljubljana, SI)

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S105

Objective: Reaching requires translating visual and proprioceptive studies. Here we describe the safety and tolerability of BG-12 in information into a motor plan. This process involves several areas patients with RRMS over 2 years in the Phase 3 CONFIRM study. along fronto-parietal motor network. The aim was to compare two Methods: Patients (18–55 years) with a diagnosis of RRMS reaching paradigms, an easy (ER) and a more demanding (DR) one, (McDonald criteria) and an Expanded Disability Status Scale (EDSS) using measures of task execution and event-related potentials (ERPs). score of 0.0–5.0 were randomized 1:1:1:1 to receive oral BG-12 240 Methods: Ten right-handed subjects performed randomly ER and mg twice (BID) or three times daily (TID), or matching placebo; or DR with their right hand. The target in DR was a small (1 cm2) square subcutaneous glatiramer acetate (GA) 20 mg/day, an active reference which appeared in random position, while the target in ER was a ten comparator arm. Safety and tolerability were assessed by continuous times larger square which position remained unchanged throughout adverse event (AE) monitoring and laboratory tests. the experiment. Both targets appeared in the right upper quadrant of Results: A total of 1,417 patients received placebo (n=363), BG- the touch screen. Subjects were instructed to reach as accurate and as 12 BID (n=359), BG-12 TID (n=344) or GA (n=351). Overall, the fast as possible in DR and as fast as possible inside square in ER. four study groups had similar incidences of AEs (92 %, 94 %, 92 % Reaction time and ERPs (64-channel EEG) were recorded and stud- and 87 % in the placebo, BG-12 BID, TID and GA groups, respec- ied. For statistical analysis we reduced the number of electrodes to 26 tively); serious AEs (22 %, 17 %, 16 % and 17 %), including serious which overly the region of interest. Statistically significant differences infections (1 %, 2 %, 2 % and 1 %); and discontinuations due to AEs were at p\0.05. (10 %, 12 %, 12 % and 10 %). The incidence of hepatic and renal Results: The reaction time of ER was significantly shorter com- events was also comparable among all study groups. AEs with inci- pared to DR (324 ms, SD 39 ms vs. 351 ms, SD 41 ms). We identified dence [=5 % higher in any BG-12 group versus placebo were early and late time intervals in which ERPs amplitudes differed sig- flushing, gastrointestinal events (diarrhea, nausea, upper abdominal nificantly between the tasks. The amplitudes were more negative in pain), upper respiratory tract infection and erythema. No opportu- the left frontal, central and centro-parietal electrodes from 72 to 152 nistic infections were reported in any study group. There were no ms in ER and more positive from 72 to 142 ms in the parietal, parieto- malignancies in the BG-12 groups, 1 in the placebo group (breast occipital and occipital electrodes bilaterally. The second time interval neoplasm) and 4 in the GA group (basal cell carcinoma, cervical in which ERP amplitudes were more positive in ER occurred in P1, carcinoma, endometrial cancer and thyroid cancer). Three deaths Pz, P2, P4, PO3, POz and PO4 derivations in the time interval from were reported: 1 each in placebo (stroke), BG-12 TID (after com- 196 to 304 ms. plications from MS relapse) and GA (suicide) groups. Conclusion: ER and DR engage similar neural networks. As Conclusion: These safety and tolerability results, combined with the expected, ER was accomplished earlier. Early amplitude differences positive efficacy data from both CONFIRM and DEFINE, further support were recorded in electrodes overlying dorsal premotor cortex, sup- BG-12’s potential role as a valuable treatment option for relapsing MS. plementary motor area, posterior parietal cortex, precuneus and visual Supported by: Biogen Idec Inc. association areas. They may reflect different approach in target selection between tasks. Late amplitude differences were recorded in electrodes overlying the right premotor cortex, posterior parietal P458 cortex, precuneus and visual association areas. Our study suggests that these differences may indicate different integration mechanisms Effect of BG-12 in subgroups of patients with relapsing- relating to internal target presentation and movement selection. remitting multiple sclerosis: findings from the CONFIRM (Comparator and an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis) ______study Poster session 2 M. Hutchinson, R.J. Fox, D. Miller, J.T. Phillips, M. Kita, E. Havrdova, M. Yang, R. Zhang, M. Novas, V. Viglietta, Multiple sclerosis: disease modifying treatment II K.T. Dawson St. Vincent’s University Hospital (Dublin, IE); Mellen Center for Multiple Sclerosis Treatment and Research (Cleveland, US); UCL P457 (London, UK); Baylor Institute for Immunology Research (Dallas, Safety and tolerability of BG-12 in patients US); Virginia Mason Medical Center (Seattle, US); Charles with relapsing-remitting multiple sclerosis: results University (Prague, CZ); Biogen Idec Inc. (Cambridge, US) from the phase 3 CONFIRM (Comparator and an Oral Objectives: In the phase 3 CONFIRM study, BG-12 (dimethyl Fumarate in Relapsing-Remitting Multiple Sclerosis) fumarate) significantly reduced the annualized relapse rate (ARR), proportion of patients who relapsed and magnetic resonance imaging study (MRI) activity, versus placebo. Here we report on the efficacy of BG- E. Havrdova, J.T. Phillips, R.J. Fox, D. Miller, M. Kita, 12 in subgroups of patients with relapsing-remitting multiple sclerosis M. Hutchinson, K. Raghupathi, H. Yuan, M. Novas, (RRMS) from CONFIRM. M.T. Sweetser, V. Viglietta, K.T. Dawson Methods: The multicentre, randomized CONFIRM study evaluated oral BG-12 240 mg twice (BID) and three times daily (TID) Charles University (Prague, CZ); Baylor Institute for Immunology versus placebo over 2 years and included an active reference com- Research (Dallas, US); Mellen Center for Multiple Sclerosis parator arm with subcutaneous glatiramer acetate (GA) 20 mg/day. Treatment and Research (Cleveland, US); UCL (London, UK); Patients (18–55 years) with a diagnosis of RRMS (McDonald criteria) Virginia Mason Medical Center (Seattle, US); St. Vincent’s and an Expanded Disability Status Scale (EDSS) score of 0.0–5.0 University Hospital (Dublin, IE); Biogen Idec Inc. (Cambridge, US) were enrolled. The primary endpoint was ARR at 2 years. The effi- Objectives: BG-12 (dimethyl fumarate) significantly reduced clinical cacy of BG-12 was evaluated in pre-specified subgroups stratified by and magnetic resonance imaging activity in patients with relapsing- baseline demographics (including age, gender and weight) and dis- remitting multiple sclerosis (RRMS) and demonstrated an acceptable ease characteristics (including relapse history, EDSS score, T2 lesion safety and tolerability profile in DEFINE, the first of two Phase 3 volume and presence of gadolinium-enhancing lesions). Rate ratios

123 S106 J Neurol (2012) 259 (Suppl 1):S1–S236

(RR) and 95 % confidence intervals (CI) were based on negative comparisons). The proportion of radiological disease-free patients binomial regression. over 2 years was also significantly higher with BG-12 versus placebo Results: A total of 1,417 patients received placebo (n=363), BG- (BID 45 % and TID 39 % vs placebo 27 %; p=0.004 and 0.038, 12 BID (n=359), BG-12 TID (n=345) or GA (n=350). Both doses of respectively). When clinical and radiological criteria were both used, BG-12 demonstrated generally consistent effects on ARR across 28 % and 26 % of patients receiving BG-12 BID and TID, respec- subgroups over 2 years. Treatment with BG-12 BID and TID reduced tively, were disease-free overall versus 15 % receiving placebo the ARR (RR [95 % CI]) versus placebo at 2 years by 47 % (0.53 (p=0.012 and 0.033, respectively). [0.38-0.74]) and 67 % (0.33 [0.23-0.49]), respectively, in patients Conclusion: Findings from this post hoc analysis of the DEFINE \40 years of age; 36 % (0.64 [0.39-1.04]) and 13 % (0.87 [0.55- study indicate that RRMS patients treated with BG-12 were more 1.37]) in patients [=40; 48 % (0.52 [0.36-0.73]) and 63 % (0.37 likely to achieve clinical, radiological, and overall disease activity- [0.25-0.55]) in patients who had\=1 relapse in the year prior to study free status over 2 years compared to those treated with placebo. entry; 34 % (0.66 [0.42-1.04]) and 28 % (0.72 [0.47-1.11]) in patients Study Supported by: Biogen Idec Inc who had[=2 relapses; 52 % (0.48 [0.30-0.78]) and 66 % (0.34 [0.20- 0.56]) in patients with baseline EDSS score \=2.0; and 37 % (0.63 [0.45-0.89]) and 37 % (0.34 [0.44-0.89]) in patients with EDSS score [2.0. Conclusion: Subgroup analyses from the CONFIRM study indi- P460 cate generally consistent effects of BG-12 on ARR across baseline Safety, tolerability and pharmacokinetics of BG-12 240 demographic and disease characteristic subgroups. The effect mg twice daily and three times daily administered appeared to be greater in younger versus older patients, consistent with other disease-modifying therapies. with and without aspirin in healthy volunteers Supported by: Biogen Idec Inc. S.I. Sheikh, I. Nestorov, H. Russell, J. O’Gorman, R. Huang, G.L. Milne, S. Stecher, M. Novas, K.T. Dawson Biogen Idec Inc. (Cambridge, US); PROMETRIKA, LLC P459 (Cambridge, US); Vanderbilt University (Nashville, US) Analysis of clinical and radiological disease activity-free Objectives: BG-12 (dimethyl fumarate) is under evaluation as an oral status in patients with relapsing-remitting multiple treatment for relapsing multiple sclerosis. In two Phase 3 studies (DEFINE and CONFIRM), BG-12 240 mg twice daily (BID) or three sclerosis treated with BG-12: findings from the DEFINE times daily (TID) significantly improved clinical and neuroradiolog- study ical endpoints versus placebo. Common adverse events reported G. Giovannoni, R. Gold, L. Kappos, D.L. Arnold, during BG-12 treatment included flushing and gastrointestinal (GI)- A. Bar-Or, K. Selmaj, A. Zhang, S.I. Sheikh, K.T. Dawson related events, mostly mild or moderate in severity and declining substantially in incidence after the first month of treatment. Here we Blizard Institute, Barts and the London School of Medicine and evaluate the safety, tolerability, and pharmacokinetics of BG-12 Dentistry (London, UK); St. Josef Hospital, Ruhr University administered with or without aspirin. (Bochum, DE); University Hospital (Basel, CH); Montreal Methods: In this double-blind, placebo-controlled study, healthy Neurological Institute and Hospital, McGill University (Montreal, volunteers were randomized to receive 4 days of treatment with BG- CA); Medical University of Lodz (Lodz, PL); Biogen Idec Inc. 12 or matching placebo, given 30 min after aspirin 325 mg or (Weston, US); Biogen Idec Inc. (Cambridge, US) matching placebo. The pharmacokinetics of BG-12 were investigated Objectives: In the 2-year, randomized, double-blind, Phase 3 DEFINE based on the primary active metabolite, monomethyl fumarate study, BG-12 (dimethyl fumarate) significantly reduced clinical (MMF), measured on Days 1 and 4 of dosing. Flushing and GI events relapses, disability progression, and magnetic resonance imaging were assessed using several patient-reported severity scales including (MRI) measures of disease activity in patients with relapsing-remit- the Global Flushing Severity Scale, Flushing Severity Scale, Overall ting multiple sclerosis (RRMS). Here we evaluate the impact of BG- GI Symptom Scale and Acute GI Symptom Scale. Potential flushing 12 on the proportion of patients with RRMS who were free of clinical mediators were also explored. and/or MRI disease activity in the DEFINE study. Results: Thirty-six subjects were enrolled in groups given BG-12 Methods: Patients aged 18–55 years with a diagnosis of RRMS 240 mg BID or TID or placebo with aspirin or placebo, and completed and an Expanded Disability Status Scale (EDSS) score of 0.0-5.0 the study. MMF concentration versus time profiles showed no were included in the study. Patients were randomly assigned 1:1:1 to evidence of accumulation and were not affected by aspirin adminis- oral BG-12 240 mg twice daily (BID) or three times daily (TID) or tration. Overall, flushing symptoms were assessed as mild and mean placebo. In the current analysis, absence of disease activity over 2 severity scores decreased over the treatment period in BG-12 groups. years was analysed as follows: clinical (no relapses or EDSS pro- Administration of aspirin further reduced flushing incidence and gression), radiological (no new or newly enlarging T2 lesions and intensity. GI-related symptoms were infrequent and assessed as mild gadolinium-enhancing lesions), and overall (no clinical and radio- in intensity in all groups. A prostaglandin D2 metabolite was elevated logical disease activity) disease activity-free status. Analyses of in some individuals treated with BG-12 and may be associated with clinical disease-free measures were performed on the intent-to-treat flushing. (ITT) population and MRI cohort, and radiological and overall dis- Conclusion: Over the 4-day dosing period with BG-12, both ease-free measures on the MRI cohort, using a Chi-square test and flushing and GI symptoms were generally assessed as mild in inten- logistic regression model. sity across all study groups, and the incidence and severity of flushing Results: The ITT analysis included 1,234 patients and the MRI decreased over time. Pre-treatment with aspirin further decreased the cohort analysis included 469 patients. The proportion of clinical incidence and severity of flushing without adversely affecting the disease-free patients over 2 years was significantly higher in both BG- overall safety or pharmacokinetic profiles (no MMF accumulation) of 12 treatment groups versus placebo in both cohorts: ITT (BID 69 % BG-12. These results suggest the potential utility of aspirin to help and TID 69 % vs placebo 49 %; p\0.0001, both comparisons); MRI mitigate flushing at the onset of BG-12 therapy. cohort (BID 63 % and TID 59 % vs placebo 39 %; p\0.0001, both Supported by: Biogen Idec Inc.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S107

P461 development for the treatment of relapsing forms of MS (RMS). The Dimethyl fumarate suppresses inflammation in vitro TEriflunomide Multiple Sclerosis Oral (TEMSO) Phase III pivotal study showed that teriflunomide reduced the annualised relapse rate via both nuclear factor (erythroid-derived 2)-like by over 30 % (p\0.001 vs placebo), and was well tolerated with a 2-dependent and -independent pathways favourable safety profile. This post hoc analysis of TEMSO data P. Bista, W. Zeng, S. Ryan, M. Yamamoto, M. Lukashev assessed the impact on HR-QoL of teriflunomide treatment by esti- Biogen Idec Inc. (Cambridge, US); Tohoku University (Sendai, JP) mating utilities (a unit of HR-QoL). Methods: A utility score, ranging from -0.59 (severe problem) to 1 Objectives: BG-12 is in late-stage development for relapsing multiple (perfect health), was derived via the EQ-5D, a standardised HR-QoL sclerosis (MS). The active ingredient of BG-12 (dimethyl fumarate questionnaire, which was administered during the study. To estimate [DMF]) reduces CNS inflammation in rodent experimental autoim- any disutility (a unit of utility lost) associated with the safety and mune encephalomyelitis (EAE). Inflammatory cytokine production by tolerability of teriflunomide administration, a multivariate regression activated macrophages/microglia is thought to contribute to CNS linear model was used, including factors associated with a potential inflammation in both EAE and MS. The disease-modifying effect of impact on change from baseline (CfB) in utility including: age, DMF in EAE is associated with activation of the nuclear factor gender, treatment, number of relapses during the study, Expanded (erythroid-derived 2)-like 2 (Nrf2) pathway and concurrent suppres- Disability Status Scale CfB scores and baseline utility score. sion of microglial activation. However, the extent of the contribution Results: In the intention-to-treat population (N=1086), utility of Nrf2 to suppression of inflammation by DMF is unclear. Here we scores CfB were available for 772 patients (71 %) at the end of the investigate whether DMF inhibits macrophage-associated inflamma- study; missing data were well balanced between the treatment groups. tion in vitro via Nrf2-dependent and/or Nrf2-independent pathways. After 2 years of treatment, the mean (SD) CfB in utility score showed Methods: Macrophage cultures derived from the bone marrow of a trend towards worsening in the placebo group and an improvement Nrf2+/+ and Nrf2-/- mice were stimulated in vitro for 6 h by 5 ng/mL in the two teriflunomide groups: placebo, -0.007 (0.22); teriflunomide bacterial lipopolysaccharide (LPS). Before LPS stimulation, some 7 mg, +0.022 (0.21); teriflunomide 14 mg, +0.001 (0.21). Using the cultures were pretreated with DMF. Total RNA was extracted, and multivariate regression model, treatment disutility estimates of teri- transcripts were analysed using quantitative real-time polymerase flunomide were not significantly different from placebo: teriflunomide chain reaction. Whole-cell protein extracts were prepared and phos- 7 mg, 0.017 (p=0.31); teriflunomide 14 mg, -0.00006 (p=0.96). phoproteins were analysed using Western blots. Conclusion: This analysis demonstrates that there is no disutility Results: With LPS stimulation, Nrf2-/- macrophages showed a (i.e. no decrease in HR-QoL measure) associated with administration 3-fold increase in interleukin (IL)-1-beta mRNA and a [300-fold of teriflunomide. These results are consistent with the characteristics increase in IL-10 mRNA, relative to Nrf2+/+ macrophages. Increased of teriflunomide, a once-daily oral therapy which was well-tolerated inflammatory capacity of Nrf2-/- macrophages correlated with and displayed a favourable safety profile during the study. increased LPS-induced phosphorylation of the proinflammatory p38 Study supported by: Genzyme, a sanofi company enzyme. LPS induced the Nrf2 target genes, Nicotinamide adenine dinucleotide phosphate quinine oxidoreductase (NQO1) and heme oxygenase-1, in Nrf2+/+ but not in Nrf2-/- macrophages. At low concentrations, DMF pretreatment suppressed the induction of LPS- P463 induced cytokines in Nrf2+/+ cells but not in Nrf2-/- cells, while at higher concentrations DMF-mediated suppression extended to Nrf2-/- Effect of severe renal impairment cells. DMF 1 mM pretreatment suppressed the induction of IL1-beta on the pharmacokinetics and tolerability and IL-10 mRNA by 68 % and 51 %, respectively, in Nrf2+/+ cells of teriflunomide compared with 15 % and 8 % in Nrf2-/- cells. DMF 10 mM pre- F. Menguy-Vacheron, P. Clot, L. Cai, Y. Su, S. Turpault treatment suppressed the induction of IL1-beta and IL-10 mRNA by sanofi R&D, Clinical Exploratory Pharmacology Department (Chilly 100 % and 96 % in Nrf2+/+ cells and by 87 % and 81 % in Nrf2-/- Mazarin, FR); Sanofi R&D China (Beijing, CN); Sanofi R&D US cells. (Bridgewater, US) Conclusions: DMF suppresses macrophage-associated inflammation in vitro via both Nrf2-dependent and Nrf2-independent pathways. Objective: Teriflunomide is a novel oral disease-modifying therapy in Inhibition of macrophage function may contribute to the therapeutic development for the treatment of relapsing forms of multiple sclerosis effect of BG-12 in MS. (RMS). Renal elimination of unchanged teriflunomide is limited. Study Supported by: Biogen Idec Inc. However, as teriflunomide is highly bound to protein and is moderately metabolised, we investigated the effects of severe renal impairment (SRI) on the pharmacokinetics (PK) of a single dose of teriflunomide and compared it to the PK in subjects with normal renal P462 function. The tolerability of teriflunomide in subjects with SRI versus Impact on health-related quality of life of teriflunomide subjects with normal renal function was also assessed. Methods: This was a single-centre, open-label study, in which a treatment by estimating utilities in patients single 14 mg dose of teriflunomide was administered to 8 adults with relapsing multiple sclerosis: results from TEMSO (males aged 18–75, women aged 45–75 years) with SRI (creatinine post hoc analysis clearance\30 mL/minute, not requiring haemodialysis) and 8 healthy P. O’Connor, A. Briggs, P. Carita, G. Be´go-Le-Bagousse controls matched by age, gender and weight. Blood samples were collected up to 1272 h after dosing to assess teriflunomide total and University of Toronto (Toronto, CA); University of Glasgow unbound (following equilibrium dialysis) concentrations. Terifluno- (Glasgow, UK); Sanofi-Aventis R&D (Massy, FR) mide non-compartmental PK parameters and geometric mean ratios Objectives: Multiple sclerosis (MS) has a negative impact on health- (GMRs; SRI versus normal) with 90 % confidence intervals (CIs) related quality of life (HR-QoL). Adverse events and tolerability were calculated. Adverse events (AEs) were also recorded. issues associated with disease-modifying therapies (DMTs) for MS Results: GMRs (90 % CI) for observed maximum plasma con- may further worsen HR-QoL. Teriflunomide is a novel oral DMT in centration (Cmax) and area under the plasma concentration versus

123 S108 J Neurol (2012) 259 (Suppl 1):S1–S236 time curve (AUC) were 1.16 [0.97, 1.39] and 1.03 [0.61, 1.74], The Royal Melbourne Hospital (Victoria, AU); University Hospital respectively. Similar ratio estimates were obtained with unbound of Sart-Tilman (Lie`ge, BE); University Hospital Basel (Basel, CH); teriflunomide parameters. Furthermore, the fraction unbound in Consorzio Mario Negri Sud (Chieti, IT); University of Bari (Bari, IT); healthy subjects (0.25 %) was similar to that in patients with SRI University of Mu¨nster (Mu¨nster, DE); Biogen Idec Inc. (Weston, US) (0.25 %). No serious AEs were reported and no subject discontinued Objectives: Evaluate factors including geographic region, time since due to treatment-emergent AEs (TEAE). During the teriflunomide- enrolment, baseline characteristics, postbaseline efficacy, and safety alone period, TEAEs were similar in number and type (5/8 vs 4/8 in in natalizumab-treated multiple sclerosis (MS) patients with and SRI and control groups, respectively). without prior treatment. Conclusion: SRI did not adversely impact the single dose PK or Methods: The ongoing natalizumab (TYSABRI) Observational tolerability of teriflunomide. Therefore, no dosage adjustment is Program (TOP) assesses long-term outcomes in natalizumab-treated necessary for patients with severe renal impairment. patients with relapsing-remitting MS in Europe, Australia, and Can- Study supported by Genzyme, a sanofi company ada. Baseline characteristics of treatment-naı¨ve and previously treated patients in TOP were compared. The association between prior treatment status and postbaseline annualised relapse rates (ARRs) was P464 examined using a negative binomial regression model. Time to What to expect one year after natalizumab improvement on the Expanded Disability Status Scale (EDSS) was discontinuation in multiple sclerosis patients analysed using a Cox proportional hazards model. Serious adverse F. Sangalli, L. Moiola, L. Ferre`, M. Radaelli, V. Barcella, events (SAEs) were compared using a Pearson Chi-square or Fisher exact test. V. Martinelli, G. Comi Results: As of June 1, 2011, 10 % (337 of 3484) of natalizumab- San Raffaele Hospital (Milan, IT) treated patients were treatment naı¨ve before starting natalizumab. Background: When natalizumab discontinuation is considered, strat- Proportions of treatment-naı¨ve patients varied significantly by country ification of the risk of progressive multifocal leukoencephalopathy (Slovakia, 0 %; Great Britain, 36 %) and time since enrolment (0-12 might be weighed with the risk of disease reactivation. Till now, months, 12 %; 13-24 months, 7 %; [24 months, 9 %). Baseline however, little is known about long-term follow-up of patients after characteristics that differed between treatment-naı¨ve and previously the drug discontinuation. treated patients included mean age (35.8 vs 37.6 years), median dis- Objective: To monitor disease activity after natalizumab ease duration (1.9 vs 7.8 years), and median EDSS score (3.0 vs 3.5) discontinuation. (all P\=0.013). Treatment-naı¨ve patients had a lower postbaseline Methods: We followed 84 patients who stopped natalizumab after ARR (0.18 vs 0.26; P=0.002) and were more likely to show at least 12 cycles and immediately started a first-line treatment. They improvement in EDSS at 3 years (hazard ratio [95 % confidence underwent periodic clinical evaluations and brain MRI scan around interval]=1.59 [1.14-2.22]; P=0.007). Treatment-naı¨ve and previously 3rd, 6th and 12th month after interruption. treated groups did not differ significantly in incidence of SAEs (4.2 % Results: We followed patients for a mean time of 16 months. vs 5.2 %; P=0.340), infection-related SAEs (0.9 % vs 1.2 %; Overall in our cohort 71.4 % of patients showed signs of disease P=0.640), or progressive multifocal leukoencephalopathy (0.0 % vs activity and time to relapse was 5.9 months. We subdivided disease 0.2 %; P=1.00). reactivation on the basis of time of its occurrence, i.e. early reac- Conclusion: Treatment-naı¨ve patients differed from previously tivation within 3rd and 4th months, late reactivation within 5th and treated patients in that they were younger, had shorter disease dura- 7th month and very late reactivation past the 7th month. Early tion and lower baseline EDSS, and were more likely to show EDSS reactivation was observed in 35 % of patients. Forty percent of improvement following natalizumab treatment. The groups also dif- patients showed a late reactivation. The remaining 25 % of patients fered significantly in geographic distribution and time of enrolment. presented a relapse and/or new T2 lesions and/or Gd-enhancing Relapses decreased in both groups, but postbaseline ARR was sig- lesions in 25 %. Due to disease reactivation, 46 % of patients nificantly lower in treatment-naı¨ve patients. SAE incidence was changed from immunomodulants to second-line therapies; interest- similar among treatment-naı¨ve and previously treated patients. ingly, half of them returned to natalizumab. Finally we tried to Updated data will be presented. identify patients showing the so-called rebound activity and we This study was supported by Biogen Idec Inc. and Elan Pharma- selected 4 cases (4,7 %) in which severity of relapses and/or number ceuticals, Inc. of new T2 or Gd-enhancing lesions was much higher than pre-natalizumab disease activity. Conclusion: Data after natalizumab discontinuation suggest that disease stability, reached on therapy, doesn’t always maintain since P466 natalizumab doesn’t cause long-term immunological changes. JCV epidemiology in MS: prevalence of anti-JC virus Therefore a careful evaluation of risk/benefit ratio of stopping na- antibodies in multiple sclerosis patients talizumab is mandatory. Moreover patients should be closely C. Bozic, M. Subramanyam, D. Paes, S. Richman, monitored to early detect signs of disease activity in order to readily change therapy if needed. T. Plavina, A. Zhang, B. Ticho Biogen Idec Inc. (Weston, US) Objectives: The objective of this study is to evaluate the prevalence of P465 anti-JC virus (JCV) antibodies in geographically diverse cohorts of multiple sclerosis (MS) patients. Baseline characteristics, treatment efficacy, and serious Methods: JCV Epidemiology in MS (JEMS) is a cross-sectional, adverse events in natalizumab-treated MS patients multicentre, multinational, epidemiological study designed to enrol without prior treatment [=2000 MS patients in Europe, Canada, and Australia. Patients with H. Butzkueven, S. Belachew, L. Kappos, F. Pellegrini, a diagnosis of MS (any type or treatment) are eligible to participate. Anti-JCV antibody testing is performed centrally using a two-step M. Trojano, H. Wiendl, A. Zhang, R. Arnold anti-JCV antibody assay. Anti-JCV antibody prevalence is estimated

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S109 as the percentage of patients with detectable anti-JCV antibodies. sensitivity, matrix interference, robustness, and reagent stability. Factors associated with prevalence such as demographic data, disease Finally, all samples (n=25) collected [=6 months prior to PML characteristics, and treatment history are also evaluated. diagnosis from 25 natalizumab-treated PML patients were shown to Results: At the time of this interim analysis, 3714 patients had be positive for the presence of JCV antibodies (100 % concordance anti-JCV antibody testing results available. The average age was 42.4 with the original assay). years, median MS disease duration was 9 years, 71 % were women, Conclusion: The validated enhanced ELISA assay for detection of 96 % were white, and 81 % had a relapsing form of MS. The overall JCV antibodies in human serum and plasma offers improved perfor- prevalence rate for anti-JCV antibodies was 57.7 % (95 % confidence mance and robustness that support the routine clinical use of the assay interval: 56.1 % to 59.3 %). There was a significant difference in anti- as a PML risk stratification tool. JCV antibody prevalence by age, which increased from 50.5 % in This study was supported by Biogen Idec Inc. and Elan Pharma- 15–29-year-old patients to 65.0 % and 65.4 % in 50–59 and [=60- ceuticals, Inc. year-old patients, respectively (P\0.0001). Females had a significantly lower anti-JCV antibody prevalence rate than males (56.4 % vs 60.7 %; P=0.015 [age adjusted]). Prevalence rate varied significantly across countries, ranging from 49 % (Australia) to 69 % (Portugal) P468 (P\0.0001 [age and gender adjusted]). No significant associations Innovative management of MS patients on natalizumab were observed between anti-JCV antibody status and race, MS type, using MSDS 3D software MS disease duration, number of MS therapies, any (prior or current) T. Schultheiß, R. Kempcke, T. Ziemssen immunosuppressant use, or MS treatment duration. University Hospital Carl Gustav Carus (Dresden, DE) Conclusion: The overall anti-JCV antibody seroprevalence rate of 57.7 % is consistent with earlier findings. There were significant Objectives: In MS, there is an increasing spectrum of highly efficient associations between anti-JCV antibody prevalence rate and age, treatment options (e.g. Fingolimod, Natalizumab) requiring an inev- gender, and country, although there were small sample sizes for some itable demand of specific risk management to detect adverse effects countries. Updated data will be reported in future publications. etc. This study was supported by Biogen Idec Inc. and Elan Pharma- Methods: Recently, we presented our innovative patient manage- ceuticals, Inc. ment system ‘‘MSDS 3D’’ as an approach to integrate data given by the physician, MS nurse and the patient. MSDS 3D allows computer- guided MS management via defined study modules. The natalizumab module was designed to evaluate patient safety on a monthly basis by P467 clinical parameters and laboratory/imaging assessments combined An enhanced ELISA assay for detection of JC virus with self-developed patient questionnaire for common signs of PML. antibodies in human serum and plasma to support Additionally, patient’s knowledge about natalizumab and PML was progressive multifocal leukoencephalopathy risk surveyed. Results: So far, more than 40 MS patients treated with natalizumab stratification are constantly monitored by MSDS 3D. Prior every infusion, a touch- P. Lee, A. Castro, M. Berman, D. Jaiswal, S. Rivas, screen based questionnaire asking for common signs of PML had to B. Schlain, T. Plavina, M. Subramanyam be completed by all patients. A survey on patients´ knowledge about Focus Diagnostics (Cypress, US); Biogen Idec Inc. (Weston, US) natalizumab consisting of 19 questions was performed every 3 months. No new cases of PML have been occurred in our patient Objectives: JC virus (JCV) infection is a prerequisite for the devel- cohort. Preliminary results indicate improved knowledge and alert- opment of progressive multifocal leukoencephalopathy (PML). The ness to PML signs over time using this education module. presence of JCV antibodies is a reliable indicator of infection with Conclusions: Knowledge survey and PML check list may both JCV and can indicate elevated risk for PML in MS patients on provide promising patient-related options to improve pharmacovigi- natalizumab. A 2-step enzyme-linked immunosorbent assay (ELISA) lance of patients treated with natalizumab and help MS experts to detect JCV antibodies was previously developed. The aim of recognising symptoms even in early stages. this research was to develop an enhanced ELISA that detects JCV antibodies with improved assay robustness and performance characteristics including consistent detection of low levels of JCV- specific antibodies. P469 Methods: The assay design was optimized by pre-coating JC virus- Natalizumab-related PML in multiple sclerosis: a case like-particles (VLP) on microtitre plates. The assay’s positive/nega- report tive cut-off was statistically established using sera from [1300 patients with MS from natalizumab clinical studies. The assay was D. Papadopoulos, A. Plafadeli, E. Zafeiropoulou, analytically validated and then used to determine the presence of JCV E. Kontogeorgi, H. Alexopoulos, A. Veretzioti, antibodies in both naı¨ve and natalizumab-treated MS patients ([=400 V. Zisimopoulou, M.C. Dalakas, A. Tavernarakis patients), as well as in natalizumab-treated patients who developed Evangelismos General Hospital (Athens, GR); University of Athens PML. (Athens, GR) Results: An enhanced assay for detection of JCV antibodies in human serum and plasma was developed. Key enhancements included Objectives: We describe a case of progressive multifocal leukoen- reduced number of samples (from 25 % to 10 %) requiring confir- cephalopathy (PML) in a 37 -year old male multiple sclerosis (MS) mation via the inhibition step of the assay and a reduced number of patient treated with natalizumab. patients with intermittently positive JCV serostatus. The seroposi- Case report: The patient was diagnosed with relapsing-remitting tivity remained similar to the original 2-step assay at 50 %-60 %. MS in 2001 following an episode of right-sided optic neuritis and was Additionally, assay robustness and ease-of-use were improved by started on interferon-beta1b. In 2008 he was changed to natalizumab stabilization of JC VLP on microtitre plates. The assay was suc- due to suffering relapses and an increase in T2-MRI lesion load in the cessfully validated to demonstrate acceptable precision, specificity, year prior to changing to natalizumab. Although clinically and

123 S110 J Neurol (2012) 259 (Suppl 1):S1–S236 radiologically stable since onset of natalizumab treatment, suspicion MAX vs MIN hazard ratio (HR) 0.64 (95 % CI 0.42–0.98); propor- of PML was raised by the patient’s complaints initially of irritability tion of patients reaching an EDSS score [=4: MIN 60.7 %, MAX and hostile behaviour and then of visual deterioration after 21 31.8 % (odds ratio [OR] 0.30, 95 % CI 0.15–0.63); proportion of monthly natalizumab infusions. MRI showed a new right occipital patients reaching an EDSS score [=6: MIN 52.1 %, MAX 13.9 % lesion with mild Gd-enhancement but JC virus DNA was not detected (OR 0.15, 95 % CI 0.07–0.33); proportion of patients with 5 or fewer by PCR in the CSF. However, within a month the patient’s vision relapses and EDSS score less than 4: MIN 16.9 %, MAX 35.7 % (OR deteriorated further and based on clinical suspicion and new MRI 2.73, 95 % CI 1.21–6.14); proportion of patients with 5 or fewer evidence of bilateral occipital lesions suggestive of PML, the patient relapses and EDSS score less than 6: MIN 16.4 %, MAX 47.2 % (OR underwent plasma exchange (PLEX) to accelerate removal of natal- 4.55, 95 % CI 2.10–9.85). Mean (SD) change in EDSS score from izumab 6 weeks after its last infusion and was started on mirtazapine baseline to LTFU: MIN 2.5 (2.01), MAX 1.2 (1.52). Time to con- (60mg/day, PO). Prednisolone (60mg/day PO) and monthly infusions version to secondary progressive MS: MAX vs MIN HR 0.31 (95 % of methyl-prednisolone 1g/day for three days were also administered CI 0.17–0.56). for 3 months to control the excessive inflammatory effects of the Conclusion: The findings of these post hoc analyses in a non- immune reconstitution inflammatory syndrome (IRIS). Diagnosis was randomized sample suggest that higher cumulative dose exposure to established with a more sensitive quantitative PCR assay after PLEX sc IFN beta-1a may be associated with better clinical outcomes at two months from first PML manifestations. He continued to deteri- Year 15 compared with lower cumulative dose exposure. orate for approximately one month after PLEX with a perception of This study was supported by Merck Serono S.A. – Geneva, light only vision bilaterally and left hemiparesis requiring unilateral Switzerland (a branch of Merck Serono S.A., Coinsins, Switzerland, assistance. Nevertheless, MRI at 4 weeks from PLEX revealed pari- an affiliate of Merck KGaA, Darmstadt, Germany). eto-temporal extension of the occipital lesions but without evidence indicative of IRIS and remained unchanged after 12 weeks from PLEX. Four months after PML presentation the patients’ condition improved slightly to detecting hand movement vision bilaterally and P471 being able to walk unassisted. Effect of two dosing frequencies of subcutaneous Conclusion: The insidious course of PML and the difficulty in distinguishing PML from MS lesions require a high level of vigilance interferon beta-1a on lesion volumes in patients and a low threshold for intervention in order to limit its destructive with a first clinical demyelinating event suggestive potential. Furthermore, lack of Gd-enhancement of MRI lesions fol- of multiple sclerosis: results of the phase III REFLEX lowing PLEX may suggest a beneficial role for high dose study extension (REFLEXION) corticosteroids in minimizing IRIS-related damage. N. De Stefano, G. Comi, L. Kappos, M.S. Freedman, C.H. Polman, B.M.J. Uitdehaag, E. Verdun di Cantogno, P470 L. Lehr, D. Issard, B. Hennessy, F. Barkhof University of Siena (Siena, IT); Ospedale San Raffaele (Milan, IT); Cumulative dose-effect of up to 15 years University Hospital Basel (Basel, CH); The Ottawa Hospital (Ottawa, of subcutaneous interferon beta-1a on clinical outcomes CA); VU University Medical Center (Amsterdam, NL); Merck in relapsing–remitting multiple sclerosis: exploratory Serono S.A. (Geneva, CH) analysis of patients from the PRISMS study Objectives: The REFLEX (REbif FLEXible dosing in early MS; L. Kappos, E. Verdun di Cantogno, P. Cornelisse, J. Kuhle, NCT00404352) study showed that subcutaneous (sc) interferon B. Uitdehaag (IFN) beta-1a 44 mcg three times weekly (tiw) or once weekly (qw) significantly reduced the risk of conversion to McDonald multiple University Hospital Basel (Basel, CH); Merck Serono S.A. (Geneva, sclerosis (MS) (2005) or clinically definite MS (CDMS) over 2 CH); VU University Medical Center (Amsterdam, NL) years, compared with placebo in patients with a first clinical Objectives: The placebo-controlled PRISMS study established the demyelinating event (FCDE). The extension study (REFLEXION; efficacy of subcutaneous (sc) interferon (IFN) beta-1a, three times NCT00813709) investigated the effects of early sc IFN beta-1a weekly, on clinical and magnetic resonance imaging measures in treatment versus delayed treatment up to 36 months after random- relapsing–remitting multiple sclerosis. Where possible, patients have ization in REFLEX. Here we present the effects on lesion volumes been followed up at up to 15 years (PRISMS-15) to examine further up to Month 36. long-term treatment outcomes in this population. Methods: In REFLEX patients were randomized to sc IFN beta- Methods: All patients in the original PRISMS study were invited 1a 44 mcg tiw or qw, or placebo for 24 months or conversion to to a single long-term follow-up (LTFU) visit up to 15 years after CDMS; all patients switched to open-label 44 mcg tiw treatment at initial randomization. Cumulative sc IFN beta-1a dose exposure was conversion. All REFLEX patients were eligible for the extension determined and clinical outcomes were assessed in the minimum study. At 24 months, patients in the placebo arm who had not yet (lowest quartile, MIN) and maximum (highest quartile, MAX) converted to CDMS started 44 mcg tiw (delayed treatment; pla- cumulative dose exposure groups. cebo/tiw); patients still receiving 44 mcg qw stayed on this regimen Results: Of the original 22 centres with 560 patients, 18 centres until CDMS; patients receiving 44 mcg tiw continued treatment. participated in the 15-year LTFU from which 61.8 % (291/471) of Original blinding was maintained. MRI scans were performed patients returned for the 15-year LTFU visit. At this visit the mean 3-monthly from baseline to month 24 or CDMS, with one scan at (standard deviation [SD]) cumulative dose of sc IFN beta-1a was 12.3 month 36. (7.4) mg in the MIN group (n=73) and 94.9 (10.4) mg in the MAX Results: 402 patients (77.8 % of REFLEX population) entered group (n=72). Patients in the MAX group experienced fewer relapses the extension study; mean (SD) age was 31.4 (8.3) years and and Expanded Disability Status Scale (EDSS)-defined clinical events 61.7 % were women. Integrated data from REFLEX and compared with patients in the MIN group: mean annualized relapse REFLEXION (delayed treatment, n=171; 44 mcg qw, n=175; 44 rate (95 % confidence interval [CI]): MIN 0.50 (0.46–0.54), MAX mcg tiw, n=171) were analysed by original REFLEX treatment 0.37 (0.33–0.40); time to 3-month confirmed EDSS progression: group. Mean (SD) change in T2 lesion volume (mm3) per patient,

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S111 baseline to last observed value (LOV) was: delayed treatment, – Conclusion: These preliminary data suggest that a high proportion 116.0 (2418.9), 44 mcg qw, –169.0 (2662.8; p=NS vs delayed of patients have good treatment adherence when using RebiSmart for treatment); 44 mcg tiw, –552.0 (2105.8; p\0.001 vs delayed self-injection of sc IFN beta-1alpha, and that good adherence can be treatment; p=0.009 vs qw). Change in T1 hypointense lesion vol- achieved even in patients who are initially fearful of injections. ume baseline to LOV was: delayed treatment, 265.4 (968.7); 44 This study was supported by EMD Serono Canada, a division of mcg qw, 215.6 (866.6; p=NS vs delayed treatment); 44 mcg tiw, EMD Canada, Inc. 83.2 (675.4; p=0.007 vs delayed treatment; p=NS vs qw). Baseline to LOV change in Gd-enhancing lesion volumes did not differ significantly between groups. Conclusion: Early treatment with IFN beta-1a 44 mg sc tiw con- P473 ferred significantly greater benefits over delayed treatment in terms of Diluent halving: a new strategy to optimise interferon changes in volumes of T2 lesions and T1 hypointense lesions. The beta-1b-related skin reactions? reduction in T2 lesion volume was significantly greater with IFN C. Zecca, N. Yawalkar, C. Staedler, C. Gobbi beta-1a 44 mg sc tiw treatment than with qw treatment. Ospedale Civico (Lugano, CH); Inselspital (Berne, CH) This study was supported by Merck Serono S.A. – Geneva, Switzerland (a branch of Merck Serono SA, Coinsins, Switzerland, an Objective: The spectrum of side effects related to interferon beta-1b affiliate of Merck KGaA, Darmstadt, Germany). (INF-1b) treatment may compromise long term treatment adherence. We report on a small sample of patients affected with multiple sclerosis (MS) who improve skin tolerability after halving the volume of the INF-1b diluent. P472 Methods: This is a preliminary observation on five MS patients Anxiety and adherence in patients with relapsing treated with INF-1b with poor skin tolerability and clinical stability multiple sclerosis using RebiSmartTM for self-injection: (no relapses in the past year, no EDSS progression in the past 2 years) preliminary results from the MEASURE study who were instructed to dissolve the established (250 lg) INF-1b dose in half (0.5 ml) the standard diluent (1.0 ml, 0.54 % sodium chloride V. Devonshire, A. Feinstein, K. Fortin solution). They were followed prospectively for 9 months. Clinical, University of British Columbia (Vancouver, CA); University of blood and safety monitoring at months 3, 6 and 9 as well as monthly Toronto (Toronto, CA); EMD Serono, Canada, a division of EMD phone interviews were performed. Visual analogue scales and Canada, Inc. (Montreal, CA) objective medical evaluation were used to assess side effect severity Objectives: Adherence to medication is critical for optimal treatment at months 3, 6 and 9. of multiple sclerosis (MS). Most disease-modifying drugs require Results: Halving the volume of the treatment diluent while parenteral administration. Minimising injection anxiety may help maintaining the same INF-1b dose was associated with significant patients maintain good adherence to treatment. RebiSmart is improvement of skin side effects profile in all patients; this designed to minimise injection anxiety when administrating subcu- improvement was sustained for 9 months. taneous (sc) interferon (IFN) beta-1a, by incorporating a hidden Conclusions: Halving the volume of the INF-1b diluent could needle and injection comfort settings. We assessed changes in represent a different therapeutic strategy to continue INF-1 b and overall anxiety and injection anxiety, and the relationship between optimize skin tolerability and adherence in some MS patients. injection anxiety and treatment adherence over a 24-week study Dr. Zecca received honoraria for speaker bureau from Teva, period. Merck Serono, Biogen Idec, Bayer Schering, Novartis. Methods: We performed a preliminary analysis of week-12 and Dr. Yawalkar has nothing to disclose. week-24 adherence data from a multicentre, single-arm, observa- Dr. Gobbi received honoraria for speaker bureau from Teva, tional, 96-week, Phase IV study to evaluate treatment adherence with Merck Serono, Biogen Idec, Bayer Schering, Novartis. RebiSmart for self-injection of sc IFN beta-1alpha in patients with MS. Adherence data were recorded in the electronic device injection log. A cut-off of[=80 % was defined as good adherence to treatment. P474 Patients were evaluated for anxiety at baseline, week 12 and week 24 using the Hospital Anxiety and Depression (HAD) scale, State Trait Quality-of-life assessment in patients with MS receiving Anxiety Inventory (STAI) and patient-reported ‘‘fear of self-injec- interferon beta-1a: a comparative longitudinal study tion’’ measured on a scale of 1–5. Patients were categorised as ‘‘not of Avonex and its biosimilar Cinnovex fearful’’ of self-injection if they had a score of 0 or 1, and ‘‘fearful’’ if R. Abolfazli, A. Hosseini, K. Gholami, M.R. Javadi, they had a score of 3, 4 or 5. Results: At week 12, 94 % of patients (n=124) were [=80 % H. Torkamandi, S. Emami adherent (95 % CI: 0.88, 0.97) to treatment. At week 24, 85 % of Tehran University (Tehran, IR); Azad University (Tehran, IR) patients (n=101) were [=80 % adherent. At baseline, week 12 and Background: Multiple Sclerosis is an autoimmune inflammatory week 24, mean (SD) HAD Anxiety subscale score was 7.1 (4.1), 5.9 disease of Central Nervous System and Quality of Life (QOL) is (4.2) and 6.0 (4.2), and mean (SD) STAI State-Anxiety score was affected by MS due to physical disability and other associated 40.6 (12.4), 36.0 (12.7) and 36.0 (12.5), respectively. Patient-reported problems. Disease modifying agents like interferon-beta (INFB) have ‘‘fear of self-injection’’ declined markedly: 67.9 % of patients were been widely utilized in this patient population however, their fre- less ‘‘fearful’’ at week 24 compared with baseline. Of the 17 patients quency and rout of administration, side effects and high cost and also who were ‘‘fearful’’ at both baseline and week 12, 88 % maintained the question whether they are truly beneficial for longer term out- good treatment adherence. Of the 36 patients who were ‘‘fearful’’ at comes on QOL needs to be further investigated. baseline but ‘‘not fearful’’ at week 12, 97 % maintained good treat- Objectives: 1) To assess QOL in patients with multiple sclerosis ment adherence; 98 % of the 57 patients who were ‘‘not fearful’’ from receiving interferon beta-1a (Avonex and Cinnovex) and 2) to com- baseline to week 12 maintained good adherence. Similar results were pare QOL in groups receiving Avonex or Cinnovex to evaluate if the recorded at week 24.

123 S112 J Neurol (2012) 259 (Suppl 1):S1–S236 more cost-effective biogeneric form of INFB (Cinnovex) has the same Significant higher health care costs (payer perspective, time affect on QOL and can be substituted for Avonex. periods: 6 months before therapy, after 6 and 12 months): before Methods: We conducted a 30-month longitudinal study and treatment, before month 6 and 12 (baseline visit: mean €1.590, SD recruited a total of 92 patients diagnosed with relapsing-remitting MS. €2.190, after 6 months: €584, SD €1.510, after 12 months: €524, SD The patients were categorized in Avonex and Cinnovex groups with €1.675, p\0.0001, n=216). Same results from societal perspective: 46 patients in each group. Quality of life was assessed using MSQOL- baseline: mean €2.511, SD €3.292, after 6 months: €951, SD €1.967, 54 four times a year at baseline and at months 4, 8 and 12 of study. after 12 months: €1.009, SD €2.780, (p\0.0001, n=167). Results: Mean age ± SD was 30.5 ± 8.9 and 32.3 ± 9.0 years in Conclusions: In a real-world-setting IM IFNb-1a therapy in Avonex and Cinnovex groups, respectively and %80.5 of patients combination with a PMP is effective in maintaining adherence and were females. The physical health composite scores were 61.8 and reducing costs. 59.8 (p-values 0.677 and 0.884) for Avonex and Cinnovex groups in This study was supported by Biogen Idec GmbH, Germany. that order. The results of the study revealed no significant difference between two groups with regards to physical health, health perception, energy, role limitations due to physical problems, pain, sexual and social function and physical health distress scores. Further, P476 interferon therapy was not significantly beneficial in improving Efficacy analysis of disease-modifying treatments patients’ QOL at baseline and after a year of treatment with either in more than 9000 German patients with MS Avonex or Cinnovex. M. Maürer, S. Domke, G. Reifschneider, P. Knorn, Conclusions: According to our study treatment with INF-b (Avonex or Cinnovex) did not significantly affect QOL after a year of S. Windhagen, H. Albrecht, G. Niemzcyk, P. Schicklmaier, therapy. and in this study, good tolerability to treatment also was K. Rehberg-Weber, C. Wernsdo¨rfer, S. Schwab shown in both groups. there was no serious adverse events which Caritas Hospital (Bad Mergentheim, DE); MS-Schwerpunktpraxis were caused medication stopped during our study. Dachsel/Domke (Chemnitz, DE); Neurocenter Odenwald (Erbach, DE); Zentrum fu¨r ambulante Neurologie (Essen, DE); Clinic Osnabru¨ck (Osnabru¨ck, DE); Neurozentrum-Riem (Munich, DE); Biogen Idec GmbH (Ismaning, DE); University Hospital Erlangen P475 (Erlangen, DE) The impact of the MS-CARE patient management Objectives: We recently showed in a large German cohort of MS programme on adherence and healthcare costs patients (TYPIC survey) that immunomodulatory treatment with in interferon-beta treated patients with multiple interferon (IFN) beta or glatiramer acetate is effective in the majority sclerosis of patients with relapsing-remitting MS (RRMS), (Maürer M et al. Z. Katsarava, K. Gottwald, B. Ehlken, S.N. Patel, Europ J Neurol. 2011). The aim of this subgroup analysis was to compare the treatment efficacy of different immunomodulatory G. Niemzcyk, K. Rehberg-Weber RRMS treatments under clinical real-life conditions. Evangelic Hospital (Unna, DE); University Hospital (Essen, DE); Methods: This was an open-label, retrospective data collection of Neurologische Praxis (Stuttgart, DE); IMS HEALTH GmbH & Co. 9916 patients from 488 German outpatient MS centers. Patients with OHG (Munich, DE); Biogen Idec GmbH (Ismaning, DE) RRMS diagnosis dating back at least 12 months who either underwent Background: Disease modifying treatments for MS such as interferon- treatment with IFN beta or glatiramer acetate or who were untreated beta have been shown to reduce the risk for disease progression. during the preceding year were enrolled. 7896 patients received Therefore adherence to treatment is essential for treatment outcome. immunomodulatory treatment. Demographic data, type of immuno- Objective: To demonstrate in a real-world–setting that a patient modulatory treatment, clinical disease activity and MRI findings (T2 management program (PMP) improves adherence to DMT and thus lesions and Gd-enhancing lesions) during the last 12 months were results in improvement of clinical outcome and decrease of health evaluated. For evaluation of differences in efficacy the following care costs. parameters of clinical disease activity over 12 months were analysed: Design and methods: Open label, multicenter, prospective, EDSS: baseline (current EDSS), EDSS 12 months ago (retrospective); observational study in Germany. 731 MS-patients in 219 centers relapses of DMTs, ARR and number of patients with relapses within were treated with IM IFNb-1a, offered PMP and followed for up to the last 12 months; MRI-findings. 12 months. PMP consisted of injection trainings, support and Results: 7284 treated MS-patients were analysed. 29,6 % regular quarterly follow-up for up to 12 months after initiation of (n=2154) of the patients received treatment with intramuscular (IM) therapy. Resource consumption of health care services was IFN beta-1a, 25,6 % (n=1865) SC IFN beta-1a, 22,5 % SC IFN beta- evaluated. 1b (n=1642) and 22,3 % (n=1623) with glatiramer acetate. The Adherence was judged as ‘‘good’’ (mean values: 2.0±1.9) on an treatment efficacy was similar in all applied DMTs under daily real ordinal scale from 1 (‘‘very good’’) to 10 (‘‘very bad’’) by the treating life conditions: similar relapses during the last 12 months (no relapse, neurologist. Primary endpoint: health-care costs in adherent versus [= 1 relapses) and annual relapse rate as well as similar EDSS-course non-adherent patients. Secondary endpoints: Clinical outcome in and MRI-findings were found. adherent vs. non-adherent patients including fatigue and QoL. Conclusions: The comparison of the documented efficacy in the Results: 731 patients (mean age: 38.2, 73.7 % female) were open-label, retrospective TYPIC-data collection demonstrates equal enrolled, 640 (88 %) finished the investigation. PMP-Participation: 6 efficacy with no significant differences among the available parenteral months after starting therapy: continuously 134/393 patients (34 %), DMTs in a large MS patient cohort under comparable conditions in temporarily 82/393 (21 %) and 154/393 (39 %) no participation; 12 real life practice. Limitations of this study predominantly involve the months after baseline: continuously 37 % (93/251), temporarily 19 % retrospective character of the survey. (48/251) and 40 % (101/251) no participation. This study was supported by Biogen Idec GmbH, Deutschland.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S113

P477 owed e.g. to pre-selection, intensive monitoring and standardized Randomised, double-blind, cross-over trial of GTR evaluation of study participants. In contrast to the situation in clinical trials, switching of DMT or treatment interruptions are common in (generic glatiramer acetate) in healthy volunteers shows daily practice. So far, little is known of how the use of previous DMT Ò similar tolerability and safety to Copaxone or drug discontinuation affects patients’ satisfaction with current J. Oberye, E. van den Tweel, M. Mulder, G. Voortman, treatment or treatment efficacy. Moreover, the factors that lead to a L. Hooftman change in treatment regimens are not well characterized. The aim of Synthon BV (Nijmegen, NL) the German study was to prospectively assess the efficacy of IM IFN beta-1a in a real-world-setting after a treatment free period of at least Objectives: GTR is developed as a generic alternative to Copaxone 3 months. (COP), in order to reduce treatment costs in Multiple Sclerosis. This Methods: Open label, multicenter, prospective, observational study was conducted to compare occurrence of local injection site study. DMT treatment was allowed previous to this 3 months period. reactions (LISR) and adverse events (AE) after subcutaneous (SC) The disease course within the previous 3 to 12 months, the type of injection of GTR and COP in healthy volunteers. preceding MS treatments as well as treatment characteristics (change Methods: Twenty subjects received SC injections of glatiramer or interruption of treatment, treatment efficacy) were assessed retro- acetate 20 mg/mL: GTR (glatiramer acetate, Synthon BV) or COP spectively preceding enrolment. Data were collected prospectively at (glatiramer acetate, TEVA). Subjects were randomized to receive baseline, 3, 6, 9 and 12 months after inclusion.. Primary endpoint was each injection separated by 4 days as sequence 1: GTR-COP-GTR- the efficacy of IM IFN beta-1a by means of disability progression COP, or sequence 2: COP-GTR-COP-GTR. The number of LISRs (EDSS) and relapse activity. Secondary endpoints included efficacy (occurrence of pain, itching, redness, swelling or lumps) was assessed as assessed by the Multiple Sclerosis Functional Composite (MSFC) immediately, 5 min, 1 h, 8 and 24 h after injection. Total LISR score score, Fatigue Severity Scale (FSS) and MRI parameters. could range from 0-5 per time point, depending on number of Results: 235 MS patients with a treatment-free period of at least 3 symptoms. Severity was scored as None, Mild, Moderate or Severe. months in 105 centers initiated therapy with IM IFN beta-1a (30 lg Safety was evaluated by vital signs and adverse event reporting. once weekly). We will present the final results regarding patients’ Results: No serious AEs were reported. The majority of AEs were demographic and history of disease. Moreover, the efficacy of IM IFN mild and resolved in 24 h. Injection site pain and vomiting were the beta-1a treatment will be outlined. Finally, we will provide infor- only events of moderate intensity (4 reports in total). After both mation about the motivations for discontinuation of preceding treatments, most frequently reported AEs were local reactions related therapies and treatment characteristics including changes of treatment to the injection (mainly Injection site pain). regimens or factors that influenced treatment interruptions. When combining all time points, 92 and 78 LISRs (9.9 % and Conclusions: The results could be useful in optimising MS treat- 8.4 % of possible reports) were reported after GTR and COP injec- ment in everyday clinical practice. tion. The estimated mean LISR score for all times combined was 0.52 This study was supported by Biogen Idec GmbH, Germany. and 0.44 for GTR and COP, respectively. From the ANOVA analysis performed it followed that these scores were not significantly different (P=0.2203). No significant differences could be demonstrated at individual time points either. Pain was the most frequently reported P479 LISR: 76.1 % and 76.9 % of LISR reports after GTR and COP, Immunomodulatory treatment of relapsing-remitting respectively. The vast majority of LISRs were considered of mild multiple sclerosis – the ASSET (Avonex Assessment severity; only pain was considered more burdensome and scored more in Multiple Sclerosis Therapy) study, an observational frequently as moderate and severe (29.7 % and 8.8 % of all pain reports, respectively). For both treatments, the highest number of study in 1354 patients LISRs was found immediately and 5 min and 1 h after injection, with M. Marziniak, T. Graf, G. Niemczyk, K. Rehberg-Weber incidental LISR reports at 8 and 24 h after injection. on behalf of the ASSET-study group Conclusion: In this exploratory trial, both GTR and COP were well tolerated by all subjects. Although no relevant difference in the Objectives: Efficacy and safety of the disease modifying treatments local tolerance and safety profile could be demonstrated, these data (DMT), interferon (IFN) beta and glatiramer acetate, have been need to be confirmed in a 2-year Phase III trial in patients which is demonstrated in pivotal clinical trials and follow-up studies in the currently conducted in over 20 countries. baseline treatment of relapsing remitting multiple sclerosis (RRMS). This trial was sponsored by Synthon BV, The Netherlands. However, the parenteral application mode as well as undesirable effects of the treatment, e.g. local injection site reactions, can negatively affect the Quality of life (QoL) and thus might negatively influence adherence and efficacy. Type, characteristic and frequency P478 of injection site reactions depend on the applied DMT, injection mode Interferon beta-1a (Avonex) as treatment option (subcutaneous [SC], intramuscular [IM]) and frequency. Valid com- for untreated MS-patients (AXIOM) parative studies which provide comparative information on cutaneous C. Kleinschnitz, G. Niemczyk, K. Rehberg-Weber side reactions of all DMTs as well on patients’ QoL under daily practice conditions are limited. Thus, a comparative study investi- University of Wu¨rzburg (Wu¨rzburg, DE); Biogen Idec GmbH gating the available DMTs in a real-life setting in a high number of (Ismaning, DE) patients is of major interest. The aim of ASSET was to prospectively Objectives: Intramuscular (IM) interferon (IFN) beta-1a is well assess treatment efficacy and tolerability (with a particular focus on established as disease modifying treatment (DMT) in patients with skin tolerability) as well as the patients‘ QoL under a stable parenteral relapsing-remitting multiple sclerosis (RRMS) or clinically isolated DMT. syndrome (CIS). Besides IM IFN beta-1a, subcutaneous (SC) IFN Methods: German open label, multicenter, prospective, observa- beta-1a, SC IFN beta-1b and glatiramer acetate are also approved tional study with MS patients undergoing treatment with an approved DMT for the treatment of MS. However, large clinical trials can DMT. Patients were to be observed for a period of 12 months. Course model only certain aspects of the patients’ everyday life, a limitation of disease, cutaneous problems, injection site reactions, overall

123 S114 J Neurol (2012) 259 (Suppl 1):S1–S236 tolerability and QoL were documented every 3 months. Primary patients in the course of treatment with the use of copaxone (glatir- endpoint was efficacy of the different DMTs (by means of relapse amer acetate) enabled evaluation of long effect of this drug on activity). Secondary endpoints were disability progression (EDSS), restoring axonal links damaged as a result of multiple sclerosis. MRI findings, tolerability and QoL (EQ5D). Results: 1354 MS-patients (median age: 42) in 76 centers were enrolled. Mean duration from first MS diagnosis until initiation of the first treatment was 30.6 (+-56.6) months and mean duration from first P481 MS diagnosis until visit 1 of the study was 93.7 (+-77.4) months. The MDA level in CNS and its influence on neurological Comparative final results are presented with focus on injection site expression during acute phase of multiple sclerosis reactions before and after enrolment into the study. They differed experimental model between treatments and influenced patients’ health related QoL. Conclusions: The results of this study will show differences in S. Ljubisavljevic, I. Stojanovic, D. Pavlovic, D. Sokolovic, nature and frequency of local injection side reaction of the different I. Stevanovic, J. Ljubisavljevic DMTs in MS. This aspect, particularly regarding the treatment related Medical Faculty Nis (Nis, RS); Military Medical Academy (Belgrade, affection of the patients’ daily life and QoL are of major relevance for RS) treatment decisions and for optimization of the individual patient’s Objective: Here we report the influence of malondialdehyde (MDA) treatment. as a measure of lipid peroxidation process on multiple sclerosis (MS) This study was supported by Biogen Idec GmbH, Deutschland. pathogenesis and its neuronal sings, during the treatment with ami- noguanidine (AG) - selective inducible nitric oxide synthase inhibitor and N-Acetyl cysteine (NAC) – oxidative scavenger, in the experi- P480 mental autoimmune encephalomyelitis (EAE), the most frequently used animal model for studying MS. Efficacy of treatment of patients with relapsing- Materials and methods: EAE was induced by the subcutaneous remitting multiple sclerosis with copaxone (glatiramer injection of myelin basic protein, bovine type, dissolved in phosphate acetate) evaluated by brain magnetic resonance buffered saline (PBS) emulsified in equal volume of the complete spectroscopy Freund’s adjuvant (CFA), on days 0 and 7 in the hind foot pad of the animals under anesthesia. Two intraperitoneal injections of Pertussis Z. Rozhkova, O. Myalovitska, T. Kobys, I. Lobanova toxin were given on days 0 and 1. Each of animals (N=49), randomly, Medical Clinic ‘‘BORIS’’ (Kiev, UA); National O.O.Bogomolets was assigned to seven groups: control (PBS), EAE, CFA, EAE+AG, Medical University (Kiev, UA); Kiev City Clinical Hospital (Kiev, AG, EAE+ NAC and NAC group. All animals were scored daily, for UA) the clinical signs of EAE. MDA was evaluated in CNS structures – Brain proton magnetic resonance spectroscopy is a useful technique cerebellums and spinal cords. for evaluation of neuronal/axonal damage and demyelization in Results: The obtained results showed that the AG and NAC multiple sclerosis. Magnetic resonance spectroscopy studies of treatment significantly reduce MDA level and ameliorate EAE clin- patients with multiple sclerosis can evaluate specific metabolites ical signs than untreated EAE animals. which we use for establishing the course of disease. The aim of our Conclusion: Lipid peroxidation process may be cause for provoke work was to measure the main brain metabolites of a group of 18 and promotion of MS, while blocking of its process resulting in patients (10 female and 8 male aged 24-46, the average age 33,2±0,4) ameliorating in clinical onset and disease activity. These results may with relapsing-remitting multiple sclerosis who were taking copaxone be useful in the new insight into mechanisms and potential targets for (glatiramer acetate) in the dose of 20mg per day and compare them therapeutic strategies in MS. with metabolite measurements in 20 patients (12 female and 8 male aged 23-40, the average age 31,4±0,7) with RRMS without treatment, which can change the course of multiple sclerosis. It has been discovered that during 36 months patients with who were taking P482 copaxone, according to the results of magnetic resonance spectros- Circulating brain endothelial tight junction proteins copy, had the increase of tNAA/Cr correlation (NAA — total in patients with multiple sclerosis N-acetylaspartate, neuronal marker indicative axonal integrity and Cr — creatine, metabolite that is responsible for energy supply of P. Annunziata, C. Cioni, L. De Santi neurons and axons) from 1,96±0,08 (before treatment) to 2,14±0,09 University of Siena (Siena, IT) (after 12 months), p\0,05 (in comparison with indices before treat- Objectives: Alterations to blood–brain barrier (BBB) have been ment), 2,17±0,1 (after 24 months), p\0,05 (in comparison with detected in multiple sclerosis (MS). Interendothelial tight junction indices after 12 months) and p\0,01 (in comparison with indices of (TJ) proteins participate in maintaining the BBB functional and control group) and 2,24±0,04 (after 36 months), p[0,05 (in com- structural integrity. Although TJ changes have been found in MS parison with indices after 24 months) and p\0,001(in comparison brains, no data exist on TJ levels in MS biological fluids. Aim of this with indices of control group). The patients of control group with study was to measure circulating TJ protein levels in serum from relapsing-remitting multiple sclerosis without treatment, which can patients with MS and to correlate them with brain magnetic resonance change the course of multiple sclerosis, showed increase of tNAA/Cr imaging (MRI) active lesions and clinical relapses. correlation from 1,92±0,07 (before treatment) to 2,02±0,08 (after 12 Methods: Serum samples were collected from 67 patients with months), p[0,05 (in comparison with indices before treatment), relapsing-remitting MS, 35 of which were on relapse and 32 on 2,14±0,07 (after 24 months), p[0,05 (in comparison with indices clinical stability, 44 sex- and age-matched normal healthy control after 12 months) and 2,28±0,05 (after 36 months), p[0,05 (in subjects (HS) and 22 patients with other neurological diseases (OND). comparison with indices after 24 months). Magnetic resonance All MS samples were collected within one month from a MRI scan spectroscopy can provide an important tool to understand the patho- and two weeks from a clinical relapse. TJ proteins (claudin-5, genesis of multiple sclerosis and evaluate the efficacy of therapeutic occludin and zonula occludens-1) were measured by sandwich- interventions. Comparison of metabolic changes that are observed in ELISA using commercial monoclonal or polyclonal antibody pairs. A

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S115 reference standard curve for each TJ protein was obtained with P484 respective recombinant proteins. To test assay specificity for each TJ Posterior circulation stroke: an underdiagnosed protein, competitive ELISA with respective recombinant protein and other unrelated control protein was performed. situation in transient global amnesia Results: In MS patients, significantly higher levels of claudin-5 O. Gungor-Tuncer, Z. Okudan, B. Aksay-Koyuncu, (584±10 ng/ml), occludin (588±9 ng/ml) and zonula occludens-1 E. Altindag, R. Tolun, Y. Krespi (579±11 ng/ml) than those of HS and OND (p \ 0.001) were found. Istanbul Science University (Istanbul, TR); Sisli Florence Nightingale There were no significant differences in TJ protein levels with respect Hospital (Istanbul, TR) to the presence or absence of gadolinium enhancing MRI lesions. MS patients on disease-modifying therapies (interferon beta-1a and -1b or Background: Transient global amnesia (TGA) is a temporary glatiramer acetate) showed significantly lower levels of occludin than amnestic condition characterized by anterograde and recent ret- those treatment-naive (p = 0.03). rograde memory disorder, with loss of place and time orientation. Conclusion: TJ proteins are detectable in serum of human subjects. Although the clinical features of TGA have been well described In MS, circulating TJ protein levels are increased independently of and numerous hypotheses developed to explain the etiopatho- the disease activity suggesting a subtle alteration to BBB architecture genesis, the exact triggering mechanism is still controversial. even in the absence of detectable MRI active lesions. Immunomod- MRI studies are generally normal, but some studies using ulatory therapy reduces serum occludin levels but not those of other serial MRIs showed that hippocampal DWI lesions could be TJ proteins. detected in the interval between 12 and 72 h, and reported that the This work was supported by a grant from the Fondazione Cassa di pathophysiologic mechanism underlying these DWI lesions is Risparmio di Volterra, Volterra, Italy. ‘‘delayed hippocampal ischemia’’. The nature of these lesions is not known. Case: A 62 year old lady presented with TGA of 10 h duration. The patient had no focal neurologic deficits, and her repeated neu- Cerebrovascular disorders II rologic examinations were normal. She had a history of hyperlipidemia and common migraine. Diffusion MRI taken 7 h after onset of symptoms showed an acute infarct on the left side of the pons. Control cranial MRI taken after 36 h of symptom onset revealed P483 two additional punctiform infarcts, in left hippocampal and frontal Cerebral amyloid angiopathy: search for pathogenetic areas. Her cervical dynamic contrast MR angiography, intracranial mutations in sporadic cases MR angiography and perfusion MR studies were normal. Serial holter D. Sangalli, B. Corra`, N. Ticozzi, L. Adobbati, V. Silani ECG’s taken during follow-up showed paroxysmal atrial fibrillation. IRCCS, Hospital San Luca, University of Milan (Milan, IT) After the attack, neuropsychologic tests were normal except for a slight disturbance in long term spontaneous recall. There was no Objectives: Cerebral amyloid angiopathy (CAA) is a neurological epileptic activity in EEG which was taken after the TGA attack. heterogeneous disorder characterised by the deposition of amyloid Warfarin therapy was initiated and in the three month follow up fibrils in the walls of cerebral vessels, which may result in lobar control, she was in good clinical condition. intracerebral haemorrhages. CAA occurs in both familial and sporadic Conclusion: This multiple arterial territory infarct pattern in our forms. The former is determined by mutations in several genes (APP, patient, with involvement of posterior and anterior circulation terri- TTR, CST3, GSN and, less commonly, PRNP and ITM2B). Sporadic tories, pointed to a cardioembolic event, and as expected, PAF was cases are more common, but, although amyloid-beta peptide is seen during follow-up. These late appearing small infarcts were undoubtedly involved, the exact pathogenetic mechanisms and the considered as residuals from the first initial ischemic insult, and role of genetics are still unknown. Only APOE epsilon 4 and epsilon 2 ischemic dysfunction of left hippocampus was probably responsible alleles have been associated respectively with CAA and major for the clinical findings. Minor posterior circulation ischemic stroke bleedings. Therefore we aimed to asses possible pathogenetic muta- can present with TGA. Therefore in patients with TGA, DWI should tions in our cohort of patients affected by sporadic CAA. be a part of routine imaging protocol and repeated if initially negative. Methods: We selected 7 patients with a diagnosis of probable At least a subset of patients having the so called ‘‘delayed hippo- CAA according to the Boston Criteria. MRI with T2-weighted Gra- campal ischemia’’ may be harboring occult thromboembolic dient Echo sequences was performed for each patient in order to phenomenon that should thoroughly be investigated. identify microbleeds and increase the sensitivity of the Criteria. Genomic DNA was isolated from peripheral blood leukocytes. The coding exons of TTR and CST3, and the amyloidogenic regions of GSN and APP were directly sequenced after PCR amplification, P485 using primers external to the exon/intron boundaries. We also geno- The importance of stress as trigger factor in childhood typed APOE in all samples. migraine: a retrospective study Results: We did not identify any genetic mutation proven to be responsible for familial CAA. A single patient was heterozygous for D. Dalla Libera, B. Colombo, G. Pavan, G. Comi APO E epsilon 2. Moreover 3 patients were heterozygous and a INSPE, Scientific Institute San Raffaele (Milan, IT) patient homozygous for the nucleotide c.73G[A polymorphism Objective: Stress is a highly subjective phenomenon that defies def- within exon 1 of the CST3 gene, resulting in Ala/Thr transition. inition and it is difficult to measure. In retrospective questionnaire Conclusion: Although mutations associated with familial CAA do studies on migrainous adults, up to 67 % patients reported psycho- not seem to be responsible for the disease in our limited series of social stress, even if they have a tendency to overestimate stress on patients, further studies on larger cohorts will clarify the role of retrospective measures. Stress-provocation studies, involving mental genetics in sporadic CAA, allowing us to identify both pathogenetic and physical stressors, have suggested more sensibility to sympathetic mutations and associated polymorphisms. and parasympathetic changes induced by stress in migraine patients

123 S116 J Neurol (2012) 259 (Suppl 1):S1–S236

So far, studies concerning stress have been published, in relation three-year cumulative recurrence frequency was significantly higher to adult migraine, while trigger factors for childhood migraine are not (36.5 %) than frequency in patients with a C-RP below the third so clearly characterized. tertile (11.5 %, p= 0.013). The aim of the study is to determine the prevalence and deter- Antihypertensive therapy did not affect the frequency of recurrent minants of stress as a migraine trigger in a pediatric population and to stroke for patients with high level C-RP. The frequency of recurrence evaluate the influence on stress of age, gender, headache subtype, was 36.5 % with antihypertensive therapy and 46.5 %, without it (p[ psychosocial variables. 0.05). Instead, for patients with C-RP level lower than third tertile Methods: This retrospective study was carried out between one- antihypertensive therapy was much more effective in secondary hundred-twenty-five consecutive out-patients assessed at Headache prevention (p \0,05). Center of San Raffaele Scientific Institute, new to our Department. By Conclusions: Recurrent stroke in patients with AH may be caused a through a semi-structured interview, parents were asked to provide a by high initial levels of C-RP whether they received antihypertensive detailed clinical history and evaluate the importance and the signifi- therapy or not. C-RP level estimation may be useful for determination cance of stress in their children’s headache, specifying the type and of secondary stroke risk group for more aggressive antiinflammatory frequency of trigger factors. therapy. Results: 72 % of patients reported a significant level of stress in determining headache. Different stress subtype were recognized: school-related stress was reported in 78 % patients (academic stress, reading exhaustion, homework, exams and fear of failure; bullying), P487 in 68 % missed sleeping hours (playstation-facebook-computer-tv in Stroke and stroke warning signs: have we late evening); in 25 %, familiar stress (nuclear atmosphere); travelling an enlightened society? in 20 %, extracurricular activity-related stress in 20 %, environmental S. Pires-Barata, R. Miradouro, S. Claro, S. Galo, C. Corzo, factors (weather or temperature change, noise, crowding) in 10 %, in 20 % extra-curricular activities related stress (sports), in 10 % life S. Lourenço, L. Rebocho ´ events (death, illness): Finally, 20 % were unable to identify trigger Hospital Espirito Santo EPE (Evora, PT) factors Stroke is considered one of the major causes of death and disability Stress-associated symptoms (such as stomachache, difficulty to worldwide. Thus, it becomes imperative not only the work on pre- concentrate, nightmares, irritability) were also present vention of risk factors, as well as campaigns that allow the Conclusion: In this monocentric study, we try to better charac- recognition of warning signs, leading to a rapid arrival of patients to terize the possible headache triggers reported in 72 % by parents as hospitals. The purpose of this paper is to analyze the perception that generical ‘‘stress factors’’ in an Italian metropolitan area. Proper the population of the municipality of E´ vora (Portugal) has about the individualized counselling of children and their parents (i.e. re- warning signs of stroke and how to react to them. scheduled time) is auspicable in order to better copy with stress. Between March 2010 and June 2011 (in two different campaigns), 535 surveys were performed by health professionals of the stroke unit. This survey consisted of socio-demographic data and issues associ- P486 ated to stroke warning signs and what to do if they had a stroke. From the 535 surveys conducted, 60 % of respondents were C-reactive protein and stroke recurrence in patients women, 23 % were between [50-60] years, 50 % had \=4th grade. with arterial hypertension When concerning the identification of the warning signs, we found O. Markulan, T. Cherenko that 71 % identified ‘‘difficulty on speaking,’’ 74 % ‘‘side mouth’’ and National Medical Academy (Kiev, UA); National Medical University 80 % ‘‘lack of strength in the arm’’. 47 % recognized the 3 stroke (Kiev, UA) warning signs. And 15 % also identified ‘‘lack of air,’’ 24 % ‘‘headache’’ and 30 % ‘‘chest pain’’ as signs of stroke. Only 47 % identified Arterial hypertension is the universal factor of ischemic stroke the 3 alert signs. To the question ‘‘what to do in case of a stroke’’, 1 % recurrence risk. High C-RP level may affect the arterial hypertension said that staying at home is the best option, 6 % would go to the (AH) correction effectiveness and in this way may worsen a sec- Health Centre, 67 % would call 112 and 32 % would go to directly ondary stroke prevention the hospital. Objectives: to study dependence between C-RP level in patients We observed that there is still a confusion among the recognition with ischemic stroke (IS) on the background of AH and frequency of of the stroke warning signs, often mistaken by the Myocardium stroke recurrence. infarction. Although most of individuals claim to call 112, there are Methods: Examination of 211 patients with primary ischemic people who go straight to the hospital, this may not facilitate the stroke (IS) on the background of AH (blood pressure [= 160/90) in activation of the ‘‘green line’’. The campaigns of recognition of the the dynamics of three-year prospective study. Among them - 55.6 % stroke warning signs, despite recent efforts, they still seem to have men and 44.4 % women, in age of 46 - 80 years (average 65,09 ± failed to reach the general population. 0,72 years). 114 (54.0 %) patients received antihypertensive therapy regularly. Serum C-RP was measured within 24 h after primary IS by ELISA method. Statistical data processing was carried out by using statistical analysis with SPSS 13 for Windows. Three-year stroke P488 recurrence were determined by Kaplan-Meyer method using Log-rank test for comparison of cumulative frequencies. Do triglycerides matter? A correlation between lipid Results: Patients that didn’t receive antihypertensive therapy profile and ischaemic stroke subtype (42,9 % versus 20,9 %, p = 0.002) had greater frequency of recur- E. Terecoasa, C. Gavan, O. Ciobanu, C. Tiu rence within three years compared to patients that took it regularly. University Hospital Bucharest (Bucharest, RO) In case of recurrent stroke patients had CRP level higher than patients without recurrence(14,66 ± 1,94 mg/l versus 9,16 ± 0, mg/l, Objectives: Current guidelines on stroke prevention focus on low p = 0.032).Patients that were treated with antihypertensive therapy density lipoprotein (LDL) cholesterol and high density lipoprotein and had C-RP level within the third tertile (from 12.9 to 48,3 mg/l) (HDL) cholesterol as they are the main lipid targets for vascular risk

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S117 reduction in patients with ischemic stroke but not on triglycerides Background and objectives: The purpose of this study is to elucidate (TG). Our aim was to assess the relationship between plasma tri- variables such as tongue strength, and rate and range of tongue glycerides levels and stroke subtypes. movement in relation to the severity of dysarthria in stroke patients. Methods: We performed a retrospective analysis of prospectively We also wished to see whether the subjective assessment of those collected data about 178 patients hospitalized for acute ischemic variables correlates with the data using quantitative measures. stroke. We considered the stroke subtype according to the TOAST Methods: Between 2008 and 2010, 158 stroke patients admitted to criteria and included patients with strokes due to cardioembolism Asan Medical Center were enrolled. The inclusion criteria were the (CE), large artery atherosclerosis (LAA) and small vessel occlusion patients with 1) acute stroke identified by diffusion weighted MRI \ (SVO). For every patient a blood sample test including LDL-cho- 7days after the onset of stroke, 2) right-handedness, 3) no previous lesterol, HDL-cholesterol and TG levels was performed on fasting neurologic or oro-pharyngeal disease, 4) no severe language/cognitive status. We defined LDL-cholesterol levels [/=100 mg/dl and TG dysfunction, and 5) no oral/buccofacial apraxia. Patients with multiple levels [/= 150 as high levels. We performed multinomial logistic lesions were excluded. A speech-language pathologist (SLP) recorded regression analysis adjusting for age, sex, presence of hypertension the speech of each patient and assessed the tongue strength and the rate and diabetes considering the group of patients with CE the reference and range of tongue movement subjectively. For an objective measure of group. the tongue strength, force transducer was used. In addition, a device was Results: We found a statistically significant relationship between designed for assessing the rate and range of tongue movement quanti- high TG and stroke subtype. High TG differentiate both the LAA tatively. The severity of dysarthria was evaluated independently by the group from the CE group and the SVO group from the CE group (P= SLP with the recorded speech data using the 5-point rating scale. 0,013 respectively P= 0,001). The presence of high TG multiplies by Results: Dysarthria was observed in 142 patients (89.8 %) and cate- 5,05 the patients’ chance of being in the LAA group (OR=5,05; gorized as 51 for mild, 37 for moderate, 44 for severe, and 10 for CI=1,4-18,1) and by 6,5 the chance of being in the SVO group profound. There was no difference in age and sex among those groups. (OR=6,5; CI=2-20,8). No statistically significant relationship was However, dysarthria was more severe in patients with left than with right found between the presence of low HDL-cholesterol (P=0,7) or high sided lesions (p\.001). In the quantitative measure, the tongue strength LDL-cholesterol (P=0,2) levels and stroke subtype. showed significant correlation with the severity of dysarthria (r=.26, Conclusion: High triglycerides levels are associated with ischemic p\.001). The rate (r=.39, p\.001) and range (r=.15, p\.05) of tongue strokes due to large artery atherosclerosis and small vessel occlusion movement also demonstrated significant correlations. The subjective but not with strokes due to cardioembolism. rating scales and objective quantitative measurement showed significant correlations for the tongue strength (r=.45, p\.001), and the rate (r=.59, p\.001) and range (r=.28, p\.001)oftonguemovement. Conclusion: The strength and the rate and range of tongue movement P489 are all highly correlated with the severity of dysarthria. The subjective MRI-based localisation of intractable hiccup after acute rating score performed by an SLP correlates well with objective measures lateral medullary infarction and is considered practical and reliable way to assess the tongue move- M.K. Kim, B.G. Yoo ments related to dysarthria in stroke patients. Also, our data confirmed that left hemisphere is dominant for articulation. Kosin University College of Medicine (Busan, KR) Objectives: Intractable hiccups are defined as hiccup persisting for more than 48 h. The relationship between lesion location of lateral medullary infarction (LMI) and intractable hiccup is rarely reported. P491 This study was designed to investigate the MR localization of Misinterpretation of clinical symptoms intractable hiccups in the LMI. Methods: We identified 9 patients with intractable hiccups by and corresponding cerebral white matter lesions in two medical record, telephone interview and brain MRI. LMI was diag- young women with Fabry’s disease nosed by clinical findings and brain MRI. MRI lesions were classified P. Flossdorf, M.D. Hesse, R. Sparing vertically as upper, middle and lower level and horizontally. University of Cologne (Cologne, DE) Results: All patients with intractable hiccups were men. Verti- cally, three patients had lesions in the upper medulla, two patients had Fabry´s disease is a X-chromosomal linked recessive lysosomal stor- lesions in the upper and middle medulla, two patients had lesions in age disease caused by the deficiency of alfa-galactosidase A. the all levels of the medulla, one patient had lesions in the middle Accumulating toxic levels of sphingolipids lead to metabolic dys- medulla, and one patient had lesions in the middle and lower medulla. function in many cell types that cause a variety of symptoms, such as Horizontally, dorsolateral and/or midlateral lesions were always angiokeratoma, corneal and lenticular opacity or cardiovascular dis- involved. All patients with LMI with intractable hiccup had vertigo/ eases. Due to the mode of X-chromosomal inheritance male patients dizziness, nausea/vomiting and dysphagia. usually present with severe symptoms at young age, women may Conclusion: These results demonstrate that intractable hiccups are present with neurological manifestations in young adulthood, such as related to the dorsolateral region of the middle and/or upper levels of strokes, polyneuropathy, vertigo, headache or acroparesthesia. medulla. We suggest that involvement of the nucleus ambiguous may Here we report two cases of female patients suffering from Fabry’s be responsible for intractable hiccups. disease. Both have been misdiagnosed and thus mistreated for many years. Patient 1 suffered from paresthesia, difficulties in fine motor skills and visual deficits at the age of 30 yrs. Although oligoclonal bands could not be detected, she was diagnosed a clinically isolated P490 syndrome (CIS), as the MRI showed multiple T2-hyperintense Assessment of tongue motor function in stroke patients lesions, and treated with steroids. Fabry´s disease was diagnosed 15 years later. Patient 2 suffered from her 1st stroke at the age of 34, the M. Kwon, D. Shin, S. Jeon, H. Song, K. Cho, D. Kang, 2nd about ten years later with the suspected cause being a vasculitis S. Kwon, J. Kim due to very slightly elevated respective laboratory parameters. Hence University of Ulsan (Seoul, KR); Korea University (Seoul, KR) she has been treated about 10 years with azathioprine. Progressing

123 S118 J Neurol (2012) 259 (Suppl 1):S1–S236 visual problems were reported at the age of 45, when the ophthal- P493 mologist found a cornea verticillata and diagnosed Fabry´s disease. Surfer’s myelopathy, first European case Since initiation of Enzyme Replacement Therapy (ERT) with Agalsidase alfa (Replagal) both patients remain clinically stable. M. Matarazzo, A. Castanõ Leon, A. Labiano Fontcuberta, Both cases represent a typical clinical presentation and course in J. Zurita Santamaria, A. Ramos Gonzalez young women with Fabry´s disease. In both the associated micro- Hospital Universitario 12 de Octubre (Madrid, ES) angiopathic white matter lesions were misinterpreted as being the Objective: The Surfer’s myelopathy (SM) is a syndrome distinguished result of a probable inflammatory process. by an acute onset (minutes to hours) of symptoms and signs of low Retrospectively, a number of symptoms - acroparesthesia, hypohi- spinal cord involvement in novice surfers, specially during or after the drosis, proteinuria, vertigo, nausea, headache and psychiatric symptoms - first surfing lesson. The etiology is an ischemic event of the anterior or ´ were typical for Fabrys disease however they did not lead to consider the central spinal cord in the low thoracic vertebral levels to the conus. ´ diagnosis. Fabrys disease is known to be a diagnostic ‘‘pitfall’’.We would The mechanism of the ischemia is not known. Several hypothesis ´ like to increase awareness and thus likelihood to consider Fabrysdisease have been proposed including Adamkievicz artery’s vasospasm, as a differential diagnosis, especially in young women presenting with avulsion of perforating vessels, transient ischemia of border-line neurological symptoms and white matter lesions, which may be care- areas, inferior vena cava occlusion and fibrocartilaginous embolism. lessly misinterpreted as multiple sclerosis. We report the first case of SM described in Europe. Methods & Results: A 25 year-old man (BMI 26) without personal or familiar history of atherothrombotic vascular disease, no smoker, P492 residing in Madrid, who works as a nurse, presents with weakness in Association of the methylenetetrahydrofolate reductase both legs after his first surfing lesson. While he was in the sea, practicing the movement to stand up on gene polymorphism with carotid distensibility the table consisting in hyperextension of spine, he noticed a sudden and intima-media thickness in patients with cerebral back pain, not irradiated, and paresthesias in both thighs. He went infarctions immediately back to the beach and started feeling weakness in both N.D. Dimitrov, A. Savov, E. Todorova-Dimitrova, lower limbs that made standing up impossible for him. The patient went to the nearest hospital where he was evaluated by I. Velcheva a neurologist and an urgent MRI was performed in which ‘‘signal Second City Hospital Sofia (Sofia, BG); Medical University Sofia changes from T9 to conus, without contrast enhancement’’ were (Sofia, BG); Military Medical Academy (Sofia, BG) described, with the diagnostic of myelitis. The association of the genetic variations of the enzyme methylene- The patient came then to our hospital where he arrived 12 h after tetrahydrofolate reductase (MTHFR) with carotid atherosclerosis the first symptoms. (CA) has been inconsistent. Some investigations showed lower dis- In the first neurological exam we found a paraparesis with prox- tensibility and higher carotid intima-media thickness (IMT) in TT imal predominance and asymmetric distribution; reflexes and homozygotes, while others revealed no association with CA or even sensibility were normal. He also related a difficulty in urinating. A less frequent CA in the TT homozygotes. new MRI was done, finding an hyperintensity of gray matter from T9 The aim of our study was to assess the MTHFR genetic poly- to conus in T2 sequence and contrast enhancement in T1, no diffusion morphism in association with carotid distensibility and IMT in sequence was carried out. Laboratory studies were normal. patients with unilateral cerebral infarctions (UCI), risk factors (RF) In the next few days the weakness improved and the neurological for cerebrovascular diseases and healthy controls. exam at discharge (8 days after) was practically normal. The only The study included 35 patients: 14 with UCI, and 24 RF for stroke treatment he received was dexamethasone 4 mg/12 h orally. A second in comparison to 21 age-matched controls. By using color duplex MRI was performed seven days after the beginning of symptoms, sonography ultrasound examination of the common carotid (CCA) with no abnormal findings. and internal carotid (ICA) arteries was performed and the blood flow Conclusion: SM is a rare syndrome consisting of spinal cord velocities, the lumen systolic and diastolic diameter and the IMT of ischemia in novice surfers. Our case presents some differences from the vessel walls were measured by standard procedure. Carotid strain, the cases described until now: the patient was not thin, the neuro- stiffness (STIF) and distensibility (DIST) were calculated. A ques- logical deficit was sudden with a quick progression from the back tionnaire for RF for stroke was filled, systolic and diastolic blood pain to the paraparesis. pressure were measured and serum lipids were examined. The polymorphism of the MTHFR gene was determined by polymerase chain reaction. The polymorphism was verified by agarose electrophoresis. Results: CC genotype predominated in the controls (11 CC P494 homozygotes, 4 TT homozygotes, 6 CT heterozygotes and CT Cardiac diastolic dysfunction is associated genotype in the RF group (8 CC homozygotes, 2 TT homozygotes, 18 with elevation of coagulability in acute cerebral CT heterozygotes. Lower DIST for the left CCA and higher IMT for the right CCA, right ICA and left ICA was found in CC homozygotes infarction patients compared to TT homozygotes in the control group, p\0.05. CT het- N. Mitsuma, D. Ito, M. Hattori, R. Nishi, K. Kawabata, erozygotes had higher IMT and DIST for the right ICA than CC S. Yamada, S. Yokoi, N. Nakai, K. Yasui, Y. Hasegawa, homozygotes and lower DIST for the right CCA than TT homozy- K. Hasegawa gotes in the UCI group, p\0.05. Higher strain and DIST and lower Nagoya Daini Red Cross Hospital (Nagoya, JP) STIF were found for the right ICA in CT heterozygotes compared to CC and TT homozygotes in controls, p\0.05. No significant data Objectives: Cardiac diastolic dysfunction proceeds development were found in the RF group. of cardiac dysfunction. Cardiac dysfunction is observed in acute Conclusion: The results of our study confirm the inconsistency of cerebral infarction, but changes of cardiac diastolic function in acute former investigations and show the possible role of CT genotype for cerebral infarction patients are not know. We made a detailed com- reducing the risk for CA. parison between various parameters measured by echocardiography,

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S119 including left ventricular function, and coagulability/fibrinolysis Conclusion: This is a rare case of a Villaret syndrome caused by a markers in acute cerebral infarction patients. fusiform aneurysm of the right internal carotid artery located in the Methods: Patients hospitalized for acute cerebral infarction were base of the skull. The probable cause of this aneurism is a sponta- examined. Cardiogenic infarction patients were excluded, resulting in neous dissection of the right internal carotid artery. 350 patients for evaluation. Blood coagulability/fibronolysis markers were measured on admission, and echocardiography performed within one week of hospitalization. Various parameters representing systolic and diastolic cardiac function were assessed: left ventricular ejection P496 fraction (EF), early inflow atrial wave (E), atrial contraction wave The relationships between progressive motor deficits (A), and mitral annulus velocity (E ‘). These parameters were sta- and therapy for branch atheromatous disease tistically analyzed for association with coagulation marker thrombin- W. Takahashi, C. Kijima, S. Yutani, A. Mizuma, antithrombin complex (TAT) and fibronolysis marker D-dimer. Results: E’ values negatively correlated with TAT (P \0.05). A S. Takizawa heights showed positive correlation with TAT (P \ 0.05). Neither Tokai University (Isehara, JP) showed correlation with D-dimer. Other parameters such as EF, E, Objective: Among the subtypes of cerebral infarction, branch ather- E/A, E/E’ showed no significant correlation with TAT or D-dimer. E’ omatous disease (BAD) is known to frequently accompany and A are both known to reflect cardiac diastolic function; decrease of progressive motor deficits in the acute stage of cerebrovascular E’ and elevation of A indicate early cardiac diastolic dysfunction. events. To assess the effectiveness of treatment for neurological Cardiac diastolic dysfunction leads to elevation of left ventricular end deterioration in BAD, we retrospectively evaluated the relationships diastolic pressure and activation of sympathetic nervous system between progressive motor deficits, functional outcomes, and treat- leading to damage of endothelial cells, resulting in increased coagu- ments for acute-stage BAD. lability. EF or E wave did not correlate with TAT or D-dimer. EF Patients and methods: The subjects were 117 individuals (male: reflects cardiac dysfunction which follows early cardiac diastolic 72, female: 45, mean age: 69±12 years) admitted to Tokai University dysfunction. E is affected by circulating plasma volume and blood Hospital between May 2008 and July 2011. All subjects were viscosity, thus varies among patients. Our result suggests that early admitted within 48 h from onset. BAD was diagnosed by using cardiac diastolic dysfunction is a direct risk factor of cerebral magnetic resonance imaging (MRI) in all subjects. The differences in infarction. progressive motor deficits among the subjects with any agent were Conclusion: Diastolic diastolic dysfunction measured as E’ or A analyzed using the Chi-square test. wave of echocardiography is a risk factor and predictor of acute Results: No significant differences were found in the prevalence of cerebral infarction. progressive motor deficits between the subgroups with and without glycerol (22 % vs 9 %), edaravone (21 % vs 20 %), anti-hypertensive agent (17 % vs 22 %), or statin agent (25 % vs 20 %). The prevalence of progressive motor deficits did not differ significantly between the P495 subgroups with anti-platelet agents (25 %) and anti-coagulation Villaret syndrome: unusual aetiology in a young male therapy (17 %). However, the subgroup taking oral anti-platelet patient agents (aspirin, cilostazol or clopidogrel) (72 %) had significantly more frequent progression of motor deficits than the group with D. Popescu, A. Mergeani, C. Laza, A. Rata, O. Bajenaru, intravenous administration of an anti-platelet agent (ozagrel) (17 %). F. Antochi Conclusion: In treatment for the acute stage of BAD, intravenous Bucharest University Emergency Hospital (Bucharest, RO) administration of anticoagulant or anti-platelet agents may be more effective than oral administration of anti-platelet agents for progres- Objective: Villaret syndrome is a neuropathy of the cranial nerves IX, sive motor deficits. X, XI and XII and sympathetic nerves in the neck with diverse etiologies usually after a compression by a mass at the base of the skull. Lesions involving the posterior retroparotid (Villaret syndrome) or the laterocondylar space (Sicard Collet syndrome) affect all the lower P497 four cranial nerves, the difference between these two syndromes Study of pH-sensitive magnetisation transfer imaging consists of involvement of the carotid sympathetic nerves in the Villaret syndrome. The etiology usually consists of neoplasm of the in hyperacute brain infarction using a clinical 1.5 Tesla skull base, especially glomus jugalare tumor, fractures and trauma of scanner the skull base, occasionally carotid aneurysm. T. Lin, M. Wei, G. Xiao, Z. Shen, P.Z. Sun, R. Wu Methods: We present a case of a young male who presented to our Shantou University (Shantou, CN); Harvard University (Boston, US) clinic two months after the onset of difficulty in swallowing, pupillary asymmetry. When cerebral nervous tissue lacks of blood and oxygen, neurocyte is At the admission the patient was conscious with normal blood altered in metabolism, following with intracellular acid–base distur- pressure, he presented an incomplete Horner syndrome on the right bance. Alteration of intracellular pH value can influence the side (without decreased sweating), and lesions of the right cranial magnetization transfer ratio (MTR). So pH-sensitive magnetization nerves IX, X, XI and XII. transfer imaging can reflect the alteration in metabolism. Using this Results: The MRI of the brain was normal; the angioMR sequence technology to image ischemic brain may make an early detection and revealed a dilatation of the internal carotid artery in the cervical prognose ischemic penumbra. In our study, twelve male cats weighing segment while the native MRI of the neck didn’t showed a clear 2.4 to 2.8 kg underwent permanent MCAO, and ischemic evolution image of hematoma in the wall of the right internal carotid artery. The was observed at a clinical 1.5-T scanner through clinical T1WI, angiography of the vessels of the base of the brain depicted a small T2WI, DWI and MT-imaging. MT-imaging readout was as spin-echo fusiform dilatation of the right internal carotid artery; the 3D recon- imaging with an offset frequency of 3.5 ppm. At last, compare the struction done on angioCT revealed the shape, caliber and orientation ability of clinical imaging and MT-imaging to detect cerebral infarct of the fusiform aneurysm. within the hyperacute stage. From the experiment results we could

123 S120 J Neurol (2012) 259 (Suppl 1):S1–S236

find that in 7 of 12 animals they displayed hypointensity in the Introduction: CCFDN is a rare genetic multisystemic disorder of occlusion side in the MT-imaging, when there were no any alterations autosomal recessive inheritance, caused by IVS6+389C[T mutation in the clinical imaging yet. In other 5 of 12 animals, we could observe in the CTDP1 gene in patients of Gypsy ancestry. The clinical the intensity alterations in DWI and MT-imaging at the same time. In manifestations include congenital cataracts, facial dysmorphism, the experiment we found that MT-imaging was sensitive to detect peripheral neuropathy due to primary hypomyelination, growth delay, infarct prior to current clinical sequences such as T1WI, T2WI and intellectual impairment and hypogonadism. DWI. Meanwhile, analysing from cerebral blood flow (CBF), the CBF Objective: To characterize cognitive performance and structural level for pH change approximates to the threshold of penumbra, so it CNS changes in affected individuals. indicates that boundary of lesion on MT-imaging may also approxi- Subjects and methods: Twenty-two patients with diagnosis mate to the penumbra. We also come to a conclusion that CEST- CCFDN, confirmed by mutation testing, underwent a detailed neu- imaging may be able to prognose ischemic penumbra. rological examination. Verbal and non-verbal intelligence, memory, National Natural Science Foundation of China (NSFC 30930027). executive functions, activities of daily living and social adaptation were assessed in 22 CCFDN patients aged 4 to 47 years. Brain magnetic resonance imaging (MRI) was performed in 20 patients. Results: Eighteen patients (81.8 %) had mild mental retardation P498 (IQ=50-70) while four patients (18.2 %) had borderline intelligence Silent brain infarctions do not influence short-term (IQ=70-80). The tests evaluating their memory and executive func- stroke outcome tions showed similar level of impairment. MRI, performed in 20 O. Ciobanu, E.O. Terecoasa, A. Poalelungi, I. Tiu, patients, demonstrated cortical atrophy in 10 patients: in 5 of them it was discreet, whereas in 5 it was well pronounced with predominant O. Bajenaru, C. Tiu involvement of the frontal areas. MRI found ventricular enlargement University Hospital Bucharest (Bucharest, RO); University of in 9 patients as well as thinning of corpus callosum in one of them, Medicine and Pharmacy Carol Davila (Bucharest, RO) focal subcortical white matter lesions in 9, lesion in the right nucl. Objectives: silent infarctions have been associated with an increased caudatus in 1; megacysterna magna – in 3, cerebellar vermis hypo- risk of stroke recurrence and of cognitive decline; controversial plasia and enlargement of the fourth ventricle in 1. results were obtained regarding the influence of silent brain infarc- Conclusion: Mild mental retardation or borderline intelligence, tions on short term outcome of ischemic strokes and implicit on the with a similar level of involvement of verbal, nonverbal skills and prognostic of rehabilitation. executive functions, is present in patients with CCFDN and is prob- Methods: We performed a retrospective analysis of prospectively col- ably enhanced by visual impairment and social deprivation of the lected data about 296 patients (157 women, 139 men) hospitalized in our affected subjects. The abnormalities on brain MRI include diffuse department for acute ischemic stroke. For every patient we included data cerebral atrophy, enlargement of the lateral ventricles, and focal regarding stroke subtype (according to TOAST classification), vascular risk lesions in the subcortical white matter, different in number and size, factors (arterial hypertension, dyslipemia, diabetes mellitus, atrial fibrilla- consistent with demyelination more pronounced in the older CCFDN tion), modified Rankin score at admission and at discharge and the presence patients. We can speculate that CCFDN hypo/demyelination mecha- of silent infarctions confirmed by brain computed tomography. nism underlies cerebral white matter damage similarly to peripheral Results: 53.55 % of women and 56.1 % of men had silent brain nervous system, bearing in mind that patients with more severe infarctions. Analyzing the possible relationship with the ischemic stroke neuropathy have bigger hyperintense lesions on T2 of MRI. There subtype we found no statistically significant difference in the prevalence isn’t a clear-cut correlation between the cognitive impairment of the of silent infarctions in different stroke subtypes (p value = 0.2). Per- CCFND patients and the brain structural changes, observed on MRI. forming bivariate analysis modified Rankin score at discharge was associated with the presence of the silent infarctions (Chi square test for trend, p=0.04) but after adjusting for age, sex, arterial hypertension, diabetes mellitus, TOAST subtype and modified Rankin score at P500 admission in a proportional odds regression model no statistically Two distal hereditary motor neuropathy families association was found (p value=0,08). Short term outcome was influ- with mutation of HSPB8 or HSPB1 enced only by stroke subtype, strokes due to small vessel occlusions having a better prognosis, and modified Rankin score at admission. B.-O. Choi, H.-K. Jung, J.W. Hyun, S.-H. Kim, Y.J. Kim, Conclusion: The presence of silent brain infarctions do not influ- J.H. Park, K.W. Chung ence short term stroke outcome. Ewha Womans University (Seoul, KR); Kongju National University (Gongju, KR) Objective: Distal hereditary motor neuropathy (dHMN), which is a Peripheral neuropathy subtype of the clinically and genetically heterogeneous Charcot- Marie-Tooth disease (CMT), shows predominant motor abnormalities on clinical and electrophysiological examination, whereas sensory abnormalities were absent. Several genes have been implicated to P499 dHMN development. In particular, mutations in small heat shock Investigation of the cognitive impairment and brain protein (HSP) genes, HSP22 (HSPB8) and HSP27 (HSPB1), have imaging characteristics of 22 patients with congenital been reported to be associated with dHMN. Both small HSPs have cataracts, facial dysmorphism, neuropathy syndrome important roles in response to stresses as molecular chaperones. In the present study, we identified two Korean dHMN families with each a T. Chamova, V. Guergueltcheva, M. Raycheva, L. Penev, HSPB8 and HSPB1 missense mutation. D. Zlatareva, S. Bichev, S. Cherninkova, I. Tournev Methods: We investigated this study to identify causative muta- University Hospital ‘‘Alexandrovska’’ (Sofia, BG); National Genetics tions from Korean CMT patients, particularly for dHMN patients. The Laboratory, Molecular Medicine Center, Medical University (Sofia, mutation screen was performed by two steps: first examination for BG) 17p12 duplication and several major CMT genes, and second

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S121 examination by the exome sequencing. The exome was captured mutation rapidly and accurately. This technique could be efficiently using the SeqCap EZ, v2.0 (Roche-NimbleGen), and next generation applied to genetic diagnostic testing and counseling for a heteroge- sequencing (NGS) was performed using the HighSeq 2000 Genome neous disorder. Analyzer (Illumina). Results: This study revealed two missense mutations from HSP genes as the underlying cause of dHMN: a novel c.422A[C (Lys141Thr) in HSPB8 and a reported c.544C[T (Pro182Ser) in P502 HSPB1. The c.422A[C in HSP22 was identified in a dHMN patient Pain-related evoked potentials in Fabry disease whose both parents unaffected and have no mutation, implicating de N. U¨çeyler, A. Kahn, D. Zeller, Z. Katsarava, C. Sommer novo case. This mutation was not found in 200 healthy controls. So University of Wu¨rzburg (Wu¨rzburg, DE); University of Essen (Essen, far, three HSPB8 mutations have been reported to be causative. DE) Interestingly, they are all p.Lys141 mutations. Because our novel mutation is also p.Lys141, this site within the alpha-crystallin domain Objectives: Fabry disease (FD) is an X-linked lysosomal storage is regarded as a hot spot for dHMN development. The c.544C[T disorder that is associated with small fiber neuropathy (SFN). We set (Pro182Ser) in HSPB1 cosegregated with affected members in the out to investigate the electrical properties of Adelta fibers in patients family. Because a mutation c.545C[T (Pro182Leu) in the nearest with FD and SFN using pain-related evoked potentials (PREP). nucleotide was reported, this site is also considered as mutational hot Methods: We studied 68 patients with FD and 15 healthy controls. spot. Patients were investigated with neurological examination, routine Conclusions: We identified two HSP mutations from Korean electrophysiology, pain and depression questionnaires and quantita- dHMN families. In recent, therapeutic effect of HDAC6 inhibitors on tive sensory testing (QST). Skin punch biopsies were taken from the transgenic models with HSPB1 mutations have been reported. lower leg and the back to determine intraepidermal nerve fiber density Therefore, this study may be helpful for development of designed (IENFD). PREP were recorded after triple stimulation at face, hands, therapy. and feet using concentric electrodes and applying twofold the current of the individual pain threshold. The N1- and P1-latencies and the peak-to-peak amplitude (PPA) were determined. Results were stratified for renal function, which is a marker of disease severity. A P501 glomerular filtration rate (GFR) of [= 60 was assumed normal, \ 60 ml/min/1.73 m2 was assumed impaired. A novel S90W BSCL2 mutation in a Charcot-Marie- Results: Neurological (50/68) and electrophysiological (63/68) Tooth family using exome sequencing combined examination was normal in the majority of cases. Males had reduced with linkage analysis IENFD at the lower leg (2.5 fibers/mm; females: 8.2; p\0.001) and H.-K. Jung, J.W. Hyun, S.H. Kim, J.H. Lee, K.W. Chung, the back (13.8; females: 24.8; p\0.01). QST revealed impaired small fiber function with increased detection thresholds for cold, warm and B.-O. Choi temperature changes in males compared to controls (p\0.001), while Ewha Womans University (Seoul, KR); Kongju National University the sensory profile of females was normal. Upon stimulation at the (Gongju, KR) hand PREP PPA was reduced in patients with reduced GFR (6 lVvs Objective: To date, only two mutations (N88S and S90L) in the 17 lV). Patients under enzyme replacement therapy also had lower Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) gene have PREP PPA upon stimulation at the hand compared to patients without been reported to cause distal hereditary motor neuropathy (dHMN), or need for treatment (8 lVvs19lV; p\0.01). Upon stimulation at the Charcot-Marie-Tooth disease (CMT). The seipin protein encoded by foot patients with impaired renal function had increased N1-latencies the BSCL2 gene is a transmembrane protein that is located in the compared to controls (197 ms vs 174 ms; p\0.05). Additionally, PPA endoplasmic reticulum, and it causes a disruption in protein glyco- were reduced in males compared to females (11 vs 19 lV; p\0.05), in sylation. We investigated the disease-causing mutation in a family patients with impaired compared to normal renal function (7 vs 16; with CMT2 using exome sequencing in combination with linkage p\0.01), and in patients under enzyme replacement therapy vs those analysis, and we examined the genotype-phenotype associations. without need for treatment (7 vs 18; p\0.01). Methods: We enrolled a family of Korean origin with axonal CMT Conclusions: Adelta-fiber function is impaired in male Fabry neuropathy (FC305; 12 males, 4 females), and applied genome-wide patients and particularly in those with renal disease. PREP recordings linkage analysis. Whole exome sequencing was performed for two are an objective additional method to investigate Adelta mediated patients. Exome capture of 44 Mb was performed with the Nimblegen pain pathways. EZ2 (Nimblegen), and captured DNA was amplified and sequenced The study was supported by an unrestricted grant from Genzyme on the Illumina Genome Analyzer II platform (Illumina). In addition, GmbH to the University of Wu¨rzburg. sural nerve biopsies were obtained from two patients. Results: We found evidence of linkage (LOD scores of 3.3) for a region on chromosome 11p11-11q13.3. Using exome sequencing, we P503 identified 20,336 coding variants in two individuals. Among these variants in this linkage region, we detected a novel S90W mutation in A whole-brain network analysis in patients the BSCL2 gene, after filtering 31 Korean control exomes and inte- with hereditary and acquired peripheral neuropathy grating the results from the two individuals. The family had axonal M.A. Rocca, P. Valsasina, R. Fazio, S. Previtali, A. Falini, CMT2 neuropathy that was confirmed by clinical, electrophysiologic, G. Comi, M. Filippi and pathologic findings. As there is a distinct difference from muta- Vita-Salute San Raffaele University (Milan, IT) tions already reported, the two patients with the novel S90W mutation showed similar sural nerve histopathologic features, although one of Objectives: The assessment of functional connectivity (FC) at resting these individuals had normal sural nerve conduction velocities. state (RS) has demonstrated the presence of functionally relevant RS Conclusions: We identified a novel mutation of the BSCL2 gene in networks (RSNs). We estimated RS FC abnormalities within and a family with CMT2. We demonstrate that exome sequencing in among RSNs in patients with acquired (A) and hereditary (H) PN, as combination with linkage analysis can be used to identify the well as their correlation with clinical variables.

123 S122 J Neurol (2012) 259 (Suppl 1):S1–S236

Methods: RS functional MRI was acquired from 13 APN, 12 HPN episodic headache, recurrent visual deficit, presence of RRFs, and patients and 18 healthy controls (HC). Independent component an A3243G mutation. Thiamine supplementation improved his analysis (ICA) was used to identify functionally relevant RSNs. symptoms. Between-group FC comparisons and correlations with structural MRI Discussion: Two siblings with A3243G mutation who presented and clinical variables were performed using SPM8 and biological with beriberi symptoms at 15 years of age, then developed mito- parametric mapping (BPM). The Functional Network Connectivity chondrial myopathy a few years later have been reported. TCA cycle (FNC) toolbox was used to assess differences of interactions among dysfunction caused by thiamine deficiency and mitochondrial dys- RSNs. function due to electron transfer chain abnormalities caused by Results: RSNs of interest included two sensorimotor RSNs, two A3243G mutation developed in these siblings when their thiamine visual RSNs, one auditory RSN, the default mode network (DMN), requirements were maximal during growth. In our patient, thiamine the executive control network (ECN), the salience network (SN), and deficiency was induced by physical load. two working memory networks (WMN). Compared to HC, PN Conclusion: Based on the findings of the patient, we postulate that patients had RS FC abnormalities in the majority of sensory and a thiamine deficiency should be considered when peripheral neurop- motor RSNs, with increased FC in the auditory RSN and decreased athy is associated with MELAS. FC in the secondary visual RSN in all PN (more pronounced in APN than in HPN patients). Decreased FC in the motor RSN was also found in APN patients. FC abnormalities of sensory and motor RSNs P505 were moderately correlated with disease duration. Functional abnormalities also involved cognitive RSNs, with decreased FC in the Autosomal dominant hereditary sensory neuropathy DMN, left WMN and SN in APN and increased FC in the SN in HPN. with chronic cough and gastro-oesophageal reflux: FNC analysis revealed increased inter-network connectivity in PN a Portuguese family patients vs. HC, mainly involving sensory and motor RSNs. FNC P. Barros, H. Morais, C. Santos, J. Roriz, P. Coutinho increase was more marked in HPN than in APN patients. Centro Hospitalar Vila Nova de Gaia/Espinho (Vila Nova de Gaia, Conclusions: RS analysis revealed diffuse RS FC abnormalities in PT); Centro Hospitalar Entre Douro e Vouga (Santa Maria da Feira, PN patients, which extended beyond the sensorimotor network. PT) Increased FNC among sensory networks is likely to reflect the presence of cross-modal plasticity phenomena among sensory modalities Background: In 2002, a family with an autosomal-dominant HSN in patients with peripheral system damage. was described in which patients had distal sensory loss usually without foot ulcers and adult onset of gastroesophageal reflux (GOR) and cough. Cough could be triggered by noxious odors and could lead to syncope. Nerve conduction velocity studies, sural, and P504 skin biopsies revealed a sensory axonal neuropathy. The disease locus in this family was linked to a 3.42 cM interval on chromosome Beriberi neuropathy in a MELAS patient with A3243G 3p22-p24 and was also confirmed in a second family with a similar mutation phenotype. Since then, rare families with this form of HSN have M. Suzuki, M. Takeuchi, Y. Shimizu, M. Kobayashi, been described. M. Iwata, S. Uchiyama Case report: Male, 74 years old. Bilateral hearing loss, with onset around 20 years old, slowly progressive. Chronic cough of more than Tokyo Women’s Medical University (Tokyo, JP) 20 years’ duration, paroxystic in nature, occurring several times a day The A3243G mutation in mtDNA is associated with MELAS and and often precipitated by characteristic odors. He also described sometimes with additional phenotypes such as sensorimotor several episodes of syncope, always in the context of severe cough; he polyneuropathy. was followed by a Cardiologist by several years and placed a pace- Method: We describe a patient with beriberi neuropathy associated maker. GOR diagnosed at age 55, requiring anti-reflux surgery ten with mitochondrial cytopathy and review the literature. years later. He was referred to the Neurology consultation by com- Result: A 21-year-old man was referred with progressive numb- plaints of numbness and burning in both legs. Family history was ness and weakness in four limbs. He had headache since childhood, notable for 2 sisters (of 4) with similar persistent lower extremity and developed a visual field deficit at the age of 19. He had a tendency numbness, GOR and paroxystic cough. Neurologic examination: algic of an unbalanced diet and experienced recurrent leg edema from the and thermal hypoesthesia in a ‘‘stocking-glove’’ pattern. EMG: neu- age of 20. He took prejudiced foods during a week-long university rographic studies consistent with sensory, axonal polyneuropathy. camp with physical exercises. Then, he developed diffuse edema and Audiometry showed sensorineural hearing loss. Other causes of cough his body weight increased 6kg. Two months later, he developed and GOR were excluded. weakness and numbness in the toes. The weakness spread from the Discussion: Serine palmitoyltransferase is a key enzyme in the lower to the upper limbs until he could barely walk aided. Exami- production of sphingomyelin. Deficiency or mutation of this impor- nation upon admission showed distal-dominant limb weakness and tant enzyme has been reported as a rare cause of autosomal dominant absent achilles tendon reflexes. A moderate all modality sensory hereditary sensory neuropathy manifesting with peripheral sensory deficit was noticed in the legs. Laboratory findings showed increases neuropathy, chronic cough, and syncope. Even more rarely, mutation in serum lactic acid and in serum pyruvic acid. Motor conduction of serine palmitoyltransferase gene in the form of distal sensory velocity was decreased and a low amplitude motor potential was axonal deficits can present along with gastroesophageal reflux with noted in the tibial nerves. Motor nerve action potentials were absent adult onset of paroxysmal cough, which can lead to syncope. The in the peroneal nerves. Sensory nerve action potentials were absent in cough is attributed to denervation hypersensitivity of the upper air- all four limbs. Concentrations of protein, lactate, and pyruvate were ways. The gene involved in this disease remains to be identified. We elevated in CSF. Muscle biopsy showed RRFs and many target fibers. report a portuguese patient with the combination of a dominantly Nerve biopsy showed acute axonal degeneration. Predominant axonal inherited sensory axonal neuropathy with paroxysmal cough, gastro- features, massive edema, and a history of dietary imbalance led us to esophageal reflux (GOR) and sensorineural hearing loss. To our consider beriberi neuropathy. Thiamine concentration in the whole knowledge is the first description of this rare disease in a portuguese blood was 16 ng/dl. A diagnosis of MELAS syndrome was made with family.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S123

P506 of both hands in a large series of patients with the most common and Variable phenotypes caused by the PMP22 S22F point genetically homogeneous CMT subtype, CMT1A. Methods: The measures were assessed in the 271 CMT1A adult mutation patients recruited in the Italian/UK trial of ascorbic acid (CMT- Y.P. Christou, P. Nicolaou, K. Kleopa, T. Kyriakides, TRIAAL/CMT-TRAUK; baseline visit): manual testing (MRC scale, L. Middleton, E. Zamba-Papanicolaou, K. Christodoulou range 0-5) of muscle strength of first dorsal interosseous (FDI) and Cyprus Insittute of Neurology and Genetics (Nicosia, CY) abductor pollicis brevis (APB) muscles of both sides; 9 hole peg test (9HPT) of both sides (seconds, average of two tests for each side after Objectives: Charcot-Marie-Tooth (CMT) disease is one of the most two test trials). Continuous data were compared either with the t test common inherited neuromuscular disorders, with a prevalence of or the Wilcoxon test and categories with the Chi square test. 17-40 per 100,000 individuals. CMT is classified into two main sub- Results: MRC mean scores (SD) were the following: FDI – groups, demyelinating (HMSN I or CMT1) and axonal (HMSN II or dominant 3.73 (0.87), non dominant 3.74 (0.96), difference -0.01 CMT2), based on electrophysiological criteria. Intermediate forms of (0.38); p=0.49; APB – dominant 3.81 (0.98), non dominant 3.83 CMT have more recently be described and classified. Inheritance can be (1.00), difference -0.02 (0.39); p=0.49; 9HPT – dominant 23.2 (6.8), autosomal dominant (AD), X-linked, or autosomal recessive (AR). The non dominant 25.1 (7.1), difference -1.86 (3.27); p\0.001). Asym- most common form of demyelinating CMT (CMT1A), is caused by a metry (1 point or more difference in MRC score) in strength was duplication of the PMP22 gene. A deletion of the same gene causes observed in 12.5 % of the patients. Dominant FDI was weaker than hereditary neuropathy with liability to pressure palsies (HNPP). Point non-dominant FDI in 20 patients, stronger in 14 patients and equal in mutations in the PMP22 gene are less common and they may cause either strength in 237 patients. As far as APB is concerned, dominant side CMT1 or HNPP. We will present, for the first time, a large series of was weaker in 19, stronger in 14 and equal to non dominant in 238 patients carrying the PMP22 S22F point mutation previously described in subjects. Ageing did not preferentially affect dominant hand strength the Cypriot population (Kleopa K et al., 2004) that have been followed up with respect to non dominant. for a long period of time, some of them for over 20 years. Conclusions: We found no significant difference in strength Methods: Clinical, neurophysiological, demographical and mole- between dominant and non-dominant hand. Dexterity was signifi- cular findings in 17 patients belonging to 5 families carrying the cantly better for the dominant hand. Our data do not support an effect PMP22 S22F mutation. of overwork in producing hand weakness in CMT1A. It will be Results: All families originate from the same village in the interesting to investigate whether this is true also for other CMT Larnaca district of Cyprus thus indicating a founder effect. types. Clinically patients present with CMT1, HNPP or a combination of Supported by Telethon-UILDM (GUP04005, GUP05007) and CMT1 and HNPP phenotypes. Eight patients have the CMT1 phe- AIFA (Italian Medicines Agency, FARM53APAH) grants in Italy and notype, four patients have the HNPP phenotype and five patients have by a grant by the Muscular Dystrophy Campaign in the UK. both CMT1 and superimposed HNPP phenotypes. The age of onset varies from 16 to 60 years old and severity is variable among individuals within a family. All the patients were investigated with upper and lower limbs conduction velocities and the median motor nerve conduction velocities ranges from 23 to 33 m/s. P508 Conclusion: In our series of patients there was an interfamilial The long-term efficacy and treatment satisfaction variability of the clinical phenotypes with also variability as far as the and quality of life in patients with MMN who self-infuse severity of the disease. The nerve conduction studies showed the same broad spectrum seen in the clinical phenotype. Generally the median high-dose subcutaneous immunoglobulin therapy motor nerve conduction velocity was not as slow as seen in the independently in the home environment PMP22 duplications. The wide spectrum of phenotypes of all severity D. Gosal, M. Braine, A. Woodall, J. Sussman, A. Marshall, scales within a family highlights the importance of considering PMP R. Jeffrey, D. Gow 22 mutation search in demyelinating CMT patients. Greater Manchester Neurosciences Centre (Salford, UK); Salford University (Salford, UK); Sheffield University (Salford, UK) Objective: Multifocal motor neuropathy (MMN) is a rare immune- mediated neuropathy. Intravenous immunoglobulin (IVIg) is the P507 mainstay of therapy. Subcutaneous immunoglobulin (SCIg) is Overwork weakness: is it relevant in Charcot-Marie- emerging as a viable alternative to intravenous therapy. The aim of Tooth disease? this study was to evaluate the long-term efficacy of SCIg in a pop- D. Pareyson, M.M. Reilly, A. Schenone, G.M. Fabrizi, ulation of patients with MMN previously treated with IVIG. In addition we appraised the patient’s experience of SCIg and ascertain T. Cavallaro, L. Santoro, G. Vita, A. Quattrone, L. Padua, if those receiving SCIg had an improved quality of life and treatment F. Gemignani, F. Visioli, L. Matilde, D. Calabrese, satisfaction compared to those receiving IVIg. R.A.C. Hughes, D. Radice, A. Solari on behalf of the CMT- Methods: All patients met the EFNS criteria for diagnosis of TRIAAL & CMT-TRAUK Group MMN, aged [=18 years and were being treated with high-dose immunoglobulin (IgG) within a UK regional neuroscience centre at Objective: It is debated whether overwork weakness occurs in the time of data collection. Patients who were deemed to be clini- Charcot-Marie-Tooth (CMT) disease. Vinci et al. (Arch Phys Med cally stable on IVIG for a minimum period of six months were Rehabil 2003;84:825) found the dominant hand to be weaker in a eligible for inclusion. Pre and post-transition assessment included series of 106 patients with different types of CMT. However, van neurophysiology at baseline and after [ 6months of therapy, regular Pomeren and colleagues (J Rehabil Med 2009;41:32) found no dif- MRC score, 9 hole peg, grip strength, and 50m timed walk. In ferences in muscle strength for the dominant and non-dominant hand addition, three self-reported questionnaires; the English validated in 28 patients with CMT type 1 and 2. The aim of the present study self-questionnaires on HRQoL (SF-36 and LQI) and treatment sat- was to compare intrinsic hand muscle strength and manual dexterity isfaction (TSQM v1.4) were administered to the study participants

123 S124 J Neurol (2012) 259 (Suppl 1):S1–S236 and a cohort (n=7) of our patients with MMN who remained on P510 IVIG. Subacute demyelinating polyneuropathy associated Results: 9 patients have been followed up for a period between 6 months-5 years. Eight patients remained clinically and electrophysi- with B-cell lymphoma and IgM antibodies against ologically stable, with three patients demonstrating significant myelin-associated glycoprotein responsive to rituximab improvement in objective measurements. One patient dropped out of P. Banfi, E. Ambrosoni, V. Mariani, M. Maffioli, trial due to inefficacy. Overall, we found an improvement in HRQoL L. Campiotti and treatment satisfaction for the SCIg patient group as measured by Hospital Circolo e Fondazione Macchi (Varese, IT) LQI, SF-36v2 and TSQMv1.4. Conclusion: SCIg is a well tolerated and efficacious alternative to Introduction: Peripheral neuropathy associated with IgM Monoclonal IVIG in MMN. We demonstrate long-lasting clinical benefit and Gammopathy of Unknown Significance (MGUS) is quite common; improvement in quality of life and treatment satisfaction. about one half of patients with paraproteinaemic neuropathy show IgM monoclonal antibodies reacting with Myelin-Associated Glycoprotein(MAG).Paraproteinaemic neuropathies caused by haematological malignancies are far less frequent . P509 Case report: A 76-year-old patient presented with a two-months history of painful paraesthesias and walking difficulty. Neurological Post-infectious acute multifocal motor neuropathy examination revealed marked ataxia, distal weakness in lower limbs, or acute motor conduction block neuropathy: can we superficial and proprioceptive sensory deficit. Electroneurography bypass the diagnosis? (ENG) documented reduced motor and sensory action potentials, pro- M. Tondelli, L. Codeluppi, S. Contardi, longed distal motor latencies and slowed sensory and motor conduction velocities; electromyography (EMG) showed fibrillations and positive E. Georgoulopoulou, J. Mandrioli, F. Valzania, G. Galassi waves documenting acute neurogenic damage in explored muscles; a University Hospital (Modena, IT) slight proteinorrachia was found on cerebro-spinal fluid examination. Background. Multifocal motor neuropathy (MMN) progresses with Haematologic screening revealed a monoclonal gammopathy with high chronic, asymmetric lower motor neuron-type weakness and minimal serum IgM, mild chain kappa proteinuria and high levels of beta-2- sensory symptoms. Diagnostic criteria include motor conduction microglobulin; high titres of IgM anti-MAG antibodies were found. A blocks (CBs) at sites not common for compression. Acute-onset low grade B-cell non-Hodgkin lymphoma CD20 positive was con- MMN (AMMN), acute motor conduction block neuropathy (AM- firmed by bone marrow biopsy. A rapid progressive course of the CBN), Guillain-Barre` syndrome (GBS), and acute onset of chronic disease was observed, with intractable pain and severe paresis of lower inflammatory demyelinating neuropathy (A-CIDP) may show initially limbs with marked ataxia The patient was not responsive to a 5-days similar clinical features, raising issue of nosological classification. course of intravenous immunoglobulin treatment (0.4 g/Kg/day), while Case report. A 65-year-old man was evaluated because of asymmetric chemotherapy for lymphoma (Fludarabine-Cyclophosphamide-Ritux- upper limbs weakness, which he developed 7 days after febrile imab) determined clinical and neurophysiological improvement enteritis. On neurological examination the limb strength was graded observed at the six-months follow-up. within 2/5 and 3/5 distally in upper limbs. There was minimal loss of Discussion: MAG is the main target of IgM monoclonal antibodies distal vibration. Deep reflexes were decreased. CSF (day 4) had in paraproteinaemic neuropathies; the clinical presentation is usually normal protein content. Electrophysiological studies (day 4, 15) a chronic symmetric sensorimotor demyelinating neuropathy with a showed definite CBs in elbow-wrist segment of right median and in predominance of ataxia over motor signs; the haematological condi- tibial nerve at popliteal fossa. Other electrophysiological parameters tion associated with this entity is MGUS, but malignancies may also were normal. Search for Campylobacter jejuni infection was negative. occur. The association between indolent B-cell lymphoma and sen- IgG antibody titer to ganglioside GM1 (day 7) was 80 times the upper sorimotor demyelinating polyneuropathy with a subacute course of limit of normal. IVIg (0,4 g/Kg/daily for 5 days) improved distal motor symptoms responsive to Rituximab may suggest that IgM strength. On day 73, probable CBs were detected in axilla-elbow autoantibodies against MAG are part of the paraprotein produced by segment of right median and between knee-ankle in peroneal nerves. lymphoma cells. Nevertheless, more observations are needed to IVIg (day 63) were repeated with improvement. IgG antibody titer to clarify the causal relationship between anti-MAG antibodies and GM1 at 90 days was persistently high. Discussion. Our patient pre- Lymphoma, and the exact pathophysiology of nerve injury in these sented an acute neuropathy with multifocal persisting CBs without cases. abnormalities in sensory nerves. The elevated titer of IgM and IgG none. antibodies to GM1 at onset and the response to IVIg suggest an immune attack to peripheral nerves. AMCBN can correspond to two different pathophysiological conditions: the GBS variant defined by P511 Capasso et al. 1 and MMN variant reported by Lefaucheur et al. 2 While in AMCBN, all CBs recover, in AMMN, CBs and features of Leprous late-onset neuropathy: an uncommon demyelination persist independently from clinical evolution. Dis- presentation of leprosy tinction is not crucial at onset because both conditions respond to O.J.M. Nascimento, M.R.G. De Freitas, W. Marques Jr., IVIg. Temporal course and Ig isotype may help to distinguish the two F. Cardoso, C. Pupe conditions. 1 Capasso M et al. Acute motor conduction block neuropathy: University Federal Fluminense (Rio de Janeiro, BR); University of another Guillain-Barre` syndrome variant. Neurology, 2003; 61; Sao Paulo (Sao Paulo, BR) 617-22 Leprosy or Hansen’s disease is the most common treatable peripheral 2 Lefaucheur JP et al. A variant of multifocal motor neuropathy neuropathy in the world. Clinical and pathological findings in leprosy with acute, generalised presentation and persistent conduction blocks. are determined by the natural host immune response to M. Leprae. J Neurol Neurosurg Psychiatry, 2003; 74; 1555-61. We previously described (Nascimento et al., 1992) cases of painful

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S125 neuropathy (PN) with no concurrent cause apart from a past history of nerves and/or spinal roots was observed in 2 patients with MFS and 1 leprosy successfully treated many years before. with AIO. The present study confirms the specificity of high titre anti- Objective: To describe the clinical, neurophysiological and his- GQ1b antibodies in diagnosis of MFS variants, including AIO, and topathological characteristics, and treatment response in 5 late-onset underlines the importance of anti-GQ1b antibodies in the pathogen- neuropathy cases appeared after previous leprosy treatment. esis of clinical manifestations. Furthermore, MRI enhancement of Patients and Methods: Five patients previously treated with mul- spinal roots or cranial nerves, frequent in GBS but anecdotal in MFS, tidrug therapy (MDT) for skin leprosy (lepromatous leprosy clinical is relatively common in our small series of cases with anti-GQ1b form), and now living in a non endemic area, were sent to neuro- antibodies, suggesting a possible diagnostic role for MRI. logical evaluation by dermatologists due to a recent onset neuropathy. They all had been excluded for an active leprosy infection or rein- fection. Electrophysiological examination with standard techniques and sural nerve biopsy were performed. Wade-Fite acid-fast stain for P513 leprosy bacilli was performed. Glucose intolerance, diabetes, other Long-term sedation with isoflurane in a case of severe metabolic or endocrine disorders, vascular or collagen diseases Guillain-Barre´-Syndrome associated or not with vasculitis, HIV, HTLV-1/2, HBV and HCV- J.C. Purrucker, S. Scho¨nenberger, J. Bo¨sel virus infections, cancer, and other causes of neuropathies were ruled Heidelberg University Hospital (Heidelberg, DE) out, clinically and laboratorially. ‘‘Ongoing-neuropathy’’ in leprosy patients who have completed MDT was also excluded. A 62-year-old patient first noticed a progressive weakness in his lower Results: The mean patient (3 male; 2 female) age was 51.4 years extremities and deteriorated rapidly. After admission, Guillain-Barre´- (46- 64). The mean time interval of the recent neuropathy from the Syndrome (GBS) was diagnosed by detection of albumino-cytological previous MDT was 20.4 years (12-26). A painful multiplex neuritis or dissociation in the cerebrospinal fluid. While nerve conducting studies polyneuropathy were observed respectively in 3 and 2 cases. Elec- showed borderline delayed distal latencies, electromyography trophysiological studies disclosed a sensory axonal neuropathy in 3 suggested neuropathy. The GBS was treated by intravenous immu- cases. Microvasculitis with no bacilli was seen in nerve biopsy in all noglobulins (IVIG) followed by plasmapheresis. During a two months cases. Neuropathic symptoms improved with prednisone. stay at our neurointensive care unit, we had to deal with respiratory Conclusion: We consider these cases as being a leprosy late-onset insufficiency and marked autonomic dysregulation, requiring a long- neuropathy (LLON) form of presentation. A delayed immune reaction term-sedation and ventilation. The autonomic dysregulations were could explain the late appearance of LLON. so severe that sedation became very challenging although several Supported by: FINEP, MCTI-CNPq traditional regimes of intravenous sedatives were applied. Eventu- ally, we successfully used an Anaesthetic Conserving Device (AnaConDa; Sedana Medical, Sweden) to apply the volatile anesthetic isoflurane for 16 days. After frequency of autonomic P512 dysregulation decreased, weaning from the ventilator was successful The clinical spectrum of neurological manifestations and we were able to transfer the patient to a neurologic rehabilitation. He was still tetraparetic, but started to move his arms and legs on his in patients with anti-GQ1b antibodies own. Speaking was possible again by using a tracheal cannula with D. Ajena, T. Cavallaro, G. Fabrizi, M. Filosto, D. Alberti, speaking valve. S. Monaco, S. Ferrari To our knowledge, the application of isoflurane for long-term University of Verona (Verona, IT); University Hospital Spedali Civili sedation in GBS has not been reported so far. We therefore report (Brescia, IT) details of this unique experience, will give a short review of alternative sedation-regimes and discuss the particularities of applying Anti-GQ1b IgG antibodies, are acute phase auto-antibodies targeting volatile agents in inflammatory disease. paranodal myelin of oculomotor nerves, neurons of dorsal root ganglia, and neuromuscular junctions of extraocular muscles which are usually detected in patients with Miller Fisher Syndrome (MFS) variants, Guillain-Barre´ syndrome (GBS), Bickerstaff brainstem P514 encephalitis (BBE), acute oropharyngeal palsy, and acute isolate Effect of carbamazepine on frog sciatic nerve ophthalmoparesis without ataxia (AIO). J. Scekic, M. Drecun, S. Vujisic The aim of our study is to review the clinical spectrum, electro- Medical Faculty, Clinical Centre of Montenegro (Podgorica, ME) physiological data and Magnetic Resonance Imaging (MRI) findings of 20 patients with anti-GQ1b antibodies. Among 2329 sera of Objectives: Anticonvulsants, such as carbamazepine, are effective in patients tested for anti-ganglioside antibodies in our Laboratory of the treatment of neuropathic pain after systemic administration. They Neuropathology from 2004 to 2011, we found 20 (14 M and 6 F) act by potentiation of gamma-aminobutyric acid transmission, subjects with anti-GQ1b antibodies. Using ELISA method anti-GQ1b reduction of glutamate mediated excitatory transmission, and block- positive sera were also screened for anti-GM1, anti-GM2, anti-GD1a, ade of voltage-gated ion channels. The objective of this study was to anti-GD1b, and anti-sulphatide antibodies. Twelve patients received determine the effect of carbamazepine after direct administration on clinical and electrophysiological diagnosis of MFS, 2 of AIO, 1 of isolated frog sciatic nerve using compound action potential (cAP) GBS, 4 of CIDP, and 1 of unclassified neuropathy. Three groups of parameters. patients were identified: low anti-GQ1b titre (=1/640) (7 subjects), Methods: Experiments were done on forty (40) frog sciatic nerves, medium anti-GQ1b titre ([1/640\=1/1260) (4), and high anti-GQ1b control cAP measurements were done after nerves were incubated in titre ([=1/2560) (9). We observed a strong correlation between high Ringer’s solution for cold-blooded animals by single electrical stim- anti-GQ1b titre and the clinical picture of MFS or AIO. Medium and ulus using stimulator and digital oscilloscope. Afterwards, nerves low titres were inconstantly associated to AIO or GBS. In 6 cases were divided into two groups of twenty (20) nerves. In each group the reactivity for anti-GD1a or anti-GD1b or anti-GM2 was also found; right frog sciatic nerve was used as a control, while the left one has only one case received diagnosis of MFS, 4 of CIDP and 1 of been experimentally tested, so that each group had its own control and unclassified neuropathy. MRI gadolinium enhancement of cranial experimental subgroup of ten (10) nerves. The nerves of experimental

123 S126 J Neurol (2012) 259 (Suppl 1):S1–S236 subgroup were put in the following solutions of carbamazepine, dis- onset of neuropathy. This analysis was similar to a previous Korean solved in dimetilsulfoxide, according to the different concentrations study, suggesting that polymorphism affects chemotherapy-induced (0.5 and 1.0 mmol/l) and the nerves of control subgroups were put in peripheral neuropathy with no ethnic bias. the dimetilsulfoxide solution. Measurements of cAP parameters were Conclusion: The pharmacogenetic approach is useful for identi- done after 15 min of incubation in carbamazepine (incubating per- fying predictors of L-OHP-induced peripheral neuropathy and may be iod). Subsequently, nerves were washed and incubated in Ringer’s used in personalized chemotherapy. solution, measuring of cAP have been done after 30, 60 and 120 min (recovering period). The obtained data were statistically analysed using the GraphPad Prism 5.0. Results: After 15 min of incubation in 0.5 mmol/l carbamazepine, P516 cAP parameters were not statistically significantly changed in relation Paroxysmal myoplegia, myopathy and neuropathy to control group while in 1.0 mmol/l carbamazepine amplitude of cAP decreased (p\0.05), and both the onset and the peak latency periods of peroneal nerves in a patient with gluten enteropathy increased (p\0.01). All nerves have recovered their function after V. Konstantinova, E. Vasileva, N. Muradyan, N. Kolev, 60 min of recovering period. M. Daskalov Conclusion: Since the amplitude is proportional to the number of University Hospital Tsaritsa Yoanna (Sofia, BG) excited fibers, carbamazepine possibly reduces nerve excitability. As the onset and the peak latency periods represent impulse conduct- Gluten-sensitive enteropathy, or celiac disease, is an autoimmune ing time along fastest and slower nerve fibers, respectively, enteropathy, triggered by intake of gluten-containing foods. Intestinal carbamazepine probably reduces conductivity along the correspond- villi are being destructed and usually a malabsorption syndrome ing fibers. It can be concluded that mechanism of peripheral nerv develops. Neurological complications appear in 6-12 % of the conduction block produced by carbamazepine is similar to local patients, due to malabsorption syndrome or/and immune-mediated anesthetics action through blockade of voltage-gated ion channels. mechanisms. The disease started in a 20-year old woman with diarrhea, vomiting, which continued recurrently for ten years. During that period she had been treated for depressive disorder. Ten years later a severe P515 malabsorption syndrome developed with diarrhea, lost of weight, Peripheral neuropathy induced by oxaliplatin is generalized fatigue. Two months later, the patient was accepted to a associated with genetic polymorphisms hospital in a coma, which lasted several hours, and paroxysmal hypokalemic myoplegia, which recovered after intravenous applica- A. Mitsuma, T. Oguri, M. Inada, Y. Ando tion of potassium. To the moment of admission to our hospital, she Nagoya University Hospital (Nagoya, JP) had diarrhea 5-6 times daily, fatigue, edema-ascites syndrome, dry Objectives: Oxaliplatin (L-OHP) is one of the key drugs for adjuvant and pealing skin, weakness in muscles, and gait disorder. The neu- and palliative chemotherapy in colorectal cancer patients. L-OHP- rological examination revealed mild proximal weakness in the upper induced neuropathy is classified into two types with acute or chronic and lower extremities, severe bilateral peroneal paresis, and slight neurotoxicity. Because the chronic neuropathy is cumulative and dose ataxia. Laboratory studies showed constellation of extended malab- limiting, reliable predictors and determining the mechanism of this sorption - anemia, hypoproteinemia, low serum levels of potassium, toxicity are required. magnesium and iron. Methods: We retrospectively studied 71 Japanese colorectal can- An EMG examination was performed with evidence of myopathy cer patients who had received L-OHP-based chemotherapy and in proximal muscles, and severe neuropathy of both peroneal nerves. explored the pharmacogenetic association between L-OHP-induced The MRT scan of the brain did not show any abnormalities. Histo- neuropathy and polymorphisms (SNPs) of the excision repair cross- pathological examination of duodenal mucosa revealed subtotal complementation group 1 (ERCC1) and glutathione S-transferase pi 1 villous atrophy, with elongation of crypts and an increased number of (GSTP1) genes. Additional analysis was performed on about 9 SNPs intraepithelial lymphocytes. After treatment, along with gluten-free in 8 genes which were reported in a genome-wide Korean patient diet, vitamins, intravenous replacement of fluids, proteins, electro- study (Won et al., Cancer 2011). All clinical events, including neu- lytes, and rehabilitation, a remarkable improvement in peroneal ropathy, were evaluated according to CTCAE v3.0. weakness was observed. Results: For the rs10486003 in TAC1 (tachykinin, precursor 1), grade 1 chronic neuropathy developed earlier in patients with C/C genotypes than in those with the reference C/T and T/T genotype (p=0.0197 by log rank test). Also, the rs797519 in DLEU7 (deleted in lymphocytic leukemia, 7), grade 1 chronic neuropathy developed P517 earlier in patients with G/G genotypes than in those with the reference Local lidocaine treatment in the management of cubital C/C and C/G genotype (p=0.0351). ERCC1 was also related to the tunnel syndrome time until onset (p=0.0453), but GSTP1 was not (p=0.422). Seven O. Karadas, H. Gul, R. Inan, U. Turk Boru other SNPs in 6 genes (forkhead box C1 [FOXC1] rs2338; integrin, alpha 1 [ITGA1] rs830884; acylphosphatase 2, muscle type [ACYP2] Erzincan Military Hospital (Erzincan, TR); Kartal Education and rs843748; B-cell translocation gene 4 [BTG4] rs4936453; calcium/ Research Hospital (Istanbul, TR) calmodulin-dependent protein kinase II inhibitor 1 [CAMK2N1] Objective: Cubital tunnel syndrome is the second most common rs12023000; phenylalanyl-tRNA synthase 2 [FARS2] rs17140129 and compression neuropathy in the upper extremity. Patients complain of rs6924717) were not correlated with it (p=0.937, p=0.359, p=0.964, numbness in the ring and small fingers, as well as hand weakness. p=0.194, p=0.778, p=0.573, p=0.573, respectively). The most sig- Advanced disease is complicated by irreversible muscle atrophy and nificant association was observed at rs10486003 in TAC1 (Cox hand contractures. This condition may be treated by both conservative proportional hazards regression analysis, p=0.036). None of the SNPs and operative means. It is claimed that local lidocaine administration were associated with the severity of chronic neuropathy. Our results in cubital tunnel reduce compression of ulnar nerve due to its anti- suggest that ERCC1 and these two SNPs would be related until the inflammatory and antiedema effects. The aim of this study is to 123 J Neurol (2012) 259 (Suppl 1):S1–S236 S127 determine the efficiency of local lidocaine on cubital tunnel syndrome Objectives: Morphometric analysis of myelinated fibres is known to with electrodiagnostic and clinical evaluations. generate relevant data widely used for the identification of several Methods: 3cc 1 % lidocaine were injected to cubital tunnels of 21 peripheral neuropathies, including demyelinising/remyelinasing extremity of 21 patients who were diagnosed as cubital tunnel syn- processes. This analysis can be achieved manually or through drome according to the clinical and electrodiagnostic evaluations. computer-based image analysis systems which vary to a certain Electrodiagnostic tests were performed and pain levels were degree of automation, allowing us to classify the measuring process recorded(according to Visual Analog Scale(VAS) before the injec- as manual, semi-automatic, or fully automatic. Due to the large tions. Same evaluations were applied 2 months after injections. number of elements to be analyzed in a single microscopic image, Results: 13 female and 8 male patient with a mean age of 41.25 manual or poorly automated methods are extremely laborious for were included in the study. Ulnar nerve sensory conduction velocity the system users. In the attempt to avoid this hard and time con- values revealed as increased on second month after injection. This suming labour, researches use computer-based techniques capable change was significant. Distal motor latency and pain levels improved of reducing or even eliminate the need of human interaction. We significantly 2 months after injection. aimed to develop a morphometry system for myelinated fibres as Conclusion: Local lidocaine administration to cubital tunnel have automated as possible, without compromising the quality of the favorable effects on cubital tunnel syndrome patients. This analysis. improvement can be seen in electrodiagnostic evaluations and clinical Methods: Semi-thin cross sections of the vestibulocochlear nerve findings. from adult guinea pigs, perfused with glutaraldehyde 2.5 % were used. We developed a pipeline of computational routines that uses a concavity based technique for fibres segmentation. This pipeline was compared to another one based on mathematical morphology tech- P518 nique, widely used in the literature. An extractor capable of extracting Ultrasonographic follow-up in ulnar neuropathy the morphometric measurements was also developed. Comparisons at the elbow were made between data obtained with the developed program to A. Rampen, D. Tavy, P. Wirtz those from manual morphometry, considered our ‘‘gold standard’’. Results: There is a clear advantage of the concavity-based HagaZiekenhuis (The Hague, NL) technique when compared to the mathematical morphology tech- Objective: Ulnar neuropathy at the elbow (UNE) is considered the nique on the automatic and correct identification of the myelin second most common entrapment neuropathy after carpal tunnel sheaths. Myelinated fibre average measurements obtained with our syndrome. Based on international guidelines, diagnosis of UNE is program were larger when compared to the gold standard method, made on clinical and electrophysiological examination. Ultrasound of due to the reduced number of small myelinated fibres automatically the ulnar nerve has been validated in recent years. Though above- identified. Nevertheless, there was a complete overlap between fibre mentioned techniques have established their part in diagnosing UNE, diameter distribution histograms obtained with both methods. no prospective study yet focused on possible short-term changes in Moreover, our program takes only 11 s for the segmentation of an ultrasonographic studies to monitor the disease or possible treatment endoneural area containing approximately 116 fibres, compared to effects. the average of 20 min taken for the manual segmentation of the Methods: Prospective cohort study including patients with clinical same image. mild UNE, i.e. sensory symptoms in the fifth digit and the medial Conclusion: We were able to develop a tool capable of automat- aspect of both the fourth digit and the hand without or with mild ically extract the morphometric features of myelinated fibres. Further weakness of the ulnar-innervated intrinsic hand muscles. On baseline improvement of the program is already under investigation in order to clinical, neurophysiological and ultrasonographic examination were achieve a better identification of the small myelinated fibres. performed. After six to nine weeks clinical examination and high- Financial support: FAPESP, CNPq, FAEPA. resolution ultrasonography of the ulnar nerve were repeated. Results: We included 66 patients with clinical mild UNE. At follow-up twenty-three patients reported clinical improvement and twenty-one deterioration; twenty-two patients remained stable. The 2 P520 mean differences in maximum area (in mm ) measured at the elbow Aortic depressor nerve unmyelinated fibre distribution was 1.99 lower (standard deviation (SD) 2.18), 0.38 higher (SD 1.95) and 0.06 lower (SD 2.42) for the three groups respectively. The dif- in long-term experimental diabetes ference in mean difference between improvement and deterioration F. Oliveira, R. Nessler, H.C. Salgado, V.P. Fazan was statistically significant (p\0.001). Comparable results were School of Medicine of Ribeiraõ Preto (Ribeiraõ Preto, BR); Central obtained for differences in maximum diameter at the elbow and area Microscopy Research Facility (Iowa City, US) ratio elbow/above elbow (p-values for difference in mean difference Objectives: Previous results from our laboratory (Fazan et al., 2006) between improvement and deterioration 0.16 and 0.001 respectively). showed myelinated fibre alterations in the aortic depressor nerve Conclusion: Repeated ultrasonography of the ulnar nerve corresponds (ADN) from rats rendered diabetic for 12 weeks (long term). Nev- with clinical follow-up in mild UNE. These measures might be used in ertheless, the unmyelinated fibres of this nerve were not yet future studies investigating therapeutic options for mild UNE. investigated. The aim of this study was to evaluate the unmyelinated fibre distribution alterations in the ADN of rats, due to long term experimental diabetes. P519 Methods: Wistar rats received a single intravenous injection of Development of a computational tool for myelinated streptozotocin (40mg/Kg) 12 weeks (N=14) before the experiments. Control animals (N=9) received vehicle (citrate buffer). Under pen- fibre morphometry tobarbital anaesthesia the ADNs were isolated and had their R. Novas, A.R. Silva, V.P. Fazan, J. Felipe spontaneous activity recorded. Afterwards, proximal and distal seg- School of Philosophy, Sciences and Languages, School of Medicine ments of the nerves were prepared for transmission electron of Ribeiraõ Preto (Ribeiraõ Preto, BR) microscopy studies as reported previously (Fazan et al., 1997; Fazan

123 S128 J Neurol (2012) 259 (Suppl 1):S1–S236 et al., 2001). Morphometry of the unmyelinated fibres was carried out P522 with the aid of computer software. Head-up tilt test and sympathetic skin response Results: Unmyelinated fibre number was significantly larger in the long term diabetic group compared to the respective control, in the assessment of the autonomic nervous system while average fibre diameter was smaller in this group. Most of the in leprosy patients endoneural capillaries were preserved in all experimental groups. H. Ulvi, R. Yigiter Unmyelinated fibre distributions were unimodal in both groups. Atatu¨rk University (Erzurum, TR); Gaziantep University (Gaziantep, Nevertheless, there was a tendency towards smaller diameter fibres TR) on proximal segments and a clear shifted to the left on distal segments, with a larger percentage of small fibres in the diabetic Backrgound: The aim of this study was to compared being more animals. effective in evaluating possible autonomic nervous system (ANS) Conclusion: Our results provide morphological support to the dysfunction in leprosy patients the sympathetic skin response (SSR) previous reports (Salgado et al., 2001) of an altered function of the and head-up tilt test which are easy and reliable methods for evalu- baroreflex in this model of autonomic diabetic neuropathy. ation of autonomic functions. References: (a)Fazan et al., Am J Hypertens 19: 153-160, 2006; Materials and methods: We studied 28 affected people (mean age: (b)Fazan et al., Hypertension 30: 693-698, 1997; (c)Fazan et al., Am J 35, 13 female and 15 male) and 35 age-matched healthy subjects Physiol Heart Circ Physiol 280: H1560-H1564, 2001; (d)Salgado (mean age: 34, 20 female and 17 male). Non-invasive head-up tilt et al., Ann NY Acad Sci 940: 20-27, 2001. test, SSR latency and amplitude from both palms, and nerve con- Support: CNPq, FAPESP and FAEPA. duction parameters were studied using an electromyogram (EMG) equipment in all the subjects. Results: The mean values of ‘’30/15’’ head-up tilt test (in patients, 0,97±0,46 vs controls, 1,12 ± 0,30 [p\0.05]) was signif- P521 icantly lower compared with the controls. Abnormal head-up tilt test Neuropathic causes of pain while sitting were more pronounced in leprosy patients with clinical orthostatic H. Arinõ, G. Barraza-Sandoval, M. Espunã, G. Lacima, J. functional abnormalities than those without orthostatic functional abnormalities. The mean latency of SSR in leprosy patients (mean Valls-Sole´ SSR latency in patients, 1.73±1.14 ms vs controls, 1.36±0.42 ms Hospital Clinic (Barcelona, ES) [p\0.05]) was significantly prolonged compared with the controls. Introduction: Pelvic floor, perineal or genital pain that increases while The mean amplitude of SSR in leprosy patients (mean SSR sitting is a conspicuous condition that can be due to neurogenic and amplitude in patients, 0.56±0.41 lV vs controls, 1.01±0,43 lV non neurogenic causes. In a two years review of patients followed in [p[0.05]) was smaller compared with the controls, but this differ- our monographic neuropathic pain outpatient clinic, we have identi- ence was not significant. Out of 28 leprosy patients, 19 (67,85 %) fied 16 (3.7 %) whose main symptom was pain while sitting and had showed abnormalities head-up tilt test and 23 (82,14 %) abnor- likely causative neuropathic lesions. malities SSR. Methods: We review the cases and describe the clinical, labora- Conclusions: SSR and head-up tilt test which can be easily and tory, neuroimage or neurophysiological signs indicative of the rapidly performed in an EMG laboratory can provide useful, objective neuropathic origin of pain. Protocolized electrodiagnostic studies information. SSR are more sensitive than head-up tilt test, but com- were carried out in all cases, including sphincter EMG, pudendal bined use of these two tests are more effective because head-up tilt nerve latency, sacral reflexes, motor evoked potentials of the pelvic test were more effective in leprosy patients with clinical orthostatic floor muscles to transcranial magnetic stimulation (TMS) and noci- functional abnormalities. ceptive contact heat evoked potentials (CHEPs) in Cz to pelvic floor Leprosy, autonomic nervous system, sympathetic skin response, stimulation. head-up tilt test Results: Patients were 8 men and 8 women. Peripheral nerve lesions were suspected in 5 patients who presented with allodynia in the nerve territory of the ilio-inguinalis, genito-femoralis, dorsal penis or pudendal nerves. Identified causes were pelvic traumatism P523 (1), surgery for inguinal hernia (1) compression by femoral bone Relationship between severity of cardiovascular cysts (1), circumcision (1) and Alcock’s canal compression after autonomic neuropathy and diabetic complications sitting for long hours during tantric sexual practices (1). Sacral or of type 2 diabetes mellitus coccyx fractures were identified in 2 women and 1 men who sustained buttock traumatisms, and giant Tarlov’s cysts (15 mm or A. Motataianu, R. Balasa, Z. Bajko more in diameter) were found in the MRI of 5 female patients. Mures County Clinical Emergency Hospital (Targu Mures, RO) Two patients had electrophysiological evidence of radicular or Background: Cardiovascular autonomic neuropathy (CAN) is the plexular lesions (multiple sacral radicular lesions in 1 and post- most frequent and clinically important form of diabetic autonomic radiotherapy neuropathy in 1). One patient with known limb-girdle neuropathy. CAN is associated with increased frequency of other myopathy had marked atrophy of the glutei muscles and severe microvascular and macrovascular complications of diabetes mellitus myopathic changes in needle EMG. In patients with either coccyx (DM). Objectives: To determine the relationships between severity of fracture or Tarlov’s cysts, EMG was often normal but a unilateral CAN and clinical parameters and diabetic complication in type 2 pudendal nerve lesion was found in one and bilaterally delayed diabetes. CHEPs were found in two. Methods: 52 patient with DM complicated with CAN (26 women Conclusion: Several types of neuropathies were identified as and 26 men) were included in this study. The prevalence of CAN potential causes of pain while sitting. Sitting may increase intrapelvic among 52 patients with type 2 diabetes mellitus was assessed by the pressure and cause nerve stretching at the roots or sites of possible five autonomic function tests by Ewing’s methodology. The patients compression or angulation, implying mechanical allodynia and other were grouped according with the degree of CAN, as early, definite forms of neuropathic pain. and severe.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S129

Results: Significant correlations were found between severity of the ethical acceptability of research protocols. Objective: To com- CAN and duration of diabetes (p \ 0.001, r = 0.59), age at onset of pare physicians, researchers in aging and IRB members on their diabetes (p = 0.01, r = -0.33), retinopathy (p = 0.001, r = 0.43) and perceptions of various risks posed by a hypothetical dementia drug ankle brachial index (p = 0.04, r = 0.28). Interestingly, there was no trial. Methods: We conducted an anonymous postal survey of phy- significant correlation between the degree of peripheral neuropathy sicians (n = 495), researchers in aging (n = 177) and IRB members diagnosed by EMG. (n = 325) from four Canadian provinces. Survey participants were Conclusions: The must important correlation between CAN and given eight short risk descriptions (e.g., ‘‘There is a 1 % possibility other micro/macrovascular complication was find with retinopathy. of death among patients taking the medicine’’) and asked to cate- There are no gender differences regarding the CAN and other micro/ gorize the level of risk on a four-point scale ranging from 1 = No macrovascular complication. Risk to 4 = Serious Risk. Multivariate analyses of variance and covariance were performed to tease out group differences in risk perceptions, identify descriptions on which groups differ, and determine whether differences in risk assessments persist after P524 controlling for age, sex, education, and religious denomination. Increased incidence of Guillain-Barre´ syndrome Results: The three groups of respondents were found to differ sig- after surgery nificantly in their risk assessments [F (16, 1934) = 3.51; p \ .001]. H. Gensicke, A. Datta, P. Dill, C. Schindler, D. Fischer Subsequent analyses indicated that researchers in aging and IRB members rated risk similarly [F (8, 458) = .75, p = .646], but dif- University Hospital Basel, University Children’s Hospital Basel, ferently from physicians [F (8, 967) = 6.41; p \ .001]. Physicians Swiss Tropical and Public Health Institute Basel (Basel, CH) ratedrisklowerthanresearchersinagingandIRBmembersonfive Background: Antecedent surgery has been described to trigger Guil- of the eight descriptions (p-values from .001 to .021). For four of lain-Barre´ syndrome (GBS). However, the evidence is poor and based these five descriptions, between-group differences in perceived risks on case reports only. persisted after controlling for age, sex, education, and religious Objective: To assess the incidence of postsurgical GBS. denomination [p-values from .001 to .007]. Conclusion: Controlling Methods: We performed a retrospective analysis of 63 GBS for potential confounders, we found significant differences in how patients admitted to the University Hospital Basel and University physicians on the one hand, and researchers in aging and IRB Children’s Hospital Basel from January 2005 to December 2010. We members on the other, perceive risks in the specific context of a calculated and compared the incidences of postsurgical and non- hypothetical dementia drug trial. Such differences could confuse exposed GBS patients in the study population and those reported prospective study participants who are solicited for dementia previously in literature. research. Results: 6 of 63 (9.5 %) GBS cases had had a surgery within 6 Study funded by an independent grant from the Canadian Insti- weeks prior to GBS. The relative risk of developing GBS during the tutes of Health Research (Grant # 200409MOP). six week period after surgery is 13.1 times higher than the normal incidence in the study population (95 % confidence interval: 5.68, 30.3; p= \0.0001), suggesting an attributable risk of 4.1 cases per 100,000 surgeries. In addition, the incidence of postsurgical GBS is P526 significantly higher than influenza vaccine-associated GBS in the Young-onset degenerative dementias in a tertiary study population (p= 0.01) as well as in comparison with previous referral hospital reported vaccine-associated GBS (p= \0.0001) and background P. Maiovis, P. Ioannidis, A. Lourbopoulos, D. Karacostas incidences (p= \0.0001) AHEPA University Hospital (Thessaloniki, GR) Conclusion: Surgery must be considered to be a potential risk factor for developing GBS. Background: Primary degenerative dementias comprise of Alzhei- mer’s Disease (AD), behavioral variant Frontotemporal Dementia (bvFTD), Primary Progressive Aphasia (PPA), Lewy Body Dementia (LBD), Corticobasal Degeneration (CBD), Progressive Dementia I Supranuclear Palsy (PSP) and Huntington’s Disease (HD). Young onset dementia includes patients younger than 65 years old, with different frequencies among various subtypes compared to late onset P525 dementia. Methods: 470 patients were diagnosed with primary degenerative Risk perceptions in dementia research: a comparison dementia from January 1, 2003 to December 31, 2010 in the Neu- of physicians, researchers in ageing and institutional rology Department of a tertiary referral center. Young onset patients review board members (\65 years old) were 89 (18.9 %). Patients were classified as AD, G. Bravo, M-F. Dubois, J. Graham, C. Cohen, S. Wildeman LBD, bvFTD, PPA, CBD/PSP, HD and their demographic characteristics were analysed. University of Sherbrooke (Sherbrooke, CA); Dalhousie University Results: From the 89 young onset dementia patients, 19 (21.3 %) (Halifax, CA); University of Toronto (Toronto, CA) were diagnosed with AD, 36 (40.4 %) with bv-FTD, 25 (28.1 %) with Effective risk communication is important when recruiting partici- PPA, 7 (7.8 %) with CBD or PSP, 1 (1.1 %) with HD, and 1 with pants for dementia studies and securing their informed consent. In LBD (1.1 %). 35 (39.3 %) patients were men and 54 (60.7 %) were the field of environmental and technological hazards, perceived risks women. Mean age was 58.4 years (range 41-65). have been found to vary across professions. Consequently, risk Discussion: Young onset dementia poses great diagnostic chal- perceptions in dementia research could vary between physicians lenge to the clinical neurologist. Reversible conditions must be ruled who may recruit study participants, researchers who solicit their out and primary degenerative dementias should be correctly classi- consent, and Institutional Review Board (IRB) members who assess fied, enabling proper counseling for the patient and family.

123 S130 J Neurol (2012) 259 (Suppl 1):S1–S236

P527 paired by age, gender and educational level was studied. A stan- Framingham Risk Score but not Framingham Stroke dardized questionnaire looking for significant stressful life events in the 3 years before the diagnosis of AD was performed to patients, Risk Profile is an independent predictor of impaired family caregivers and control individuals. cognitive function among older people, free Results: In the AD group, 78 patients (73 %) presented a history of of cardiovascular disease significant stressful life events, 2.1 years (SD 1.3 y) before the onset Z. Tufekcioglu, S. Ergecer, R. Krespi, O. Tuncer, R. Tolun, of the symptoms. The most common findings in the AD group were: couple death (21 cases), child death (14 cases), history of assault or Y. Krespi violent theft (20 cases), history of car accident without severe injuries Istanbul Science University, Istanbul Florence Nightingale Hospital, (10 cases). Other stressful situations were marked financial problems, Istanbul Arel University (Istanbul, TR) bereavement, retirement, adaptative changes due to migrations and Background: Vascular risk factors contribute to cognitive impairment, diagnosis of severe somatic disease in the family. In the control which may be the earlier manifestation of vascular brain injury. This group, only 18 individuals (24 %) recognized a similar stress factor in study examined the relationship between 10-year risk for coronary the previous 3 years. heart disease (CHD) or stroke and cognitive function in older people, Conclusions: In our study, we observed an association between free of cardiovascular disease. stressful life events preceding the onset of dementia symptomatology Methods: Participants were consecutive attenders of a ‘‘primary in a high percentage of our patients. Different authors hypothesized vascular prevention clinic’’, between 2009 -2010. The Framingham that stress could trigger the degenerative process in AD and growing Risk Score (FRS) and Framingham Stroke Risk Profile (FSRP) were evidences suggest a dysfunction in the neuroendocrine and immune used to assess 10-year risk of CHD and stroke, respectively. Cognitive system. According our results, we can establish a relationship function was measured with Montreal Cognitive Assessment Scale between several stressful life events and the onset of the initial (MoCA). Cognitive status (CS) was categorized as impaired symptoms of dementia. It is an observational finding and does not (MoCA\=21) vs. normal as previously validated in the Turkish imply direct causality. Futures studies are required to examine this population. Correlations between cognitive status and FRS or FSRP association in more detail and to explain the possible mechanisms of were analyzed with multivariate logistic regression analyses. Age, this relationship. gender, education level, other potential correlates of cognitive ability (depression, physical activity, obesity, alcohol consumption, family history of dementia) and treatment for hyperlipidemia and diabetes P529 were included in the analyses. Results: The sample consisted of 167 individuals (40 men and 127 Alzheimer’s disease biomarkers in diagnosis of post- women). Mean age was 68 (SD: 6 Range: 28). Mean FRS and FSRP stroke cognitive impairment were 8(3-20) and 7(4-11) respectively. Fifty five individuals ( %33) M.A. Cherdak, N.N. Yakhno had impaired CS. Individuals with higher FRS (increment by 10 % in I.M.Sechenov First Moscow State Medical University (Moscow, RU) FRS) had more impaired CS (adjusted OR: 1,669, 95 %CI 1,038 to 2,682). No association was shown between FSRP and CS. Higher age, Objective: To evaluate different types of cognitive impairment (CI) in lower education level, absence of alcohol consumption and absence of ischemic stroke patients depending on profile of biomarkers of Alz- treatment for hyperlipidemia were the other independent predictors of heimer’s disease (AD). impaired CS. Methods: 29 patients (59 to 85 y.o., mean age - 72.7 ± 6.8 years) Conclusion: Our findings indicated that in older individuals, free at the acute phase of ischemic stroke without other severe medical of cardiovascular disease, global vascular risk is associated with conditions, psychiatric disorders or aphasia were studied. All patients impaired cognitive function which was accounted for by FRS rather underwent neurological and comprehensive neuropsychological than FSRP. This association was demonstrated with the use of a examination; additional measurement included Informant Question- simple and standard neuropsychological test in routine clinical naire on Cognitive Decline in the Elderly (IQCODE). Types of CI setting. were defined according to currently established criteria. Assessment of AD biomarkers included beta-amyloid(1-42) (Abeta42), total and phosphorylated tau-proteins (P-tau) in cerebrospinal fluid (CSF); APOE genotype; hippocampal atrophy on MRI (rated according to P528 Scheltens scale). Positive AD profile (AD+) was established accord- Development of Alzheimer’s disease and recent stress ing to P-tau/Abeta index [ 0.0867. Results: AD+ profile was revealed in 9 of 29 patients. There was events no significant difference in stroke severity between patients in AD+ E. Reich, C. Torres, E. Arias, M. Carlino, E. Halac and AD- groups. Poststroke CI in AD+ patients were more severe Hospital Julio Mendez, Buenos Aires University (Buenos Aires, AR) (all patients in AD+ group had dementia; dementia rate in AD- group 45.0 %, p\0,05). According to the IQCODE, prestroke CI Background: The sporadic nature and late onset of most AD cases occurred in 58.6 % patients (AD+ — 55.5 %; AD- — 60.0 %). could suggest that aside from biological determinants, environmental Groups differed significantly in severity of poststroke CI with no factors such as stress may play a role in the development and pro- difference in severity and incidence of prestroke CI. CI in AD+ gression of the disease. group more often included memory disturbances (especially of Recent data implicated stress as a potential risk factor in devel- ‘‘hippocampal’’ type), impairment of nominative speech function opment of AD. The present study aims to analyze the relationship and executive functions (in all cases p\ 0.05) with similar visual- between recent stressful life events and the development of AD. spatial disturbances. Hippocampal type of memory disorders was Methods: We studied 107 patients with clinical diagnosis of present in all AD+ patients and 8 of 20 patients in AD- group probable AD, according validated criteria, in mild to moderate stages. (according to MRI such patient in AD- group more often had lesions The medium age was 72 years and the educational level was 8.1 of temporal lobes). APOE4 was present in 67 % AD+ and 19 % years. The meantime elapsed from the diagnosis or the initial AD- patients. Hippocampal atrophy was more profound in AD+ symptoms was 2.5 years. A control group of 76 healthy individuals, group (p\0.05).

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S131

Conclusions: Concomitant AD increases risk of CI after stroke. evaluated 20 patients with mild to moderate Alzheimer’s disease, and Mixed etiology of CI can be supposed due to neuropsychological we correlated their scores on Neuropsychiatric Inventory syndromes evaluation, but needs confirmation with use of AD biomarkers. (apathy, hyperactivity, affective syndrome and psychosis) with maps of connectivity in the default mode network and salience network. We also compared patients with Alzheimer’s disease to 17 healthy elderly controls regarding default mode network and salience network connectivity P530 and grey matter density, as measured by voxel-based morphometry. All Asymmetry in regional cerebral blood flow subjects underwent a 10 min task-free fMRI at 3 Tesla. in Alzheimer’s disease: association with clinical features We found correlation between decreased connectivity in the posterior cingulate area of the default mode network and apathy, and Y. Uchiyama, M. Iwata, H. Hashida, S. Uchiyama between increased connectivity in the anterior cingulate area of the Tokyo Women’s Medical University, Japanese Red Cross Medical salience network and hyperactivity syndrome (agitation, irritability, Center (Tokyo, JP) aberrant motor behavior, euphoria and disinhibition). These areas Objectives: The purpose of the present study was to determine the were not atrophic in our patients. We found that alterations in the frequency and degree of asymmetrical regional cerebral blood flow intrinsic connectivity of neurofunctional networks may, at least in (rCBF) as well as relationships between clinical features of Alzhei- part, be responsible for behavioral syndromes in Alzheimer’s disease mer’s disease (AD) and asymmetric rCBF at initial assessment. patients, even in areas without significant structural grey matter Methods: We retrospectively selected 59 patients diagnosed with pathology. AD based on the National Institute on Aging-Alzheimer’s and Association workgroups on diagnostic guidelines for Alzheimer’s disease for probable AD who had no remarkable stroke lesions or vascular stenosis. We then analyzed their clinical features including P532 age, duration of disease, Hasegawa Dementia Scale revised (HDS-R), The Golgi apparatus in Alzheimer’s disease brain MRI and N-isopropyl-p-(123) I-iodoamphetamine single photon S. Baloyannis emission computed tomography (123I-IMP SPECT) findings. The Aristotelian University (Thessaloniki, GR) SPECT data of all 59 patients were analyzed using three-dimensional stereotactic surface projections (3D-SSP) and by stereotactic extrac- Alzheimer’s disease (AD) is a devastating disorder of the central tion estimation (SEE). The extent of a significantly decreased rCBF nervous system, involving progressive cognitive impairment, char- and the absolute value of a bilateral difference between each hemi- acterized by profound memory loss, learning inability, behavioral sphere were determined based on SEE findings. changes, resulting in a vegetative state eventually. The aetiopathology Results: The extent of a significantly decreased rCBF was 14.6 ± of A D, remains still unknown, in spite of the continuous research 6.7 % and 14.1 ± 5.0 % in the right and left hemispheres, respec- efforts. The implication of Alphabeta peptide, APP, hyperphospho- tively in all patients. The absolute value of the bilateral difference was rylated Tau protein and synaptic pathology, may contribute in the 5.4 ± 5.0 %. The bilateral difference in the extent of a decreased formation of neuritic plaques, the neuronal loss the synaptic changes rCBF of nine patients was over 10 %, and over 17 % in three of them. and the cytoskeletal alterations, which are the morphological hall- In these patients with a greater bilateral difference, the duration of marks of AD, without explaining sufficiently the innermost disease was significantly longer (P = 0.04) than in the other patients. pathogenetic mechanisms of the disease. Morphological alterations of Age and the HDS-R did not significantly differ between the two the neuronal organelles, mostly concerned the mitochondria, have groups. been described in AD, from the ultrastructural and histochemical Conclusions: About 15 % of patients with AD have [ 10 % point of view. In the present study we attempted to describe the bilateral difference in the extent of a decrease in rCBF at initial morphological alterations of the Golgi apparatus (GA) in early cases assessment. These patients have a longer duration of disease than of AD, in biopsy and post mortem material, studied in electron other patients. Our results revealed that patients with a greater microscopy. It is known that GA plays an important role in glyco- bilateral difference in the extent of decreased rCBF might develop sylation, sulfation. proteolytic processing and trafficking of protein AD earlier. systems, synthesized in the endoplasmic reticulum of neurons and glial cells. The hyperphosphorylation of tau protein, a phenomenon tightly associated with the pathogenesis of AD, is also related with the pathophysiology of GA. In eight cases of Alzheimer’s disease we P531 observed a marked fragmentation of GA in the perikaryon of poly- Neuropsychiatric syndromes in AD are related hedral and pyramidal cells of the hippocampus, the large triangular to functional connectivity alterations in Default Mode neurons of the frontal cortex as well as the Purkinje cells of the and Salience networks cerebellum. The fragmentation of Golgi apparatus may be related to the action of gamma-secretase on APP, it may be associated with the M. Balthazar, F. Pereira, T. Lopes, E. Silva, B. Campos, alterations of microtubules and with loss of dendritic spines and the N. Duncan, A. Coan, F. Stella, G. Northoff, B. Damasceno, alterations of the dendritic arborization, which is prominent even in F. Cendes the early cases of Alzheimer’s disease. University of Campinas (Campinas, BR) Neuropsychiatric syndromes are highly prevalent in Alzheimer’s disease, but their neurobiology is not completely understood. New P533 methods in functional magnetic resonance imaging, such as intrinsic A double-blind, placebo controlled cross-over trial functional connectivity or ‘‘resting-state’’ analysis, may help to clarify of adjunction of donepezil to atypical antipsychotics this issue. The default mode and salience networks are among the most plausible candidates to be associated with mental dysfunctions for cognitive impairment in schizophrenia in Alzheimer’s disease because neurofunctional networks are the F. Fadaii elementary units of the cerebral organization of mental life. We University of Social Welfare (Tehran, IR)

123 S132 J Neurol (2012) 259 (Suppl 1):S1–S236

Rationale: Cognitive dysfunctions in schizophrenia commonly affect P535 attention, memory and executive functions, interfere with functional Parkinsonism-dementia-ALS complex phenotype outcome and are difficult to treat. Previous studies have implicated the cholinergic system in cognitive functioning. Impaired cholinergic in an African-American patient activity might be involved in schizophrenia. Hence the role of cho- D. Kassar, P. Chand, S. Iyadurai linesterase inhibitors (ChEI) as adjunctive therapy is under study. Saint Louis University (St. Louis, US) Method: We conducted a 12 wk double blind, crossed- over trial of Objective: To report a case of PDA phenotype in an African-Amer- donepezil, at doses of 5 mg/day or placebo for 6 weeks, added to ican patient. ongoing atypical antipsychotics in 24 stable schizophrenic in-patients Background: Amyotrophic lateral sclerosis (ALS)/Parkinsonism who were diagnosed according to DSM-IV-TR criteria and had been dementia complex (PDC) is a complex, endemic disorder described in on a stable dose of a high-potency atypical antipsychotic for a min- patients from Guam and the Kii peninsula of Japan. Patients with this imum period of 3 months. After a two weeks wash out period they complex disorder exhibit features of Parkinsonism, akinesia, masked crossed over to the alternate condition for 6 additional weeks. At facies, dysarthria, mental slowness, apathy, depression and gait baseline, 6 and 12 wk, patients were evaluated with the Positive and abnormalities and features of ALS. An environmental cause has been Negative Syndrome Scale (PANSS), Mini-Mental State Examination suggested. However, recently 4 patients from central Europe were (MMSE),Wisconsin Card Sorting Test (WCST) and Wechsler reported to satisfy criteria for PDA, supporting the notion that this Memory Scale Revised Edition (WMS-R). complex disorder may not be purely environmental in origin. Results: All the data were analyzed with both repeated measure- Method: Case report ment analysis of variances and paired T-test. A modest treatment Results: A 59-year old previously healthy, functional African- effect was found for donepezil treatment period in improving American man developed progressive cognitive decline over a period Wechsler Memory Scale Revised Edition (WMS-R). Negative sub- of 2 years. The patient was initially found to have subtle memory scale of PANSS was also improved by donepezil. disturbances, which quickly evolved to an inability to work. Within Conclusion: our study highlights the modest sufficiency of evidence the next few months, the patient lost his ability to speak, eat and to prove ChEI efficacy in the treatment of cognitive dysfunctions and swallow. On neurological exam, the patient was awake and alert, improving negative symptoms in schizophrenia. Larger trials with suf- but anarthric, able to follow simple commands. He had normal ficient duration (at least 6 months) are needed to resolve this issue extra-ocular movements, bifacial diplegia, dysphagia, and positive Glabellar sign. Motor exam showed normal strength, diffuse muscular atrophy, rigidity and bradykinesia. Diffuse hyper-reflexia with sus- P534 tained ankle clonus, positive jaw jerk reflex, primitive reflexes and Oral choline intake-related hypersexuality frontal release signs were noted. Cerebrospinal fluid evaluation, including 14-3-3, was normal. Brain MRI showed fronto-temporal R.S. Calabro`, F. Cordici, P. Bramanti atrophy. Brain FDG-PET showed fronto-temporal hypometabolism. IRCCS Centro Neurolesi ‘‘Bonino-Pulejo’’ (Messina, IT) EMG/NCS revealed diffuse, ongoing denervation in 3 body segments. Objective: Hypersexuality refers to extremely frequent or suddenly Conclusion: Here we describe an African-American patient with increased sexual urges or sexual activity and it is usually associated to constellation of signs similar to what has been previously described in neurodegenerative disorders or to brain injury mainly involving the PDA patients from Guam/Kii. To our knowledge, this is the first temporal lobe. Choline is a water-soluble essential nutrient, grouped report of a non-Guamanian, non-caucasian patient from the American within the B-complex vitamins and used as a dietary supplement in continent, with PDA, supporting a possible non-environmental, different diseases including liver, psychiatric and neurological dis- genetic cause. Additional neuropathological and molecular studies orders such as Alzheimer Disease. will be helpful in analyzing this disease further. Herein we report an elderly patient affected by mild cognitive impairment (MCI) who experienced a pathological increase in libido after choline intake. Methods and Results: An otherwise healthy 79-year-old man came P536 to our observation for memory deficits. Cognitive impairment associated with anti-glutamic Neurological examination, hemotochemical tests, and brain CT acid decarboxylase autoimmunity and type 1 diabetes were within the normal range. Neuropsychological evaluation showed an isolated deficit of short M. Takagi, E. Mori term memory with no functional impact on daily activity. Thus, MCI Tohoku University (Sendai, JP) diagnosis was supposed and oral choline supplementation was pre- Background: Glutamic acid decarboxylase (GAD) is the rate-limit- scribed, but it was withdrawn after 3 weeks because the patient ing enzyme in the synthesis of gamma-aminobutyric acid (GABA). presented with a pathological increase in libido with sexual urges, Anti-GAD antibodies (GADA) are associated with the progression even in inappropriate places. Moreover, while on choline, the patient of stiff person syndrome and other neurological disorders, as well as reported a significant improvement in erectile function. Hypersexu- the immune-mediated diabetes. Whereas GABA is one of the most ality recovered after 5 days of choline withdrawal. widely distributed neurotransmitters in the cerebral cortex, the Conclusion: To the best of our knowledge, this is the first report on cognitive symptoms of GADA-positive patients are not well choline-related hypersexuality. Choline (tetramethylglycine) is the pre- understood. Diabetes is increasingly recognized as a risk factor for cursor of acetylcholine, a parasympathetic neurotransmitter that facilitate dementia; however, the relationship between diabetes and dementia genital blood flow engorgement. Moreover, choline may be converted in is unclear. TMG (trimethylglicyne) and DMG (dimethylglycine), which may be Objective: The aim of this study was to assess cognitive function considered as libido boosters since they are involved, as methyl donors, in in middle-aged patients with GADA-positive diabetes using subjects the metabolism of various hormones and neurotransmitters implicated in with GADA-negative type 2 diabetes as controls. mood and sexual pleasure. Thus, both these centrally and peripherically- Patients and Method: Patients were selected from the diabetic action mechanisms may have played a pivotal role in inducing hyper- outpatients aged 35-65 years. Seventeen patients with GADA-posi- sexuality and improvement in erectile function. tive diabetes (10 females and 7 males; mean age=47.9 ± 7.9) were

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S133 enrolled. The control group was comprised of 17 patients with association between arterial stiffness and cognitive impairment in GADA-negative type 2 diabetes (10 females and 7 males; mean T2D. age=51.9 ± 8.0). The cognitive performance was assessed using the mini mental status examination (MMSE), Wechsler Adult Intelligent Scale 3rd edition (WAIS-III), verbal fluency test, trail making test, Wechsler Memory Scale-story recall, and Rey-Osterrieth complex P538 figure test (RCFT). MRI was performed to evaluate the severity of Neuropsychiatric disorder as presentation T2 hyperintensity lesions using the Scheltens scale. Voxel Based of insulinoma Morphometry (VBM) was performed to assess the gray matter P. Guimara˜es, A. Veiga, A. Costa, A. Velon, J. Gabriel, volume. Result: The characteristics of patients including the number of M. Silva patients with cardiovascular risk factors and diabetic microangiop- Centro Hospitalar de Tra´s-os-Montes e Alto Douro (Vila Real, PT) athies were comparable in both groups. The performance of Introduction: Sudden behavioral disorders requires differential phonemic verbal fluency was lower in the GADA-positive group (p diagnosis between organic etiology, often manifestation of epilepsy, = 0.02). In the GADA-positive group, 6 patients (35 %) had the and psychiatric disorders as hysteria and psychogenic seizures. The scores below the age-adjusted cut off points of RCFT delayed recall, case described below highlights that evaluation must exclude a lot of whereas none in the control group had abnormal score (p = 0.02). organic etiologies before think about psychiatric causes. Case TherewerenodifferencesintheScheltensscaleandthegraymatter Report: Woman, 55 years-old, obese, followed in a psychiatric volume. department with diagnosis of Major Depression and history of Conclusion: Our study showed that GADA-positive diabetic behavior disorder episodes interpreted as hysteria. In the follow-up patients have an increased risk of cognitive decline compared to there was recurrence of these manifestations, which led to the dif- patients with type 2 diabetes of comparable diabetic severity. Exec- ferential diagnosis with epileptic seizures. After the failure of utive dysfunction and memory impairment may occur in middle-aged antiepileptic and antidepressant treatment she was admitted in a GADA-positive population. It also showed that GADA may be neurological department for further investigation. Home-video associated with isolated cognitive decline in the absence of other documentation showed episodes of sudden onset of psychomotor neurological complications. slowing, followed by bizarre behavior, vocalizations and movements of the limbs, followed by depressed level of consciousness. Interictal EEG and CT brain were normal. The evaluation of one of P537 these episodes showed hypoglycemia in capillary analysis and led to the work-up of hypoglycaemic states. Laboratorial tests showed high Increased pulse wave velocity in patients with type 2 values of C-peptide ([7 ng/ml) and subsequently the abdominal CT diabetes and cognitive impairment angiography identified an hypervascularizated pancreatic tumor S. Mehrabian, M. Raycheva, A. Gateva, P. Angelova, compatible with insulinoma which was confirmed after resection in G. Todorova, M. Traykova, T. Stankova, Z. Kamenov, histological examination. It should be noted that the removal of the tumor resulted in complete resolution of this clinical picture. Con- L. Traykov clusion: Hypoglycemia can course with neurological and psychiatric University Hospital Alexandrovska (Sofia, BG) manifestations. The diagnosis of insulinoma should be considered in Introduction: Pulse wave velocity (PWV) is an accepted index of patients with unusual neurological symptoms, as well as in epileptic arterial stiffness and is measured at different sites of the arterial tree, patients refractory to antiepileptic drugs. (video support). such as carotid-femoral pulse wave velocity (CF-PWV) and carotid- radial pulse wave velocity (CR-PWV). Few studies have investigated the relationship between pulse wave velocity and cognitive impair- P539 ment in patients with type 2 diabetes (T2D). Objective: To evaluate the relationship between pulse wave Extracellular amyloid-beta deposits as the major source velocity and cognitive functions in patients with T2D. of the intracellular amyloid cascade, an in vivo study Methods: We studied 39 patients with T2D and 22 normal control focused on mitochondrial damage (NC) subjects. Blood pressure was measured in a sitting and standing S. Rosales-Corral, J. Cruz-Ramos, G. Lo´pez-Armas, position. The pulse wave velocity measurements were taken with the PulsePen (one tonometer). We examined cognitive functions using a D-X. Tan, D. Acunã-Castroviejo, R. Reiter comprehensive battery of neuropsychological tests, assessing the University of Texas (San Antonio, US); Centro de Investigacioń main cognitive domains. Patients with diabetes were classified into 2 Biome´dica de Occidente del Instituto Mexicano del Seguro Social categories according to their cognitive status: normal cognitive (Guadalajara, MX); University of Granada (Granada, ES) functioning and mild cognitive impairment (MCI). Objectives: The hypothesis is: due to its amphipathic nature, its Results: In T2D patients, 57±8 years of age (female 53 %), 51 % physicochemical functions and aided by the induced oxidative stress, (n=20/39) had normal cognitive functioning and 49 % (n=19/39) had amyloid-beta (AB) paves its own pathway in brain, from the extra- MCI. Pulse wave velocity (CF-PWV and CR-PWV) appears signifi- cellular space to mitochondria where it disrupts membrane cantly higher in subjects with T2D than in NC after adjustment for organization and causes energetic dysfunction. This mechanism of age and SBP/DBP (p\0.05). In T2D patients, a significant relation- membrane permeabilization induced by AB and its own internalization ship was observed between CF-PWV and cognitive status. Type 2 might be the major source of intracellular amyloid. Thus, the objective diabetes patients with MCI had significantly higher CF-PWV than was to demonstrate how an extracellular source of AB (intracerebrally those with normal cognitive function (10.9±2.1 vs. 9.2±1.8, p\0.05). injected fibrillar AB) penetrates cells and then invade mitochondria, Conclusion: Our results are in line with previous data suggest that causing membrane disorganization and mitochondrial dysfunction. arterial stiffness of both elastic and muscular arteries is increased in Methods: The effects of AB1-42 intrahippocampal injection were patients with T2D as evidenced by increased PWV measured at dif- compared against the effects derived from the intrahippocampal ferent sites of the arterial system. Furthermore, we revealed an injection of PBS or H2O2. Additionally, animals receiving AB1-42

123 S134 J Neurol (2012) 259 (Suppl 1):S1–S236

(10-4 M) or H2O2 (200lM) injections were subdivided into two P541 groups: with or without antioxidant treatment (melatonin). The cel- Genetics and expression analysis of the transcription lular and subcellular immunoreactivity for AB was explored by light microscopy and immunoelectron microscopy. Mitochondrial free factor Sp4 in patients with Alzheimer’s disease radicals were evaluated using a rosamine derivative. The number, and frontotemporal lobar degeneration form and distribution of mitochondria were evaluated using a selec- D. Galimberti, C. Villa, C. Fenoglio, M. Serpente, tive fluorescence staining. Oxygen uptake, ADP/O ratios and R. Ghidoni, L. Benussi, A. Marcone, S. Cappa, F. Clerici, respiratory control ratios (RCR) were studied by oxygen electrode techniques and the ATPase hydrolytic activity was measured by M. Franceschi, I. Rainero, S. Gallone, E. Ridolfi, L. Ghezzi, colorimetric assay of free orthophosphate. An analysis of the lipid R. Bonsi, C. Cerami, G. Binetti, C. Mariani, N. Bresolin, composition of mitochondrial membranes was carried out by using E. Scarpini gas–liquid chromatography and HPLC. University of Milan, IRCCS Hospital (Milan, IT); IRCCS S.Giovanni Results: We report here that exogenous AB forms deposits in the di Dio Fatebenefratelli (Brescia, IT); Vita Salute University, S. extracellular space, then enters inside the cells particularly through Raffaele Hospital (Milan, IT); University of Milan, Hospital Sacco the axons causing demyelination and, finally, it locates inside the (Milan, IT); IRCCS Multimedica (Milan, IT); University of Turin mitochondria where it causes severe structural and functional dam- (Turin, IT) ages linked to free radical overproduction and significant alterations in mitochondrial membrane lipids. Background: Transcription factor Sp4 (Specificity protein 4) levels Conclusion: Our approach to the in vivo study of the AB1-42 are increased in the brain of patients with Alzheimer’s disease (AD), peptide, the predominant neurotoxic form of AB, was to inject the and Sp4 colocalizes with neurofibrillary tangles. Moreover, Sp4 is a peptide directly into the hippocampus and then examine the rela- susceptibility gene for Bipolar disorder and Schizophrenia which tionship with membrane lipids, in order to explain how AB penetrates share many clinical features with Frontotemporal Lobar Degeneration the cell, approaches the mitochondria and causes the well-known (FTLD). severe dysfunction of this organelle. According to our results, we may Aims: To carry out an association study of Sp4 gene in a population infer that extracellular AB, through a re-entrance mechanism, could of 352 patients diagnosed clinically with AD, 290 patients with FTLD be the major feeding source of the intracellular AB cascade. and 341 age-matched controls. To carry out a transcription analysis. Methods: The distribution of three tagging Single Nucleotide Polymorphisms (SNPs), covering 100 % gene variability, was determined through allelic discrimination. Expression analysis was P540 performed in Peripheral Blood Mononuclear Cells (PBMC). Psychotic symptoms in a frontotemporal dementia Results: No significant differences in either allelic or genotypic cohort frequency of the three SNPs were found (P[0.05). Stratifying ´ according to gender, a trend towards to a decreased frequency of the S. Rocha, F. Sousa, A. Machado Sp4 rs9639379 T allele was observed in male AD patients as com- Hospital de Braga (Braga, PT) pared with male controls (27.9 versus 32.5 %; P=0.057, OR: 0.60, CI: Background: Frontotemporal dementia behavioral variant (bvFTD) 0.37-0.98). A significant increased Sp4 relative expression levels in results from severe frontotemporal degeneration, leading to profound PBMC was observed in patients with AD (7.652±1.405 versus personality and social conduct changes. Delusional and hallucinatory 3.960±0.991, P=0.050) and a similar trend was seen in patients with symptoms have been traditionally regarded as infrequent. Herein we FTLD, as compared with controls (7.816±2.002 versus 3.960±0.991, try to establish its prevalence using our cohort of bvFTD patients. P=0.084). Methods: Cross-sectional observational study, using a standard- Conclusions: According to these results, Sp4 gene does not act a ized chart for data collection. susceptibility factor either for AD or for FTLD. However, the Results: We included 64 patients (36 women) with a current increased production of Sp4 mRNA may result in aberrant expression average age of 71 years [46-88]. The average age at the disease onset of downstream target genes, possibly contributing to the pathogenesis was 66 years [44-87] and the mean follow-up was 2 years. The of both diseases. average GDS was 5. Family history of dementia was reported in 34 %. Previous psychiatric disorders occurred in 44 % (depression was the most common) and 30 % had current depressive symptoms. Motor neuron disease Neuropsychological assessment values were: MMSE 14 ± 10, ADAS-Cog 25± 16, NPI 18 ± 13, FAB 10 ± 6 and FBI 24 ± 10. Parkinsonism signs were found in 15 % and motor neuron disease (MND) signs in 3 %. The overall prevalence of psychotic symptoms P542 was 42 % (delusions 20 %, hallucinations 12 %, both 10 %). No Increased expression of valocin-containing protein delirium type predominated, but hallucinations were mainly of the in the skin of patients with amyotrophic lateral visual modality. There was no statistical correlation between the occurrence of psychotic symptoms and onset age, MND signs pres- sclerosis. An immunohistochemical study ence, pattern of atrophy on CT/MRI or hypoperfusion on SPECT. S. Ono, H. Ishikawa, K. Yasui, T. Yamano, M. Nomura, Discussion: This particular study design can easily overlook occult T. Watanabe, H. Mikami, K. Higashida, H. Fukazawa, and remote symptoms, thus underestimating the true prevalence of T. Tsukie, M. Suzuki this kind of phenomenology in bvFTD patients. Even so, delusions Teikyo University Chiba (Ichihara, JP) and/or hallucinations prevalence in our sample is much higher than previously reported. Additionally, we could not see, as it has also Objectives: So far studies of the skin of amyotrophic lateral sclerosis been described by others, any association between psychotic symp- (ALS) have shown unique pathological and biochemical abnormali- toms and earlier onset age or MND signs presence. Prospective ties in collagen, elastic fibers, and the ground substance. The lack of studies are warranted to more accurately estimate the true prevalence bedsore formation even in the terminal stages in ALS patients is of psychotic symptoms in FTD. considered characteristic. The valocin-containing protein (VCP) is

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S135 one of the most evolutionarily conserved proteins that is ubiquitous onset, 18 % for upper limb onset and 16 % for bulbar onset. No and abundant in cells accounting for more than 1 % of total cellular patient with a rapid spread pattern (two regions within 3 months from proteins. VCP was implicated in the pathogenesis of neurodegener- onset) survived [5 years. ative diseases. Specifically VCP was found in the pathologic lesions Early manifestations of bulbar symptoms within 1 year were in Alzheimer’s disease, Parkinson’s disease, ALS, and polyglutamine associated with worse survival (p\0.001) although no significant repeat diseases. It is unknown, however, whether VCP-positive difference in survival was seen between groups with and without (VCP+) structures are present in ALS skin. bulbar symptoms (p0.51). Methods: Skin biopsy specimens were taken from the left biceps In terms of cumulative occurrence, symptoms spread longitudi- from 20 sporadic ALS patients (61.0 +- 9.4 years) and 20 control nally to adjacent regions. Bulbar function remained preserved in subjects with other neurologic disorders (62.3 +- 9.8 years). Routine 27 %, lower limb function in 10 % and upper limb function in 2.7 %. formalin-fixed paraffin-embedded 6 micrometer sections were Conclusion: The interval between onset and involvement of the immunostained according to standard techniques. A densitometric second region is an important predictor of survival. The data support analysis was performed using an image analysis system. the contiguous anatomical propagation of lower motor neuron Results: Numerous VCP+ cells were observed in the epidermis in involvement in sporadic ALS. ALS patients, which became more marked as ALS progressed, and a small number of cells were seen in controls. VCP immunoreactivity of VCP+ cells was markedly positive in the epidermis and moderately positive in some dermal blood vessels and glands in ALS patients. P544 These findings became more conspicuous as ALS progressed. On the Genetic screening of C9ORF72 hexanucleotide repeat other hand, VCP+ cells of the epidermis, dermal blood vessels and glands in control subjects showed a weak positive reaction even after expansion in 244 Italian patients affected repeated antigen-retrieval trials. The proportion of VCP+ cells in the by amyotrophic lateral sclerosis epidermis in ALS patients (64.0±8.8 %) was significantly higher with and without frontotemporal dementia (p\0.001) than in controls (16.6±16.0 %). There was a significant A. Govoni, R. Del Bo, D. Galimberti, C. Fenoglio, positive relationship (r=0.59, p\0.01) between the proportion and duration of illness in ALS patients. The optical density of VCP+ cells F. Magri, G. Riboldi, M. Ranieri, E. Scarpini, N. Bresolin, in the epidermis in ALS patients (17.7±4.0) is markedly stronger S. Corti, G. Comi (p\0.001) than in controls (12.4±4.2). There was a significant posi- Hospital Maggiore (Milan, IT) tive relation (r=0.61, p\0.01) between the immunoreactivity and Objective: Amyotrophic lateral sclerosis (ALS) and frontotemporal duration of illness in ALS patients. dementia (FTD) are two fatal neurodegenerative diseases; they are Conclusion: The data suggest that changes of VCP in ALS skin are two extremes of a spectrum of clinically, pathologically and genetic likely to be related to the disease process and that metabolic altera- overlapping disorders. Several genes have been discovered as caus- tions of VCP may take place in the skin of patients with ALS. ative for familial and sporadic ALS, namely SOD1, TARDBP, FUS, OPT, VCP and UBQLN2. Recently, an expanded GGGGCC hexanucleotide repeat in a noncoding region of C9ORF72 has been P543 observed in a number of ALS and FTD patients from different geo- Onset and spreading patterns of lower motor neuron graphical regions of origin, making it the most common genetic cause of these diseases identified to date. To define the contribution of involvements predict survival in sporadic amyotrophic C9ORF72 gene expansion to the etiopathogenesis, here we present lateral sclerosis genetic analysis from a large cohort of Italian patients affected by F. Kimura, C. Fujimura-Kiyono, S. Ishida, T. Hosokawa, ALS and FTD/ALS. H. Nakajima, H. Tani, Y. Hirose Methods: All patients (n=244) referred to the ‘‘Department of Neurology-Policlinico Hospital, Milan’’. They fulfilled the El Escorial Osaka Medical College (Takatsukishi, JP) criteria for probable or definite ALS and the Neary criteria for FTD. Objective: The contiguous propagation of TDP-43 from the first Informed consent was obtained for blood collection and genetic affected motor neurons to adjacent neurons may be one of the analysis from each subject. Mutations in SOD1, ANG, TARDBP, mechanisms for spreading of lower motor neuron symptoms observed FUS/TLS, OPTN, VCP, UBQLN2, MAPT and PGRN genes were in patients with sporadic ALS. excluded. The hexanucleotide expansion was determined by repeat- The aim is to define patterns of spread through the order of primed PCR assay, as reported. lower motor neuron involvement (first, second or third order), Results: The hexanucleotide expansion was observed in 6/19 relationships between interval or sites of affected areas from onset familial ALS (FALS) and 10/209 sporadic ALS (SALS) patients; in to involvement of a second region, and prognosis, including 5 year addition, it was detected in 3/16 families affected by FTD+ALS. survival, normal preservation of motor function at onset of respi- Conclusion: Here, we report a mutational screening of the ratory symptoms and cumulative occurrence of each region and C9ORF72 hexanucleotide repeat expansion performed in a large direction of spread. cohort of ALS and ALS/FTD patients. The expansion accounts for Method: 150 patients with sporadic amyotrophic lateral sclerosis around 25 % of FALS and familial FTD-ALS cases and 4.8 % of (ALS) underwent follow-up at 3 month intervals until the appearance SALS cases, thereby establishing that C9ORF72-linked ALS/FTD of respiratory symptoms. Symptom appearances were determined represents a high proportion of cases also in Italy. The clinical phe- using the revised version of the ALS Functional Rating Scale. notype associated to C9ORF72-mutated patients is not homogeneous: Result: Median survival with combined type onset (two regions variability has been observed in terms of age of onset and type of simultaneously) was shorter (18 months) than with bulbar onset (26 progression. The study supports the possible pathological role of months, p0.01). The interval from onset to involvement of the C9ORF72 in motor neuron disease and frontotemporal dementia. second region correlated significantly with survival, independent of However, the relationship between expansions and the clinical phe- particular combinations. 5 year survival rate was 21 % for lower limb notype remains to be clarified.

123 S136 J Neurol (2012) 259 (Suppl 1):S1–S236

P545 where mutant SOD1 is linked to familial ALS. A role of wild type Neuropsychological profiles of patients with primary SOD1 in protein aggregation has been suggested, but is not well understood. Wild type (WT) SOD-1 may participate in the aggre- lateral sclerosis and amyotrophic lateral sclerosis gation process, thereby contributing to neurodegeneration. The goal E. Canu, F. Agosta, N. Riva, A. Chio`, V. Silani, A. Calvo, of this ongoing project is to investigate the SOD-1 protein aggre- S. Iannaccone, G. Comi, M. Filippi gation behavior in a new cell culture model of ALS, utilizing stem Vita-Salute San Raffaele University (Milan, IT); University of Turin cell-derived motor neurons. (Turin, IT); University of Milan, IRCCS (Milan, IT) Methods: We expose cultured neuronal cells that over-express mutant or wild type SOD1 to wild type or mutant SOD1 rhodamine- Objective: To investigate the cognitive profile of patients with pri- labeled seeding fibrils. We study the recruitment of mutant and WT mary lateral sclerosis (PLS) compared with patients with amyotrophic SOD1 into aggregates formed by the multimer seeds with immuno- lateral sclerosis (ALS). cytochemical methods and mass spectrometry. The protein aggrega- Methods: A neuropsychological test battery was administered to tion behavior is correlated with the viability and morphology of the 26 non-demented PLS (age 63 ± 9 years; ALSFRS-r 36±6; disease cells. duration 101±56 months) and 28 non-demented ALS patients (age Results: Neuralized SY5Y cells and human embryonic stem cell- 61±9 years; ALSFRS-r 38±8; disease duration 22±18 months). The derived motor neurons that have been transfected to express WT or assessment investigated global cognition, executive functions mutant SOD-1 take up seeding fibrils. SY5Y cells which have been (including fluency indices controlling for motor disabilities), reason- seeded with mutant G93A-SOD1 fibrils show a reduced survival time ing, visuo-spatial abilities, verbal and visuo-spatial memory, when compared to cells that have been seeded with WT- SOD. language, mood and behaviour. According to Strong criteria (2009), Conclusion: The data thus far from this ongoing study have pro- those patients who scored below the 5th percentile compared to vided evidence that mutant SOD1 fibrils are toxic for neuralized normal population on at least 2 distinct cognitive tests sensitive to SY5Y. We are continuing this project using stem cell-derived motor executive functions were considered to have cognitive impairment. A neurons as the affected cell type in ALS to study the development and diagnosis of behavioral impairment was made in the presence of 2 the composition of the intracellular aggregates. behavioral/mood abnormalities. This work has been supported by National Institutes of Health Results: PLS and ALS patients had similar age, gender and disease grant (P01) NS-49134. severity, and differed in terms of disease duration (p\0.001). Com- pared to ALS, PLS patients showed lower performances in phonemic and semantic fluency indices (p\0.05). They performed similarly in the other tests. According to the Strong criteria, only one PLS (4 %) and one ALS (3.5 %) patients were found to be cognitively impaired. P547 Two PLS (8 %) and 2 ALS (7 %) patients scored below the 5th Evolution of bulbar impairment in amyotrophic lateral percentile in one executive and one non-executive tests (memory or sclerosis language). Three ALS (11 %) patients failed in one executive test and V. Duek, G.E. Rodriguez, R.C. Rey, R.E. Sica, M.I. Rosa in more than one test within another domain (memory or language). Hospital Ramos Mejia (Buenos Aires, AR); University of Buenos One PLS (4 %) presented with a decline in only one executive test, Aires (Buenos Aires, AR) while 4 PLS (15 %) and 6 ALS (21 %) patients failed in only one non-executive test (PLS: 3 language, 1 memory; ALS: 4 language, 1 Objective: To determine the evolution of speech, swallowing and memory, 1 reasoning). No patient was classified as behaviourally voice of patients with amyotrophic lateral sclerosis. impaired. Method: Between 2003 and 2010 126 patients with ALS were Conclusions: PLS and ALS patients showed cognitive deficits evaluated. Mean age was 53.98 years (19 - 79). Diagnosis was made which can be captured by a comprehensive neuropsychological based on criteria defined in the Escorial. Articulation, swallowing, assessment. In all patients, the cognitive deficits involved not only voice and oral-facial praxis were evaluated (by two speech therapists, the executive functions but other domains such as memory and MIR and VD). We used a scale (scale WD) ranging from 1 (normal language. Compared to ALS, PLS patients performed lower on tests function) to 5 (total loss of function) to assess each ability. Average assessing verbal fluency. Whether this is due to the longer disease follow up time was three months; patients were evaluated 3 times duration or to a specific tissue damage needs to be investigated (baseline, one and two). All patients were offered the same treatment further. according to their disability. They were all given the same general recommendations. Results: Between baseline (bl) and one, stability on swallowing and oral facial praxis was observed (swallowing bl = 2.6 ± 0.99, P546 swallowing 1 = 2.56 ± 1.05, p = ns, 2.73 ± praxis bl = 0.98, praxis 1 = 2.71 ± 1.07, p = ns). Between assessments one and two, there was Evaluation of SOD-1 protein aggregation in cell culture a significant deterioration in all functions. In reference to the voice models of ALS and articulation, the rate of decline was lower (bl-1 = 0.065 points/ A. Masoumi, J. Loeterman, M. Chattopadhyay, E. Low, month; voice bl-1 = 0.065 points/month) between baseline and A. Pfeiffer, A. Methner, M. Wiedau-Pazos assessment one than between assessment one and two (1-2 = 0.195 articulation points/month, 1-2 voice = 0.195 points/month). UCLA (Los Angeles, US); Heinrich Heine University (Du¨sseldorf, Conclusion: During the first period (baseline assessment to one), DE) the evolution of these patients in speech, swallowing, voice and oral Objective: Many neurodegenerative diseases such as Alzheimer’s facial praxis was stable and with a slow rate of deterioration. This is disease, Huntington’s disease and amyotrophic lateral sclerosis likely due to both treatment indications as well as the existence of a (ALS) are characterized by the accumulation of protein aggregates. larger number of motor neurons capable of responding at disease Large protein aggregates are seen in later stages of motor neuron onset. The second period (assessment one to two) showed a marked degeneration linked to ALS, when motor neurons are dying. worsening of all studied functions and faster decline. This is probably Mounting evidence points to a role of protein aggregation in cases explained by the progressive death of motor neurons in the brainstem.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S137

P548 Methods: the research was conducted in the city of Porto Alegre, First symptoms and the pathway to diagnosis capital of the State of Rio Grande do Sul, Brazil. According to data of the national census of 2010, the population of Porto Alegre was for patients with amyotrophic lateral sclerosis: 1,409,351 people living in an area of 476.3 km2. All local clinics and a retrospective analysis of the United States centres hospitals that provide specialized assistance to patients with neuro- for Medicare and Medicaid services: medicare muscular disorders were contacted and provided the requested longitudinal claims database information on the patients diagnosed with ALS and followed-up from 2009 to 2010. All neurologists or neurosurgeons were contacted S. Kulke, D. Fitzhenry, L. Grant, D. Martyn, P. Meswani through a message of the Rio Grande do Sul’s Society of Neurology Biogen Idec (Weston, US); Trinity Partners LLC (Waltham, US) and Neurosurgery requesting information from patients diagnosed Objective: This analysis was conducted to investigate the initial with ALS followed up from 2009 to 2010. Finally, the regional symptoms and the time to diagnosis for patients with Amyotrophic association of people with amyotrophic lateral sclerosis was contacted Lateral Sclerosis (ALS) in the United States (US) Centers for Medi- and also provided information on patients registered in the referred care & Medicaid Services Medicare longitudinal claims database. years. The data collected were stored in an Access database and Methods: Quarterly Medicare claims data (5 % patient sample with analysis was made using SPSS. Prevalence stratified by gender and full inpatient, outpatient and physician office claims) were analysed to age was also calculated. determine the pre-diagnosis ALS patient journey. Patients[65 yrs old, Results: on July 31, 2010, 70 patients were alive and diagnosed with [=2 ALS claims (specifically ICD-9 code 335.20) occurring with amyotrophic lateral sclerosis. Considering the population living between Q1 2007-Q4 2009, who were enrolled in Medicare[=2 years in the city in the same period (1,409,351), the estimated prevalence prior to first ALS claim (diagnosis) were included. Codes related to the was 5.0 cases per 100,000 people (95 % CI, 3.9-6.2), being higher for 1st ALS symptom could be diagnosis- or procedure-related. Data on men (5.2/100,000 95 % CI, 3.6-7.2) than for women (4.8/100,000 the most common first symptom of ALS, time from first ALS symptom 95 % CI, 3.4-6.5). The prevalence increased with age peaking in the to diagnosis (measured in quarterly time periods), and patient diag- age group 70-79 years in both genders. noses/tests conducted prior to ALS diagnosis were extracted. Conclusion: this study is the first to estimate the prevalence of Results: A total of 399 patients met the inclusion criteria and ALS in Brazil. It is also one of the first studies of its kind in Latin were analysed. The most common initial ALS symptoms were America. Therefore, an extensive investigation of ALS cases in limb-related (muscle weakness, gait abnormalities), respiratory specialized centers was performed, including contact with neurolo- (shortness of breath, wheezing, cough), and bulbar (speech distur- gists and also through the regional association of people with bance, voice resonance disorder, dysphagia). Limb onset of ALS amyotrophic lateral sclerosis, which is very active in the region. The (73 %) was more common than bulbar onset (17 %), consistent findings of this study show that the prevalence of amyotrophic lateral with published literature. Nine percent of patients presented with sclerosis in the city of Porto Alegre is similar to that reported in other both limb and bulbar onset. The median time to diagnosis from parts of the world. symptom onset, defined by the first appearance of a symptom, that in retrospect was defined as ALS-related (i.e. respiratory difficulties or weight loss), was approximately 2.5 yrs while time from a P550 specific limb or bulbar symptom to diagnosis was approximately 1.8 yrs. Patients with limb onset ALS had a longer time to diag- Hirayama disease: effect of neck flexion nosis from first specific limb/bulbar symptom (2 yrs) than those on somatosensory-evoked potentials and magnetic with bulbar onset (1 yr). A large proportion of patients (72 %) had resonance imaging their first symptom 3.75 to 1.5 yrs pre-diagnosis. Most common G. Piscosquito, E. Salsano, F. Prada, V. Scaioli, tests conducted before or during the quarter of diagnosis included sensory (78 % of patients) and motor nerve (79 %) conduction L. Chiapparini, M. Savoiardo, G. Lauria, C. Marchesi, tests. The majority (83 %) of ALS patients were diagnosed by a N. Milani, D. Pareyson neurologist outside an ALS treatment center. Istituto Neurologico ‘‘C. Besta’’ (Milan, IT) Conclusions: This analysis confirms that there is a delay in diagnosing ALS in the US Medicare population, similar to that observed Objective: To report a series of seven Italian patients with Hirayama in the general population. The development of educational and other Disease (HD) and to investigate electrophysiologically (with tools that can improve recognition and diagnosis of ALS is warranted. somatosensory evoked potentials - SEPs) and radiologically (with This research was funded by Biogen Idec. spinal MRI) the dynamic changes of the cervical dural sac and spinal cord during neck flexion in HD. This is a rare disease characterized by juvenile unilateral or asymmetric wasting and weakness of distal P549 upper limb muscles, due to abnormal forward displacement of the cervical dural sac. Prevalence of Amyotrophic Lateral Sclerosis Methods: Seven patients with a diagnosis of HD according to in the south of Brazil predefined criteria (1) were recruited. All patients underwent SEPs E. Linden Junior, J. Becker, R.S. Scalco, F.T. Rotta, and spinal MRI both in neutral and fully flexed neck position. Par- P. Schestatsky, C.D. Marrone, I. Gomes ticular attention was paid to SEP N13 wave, and to MRI evidence of cord atrophy, intramedullary signal changes, cord compression, pos- ´ Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS) terior epidural tissue, and loss of dural attachment. IgE levels were ´ (Porto Alegre, BR); Hospital Santa Casa de Misericordia de Porto assessed in 6 patients. ´ Alegre (Porto Alegre, BR); Hospital de Clınicas de Porto Alegre Results: There were 6 males and 1 female, with a mean age at onset (HCPA) (Porto Alegre, BR) of 19 years (range 15-32). Six of the patients had unilateral or asym- Objectives: the purpose of the present study was to determine the metric weakness and wasting of distal upper limbs, whereas one had prevalence of amyotrophic lateral sclerosis in the city of Porto Al- proximal involvement prevailing on distal. No patient had sensory egre, Brazil, as well as presenting the prevalence by age group and abnormalities at clinical examination. Serum IgE levels were gender. increased in 3 cases (range 926-1364 U/L; n.v.=10-180). Spinal MRI

123 S138 J Neurol (2012) 259 (Suppl 1):S1–S236 revealed anterior displacement of the posterior dura of the cervico- members may signify that there is an inherited trait. 3) There is no (thoracic) spinal cord on neck flexion in 4 out of 7 patients. In one case remarkable change of sensory NCS with time, suggesting that sen- detachment was anterior rather than posterior, whereas in two cases no sory involvement is caused by a different pathomechanism from dural abnormality was found on neck flexion. Cervical intramedullary motor neuronopathy. signal abnormalities were found in 4 cases. All patients showed normal N13 potential at SEPs in neutral position, whereas neck flexion caused N13 amplitude reduction and/or latency prolongation in all patients (more evident on the clinically involved side). P552 Conclusion: The role of SEPs in HD assessment is debated. Neck Genetic correction of spinal muscular atrophy-induced flexion produced significant changes in N13 potentials in all our HD patients whereas only four of seven had MRI changes suggestive of pluripotent stem cells and motoneurons as a disease HD. Therefore, SEPs proved more sensitive than MRI in diagnosing model and cell source for transplantation HD. We suggest that neck flexion corner at the MRI and SEPs must G. Riboldi, M. Nizzardo, M. Nardini, C. Simone, be standardised and not inferior to 35 degrees (2). M. Falcone, D. Ronchi, C. Donadoni, S. Salani, F. Magri, References: 1. Hirayama K. Juvenile muscular atrophy of distal upper extremity (Hirayama disease). Intern Med. 2000;39:283-90. 2. Hou C F. Rizzo, M. Ranieri, A. Govoni, I. Faravelli, C. Zanetta, et al. How does the neck flexion affect the cervical MRI features of N. Bresolin, G. Comi, S. Corti Hirayama disease? Neurol Sci. 2012 Jan 3. [Epub ahead of print]. Hospital Maggiore (Milan, IT) Objective: Spinal muscular atrophy (SMA) is the first cause of mortality in young children for genetic disease, leading to generalized P551 progressive muscular weakness and atrophy. Patient specific motoneurons can be derived from induced pluripotent stem cells (iPSCs) Sensory neuropathy of X-linked spinobulbar muscular obtained by reprogramming somatic fibroblasts. The aim of the atrophy present work is to genetically correct SMA iPSCs and motoneurons J.Y. Kim, K.D. Park, S.M. Kim, I.N. Sunwoo using single-stranded oligonucleotides in order to demonstrate the Kwandong University (Goyang, KR); Ewha Womans University feasibility of this therapeutic strategy in SMA. (Seoul, KR); Yonsi University (Seoul, KR); Sunwoo & Cho Methods: iPSCs have been obtained reprogramming fibroblasts Neurology Clinic (Seoul, KR) from a SMA patient and his father using a non-viral method through nucleofection of six reprogramming factors carried by non integrating Objectives: X-linked spinobulbar muscular atrophy (X-SBMA) is an oriP/EBNA1 vectors. We administered sequence-specific ODNs into inherited motor neuronopathy characterized by slowly progressive iPSCs to direct the exchange of a T to C at position +6 of exon 7 in weakness and atrophy of proximal spinal and bulbar muscles. How- SMN2 gene resulting in the genetic conversion of SMN2 into SMN1. ever, it is known that subclinical sensory neuropathy can be found. After characterization, iPSCs were differentiated into motoneurons. However, there is no longitudinal study on the time variance of We analyzed morphometric, histochemical and neuropathological sensory neuropathy. The objective of this study is to clarify the features of iPSC-derived motoneurons in vitro and in vivo after electrophysiologic features of sensory neuropathy by cross-sectional transplantation into the spinal cords of SMA mice. We also investi- and longitudinal methods. gated survival and neuromuscular function of transplanted SMA Methods: We analyzed all electrophysiologic data of X-SBMA mice. patients who were genetically confirmed. Clinical and electrophysi- Results: We obtained SMA corrected cell lines without exogenous ologic reports were collected, who had undergone: (1) at least three sequences. Non-viral SMA-iPSC are indistinguishable from healthy sensory nerve conduction study (NCS) (median, ulnar and sural iPSCs and derived motoneurons reproduced disease-specific features nerves), (2) at least four motor NCSs (median, ulnar, peroneal and (reductions in cell number, cell size, and axon length). After genetic tibial nerves), (3) bilateral H-reflexes, which were obtained by stan- correction with SMN2 sequence-specific ODNs we obtained pheno- dard techniques. typically rescued motoneurons which were transplanted into SMA Results: The data of total 41 patients in 37 families were analyzed. mice spinal cord. Microarray analysis showed restoration of wild type There are four in one family and two in the other family. The mean profile in SMA iPSC derived motoneurons after gene correction. age of subjects was 51.6 years at the examination. Eleven patients In vivo analysis also showed increased life span ([50 %) and (26.8 %) of them presented sensory symptoms. Actually, lost or improved phenotype in SMA mice transplanted with wild-type and reduced sensation of distal parts in upper and/or lower extremities corrected SMA motoneurons. was detected in 7 patients (17.1 %). Conclusions: We generated genetically corrected patient-specific Of the 41 patients, abnormality of sensory NCS was identified in iPSCs and derived motoneurons free of exogenous elements. These 26 (63.4 %), whereas abnormality of motor NCS was found in 17 results represent an important achievement in the development of (41.5 %). Sensory nerve action potentials (SNAPs) of sural or ulnar novel therapeutic approaches in SMA. nerves had low amplitudes or were unelicitable in all of them (100 %). Eleven patients had follow-up tests after many years (mean: 8.6 years), in which no or minimal change of sensory NCS was noted, as there was no change in sensory symptoms of patients. There was electrophysiologic similarity between the members of two families, P553 respectively. White-matter damage in pure and complicated Conclusions: In this study, subclinical sensory neuropathy was hereditary spastic paraparesis not commonly found in X-SBMA patients, compared to previous M. Filippi, M. Scarlato, F. Agosta, A. Scarale, E. Canu, studies. The characteristics of sensory involvement can be summarized as followings; 1) The pronounced feature of sensory M.T. Bassi, S. Benedetti, E. Pagani, M. Ferrari, A. Falini, abnormality is undetectable SNAP or reduced amplitude, especially M. Sessa, G. Comi of sural or ulnar nerves. It suggests that sensory neuropathy in Vita-Salute San Raffaele University (Milan, IT); E. Medea Scientific X-SBMA is an axonal process. 2) A similarity between the family Institute (Bosisio Parini, IT)

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S139

Objective: Thin corpus callosum with or without periventricular white based approach showed that, compared with healthy controls, PLS matter (WM) abnormalities and variable patterns of WM atrophy patients had: (i) an increased connectivity to the right primary SMC in have been described in hereditary spastic paraparesis (HSP) patients. the left precentral and supramarginal gyri; and (ii) an increased However, the different topography of brain WM damage in pure and connectivity to the left primary SMC in the right vermis of cerebellum complicated HSP has not been investigated yet. To investigate brain and precuneus. In PLS patients, the enhanced sensorimotor connec- WM damage in patients with pure and complicated HSP. tivity was associated with more severe disability, longer disease Methods: Forty-seven HSP patients (21 pure, 26 complicated) duration, and a more rapid rate of progression. underwent clinical and neuropsychological assessment, genetic Conclusions: PLS patients showed an enhanced RS connectivity in screening, and structural and diffusion tensor (DT) MRI. Nineteen regions that directly subserve or support the motor control. The healthy controls were also studied. Tract-based spatial statistics and observation that those patients with the highest disability and rates of voxel-based morphometry were used. disease progression had the greatest functional connectivity lends Results: In the pure HSP group, there were 11 patients carrying a support to a pathogenic loss of local inhibitory circuitry, rather than SPG4 mutation and one patient with a SPG3A mutation. In the cHSP only compensatory recruitment. group, SPG5 (one case), SPG7 (one case), SPG10 (one case), SPG11 (three cases), and SPG15 (two cases) mutations were found. Although complicated HSP patients performed lower than healthy controls and pure HSP patients in most of the investigated cognitive domains, cognitive deficits in memory and executive functions were also P555 present in pure HSP patients. A distributed pattern of microstructural Cervical cord atrophy in patients with amyotrophic WM damage involving most of the corpus callosum, corticospinal lateral sclerosis: global and voxel-based analyses tracts, and main corticocortical associative tracts, bilaterally, was M. Filippi, P. Valsasina, F. Agosta, N. Riva, M. Copetti, found in both pure and complicated HSP patients compared to controls. In pure HSP patients, WM damage involved mainly the D. Caputo, M. Perini, F. Salvi, A. Prelle, G. Comi posterior brain regions, while in complicated HSP it was equally Vita-Salute San Raffaele University (Milan, IT); IRCCS Casa distributed in the anterior frontal and posterior parietal WM. Com- Sollievo della Sofferenza (San Giovanni Rotondo, IT); Scientific pared to HC, pure and complicated HSP patients showed WM volume Institute Fondazione Don Gnocchi (Milan, IT); Gallarate Hospital loss in the mid-body and splenium of the CC, and brainstem, bilat- (Gallarate, IT); Hospital Bellaria, University of Bologna (Bologna, erally. Complicated HSP patients also showed atrophy of WM IT); Hospital Maggiore di Crema (Crema, IT) adjacent to the left primary motor cortex. Objectives: Studies assessing cervical cord atrophy in patients with Conclusions: DT MRI showed that both pure and complicated amyotrophic lateral sclerosis (ALS) measured the cross-sectional area HSP are associated with a distributed WM damage to the cortico- at a single anatomical level (C2/C3). A new semi-automatic method spinal, inter-hemispheric, and association tracts, suggesting that HSP based on active surfaces (AS) has been recently introduced. In this is a multisystem disorder, with involvement outside the motor system. study, we applied this technique to high-resolution 3D T1-weighted images of the cervical cord to obtain a measure of global cervical cord atrophy and to perform a voxel-based cord atrophy assessment in P554 patients with ALS. Methods: 3D T1-weighted scans of the cervical cord were Resting state functional connectivity alterations acquired from 33 patients with sporadic, mild ALS (mean ALS of the sensorimotor network in primary lateral sclerosis Functional Rating Scale score: 28, range 12-41) and 26 sex- and age- M. Filippi, F. Agosta, E. Canu, A. Calvo, A. Chio`, N. Riva, matched healthy controls. Normalized cervical cord cross-sectional V. Silani, S. Iannaccone, A. Falini, G. Comi area (CSAn) was measured by the AS model. The AS method was also used to create output images reformatted in planes perpendicu- Vita-Salute San Raffaele University (Milan, IT); University of Turin larly to the estimated cord centre line. Unfolded cervical cord images (Turin, IT); University of Milan, IRCCS (Milan, IT) were co-registered into a common standard space, and smoothed cord Objective: Analysis of resting-state fMRI (RS fMRI) reveals the binary masks, produced using the cord outlines estimated by the AS temporal correlation between the low-frequency spontaneous fluctu- approach, were used as input images for spatial statistics. Between- ations in the resting whole-brain. Such fluctuations form functionally- group comparisons of CSAn were performed with a linear regression distinct networks, and resting state fMRI has a potential clinical value model adjusted for subject’s age. A non-parametric kernel estimator as a sensitive marker in several disease states. This study investigated was used to obtain smoothed plots of CSA along the cervical cord. the functional connectivity of the sensorimotor network in patients SPM8 (two-sample t test, adjusted for age, sex and total cervical cord with primary lateral sclerosis (PLS). volume) was used to perform voxel-based comparisons of cervical Methods: RS fMRI was obtained in 24 PLS patients (mean age cord atrophy. 63±9 years; mean ALS Functional Rating Scale score [ALSFRS-r] Results: Average cervical cord CSAn was significantly lower in 37±6; mean disease duration 102±58 months) and 26 healthy con- ALS patients vs. controls (p=0.007). From C1 to C7, a net separation trols (mean age 64±10 years). Independent component analysis (ICA) of the CSAn plots of ALS patients and those of healthy controls was was used to explore the functional connectivity of the sensorimotor detected (p=0.04). Normalization of T1-weighted images was suc- network. Furthermore, regions functionally connected to the right and cessfully run for all subjects. Within-group average probability maps left primary sensorimotor cortex [SMC] were obtained in controls and of the cervical cord were created for controls and ALS patients. PLS patients using a seed correlation analysis. In PLS patients, Significant clusters of cord atrophy were found in ALS patients vs. multiple regression models were performed to assess the association healthy controls, which were mainly located in the anterior sections at between RS connectivity and the clinical variables. C1/C2, and in the posterior and lateral cord columns at C4, C5 and C7 Results: No difference was found in terms of age and gender levels. between PLS patients and healthy controls. Using ICA, an increased Conclusions: Significant atrophy could be detected along the sensorimotor network connectivity in the right precentral gyrus was entire cervical cord in ALS patients. Normalization of 3D T1- found in PLS patients compared with healthy controls. The seed- weighted cervical cord images allowed us to assess the regional

123 S140 J Neurol (2012) 259 (Suppl 1):S1–S236 distribution of cord tissue loss. The regional assessment cord atrophy are challenging for neurologists. The differential diagnosis against might improve our understanding of the pathobiology of ALS. the complete locked-in-syndrome (LiS) may also be difficult. We aimed to investigate a) neurologists’ diagnostic accuracy based on clinical case vignettes, b) their attitudes towards life-sustaining General neurology II treatment (LST), and c) further ethical aspects in the care of these patients. Methods: A case-based online survey with a randomized presentation of VS, MCS and LiS case vignettes was conducted among P556 members of the German Society for Neurology. The vignettes were Noninvasive positive pressure ventilation for conscious drafted by an international expert panel. disturbed patients with central nerve system disease Results: The 503 participating neurologists (response rate 16.4 %) was a representative sample of the society’s members. Case vignettes to avert extubation failure were accurately diagnosed by 86 % of the participants. The LiS case H. Shigemasa, S. Michita, H. Satoshi, K. Naoki was diagnosed more accurately (94 %) than the VS case (79 %) and Tosei Municipal Hospital (Seto, JP) the MCS case (87 %, p\0.001). While only 6 % of the neurologists regarded VS patients to be aware, 46 % believed they would expe- Background: Patients with central nerve system disease are usually rience hunger and thirst, and 77 % thought they were able to feel pain. with conscious disturbance. Post-extubation respiratory disorder is Limiting LST was considered by 92 %, 91 % and 84 % of the par- still big problem and difficult to predict. NPPV has been demonstrated ticipants who accurately diagnosed the VS, LiS and MCS case, to be effective in preventing the need for endotracheal intubation in respectively (p=0.09). While most participants agreed to withhold some patients who present with acute respiratory failure. It is also cardiopulmonary resuscitation, only a minority considered limiting used for patients who develop acute respiratory distress after extu- artificial nutrition and hydration. Neurologists regarded estimating the bation. But there are no coherent criteria especially for the patient of prognosis and determining the patients’ wishes as most challenging. central nerve system disease. Conclusions: In contrast to retrospective clinical studies, the rate Purpose: We applied NPPV for 5 patients in empirical way. We of misdiagnosis was rather low in our study. The neurologists’ atti- assessed effectiveness of NPPV to compare with standard medical tudes were mostly in favour of limiting LST. The degree of awareness therapy in preventing the need for endotracheal reintubation for the seems to be less relevant for treatment decisions than the clinical unconscious patients of central nerve system disease that developed appearance and the kind of treatment measures. The study identified respiratory distress after extubation. important shortcomings in the care of patients with disorders of Objective: From May in 2007 to April in 2010, 253 patients with consciousness. central nerve system disease were treated in our ICU under endotracheal intubated state. Methods: Patients were extubated after they had met Spontaneous Breathing Trial (SBT) criteria. Thirteen Patients developed respiratory P558 distress after extubation. Rate of reintubation or tracheotomy, hospital Transient global amnesia after gastroscopy mortality, Glasgow coma scale (GCS) at extubation, Acute Physiologic Assessment and Chronic Heath Evaluation (APACHE) score were S. Cesar, S. Perdigao measured and evaluated both NPPV group and non-NPPV group. ULSAM (Viana do Castelo, PT) Results: 253 patients consist of 117 male and 117 female, stroke: Introduction: Transient Global Amnesia (TGA) is an amnesic syn- 130, brain tumor: 72, headtrauma: 9, age ave 59.5 (0*88). NPPV drome of sudden onset and complete remission within 24 h. During group consists of age 71-79 (mean 74), stroke: 4, brain tumor: 1. In the episode the patient’s behavior is normal except for the repetitive NPPV group 1/5 patients needed reintubation, and hospital mortality questioning about his immediate circumstances. TGA may be asso- was 0/5. non-NPPV group consists of age 53-83 (mean 70.3), stroke: ciated with emotional experiences, pain, exposure to cold water, 6, brain tumor: 1, headtrauma: 1. In non-NPPV group 5/8 patients exercise and sexual intercourse. Minor diagnostic procedures pre- needed reintubation, and hospital mortality was 2/8. For NPPV and cipitating onset TGA such as gastroscopy or colonoscopy have been non-NPPV group, GCS at extubation was 7-15(mean 13.4) and 3-15 reported. We present a patient who developed TGA after gastroscopy. (mean 10.5) respectively. APACHE score was 7-30 (mean 18.5) for Case report: A 59 year old woman, caucasian, with no previous NPPV group and 5-25 (mean 14.8) for non-NPPV group. medical problems, underwent an upper GI endoscopy (about 15 min Conclusion: In this pilot study, our results suggested patient with duration by a gastroenterologist with 25 years of experience) per- GCS of 13 or higher and APACHE score less than 14 can be good formed with topical pharyngeal lidocaine spray. No biopsies were candidate for NPPV. executed. Fifteen minutes after leaving the endoscopy room and while waiting for her husband, a neighbour noticed she was repeatedly asking, ‘‘why am I here and why was I submitted to the gastros- P557 copy?’’. She appeared unable to remember anything she was told and kept asking the same questions. The episode lasted for 30 min. On Diagnostic accuracy and treatment decision-making examination, two hours after the onset of symptoms, she had a normal in disorders of consciousness and the locked-in- blood pressure and heart rate. Neurologic examination was normal syndrome: a survey among German neurologists except for the anterograde amnesia. Cranial CT scan was negative. K. Kuehlmeyer, E. Racine, N. Palmour, E. Hoster, Her EEG detected no epileptic activity and brain MRI was normal. The patient had no history of similar episodes or of epilepsy. Two G.D. Borasio, R.J. Jox months later she maintained the gap of 30 min with normal neuro- University of Munich (Munich, DE); Institut de recherches cliniques logical examination and had no recurrence of the episode. and McGill University (Montreál, CA); University of Lausanne Conclusion: TGA is commonly considered a benign syndrome and (Lausanne, CH) there are few cases of TGA following medical procedures such as Objectives: Diagnosis and treatment decision making for patients in gastroscopy using topical anesthesia. Autonomic dysfunction or the vegetative state (VS) or the minimally conscious state (MCS) emotional stress during the endoscopic procedure can be the eliciting

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S141 events involved. Vascular and epileptic etiologies were excluded, 32yo she had two thrombophlebitis. Shortly after, she developed uni- leaving the gastroscopy as the only risk factor identified in this case lateral decrease of vision. An optic neuritis was presumed and treated for the TGA. with steroids. By that time she was diagnosed with Behçet disease based on clinical criteria. Two months later she started disturbed behaviour consistent with a psychotic episode requiring hospitalization. Since then she has been treated with olanzapine, remaining stable until 45yo, when P559 she had a new psychotic episode with delusion speech, disinhibition and Hypertrophic pachymeningitis as a neurological dysthymic mood, requiring new admission. Neurological examination manifestation of p-ANCA angiitis was normal. She was diagnosed with a bipolar disorder. The brain I. Xydakis, E. Papageorgiou, K. Psychoyios, V. Koukouni, magnetic resonance imaging (MRI) showed multiple small hyperintense focus at T2, DT and FLAIR, scattered in the subcortical white matter, G. Gkekas compatible with inflammatory nature. Cerebrospinal fluid (CSF) General Hospital of Nikaia, Piraeus (Nikaia, GR) showed three oligoclonal IgG bands unmatched in serum. Electroen- Introduction: Chronic pachymeningitis (CP) is a rare disorder causing cephalography was normal. intracranial or spinal focal or diffuse fibrosis of the dura matter in the Comments: In this case the affective disorder could be interpreted course of infectious, neoplastic or autoimmune diseases. Neurological as a neurological manifestation of Behçet disease. This relationship is manifestations include headache, vomiting, cranial nerve palsies, supported by the abnormalities on MRI and in the CSF. Although rare raised intracranial pressure and focal neurological deficits. We report these reports are important for the understanding of psychiatric dis- a case of a patient with a known positive p-ANCA angiitis who orders, as they suggest an organic cause or contribution in some cases. presented with headache and cranial nerve palsy due to cranial pachymeningitis. Case History: A 72 year old male with a known history of a P561 positive p-ANCA angiitis with renal involvement presented with Quantification of brain metabolite concentration deteriorating long-standing headache and diplopia due to left abdu- of frontal cortex and posterior cingulate gyrus cens palsy. The patient had been under immunosuppressive therapy which was discontinued due to complicated cholecystectomy. The in the healthy mid-life and elderly persons through brain MRI demonstrated enhancement of dura matter. The finding proton magnetic resonance spectroscopy was also present in a previous imaging and it was attributed to sub- P. Zhang, Z.W Shen, H.Y. Dai, Y.Y. Xiao, R.H. Wu arachnoid hemorrhage. A further investigation for systemic angiitis Shantou University (Shantou, CN) with brain and renal angiography was performed, demonstrating significant narrowing of extracranial arteries and to a lesser degree Objective:To study the metabolite characteristic and concentration of left diffuse narrowing of intracranial arteries, while renal arteries were frontal cortex and left posterior cingulate gyrus using proton magnetic normal. A chest CT scan also revealed pulmonary fibrosis in lower resonance spectroscopy in healthy mid-life and elderly persons. lung fields. The lumbar puncture revealed intracranial hypertension, Methods: 1H-MRS data of 26 healthy adults from 40-70 years were high levels of protein with normal glucose, while testing for viruses, divided into three groups (40-50years, 51-60years and 61-70years).They mycobacterium tuberculosis and bacterial infection and cytology were collected by GE 1.5-T MR scallner and the multi-voxels were located exam were negative. Autoantibody serum testing showed positive over in the Semiovale center (TR/TE=1500ms/35ms). The data spectra in ANA and p- ANCA titers with negative anti-PR3, anti-MPO titers. left frontal cortex and left posterior cingulate gyrus were measured by the Considering the imaging findings, serum and CSF results, a diagnosis SAGE software and post—processed using the functool software. of pachymeningitis was established as part of underlying ANCA Results: The calculated concentrations of N-acetylaspartate positive angiitis. The patient was treated with intravenous predniso- (NAA), creatine (Cre), choline (Cho), and myo-inositol (MI) in left lone with gradual improvement of his neurological condition. A frontal cortex were (4.60±2.80) mmol/L, (4.25±1.32) mmol/L, second lumbar puncture revealed normal intracranial pressure, mild (1.57± 0.65) mmo1/L, and (4.88±2.32) mmo1/L, and in left posterior lymphocytic pleocytosis and reduced levels of protein. cingulate gyrus were (6.84±2.10) mmol/L, (5.16±1.64) mmol/L, Discussion: Although chronic pachymeningitis is not a common disor- (1.19±0.46) mmo1/L, and (4.91±2.50) mmo1/L. Results showed that der and its clinical manifestations are not specific, it should be considered in the older persons get a higher MI both in left frontal cortex and left differential diagnosis of neurological manifestations of underlying systemic posterior cingulate gyrus, MI/Cre in left posterior cingulate gyrus and angiitis. Early recognition and treatment of the autoimmune etiology is a lower ratios of NAA/Cre in the left posterior cingulate gyrus. Cho necessary for preventing definite neurological impairment. and Cho/Cre of the group 51-60years were higher in left frontal cortex than other groups. Conclusions :There are variations of the metabolites between the healthy mid-life and elderly persons in the frontal cortex and left P560 posterior cingulate gyrus by Quantitative analysis of in vivo proton Psychotic relapses in Behçet’s disease MR spect. The concentrations of MI, MI/Cre are higher and NAA/Cre I. Moreira, F. Teixeira, I. Almeida, E. Santos lower in the elderly persons than the youngers. Hospital Santo Antońio, Centro Hospitalar do Porto (Porto, PT); Hospital de Ponte de Lima (Ponte de Lima, PT) Introduction: Behçet disease is a multisystemic vasculitis of unde- P562 termined etiology. The central nervous system is involved in about Acute effects of alcohol on human brain: a resting-state 20 % of the cases. The most common presentations of neuro-Behçet fMRI study are aseptic meningoencephalitis, focal neurological deficits and brain H.Y. Zheng, L.M. Chen, L.M. Kong, W.B. Zheng stem syndromes. Psychiatric disorders may also develop, but affective Second Affiliated Hospital, Shantou University (Shantou, CN) disorders are extremely rare. Case report: A 46yo woman, started at 30yo with asymmetric pol- Background and purpose: Prior studies report that amplitude of low- yarthritis, erythema nodosum, oral ulcers, genital ulcers and uveitis. At frequency Fluctuations (ALFF) and regional homogeneity (ReHo) in

123 S142 J Neurol (2012) 259 (Suppl 1):S1–S236 the blood oxygenation level dependent (BOLD) signal are used to with another medical or neurological condition that could explain their assess functional connectivity between different brain regions in presenting symptoms. It is important, when assessing and treating patient resting-state functional magnetic resonance imaging (fMRI). Our with apparent CD, to remain attentive, throughout treatment, to the objective was to assess the value of ALFF and ReHo in detecting the possibility of other conditions that might explain the symptomatolgy. acute effects of alcohol on healthy human brains. Materials and methods: Thirty-two healthy volunteers were studied with conventional MR imaging and resting-state fMRI prior to and after the initiation of acute alcohol administration. With fMRI P564 data acquired during resting state from different breath alcohol con- The broadened spectrum of Caspr2 antibodies: a case centrations (BrACs), we used a ALFF and ReHo method to investigate spontaneous neural activity in the resting state. BrACs of limbic encephalitis with myoclonus and dyskinesias were measured at each time point after drinking to estimate blood B. Balint, J. Regula, K. Wandinger, S. Jarius, alcohol concentrations (BACs). B. Wildemann Results: No abnormalities were found by conventional MR University Hospital Heidelberg (Heidelberg, DE); Institute of imaging at every time point of all subjects. Compared to the prior Experimental Immunology, affiliated to Euroimmun AG (Lu¨beck, alcohol administration, the fMRI analyses showed increasing ReHo in DE) cerebellum, frontal lobe, right internal capsule, left lentiform nucleus, left caudate nucleus, left hippocampal gyrus, left parietal lobe, and Limbic encephalitis (LE) is frequently associated with antibodies (ab) increasing ALFF in the left Caudate Nucleus, left hippocampal gyrus, binding to cells or lysate from cells transfected with voltage-gated left frontal lobe after acute alcohol administration. It also showed potassium channels (VGKC). Recently it has been shown that these decreasing ReHo in the right frontal lobe, left anterior cingulate antibodies may not target VGKC itself but associated proteins, which cortex, right temporal lobe, right hippocampal gyrus and decreasing co-precipitate in diagnostic test systems (Irani et al. 2010). Specific ALFF in the cerebellum, frontal lobe, right temporal lobe and right target structures include contactin-associated protein-2 (Caspr2) parietal lobe. BrAC was significantly increased to reach a peak at 0.5 localised at the juxtaparanodes of myelinated axons. So far, the h of both doses and decreasing gradually. clinical picture of Caspr2-ab associated disorders is based on retro- Conclusion: This resting-state fMRI indicates that brain regions spective identification of patients seropositive for VGKC-ab or with implicated are affected by alcohol and might provide a neural basis the classical features of LE and peripheral nerve hyperexcitablity for alcohol’s effects on behavioral performance. (Irani et al. 2010, Lancaster et al. 2011). Here, we report on a patient with acute LE, myoclonus, ataxia and dyskinesias in whom Caspr2-ab were detected in the absence of VGKC-ab. This 49 year old woman developed over a few weeks the P563 full blown picture of epilepsy, rapidly progressive cognitive decline, Prevalence of unrecognised neurological diagnoses psychotic symptoms, ataxia, dyskinesias, spontaneous generalised ´ in patients referred with conversion disorder myoclonus altogether with Babinskis sign and primitive reflexes. Whilst testing for infectious diseases and other autoimmune antibodies P. Rosebush, M. Mazurek was negative, Caspr2-ab were found. After exclusion of a possible McMaster University (Hamilton, CA) paraneoplastic aetiology, she was treated with high dose prednisolone Objectives: To determine the frequency with which patients referred and azathioprine and made a fairly quick and favourable recovery. with a diagnosis of conversion disorder (CD) are eventually diag- Whilst attempts to characterise the Caspr2-ab associated syndrome nosed with a medical or neurological condition that can fully explain were based on a limited retrospective analysis, this case illustrates their initial presentation. that the clinical presentation might be broader than previously thought Methods: We assessed and followed, over the course of 15 years, and even resemble the picture of prion disease. Awareness of this is 156 patients consecutively referred to our neuropsychiatry service important since non-paraneoplastic Caspr2-ab associated disorders with a diagnosis of CD, who were not involved in litigation. All are responsive to immunotherapies, whilst in paraneoplastic cases patients had been assessed by one or more neurologists and in the vast recognition might lead to diagnosis and treatment of the underlying majority of cases, the referral came directly from a neurologist. tumour. Results: Demographic characteristics were as follows: sex: F=121, Notably, Caspr2-ab were found in the absence of VGKC-ab. Only M=35; Mean age: 36.9 years; Mean duration of CD: 38 months recently, another Caspr2-ab positive, VGKC-ab negative retrospec- (range= 1month -20 years). CD type: pseudoseizures (32 %), paral- tively identified patient was described. The currently used standard ysis (27 %), abnormal movements (20 %), other (20 %). 70 % were radioimmunoprecipitation assay, which uses cell extract, might thus totally disabled and 75 % of patients had another co-morbid psychi- not be sensitive enough to detect Caspr2-ab in all cases and might atric diagnosis. Following referral and during follow-up, 18 patients need to be complemented by Caspr2-specific methods. (12 %) were diagnosed with primary non-psychiatric conditions In conclusion, we wish to point out that specific Caspr2-ab testing including: seizure disorder (n=4) paraneoplastic syndrome (n=2), should be considered (i) in a broader clinical spectrum and (ii) even if dystonia (n=2), mitochondrial disorder (n=1), plexopathy (n=1), VGKC-ab are negative. Correct and early diagnosis is of high complex regional pain syndrome (n=1), neurological migraine (n=1), importance for treatment and prognosis. multiple sclerosis (n=1),herniated lumbar disc (n=1), urethral cys- tocoele (n=1), cortical basal ganglionic degeneration (n=1), retinal degeneration (n=1) and labyrinthine disturbance (n=1). Twelve of the 18 (70 %) had no prior or co-morbid psychiatric illness. 86 % of P565 patients with CD who engaged in treatment recovered fully. FFT: an effective tool to prove the degree of neuronal Conclusions: The literature suggests that approximately 4 % of insult after focal cerebral ischaemia in animal model individuals diagnosed with CD are found, in follow-up, to have another diagnosis that can fully account for their presentation. Our S. Paul, P. Bhattacharya, A. Pandey, N. Sharma, data would suggest that this is an underestimation. In this large series, R. Patnaik followed for 15 years, 12 % of patients were eventually diagnosed Banaras Hindu University (Varanasi, IN)

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S143

The present paper envisages Mathematical modeling of induced focal produced by the bacterium Clostridium botulinum (and rarely by C. cerebral ischemia in animal model using EEG data with the help of butyricum and C. baratii). There are seven distinct neurotoxins (types Fast Fourier Transformation. It was intervened and analysis was A-G) that Clostridium botulinum produces, but types A, B, and E (and undertaken to ensure actual correlation of the different mathematical rarely F) are the common that produce the flaccid paralysis in paradigms. The EEG data was obtained from specific regions of rat humans. brain and was processed by FFT modeling in MATLAB platform. The clinical syndrome of botulism can occur following ingestion The assessment of long lasting functional outcome and to prevalent of contaminated food, from colonization of the infant gastrointestinal classical approach to study stroke was necessitated and therefore tract, or from a wound infection. highly recommended to evaluate the efficacy of therapeutic strategies In this case report we described a women with botulism intoxi- in relation to EEG in animal model of brain stroke. It has been cation on her 16 week of pregnancy. She was admitted in intensive explored to develop an animal model which can manifest the true care unit of ‘‘St. Grigor Lusavorich’’ MC. She was treated with bot- condition of brain stroke, related motor function deficit. This math- ulism antitoxin ABE. The pregnancy was going on without ematical modeling specifically Power Spectrum Density analysis was complications, although the patient was under ALV. On 29 week done to correlate the prevalent condition with the normal condition pregnancy performed cesarean operation, delivered healthy baby. The and condition after pharmacological intervention. patient continue to stay under ALV. She is in vegetative state till now. In literature we found 3 cases of botulism intoxication in pregnant woman. Overviewed literature data shows that botulinum antitoxin has no contraindication for using during the pregnancy. And our data P566 also confirm possibility of good outcome of pregnancy in patient with Eclampsia without pre-eclampsia - a diagnostic botulism. challenge W. Heide, J. Stewen, G. Klefer, Z. Gumienny Allgemeines Krankenhaus Celle (Celle, DE) P568 Background: Eclampsia is a systemic disease of advanced pregnancy Congenital skin pedicles, neuronal migration disorder with neurological symptoms compatible with a posterior reversible and limb anomalies: case report of disorganisation-like encephalopathy syndrome (PRES). We present 3 cases with neuro- syndrome overlapping with amniotic band sequence logical manifestations, not associated with symptoms of preeclampsia (edema, proteinuria, arterial hypertension). R. Rocha, M. Sampaio, D. Alves, S. França, M. Vila Real, Case reports: All 3 patients (first pregnancy) developed progres- M.-L. Silva, M. Leaõ sive left fronto-temporal headache and blurred vision, 2 of them in the Centro Hospitar de Saõ Joaõ (Porto, PT); Centro Hospitar de Vila 26th week of pregnancy, the other 2 days after delivery. Two cases Nova de Gaia (Porto, PT) showed right homonymous hemianopsia, hemisensory loss, progres- Introduction: Congenital skin pedicles are very rare lesions and seem sive aphasia and mild complex-partial epileptic seizures. There were to be a distinctive attribute of human phenotype resembling mouse no signs of edema. Blood pressure was normal, as well as laboratory disorganization model. A review of recent published literature investigations of blood and CSF. The EEG exhibited focal slowing showed a recurrent association of skin pedicles, amniotic band with theta and delta activity over the whole left hemisphere, one case sequence and several different types of brain malformations. also transient spike-wave activity of left occipito-temporal origin. Case report: Male, 23 years old, born at term and uneventfully Cerebral MRI was normal in the beginning, further controls showed from nonconsanguineous parents. He has no facial dysmorphism or mild T2-hyperintense edema of the left temporo-occipital white signs of congenital aplasia cutis. He has two skin pedicles in the right matter. The third patient developed mild ataxia, a single generalized popliteal region and a clefted right nipple. The examination of the tonic–clonic seizure and brain edema in both cerebellar hemispheres. hands reveals a constriction ring of 4th left finger, partial syndactily Cerebral blood flow velocities in transcranial duplex sonography of all fingers and partial agenesis of the right 2nd and 3rd fingers and (TCD) were elevated in all 3 cases and showed turbulences, most of the left 2nd finger. Feet disclose partial syndactily of all toes, pronounced in the left internal carotid and medial cerebral arteries. except for 1st/2nd, and 5th toes distal phalanges agenesis. He has a After caesarian delivery and under intravenous therapy with magne- congenital perisylvian syndrome, manifesting as spastic disartria, sium (in 1 case additionally with valproic acid) neurological bulbar dysfunction and bilateral perisylvian polymicrogyria. In symptoms and MRI abnormalities recovered slowly, but completely. addition, brain MRI shows bilateral perisylvian closed-lip schizen- Conclusions: Neurological symptoms of cerebral origin in cephaly, right temporo-occipital periventricular heterotopia, absent advanced pregnancy often indicate eclampsia, even in the absence of interventricular septum and moderate brain atrophy. pre-eclamptic symptoms. Focal slowing of EEG activity, elevated Conclusion: To the best of our knowledge, there are only a few blood flow velocities in TCD and the development of PRES-like case reports in which periventricular nodular heterotopia has been edema in posterior brain regions in MRI are key findings for diag- associated with amniotic band sequence. The present case discloses nosis. Therapy often requires early delivery by caesarean section and not only those malformations, but also skin pedicles, thus enlarging intravenous magnesium. the phenotypic spectrum of those non-randomly occurring anomalies. This phenotype is clearly evocative of disorganization-like syndrome, previously reported in less than 20 patients. P567 Case of neurobotulism in pregnant women A. Soghoyan, M. Baklavajyan, A. Minasyan, G. Manukyan, P569 L. Zubalova Cranial and extracranial pain pressure thresholds Hospital St.Grigor Lusavorich (Yerevan, AM) evaluated in chronic and episodic migraine Botulism is a serious illness that causes flaccid paralysis of muscles. It O. Grosu, I. Moldovanu, N. Diaconu is caused by a neurotoxin, generically called botulinum toxin, Institute of Neurology and Neurosurgery (Chisinau, MD)

123 S144 J Neurol (2012) 259 (Suppl 1):S1–S236

Objectives: To estimate pressure pain thresholds (PPT) in chronic levels occurring in brains of female rats of 3 months (young), 12 migraine(CM) patients (n=32) and episodic migraine(EM) patients months (adult) and 24 months (old) age groups, and to see whether (n=12) in the whole body not only in cervical or cranial region. these changes are restored to normal levels after exogenous admin- Methods: Migraine patients referred to the Headache Center at the istration of estradiol. National Institute of Neurology and Neurosurgery was consecutively Methods: The aged rats (12 and 24 months old) (n= 8 for each selected. All patients underwent neurological examination, evaluation group) were given subcutaneous injection of 17b-estradiol (0.1 lg/g of anxiety and depression. The migraine diagnosis was established body weight) daily for one month. After 30 days of hormone treat- according to the criteria of International Classification of Headache ment, experimental animals of all the groups were sacrificed and Disorders (ICHD II). PPT was obtained bilaterally by mechanical brains were isolated for further study. pressure algometry, from the 16 anatomic points (ophthalmic nerve, Results: The results obtained in the present work revealed that temporalis muscle, median nerve, radial nerve, ulnar nerve, Achilles normal aging was associated with significant increases in the activity tendon, thenar eminence, suboccipital muscle insertions, trapezius of monoamine oxidase, calcium homeostasis, genomic DNA degra- muscle, supraspinatus muscle, second rib, lateral epicondyle, gluteal, dation, 4- hydroxynonenal and protein oxidation levels in the brains great trochanter, knee) using Somedic algometer (SBMEDIC elec- of aging female rats, and a decrease in membrane polarization. Our tronics, Sweden). Each point was pressed three times and average was data showed that exogenous administration of E2 brought these analyzed. Were used SPSS software, student test, Pearson correlation, changes to near normalcy in aging female rats. average, standard deviation. Conclusions: It can therefore be concluded that E2’s beneficial Results: Study sample consist of 44 patients divided in two groups: effects seemed to arise from its, antioxidant and antilipidperoxidative 12 patients with episodic migraine, mean age 41.5±11.9 and 32 effects, implying a therapeutic potential drug for age related changes. patients with chronic migraine mean age 37.87±15.7. PPT were Based on our studies and others, we conclude that E2 have therapeutic obtained from each point as an average of three consecutive appli- potential for adjunctive therapy along with dopamine replacement cations, from the each side of the body. Mean PPT (for all 16 in PD. examined points) in the episodic group was 436.74±74.34 kPa and chronic migraine 380.98±118.08 (p = 0.067). When was examined each point separately, came out that in the CM group pain pressure thresholds was lower than in EM group for five application points: Child neurology Achilles tendon (CM vs EM 627.67±161.29 vs 526.02±178.78, p=0.049), thenar eminence (CM vs EM, 527.89±69.84 vs 419.0±165.10, p=0.018), suboccipital muscle insertions (CM vs EM, P571 337.93±90.57 vs 283.95± 79.97, p=0.033), greater trochanter (CM vs Nonconvulsive status epilepticus in Egyptian children EM, 623.75±171.35 vs 511.68 ±168.78, p=0.031) and knee (CM vs EM, 451.37±134.49 vs 362.23±134.65, p=0.031). Pearson correla- N. Kitchener, G. Khairalla tion with anxiety, depression and age revealed good correlation of General Organization for Teaching Hospitals (Cairo, EG) pain pressure threshold with age in episodic migraine group (r = Introduction: The recognition of convulsive status epilepticus is 0.86). Negative correlation with anxiety and depression was in both clinically obvious and easily diagnosed. However, the recognition groups. and diagnosis of non-convulsive status epilepticus (NCSE), espe- Conclusion: Pain pressure thresholds are decreased in chronic cially in children, is more difficult. Objective: A retrospective study migraine as compared to episodic migraine not only in cervical and of NCSE to define the syndrome, its classification, frequency, pro- cranial region but in the whole body and can reflect central and posed etiology and symptomatology. Patients and Methods: records peripheral sensitization. of 56 children with the diagnosis of NCSE presented between June 2006 and December 2010 were reviewed. Children were classified according to clinical presentation, EEG pattern and neuroimaging P570 results into: a) Typical absence NCSE, b) Atypical absence NCSE, c) Simple Partial NCSE, and d) Complex Partial NCSE. Results: Of Mechanisms for the protective effects of 17-beta- the 56 Patients, 23 were males and 33 females. Age ranged from estradiol: relevance to depressive symptoms 6.2-14 years. Clinically, 57 % of the children suffer from complex in Parkinson’s disease partial NCSE, 31 % from atypical absence NCSE, 7 % from typical P. Kumar, R. Kale, N. Baquer absence NCSE, and 5 % from Simple Partial NCSE. Cryptogenic etiology is the most frequent (47 %), followed by vascular insults Jawaharlal Nehru University (New Delhi, IN) (18 %). Parkinson’s disease (PD) is a neurodegenerative disease and a Conclusion: children have a higher risk of NCSE than adults. In this movement disorder characterized by loss of dopaminergic neurons in study, most children are known epileptics; cerebrovascular insults were the substantia nigra causing dopamine depletion in the striatum. the second frequent cause of NCSE, after cryptogenic. Clinical suspi- Neurodegeneration in PD occurs due to multiple pathways including cion, EEG or long trace EEG, permits early diagnosis and intervention. oxidative stress, mitochondrial damage, protein aggregation. These changes increase during menopausal condition in females when the level of estradiol is decreased. Recently, there has been a growing interest in the action and functions of the ovarian steroid hormone P572 estradiol, particularly on whether they are neuroprotective for such Somatic mosaicism for a novel mutation in the MPZ age related disease and neurodegenerative conditions like stroke, PD gene and Alzheimer’s disease. P. Lassuthova`, J. Haberlova`, J. Kraus, P. Seeman Objective: The objective of this study was to investigate protective Charles University (Prague, CZ) potential of 17beta estradiol (E2) treatment on the activity of monoamine oxidase, calcium homeostasis, membrane polarization, Objectives: Mutations in the MPZ gene are a frequent cause of genomic DNA degradation, 4- hydroxynonenal and protein oxidation hereditary motor and sensory neuropathy (HMSN). We report a

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S145 family with a patient affected by HMSN III (also called Dejerine- total score was excellent, with ICC = 0.94 (95 %CI: 0.92-0.96) for Sottas) with a novel mutation p.Gly93Ala in the MPZ gene. test–retest reliability and ICC = 0.93 (95 %CI: 0.91-0.96) for inter- Patients and Methods: A proband is a 6 year old boy. He presented rater reliability. with hypotonia, gait disturbances, flat feet, and absence of tendon Conclusion: This study concluded that the Motor Praxis Ability reflexes. Nerve conduction study showed severe slowing of conduc- Test (MPAT) has an acceptable reliability and validity for clinical tion velocities (8 m/s) and small amplitudes. CMT1A was previously assessment of motor praxis ability in Thai children with dyspraxia, excluded. Patient is a sporadic case in the family, both parents and aged between 5 to 8 years. one sister are healthy. Direct sequencing of all 6 coding exons of the MPZ gene was performed. SnapShot analysis targeted to the p.Gly93Ala mutation was done. Results: A novel mutation p.Gly93Ala in the MPZ gene was P574 detected in this patient. The mutation was evaluated as pathogenic by several algorithms, including Poly-Phen2. A causal mutation Childhood-onset torticollis p.Gly93Glu was previously described at this codon. D. Momcilovic-Kostadinovic, A. Potic Other family members were tested for the presence of p.Gly93Ala. University of Belgrade (Belgrade, RS) Mutation was not detected in patient‘s father. This mutation was detected in the mother in small percentage Introduction: Torticollis is not a rare problem in childhood neurology, probably as a result of a somatic mosaicism. The mutation probably often raising many differential diagnostics dilemmas important to be originated de novo during the early embryonic state of patient´s solved properly as implicate burdening diagnostic and treatment mother and is present in a fraction of somatic but also germ cells. procedures patients should be exposed to. Mutation p.Gly93Ala was detected by direct sequencing and also by Methods: The retrospective study included 29 patients mean age the SnapShot analysis. The mutation is present in 12-15 % cells in the 10 years (3-17) presenting with torticollis as the initial clinical DNA sample from peripheral blood. Afterwards, analysis from a manifestation. The mean follow-up duration was 10 years. All the mother‘s saliva DNA sample confirmed the presence of the mutation patients underwent neurologic, neuroophthalmologic and psychologic in different tissue, as well, in approximately the same percentage. examinations as well as electroencephalography (EEG), evoked Clinically, mother is healthy, without any signs of peripheral potentials, electromyoneurography (EMNG) and magnetic resonance neuropathy. Electrophysiological examination showed normal nerve imaging (MRI). conduction velocities and only slightly reduced amplitudes on both Results: 20.7 % of the patients were diagnosed with primary motor and sensory nerves in lower extremities. We therefore propose juvenile dystonia with torticollis as the initial focal sign of the dis- that the presence of 15 % of cells with MPZ mutation in carrier does order (cervical dystonia); 34.5 % of the patients had posttraumatic not have any influence on the clinical phenotype nor affects normal torticollis; 17.2 % of the patients were with iatrogenic drug-induced myelination of peripheral nerves. There is a 12-15 % risk transmis- torticollis (antipsychotics, antiemetics usage); 10.3 % of the children sion of this mutation onto her offspring. were diagnosed with ocular torticollis; torticollis was of psychogenic Conclusion: It is advisable to consider somatic mosaicism in origin in 10.3 % of the patients, whereas in 6.9 % of the studied an families with sporadic disease occurrence. This information is intracranial posterior fossa expansive process was found. In all the important especially for neurogenetic counselling. Somatic mosai- patients diagnosed with primary torsion dystonia MRI and neuro- cism in this carrier did not manifest clinically. physiologic studies were normal as well as in the children with Supported by IGA MH CR NT 11521-4. psychogenic and iatrogenic torticollis. In all the patients with post- traumatic and iatrogenic torticollis and in one patient with endocranial expansive process torticollis developed acutely. Acute or subacute onset of the clinical signs was observed in 65.5 % of the children, while in the remaining 34.5 % the symptoms developed gradually. P573 Left- or right-sided laterocollis was recorded in 72.4 % of the Psychometric properties of the Motor Praxis Ability patients, retrocollis in 20.7 % and anterocollis in 6.9 % of the Test patients. Retrocollis, a rare initial symptom of the disease, was K. Ruttanathantong, W. Siritaratiwat, S. Sriphetcharawut, observed in 33.3 % of the children with primary juvenile dystonia. One child with psychogenic disturbance, one with intracranial J. Saengsuwan expansive process and two children with drug-induced problem also Khon Kaen University (Khon Kaen, TH); Chiang Mai University exhibited retrocollis as the initial clinical manifestation. (Chiang Mai, TH) Conclusion: Posttraumatic torticollis was the most frequent and Objective: The Motor Praxis Ability Test (MPAT) is designed to usually the most benign entity in our study. Intracranial predominantly assess motor praxis ability in children with Pervasive Developmental posterior fossa expansions were the rarest but the most dangerous cause Disorder (PDD), aged between 5 and 8 years. The MPAT was a of childhood torticollis indicating that the acute onset of torticollis may child’s performance measure consisted of seven domains, 39 items. not always reflect a benign nature of the underlying disorder. The child’s performance based assessment tool may be method to determine their motor praxis ability: to recognize and know how to operate with the objects appropriately. The current study aimed P575 to examine the preliminary psychometric properties of the Motor Praxis Ability Test (MPAT). Carpal tunnel syndrome due to tenosynovitis Method: Employing an expert panel discussion method, the MPAT in a four-year-old child has shown well-establish content validity. The examination of internal G. Genç, K. Karabacak consistency, test–retest reliability and inter-rater reliability, were Maresal Cakmak Military Hospital (Erzurum, TR) conducted in 40 children with dyspraxia aged between 5 to 8 years. Results: The analysis of Cronbach’s alpha coefficient revealed an Introduction: Carpal tunnel syndrome (CTS) is the most common acceptable internal consistency of the MPAT in all domains (alpha peripheral compression neuropathy. Although most cases are idio- ranged from 0.61 to 0.90). Test–retest and inter-rater reliability for the pathic, CTS is also associated with some systemic conditions, such as

123 S146 J Neurol (2012) 259 (Suppl 1):S1–S236 rheumatoid arthritis, hypothyroidism, diabetes mellitus, acromegaly, P577 pregnancy and space occupying lesions. CTS is rarely seen in children Dysgraphia in children with assymetric bilingualism and has usually a different clinical presentation compared to adults. Because of this, it may be difficult to make the diagnose. CTS in S. Golubovic, N. Novakovic children has also different etiologies. Mucopolysaccharidosis (MPS) Faculty of Special Education and Rehabil (Belgrade, RS) and family history are seen in the majority of the patients. The other Objectives: The Vlachs of Serbia are an ethnic minority of Serbia, causes of CTS in children are rarely reported in literature. We present culturally and linguistically related to Romanians. a four-year old child with carpal tunnel syndrome secondary to Methodology: The sample consisted of 22 children (from totally tenosynovitis. 113 tested) in early school age, from five rural primary schools around Case report: A 4-year-old girl was brought to our hospital by her Svilajnac and Zabar. 13 children had dyslexic dysgraphia, and 9 had mother because of the persistent pain and numbness in her right hand graphomotor dysgraphia. The study was performed with Abbreviated especially in nights, for one week. The girl described the numbness as version of Semantic test – S. Vladisavljevic, Three-dimensional test ‘the feeling after hitting her hand to the wall by accident’. There was of reading (H. Sax) for assessment of written speech, Scale for no history of any trauma. Neurological examination revealed pares- assessment of dysgraphia of writing (A zheipiarepa, O3iaC), and thesia in first three fingers and positive Tinel’s sign. There was no assessment of performance of graphomotor line (Lillian Lirsa). motor deficit. The thenar muscles were not atrophic. Nerve conduc- Results: Obtained results show that there is a statistically signifi- tion studies of the median nerve showed a decrease sensory nerve cant difference (pi 0.02) on the semantic test in asymmetrically conduction velocity across the wrist and increased distal motor bilingual children regarding to the type of dysgraphia, which means latency. Neurophysiological studies of the other nerves which were that asymmetrically bilingual children with graphomotor dysgraphia performed to exclude Hereditary Neuropathy with Liability to Pres- showed better scores on the semantic test than asymmetrically sure Palsy were normal. Lysosomal storage disease was ruled out. bilingual children with dyslexic dysgraphia. There was a statistically Radiographs and ultrasonography of the right hand were unremark- significant difference (pi 0.04) in the average speed of reading able; but magnetic resonance imaging (MRI) demonstrated a between asymmetric bilingual children regarding to the type of dys- compression of the nerve due to tenosynovitis as a focal enhancing graphia. There is also statistically significant difference (pi 0.01) in lesion. A conservative treatment was initiated. In her one month the average number of errors regarding to the type of dysgraphia. follow-up visit, it was observed that her symptoms recovered com- Asymmetric bilingual children with graphomotor dysgraphia make pletely with this therapy. less number of mistakes than the asymmetric bilingual children with Discussion: Although the numbness, tingling, nocturnal pain, dyslexic dysgraphia. Tinel’s sign and Phalen’s sign were often absent in CTS in childhood, Conclusion: Asymmetric bilingual graphomotor dysgraphic chil- it should be consider that these symptoms may also occur as our case. dren on average remember more facts than asymmetric bilingual As the CTS in childhood presents milder and more unspecific children with dyslexic dysgraphia. symptoms than in adults, every child with even mild symptoms must be thoroughly examined. However surgical treatment is almost always necessary in CTS patients with MPS, we think that CTS may improve with a conservative treatment especially in the absence of P578 space occupying lesions. Pragmatic competence in children with dysgraphia S. Golubovic, G. Colic Faculty of Special Education and Rehabil (Belgrade, RS) P576 Pragmatic ability, in other words communicative competence is Primary cerebral hydatid cyst in a four-year-old child related to pragmatic knowledge and awareness when particular lin- G. Genç, T. Hosbul guistic constructions are used on the most efficient way. Pragmatic Maresal Cakmak Military Hospital (Erzurum, TR) ability means development of language system, cognitive development, memory capacity, ability of making conclusions, integration of Background: Hydatid cyst is a parasitic infestation and usually pre- information’s during following of companions intentions, and previ- sents in the liver and lung. Cerebral hydatid cyst is very rare. The ous knowledge about the world (experience). differential diagnosis of cerebral cystic echinococcosis includes Methodology: Sample consisted of 80 pupils of primary school abscess, cystic tumor, arachnoid cyst, and porencephalic cyst. We ‘‘Cirilo and Metodije’’ in Belgrade, both genders of age between 8 and aimed to present a four-year-old child with cerebral hydatid cyst in 12 years. Children were examined with Test of Pragmatic Language – this report, and review of the clinical and MRI findings because of its TOPL of authors Diana Pheleps – Therasaki & Thrisha Pheleps – rarity and significance of neurological findings. Gunn individually with goal of evaluation of pragmatic, or in other Case Report: A four-year old child was brought by his father to words, social dimension of speech, with norms for children of age our hospital with the complaints of weakness of the right arm and between 5 and 13 years. TOPL consists of 44 questions which are read hand. Neurological exam revealed the monoparesis in the right upper by examiner, and examinee answers on them. For all items (44) there limb. His father told that his son was feeding a dog. Brain MRI are pictures, and it is used narration and context of the stories which showed a cystic lesion resembling a hydatid cyst. Other studies for are close to natural, everyday communication and social interactions. investigating the origin of parasitic infestation revealed no pathology, The main goal of using this test is overall introspect of pragmatic so it was accepted as primary cerebral hydatid cyst. The child was or social language abilities of examined population. Items of this test operated. He recovered partially after surgery, and he was going on are grouped in six essential components of pragmatic abilities. Sub- physiotherapy. scale A - physical surrounding; Subscale B – companions; Subscale C Conclusion: It should be considered that cerebral hydatid cyst may – theme; Subscale D – objective (speech act); Subscale E – visual- occur in especially children who feed a dog or share the house with a gesture allude; Subscale F – abstraction. dog. Early diagnosis and management is very important because of Result: Concerning the fact that children with dysgraphia harder the possibility of the presence of life-threatening findings. begin, maintain, change, elaborate and finish theme in our research,

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S147 they achieved significantly worse results on the test of pragmatics Objectives: Multiple sclerosis (MS) is a chronic inflammatory disease related to children without dysgraphia. In other words, the worst of central nervous system. In the present study, we determined the results are achieved on subscales which are dealing with themes and 3-year follow-up levels of adipokines including leptin, adiponectin, companions in conversation which shows that development of prag- adipsin and resistin in the sera of patients with MS and analysed their matic competence is conditioned with, among the rest, acquiring of association to various clinical parameters including disease activity the life experience, and also language knowledge. In the group of and progression. children with language, or in other words, dyslexic dysgraphia, there Methods: The study was a 3-year prospective follow-up study that are more left-handed children. included 60MS patients, 20 subjects with clinically isolated syndrome (CIS) and 30 healthy controls who underwent neurological examination for 3yrs. Plasma adipokine levels were measured using enzyme ______immunoassay. Results: At the baseline and 1-year follow-up, CIS patients Poster session 3 showed higher levels of resistin than RRMS group (p\0.05). Comparison between the CIS and CIS converted group, the baseline levels of adiponectin seemed to be increased in those subjects who Multiple sclerosis: variants and symptomatic converted to CDMS (p\0.01). The highest levels of adipsin were treatment found in progressive subtypes, while in RRMS adipsin levels remained low during the whole 3-year period (p\0.05). In RRMS group, the levels of adipsin seemed to correlate positively with disability status and progression index (PI) (p\0.05). In PPMS P579 group at the 2yr follow-up, the levels of leptin seemed to correlate Applicability of the revised MRI criteria for multiple with the PI (p\0.05). sclerosis in patients presenting with clinically isolated Conclusions: Our data suggest that leptin, adipsin and resistin syndromes in Russian population might contribute to the development of disability and progression of the disease, while adiponectin seems to be a candidate for moni- I. Shalenkov, B. Shahov, A. Belova toring conversion of CIS to definite MS patients. These adipokines Nizgma (N. Novgorod, RU); NIITO (N. Novgorod, RU) are important in MS pathogenesis and might be potential Objective: to compare the ability of old (2005) and new (2010) sets of biomarkers. MRI criteria (to be used to early diagnose MS in Russian population The study was financially supported by Competitive Research Methods: We report on 51 retrospectively (from 2008 to 2011) Funding of Tampere University Hospital (9M048 and 9N035). recruited patients presenting with clinically isolated syndromes (CIS) suggestive of multiple sclerosis (13 men, 37 women; median age 29±6,1 years): 11 with unilateral optic neuritis, 15 with a brain stem syndrome, 6 P581 with a spinal cord syndrome, and 19 with multifocal lesions. Patients were followed clinically until they developed clinically definite multiple scle- IG-M status in benign multiple sclerosis rosis (CDMS), or for a mean of more than three years if they did not. Their J. Millań-Pascual, L. Turpıń-Fenoll, M. Garcıá-Torres, baseline and follow-up brain and spinal cord MRI studies were retro- M.I. Garcıá-Sańchez, G. Izquierdo-Ayuso spectively evaluated. The sensitivity and specificity of the two sets of MRI Complejo Hospitalario ‘‘Mancha Centro’’ (Alca´zar de San Juan, ES); criteria were calculated. In addition positive (PPV) and negative (NPV) University ‘‘Pablo de Olavide’’ (Seville, ES); Biobanco Hospital predictive value for conversation from CIS to CDMS were determined. Universitario ‘‘Virgen Macarena’’ (Seville, ES); Neurology Service Results: 33 patients (65 %) converted to MS during follow-up. In Hospital Universitario ‘‘Virgen Macarena’’ (Seville, ES) 18 cases (35 %) another than MS diagnoses (migraine, vascular diseases, toxic and traumatic encephalopathy) were established. The Background: Benign multiple sclerosis (BMS) patients show a long- sensitivity specificity, PPV and NPV of the 2005 McDonald criteria (in term mild disability. Due to the elevated cost of immunomodulatory %) were respectively 69, 94, 96 and 63, while that of modified criteria treatment, its side effects and its moderate efficacy the identification were correspondingly 87, 100, 100 and 90. Because of high MRI price of these patients has relevant therapeutic implications. The presence only 41 % of CIS patients passed full baseline MRI examination of Ig-M oligoclonal bands (MOB) in cerebrospinal fluid is related to a included brain gadolinium-enhancing and spinal cord gadolinium- worse prognosis with higher EDSS scores in few years and a poor enhancing scans, 87 % among them met both dissemination in space response to immunomodulatory treatments. Indeed, some groups have and dissemination in time criteria of MS from baseline MRI findings. proposed a more aggressive treatment in patients with a positive Conclusion: In conclusion, the specificity, sensitivity and predictive MOB. value of new criteria among Russian population are the similar to whose Objective: To describe the features of cases diagnosed of BMS which was calculated by international panel in Europe. The possibility to included Ig M OB in two centers: a tertiary care hospital and a sec- establish the MS diagnosis early based on the baseline MRI findings is ond-level hospital during a three-month period. Our work hypothesis very important but the high MRI price is a limitation factor as yet. was that MOB would not be a common finding in a sample of BMS Nizhny Novgorod State Medical Academy patients. Material/methods: Epidemiological data were retrospectively collected on 33 patients with disease duration for at least 10 years, available Ig-M-OB result and a EDSS score \= 3 at 10 years of P580 evolution. Although there is no a consensus definition for ‘‘benign The blood adipokines and their association to disability MS’’ we define a minimal disease evolution with an EDSS score\=3 status and progression index in multiple sclerosis: for at least 10 years since diagnosis as ‘‘benign MS’’. Results: 33 patients were recruited, 24 female. Mean age at a three-year follow-up study onset 29,20 (standard deviation (SD) 9,55); 16 patients were MOB R. Natarajan, M. Raunio, E. Moilanen, I. Elovaara positive. Several characteristics were compared between MOB University of Tampere (Tampere, FI) positive and negative patients. Mean age at onset, first symptoms

123 S148 J Neurol (2012) 259 (Suppl 1):S1–S236

(sensory, motor, optic neuritis, cerebellum and brainstem), EDSS irreversible disability and relapse rates. Although physical and psy- score at diagnosis, EDSS score at five and ten years of evolution, chological sequelae of MS are known to negatively impact on quality last EDSS score, time to a second relapse, multiple sclerosis of life, the association of age at onset with quality of life measures has severity score (MSSS), total number of relapses and relapse rate not been fully explored. showed no statistical difference between groups and no correlation Methods: 102 MS patients completed assessments, including a with a more favourable long-term disability (lower last EDSS locally validated questionnaire that estimates current Extended Dis- score). Only EDSS score at five years of evolution showed a trend ability Status Scale (EDSS) score, and the General Health to a higher result in MOB positive patients (p 0,058). 21 % of total Questionnaire 30 (GHQ30) as a measure of quality of life. Student’s patients were on treatment with immunomodulatory drugs (4/33 t-test was used to compare overall GHQ30 score for patients with age interferon beta or glatiramer acetate and 3/33 natalizumab) at 10 at onset under the age of 30 and over the age of 30, as well as scores years of evolution. Lastly, 15,15 % of total patients (5/33) had a for sub-components of the GHQ30. Statistical modelling was per- last EDSS score [ 3 (range 3,5-10) but only one was Ig-M OB formed using SPSS v19. positive. Results: 80 patients were female. 50 patients had relapsing Conclusion: Benign MS is a controversial entity in the natural remitting MS and 39 patients had SPMS. 41 patients were under history of the disease. In our series biological markers as Ig-M OB the age of 30, and 61 were older than 30 at the onset of disease. have no shown correlation with any feature of the evolution of benign Mean current age was 40.8 in the younger age at onset group and MS, and its presence is not necessarily related to a worse long-term 52.7 in the older age at onset group. There was no significant evolution. difference in current EDSS score in the two groups. GHQ30 total score was significantly higher in the group with disease onset under 30 (p=0.008), indicating a poorer quality of life. Within GHQ30 sub-categories, there was no significant difference between groups P582 for anxiety (p=0.19) or incompetence (p=0.26). However in the Differences in oligoclonal bands and visual-evoked younger age at onset group scores for depression (p=0.003), coping potentials in patients with radiologically and clinically (p=0.03) and social dysfunction (p=0.003) were significantly isolated syndrome higher. Conclusions: Our results suggest that despite a similar level of I. Adamec, M. Radmilovic, V. Posavec, A. Skvorc, disability, patients with a younger age at onset of MS have a poorer M. Boskovic, T. Gabelic, I. Milivojevic, B. Barun, I. Zadro, quality of life than those who are older at disease onset, and that M. Habek increased levels of depression symptoms, poor coping and social Univesity Hospital Center Zagreb (Zagreb, HR); University of Zagreb dysfunction contribute significantly to this difference. Our study (Zagreb, HR); General Hospital Zadar (Zadar, HR) shows no evidence for increased levels of anxiety in the younger onset MS group. Psychological interventions aimed at improving Background: The aim of this study was to determine the prevalence of coping strategies and maintaining social roles may be of particular CSF and VEP abnormalities, and ANA titers in patients with clini- benefit in patients who are younger at disease onset. However, further cally and radiologically isolated syndrome (CIS and RIS). research is required to elucidate the factors underlying these Patients and methods: We gathered records from 330 hospitalized differences. patients diagnosed with CIS/RIS in the three year period. Symptoms, CSF findings, VEP and ANA titers were analyzed. Results: Transverse myelitis was the presenting symptom in 32.7 % (108) of our patients, optic neuritis in 22.7 % (75), P584 brainstem/cerebellar symptoms in 19.4 % (64), hemispheral symp- Age of onset effects on relapse rates in multiple sclerosis toms in 2.7 % (9) and multifocal symptoms in 15.2 % (50) of K.E. Harding, P. Moore, M.D. Cossburn, G. Ingram, patients. We identified 24 (7.3 %) patients with atypical or no symptoms – RIS cohort. Positive OCB were found in 75.5 % (249) T.P. Pickersgill, N.P. Robertson patients. When we divided the patients into CIS and RIS groups Cardiff University (Cardiff, UK); University Hospital of Wales the presence of OCB was 82.4 % and 44 % respectively. VEP was (Cardiff, UK) performed in 87.3 % (288) patients and prolonged latencies were Objectives: Age at onset (AAO) has been shown to affect a number of found in 39.6 % (114) of them. ANA were positive in 15.2 % (50) early features of multiple sclerosis (MS) including degree of recovery of our patients. RIS patients had statistically significant lower from first event, and time to accumulation of fixed disability. Cross percentage of positive OCB and positive VEP (p= 0,002 and 0.001, sectional epidemiological studies also suggest that AAO modifies respectively). relapse frequency. However, longitudinal effects of AAO on proba- Conclusion: Detection of OCB and VEP still have an important bility of occurrence of relapse over the course of the disease have not role for satisfying the ,,no better explanation for the clinical presen- been described in detail and may have significant implications for tation ‘‘criteria when presented with a patient with a first design of interventional studies targeted at the early inflammatory demyelinating episode. phase of disease. Methods: Logistic regression was used to analyse effect of AAO on annualised relapse rates (ARR) following index event over a P583 period of 16 years after disease onset in a population based cohort of patients in SE Wales in whom detailed prospective clinical data was Age at onset affects quality of life measures in multiple available. Incident events were excluded from analysis and results sclerosis corrected for gender and disease course. Statistical modelling was K.E. Harding, P. Moore, J. Feeney, N.P. Robertson performed using R version 2.10.1. Cardiff University (Cardiff, UK) Results: Patterns of relapse frequency in 1836 patients experiencing 6408 relapses were analysed. 1284 (69.9 %) of patients were Background: Age at onset of multiple sclerosis (MS) is known to female. 743 (40.5 %) had relapsing remitting disease, 698 (38.0 %) modulate the clinical manifestation of disease such as mean time to had secondary progressive disease, and 197 (10.7 %) had primary

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S149 progressive disease. Mean AAO was 32.6 years (SD 10.7 years). Identifying genetic variants that affect the outcome of a drug could There was a mean of 0.41 relapses per patient in the first year of help to optimize the patient´s treatment. By giving the right drug disease, and this decreased exponentially over subsequent years. AAO according to the patient’s genotype the risk of developing NAbs and was a significant predictor of relapse frequency for each year fol- the risk of using a drug that lacks efficacy can be reduced. lowing diagnosis (p\0.001). Disease course was a significant This study was supported by an unrestricted research grant from predictor of relapse during the first four years of disease (p=0.004) but Biogen Idec. not thereafter and gender was not associated with probability of relapse frequency at any time point. Conclusions: Our results suggest that in addition to previously recognised effects on disability progression and recovery from P586 relapse, AAO also determines relapse frequency and has a persis- Patterns of regional grey-matter atrophy associated tent effect on ARR for more than 10 years after disease but contrary with PASAT and SDMT performances in relapsing- to popular belief is unaffected by gender. In addition to impacts on remitting multiple sclerosis patients service provision and modelling of therapeutic trials, this also has implications for future research as an understanding of why G. Riccitelli, M.A. Rocca, E. Pagani, V. Martinelli, younger patients experience a greater relapse frequency may help M. Radaelli, A. Falini, G. Comi, M. Filippi to elucidate pathological mechanisms of the inflammatory phase of Vita-Salute San Raffaele University (Milan, IT) disease. Objective: The symbol digit modalities test (SDMT) has been proposed as a promising alternative to the paced auditory serial addition test (PASAT) to evaluate sustained attention, concentration and speed P585 of information processing in multiple sclerosis (MS). We investigated HLA-DRB1*15 and HLA-A*02 are associated the relationship between performance at PASAT and SDMT and the patterns of regional gray matter (GM) atrophy in patients with with higher risk of developing neutralising antibodies relapsing remitting (RR) MS. and clinically relevant titres against interferon-beta Methods: 3D T1-weighted images were acquired from 51 RRMS in multiple sclerosis patients, who were evaluated with PASAT and SDMT tests. Regional J. Link, M. Lundkvist, K. Fink, C. Hermanrud, B. Brynedal, GM atrophy was assessed using VBM and SPM8. GM regions commonly atrophied during the performance of the PASAT and A. Fogdell-Hahn, I. Kockum, J. Hillert SDMT were investigated using a conjunction analysis, while GM Karolinska Institute (Stockholm, SE) regions selectively atrophied during each of the two tests were Objective: Investigate if certain human leukocyte antigen (HLA) class investigated using an exclusively masking procedure. I and II alleles are associated with the susceptibility to develop Results: In RRMS patients, poor PASAT performance was asso- neutralizing antibodies (NAbs) in a Swedish cohort of patients with ciated with GM atrophy in the bilateral caudate nucleus, left multiple sclerosis (MS) treated with interferon-beta (IFN-beta) and cingulum, right inferior frontal gyrus (IFG), bilateral middle frontal whether or not an association with clinically relevant NAb-titers gyrus (MFG), right superior frontal gyrus (SFG), right middle tem- exists. poral gyrus (MTG), bilateral superior temporal gyrus (STG), bilateral Background: A significant proportion of MS patients receiving postcentral gyrus, right supramarginal gyrus, left inferior parietal IFN-beta therapy develop NAbs, which at high titers inhibit the lobule (IPL), right superior parietal lobule (SPL), right middle and therapeutic efficacy. However, NAbs only occur in a subset of superior occipital gyri, and bilateral cerebellum (r values ranging patients, which indicates that factors like the carrying of different from 0.48 to 0.64). Performance at SDMT correlated with GM atro- HLA alleles and the interaction of treatment with HLA could be phy in the left cingulum, right postcentral gyrus, left IPL, left SPL and involved in determining the risk for developing NAbs. bilateral cerebellum (r values ranging from 0.47 to 0.68). Common Materials and methods: 419 patients with known HLA status regions of GM atrophy were detected in the left cingulum, left IPL, matched the strict criteria for NAb-positivity (n=230) and NAb- and left cerebellum. PASAT performance was associated with negativity (n=189). Precise titers were measured with RT-PCR (MxA selective atrophy in the bilateral caudate nucleus, left MFG, right expression). Cut-off for clinically relevant titers was a NAb-titer STG, right supramarginal gyrus, and left IPL, while SDMT perfor- higher than 150 TRU/ml. Statistical dependencies were evaluated mance had a selective association with atrophy in the right with Chi-square test, logistic regression and Wilcoxon rank sum test. cerebellum. Results: The development of NAbs and clinically relevant titers Conclusions: Deficits at SDMT and PASAT are associated to was positively associated with HLA-DRB1*15 allele frequency. distinct patterns of regional distribution of GM atrophy in patients Stratification on treatment revealed that DRB1*15 carriage was with RRMS. associated with clinically relevant titers in Rebif users. HLA-A*02 Study funding. This study was partially supported by a grant from was associated with higher risk of developing NAbs and clinically FISM/2008/R/13. relevant titers when using Betaferon. Conclusions: For each IFN-beta treatment the immunological environment and predisposition of HLA allele groups seem to influ- P587 ence the outcome of NAb development and clinically relevant titers within our material. DRB1*15 had a greater impact on NAb devel- Grey-matter damage predicts the accumulation opment in patients using Rebif, which has an IFN-beta-1a of disability and cognitive impairment 13 years later formulation, implicating the importance for CD4+ T-cells in acti- in patients with multiple sclerosis vating B-cells into plasma cells. The association of a HLA class I M. Filippi, M.A. Rocca, P. Preziosa, M. Copetti, allele with NAb development in Betaferon users suggests that a T-cell independent pathway might be involved, especially as Betaferon has G. Riccitelli, G. Comi an IFN-beta-1b formulation and tend to aggregate more often due to Vita-Salute San Raffaele University (Milan, IT); Biostatistics Unit, the lack of glycosylation. IRCCS Casa Sollievo Della Sofferenza (San Giovanni Rotondo, IT)

123 S150 J Neurol (2012) 259 (Suppl 1):S1–S236

Objective: In multiple sclerosis (MS), the relationship between con- reported. Most common presenting symptoms were alteration of the ventional MRI findings and the clinical evolution of the disease is level of consciousness, motor deficits, seizures and sensory distur- weak. Magnetization transfer (MT) MRI can provide markers bances. All patients had disseminated T2 lesions in the MRI of the reflecting the most disabling features of MS pathology. We assessed brain, affecting particularly the basal ganglia and the periventricular the value of conventional and MT MRI quantities of normal- and subcortical white matter, some of which also showed Gd appearing white matter (NAWM) and gray matter (GM) damage and enhancement. Spinal cord involvement was detected in 4 patients. 4 their 12-month changes in predicting the long-term accumulation of of the patients had a pathological EEG. CSF findings included an disability and cognitive impairment in MS. increase in the cell count in 4 cases, BBB disruption in 4 and path- Methods: Conventional and MT MRI scans of the brain were ological IgG index in one of the patients. Oligoclonal bands were obtained at baseline and after 12 months in 73 patients, who were detected in only one patient. All patients were treated with high doses followed prospectively with clinical visits for a median period of 13 of intravenous methylprednisolone, followed by a gradually tapered years (range 12-17 years). At 13-year follow up, a neuropsycho- 2-4 month peros corticosteroid treatment, except for one case, in logical assessment (Rao’s Brief Repeatable Battery) was also which IVIg was preferred, due to pregnancy. Antiepileptic drugs were performed whenever possible. At baseline and at 12 months, T2- also used in 4 patients. Full clinical recovery within 12 months was hyperintense and T1-hypointense lesion volume, GM fraction, WM achieved in 7 patients, 2 were left with residual neurological deficits fraction, thalamic fraction, average lesion MT ratio (MTR), average and 1 patient died, due to secondary complications. Follow-up MRI GM MTR, average NAWM MTR and thalamic MTR were mea- after 12 months demonstrated incomplete radiological resolution in 6 sured. A multivariate analysis, adjusted for follow-up duration, was cases. performed to establish which variables were significant and inde- Conclusion: ADEM is a rare, though existent disease of the pendent predictors of long-term neurological deterioration and adulthood. Early diagnosis and treatment seem to contribute to a cognitive impairment. better prognosis and outcome. Therefore ADEM should always be Results: At 13-year follow-up, EDSS rating was performed in 67 included in the differential diagnosis of cases characterized by an patients. In 31 of them a neuropsychological evaluation was also acute multifocal neurological dysfunction. performed. Forty-two patients (63 %) showed a significant disability worsening (death=7 patients) and 30 % were cognitively impaired. The multivariate model included baseline GM MTR (p=0.01, OR=0.97), GM MTR percentage change after 12 months (p=0.005, P589 OR=1.22), and percentage reduction of GMF after 12 months (p=0.1, Assessment of clinical characteristics and conversion OR=0.91) as independent predictors of disability worsening at 13 to Neuromyelitis optica in first-episode acute myelitis: years (r2=0.22, C-index=77 %). Baseline GM MTR (p=0.06, a retrospective study of 36 cases OR=0.83) and disease duration (p=0.04, OR=1.97) were the only variables associated to cognitive impairment (p=0.06, OR=0.83, S.Y. Kim r2=0.86, C-index=99 %). Ulsan University Hospital (Ulsan, KR) Conclusions: GM damage is one of the key factors associated with Objective: To identify clinical characteristics and risk of development long-term accumulation of disability and cognitive impairment in MS. of NMO in Korean patients with AM. This study was partially supported by a grant from Fondazione Methods: First episodes of AM were retrospectively identified in a Italiana Sclerosi Multipla (FISM 2010/R/18). single institution. The diagnosis was based on the Transverse Myelitis Consortium Working Group criteria. Patients were excluded if they had a history of prior CNS demyelinating diseases including optic P588 neuritis or transverse myelitis, or had been followed up less than 18 months. Information regarding demographics, clinical status, labora- Acute disseminated encephalomyelitis in adults tory work-up, magnetic resonance imaging of the spine and brain, and T. Tsironis, D. Kiourtidis, M. Krommyda, D. Tsiptsios, electrophysiological assessment were collected. Patients with first- P. Petrou, E. Katsioulis, G. Deretzi, E. Koutlas, ever AM were classified into three groups, depending on their clinical A. Tichalas, I. Tsiptsios course: monophasic AM, recurrent AM, and NMO (including NMOSD). We compared various clinical, laboratory and radiological Papageorgiou General Hospital (Thessaloniki, GR) features between groups. Objective: Acute disseminated encephalomyelitis (ADEM) is an Results: Of 36 patients with first-ever AM, 15(41.6 %) were immune mediated inflammatory demyelinating disease of the central men, 15(41.65 %) experienced clinical relapse and mean segmental nervous system (CNS). It usually occurs following a recent infection length of spinal cord involvement was 4.94. Eight (22 %) out of 36 or vaccination and differs from Multiple Sclerosis (MS) in the fact patients were finally diagnosed as NMO or NMOSD over a mean that it is usually a monophasic entity with a benign course, eventually follow-up period of 40.5 months. 4 patients (one with recurrent leading to a complete or almost complete recession. ADEM is con- myelitis, one with monophasic myelitis, and two with NMO) were sidered a rare childhood disease, with an incidence of 8/100.000 per seropositive for anti-AQP4 antibodies. NMO and NMOSD occurred year and is even rarer in adult populations. Our objective is to present predominantly in female patients compared to monophasic and the three-year experience of a tertiary Greek Hospital in adults with recurrent AM. Sensory level,, sphincter symptoms, abnormal mag- ADEM. netic resonance imaging findings in the brain, and abnormal Methods: Our research is based on data collected by our Neurol- somatosensory evoked potentials were not related to NMO conver- ogy Department, during 2008-2010. All patients included in this sion. In the NMO group, the mean onset age was 43.5±11.8, which research were followed-up for at least 12 months in our MS Outpa- was significantly younger than the monophasic (57.7±1.8) and tient Clinic. recurrent (43.8±14.1) group (p=0.08). Also, the mean longitudinal Results: Among 4.500 patients admitted to our Neurology Clinic involvement segment of spinal cord on T2-weighted images were during a 3 year period, 10 were diagnosed with ADEM (mean age 7.29 and was significantly longer than the monophasic (3.66±1.125) 36,4 years. female/male ratio 8/2). In 6 cases a recent infection was and recurrent (6.43±2.936) groups (p=0.015). Conclusions: In the

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S151 present study, nearly half (41 %) of the patients experienced a P591 clinical relapses. This finding suggests that Korean patients with Painful tonic spasm in neuromyelitis optica: incidence, first-ever idiopathic AM are at a relatively high risk for relapse. Also, in Korean patients with first-episode AM, the mean length of diagnostic utility, and clinical characteristics spinal cord involvement was longer than three vertebral columns S.M. Kim, B. Kim, M. Go, B. Yoon, J. Sung, K. Park, which is compatible with LETM (longitudinally extensive trans- K.W. Lee verse myelitis). Factors such as being female, young age of onset, Seoul National University Hospital (Seoul, KR); Korea University and longer involvement of longitudinal segment of spine, are also Hospital (Seoul, KR); Center for Genome Science; Korea National associated with conversion to NMO. Institute of Health (Osong, KR); Seoul National University Bundang Hospital (Gyeonggi, KR) Objective: To evaluate the diagnostic utility and clinical character- P590 istics of painful tonic spasm (PTS) in neuromyelitis optica (NMO). Methods: This is a retrospective study performed in two major Idiopathic recurrent myelitis: clinical, laboratory, MRI, referral hospitals. Forty patients who had NMO spectrum disorder and electrophysiological characteristics and risk factor with anti-aquaporin4 (anti-AQP4) autoantibody or met the revised of recurrence diagnostic criteria for definite NMO (NMO group); 35 patients with S.B. Kwon, S.S. Hong, J.H. Park, S.H. Suk, S.Y. Kang, multiple sclerosis (MS group); and 41 patients with idiopathic acute transverse myelitis without anti-AQP4 antibody (iATM group). The S. Jung, S.H. Hwang, K.H. Kwon incidence and clinical characteristics of PTS in the different groups, Hallym University (Seoul, KR); SoonChunHyang University diagnostic value of PTS in identifying patients with NMO, and pre- (Seoul, KR); Sangyepaik Hospital, Inje University (Seoul, KR); dictors of PTS in NMO. Ansan Hospital, Wonkang University College of Medicine Results: The incidence of PTS was significantly higher in the (Seoul, KR) NMO group (25.0 %) than in the MS (2.9 %) or iATM (2.4 %) Objectives: Idiopathic acute transverse myelitis (IATM) is a neuro- groups. Most of the PTS attacks (80 %) in the NMO group occurred logical syndrome of unknown etiology resulting from inflammation of after a mean interval of 48.1 days from the onset of the first myelitis the spinal cord. Recently two Korean studies suggested idiopathic attack and were not accompanied by another demyelinating attack recurrent myelitis (IRM) might be a distinct disease entity from with its onset. PTS associated with myelitis had a specificity of recurrent transverse myelitis with MS and recurrent LETM is a new 98.7 % for identifying the NMO group. Myelitis at disease onset was clinical entity rather than being a limited form of NMO in Koreans. a predictor of PTS in the NMO group (RR = 6.545, presence vs. So We undertook this study to clarify the clinical, laboratory, MRI, absence). and electrophysiological characteristics and risk factor of recurrence Conclusions: PTS is a common symptom in NMO. PTS associated of Korean IRM. with myelitis is relatively specific to patients with NMO and is most Methods: The IATM was identified following exclusion of the commonly observed during recovery from the first myelitis attack. cases associated with SLE, Sjoegren’s syndrome, herpes zoster, NMO patients presenting with myelitis at disease onset appear to be at cytomegalovirus, infectious myelitis, NMO, and clinically defined higher risk for developing PTS compared with other NMO patients. MS. We analysed the clinical, Laboratory, MRI, and Electrophysio- logic Findings in IRM. We also defined risk factors in patients with IRM that predict relapses by comparison with idiopathic monophasic myelitis (IMM). P592 Results: We identified 41 patients with a final diagnosis of IATM Anti-aquaporin 4 antibody test in idiopathic from Jan 2005 to Dec 2009. The follow-up time ranged from 31 to demyelinating disease of the central nervous system: 451 weeks (mean 105.2). IATM remained a IMM in 29 patients positive rate and clinical application in Korean cohort (70.7 %) and recurred as IRM in 12 patients (29.3 %). Of the 12 cases of IRM, the majority of patients were male (9/12, 75 %). Mean of 126 patients age at first myelitis was 42.4±10.3 years. IRM showed severe motor S.M. Kim, B.J. Kim, B.N. Yoon, J.J. Sung, K.S. Park, K. Lee impairment in 3 patients (25 %), sphincter dysfunction in 4 patients Seoul National University Hospital (Seoul, KR); Korea University (33.3 %), and 2.8 EDSS on the last clinical visit. On the MR fea- Hospital (Seoul, KR); Seoul National University Bundang Hospital tures, IRM showed LETM in 7 patients (58.3 %), 3.3 vertebral (Seongnam, KR) segment involvement (range 1-8), extended central gray matter Objective: To evaluate anti-aquaporin4 antibody (anti-AQP4 Ab) lesion in 9 patients (75 %), contrast enhanced lesions in all patients, positivity and its diagnostic utility Korean patients with idiopathic lowsignalinT1weightedimagesin1patient(8.3%),andnobrain inflammatory demyelinating diseases of the central nervous system MRI lesions. CSF study revealed pleocytosis (mean 64.5/ul) in (IIDDs). 35.2 % and mean protein 41.6mg/dl. IgG index was 0.33±0.35 and Methods: In total, 126 consecutive patients with IIDDs, who increased in 8.3 %. Somatosensory evoked potentials showed underwent anti-AQP4 Ab testing, were included from the cohort of abnormalities in 50 % of IRM. Oligoclonal bands were all negative. two major referral hospitals in Korea. The positivity of anti-AQP4 Ab Factor associated with relapse in IATM patients according to test and clinical characteristics in individual diagnostic groups, with logistic regression analysis was vertebral segment length of spinal stepwise application of current diagnostic criteria for NMO, other cord lesion. NMOSD, and MS, were assessed. Conclusion: Korean IRM shows several peculiar characteristics Results: The overall positivity of anti-AQP4 Ab testing was including male predominance, frequent LETM, extended gray matter 20.6 % in our patients with IIDDs, and it was high (90 %) in the lesion, and contrast enhancement lesion. The vertebral segment length NMO group but relatively low (26.8 %) in the other NMOSD. High of spinal cord lesion is predictor of relapse in IATM patients. These male predominance (78.8 %) and more monophasic disease course findings may provide prognostic information and therapeutic impli- were significantly associated with negative anti-AQP4 Ab test among cations for Korean patients with IATM. patients with longitudinally extensive transverse myelitis. Once

123 S152 J Neurol (2012) 259 (Suppl 1):S1–S236 patients with other NMOSD with anti-AQP4 Ab or NMO were periventricular with big contrast enhancing lesion involving the right excluded, the positivity of anti-AQP4 Ab testing was very low in cerebral peduncle & midbrain, then she had been diagnosed as patients with MS (0 %) or the other IIDDs (2.6 %). The clinical ADEM disease & she received IV solumedrol with oral antiepileptic characteristics of our MS patients were similar with those previously drugs, clinically she had no neurological deficit. She remained sta- reported in Western populations. ble, fit-free for 1.5 year then she was presented with slurred speech Conclusions: The anti-AQP4 Ab positivity in Korean patients with & unsteadiness followed by tonic–clonic convulsions few days IIDD was relatively high. Though current criteria for other NMOSDs later(June 2010)MRI brain showed multiple focal high signal was not specific to the presence of anti-AQP4 Ab, they can be sen- intensity areas in T2&low in T1 periventricular & subcortical white sitive in identifying patients who have high risks for it. Prior matter of both cerebral hemispheres with involvement of subcortical screening of NMO and other NMOSD with anti-AQP4 Ab seem to be U fibers(mainly at the right side),it involves the right cerebral essential in the differential diagnosis of IIDDs in Korean cohort. peduncle & those lesions are bilateral with asymmetrical distribution,& there is punctuate enhancement of midbrain lesion. With normal cerebellar hemispheres bilaterally she had been diagnosed as Relapsing ADEM disease & received IV solumedrol with impres- P593 sive improvement clinically & radiologically & She had no NMO-IgG antibody in Neuromyelitis optica: sensitivity neurological deficit. 3 months later MRI brain showed decreased and specificity in Iranian patients number of white matter lesions& no enhancement, & 6months later M.H. Harirchian, R. Shasia, A. Tafakhri, F. Mohammadi, MRI brain showed new cerebellar lesions bilaterally & disappearing of the brain stem lesion. 3 months later(March 2011)she had slurred V. Aghamolaee speech & MRI brain showed brain atrophy involving both cerebral Tehran University of Medical Science, Iranian Center for hemispheres more on the left side, with disappearing of the previous Neurological Research (Tehran, IR) lesions & appearing of new ones involving both basal ganglia Background: Neuromyelitis optica is an inflammatory demyelinating symmetrically & other areas of white matter, periventricular & disease (IDD) of the CNS which mainly affects optic nerve and spinal subcortical frontal areas bilaterally. The vasculitis screen was nor- cord. Recently, NMO antibody has been implicated in the patho- mal & CSF analysis showed normal proteins & cells with negative genesis of NMO. The sensitivity and specificity of this test has been OCBs. she received IV solumedrol & got full improvement clini- different in west compared to Asian reports. We aimed to evaluate the cally, but no radiological changes. 9 months later (Jan. 2012) she sensitivity and specificity of NMO antibody assay among IDD had a 3rd attack of tonic–clonic convulsions with mode instability & patients with overlap symptoms with NMO. depression, she had been treated & stabilized with a different type Methods: Based on laboratory, physical examination and imag- of antiepileptic drugs & clinically she is stabilized with no neuro- ing studies, eligible patients referred to our MS clinic within logical deficit at all, & new MRI brain is done & it was worse with December 2009 to June 2011, have been enrolled in this study. remarkable different new lesions & changes that made re-evaluate Recruited patients were 34 definite NMO patients discarding NMO the case & proceed with other investigations still ongoing right now, antibody status, 34 multiple sclerosis patients matched in age and & consider other differential diagnosis list involving Leukodystro- activity of the disease with NMO patients which had history of optic phy diseases as Alexander diseases. neuritis or myelitis and 45 patients with demyelinating optic neuritis or myelitis attacks neither fulfilling criteria of MS nor NMO. Patient’s characteristics recorded in pre-specified questionnaires. P595 Anti-NMO antibody was detected by indirect immunofluorescence method. Prolonged-release fampridine shows consistent efficacy Results: NMO antibody was positive in 11(32.3 %), 0(0 %), across sub-groups of multiple sclerosis patients 3(10 %) and 1(7.1 %) patients with NMO, MS, demyelinating mye- P. Stourac, N. Putzki litis and both demyelinating myelitis and optic neuritis respectively. Masaryk University and Faculty Hospital Brno (Brno, CZ); Biogen NMO antibody was 32.3 CI 95 %(19.1 to 49.1) sensitive to detect Idec (Zug, CH) patients with NMO. Its specificity to differentiate NMO patients from MS patients was 100 % CI 95 % (90 % to 100 %) and was 94.9 % CI Objectives: Phase 3 trials of prolonged-release (PR) fampridine tab- 95 % (87.6 % to 98.0 %) to differentiate NMO from MS and other lets (dalfampridine extended release in the US) showed clinically demyelinating diseases. meaningful improvements in walking ability in 38 % of multiple Conclusion: Our results showed that although NMO antibody is sclerosis (MS) patients. We assessed the response to PR-fampridine highly specific for NMO it is not highly sensitive. Meanwhile, this across a range of baseline characteristics in patients included in these test allows earlier diagnosis of NMO and differentiating it from other Phase 3 trials. IDD with overlap symptoms. Methods: Three groups of subjects from MS-F203/MS-F204 were analysed: placebo (n=190), treatment non-responders (n=214) and treatment responders (n=129). A responder was defined a priori as a subject who walked faster on the Timed 25-foot Walk on at least 3 of P594 4 on-treatment visits compared to the fastest of 5 off-treatment visits. Relapsing ADEM versus other inflammatory Sub-groups were defined by the following characteristics at baseline: demyelinating diseases (case study) disease course, disease duration, expanded disability status scale (EDSS) score, disease-modifying therapy (DMT) use, and presence or E. Darmun, N. Habib absence of spasticity (Ashworth score) and muscle weakness (Lower AOA Hospital of Tripoli (Tripoli, LY) Extremity Manual Muscle Test). An 18 years old libyan girl presented with an attack of sudden onset Results: The lowest and highest of percentage of subjects who of tonic–clonic convulsions 4 years ago(Nov. 2008),she was stabi- responded to PR-fampridine grouped by baseline characteristics were: lized then MRI brain was done & showed few demyelinating lesions disease course 30 % (relapsing-remitting) to 42 % (progressive);

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S153 disease duration 34 % in patients with MS up to 7.0 years to 43 % in P597 patients with MS for more than 18.8 years; EDSS 5.5 or less 35 % to Evaluation of gait in patients treated with prolonged- EDSS 6.5 or greater 41 %; use of DMTs 37 % for any and 40 % for none; and spasticity and muscle weakness present 31 % and absent release fampridine in clinical practice 39 %. For the lowest and highest response rates for each baseline J. Lizrova Preiningerova, K. Kolarikova, E. Havrdova characteristic as listed above, the percentage change in walking speed 1st Faculty of Medicine and General University Hospital (Prague, CZ) (absolute change in walking time) were: disease course 27 % (-2.8 s) Objectives: We report our initial observations with the evaluation of and 22 % (-2.5 s), respectively; disease duration 24 % (-2.3 s) and gait in patients treated with prolonged-release (PR) fampridine in 23 % (-2.4 s); EDSS 26 % (-1.8 s) and 27 % (-3.7 s); use of any clinical practice. DMTs 26 % (-2.8 s) and no DMT 23 % (-2.7 s); spasticity and Methods: PR-fampridine is a new treatment indicated to improve muscle weakness present 28 % (-4.3 s) and absent 24 % (-2.4 s). speed of walking in patients with multiple sclerosis. MS patients with Both the percentage change in walking speed and absolute change in impairment of walking were started on PR-fampridine on first come walking time were significantly different from placebo (p\=0.001) first serve basis and followed by the same clinician over time. Patients for all comparisons. reported their impression of PR-fampridine effects after at least 2 Conclusion: The percentage of patients who responded to PR- weeks. Sixteen out of 17 patients initially reported positive effects. fampridine was relatively consistent across all sub-groups analysed. One of the patients later changed her opinion about the efficacy of the In responding patients, the percentage increase in walking speed and drug. Because of a high proportion of patients reporting positive the absolute change in walking time were also similar across sub- effects, we asked patients to come in without using the drug for 24 h groups and significantly greater than in the placebo groups. These and measured their change in speed of walking at 1 h and 2 h post analyses confirm the consistency of response to PR-fampridine in MS drug administration to document the effects of the drug. Multiple patients with walking impairment. sclerosis walking scale MSWS-12 was obtained just before the first Original studies were funded by Acorda Therapeutics and these prescription and than during the treatment. analyses by Biogen Idec. Results: One patient never came for the test. The group of 14 tested patients who self-reported positive effects had mean age 49 (36-69), man:woman ratio 8:6, mean MSWS12 before PR-fampridine 42 (20-53), mean 25FWT before PR-fampridine 11.69 s. The proportion of patients who had an increase in speed at 2 h post dosing of P596 at least 20 % was 21 % (change in MSWS12=-7.69), increase of at A double-blind, placebo-controlled, study of oral MS14, least 18 % was 43 % (change in MSWS12 = -5.5) and increase of at a herbal-marine drug, on walking ability in multiple least 15 % was 64 % of patients (change in MSWS12 = - 4.75.) Five sclerosis patients out of 14 patients had an increase in speed of walking of 12 % (9- 13 %) Mean change in MSWS12 was -4.7. All patients continued to S.M. Nabavi, M. Naseri, H. Rezaeezadeh, K. Ghareguzli, report positive effects of the treatment. V. Shayegannejad, M. Ghafarpoor, S. Faghihzadeh Conclusion: The proportion of patients who self-reported positive Shahed University (Tehran, IR); Shahid Beheshti University (Tehran, effects of PR fampridine was higher than expected from clinical trials. IR); Isfahan University (Tehran, IR); Tehran University (Tehran, IR); It is more difficult to control in clinical practice variables that can Tarbiat Moddares University (Tehran, IR) influence outcome of the T25FW test (such as different shoes, temperature etc.) Evaluation of the change in speed at the clinic within Objective: Since There is no cure for MS, alleviation of the 2 h post dosing eliminates those factors. Even patients who improved symptoms, enhancement of their quality of life and improvement the speed of walking by about 12 % continued to report positive of the mobility and independency of the patients may be worth effects of the treatment and did not want to discontinue the drug. full as treatment options. One of the major symptom experienced by the vast majority of people with MS is difficulty in walking that interferes with all aspects of their activity of daily living. MS14 is a natural (herbal-marine) product which has been used P598 for multiple sclerosis based on anecdotal evidences in Traditional The effects of combined model of training exercise Iranian Medicine. This is an immune-modulator and anti-inflammatory drug that in a placebo controlled, double blind, cross in functional indexes, fatigue, quality of life and some over clinical trial in MS patients with cerebellar ataxia showed biomarkers of MS patients an improvement in the domain of motility and mobility (lower M.R. Kordi, S.M. Nabavi, S. Khodadadeh, N. Maghsoodi, limb) in the equality of life(QOL). Also the results indicated that L. Anoosheh, M. Asadi, B. Sanglagi MS14 had benefits on other aspects of quality of life in these Tehran University (Tehran, IR); Shahed University (Tehran, IR); Iran patients. MS Society (Tehran, IR) Methods: In this study we evaluated the effects of oral MS14 on Ashworth scale, walking (time get up and go; and timed 10m walk) Objective: to compare three combined model of training on serum level and International Physical Activity Questionnaire items. (IPAQ: long Ghrelin some cytokines(IL10, TNF alpha, IF gamma), functional indexes, form). fatigue, quality of life and EDSS in patients with Multiple Sclerosis. Results: Results showed no significant changes in vital signs, Method: 48 volunteer definite MS patients were recruited biochemical, hematological, liver and kidney function tests. More- and divided into four groups including: experimental 1(n=12), over, the improvement of patients’ mobility in timed to 10meter experimental 2(n=12), experimental 3(n=12) and control (n=12). walking test was significant in comparison to before onset of the Combined training model consisted of: progressive aerobics and treatment and the placebo group (p-value: 0.05). Also these results resistance training. Aerobic training with bicycle and treadmill, per- suggested that MS14 step up Total Moderate Intensity and Total formed at 40-70 % of maximal heart rate and progressive form of Physical Activity Scores (p-value: 0.03). resistance training of lower extremities did according to 1RM from 50 Conclusion: The potential benefits of oral MS14 on QOL in MS to 70 %. Experimental 1,2 and 3 groups performed 3 aerobics training patients by improving walking could be detected by this trial. sessions and 1 resistance training session, 2 aerobics training sessions

123 S154 J Neurol (2012) 259 (Suppl 1):S1–S236 and 2 resistance training session and 1 aerobics training sessions and Conclusion: These results provide preliminary evidence for the 3 resistance training session in a week for 8 weeks, respectively. feasibility and efficacy of a mindfulness intervention for improving Statistics analysis for independent groups was done by ANOVA and symptoms of stress in patients with MS. significance level was considered at 0.05. No conflict of interest. Results: 35 MS patients could successfully terminate the study period (9 person in group 1,8 person in group 2,10 person in group 3 and 8 person in control group) (with mean age; 33.82±7.68 years mean weight; 65.56±11.43kg, BMI; 24.34±4.06kg/m2, EDSS 1.78±0.85). Statistical analysis demonstrated that IL-10 increased in P600 group 3 after training period. TNF-alpha decreased in group 1 and 2, Prevalence of bladder dysfunction in patients whereas it increased in group 3. There were no significant changes in with multiple sclerosis serum Gherlin in any groups. Balance significantly improved in group S. Papachilleos, S. Katsavos, M.E. Evangelopoulos, 1 after training; distance of 6 min walking significantly increased in 1 and 2 groups. E. Andreadou, P. Davaki, A. Rombos, K. Sfangos Strength of left leg significantly improved in 1 and 3 groups. Also Eginition Hosptital, University of Athens (Athens, GR) there was improvement in fatigue scale, quality of life, speed of 10 Bladder dysfunction may occur during the course of multiple scle- and 20-meter walk, mobility and EDSS in all experimental groups. rosis. Although bladder symptoms affect severely patients’ quality of Overall, it seems that group 1 experienced more improvement in life, they may be often overlooked, especially if they occur at the comparison to the other groups. early stages of the disease. Our results showed that 8 weeks of selected exercises in a com- The purpose of the present study was to access the prevalence of bined model decreased the serum levels of cytokines (IFNgamma, bladder dysfunction in MS patients and investigate its association TNFalpha, IL-10)in MS patients, also associated with an significant with clinical disease parameters. improvement in some functional clinical indexes; and disability Five hundred and twenty out of 1500 consecutive patients, fol- levels. lowed at the Unit of Demyelinating Diseases at the Neurology No conflict of interest. Department of the University of Athens between 2004–2011 were screened. We reviewed demographic data, clinical features, clinical course, MRI and cerebrospinal fluid data to identify patients with P599 bladder symptoms. Three hundred and eighteen patients with Relapsing Remitting MS The effects of Mindfulness-based Stress Reduction (RRMS) (mean age: 39.34±10.75years), 115 patients with Clinically programme on physical symptoms, quality of life, Isolated Syndrome (CIS) (mean age: 36.52±10.39 years), 45 patients and mental health in patients with multiple sclerosis with Primary Progressive MS (PMS) (mean age: 48.55±10.28 years) S.H. Granmayeh, M. Besharat, S.M. Nabavi, S. Sadeghi, and 42 patients with Secondary Progressive (SPMS) (mean age: 47.22±9.31 years) were evaluated. Bladder dysfunction was found in A. Imani 102/350 (33 %) patients with RRMS, 10/115 (8 %) patients with CIS, Tehran University (Tehran, IR); Shahed University (Tehran, IR); 30/45 (66 %) patients with PMS and 32/42 (76 %) patients with Buffalo (Buffalo, US) SPMS. A significantly higher prevalence of bladder dysfunction was Background: MS is a disease of the central nervous system affecting found in patients with SPMS (p\0.001) and PMS (p\0.001) com- young population with all economic, financial, social, and psycho- pared to those with RRMS and CIS. logical aspects of individual, family, and community. Performing RRMS patients with bladder symptoms (urgency) had significantly continuous care leads to chronic stress in caregivers of patients and higher EDSS (2.58±0.98 versus 1.83 ± 0.84, p\0.001), pyramidal this in turn threatens their mental health and quality of life. dysfunction (1.71± 0.9 versus 1.07±0.76, p\0.001), and sensory Objective: A Randomized controlled trial was conducted to dysfunction (0.97±0.88 versus 0.66±0.82, p=0.015) compared to investigate the impact of a Mindfulness- Based Stress Reduction those without bladder symptoms. No correlation between bladder (MBSR) program on physical symptom severity, quality of life, and symptoms and sensory-motor deficiencies (EDSS) could be estab- mental health in patients with Multiple Sclerosis. lished in PPMS and SPMS patients. Bladder symptoms in RRMS and Interventions: MBSR is based upon concepts of mental training PMS patients presented 6.39±5.7 and 3.22±2.8 years after disease that propose that non-judgmental awareness of moment-to-moment onset respectively. Bladder dysfunction was the initial symptom in experience. The main aim of MBSR program is to systematically 6/115 (5 %) patients with CIS and in 22/350 (7 %) patients with develop the skill of being present with internal experience(body RRMS. sensation, thoughts, and mood) and with external experience(inter- Bladder symptoms present frequently in RRMS patients but they actions with others, actions in the world), and interplay between these are often underestimated or not attributed to the disease. On the two through the following mindfulness technique: Body scan, mindful contrary, the majority of PMS patients present bladder dysfunction. yoga, and mindful sitting. Its impact on the quality of life at the early stages of the disease as Method: Patients diagnosed with definite MS have been random- well as the increased risk of upper urinary tract complications, at the ized to either an immediate MBSR program (n=12) or waitlist (n=12). progressive stages, indicates the need of a controlled monitoring of The intervention consisted of a weekly MBSR group lasting 2.5 h for the neurogenic bladder in MS patients 8 weeks plus a 6 h retreat. Patients completed questionnaires pre- and post- intervention or waitlist period. And the questionnaires included SF-36, MHI, MSSE, and MAAS. P601 Results: Preliminary analyses revealed the treatment group had fewer overall symptoms of stress, decreased anxiety post- treatment. Smoking and disease progression in MS Improvement was observed in physical symptom severity, quality of A. Manoucherihnnia, C. Tench, R. Bibani, J. Maxted, life, and mental health for MBSR group. Further quantitative analysis J. Britton, C.S. Constantinescu is coming. University of Nottingham (Nottingham, UK)

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S155

Multiple Sclerosis (MS) is the major cause of neurological disability role of these miRNAs in MS. Moreover, the generalized trend towards in young adults. While the increasing importance of MS has prompted miRNA down-regulation observed could determine an over-expres- a surge in research into the disease, there are still gaps in our sion of target gene likely involved in the disease pathogenesis. The understanding of MS, particularly with regard to the role of envi- possibility to determine extracellular miRNAs could represent a new ronmental factors. Though smoking is a frequently studied health source for both biomarker identification and therapy target discovery. behavior in many chronic diseases, its potential contributory role in development and progression of MS remains to be elucidated. Here we explore, for the first time in a very large UK MS cohort the link between the exposure to tobacco smoke and the progression of dis- Cerebrovascular disorders ability in MS. Methodology: Study subjects were patients with clinically definite MS on the database of the Nottingham University Hospital MS clinic. Patients’ lifetime smoking status, disability (EDSS) and MS severity P603 score (MSSS) were obtained from the medical notes. The effects of Paucisymptomatic post-traumatic bilateral internal smoking were assessed using ordered logistic and linear regression carotid artery dissection – case presentation analysis. EDSS scores were modelled both as categorical and linear C. Laza, D. Popescu, A.C. Mergeani, O. Bajenaru, variables. All regression models were adjusted for age, sex, type of MS at the onset of the disease, usage of immunomodulatory treatment F. Antochi and disease duration. University Emergency Hospital (Bucharest, RO) Results: This cross sectional study of a large UK cohort of MS Objectives: to present the case of a 38 year-old patient admitted to our patients showed a 1:2 male:female distribution. The mean age was 49 ward for short episodes of impaired speech occurring in the last 12 h years and mean disease duration was 17 years. 48.56 % were prior to admittance. Two days before the onset of the speech diffi- Relapsing-Remitting, 39.90 % Secondary Progressive and 11.55 % culties he had an episode of right upper limb paresthesia (numbness) were Primary Progressive. 50.39 % were never smoker, 49.61 % were lasting a few hours. The patient reports a sudden movement of the ever smoker at the time of the disease onset. Regression analysis head and neck four days before admittance – recovery movement for showed significant increase in disability and severity scores in ever a fall on an inclined surface. smokers compared with never smokers regardless of the statistical Methods: the patient is a former smoker and occasional alcohol methods. consumer. He denies drug abuse and has no history of significant Conclusion: Our data showed that smoking has a significant cardiovascular pathology. He has multiple chronic dental inflamma- negative effect on the disease progression. Smoking cessation appears tory foci but inflammatory tests were unremarkable. On admission the to be beneficial for MS. patient was stable, with a normal general and neurological examination. The laboratory tests revealed only a slightly elevated serum uric acid. The cerebral magnetic resonance imaging (MRI) showed P602 multiple zones suggestive of subacute ischemic infarcts in the left cerebral hemisphere in the middle cerebral artery territory. The cer- Cell free microRNA and multiple sclerosis: possible vical region MRI showed turbulent blood flow in both internal carotid promising biomarkers? arteries. The ultrasonographic Doppler examination of the cervico- D. Galimberti, C. Fenoglio, E. Ridolfi, M. Serpente, cerebral arteries confirmed bilateral internal carotid artery dissection C. Cantoni, M. De Riz, A. Pietroboni, C. Villa, L. Piccio, without identifying blood clots at this time. The cerebral digital substraction angiogram was normal. N. Bresolin, E. Scarpini Results: antithrombotic therapy was initiated and the patient University of Milan, Fondazione Ca` Granda, IRCCS Hospital (Milan, remained free of symptoms for the remainder of hospitalization. The IT); Washington University (St. Louis, US) three months follow-up ultrasonographic Doppler examination of the Background: Emerging evidence underlines the importance of cervico-cerebral arteries and the cervical region MRI were normal micro(mi)RNAs in the pathogenesis of Multiple Sclerosis (MS). and the cerebral MRI reexamination showed a left temporo-occipital Aim: The main aim of this study was to asses the distribution of cortico-subcortical heterogeneous hyper-/hypo-signal FLAIR lesion, extracellular miRNAs in serum samples from MS patients. without diffusion restriction suggestive for vascular sequela. The Methods. A SAbiosciences miRNA PCR array containing 88 patient was switched to double antiaggregant therapy and remained common miRNAs was initially used to test miRNA levels by real asymptomatic to the present moment. time PCR in serum from 4 patients with Relapsing Remitting (RR)- Conclusion: we chose to present this case because of the pauci- MS, 4 with Primary Progressive (PP)-MS and 4 age matched controls. symptomatic clinical tableau of a potentially cataclysmic pathology. Best hits were replicated by Real time PCR in an additional replication cohort consisting of 15 serum samples from MS patients and 15 from controls. For the replication, TaqMan assays were used and RNU48 and miR24 were employed as endogenous controls. P604 Results: A generalized down-regulation of miRNA levels was Clinical features of primary ischaemic stroke in atrial observed in patients as compared with controls. Statistically signifi- fibrillation patients cant decreased levels of miR-23a, miR-15b and miR-223 were N. Diaconu, A. Grosu, G. Pavlic, C. Gratii observed in patients compared with controls (-2.0 fold regulation, -2.9 Institute of Cardiology (Chisinau, MD); Institute of Neurology and fold regulation and -3.9 fold regulation respectively, P\0.05). Results Neurosurgery (Chisinau, MD) were replicated in the second independent cohort of MS patients. Conclusions: This is the first attempt to determine circulating Background: Stroke caused by atrial fibrillation (AF) has a more miRNAs in MS. Interestingly, miR-223 and miR-15 were already severe evolution, followed by irreversible neurological sequelae and found to be de-regulated in cells from RRMS patients, suggesting a high mortality, that’s why its prevention by identification of risk

123 S156 J Neurol (2012) 259 (Suppl 1):S1–S236 factors and adequate antithrombotic treatment is of significant P606 importance in the management of AF patients. The study aim was to Early and late mortality in patients with stroke determine th impact of AF for stroke occurence and evolution in patients without antecedent thromboembolic events. I.V. Pershyna Methods: It is a retrospective study of all patients with Kharkiv Medical Accademy (Kharkiv, UA) primary ischemic stroke admitted during a year in a large municipal Stroke is associated with a high risk for death, especially in the first hospital. few weeks after the attack. Results: Primary ischemic stroke developed in 519 (70,6 %) Purpose. To identify the frequency and causes of early and late from the total number of 735 examined patients. AF was noted in mortality in patients with stroke. 27.8 % (144/519). AF patients were older than patients with sinus Methods. A 3-year follow-up of 1091 patients with acute stroke rhythm (70,3±0,76 vs 64,4±0,57 years, p\0,001), the majority were treated at the Kharkov City Centre for Acute Cerebrovascular females- 54,2 % (78/144), and with a large spectrum of comorbid- Pathology (Ukraine) have been conducted. ities: ischemic cardiac disease (81,9 % vs 43,7 %; p\0,001), acute Results. Death occurred in 221 patients (20.2 %) within 30 days myocardial infarction (1,4 % vs 0,8 %, p\0,01), old myocardial after stroke onset. The mean age was 68,14 (± 0,75) years. Among infarction (22,9 % vs 11,5 %; p\0,001), heart failure (96,5 % vs these men 48.9 %, women 51.1 %. Ischemic stroke (IS) was diag- 53,1 %; p\0,001), and rheumatic valve disease (10,4 % vs 2,1 %; nosed and confirmed by autopsy in 48.9 %, hemorrhagic stroke (HS) - p\0,001). The majority of cases (77 %) developed a constituted in 51.1 %. The IS and HS ratio was 1/1. The dominant causes of death stroke, mostly in AF group (84 % vs 74,3 %, p\0,05). Sinus rhythm were due to neurologic complications in 79.2 % of patients (blood patients had less severe forms of stroke, like minor, lacunar stroke breakthrough into the ventricles of the brain in 10.7 %, brain swelling and transient ischemic attacks. AF patients had more severe signs of and dislocation of the stem in 68.5 %), cardiac complications in cerebral damage (like consciousness disturbance, walking distur- 8.4 % of patients, pneumonia in 10.2 %, pulmonary embolism in bance and language impairment) on admission vs. sinus rhythm 2.2 %. For survived patients the 1-year, 2-year, 3-year mortalities patients (56,9 % vs 21,2 %, p\0,01), having also a higher hospital were 18 %, 26 %, and 48 % respectively. The main causes of late mortality (27,8 % vs 11,8 %, p\0,001). Among patients with high mortality were as follows: cardiovascular disease (CVD) - recurrent thromboembolic risk after stroke (CHA2DS2VASc [=2) only stroke in 53.5 %; heart disease in 23.5 %, oncology in 12.3 %, sui- 10,9 % had anticoagulant treatment with only 4,9 % within the cide in 2.7 %, unknown in 8 %. optimal therapeutic range (INR 2.0-3.0). Almost half of this group Conclusions. Particular attention in the short-term outcomes (47.1 %) continued aspirine treatment, in disagreement with current should be given to adequate treatment of cerebral edema, thrombosis guidelines. and cardiac pathology. Measures on the secondary prevention of Conclusions: Patients with AF without previous thromboembolic CVD are crucial in reducing of stroke mortality rate in the long-term events have a high stroke risk, with severe evolution. Oral antico- period. agulation in patients with AF and high thromboembolic risk remains very insufficient in the Republic of Moldova. P607 P605 Spectrum of oculomotor disorders in brainstem strokes The relationship between anti-coagulation therapy K. Antonenko and acute-stage recurrent embolism in patients National O.O. Bogomolets University (Kiev, UA) with cardiogenic stroke Diagnosis of brainstem stroke can often be challenging, particularly in C. Kijima, S. Yutani, W. Takahashi, S. Takizawa, S. Takagi the acute stage when CT scans and MRI picture are normal or show only subtle changes. Tokai University (Isehara, JP) Objectives: To evaluate the significance of oculomotor disorders Objective: To assess the role of anti-coagulation therapy for recur- for clinical diagnostics of acute brainstem infarcts. rent acute-stage embolism in cardiogenic embolic stroke, we Materials and methods: The comprehensive clinical and MRI- retrospectively evaluated the relationships between anti-coagulation examination of 83 consecutive patients (43 men and 40 women, mean therapy and recurrent embolism during admission in patients with car- age 62,4±10,3) with acute ischemic brainstem stroke, admitted diogenic stroke. between 2007-2011, was performed. The frequency of various neu- Subjects and Methods: The subjects were 546 patients who were rological symptoms, including oculomotor disorders, was analyzed in admitted to Tokai University Hospital with cardiogenic ischemic relation to the three parts of brainstem. stroke from September 2004 to August 2011. The series, dosage or Results: 42 (51 %) of the ischemic lesions were located within the duration of anti-coagulation therapy (heparin, warfarin or dabigatran) pons, 27 (33 %) within the medulla and 14 (16 %) within the mid- was checked, and the relationships between the treatments and brain. Oculomotor disorders were seen in all patients with midbrain recurrent embolism (of the brain or other organs) during admission lesion: isolated oculomotor nuclei palsy without dysfunction of long were evaluated in all subjects. tracts – in 2 patients (14 %) or combined with crossed brainstem Results: Of the 546 subjects, embolism recurred in 35 patients syndromes – in 8 (58 %) patients (Weber syndrome – in 5, Benedict – (6.4 %) (ischemic stroke: 25, others: 10). Twenty-two subjects (63 %) in 2, Claude – in 1), Parinaud’s syndrome – 14 %, paresis of the had recurrence within 7 days after onset; 13 (37 %) had recurrence vision downstairs in 7 %, vertical one-and-a half syndrome in 1 after 7 days. The subjects begun anti-coagulation therapy within 7 patient (7 %). Oculomotor disorders in pontine strokes manifested days tended to have a lower prevalence of recurrence than them begun Raymond-Cestan syndrome – in 1 patient, Foville superior syndrome it after 7 days. Recurrence rates in the subgroups initially receiving – in 4 patients (9,5 %), Foville inferior syndrome – in 3 patients heparin (6.0 %), warfarin (4.5 %), or both (0 %) were significantly (7,1 %) and horizontal one-and-a-half syndrome – in 2 patients. lower than those in subjects not receiving any anticoagulant (13 %). Conclusions: Attentive estimation of oculomotor abnormalities Conclusion: Anti-coagulation therapy within 7 days after the ini- together with another clinical symptoms, or even isolated, and tial events in the cardiogenic stroke may be effective for the radiological correlations has significant value in the topical and prevention of recurrent embolism in the acute stage of stroke. clinical diagnostics of ischemic brainstem lesion.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S157

P608 most often cause of ischemic stroke is an acute occlusion of brain Acute basilar artery occlusion: safety and efficacy arteries which can be demonstrated in more than 70 % of patients in the first 6 h after symptoms onset. Early recanalization is associated of different treatment strategies and predictors of good with a significantly higher chance of independency after 90 days with outcome a significant reduction of mortality. Except intravenous thrombolysis T. Dorna´k, R. Herzig, D. Sˇkoloudı´k, D. Sˇana´k, M. Kuliha, (IVT), several pharmacological and endovascular mechanical meth- M. Roubec, M. Herman, V. Procha´zka, M. Kra´l, ods are studied. Case report: A 55-years-old male was admitted to the Stroke Unit T. Veverka, A. Ba´rtkova´, P. Hlusˇtı´k, M. Kocher, with left sided hemiparesis, left facial palsy, dysarthria, eye deviation P. Kanosky, J. Zapletalova´ and neglect syndrome (NIHSS 20 points) lasting 105 min. Brain Comprehensive Stroke Centre (Olomouc, CZ) computed tomography (CT) was normal, CT angiography detected Objective: Acute ischemic stroke (AIS) caused by basilar artery T-occlusion of internal carotid artery. IVT was applied without occlusion (BAO) is often associated with a severe and persistent improvement of clinical deficit. Patient was transferred to angiogra- neurological deficit and a high mortality rate. Various treatment phy where the persistent ICA occlusion was detected. Successful concepts are being used. The aim was 1) to assess the association mechanical recanalization using pRESET thrombectomy device and between outcome and treatment type and 2) to identify predictors of stenting of residual stenosis of middle cerebral artery was performed good outcome. 4 h after stroke onset. Control brain CT detected malignant ischemia Methods: The set consisted of 50 consecutive AIS patients with with 10 mm midline shift. Acute decompressive craniectomy was radiologically confirmed BAO (37 males; mean age 64.7±12.4 performed. Neurological deficit rapidly improved with mild left sided years). Stroke severity at the time of treatment was assessed as severe hemiparesis and mild left facial palsy (coma, locked-in state, tetraplegia) or mild to moderate. 30-day out- Conclusion: Early recanalization of brain artery occlusion come was assessed using a modified Rankin scale (mRS) with good increases the probability of independence in acute stroke patients. outcome defined as score 0-3. The following treatments were used: Malignant infarction is one of life-threatening complications in these antithrombotic treatment only (AT) including antiplatelet drugs or patients. Early decompressive craniectomy is a life-saving therapy systemic anticoagulation; intravenous thrombolysis alone (IVT); IVT indicated in patients with malignant infarction. with subsequent intraarterial therapy (IVT+IAT); intraarterial therapy alone (IAT) which comprises local thrombolysis, mechanical thrombectomy, stenting, sonothrombolysis or combination of these. Other P610 observed factors were age, mRS score before stroke onset, time to Post rtPA CT brain may not routinely be performed treatment, recanalization rate. Results: AT was used in 8, IVT in 12, IVT+IAT in 13, IAT in 17 in all stroke patients in limited-resource situation patients. Good outcome was found in 0 AT, 2 (16.7 %) IVT, 7 P. Dharmasaroja, S. Muengtaweepongsa, U. Boonaurana, (53.8 %) IVT+IAT, 3 (17.6 %) IAT patients (p[0.05). The following P. Dharmasaroja statistically significant differences were found between patients with Thammasat University (Klong Luang, TH); Mahidol University good vs. poor outcome: mean age 54.2 vs. 68.0 years (p=0.0004); (Bangkok, TH) successful recanalization 91.7 % vs. 47.4 % (p=0.008); presence of severe neurological deficit 25.0 % vs. 65.8 % (p=0.02). Logistic Routine neuroimaging of the brain is performed after intravenous regression analysis identified age (OR=0.875, 95 % CI: 0.798-0.958; recombinant-tissue-plasminogen activator (rtPA) treatment in most p=0.004), presence of severe neurological deficit (OR=0.079, 95 % patients with acute ischemic stroke. However, in situation where CI: 0.009-0.701; p=0.023), time to treatment (OR=0.602, 95 % CI: resources are limited whether a follow-up computed tomography (CT) 0.009-0.701; p=0.035) as significant independent predictors of good should be performed on each patient post rtPA is unknown. The outcome. purpose of this study is to investigate the need of a follow-up CT in Conclusion: In the presented study, most patients received IAT. patients with acute stroke after rtPA treatment. An apparent (although statistically insignificant) trend for better Methods: Patients who were treated with intravenous rtPA were outcome was observed in the IVT+IAT group. Age, severe neuro- included. Clinical symptoms/signs of the patients were evaluated at logical deficit, time to treatment were identified as significant 24 h after rtPA treatment compared with baseline NIHSS. Another independent predictors of good outcome. CT brain was done within 24-36 h after receiving rtPA. The need of a Supported by the grants NT/11386-5/2010, NT/11046-6/2010 follow-up CT after rtPA treatment was assessed by comparison of the (IGA MH CR), CZ.1.05/2.1.00/01.0030. early clinical changes with the CT brain results that would affect the management plan; presence of hemorrhagic transformation, malignant MCA infarction, cerebellar infarction. Results: 200 patients were included. Nineteen patients (9.5 %) had early complete recovery. CT post rtPA reviewed no change in these patients. In 105 patients who had early improvement with NIHSS at P609 24 h 1-10, follow-up CT findings did not change plan of management Combined treatment of acute ischaemic stroke – a case in 85 % of the patients. Follow-up CTs may help in planning further report management in 65 % and 67 % of the patients who had NIHSS[10 at P. Kostalova, E. Hurtikova, M. Roubec, M. Kuliha, 24 h and early worsening, respectively. Conclusions: CT post rtPA may not be required in most patients D. Skoloudik with clinical improvement and NIHSS at 24 h 0-10. However, in University Hospital Ostrava (Ostrava, CZ) patients with residual severe deficit (NIHSS[10 at 24 h) post rtPA or Background: Stroke is one of the most frequent causes of mortality, patients with early clinical worsening or suspected posterior circula- morbidity and disability of population in developed countries. The tion stroke, CT post rtPA were still needed.

123 S158 J Neurol (2012) 259 (Suppl 1):S1–S236

P611 for SBI and LI were obtained by receiver operating characteristic The clinical implications of lesion patterns in small deep curve (ROC) analysis. Results: Plasma levels of MIG, SCF and ICAM1 have been found infarcts to be significantly higher in SBI patients than in controls, while in LI D.E. Kim, B.H. Cho, H.J. Jung, K.H. Choi, M.S. Park, patients IL16, and ICAM1 were significantly higher, and SCGFb S.M. Choi, S.H. Lee, B.C. Kim, M.K. Kim, K.H. Cho, significantly lower, than in controls. Other immunological markers, J.T. Kim, T.S. Nam, J.H. Lee namely IL12p40, MIF and MCP1, had similar levels among SBI, LI Chonnam National University Hospital (Gwangju, KR) and control subjects. Interestingly, SBI subjects showed significantly increased levels of Background: The mechanisms underlying small deep infarcts in the IL18, SCF and SCGFb when compared to LI patients. Conversely, LI subcortical area are unknown. Infarcts resulting from the occlusion of patients showed significantly higher levels of IL16 with respect to the orifice of the branch, branchatheromatous disease (BrAD) tend to SBI group. extend to the basal surface, whereas lacunar infarcts (LI) caused by According to the ROC analysis, the expression of ICAM1 seems lipohyalinosis usually produce an island of ischemic tissue within the to be predictive for both SBI and LI, with the highest predictive value parenchyma. We hypothesized that the two aforementioned types of for SBI patients. Higher values of MIG and SCF seem to be predictive small deep infarcts are distinct clinical entities. In addition, we of SBI development. Conversely, increased IL-16 together with lower thought that coronal MRI can be used to determine whether ischemic levels of SCGFb seem to be predictive factors for LI. lesions in the subcortical area are isolated or linear and extend to the Conclusion: Plasma levels of neuroinflammation-related mole- basal surface. cules indicate that inflammation takes place both in SBI and LI Methods: This was a retrospective study of acute stroke patients patients, being differentially expressed in the two conditions. (within 48 h of symptom onset) consecutively admitted to our tertiary stroke center between Oct 2007 and May 2012. We included patients with small deep infarcts in the subcortical area (lesions with a longest P613 diameter \ 20mm on axial DWI). We divided the patients into two groups as follows; (1) those with isolated lesions (IL) were defined as an Time-dependent changes in carotid-femoral pulse wave IL (with round or oval shape) in the parenchyma and (2) those with velocity in patients after ischaemic stroke linear lesion (LL) were defined as a lesion extending to the basal surface M. Kwarciany, D. Gasecki, K. Kowalczyk, A. Rojek, on coronal DWI. We assessed the neurological status during admission W. Nyka, K. Narkiewicz using the NIHSS scores. Progressive motor deficits (PMD) were defined Medical University of Gdansk (Gdansk, PL) when the NIHSS scores increased by 2 or more points from the baseline NIHSS scores during the 5 days after symptom onset. Background: Increased aortic stiffness, reflected by elevated carotid- Results: This study analyzed a total 248 patients (IL=124 and femoral pulse wave velocity (CF-PWV) has been shown to be higher LL=124). PMD, white matter hyperintensities, and microbleeds were in patients with acute ischemic stroke than in controls. It is also observed more frequently in IL than LL (p\0.05), whereas arterial known that ischemic stroke is associated with hypertensive response. stenosis was more frequent in LL than IL. The independent factor Time-dependent changes in CF-PWV, and their relationship with associated with PMD were lesion diameters on coronal DWI (OR, 1.79; blood pressure alternations after acute phase of stroke are unknown. 95 % CI, 1.012-1.151); p=0.021) by multivariate logistic regression. Methods: 24 patients (age 60.7 ± 10.9 years, NIH Scale score 6.4 Conclusions: This study demonstrated that patterns of IL and LL ± 5.5, mean ± SD) with ischemic stroke, admitted within the first from small deep infarcts had different imaging and clinical findings. 48 h from stroke onset, were enrolled to the study. CF-PWV was The LL patterns of small deep infarcts have a higher risk of PMD than measured non-invasively with applanation tonometry (Sphygmo- the IL patters. Cor) at day 7 and at day 30 after stroke. Relative brachial SBP and CF-PWV changes were calculated using the following formula: (baseline – final)/baseline. The correlation between examined variables was assessed by Pearson’s coefficients. P612 Results: At day 30, both the mean CF-PWV (9.0 ± 2.0 versus 9.9 Immunological profile of silent brain infarct ± 2.2 m/s; p=0.02), and SBP (135.8±20.0 versus 146.1±22.6 mmHg; and lacunar stroke p=0.02) were significantly lower than on day 7 after stroke. Relative K. Nardi, D. Chiasserini, V. Di Piero, M. Silvestrini, change of CF-PWV was strongly associated with relative change of SBP (r=0.65; p=0.001). C. Marini, P. Eusebi, P. Calabresi, P. Sarchielli, L. Parnetti Conclusion: Carotid-femoral PWV is higher during early phase of University of Perugia (Perugia, IT); University of Rome (Rome, IT); ischemic stroke than 30 days after stroke. The decrease of aortic University of Ancona (Ancona, IT); University of L’Aquila stiffness is associated with the parallel decrease of SBP. (L’Aquila, IT); Epidemiological Departement (Perugia, IT) Background: Neuroinflammation is believed to be involved in the pathophysiological mechanisms of silent brain infarcts (SBI). How- P614 ever, the immunological profiles of patients with SBI have been scarcely investigated. Stent-assisted angioplasty in patients with Moyamoya Methods: Twenty-one SBI subjects, 28 patients with recent lacu- disease: long-term clinical and angiographic follow-up nar infarction (LI), and 31 healthy subjects were enrolled. In plasma results samples, a panel of immunological markers (MIG, CTACK, IL16, B.H. Lee, M.S. Kim, S.J. Lee, M.S. Park, S.H. Jang SDF1a, MCP1, SCF, SCGFb, HGF, IL3, ICAM1, VCAM1, IL18, Eulji University Hospital (Daejeon, KR) INFa2, MIF, IL12p40, IL2Ra, TRAIL) were determined. Samples TM were analyzed by Luminex xMAP technology. Immunological Objectives: To report long-term clinical and angiographic follow-up parameters were adjusted for age, gender and vascular risk factors results of stent-assisted angioplasty for patients with moyamoya using non-parametric ANOVA. Predictive values of cytokine levels disease.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S159

Methods: Between May 2002 and May 2011, stent-assisted angi- P616 oplasty was performed in 12 patients(M:F = 5:7, mean age : 44 years Lower cranial nerve palsies as the sole pointers ranged from 27 to 58).They were all symptomatic (transient ischemic attack(TIA) in ten and ischemic stroke in two patients).Drug-eluting to internal carotid artery dissection stent was used in all patients except one. We retrospectively analyzed S. Rocha, R. Carvalho, J. Fernandes, C. Ferreira, technical success, the procedure-related complication, and the clinical A´. Machado and angiographic follow-up results. Hospital de Braga (Braga, PT) Results: Technical success was achieved in ten patients. There were two vessel ruptures during procedure. One patient was rescued Background: Spontaneous dissection of the internal carotid artery without neurologic complication using temporary balloon occlusion (ICA) is an important cause of stroke in young patients. The most and another stent insertion. The other patient was rescued without frequent initial symptom is headache. Horner’s syndrome, cranial neurologic complication after intentional middle cerebral artery nerve palsies and focal ischemic signs can also be seen. occlusion using induced thrombosis. There was no procedure-related Case report: 1) A 54-years-old hypertensive woman was seen mortality or morbidity. There was no more TIA in all patients for a 9-day history of severe right-sided headache, chewing diffi- immediately after procedures. Angiographic follow-up was available culty and slurred speech. Examination disclosed right hypoglossal in seven patients(mean: 16.9 months, range: 3-37).Instant restenosis nerve palsy. MRI with angiography showed a pseudoaneurysm in developed in three patients and all were symptomatic. the right cervical ICA, with distal arterial stenosis, suggesting sub One patient showed instant restenosis on 7, 13, and 19 month after adventitial dissection; there were also other arterial irregularities initial stenting pointing to probable fibromuscular dysplasia. 2) A healthy 53-year- and after 3rd angioplasty, restenosis did not develop on serial old woman was admitted with a 3-day history of left-sided head- angiogram up to 37months. Another patient showed restenosis on 7 ache, vomiting and chewing and speaking difficulties. Examination month after initial stenting and after angioplasty, restenosis did not showed left IX, X and XII nerve palsies. MRI revealed left ICA develop on serial angiographic follow-up up to 33 month after initial dissection, with sub adventitial pseudoaneurysm. Both patients stenting. The other patient showed restenosis on 6 month after initial had no recent cervical trauma history, were hypocoagulated when stenting and after angioplasty, restenosis did not develop on 3 month the diagnosis was done, and fully recovered over the next 3-4 follow-up angiogram. Clinical follow-up was available in all patients weeks. (mean: 31.7 months, range: 8-72).There were TIAs in three patients Discussion: The main mechanism of lower cranial nerve palsy in with restenosis. There was no bleeding or stroke in all patients. ICA dissection is ischemic injury, both from direct compression by Conclusion: Stent-assisted angioplasty in patients with moyamoya the pseudoaneurysm (affecting small nutritive vessels), as from disease showed higher rates of vessel rupture and restenosis. How- compression of the ascendant pharyngeal artery (branch from the ever, stent-assisted angioplasty could be another treatment option for external carotid). In our patients the former mechanism seems to be some patients with moyamoya disease in the future. Further study more determinant in patient 1, and the later mechanism seems to should be necessary. cause a more widespread ischemic damage in patient 2. These cases illustrate that isolated cranial nerves palsies, especially when associated with head or neck pain, point to ICA dissection, and should prompt for its immediate search. P615 Comparing the relative frequency of prothrombin (G20210A) genemutation in patients with stroke P617 M. Saadatnia, M. Tajmirriahi, M. Salehi, G. Amini Diagnostic yield of echocardiography in stroke: should Isfahan University of Medical Science (Isfahan, IR) we improve patient selection? Background: Stroke in young adults is a known but abnormal disease. S. Secades-Gonza´lez, M. Martıń-Fernańdez, C. Corros- Several recent studies have discussed the correlation between exis- Vicente, J.M de la Hera-Galarza, M.L Rodriguez-Sua´rez, tence of coagulation factors such as V Leiden and Prothrombin Mutation (G20210A) as risk factors in incidence of stroke. Therefore, D. Leoń-Durań, M. Barreiro-Pe´rez, E. Fernańdez-Garcıá, despite recent researches on correlation between the V Leiden factors, E.M Benito-Martıń, J.P Flo´rez-Munõz, E. Velasco-Alonso, the necessity of conducting further studies is required. The present J.L Lambert-Rodriguez study reviewed the frequency of Prothrombin gene mutation and its Universitary Central Hospital of Asturias (Oviedo, ES) impact on incidence of ischemic stroke in Iranian youth without classical risk factors for stroke. Background and Objectives: Between 15-30 % of strokes are sec- Methods: This was a case–control study with convenient sampling ondary to cardiovascular causes. The application of echocardiography method on seventy six 18 to 50-year-old people provided that they did is common as part of the diagnostic protocol. The progressive satu- not have classical risk factors for stroke. They divided into two groups ration of echocardiography laboratories makes it advisable for a including 22 patients with ischemic stroke (15 males and 7 females) critical assessment of the requests. The aim of our study is to analyze as the case group and 54 healthy people (17 males and 37 females) as the diagnostic yield of echocardiography in patients with a diagnosis the control group within 26 months (23-9-2007 to 21-11-2009) in Al- of stroke in a tertiary hospital. Zahra Hospital, Isfahan. Methods: We retrospectively analyzed all echocardiograms per- Results: Prothrombin was not found in any of the studied patients. formed during a year in patients referred from the neurology Heterozygous mutation was observed in one of the samples of the department with a diagnosis of stroke. It assesses the diagnostic control group (relative frequency = 1.85 %). efficacy of the test and its contribution to the aetiology of these Conclusion: According to the results of the present study, despite patients in terms of major and minor echocardiographic findings as proving the effect of Prothrombin gene mutation on incidence of recommended by the European Society of Cardiology. venous thrombosis, it does not seem this factor, as an independent Results: We analyzed 405 consecutive patients (57 % males, mean factor, can be considered as a risk factor to create ischemic stroke in age 64.5 ± 14.2 years) and the following clinical features were pre- people who do not have other risk factor. sented: hypertension (43 %), diabetes (27.7 %), dyslipidemia

123 S160 J Neurol (2012) 259 (Suppl 1):S1–S236

(35.6 %), atrial fibrillation (10.4 %), smoking (44, 7 %) and previous P619 heart disease (27.2 %). Pathological findings were observed in the Stroke - morbidity, mortality and air pollution. Follow- electrocardiogram in 17 % of patients and heart murmur was detected in 13.1 %. Echocardiography was performed transthoracic (TTE) in up of patients of the ‘‘districts VIII-XII of Budapest’’ 100 % of the sample (agitated saline in 11.4 %) and transesophageal project in two districts of the Hungarian capital echocardiography (TEE) at 9.6 %. For analysis, the sample was A. Folyovich, M. Darańyi, A. Majoros, I. Vastagh, A. Ajtay, divided into two groups: embolic stroke 29.9 % (121) and non Z. Laki, K. Erdei, A. Ke´ri, K.L. Kovacs, B. Gunda, L. Lenti, embolic stroke, the rest. Major criteria were found in 5 % (6) of the embolic and 0.7 % (2) of non-embolic. Minor criteria were found in Z. Danos, D. Bereczki 29.8 % (36) of the embolic and 10.6 % (30) of non-embolic. As Szent Jańos Hospital, Semmelweis University, Hungarian embolic stroke predictors in our sample we found hypertension (OR Meteorological Service (Budapest, HU) 1.8, 95 % CI (1.16-2.82), p = 0.009), atrial fibrillation (OR 3.27, 95 % Objectives: In the ‘‘Districts VIII-XII of Budapest’’ project, demo- CI (1.7-6.2) p = 0.0001) and previous heart disease (OR 2.48, 95 % graphic data of 345 patients with acute stroke in 2007 were collected CI (1.57-3.94) p = 0.0001). from two districts of the Hungarian capital with significantly different Conclusion: According to our results, the routine echocardiogra- life circumstances (154 patients from district VIII and 191 from phy at non-embolic strokes has a low diagnostic yield. Proper district XII), and clinical course of the patients was analyzed. A data selection of patients could help to save resources and reduce the base was created and used for several substudies. District VIII with a routine practice of diagnostic tests with low profitability lower standard of living has nearly six times higher population density and a small fraction of the greenbelt area, compared to the wealthier district XII. The latter district has public roads and squares with high traffic intensity. Data from international studies indicate P618 that air pollution increases the risk of acute cardiovascular events, such as myocardial infarction and ischemic stroke. Previous data of Evolving ischaemic cortical vasculopathy in cerebral our project demonstrated that the onset of stroke and resulting death amyloid angiopathy: report of three cases occurs at a significantly earlier age in district VIII. Therefore, we E. Altindag, O.G. Tuncer, B.A. Koyuncu, Y. Bekmezci, examined whether less favorable morbidity and mortality rates are R. Tolun, Y. Krespi correlated with higher level of air pollution. We assumed that the latter is affected by higher income in several ways, that allows Florence Nightingale Hospitale (Istanbul, TR); Istanbul Bilim apartments with larger floor space, less crowded residential areas and University (Istanbul, TR) a higher traffic intensity, at the same time. Objectives: Cerebral amyloid angiopathy (CAA) is a small to medium Methods: All stroke patients were followed-up, using a compre- vasculopathy which can rarely be associated with ischemia. We hensive data form filled out together with the GP of the patient. It – herein report 3 cases to better characterize CAA related ischemic anonymously – included pre-stroke history, risk factors, treatment of syndromes. vascular event and adherence to therapy, as well as health status in Cases: Case 1: A-69 year’s old man was under oral anticoagulant 2010. In this substudy, data of meteorological stations (PM10, NO, therapy since 1 month after transient ischemic attacks (TIA) and a NO2, NOx, SO2, O3) were analyzed and correlated with the above right frontal cortical punctate infarction of undetermined origin. He data season by season. The station in district VIII is located in the presented with a left temporoparietal lobar hemorrhage with an INR center of the densely populated area. Data from two stations were of 3.34. Retrospective evaluation of MRI examination demonstrated a used in district XII, since it has high traffic zones with apartment right frontoparietal sulcal hyperintense lesion in F.L.A.I.R sequence, houses, in addition to suburban areas. showing enhancement in T1 and associated cortical microbleeds and Results: Air pollution data of the three meteorological stations foci of superficial siderosis. were significantly different, but there was no remarkable seasonal Case 2: A-85 year’s old man presented with TIA of unknown difference at a certain location. By far the worst air pollution values etiology. Baseline MRI revealed a left frontoparietal sulcal hyper- were measured in the high traffic zone of district XII, and the best intense lesion in F.L.A.I.R sequence with enhancement in T1. On ones in the greenbelt areas of this district. Values from district VIII 5th day control MRI, a new cortical punctate DWI lesion and were in between. extensive superficial siderosis were seen. One year later sulcal lesion Conclusion: Higher level of air pollution increases the risk of disappeared and a new microbleed was visible in the right temporal stroke events, but its effect is strongly associated with socio-cultural cortex. factors, therefore, its role alone cannot be evaluated. Case 3: A-70 year’s old man presented with TIA of unknown etiology. Baseline MRI showed a right parietal sulcal hyperintense lesion in F.L.A.I.R sequence, showing enhancement in T1 and few Pain and headache cortical microbleeds and foci of hemosiderosis. A new cortical punctate DWI lesion appeared in the same location 4 days later. A new silent sulcal lesion appeared in the right temporooccipital region with a new DWI lesion in the occipital region, the previous P620 parietal lesion had disappeared in 3rd month MRI. New cortical mi- Vascular abnormal loops causing trigeminal neuralgia crobleeds were detected ten months later. – an atherosclerosis consequence? Conclusion: Our cases indicate that contrast-enhanced leptome- D.I. Cuciureanu, E. Moldovanu, A. Cuciureanu ningeal lesions may be seen in TIA or minor ischemic strokes patients University of Medicine and Pharmacy Gr. T. Popa (Iasi, RO); of unknown etiology. This evolving cortical ischemic vasculopathy Emergency Hospital Prof.Dr. N. Oblu (Iasi, RO) can be related to CAA and may add to the clinical spectrum of contrast-enhanced leptomeningeal lesions previously described as Purpose: Symptomatic trigeminal neuralgia can be the clinical man- part of rapidly progressive encephalopatic CAA. ifestation of vascular abnormal loop compressing trigeminal roots.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S161

We try to find a correlation between the highs level of LDL choles- groups B and C in average HIT-6 score (62.1 ± 6.9 vs 61.2 ± 7) and terol as marker of vascular atherosclerosis and vascular anomaly. percentage of cases with HIT-6[=55(94.6%vs80.9%) Method: We reviewed the clinical findings and laboratory data of Conclusion: CM with or without MO represents a burdensome 46 patients hospitalized for trigeminal neuralgia in our neurological group of patients in our headache clinic. Adverse headache impact service during past 3 years. All patients received biochemical, measured with HIT-6 is significantly increased in persons with CM, hematological investigation, 3-D MRI volume acquisition with con- regardless of the presence of MO. trast injection and thin cuts. Results: We find a female predomination in sixth and seven decade of life. Clinical manifestation was: 20 idiopathic trigeminal neuralgia and 26 symptomatic trigeminal neuralgia. After standard investigation P622 we revealed in the second group: tumoral causes – 4 cases, dental Migraine mimicker: under the surface an eosinophilic causes 7 cases, 2 cases posttraumatic neuralgia and 13 cases with granuloma vascular contact with the trigeminal nerve at the pons (4 superior and 7 D. Dalla Libera, B. Colombo, G. Dalla Costa, R. Messina, inferior cerebellar artery loops, 2 enlarged veins). In vascular contact group we find 9 patients with history of more 5 years dyslipidemia. 8 D. De Feo, V. Martinelli, G. Comi patients underwent surgical decompression with god results after 6 INSPE, Scientific Institute San Raffaele (Milan, IT) month follow –up. We report 2 cases of 58 and 64 years women with Objective: to illustrate a case report of Langerhans cell histiocytosis old history of trigeminal neuralgia, decreasing clinical response for presenting with headache. medication that underwent MRI investigation resulting in abnormal Methods: case report. vascular loop with multiple hyperintense intravascular atherosclerotic Results: We report the case of a 29-years-old hispanic girl who lesions. Surgical procedure ending in sustained pain relief. presented with headache, localised unilaterally, on right fronto-tem- Conclusions: Even we studied a small series of cases, we poral side, of moderate to severe intensity, dull in character, hypothesized a direct correlation between highs and persistent LDL persistent, not relieved even by non-steroidal anti-inflammatory levels and the possibility of abnormal vascular loops. drugs, that occurred daily on the last 2 months. The patient had no history of headache or family history for headache. On inspection right fronto-temporal swelling was evident. General examination was normal (no lymphadenopathy or hepatosplenomegaly), such as neu- P621 rological examination and blood tests. She performed brain CT that Headache impact of chronic and episodic migraine: showed an irregular, osteolytic lesion. Magnetic resonance imaging results in a series of 1113 patients (MRI) of the brain was able to confirm an intradiploic lesion within the right fronto-temporal bone. Surgical excision of the lesion was P. Mulero, A.L. Guerrero, M. Pedraza, A. Sańchez, performed and the disease was diagnosed pathologically: hematoxy- L. Sierra, S. Herrero, B. Aylloń, A.B. Go´mez, A. Garcıá, lin-eosin and immunohistochemical staining, disclosed a diagnosis of J. Baroń, I. Munõz, R. Fernańdez Langerhans cell histiocytosis (LCH) in the form of eosinophilic University Hospital (Valladolid, ES) granuloma (S100 and CD1 positive, evidence of Birbeck granules). A chest CT ruled out other sites of disease. Presence of other Objectives: Migraine is one of the leading causes of all years lived osteolitic lesion was excluded and skin examination was normal. with disability among all ages. According to the International Clas- Thus, radiotherapy or systemic therapy was not required. After sur- sification of Headache Disorders 2-revised (ICHD-2R), chronic gery, the patient well-recovered from her symptomatology. Patient migraine (CM) patients present at least 15 days of headache per did not demonstrate any evidence of distant or recurrent disease at month, 8 of them fulfilling pain characteristics and associated 1year follow-up. symptoms of migraine. Medication overuse (MO) is defined as reg- Conclusion: Langerhans cell histiocytosis (LCH), also known as ular use during more than 3 months of symptomatic treatments on histiocytosis X, is a rare disorder (incidence ranges from 0.5 to 5.4 more than 10 or 15 days per month depending on type of drugs. We cases per million persons per year),characterized by clonal prolifer- aim to characterize and compare demographic profiles and headache ation and excess accumulation of pathologic Langerhans cells causing impact for patients with CM, with or without MO, and episodic local or systemic effects. In fact, it represents a heterogeneous group migraine (EM) in a large series. of disorders, with presentations ranging from the fulminant, to those Methods: We considered patients attended in an outpatient head- that spontaneously involute without any lasting sequelae. Thus, ache clinic in a tertiary hospital from January 2008 to January 2012. patients need to be risk-stratified based upon the number of organs We gathered demographic and nosological characteristics of each involved and degree of organ dysfunction. In childhood skull lesions patient. EM (Group A) was diagnosed accordingly to ICHD-II cri- are often described, while in adults it is a rare presentation, involving teria. For migraine with MO headache (MOH) (Group B) and CM especially orbital lesions. The etiology remains unknown, whether (Group C) we considered ICHD-2R criteria. We administered six- LCH represents an abnormal immune response to an unidentified item Headache Impact Test (HIT-6), designed to provided a global antigen or whether it is truly a neoplastic process, if the site of disease measure of adverse headache impact. is unifocal usually the prognosis is excellent. Results: Out of 1668 patients attended in our clinic during inclusion period, 1113 (66.7 %, 260 males, 853 females) were diagnosed of migraine. Among them 727 (65.3 %, 191 males, 536 females) were included in group A, 225 (20.2 %, 39 males, 186 females) in group B, P623 and 161 (14.5 %, 30 males, 131 females) in group C. When comparing R-r interval variation and the sympathetic skin episodic migraine (Group A) with chronic migraine patients (Groups B response in the assessment of autonomic function and C) we found more female patients in Group A (82.1 % vs 73.7, p: in migraine patients 0.002). In CM and MOH cases average HIT-6 score (61.7 ± 6.9 vs 57.5 ¨ ¨ ± 9.1, p\ 0.001), and percentage of patients with at least substantial H. Ulvi, R. Demir, L. Ozel, G. Ozdemir, A. Ertekin, (HIT-6 [= 55) headache-related impact (84.1 % vs 61.9 %, p\0.001) R. Aygu¨l were significantly higher than in EM. We found no difference between Atatu¨rk University (Erzurum, TR)

123 S162 J Neurol (2012) 259 (Suppl 1):S1–S236

The aim of this study was to evaluate possible cardiovascular auto- P625 nomic dysfunction in migraine patients with the R–R interval The efficacy of intranasal lidocaine application variation (RRIV) measurement and the sympathetic skin response (SSR), which are easy and reliable methods for evaluation of auto- in tension migraine nomic functions. We studied 34 migraine patients in headache- free O. Karadas, H. Gul, C. Cemberci, B. Ozturk, U. Turk Boru, intervals (mean age: 37.81, range 19-57 years; 21 females and 113 Z. Odabasi males), all without any known heart disease, and 29 age-matched Erzincan Military Hospital (Erzincan, TR); Kartal Education and healthy subjects (mean age: 49.76, range 24-48 years; 12 females and Research Hospital (Istanbul, TR); Gulhane Military Medical 17 males). RRIV during at rest and deep breathing, and SSR were Academy (Ankara, TR) studied in all the subjects. The mean values of RRIV in patients with migraine both during at rest (mean RRIV in patients, 50.16 % Objective: Until recently, most clinicians believed that migraine was ±38.77 % vs. control, 20.81 % ± 10.09 %[p\0.05]) and during deep simply a vascular condition, induced by blood vessel dilation. Today, breathing (mean RRIV in patients, 55.20 % ± 32.72 % vs. controls, new insight suggests that the pathophysiology of migraine is much 27.83 % ± 15.60 % [p\0.005]) were significantly abnormal com- more complex. The multi-mechanistic approach to migraines holds pared with the controls. The mean latency and amplitude of SSR in that headache pain results from a chain of events that are both vas- patients with migraine (mean SSR latency in patients, 1.43 ± cular and neurological. Migraine pain is induced not only by the 0.35 ms vs. controls, 1.30 ± 0.41 ms [p[0.05]; mean SSR amplitude widening of blood vessels, or vasodilation, but begins with inflam- in patients, 1,08 ± 0.57 lV vs. controls, 1.02 ± 0.56 lV[p[0.05]) mation, leading to pain reception, or nociception, and central and were no statistical significance compared with the controls. No peripheral sensitization. Preventive treatment with beta-blockers, correlation was observed between patient age, and duration of antidepressants, and antiepileptics have wide range side effect profiles migraine history and abnormalities RR interval. Patients with and new therapies are needed. However, further studies are needed to migraine have autonomic dysfunction during routine daily activity in bring out new treatment options. the headache-free period. In this study we aimed to investigate the effectiveness of intranasal lidocaine application through regulation of the anti-nociceptive systems in migraine treatment. Methods: 22 patients diagnosed as migraine with a history of at P624 least 6 months, were included in the study. Intranasal lidocaine was Botulinum neuro-toxin type A in the treatment applied to each patient, including both sides. Patients were kept under of migraine associated with pericranial tenderness observation for half an hour, for probable side effects after treatment. Patient’s number of painful days in a month and pain severity (VAS- O. Karadas, H.L. Gul, U. Ulas, Y. Kutukcu, Z. Odabasi visual analog scale) were recorded before the treatment, then at the 6 Erzincan Military Hospital (Erzincan, TR); Kartal Education and week and 12 week after treatment. Research Hospital (Istanbul, TR); Gulhane Military Medical Results: When compared to pre-treatment period, intranasal Academy (Ankara, TR) application of local lidocaine in migraine patients caused improve- Objective: Migraine is a primary headache presenting with attacks, ments at the number of painful days per month and pain severity associated with autonomic and neurological symptoms, it is a group assessed by visual analog scale. Improvements in these parameters of syndromes. In migraine with low pain threshold associated with were statistically significant (p \0.05). genetic factors, central nervous system was found to be hyperex- Conclusion: Intranasal application of local lidocaine can be used citable. Preventive treatment with beta-blockers, antidepressants, as an effective method in the treatment of migraine. and antiepileptics have wide range side effect profiles and new therapies are needed. However, further studies are needed to bring out new treatment options. The aim of our study is to investigate the effectiveness of Botulinum Neuro-toxin Type-A (BoNTA) in P626 the treatment of migraine associated with pericranial tenderness Cerebral hemodynamic effects of rizatriptan (PT). and frovatriptan during migraine attack Methods: 20 migrainous patient with PT were included in the B. O¨ztu¨rk, O¨. Karadas, U¨. Ulas, Z. Odabasi study. 100 units of Botox injections were applied to the pericranial Gu¨lhane Medical Academy (Ankara, TR); Erzincan Military Hospital muscles for each patient. The fixed sites injected are: procerus, cor- (Erzincan, TR) rugators, frontalis, temporalis, occipitalis, cervical paraspinalis and trapezius muscles. In addition, follow-the-pain sites were added Migraine is a complex disease and has been known for many years, depending on the patient’s headache distribution and areas of ten- but its mechanism and reason are still unclear. Different cerebral derness on examination as follows: temporalis, occipitalis and hemodynamic changes were observed at different stages of a trapezius. Severity of headache was evaluated by VAS (Visual migraine attack. After oligemia that appears with Cortical Spreading Analogue Scale) and number of days with headache per month were Depression (CSD) vasodilatation is observed with the termination of recorded before treatment and 6 and 12 weeks after treatment. CSD. The study results about cerebral hemodynamics are contra- Results: Number of days with headache per month were dictory. For this reason, we aimed to investigate cerebral 16.48±4.20 before treatment, 10.35±5.43 at 6 week after treatment hemodynamic effects of frovatriptan and rizatriptan, which are often and 9.54±3.84 at the 12 week after treatment. Severity of headache used in the treatment of acute migraine attack. 40 patients migraine was 88.56±7.21 before treatment, 67.55±9.50 six weeks after treat- with aura using rizatriptan (n=20) and frovatriptan (n=20) and 20 ment and 68.40±8.20 eleven weeks after treatment (statistically healthy individuals were included to our study. Cerebral blood flow significant, p\0.05). Frequency and severity of headache before velocities and Breath-Holding Indexes (BHI) were recorded bilat- treatment were significantly decreased at the 6 week after treatment erally from Middle and posterior cerebral arteries. 1 h after and this significance continued at the 12 week after treatment (sta- treatment and 1 week after attack all procedures were repeated. We tistically significant, p\0.05). observed similar values of cerebral blood flow velocities and BHIs Conclusion: BoNTA treatment by using follow-the-pain may be in all patients with migraine during attack free period compared to useful in the treatment of patients with migraine associated with PT. control group. All cerebral vascular structures investigated in the

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S163 study in migraine patients had significantly lower cerebral blood these studies, it has been believed that the intracranial vessels have an flow velocities and higher values in BHI’s during attack. After the important role in migraine pathophysiology, although neuronal use of rizatriptan and frovatriptan for attack the changes in hemo- mechanisms have been disclosed as primary point of interest. We dynamics were disappeared. As a result, during the attack in aimed to assess neurovascular reactivity at posterior cerebral arteries migraineurs with aura, vasodilatation is developing. In addition, to visual stimulus using transcranial Doppler ultrasonography in higher vasomotor reactivity in migraineurs during attacks support patients with migraine with or without aura. the vascular hypersensitivity in migraine pathophysiology. Triptans, Materials and methods: The study included 50 patients with acting as vasoconstrictor agents were able to stop the over- vaso- migraine without aura, 27 patients with migraine with aura, and 26 dilatation during attack. In other words: it is possible to say that healthy subjects as control. All patients underwent 2 times exami- triptans show their antimigraine effects by eliminating the vascular nation of visual stimulation using transcranial Doppler during hypersensitivity during the acute attack. headache phase and at least 5 days later of headache phase as headache-free period. Results: Neurovascular reactivities to visual stimulation amongst the patients with migraine with or without aura and controls are not P627 significant both during attack and attack-free periods. However, Quantification of cortical thickness and cortical surface neurovascular reactivity to visual stimulation on the headache side area abnormalities in patients affected by migraine (32 %) in patients with migraine without aura was found significantly R. Messina, M.A. Rocca, P. Valsasina, B. Colombo, lower comparing to non-headache side (37 %) during attack (p\0,001). In addition, the reactivity on the headache side is found A. Falini, G. Comi, M. Filippi lower during attack (35 %) than those of attack free period (39 %) in Vita-Salute San Raffaele University (Milan, IT) patients with migraine with aura (p\0,04). Objective: Structural and functional MRI techniques have contributed Conclusion: The study presented here is the neurovascular reac- to improve the understanding of the pathophysiology of migraine, by tivities of the posterior cerebral arteries to visual stimulation during showing that, despite its episodic nature, migraine can result in attack period and attack-free period in patients with migraine with or abnormalities of CNS morphology and function. We quantified without aura. The patients with migraine without aura has lower abnormalities of cortical thickness (CT) and cortical surface area reactivity on the headache side comparing to non-headache side (CSA) in patients suffering from migraine and assessed how they during attack period and the patients with migraine with aura has differ according to patients’ clinical (migraineurs with [MWA] or lower reactivity on the headache side during attack period comparing without [MWoA] aura) and radiological (presence or absence of white to attack free period. These results may point out that patients with matter lesions [WMls]) characteristics. migraine without aura have lower neuronal energy reserve regardless Methods: Using a 3.0 Tesla scanner, T2- and 3D T1-weighted headache attack than those of patients with migraine with aura. On the images were acquired from 63 migraine patients and 18 healthy con- other hand, spreading depression during aura phase in patients with trols. Cortical reconstruction and CT/CSA were performed using migraine with aura may have a protective effect on neuronal energy FreeSurfer analysis suite. A vertex-by-vertex statistical analysis was reserve. Additionally patients with migraine with aura have higher used to perform between-group comparisons (migraineurs vs. controls, neuronal excitability comparing to patients with migraine without MWA vs. MWoA, patients with WMls vs. those without WMls), and to aura might be supposed. assess the correlations between CT/CSA and clinical (disease duration, number of attacks) and radiological (T2 lesion load) characteristics. Results: Compared to controls, migraine patients experienced P629 distributed CT and CSA abnormalities. A decreased CT and CSA in lateral frontal lobes and an increased CT in medial fronto-parietal Tension-type headache in older-aged men and women: regions was detected in areas belonging to the ‘‘pain matrix’’. CT clinical and sonographic characteristics increase was also detected in the temporal lobe, including MT/V5 and Y. Abramenko, N. Iakovlev, T. Slyusar V1. Conversely, CSA of MT/V5 was decreased. The regional distri- Tver State Medical Academy (Tver, RU) bution of cortical abnormalities differed according to patients’ clinical and radiological characteristics. Compared to MWoA, MWA showed Objectives: Tension-type headache (TH) affects 27 % of older-aged an increased CSA in the central sulcus that was significantly corre- persons and is combined with co-morbid affective, asthenic and lated with disease duration and the number of attacks. insomnia disorders. The abnormal venous outflow from the brain Conclusions: Abnormalities of CT and CSA (which are partially must contribute to TH pathogenesis. The aim of the study was to find independent) occur in patients with migraine and involve areas which sex differences of clinical presentation, co-morbid disorders and are part of the visual and the ‘‘pain matrix’’ networks. These abnor- cerebral hemodynamic changes in older-aged patients with TH. malities may be the consequence of recurrent neuronal activation, due Methods: Fifty two women with TH (mean age 64.3) and 36 to the repetition of migraine attacks, or represent a phenotypic bio- matched by age and education men-patients (mean age 65.0) were marker of the disease. examined using clinical interview, headache diary, Russian Federal Somnology Centre Inventory, Multidimensional Fatigue Inventory, Holmes-Rahes scale to evaluate the psychosocial stress, Beck P628 Depression Inventory and State-Trait Anxiety Inventory. Cerebral hemodynamic changes were examined by means of transcranial Assessment of neurovascular reactivity at posterior duplex scanning. cerebral arteries to visual stimulation in migraine Results: The comparative analysis revealed statistically significant headaches difference between older-aged women and men with TH in headache G. Tekgo¨l Uzuner, N. Uzuner intensity (VAS, 4.7 vs. 4.0), attack duration (5.6 vs. 4.2 h) and frequency per month (10.1 vs. 7.2) (p\0.05). In women group the TH Osmangazi University (Eskisehir, TR) attacks were more often accompanied by anorexia, photophobia or Aim: Till now, lots of clinical and experimental studies to understand phonophobia than in men group (p\0.05). Compared to women, men- migraine pathophysiology have been done. According to the results of patients had lower levels of reactive and personal anxiety, depression,

123 S164 J Neurol (2012) 259 (Suppl 1):S1–S236 asthenia and psychosocial stress (p\0.01). Sleep disorders prevailed P631 in women-patients. No significant difference was obtained between Trigeminal pain is suppressed by non-invasive vagal older-aged women and men with TH in sonographic characteristics of arterial cerebral blood flow. Women-patients were characterized by nerve stimulation in a rat headache model more severe abnormal venous outflow from the brain. The sono- M. Oshinsky, M. Cooper, B. Simon graphic characteristics of venous cerebral blood flow were strongly Thomas Jefferson University (Philadelphia, US); ElectroCore LLC correlated with headache intensity and depression level. In women (Morris Plains, US) with TH the above indicated correlations were more severe (p\0.01) Objectives: To study the action of acute, non-invasive vagal nerve than in men-patients (p\0.05). stimulation (nVNS) on trigeminal pain. Conclusion: Tension-type headache in older-aged women is Methods: Using a rat model of recurrent trigeminal pain, we tested characterized by the increase in attack intensity, duration, frequency the ability of nVNS to suppress the behavioral response elicited by and manifestation of accompanied symptoms. Co-morbid emotional periorbital von Frey stimulation. In this model, dural nociceptor disorders and sleep abnormalities, abnormal venous outflow prevailed activation is induced by infusing an inflammatory soup (IS) through a in women-patients. The received data require partly different diag- dural cannula in awake rats. This is repeated 3 times per week for 4 nostic and therapeutic approaches in older-aged men and women with weeks. This models the transformation of episodic to chronic pain TH. seen in chronic migraine. Repeated dural nociceptor activation leads to a state of secondary chronic pain on the face, which closely mat- ches the pattern of referred pain in the migraineur. One week after the last infusion, under isoflurane anesthesia, an P630 Elizabethan collar with electrodes was positioned on the shaved skin Pericranial tenderness during attacks in cluster of the neck over the vagus nerve and the animal was stimulated for 1 min. Isoflurane anesthesia (3 %) lasted up to 5min. The nVNS signal headache patients consisted of 1ms bursts of 5 kHz sine waves repeated at 25 Hz. The K. Takagi, K. Yamazaki, M. Arai, S. Nojima, H. Kobayashi, peak voltage applied via the two small metallic electrodes was *22 L. Tonguk V. The control for nVNS was collar placement, but the stimulator was Tokyo Medical University, Ibaraki Medical Center (Inashikigun, JP) not turned on. Results: Following the 10 infusions of the IS, the rats had allodynia Objectives: According to the international classification of headache with morning thresholds of \2g (n=13). All of the rats responded to disorders 2nd edition, pericranial tenderness (PCT) mechanisms are nVNS stimulation with a significant increase in their periorbital pain most likely to play a role in tension-type headaches (TH). In our threshold within 5 min (p\0.01, on-way ANOVA). This rapid effect former study we revealed that PCT frequency with patients who have was maintained for 3.5 h after the stimulator was turned off. Twenty- a migraine (M) is statistically significant (Chi-square test P\0.025) four hours after the stimulation, the next morning, all of the rats had when compared with the total headache data. This time we investi- returned to the pre-nVNS von Frey pain threshold levels. gated the relationship between the PCT and the cluster headache Conclusion: In a rat model of recurrent headache, trigeminal pain (CH). and allodynia are suppressed by 1min of nVNS. This effect lasts for at Methods: We studied the PCT during headache attacks, shoulder least 3.5 h after stimulation. stiffness (SS) during headache attacks, SS in daily life and the effects Funding: NIH/NINDS: 1R01-NS061571 (PI:MLO), ElectroCore of massaging using questionnaires given to 49 outpatients with CH LLC (PI:MLO). (34 males, 15 females, with an average age of 36.3 years) from May 2007 to November 2011. Results: Clinical characteristics of the 49 CH patients were observed as follows; the interruption of sleep caused by headache P632 attacks, 37 patients (28 males and 9 females), the autonomic symptoms Japanese SUNCT/SUNA – two case reports and review during headache attacks, 41 patients (30 males and 11 females), the of the literature agitation before or during headache attacks, 10 patients (8 males and 2 Y. Ito, A. Ogura, K. Imai, S. Nisida, T. Kato, T. Yasuda females), the prodromal SS, 12 patients (10 males and 2 females). Of Toyota Memorial Hospital (Toyota, JP) the 49 CH patients, 30 patients (19 males and 11 females) feel SS in daily life, 32 patients (21 males and 11 females) feel SS during Purpose and methods: Short lasting unilateral neuralgiform headache headache attacks more than SS in daily life including the patients that attacks with conjunctival injection and tearing: SUNCT (primary do not feel SS in daily life, 9 patients (8 males and 1 female) who do cephalalgia classified as 3.3 in ICHD-II) and short lasting unilateral not feel SS in daily life feel SS only during CH attacks, whereas 7 neuralgiform headache attacks with cranial autonomic symptoms: patients (6 males and 1 female) who do not feel SS during CH attacks SUNA (primary cephalalgia as A3 in appendix of ICHD-II) are rare feel SS only in daily life. 39 patients (27 males and 12 females) had unilateral trigeminal headache with autonomic symptoms including PCT during CH attacks. This is 80 % of all CH patients and higher conjunctival injection, dacryorrhea, nasal obstruction, rhinorrhea and than 76 %, the ratio of PCT of all M patients in our former study. In blepharedema. The incidence of SUNCT/SUNA remains unknown in reference to our former study 61 % of all TH patients and 61 % of all Japan and therapeutic strategy for SUNCT/SUNA is not established headache patients had PCT. Additionally in our present study, mas- yet. We experienced two cases of SUNCT/SUNA patients (SUNCT saging had prophylactic effects or curative effects during CH attacks in 29 year-old man and SUNA 34year-old woman) and reviewed 7 patients (5 males and 2 females) of the 49 CH patients. reported cases of Japanese SUNCT/SUNA. Conclusion: We revealed that CH patients as well as M patients Results: Thirteen cases (10 SUNCT and 3 SUNA patients) feel PCT more frequently than TH patients. PCT in CH seems to involving 9 men and 4 women are reported in Japan. The average age appear sometimes as a kind of prodrome or as an abnormal muscle is 51+-21 years old (18-81year). Cephalalgia is recognized on the left contraction against severe headache attacks. We believe this may side in 9, right in 2, both in 1 and unclear in 1 patients. Duration from provide new clues to resolve the pathogenesis of CH and that there is the onset to the diagnosis ranged from 4 days to 15 years. As for the a possibility that muscle contraction reduction has prophylactic or treatment, triptans were not effective in general, and several anti- curative effects in a part of CH patients. convultants like gabapentin, topiramate, lamotrigine and zonisamide 123 J Neurol (2012) 259 (Suppl 1):S1–S236 S165 were effective. In some cases, these antiepileptic drugs dramatically nausea, and mild to moderate intensity. The pain lasted for minutes or reduced the headache and autonomic attacks soon. The long-term usually half an hour and pain attacks repeated 2-3 times a month. clinical course under medication are good and as a whole, recurrence Case 2: The 50-year-old female patient has had complaints of was not reported even after reducing or quitting the medications. headache for 30 years with similar characteristics as in case 1 which is Conclusions: The incidence of SUNCT/SUNA may be underesti- only triggered by yawning. The patient also had more attacks than mated. Though some antiepileptic drugs are effective, long-term case 1 and sometimes 2-3 times a day. clinical course of this headache is not elucidated and the timing to The cases had no accompanying autonomic symptom. None had reduce or quit the medication is not established yet. Establishment of migraine history and temporomandibular joint dysfunction. Neuro- the therapeutic standard plan of SUNCT/SUNA is expected. logical and oral examinations, brain magnetic resonance imaging, cranial nerve electrophysiological testing and skull X-rays of patients were normal. Body mass indexes were 56 and 58 in Case 1 and 2 respectively. P633 Conclusion: Yawning may be considered as a premonitory New-onset headache in people over 50 years old symptom in some migraine patients. Prodromal symptomatology like mood changes, yawning, drowsiness are associated with dopaminer- A. Pashapour, A. Taheraghdam, P. Pashapour, gic activation in migraine patients. It is well known that S. Pashapour hypothalamus is the primary organ in controlling various biological Tabriz University of Medical Sciences (Tabriz, IR) rhythms and arrangement of many endocrine and autonomic functions. Hypothalamic dysfunction in obese patients can lead yawning Background and purpose: Headache is one of the most common headache through similar mechanisms as pathophysiology of problems among people that referred to clinics of neurology and it’s migraine by interacting dopaminergic systems. prevalence is about 90 %.Although most of headaches are benign but some of secondary headaches are in the base of serious pathological problems. Since secondary headaches are more common in old ages (people over 50) this study is performed about this type of headaches P635 as a pilot study and surveys 100 patients over 50 years old with new Migraine with persistent aura without infarction onset headache. The goals of this study was evaluation of headache types with beginning after 50 years old. associated with periventricular heterotopia: a case Materials and methods: 100 patients with new onset headache that report were over 50 years old selected among the patients of neurology D. Vanghelie, R. Gurgu, N. Ploscutanu, C. Panea clinics. A medical history with exact points about the headaches of Elias University Hospital of Emergency (Bucharest, RO) people over 50 years old was taken then the physical examination was performed by neurologist and abnormal findings detected. Since all of Case report: We want to present the case of a 39 years old female, the headaches in this study was new onset, neuroimaging in all who presented to our hospital for visual disturbances (,,stroboscopic patients and serologic test in some of them that was necessary for sight’’), followed by right-sided hemicrania. The patient reported two diagnosis requested. The first diagnosis based on clinical finding episodes with similar symptomatology in the preceding year, each compared with the results of para clinical findings. with a duration of approximatively 72 h. She had no family history of Then all of the cases studied about their age/sex/quality of pain/ neurological deficits, an unremarkable previous medical history and a most common symptom/Environmental factors that improve or worse normal intellect. Neurological examination revealed right hemianopia the headache and response to treatment and most common abnormal and alexia, that persisted for approximatively 24 h. Brain MRI findings in physical examination. showed a complex cerebral malformation, including left hemim- Results: This study showed that secondary headaches are responsible egalencephaly, bilateral occipital and temporal periventricular for 68 % of new onset headache in people over 50 and these headaches heterotopia and enlargement of left lateral ventricle, without any sign are in the base of pathologic etiologies. This new onset headache occur of infarction. The interictal scalp EEG was abnormal, with bilateral more commonly in female and in the age 50-60. the median age is 61/68. spike discharges and pronounced photic driving. In 61 % of this patients the findings of brain CT- scan are compatible with Discussion: Malformations of cerebral cortical development are the first diagnosis based on clinical findings. In 39 % of patients CT-scan common anomalies of the brain, typically causing developmental has complementary informations. The most common secondary head- delay or seizures that are classically thought to begin in childhood. ache was subarachnoid hemorrhage and the most common primary There are however reported cases in which evidence of neurologic headache was migraine. Nausea was the most common symptom and dysfunction was first noted in adulthood, usually as epilepsy. The abnormal fundoscopy was the most common sign. particularity of our case is migrainous headache with persistent aura (but with duration of less than the classical 1 week) without infarction, and an abnormal EEG in the absence of seizures or intellectual deficits in an adult female with cerebral heterotopia. P634 Yawning headache associated with morbid obesity: presentation of two cases P636 Y. Kaplan, H. Karaer, S. Kurt, O. Kamisli New daily persistent headache and radiologically Inonu University (Malatya, TR); Gaziosmanpasa University (Tokat, TR) isolated syndrome: would you treat? Objectives: There are few case reports about headache triggered by D. Aguiar de Sousa, R. Geraldes, J. Sa´ yawning. On this poster we present two cases presumed with yawning Santa Maria Hospital (Lisbon, PT) headache associated with morbid obesity. Case 1: The 32-year-old female patient has had complaints of Introduction: New daily persistent headache (NDPH) is a recognized headache only triggered by yawning for 12 years. The pain has been form of chronic daily headache rarely associated to CNS localized on bilateral temporal region and throbbing, associated with inflammation.

123 S166 J Neurol (2012) 259 (Suppl 1):S1–S236

Case report: 33 year old female with previous history of infrequent P638 tension headaches. At the age of 27, while travelling on bus, she refers Complex neurological involvement in progressive a sudden onset headache, with pressure like character in both ears that persisted since then with periods of exacerbation but no total remis- hemifacial atrophy: first case with persistent idiopathic sions. No migraine features or any history of extracranial infection, facial pain surgery or stressful life events was reported. She had several ETN G. Dalla Costa, D. Dalla Libera, B. Colombo, evaluations, being referred to a neurologist 1 year after onset. Neu- V. Martinelli, G. Comi rological examination was normal. MRI showed multiple San Raffaele Hospital (Milan, IT) hyperintense T2 white matter lesions ([9), including in corpus callosum and periventricular, with no gadolinium enhancement. MRI Objectives: to describe a case of Parry Romberg Syndrome (PRS) venography was normal. Lumbar puncture was performed with associated with complex neurological involvement and Persistent opening pressure of 150 cmH2O, normal cytological and biochemical Idiopathic facial Pain according to IHS criteria. study. Microbiological examinations were negative as well as VDRL Methods: Observational case report. and Lyme serology. Three unmatched oligoclonal bands were present Results: A 50-years-old Caucasian woman was referred to our in the CSF (but not in serum). Apart from single positive anti- hospital because of intractable partial epilepsy and episodic facial phospholipid determination (in three), autoimmune (ANA, anti- pain beginning at age 36. She had unremarkable family history and dsDNA, antiSSA, SSB) and viral (HIV, CMV, EBV) studies were normal motor and mental development. When she was in her twenties unremarkable. Evoked potentials were normal. Two years after she noticed a skin lesion on right parietal side of the scalp, that headache onset she was depressed and complaining of persistent pain progressed toward the right frontotemporal region in 10 years At 35 that did not remitted with trials of NSAI (with no abuse), amitriptylin, years old, she suffered from blurred vision: an ophthalmologic topiramate, pregabalin or gabapentin. There were no other complaints examination revealed a right eye retinitis. She went on cyclosporine or neurological signs. A new MRI showed new T2 supratentorial therapy since then, due to a suspected diagnosis of Behcet’s disease. lesions, one of then with gadolinium enhancement. The patient con- At age 37 she began to suffer from partial epilepsy refractory to sulted multiple physicians and, considering MRI based dissemination medications and persistent facial pain. Brain MRI showed a T2 in time and refractory NDPH, therapy with IFN-beta1a was initiated. hyperintense lesion in the right temporal lobe with associated focal After a period of 2 years with IFN, 6 years after headache onset, she cortical atrophy. In the following years brain MRI showed slow referred improvement in intensity but persistent pain. There were progression of the T2 hyperintense lesion, finally affecting all the other complaints or neurological signs right cerebral hemisphere. Brain AngioMRI was normal. The patient Conclusion: We report a patient that met criteria for NDPH and slowly developed left hemiparesis and slight cognitive impairment. radiologically isolated syndrome (RIS), an association not previously Facial pain converted during years in a chronic form classified as a described. It was reported a tendency for stabbing headaches during persistent idiopathic facial pain according to ICHD-II. In fact, she relapses in MS but whether the occurrence of persistent headache can reported a daily dull and aching pain of moderate intensity, persistent be regarded as an initial event remains to be determined. The path- for all the day, localized in right temporo-parietal side with no ophysiology of NDPH is largely unknown and, as in RIS, it is crucial associated neuro-vegetative symptoms. Immunological tests (ANA, to exclude secondary causes. Consensual risk stratification of patients LLAC, C3, C4, RF, pathergy test, HLAB51) were all normal. A with RIS and refractory headache is still needed to guide treatment in diagnosis of linear scleroderma en coup de sabre for her right parietal these cases. skin lesion was suggested, and a diagnosis of Parry Romberg Syn- drome was assigned because of the clinical and neuroradiological features specifically ipsilateral to the craniofacial abnormality. Cyclosporin was discontinued and a good control on epileptic P637 crisis and pain was achieved thanks to Levetiracetam and Topiramate. A case of cluster headache accompanying myoclonus Conclusions: Parry Romberg is a rare syndrome of unknown ori- and hemiparesis gin characterized by hemiatrophy of the face along with various H.M. Park, S.K. Park, K.T. Kim ocular and CNS abnormalities (20 % of the cases). This is the first case reported of Parry Romberg Syndrome associated with complex Gachon University, GIl Hospital (Incheon, KR) neurological involvement (hemiparesis and epilepsy) and Persistent Background: Cluster headache is a primary headache disorder char- Idiopathic facial Pain, with good response to Levetiracetam and To- acterized by periodic, episodes of intense headache accompanied by piramate treatment. autonomic symptoms. We report an unusual clinical presentation of cluster headache which was preceded by myoclonus and accompanying hemiparesis. P639 Case report: A 26-year-old man visited hospital for recurrent jerky movements on his left-side face and neck area for 3 days. Jerky Non-traumatic pneumocephalus with intracerebral air movements lasted for 3 days and disappeared without specific treat- filled cavity. A case presentation ment. On tenth day after onset of jerky movements, he developed a D. Fabo, P. Vegso, H. Richter, A. Papp, A. Sakovics, series of unilateral severe headache accompanying autonomic L. Finta, A. Kamondi symptoms lasting 1 or 2 h. According to ICHD-2, he was diagnosed National Institute for Neuroscience (Budapest, HU); Semmelweis as having cluster headache. Twice out of 16 severe headache attacks University (Budapest, HU) were accompanied by dysarthria and hemiparesis. Electroencepha- lography (EEG) during hemiparesis showed diffuse lateralized slow Objective, Methods: Case presentation of a patient with sudden onset activity on the ipsilateral hemisphere of the headache side. His headache. headache accompanying hemiparesis disappeared after medical Results: The 37 years old women presented at the department six treatment of cluster headache. days after her sudden onset and progressing headache. The patient Conclusions: We describe a case of cluster headache accompa- complained intensive pulsatile headache localized to the frontal area nying hemiparesis, which was preceded by myoclonus. We also and the tip of the head that became worst moving her head. This was delineate possible mechanism of this case. different from her usual tension type headache. The neurological

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S167 status was normal. The brain CT, and skull X-ray showed a 5.5cm perception thresholds). No significant differences in any of the static largest diameter cavity in the left frontal lobe filled with air along QST parameters were observed between CNP and non-CNP MS with significant amount of air in the subarachnoid space. Brain MRI patients with the only exception of the ,,paradoxical cold sensation‘‘, resulted dorsally displaced midline structures, and relative absence of i.e. a warm stimuli perceived as a cold sensation, which were reported space occupation due to the large frontal intracerebral lesion. Lumbar in 2 CNP (and no non-CNP) MS patients, while ,,paradoxical heat puncture resulted low CSF pressure. Liquor scintigraphy resulted sensation‘‘, i.e. a cold stimuli perceived as a burning hot painful depressed circulation of CSF, low activity of the tracer reached the sensation was found in about a quarter of both the CNP and non-CNP level of the ventricles, and we found no CSF leakage. The patient MS patients. Nosuch paradoxical sensation was observed in any of the remained afebrile with i.v. ceftriaxon. The headache eased during the healthy controls. A trend towards less efficient temporal summation first two weeks, and the subsequent CT scans showed graded of thermal stimuli was observed in MS patients, particularly in CNP- replacement of air with CSF. We tried to repeat the liquor scintig- MS subgroup A significant DNIC-like effect was demonstrated in raphy applying the tracer cisternally. As the needle entered the both groups without any significant differences between them. subarachnoid space, the patient felt sudden intensive headache, thus Conclusion: Only minor differences in sensory and pain percep- we omitted the tracer injection. Repeated CT scan showed increased tion were observed between CNP and non-CNP MN patients. amount of air in the subarachnoid space and in the frontal cavity. The air was replaced again gradually with CSF, and the patient became symptom free after additional 2 weeks. After 3 years of symptom P641 freedom, the patient experienced water like rhinorrhea and repeated The influence of hypophyseal-gonadal system liquor scintigraphy resulted liquor leakage into the ethmoid cells. The suspected ethmoid cells, and the frontal sinus had been closed sur- on the formation of tension-type headache in women gically. According to the patient medical history at birth the umbilical of reproductive age chord was curled around the neck, and it retained the baby within the H. Derevyanko birth canal. The delivery was finished using forceps that caused some Clinic of Bashkir State Medical University (Ufa, RU) cranial deformity, which normalized after some years. Conclusions: We concluded that at birth the forceps and the Objective: The study of general pathophysiological regularities and hypoxia caused closed skull injury near the nasion, and a porence- the role of psychoemotional and endocrine disorders in formation of phalic cyst. Due to a non-stable defect of the dura occasional liquor tension headache in women of reproductive age. leakage might have happened resulting chronic liquor hypotension, Methods: The complete clinical-neurologic examination was made and tension type headache. After a suspected sinusitis this defect to all patients using the developed record for patients with primary might have been opened and the suddenly entering air normalized the cephalgia. In blood serum, in luteinizing and follicle phases we pressure closing the leakage instantly. evaluated the content of estradiol, testosterone, progesterone, follicle- stimulating hormone (FSH), luteinizing hormone (LH) and cortisol. The immunoradiometric method was used to determine the hormone concentrations in conformity with the programs attached to reagents. P640 Neuropsychological examination was focused on the assessment Evaluation of sensory and pain perception of psychological state (i.e. level of depression and anxiety); to do that and mechanisms of central modulation of pain we applied the Beck scale as well as the Hamilton and Spilberg one. For quantitative estimate of appreciation of pain in points, the visual- perception in patients with multiple sclerosis (a pilot analog scale for pain evaluation was used. study) Results: 1. At moderate personal and reactive anxiety and M. Hnojcikova, E. Vlckova, I. Okacova, P. Praksova, depression, in women with chronic tension headache the increased S. Bursova, J. Bednarik on behalf of CEITEC – Central cortisol in blood was found. 2. In a follicle phase the women with chronic tension headache European Institute of Technology, Masaryk University had the increased luteinizing and follicle-stimulating hormones, while Introduction: Multiple sclerosis (MS) is considered as a suitable in a luteinizing phase-the increased progesterone. Estradiol, testos- model for central neuropatic pain (CNP). Knowledge of sensory terone and cortisol were increased as in the luteinizing, as in the profile and function of central modulation of pain perception in CNP follicle phases of the ovary cycle. Quantitatively, the hypothesis- patients may help to reveal underlying mechanisms of CNP, which ovary and hypothesis-adrenal cortex hormones in patients with epi- are still not fully understood. sodic tension headache were within the normal range in both phases Patients and methods: A detailed evaluation of sensory and pain of the ovary cycle. perception and of mechanisms of central modulation of pain per- 3. In women of reproductive age with chronic tension headache, ception using an extensive battery of bedside and quantitative sensory cephalgia accompanied by moderate reactive and personal anxiety testing (QST) was performed in 17 patients with MS (11 men and 6 and evident depression during the ovary cycle becomes more inten- women, median age 31, range 19-56 years) and 20 healthy volunteers sive. The women with episodic tension headache demonstrated low (8 men and 12 women, median age 34, range 23-55 years). Seven of anxiety and absence of depression in follicle and luteinizing phases. the MS patients fulfilled the current diagnostic criteria for central Conclusion: The obtained data allow us to trace the pathogenic neuropathic pain (CNP-MS subgroup), while no pain was recorded in correlation among chronic tension headache and hormonal deviations. the remaining 10 MS patients (non CNP-MS subgroup) and healthy controls. The testing included both static and dynamic QST methods. Among others, magnitude of conditioned pain modulation (diffuse noxious inhibitory control (DNIC)-like effect) and temporal sum- P642 mation (TS) using thermal stimuli were assessed. Efficacy of sodium oxybate in episodic cluster Results: Comparing to healthy controls, MS patients (irrespec- headache: case report tively to the presence of CNP) showed the decreased perception of most of the sensory modalities examined (e.g. decreased cold per- H. Hidalgo, V. Uhl, A. Gantenbein, P. Sańdor, U. Kallweit ception thresholds and increased warm, tactile and heat pain Kamillus-Klinik (Asbach, DE); University Hospital (Zurich, CH)

123 S168 J Neurol (2012) 259 (Suppl 1):S1–S236

Background: Cluster headache is a disabling and severe trigeminal P644 autonomic headache disorder. Common therapeutic interventions Chronic pelvic pain in irritable bowel syndrome: includes application of oxygen and triptan medication. Limited data are available on the efficacy of sodium oxybate in long term therapy another burden to deal with in chronic cluster headache. D. Georgescu, C. Georgescu, L.A. Georgescu, M. Simu Case report: We report the case of a 60-year-old gentleman University of Medicine (Timisoara, RO) suffering from episodic cluster headache for 15 years with attacks Objectives: Fighting pain in irritable bowel syndrome(IBS) is not of intense unilateral (usually right-sided) headaches accompanied such an easy task due to the complexity of involved pathogenic by ipsilateral conjunctival injection, lacrimation, rhinorrhea, pathways. The aim of this study was comparing efficiency of Gab- sweating and flush. Episodes of headache occurred once to twice a agamma alone versus Gabagamma half dose plus Probiotics and year with attacks usually twice a day in the early mornings for Dimeticone in mitigating the pelvic complaints in IBS patients, based approx. four weeks with an attack duration of 15 to 90 min. The on the observation that one of the major factors triggering the pelvic patient tended to avoid sleep in order to prevent attacks. Treatment pain process is distension of the colon. with oxygen inhalation and zolmitriptan 5mg, if applied early Methods: 30 female patients, mean age= 38,76±15,51 years, with enough, was partially effective in reducing the attack duration from diagnosed IBS according to Rome II criteria, suffering from chronic 90 to 15min. pelvic complaints were enrolled in this study after ruling out other In March 2010 the patient was admitted to our clinic for suf- causes of pelvic pain Each patient was thoroughly examined and the fering for 3 days from attacks which could not be interrupted by the intensities of each symptom were scored according to Gastrointestinal patient’s usual medication. We started treatment with sodium oxy- Symptom Rating Scale (GSRS), on a 7-graded Likert scale from 0 = bate (SO), in a dosage of 1.5 g taken immediate before going to no symptoms to 6 = very severe symptom. The following symptoms bed). The next day, the patient described a headache night. were assessed prior and after 3 months of treatment: dyspareunia, Continuing treatment for one more week, no more attacks occurred. cystalgia, urinary urge. Patients were randomly devised in 2 groups, Since then, he applies SO in the above dosage when cluster head- each of 15 patients. First group received Gabagamma in increasing ache attacks occur, which occurred 2 times since then with 2 single dose till 1200mg/day, the second group received half doses of Gab- attacks. agamma(600mg/day) associated to Probiotics (1 billion strains/ Discussion: This case suggests that SO may not only be a thera- capsule Lactobacillus acidophilus 50 % and Bifidobacterium bifidus peutic option in chronic cluster headache patients, but might be 50 %),3 capsules/day plus Dimeticone 80 mg, 3x2 chewing pills/day effective episodic cluster headache. for 3 months. Results: First group had the following scoring : prior therapy dyspareunia=2,93±0,88. cystalgia=3±1,31, urinary urge=2,58±1,25; after therapy: dyspareunia=2,20 ±0,77 (p=0,0022), cystalgia=2,2± P643 0,86 (p=0,058),urinary urge=2,07±0,73(p=0,26).Second group had the following scoring prior therapy: dyspareunia=3,13±1,06, cystal- Small nerve fibres involvement in fibromyalgia gia= 2,73±1,16 urinary urge=1,87±1,13; after treatment: dyspareunia= R. Liguori, M.P. Giannoccaro, A. Incensi, V. Donadio 1,6±0,63 (p\0,0001), cystalgia=1,40±0,50 (p=0,0003), urinary urge= University of Bologna (Bologna, IT) 0,66±0,61 (p=0,0011). Conclusions: This study revealed that Gabagamma as high dose Objectives: Fibromyalgia (FM) is a chronic syndrome of unknown monotherapy has a significant response only in mitigating dyspareu- etiology primarily characterized by widespread pain accompanied by nia. Gabagamma at lower doses, but associated to Probiotics and muscle stiffness, fatigue, unrefreshing sleep, cognitive disturbances Dimeticone resulted in an increased response and all the assessed and mood disorders with impairment of daily activities. A possible complaints were significantly alleviated. role of small nerve fibres underlying FM pathogenesis has been suggested. The aim of the study was to investigate the presence of small fibres neuropathy (SFN) in FM patients. Methods: We studied 20 consecutive subjects affected by primary Dementia II FM. Patients underwent neurological examination, nerve conduction studies and skin biopsies from distal leg and thigh. Specimens were fixed, sectioned and incubated with primary antibodies, including the P645 pan-neuronal marker protein gene product 9.5 (PGP 9.5), collagen IV and specific autonomic antibodies as vasoactive intestinal peptide The memory fair: a simple tool to reach populations (VIP) to mark cholinergic fibres innervating sweat glands and dopa- at risk for developing AD mine beta hydroxylase (DBH) to visualize adrenergic fibers N. Bregman, O. Moore, K. Regev, B. Irina, N. Giladi, innervating blood vessel and erectors muscles of hair. The epidermal E. Ash nerve fibers density identified by PGP 9.5 was calculated per linear Tel Aviv Sourasky Medical Center (Tel Aviv, IL) millimetre (mm) of epidermis. Twenty age-matched healthy subjects without clinical signs of neurological dysfunctions were used as The early detection of people at risk for developing Alzheimer’s controls. disease (AD) is one of the major difficulties in the field of therapy Results: Nerve conduction studies were normal in all patients. development. The Center for Memory and Attention Disorders within SFN was diagnosed in 6/20 FM patients, because of reduction in the department of Neurology at Tel Aviv Sourasky Medical Center epidermal nerve fibers density. In these cases abnormalities of both organized a ‘Memory fair’ for the public aimed to serve as a tool to adrenergic and cholinergic fibers innerving cutaneous annexes were reach pre-symptomatic individuals and those with possible Mild also observed. Cognitive Impairment (MCI) at risk for developing AD. Conclusion: A subset of FM subjects presents a SFN which may Methods: The general Israeli public over age 50 was invited to contribute to sensory and autonomic symptoms observed in this participate in the fair via publicity in print and television media. condition. Skin biopsy should be considered in diagnostic workup of Participants visited interactive stations where they received infor- FM. mation about risk factors for cognitive decline and participated in

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S169 physical and mental training exercises. Additionally, several open semantic knowledge or discourse. Subtle language disorders could be lecture sessions were provided on issues related to the prevention and promoted by the dysexecutive syndrome. early detection of cognitive decline and AD. Interested participants were also invited for a free cognitive evaluation using the Montreal Cognitive Assessment (MoCA) followed by a personal interview with a neurologist. Participants completed a brief demographic and health P647 information questionnaire. Data was analyzed using t-test and Chi- Episodic memory differences in Alzheimer’s disease, square tests for continuous and categorical data respectively. frontotemporal dementia, and dementia with Lewy Results: 160 subjects (mean age 70±9, 27 % M) completed the bodies/Parkinson’s disease dementia assessment process. The average MoCA score was 24.01±3.75. 67 subjects (41.8 %) had MoCA scores of [=26, 61 subjects (38.1 %) A. Economou, C. Routsis, A. Tsapanou, S. Matsi, had scores between 22-25, and 32 subjects (20 %) had scores of T. Kontaxis, A. Bonakis, N. Kalfakis, A. Kyrozis, \=21. There were no significant differences in average MoCA scores S.G. Papageorgiou between age groups (60-64, 65- 69, 70-74, 75-79). University of Athens (Athens, GR) 37.3 % of fair participants reported a family history of severe memory impairment and 36.5 % reported a history of depressive Objectives: Despite extensive research on memory performance in symptoms. 72.6 % had subjective concerns of memory impairment. different dementias, no clear conclusions have emerged and memory Self report of memory concern was significantly higher in the group differences often do not persist once demographic variables are with the lowest MoCA scores compared with the group with the controlled for. We compared Alzheimer’s disease (AD) patients, highest MoCA scores (p\0.01). Individuals with MoCA scores of frontotemporal dementia (FTD) patients, and dementia with Lewy 22-25 and self concern for memory impairment established an upper bodies/Parkinson’s disease dementia (DLB/PDD) patients on the 5 estimate of MCI prevalence of 30.7 % in the assessed population. Words Test (Dubois, 2000), a brief test of verbal memory that con- Conclusions: Conducting a ‘‘memory fair’’, an easily accessible trols for encoding of information, with overall cognitive functioning and enjoyable public event, can serve as a simple and relatively low- and demographic variables as covariates. We specifically examined cost tool to identify people at risk for developing dementia and AD. the extent to which the patient groups benefit from the provision of This tool can be used to increase awareness about preservation of cues relative to free recall (immediate and delayed). cognitive function in the general population. Methods: Participants: Three groups of patients from a memory clinic: 106 AD patients, 49 FTD patients, and 26 DLB/PDD patients (8 DLB, 18 PDD patients). Measures: The 5 Words Test requires the recall 5 unrelated words read by the examinee, with cues provided P646 during study to facilitate encoding. Free and cued recall are assessed Subtle language in patients with Alzheimer’s disease immediately afterwards and after 5 min. Procedure: Patients received a battery of tests that included a Greek version of the modified Mini M. Rousseaux, P. Dei Cas, S. Connin, A. Tillard Mental State Examination (mMMSE). CHRU de Lille, Hospital Swynghedauw (Lille, FR); University de Results: FTD patients were younger than both AD and DLB/PDD Lille 2 (Lille, FR) patients (all ps \ .0001), as expected, and more educated than DLB/ Introduction: Subtle language is in relationship with higher level PDD patients (p\.01). The groups did not differ in mMMSE scores. knowledge and usage of language. It comprises of elements of meta- Age and education correlated with mMMSE (all ps \ .0001), and language and pragmatics, which is the use of language by interacting education correlated with the 5 Words Test (all ps \ .01). Repeated communication partners. Patients with Alzheimer’s disease (AD) measures analyses with Trial as within-subject factor, Group as classically show lexical and syntactic disorders of progressive onset, between-subject factor and age, education (years), and mMMSE with word finding difficulties, reduced verbal fluency, and impaired scores as covariates showed a Trial by Group interaction. AD patients comprehension. However, subtle language has never been analyzed. showed a steeper decrease in performance from immediate cued recall Our aim was therefore to evaluate this language in a population of AD to delayed free recall. DLB/PDD patients benefited more from cues in patients with moderate to moderately severe dementia. delayed recall than the other 2 groups. No differences among the Methods: We included 25 patients with the classical disease cri- groups were found in immediate recall. teria and a MMSE [ 15/30. The subtle language was analyzed by 15 Conclusion: Lack of significant differences in immediate free and tests: definitions, evocation of names from definitions, concatenation cued recall among the 3 groups, once demographic factors and cog- of phrases, synonyms, procedural discourse, verbal logic, polysemy, nitive functioning were covaried and encoding was controlled for, intruders, absurd, differences, proverbs, declarative discourse, ant- indicates no differences in immediate memory. The larger decrease in onyms, figurative expression, and argumentative discourse. There performance from immediate cued recall to delayed free recall in AD were three levels of increasing difficulty in each test. Patient per- patients cannot be attributed to differences in encoding but to more formance was compared to that of an equivalent group of normal rapid forgetting. The greater benefit of cues for the DLB/PDD patients control subjects (age, education level, gender). is consistent with a retrieval deficit. Results: Multivariate analysis showed a significant (p \0.05) overall deficit of patients, with preferential impairment of verbal logic, differences, proverbs and figurative expressions. But definitions P648 and discourses were relatively preserved. There was an effect of difficulty level, because deficits mostly affected difficult subtests. Nonverbal memory differences in Alzheimer’s disease, These disorders correlated with the severity of dementia (Dementia frontotemporal dementia, and dementia with Lewy Rating Scale), conventional tests of aphasia (verbal fluency, naming) bodies/Parkinson’s disease dementia and the dysexecutive syndrome (Trail Making Test), but not with S.G. Papageorgiou, A. Economou, C. Routsis, episodic memory disorders. Discussion: At the early stages of Alzheimer’s disease, patients A. Tsapanou, T. Kontaxis, S. Matsi, A. Bonakis, have relatively selective impairment of certain subtle language skills, A. Kyrozis, N. Kalfakis with respect to other simpler language skills including verbal University of Athens (Athens, GR)

123 S170 J Neurol (2012) 259 (Suppl 1):S1–S236

Objectives: Visual memory performance in different dementias might devised in our department. These test batteries also included evalu- be confounded by visual-perceptual deficits and/or attentional ating the perceptual abilities to recognise faces and non-emotional impairments. To address these issues, we compared Alzheimer’s prosody. disease (AD) patients, frontotemporal dementia (FTD) patients, and We compared 7 patients with initial FTD (6 males, 1 female; mean dementia with Lewy bodies/Parkinson’s disease dementia (DLB/ corrected MMSE= 24,9), 8 patients with initial AD (2 males, 6 PDD) patients on the 5 Objects Test, a brief test of memory for females; mean corrected MMSE= 25,8) with 15 healthy subjects location of 5 everyday objects, which does not require construction, matched for age and educational level. controlling for overall cognitive functioning and demographic Results: FTD patients were impaired in the Faux Pas Test (general variables. score p\ 0.001; Faux Pas stories score p\ 0.001), in the RMV (p\ Methods: Participants: Three groups of patients from a memory 0.001), and in the subtests of the emotional batteries aimed at clinic: 106 AD patients, 49 FTD patients, and 26 DLB/PDD patients assessing the emotional abilities (FARB-v3: p= 0.001; FARB-v4: p\ (8 DLB, 18 PDD patients). Measures: The 5 Objects Test requires the 0.005; FARB-v5: p\ 0.005; PARB-u3: p\ 0.005; PARB-u4: p\ recall of the locations of 5 everyday objects, 4 of which are placed on 0.001). AD patients showed defective performances in the Faux Pas the 4 corners of two adjacent sheets of paper (A4), and the 5th is Test (general score p=0.008; Faux Pas stories score p=0.01), in a non- placed in the pocket of the examiner. The task is repeated until perfect emotional subtest of FARB (FARB-v2: p\0.001), and in two subtests performance is achieved or up to 4 trials, with a delayed recall after of the emotional batteries requiring good memory abilities (FARB- 5 min (maximum total score=25). The examiner guides visually and v5: p\ 0.001; PARB-v4: p\ 0.001). verbally the examinee in placing the objects before each trial to We found lacking ToM and emotional abilities in FTD. On the ensure encoding. Procedure: Patients received a battery of tests that other hand, impaired performances in emotional and ToM tasks in AD included a Greek version of the modified Mini Mental State Exami- patients could be attributed to non-emotional deficits. nation (mMMSE). Conclusion: FDT patients are defective in several social abilities Results: FTD patients were younger than both AD and DLB/PDD including cognitive perspective taking and understanding social and patients (all ps \ .0001), as expected, and more educated than DLB/ basic emotions. These could be the basis of the emotional and PDD patients (p\.01). The groups did not differ in mMMSE scores. behavioural deficit found even at the early stage of FDT. Age and education correlated with mMMSE (all ps \ .0001) but not with the 5 Objects Test. Univariate analyses with age, education (years), and mMMSE scores as covariates revealed lower performance of AD patients relative to the other groups (AD: 15.91 ± 6.35, P650 FTD: 21.55 ± 5.44, DLB/PDD: 20.77 ± 5.98, all ps \ .0001). Repeated measures analyses with Trial as within-subject factor, Verbal and visuoperceptive semantic association Group as between-subject factor and the above covariates showed in aMCI and AD patients lower performance of AD patients compared to the other two groups D. Di Giacomo, L.S. De Federicis, N. Caputi, on all trials. A Trial by Group interaction revealed a steeper decline D. Passafiume from Trial 4 (immediate recall) to delayed recall in the AD group University of L’Aquila (L’Aquila, IT) compared with the other two groups. Conclusion: AD patients were more impaired on a memory test Objectives: The semantic impairment in Alzheimer’s patients was that requires no visual-perceptual ability or construction, and minimal been largely studied. The deficit was observed by analyzing the cat- language comprehension and production, with more impaired egorization process, the event recalls, the recognition of the word/ immediate recall and more rapid loss of information. The results picture. Few studies were conducted on loss mechanisms of the cannot be attributed to attentional or visual-perceptual deficits. knowledge and in specify in the degradation of semantic store and the decrease of categorization ability (see Peraita, 2004). Few studies were oriented to verify the semantic associative ability. Passafiume (2012) suggested the in the semantic degradation in the dementia the P649 information were lost by processes that initially interest the abstract Frontotemporal dementia and Alzheimer’s disease: relations and later on, with the progression of the cognitive degen- cognitive and affective theory of mind abilities eration, the relation more related at the perceptual storage system. C. Sola, F. Benuzzi, M. Molinari, P.F. Nichelli Aim of study is to verify the progression of the loss of associative relations in cognitive deterioration not only in the dementia but in University of Modena and Reggio Emilia (Baggiovara, IT); Ausl Mild Cognitive Impairment already. Modena (Modena, IT) Methods: The sample recruited in the study was divided in 4 Objectives: Theory of Mind (ToM) encompasses a heterogeneous groups: a) 19 subjects with Amnestic Mild Cognitive Impairment group of abilities that guide people in their social interactions. ToM (aMCI) (mean age 71,0); 16 patients with mild Alzheimer’s Disease abilities require attributing thoughts, intentions, and beliefs to others (AD) (mean age 72,0); 20 patients with moderate AD (mean age and involve several processes, including cognitive perspective taking 74,3); 20 Normal Control (NC) (mean age 68,3). An experimental (cognitive ToM) and understanding emotions (affective ToM). This tasks battery carried out to evaluate the verbal and visuoperceptual study was aimed at assessing whether a deficit in cognitive and/or semantic association abilities and to naming tasks (verbal naming and affective ToM could explain the behavioural and emotional deficit visuoperceptive naming). Results. Our results suggest a progressive found in patients with degenerative diseases (Frontotemporal impairment in the categorization ability tested by each experimental Dementia, FTD, and Alzheimer Disease, AD). condition: in the naming tasks the AD patients have worse perfor- Methods: Cognitive ToM abilities were tested using the Faux Pas mances than NC and aMCI subjects. The statistical analysis show the Test. Affective ToM abilities were assessed through the ‘‘Reading the performance in associative relations decreasing in the pathological Mind from the Eyes’’(RME) and ‘‘Reading the Mind from the Voi- groups and evidence the similar trend in semantic degradation both in ce’’(RMV) tests, that provide information on the capability to identify visuoperceptual and verbal semantic associative tasks(F(12, social emotions. In addition, we evaluated the ability to recognize 177,5)=8,2, p=0,000). The most interesting difference are in the basic emotions by means of the Facial Affect Recognition Battery comparison between the performance of aMCi and AD groups. The (FARB) and of the Prosodic Affect Recognition Battery (PARB), both trend is confirmed even analyzing the performance of each of the 4

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S171 associative relation examined (the Function relation is the better amplified by spatial neglect. However, we do not know the specific preserved, while the Superordinate relation is the worse). influence of hemianopia and space of perception on this perception. Conclusions: Our data seems to confirm the degradation of Here, we analysed the respective influences of spatial neglect, hem- semantic store and to clear up the loss of semantic associative rela- ianopia and hemispace on the subjective vertical in patients with right tions They suggest a degradation process based on gradual loss that in hemispheric stroke. first time involve the information linked in abstract cognitive area and Methods: Patients suffered a relatively recent unilateral right in a second time the information better related to the perceptive hemisphere stroke (MRI or CT). Neglect was analyzed by paper and storage. pencil tests and hemianopia by clinical examination in the primary This study was supported by a National Grant of Italian Minister position of gaze and/or Goldmann perimetry. Twelve patients had of University and Research (MIUR)(Future in Research, 2008). neglect and hemianopia, five were neglect without hemianopia, three had pure hemianopia and 13 were free of visual difficulties. They were compared to 14 healthy subjects. The task consisted in placing a luminous rod to the vertical, either in the mid-sagittal plane or in the P651 right or the left hemispace. Mental rotation in patients affected by dementia Results: In comparison with C (-0.4) and N–H- (-1.4) groups, L.S. De Federicis, D. Di Giacomo, D. Passafiume patients with visual difficulties showed a significant (p\0.05) counter- University of L’Aquila (L’Aquila, IT) clockwise deviation (CDD), which was greater for the N+H+ (-7.9) than for the N+H- (-3.9) and the N–H+ (-3.8). In addition, a three Objectives: Many studies show an early presence of verbal deficit in factors ANOVA of neglect (present, absent), hemianopia (present, dementia. Some studies report deficit in visuospatial task but the absent) and rod location (left, center, right) showed that the mean ability of mental rotation in subjects with cortical damage has been CDD was increased by each of the three factors, without interaction largely unstudied. Moreover the few studies on mental rotation ability between neglect and hemianopia. The rod location tended to interact in dementia have used two-dimensional stimuli. The goal of our with neglect and hemianopia, because the CCD was more severe in research is to study the performances of subjects with neurodegen- the left contralesional position of the rod when either neglect or erative pathology in mental rotation tasks with two-dimensional and hemianopia were present. We also found a significant increase in three-dimensional stimuli. variability (SD values), depending on the group (N+H+[N+H-[N– Methods: Thirty patients with mild Alzheimer’s disease (AD) and H+ [ N–H- [ C). thirty elderly subjects (normal control – NC) were assessed using the Conclusion: Our study reinforces the idea that neglect and hemi- Mini-Mental State Examination (MMSE), a standardized neuropsy- anopia both impair the perception of the visual vertical, with chological test and two experimental tasks developed ad hoc. The first independent and cumulative effects. The SV deviation represents a experimental task is the ‘‘Unusual Pictures’’ that use two-dimensional useful marker of the severity of stroke. stimuli (pictures) and is the adaptation of the test of Warrington and Taylor (1973); the second experimental task is ‘‘Spatial Rotation’’ that use the three-dimensional stimuli (modeling) and inspired to works of Butter et al. (1970). P653 Results: For statistic analysis we adopted an alpha level of 0.05 for every analysis. In order to test the difference among groups and Cognitive impairment correlates with ventricular between tasks, transformed data were submitted to a 2x3 Analysis of enlargement and event-related potentials (P300) variance for repeated measure, with two factors (groups) and three in patients with subjective memory complaints treatments (experimental tasks: usual and unusual vision and spatial N. Tevzadze, M. Janelidze rotation). Result showed differences between groups (p\0.001) and S. Khechinashvili University Hospital (Tbilisi, GE) between tasks (p\0.001), and the presence of interaction groups by tasks (p\0.001). Post hoc analysis showed a significant different Background/Aims: It is known that dementia takes many years to between AD and NC in tasks using both two-dimensional and three- develop. The process begins with the development of progressive dimensional stimuli but there isn’t a difference between two groups in memory impairment, slowing of brain processes. The event-related performances of tasks that not use the manipulation of stimuli. potential (ERP) P300 is a marker for cognitive impairment in Conclusion: Our conclusions are that in the early stage the subjects dementia. The aim of this study was to determine the changes of with AD is already present a visuospatial deficit but this does not P300 parameters in patients with subjective complains of memory depend by stimuli used but depend on the task. It’s clear that the use disturbances in relation to the presence/absence of CT/MRI of ability of mental rotation is very difficult for subject with early abnormalities. cortical damage even in tasks that use the three-dimensional stimuli Method: Auditory event-related potentials, P300 were recorded in that require a lower abstraction. 14 patients with memory complains and 15 healthy controls of the This study was been supported by Strategic Grant of Italian same age range (58-67 years). MMSE (mini–mental state examina- Minister of Health (2007 Grant). tion) in all subjects was normal - 29-30 scores. 7 patients with memory complains and 4 healthy subjects had ventricular enlargement/cortical atrophy due to CT/MRI findings. We examined auditory-cognitive P300 potentials and evaluated their correlation P652 with subjective complains and CT/MRI data. Additive influence of spatial neglect, hemianopia Results: P2N2P3 latencies were significantly longer and the N2P2 and hemispace on the subjective vertical amplitude were significantly lower in patients 9 patients with memory A. Saj, J. Honore´, T. Bernati, M. Rousseaux complains. 6 of them had ventricular dilatation and mild cortical atrophy. P300 prolonged latency was hardly associated with degree of University of Geneva (Geneva, CH); CHRU de Lille, Hospital ventricular dilatation and patients neuropsychological status. No Swynghedauw (Lille, FR) changes of P300 (ERP) were revealed in control cohort. Objectives: The perception of the vertical is frequently shifted to the Conclusion: An impaired auditory cognition determined by P300 contralesional side in patients with hemispheric lesions, and this is (ERP), correlating with presence of CT/MRI abnormalities - degree of

123 S172 J Neurol (2012) 259 (Suppl 1):S1–S236 ventricular dilatation and cortical atrophy - proves to be a sensitive Method: NeuroPsychiatric Inventory questionnaire of 100 con- marker of slight memory complains. The brain structural changes in secutive patients with PD, divided according to the age of onset, in this patients, related to P300 significantly longer latency may indicate early (\60 years) and late ([60years) groups. an increased risk for developing mild cognitive impairment or Results: The two-way ANCOVA model revealed that the duration dementia. Further investigations are necessary to confirm this of the disease had a significant influence on the levels of apathy, hypothesis. F(1,99)=6.55, p\0.05. A significant main effect of onset time on apathy was observed (after controlling for the influence of the duration of the disease on apathy) F(1,99)=5.84, p\0.05. Individuals with early onset had lower levels of apathy as compared to the individuals P654 with late onset PD. Moreover, females have greater levels of Profile of neuropsychological dysfunction in normal depressive symptomatology than males, F(1,99)=5.48, p\0.05. A pressure hydrocephalus: not just executive dysfunction significant interaction effect between gender and time of onset on P. Bugalho, L. Alves, O. Ribeiro depression levels was observed F(1,99)=4.10, p\0.05. The difference on depression levels between males and females is significantly Hospital Egas Moniz; CEDOC (Lisbon, PT) greater in individuals that developed early onset PD as compared to Objectives: Although cognitive dysfunction is one of the principal the individuals that developed late-onset PD. complaints in Normal Pressure Hydrocephalus (NPH) patients, the Conclusion: Apathy is more pronounced in late onset PD. Female nature of the deficits is still not completely understood. The proposed patients with PD are more prone to depression than males. This dif- physiopathology of the disease argues in favor of frontal dysfunction, ference is even more pronounced in early-onset PD. These findings but this remains to be fully proved. Our objective was to characterize could have a clinical applicability. the type of cognitive deficits in NPH. Methods: 17 NPH patients were compared to 14 age and education matched controls in relation to depression (Geriatric Depression Scale), global cognitive function (Mini-mental state examination), verbal P656 memory (word recall task of the WAIS-WR), impulse control (Stroop), Computerised cognitive training relieves depression verbal fluency (VF), working memory (digit span-DS), attention (letter and improves executive control in depressive disorder cancelling-LC), visuo-spatial reasoning (Raven colored matrices-RCM) M. Preiss, E. Shatil, R. Cermakova and visuo-constructive ability (Ray complex figure-RCF). To compare Prague Psychiatric Center (Prague, CZ); Max Stern Academic performance between the different tests, each score was normalized by College of Emek Yezreel, CogniFit Ltd, Yoqneam Ilit the following formula: normalized score = 1 – (median score of the (Jezreel Valley, IL) patients/median score of the controls), which represents an alternative nonparametric procedure for parametric z -transformation. We calcu- Objectives: Depression is the fourth leading cause of burden; physi- lated three composite domain normalized scores: memory (WR), visuo- cal, emotional, social and economic problems (Murray and Lopez, spatial (RCM + RCF) and executive/attention (stroop + LC + DS + VF) 1996; Williams et al.; 2000). Cognitive deficits persist during functions. Finally, we calculated the relative proportions of impairment remission, and some types of cognitive deficits represent fundamen- in each cognitive domain to whole cognitive impairment. tals trait characteristics. In comparison with cognitive training in Results: NPH performed significantly worse than controls in all hospitalized patients, there is a minimal knowledge about the effec- the tests, except GDL and DS. Normalized scores were higher for tivity of home-based, computerized, individualized cognitive training RCF (0.75), followed, by decreasing order: RCM (0.41), VF (0.33), program. Stroop (0.32), WR (0.27) and LC (0.06) The proportion of visuo- Methods: This 8 week interventional home-based study investi- spatial dysfunction (53 %) was higher than executive/attention gated the effects of cognitive training on mood and cognitive (21 %) and memory dysfunction (26 %). performance (neuropsychological functioning and everyday func- Discussion: NPH patient displayed a wide set of cognitive deficits, tioning) in individuals with major depression during remission. involving diverse cognitive domains, not restricted to the frontal Participants were allocated to either the cognitive training group or lobes. In fact, comparative analysis showed a preponderance of non- control group. Mood and cognitive performance were assessed at executive deficits and in particular of parietto-occipital dysfunction. baseline as well as following training. Participants were instructed to There are several alternative explanations for this unexpected finding: complete a 20-30 min session three times a week for the duration of coexistence of a neurodegenerative condition affecting posterior eight weeks (24 total sessions). A total of 61 participants were ini- regions; direct effect of occipital horn dilation on posterior white tially enrolled. Thirty five (18 in the computer training group and 17 matter; increased difficulty of visuo-spatial tests, which could involve in the control group) completed the study. participation also of frontal lobe structures. Results: General linear models for repeated measures were used to evaluate between-group differences in the mood and in the seven executive control variables. Differences between the groups were explored for six executive control abilities (Shifting, Divided Atten- P655 tion, Inhibition, Working Memory, Short-Term Memory and Depression and apathy in Parkinson’s disease: studying Vigilance in an Eye-Hand Motor Task) as well as for the Global the effect of gender and time of onset Executive Control score, averaged from those six variables. Training A. Tsapanou, S. Matsi, I. Beratis, C. Routsis, A. Bonakis, group changed (in positive way) in one measure of everyday functioning. The groups did not differ in mood characteristics at the N. Kalfakis, A. Kyrozis, S.G. Papageorgiou beginning of the study, while measure within group change, indicate University of Athens (Athens, GR) that improvement occurred mostly for the cognitive training group. Objectives: 40 % of patients with Parkinson Disease (PD) suffer from Conclusion: Computerized cognitive remediation program depression, more often occurring in the advanced stages of the dis- improved subjective everyday functioning and mood in remitted ease. Aim of the study: to investigate the effect of gender and disease depressed patients. duration on depression and apathy in patients with PD. This project was supported by the grant MSMT 1M0517.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S173

P657 nerves, no response to articulate abilities was seen with injection of a Diagnostic criteria for the behavioural variant cholinesterase inhibitor. Serum antibodies (Acetylcholine receptor, Muscle specific kinase, Voltage gated calcium channel) were negative; of frontotemporal dementia – revision of two criteria the spinal fluid was normal including tau protein. MRI revealed a system frontotemporal atrophy especially of the left perisylvian region, a S. Costa, M. Suarez, S. Antoń, A. Lheo´ cerebral scintigraphy showed a left temporoparietal hypoperfusion. On Hospital Professor Doutor Fernando Fonseca EPE (Amadora, PT); formal speech testing no deficits in perception or naming were detected, Hospital de la Santa Creu I Sant Pau (Barcelona, ES) minimal deficits were seen in generation of words. Reading perception and writing were intact. On neuropsychologic testing moderate deficits Background: The consensus criteria published by Neary and col- in verbal and visual memory and mild deficits of attention and executive leagues in 1998, has been the standard for behavioral variant of functions were detected. Frontotemporal Dementia (bvFTD) diagnosis. But some limitations Conclusion: Though MRI and brain perfusion studies were com- have become apparent, including ambiguity of behavioral descrip- patible with primary progressive aphasia as a variant of FTLD, our tions, inflexibility in the applications of criteria, and low sensitivity in patient did not have aphasia on speech testing while neuropsychologic early stages of the disease. The International bvFTD Criteria Con- testing was compatible with a mild dementia still compensated in sortium (Rascovsky, et al.) developed last year, new revised daily living. If the university education and the maintained intellec- guidelines, with greater sensitivity, for the diagnosis of bvFTD. tual interests of our patient might have masked aphasia or if the Objectives: Revision of diagnostic and research criteria for presented case represents a distinct subgroup of FTLD may be subject bvFTD. Clinical comparison of the two system diagnostic criteria. of future analysis of cases with FTLD. Methods: Retrospective revision of clinical charts of patients with the bvFTD clinical suspicion, from a Memory Unit. All patients had a complete investigation, and were evaluated by at least two neurologists. Results: Twenty nine patients were included, 12 female and 17 P659 male, median age of 64±10 years, and 51,1 % with positive family Functional connectivity during resting state functional history (two patients with identified genetic mutation). All of patients MR imaging in the semantic variant of primary fulfilled 2011 Criteria diagnosis for possible bvFTD but instead only 65 % of them fulfilled 1998 Criteria. All of them because of presence progressive aphasia of exclusion features, being spatial disorientation and early severe F. Agosta, L. Sarro, E. Scola, E. Canu, A. Marcone, amnesia the most frequent. Only 55 % of patients fulfilled 2011 G. Magnani, M. Franceschi, S.F. Cappa, A. Falini, Criteria diagnosis of probable bvFTD, mostly because of not com- G. Comi, M. Filippi patible imaging. Conclusions: The results of our series are in accordance with lit- Vita-Salute San Raffaele University (Milan, IT); IRCCS Multimedica erature. The major advances of the 2011 Criteria are: diagnostic (Castellanza, IT) hierarchy, greater flexibility, incorporation of genetic and neuroim- Objective: Semantic deficits in the semantic variant of primary pro- aging findings and clearer operational definitions. gressive aphasia (svPPA) have been attributed to grey matter (GM) Future prospective studies are needed to accurate specificity and damage to the anterior temporal lobe. However, since the brain reliability of these new diagnostic guidelines. functions through highly interactive networks, the role of altered functional connectivity needs to be considered. The analysis of functional connectivity of the resting state (i.e., RS fMRI), which is easy to be obtained and does not suffer from performance confounds P658 in case of cognitively impaired individuals, has been largely used to Primary progressive dysarthria without aphasia elucidate brain functional organization in Alzheimer’s disease as a variant of frontotemporal lobe degeneration patients. Up to now, there is no study investigating RS functional M. Grznarova, U. Hofstadt-van Oy, S. Wolf, M. Strotzer, alterations in svPPA patients. The aim of this study was to use RS fMRI to investigate the functional connectivity within brain networks P. Oschmann in patients with svPPA. Klinikum Bayreuth (Bayreuth, DE) Methods: RS fMRI scans were obtained from 9 svPPA patients Frontotemporal lobe degeneration (FTLD) can lead to dementia with and 29 age- and sex-matched healthy controls. Independent compo- early progressive personality changes and behavioural problems or nent analysis identified the executive, salience, default mode (DMN), distinct clinical subgroups like primary progressive aphasia and attention/working memory networks. Within-group and between- or semantic dementia. Magnetic resonance imaging (MRI) may group RS fMRI comparisons were performed with SPM8. demonstrate lobar degeneration; post mortem neuropathology is het- Results: Compared with healthy controls, svPPA patients showed erogeneous with detection of tau-positive and tau-negative patients. a decreased functional connectivity of the executive network in the Case report: A 71 year old retired female teacher in otherwise good ventral medial frontal regions and superior temporal pole. SvPPA health presented with a two year history of progressive dysarthria were also characterized by a decreased connectivity of the symmetric without any swallowing problems. Personality, cognitive function and attention network, mainly involving the left insula, bilateral inferior intellectual interests were maintained as activities of daily living as orbital regions, and left superior parietal and posterior cingulate gyri. witnessed by patient and her husband. Unarticulated verbal expression Within the left-lateralized frontoparietal network, svPPA patients had led to some social retreat and moderate depression. Neurologic showed a decreased connectivity in the left superior frontal gyrus. No examination on admission revealed a severe dysarthrophonia with alterations were found in the salience, DMN, and right frontoparietal impaired articulation movements and was otherwise normal, a laryn- networks in svPPA patients compared with controls. goscopy showed normal pharyngeal and vocal chord anatomy. Conclusion: The results of this study suggest that RS fMRI has the Neurophysiologic examination of peripheral nerves and muscles sensitivity to detect functional abnormalities of large-scale neuronal including the tongue were normal as were magnetic stimulation networks in svPPA patients. SvPPA seems to be associated with an including triple stimulation technique to hand- and leg muscles. No altered connectivity of the frontal and frontoparietal networks sub- decrement was found with repetitive stimulation of accessory and facial serving executive functions and modulation of attention.

123 S174 J Neurol (2012) 259 (Suppl 1):S1–S236

P660 Jakob disease (sCJD) from the familial form (fCJD) and other A case of vanishing white-matter disease due rapidly progressive dementias. Methods: 37 consecutive patients were diagnosed as probable or definite sCJD(n=12), fCJD(n=10) and to the c.260C[T (p.Ala87Val) EIF2B3 mutation a group of nonprion dementias or confusional states, later defined as L. Ghezzi, M.T. Bassi, A.M. Pietroboni, G.G. Fumagalli, viral encephalitis, Hashimoto’s encephalopathy, PS1 mutation, hal- A. Arighi, M. Rango, M. De Riz, F. Jacini, D. Galimberti, lucinogen related disorder (n=15). We compared symptoms, N. Bresolin, E. Scarpini biological markers, EEG, and standardized MRI, rated for abnor- University of Milan (Milan, IT); IRCCS E. Medea (Bosisio Parini, IT) malities by an experienced neuroradiologist (AG) blind to diagnosis. Results: Mean age in fCJD was 53 vs 59 in sCJD (NS). In fCJD, the Background: Vanishing White Matter (VWM) is one of the most symptoms often look like sCJD: ataxia, dementia, myoclonus. They prevalent inherited childhood leukoencephalopathies. Initially appear earlier but duration of the illness is usually longer. We found described in children, the disease presents with cerebellar ataxia and a solid relationship between the clinical manifestations and EEG. less prominent spasticity. More recently it has became apparent that The time between the onset and MRI was significantly longer in VWM has wider clinical spectrum than originally described, with age fCJD (7.4 months vs 3.9 in sCJD). Genotype at PRNP, confirming at onset inversely related to clinical severity. The initial clinical signs the familial form in 10, consisted of 7 E200K and 3 T188R muta- in adults consist of epileptic seizures, complicated migraine, presenile tions. Global cortical atrophy was reported in 6 fCJD subjects, dementia and psychiatric symptoms. Many affected women experi- subcortical in 5 and cerebellar atrophy in 5. Eight fCJD exhibited ence a combination of leukoencephalopathy and primary amenorrhea cortical hyperintensities in DWI, not apparent in 4 inT2 and FLAIR or premature ovarian failure, a condition named ovarioleukodystro- sequences. Symmetrical or asymmetrical hyperintensity in caudate phy. Mutations in any of the genes encoding the 5 subunits of and putamen are characteristics of CJD (64 %). Two cases with eukaryotic initiation factor 2B (eIF2B1, 2, 3, 4 and 5) can indepen- posteromedial thalamic and cortical hyperintensities showed dently cause VWM. More than 120 mutations have been reported to enhancement in T1 with gadolinium. ADC values were significantly date; most reside in EIF2B5 and EIF2B2. reduced in the head of the caudate, putamen, posterior thalamus, Objectives: To describe a case of adult onset (VWM) disease due convexity cortex, cingulate gyrus and insula. DWI/ADC in cortex to the rare EIF2B3 mutation c.260C[T (p.Ala87Val). and basal ganglia did not show abnormalities in 88 % of controls, Methods: Neurological examination, brain MRI, neuropsycho- 16 % of fCJD and 12 % of sporadic cases. In CJD, normal ADC logical testing and DNA sequencing were performed. map is seen in most of the patients with more than 11 months of Results: The patient, a 66 years old woman, presented with pro- evolution and generally shows typical restriction before this time gressive walking impairment associated with behavioural and (Chi-square, p=0.033). Conclusion: MRI cannot distinguish the cognitive disturbances, associated with primary ovarian failure (at 24 familial from the sporadic form of CJD and typical images are years of age). Neurological examination showed lower limbs hyper- generally not found after month11. Nevertheless, DWI and ADC tonia, spastic paraparesis, brisk reflexes, Babinski sign in the right map in the caudate, putamen, insula and cingulate offer the best foot, dysdiadochokinesia, and ideomotor apraxia. Mood deflexion was sensitivity and specificity for diagnosing CJD in early stage and also present. Brain MRI T2-weighted images showed symmetric should be added to the diagnostic criteria. diffuse signal abnormality in the hemispheric white matter, sparing the U fibers; DWI images showed diffusion restriction; cortical subcortical atrophy was also reported. Neuropsychological testing showed planning, praxis and visuospatial memory deficits associated Epilepsy with less prominent abstraction and lexical retrieval impairment. DNA sequencing showed the presence of the EIF2B3 mutation c.260C[T (p.Ala87Val). P662 Conclusions: Here, we described the case of a 66 years old woman with a 5 years history of progressive walking impairment and cog- Predictors of effectiveness of the first antiepileptic drug nitive decline associated with primary ovarian failure (at 24 years of in elderly patients with epilepsy age). The patient was a carrier of the rare EIF2B3 mutation c. S. Lukic, M. Spasic 260C[T (p.Ala87Val.). This mutation was described only once Clinic of Neurology Nis (Nis, RS) before in literature in a childhood onset case. Our description enlarges the spectrum of phenotypic heterogeneity among patients with the Objectives: Assessment values of the initial clinical predictors of same mutation. effectiveness of the first antiepileptic drug in the elderly patients with epilepsy. Methods: Prospective longitudinal study included consecutive series of elderly with newly diagnosed partial epilepsy. Inclusion P661 criteria were: 1) Subjects with untreated, newly diagnosed epilepsy having at least two well documented, unprovoked, clinically evalu- MRI abnormalities in familial and sporadic ated and classified partial seizures (with or without secondary Creutzfeldt-Jakob disease generalization) or generalized tonic–clonic seizures (without clear M.-C. Boll, A. Guadamuz, R. Eskenazi, F. Chico Ponce de focal origin) within last 12 months, 2) Subjects had no previous use of Leoń, Y. Martinez, M.E. Alonso an AED, 3) Subjects have a documented electroencephalogram (EEG) National Institute of Neurology and Neurosurgery (Mexico City, within last 12 months compatible with localization-related epilepsy MX); Hospital Infantil de Mexico (Mexico City, MX) (to exclude primary generalized epilepsy), 4) Subjects have a documented computed axial tomography scan or magnetic resonance Prion diseases are a group of fatal neurodegenerative disorders that imaging scan confirming the absence of a progressive neurological occur in inherited, acquired and sporadic forms. Objective: to lesion within last 12 months, 5) Subjects who are able and willing to evaluate the usefulness of MRI, in particular, diffusion-weighted follow investigational study procedures, maintain a seizure diary, and imaging (DWI) and ADC map (apparent diffusion coefficient) in report adverse events., 6) Subjects who are able and willing to give gray matter regions of interest, to distinguish sporadic Creutzfeldt- written informed consent.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S175

Patients were following minimum 12 mounts after initiation of P664 therapy. Primary endpoint was seizure control (with or without sei- Correlation between ictal EEG and ictal SPECT studies zures). Potential predictors are analyses from dataset available on initial clinical evaluation and included demographic data, history risk in refractoryepilepsy factors, neurology findings, neuroradiology and EEG findings as well P. Guimara˜es, J. Lopes, J. Ramalheira as characteristics of pharmacotherapy. Centro Hospitalar de Tra´s-os-Montes e Alto Douro (Vila Real, PT); Univariate logistic regression equations were computed for each Centro Hospitalar do Porto - Hospital Geral de Santo Antońio (Porto, potential predictor variable. Variables were included in the multi- PT) variate analysis if the univariate p value was \=0.25. A backward Objectives: To establish correlation between the ictal surface elec- selection procedure was then used to select a subset variables. Sta- troencephalogram (EEG) pattern and ictal perfusion on Single Photon tistical significance were defined for alpha = 0.05 Emission Computed Tomography (SPECT). Results: 45 elderly patients were included in this study. 25 remain Methods: A retrospective study of consecutive patients admitted in seizure free after 12 mounts of follow up. Regression analyses neurophysiology department over four years with refractory epilepsy demonstrated that etiology particularly depression traumatic brain (lesional and non-lesional), in which it was possible to obtain an ictal injury and depression are the most important predictor variables for SPECT. Proceeded to compare the respective electrical paroxysmal bad therapeutically response. onset and perfusion pattern. Conclusion: This study may support hypothesis that neurobio- Results: We obtained a total of 31 patients, mostly female (65 %), logical processes that underpin psychiatric comorbidity may interact and an average age of 26 years-old. Of the total, based on the with those producing seizures to increase the extent of brain dys- investigation carried out by magnetic resonance imaging (MRI), we function and thereby the likelihood of developing bad therapeutic obtained a total of 23 patients with lesional epilepsy (48 % of cases response in elderly. with imaging criteria for mesial temporal lobe sclerosis) and 8 patients with non-lesional epilepsy. The ictal EEG was lateralized in 63 % (n = 5) of non-lesional epilepsy cases and in 83 % (n = 19) of P663 cases with lesional type. In the first the ictal EEG showed no later- Effect of ketogenic diet on electroencephalographic alized epileptiform activity and the SPECT in 67 % of them defined regions of hyperperfusion in concordance with the ictal semiology. It epileptiform discharges during ketogenic diet initiation is noted, in the subgroup with a non-lesional epilepsy, a patient with a in adults with refractory epilepsy frontal lobe seizure phenomenology consistent with paroxysmal J. Janousek, L. Goldman, A. Barber, E. Pavelova, P. Klein activity in EEG but not with the SPECT perfusion pattern. In the 4 Mid-Atlantic Epilepsy and Sleep Center (Bethesda, US) lesional cases with not lateralized EEG, SPECT revealed in all localizing hyperperfusion areas. The ictal EEG was concordant with Rationale: Ketogenic diet (KGD) is effective treatment of refractory hyperperfusion in 95 % of subjects studied with lesional epilepsy. epilepsy in children. There is little experience of its use in adults. Conclusion: The demonstration of the positive correlation of EEG There have been few reports of KGD effect on electroencephalogram and ictal SPECT as well as the ability to define the epileptogenic zone (EEG). The goal of the present pilot study was to determine whether even when the ictal electrical pattern is not found make SPECT useful (a) KGD initiation is associated with EEG changes and (b) these as a diagnostic tool in the work-up before surgery. changes correlate with changes in serum glucose and urine ketones. Methods: 11 patients with refractory epilepsy (8 women, 3 men, age range 24-65) were treated with KGD and underwent continuous EEG monitoring during KGD initiation. KGD consisted of 3:1 [fat] : P665 [protein+carbohydrate] ratio and caloric restriction of 1600 kiloca- Non-convulsive status epilepticus: one-year review lorie/day. Patients were hospitalized for 4-5 days for KGD initiation, P. Guimara˜es, A. Costa, R. Choraõ, J. Gabriel with a 24-48 h fast followed by graduated daily caloric increase and Centro Hospitalar de Tra´s-os-Montes e Alto Douro (Vila Real, PT) 100 % caloric intake upon discharge. Serum glucose and urinary ketones were checked during hospitalization. Long term continuous Objectives: Epidemiological, etiological, syndromic, neurophysio- EEG monitoring was started on the first day of the fast, and was logical and therapeutic characterization of non-convulsive status continued for 4-5 days. 32 channel monitoring EEG system was used. epilepticus. The whole EEG was reviewed manually in 10/11 patients, and Methods: A retrospective study of patients admitted in the emer- interictal epileptiform discharges [(IEDs): spikes and sharp waves] gency room in 2011 whose electroencephalogram was compatible were counted. with non-convulsive status epilepticus. Proceeded to their analysis in Results: 6 patients had primary generalized epilepsy with gen- the epidemiological, etiological, syndromic, neurophysiological and eralized tonic–clonic seizures (n=5) and absence and myoclonic therapeutic dimensions. seizures (n=3). 5 had cryptogenic localization-related epilepsy of Results: We obtained a total of 17 individuals, mostly female temporal (n=3), and frontal (n=1) lobe foci. 1 had symptomatic frontal (59 %) and a mean age of 70 years-old [22-94]. The non-convulsive lobe and generalized epilepsy. Seizure duration ranged from 14-51 status epilepticus was inaugural in 94 % (n = 16) and 29 % (n = 5) had years, prior antiepileptic drugs (AEDs) from 1-6, and current AEDs a history of epilepsy. Complex partial seizure was the most common from 1-4. AEDs were held constant in 9/11 patients during the study. (65 %) and disturbance of speech/language, the most common neu- There was reduction in the mean hourly IEDs rates from 55.2 IEDs/ rological sign (71 %). The electroencephalogram lateralized hour on day 2 to 4.7 IEDs/hour on day 4 of KGD treatment (p\0.01). epileptiform activity in 88 % (n = 15) of patients and there was a Hourly IEDs rate declined from KGD day 1-2 to KGD day 3-5 in predominant anterior ictal rhythm in 53 % (n = 9). Symptomatic eti- 11/11 patients. Three patients experienced seizures on 2nd day of ology was the most frequent (71 %) and the vascular injury more often KGD treatment. There was no correlation between spike frequency identified (75 %). With regard to the antiepileptic treatment regimen in and serum glucose or urine ketone levels. polytherapy was more often used. The infectious respiratory compli- Conclusion: Initiation of KGD was associated with reduction of cation was the most common complication and it was found in 67 % (n IEDs in this small series of patients. A larger study is warranted. = 8) of patients. The prognosis was unfavorable in 5 subjects (29 %).

123 S176 J Neurol (2012) 259 (Suppl 1):S1–S236

Conclusion: We highlight in our analysis the high average age and oxcarbazepine- 11, 2 %, phenobarbital- 9, 6 %, phenytoin, ethosux- concordant etiology. The ineffectiveness of monotherapy alerts us to imide- 6, 4 %, gabapentin- 4, 0 %, pregabalin- 0, 8 %. The most expedite the recognition of an entity, which is associated with high frequent used dosages of AEDs were (after hospitalization): valpro- morbidity and significant mortality. (Video documentation). ate- 1000 mg (42, 5 %), carbamazepine 600 mg (48, 3 %), lamotrigine 200 mg (31, 6 %), clonazepam 2mg (48, 3 %), topiramate- 100 mg (28, 6 %), oxcarbazepine- 900 mg (35, 7 %), phenobarbital 100 mg (66, 6 %), gabapentin 300 mg, 600 mg, 1200 P666 mg, 1600 mg, 1800 mg (each 20 %), pregabalin 75 mg (100 %). After Bone mineral density in adult patients treated hospitalization usage of some AEDs increased: valproate- for 10, 4 %, carbamazepine- for 24, 8 %, clonazepam and phenobarbital with different antiepileptic drugs (each increased for 3, 2 %). S.A. Beniczky, J. Viken, L.T. Jensen, N. Becser Andersen Conclusion: The most frequently used AEDs were valproate, Glostrup University Hospital (Glostrup, DK) carbamazepine and lamotrigine for the treatment of DRE in Latvia. In Objectives: There is considerable evidence suggesting, that older our study we found that gabapentin was used less than expected, but antiepileptic drugs (AEDs) and some of the newer ones decrease bone the use of clonazepam had considerable role among patients with DRE. The patients who were identified with DRE were much less mineral density (BMD). However, there is only limited and con- than 22, 5 % of epilepsy patients as mentioned in literature, and it flicting data concerning the effect of levetiracetam on BMD. The objective of this study was to compare the incidence of decreased could be explained as the patients with DRE are treated mostly out of department. BMD between patient treated with different AEDs. Methods: In this cross-sectional study we analysed data from 96 consecutive adult outpatients treated with AEDs for more than 2 years, and who underwent measurement of the BMD. We compared P668 the incidence of decreased BMD among the patients treated with 6 Reorganisation and distribution of tau protein different AEDs: carbamazepine, oxcarbazepine, valproic acid, lami- trigine (LTG), topiramate and levetiracetam (LEV). in patients with temporal lobe epilepsy Results: In accordance with previous studies, we found that Y. Lekomtseva, G. Gubina, T. Gorbach, M. Whittington decreased BMD was less often found among patients treated with Kharkiv National Medical University (Kharkiv, UA); University of LTG as compared to other AEDs. Reduced BMD was present sig- Newcastle (Newcastle-upon-Tyne, UK) nificantly more often among patients treated with LEV. There was Object: We have discovered the dysfunctional hyperphosphorylated no significant difference concerning age and sex between these Tau (hp-Tau), its distribution and quantification in temporal lobe groups. epilepsy (TLE). Conclusion: Our data suggest that patients on long-term treatment Methods: Cryostat sections were collected from five TLE patients with LEV have a higher risk for affection of bone mineralization. and one control who had neurosurgical respective treatment for immunofluorescence staining with primary monoclonal anti-Tau-5 and clone-2 antibodies; digital images were normalized for immunofluorescence quantification, results were expressed as integrated P667 optical density (OID). Drug-resistant epilepsy: clinical practice of medical Results: We found accumulation of phosphorylated Tau (p-Tau) therapy in Latvia inclusions and aggregations predominantly in somato-axonal com- O. Zaiferte, D. Pastare, L. Obuhovica, E. Vitols partment of pyramidal neurons of temporal cortex (TC) in TLE associated with revealing of Tau-5 and Tau-2 immunopositive neu- Riga Eastern University Hospital (Riga, LV); Riga P.Stradins ronal spheroid dot-like inclusions diffuse scattered predominantly University Hospital (Riga, LV) throughout cortical IV, III layers of high OID and decreasing of Introduction: The International League Against Epilepsy(ILAE) has axonal Tau-5 immunolabeling. Quantification of tau-immunoreactive developed a global consensus definition of drug resistant epilepsy to neurons demonstrated a statistically significant decrease in the num- improve patient care and facilitate clinical research. Drug resistant ber of tau-5-immunoreactive neurons in all TLE cases. This study also epilepsy (DRE) is defined as failure of adequate trials of two tolerated demonstrated abnormal accumulation of hp-Tau in the somatoaxonal and appropriately chosen and used antiepileptic drug (AED) sched- compartment of pyramidal neurons as pre-tangle associated neuritic ules (whether as monotherapies or in combination) to achieve clusters and inclusions of hp-Tau deposits; they represented degen- sustained seizure freedom. It has been estimated that up to 22,5 % of erating neuronal process, and were clusters of abnormal swollen and patients with epilepsy have DRE. globular neuritis. This study revealed the extracellular protein Objectives: The aim of study was to gain data about treatment aggregations containing hp-Tau and p-Tau not associated with cells in practice of DRE in our country. almost all cortical layers that can indicate: these inclusions could Methods: we retrospectively analyzed 125 patients with DRE occur independently to related Tau intraneuronal aggregations. These according to ILAE definition, these patients were selected out of 1 depositions of Tau insoluble aggregates contribute to Tau-mediated 947 patients who were hospitalized with epilepsy diagnosis at neu- neurodegenerative process in TLE. Hyperphosphorelation of Tau is a rology department in Riga during five year period from 2006 till 2010. condition that disrupts the intracellular trafficking impairing neuro- The patients were analyzed for clinical data: seizure onset age, seizure transmission in association with formation of intracellular inclusions frequency and other, with particular interest in medical therapy before of p-Tau immunoreactive positive granules, these deposits situated and after hospitalization, and the dosages of AEDs for epilepsy predominantly around nuclei and in the somato-axonal neuronal treatment. compartment. Results: 125 patients were included in the study (mean age 45 Conclusion: Intracellular neuronal aggregations and dot-like years; 53, 72 % were male).The medical therapy used for treatment: inclusions containing hp-Tau-5 and Tau-2 in TLE may lead to con- valproate- 58,4 % of patients were treated, carbamazepine- 48 %, stitutive microtubule-associated protein aggregations which could lamotrigine- 30, 4 %, clonazepam- 23, 2 %, topiramate- 22, 4 %, reproduce secondary neurodegeneration in TLE associated with

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S177 epileptic lesion. These findings suggest that TLE has Tau-mediated strokes. We evaluated 2 patients with severe neglect syndromes pyramidal neurodegeneration without tauopathy in which pathologi- thought due to strokes, but seizures and SE were the correct diagnosis. cal Tau transferring or re-accumulation in TC may be associated with Methods: Review of clinical history, neurologic exam, imaging, occurrence of focus. and EEGs on 2 patients with severe hemispatial neglect. Results: An 80 yr old L-handed woman was noted to not use her L hand for tasks, though she could move it. She had not had sei- P669 zures but had vascular risk factors. Consultation was sought for profound L neglect. She was inattentive to the L visual field and did Epileptic seizures and electroencephalographic findings not recognize her L hand when held in front of her face; she was in cerebral X-linked adrenoleukodystrophy unaware of her deficits. She had an upward (‘parietal’) drift of the A. Potic, D. Momcilovic-Kostadinovic, A. Rovelli, P. Corti, outstretched arm. Strength and language use were normal. The D. Grioni, T. Smiljkovic, J. Potic Stroke team diagnosed a R hemisphere embolic stroke, but MRI with diffusion weighted imaging showed no evidence of ischemia. University of Belgrade (Belgrade, RS); University of Milan-Bicocca EEG showed R parietal background suppression, plus 3 electro- (Monza, IT); University of Milan-Bicocca (Milan, IT) graphic seizures and later, R parietal periodic discharges. Objective: X-linked adrenoleukodystrophy (XALD) patients with Levetiracetam (LEV) was started. The neglect resolved within hours cerebral demyelination may present with epileptic seizures along with and did not recur. the other symptoms of the disease. The aim of the study was to A 62 yr old R-handed woman had surgical evacuation of a R evaluate epileptic seizures and electroencephalography (EEG) find- subdural hematoma 1 year earlier, with subsequent frontal partial ings in two most frequent cerebral XALD types: childhood cerebral seizures with L arm and face twitching. Seizure control was good on XALD (CCXALD) and adrenomyeloneuropathy (AMN) with cere- LEV, but it was stopped when she had mood swings and struck a bral involvement. nurse. Consultation was sought for ‘confusion.’ On exam, she was Methods: Medical records and EEG findings in seven CCXALD inattentive to all on the L. She had finished eating without touching boys and four adult males with AMN and cerebral involvement who any food on the L side of the plate. Strength was normal, with no exhibited epileptic seizures during the XALD course were retro- jerking movements. Language was fluent. Head CT showed no spectively studied. At least two EEG studies at different disease change from earlier. EEG showed frequent R parieto-temporal sei- stages were performed for each patient. The cerebral disease severity zures (electrographic SE). LEV was restarted; seizures ceased. was designated as stable, slowly progressive and advanced disease. In Frequent R parietal discharges decreased over a week and the neglect the CCXALD group, stable cerebral disease comprised 14 % of the resolved. patients, while slowly progressive and advanced cerebral disease had Conclusion: Parietal seizures may produce focal sensory symp- the equal occurrence (43 % of the CCXALD patients). In the AMN toms; a few cause pain syndromes. Seizures with primarily perceptual group, 75 % of the patients had advanced cerebral disease, whereas or cognitive dysfunction are seldom diagnosed, possibly because of slowly progressive cerebral disease affected 15 % of the patients. No the lack of motor signs. Especially without earlier seizures, sudden disease modifying therapy was applied except haematopoetic cell onset of new hemispatial neglect suggests an acute stroke, but sei- transplant in one CCXALD boy during the disease asymptomatic zures and SE can also explain neglect syndromes. When other studies stage which later evolved into advanced cerebral disease and even- are non-diagnostic (and of course, after prior seizures), EEG moni- tually stabilised. toring for patients with unexplained (neglect or other) syndromes can Results: Regardless of the disease type, seizures were of focal or help diagnose seizures; many are reversible readily with multifocal origin in 85 % of the studied and primary generalised in anticonvulsants. the remaining 15 %. Epileptic seizures were the first cerebral disease The authors have no disclosures or conflicts of interest. symptom in two CCXALD patients (29 % CCXALD) and one AMN patient (25 % AMN). The only seizures appearing before the cerebral disease commencement were febrile convulsions in one CCXALD boy. Frequent intractable seizures were recorded in 43 % of the CCXALD patients and 50 % of the AMN patients in both slowly P671 progressive and advanced cerebral disease. Seizures were easily Systemic lupus erythematous and status epilepticus: controlled in all the other studied patients. At the first clinical rec- a clinical case ognition of the cerebral disorder EEG showed mild background S. Cesar, S. Perdigao activity slowing in 86 % of the CCXALD patients and 100 % of the ULSAM (Viana do Castelo, PT) AMN patients. The slowing was gradually becoming more severe and was often accompanied by paroxysmal discharges as the cerebral Introduction: Systemic lupus erythematous (SLE) is an autoimmune disorder was advancing. Burst-suppression EEG patterns almost multisystem disease, often associated with abnormal function of the always indicated poor outcome. Conclusion: Unlike the EEG findings, central and peripheral nervous system. Neuropsychiatric involvement epileptic seizures did not always correlate with the cerebral disease in systemic lupus erythematosus is considered to be one of the major severity in the XALD patients we studied. manifestations of the disease. Seizures can occur at any time in the course of SLE, and in some studies, up to 11 % of neuropsychiatric manifestations of SLE occur before the disease is diagnosed. We present a case of a young girl with SLE presenting as status P670 epilepticus. Severe hemispatial neglect as a manifestation Clinical case: An 18-year-old female, caucasian, student, with no of seizures and status epilepticus previous medical problems, was admitted to the emergency depart- A.C Schomer, F.W. Drislane ment in status epilepticus, with normal vital signs. One month prior to admission her physician prescribed low dosage of oral steroid for non Harvard University (Boston, US) specific and non pruriginous malar skin lesions. The full blood count, Objectives: Parietal seizures and status epilepticus (SE) are seldom sedimentation rate, C-reactive protein, viral serologies and CSF diagnosed. Most patients with hemispatial neglect have parietal analysis were normal. Immunologic and thrombotic studies were

123 S178 J Neurol (2012) 259 (Suppl 1):S1–S236 positive for antinuclear antibodies. Renal function showed an underlying genetic alterations could give us clues to the understand- increased protein excretion ([0.5g/day) and brain MRI revealed ing of this syndrome. multiple diffuse lesions compatible with vasculitic etiology. Hence, the clinical, laboratorial and radiologic results were suggestive of SLE and the patient underwent anti epileptic and immunosuppressive therapeutics. P673 She was discharged two weeks later with no epileptic seizures Insulinoma presenting as refractory seizure disorder recurrence and the follow-up brain MRI six months later revealed P. Correia, R. Panchani, A. Gupta, R. Ranjan, partial resolution of the multiple lesions. C.S. Agrawal Conclusion: Epileptic seizures usually occur in the context of Sir Ganga Ram Hospital (New Delhi, IN) important disease activity in younger individuals, being considered to increase the risk of morbidity and mortality. The etiology of seizures Introduction: Hypoglycemia caused by an insulinoma is a readily is multifactorial: anti-phospholipid antibodies and lupus anticoagulant treatable condition that should be considered in the differential have been described to convey an increased risk of neurological and diagnosis of intractable seizures. The following case report highlights thrombotic disorders. Status epilepticus is a rare manifestation of the need for careful reassessment of all seizures that are atypical and systemic lupus erythematous, however in our case was the first refractory to medication. manifestation of the disease. Case report: A 29 yr male presented with 1yr history of multiple seizure episodes, as frequent as 3-4 per week despite being on carbamazepine, sodium evaporate & clobazam. Episodes were uncannily similar in that they occurred in the early hours of morning & were P672 episodic stereotyped confessional spells characterized by abnormal Familial transient epileptic amnesia. Report of three posturing, perioral & eyelid twitching & unresponsiveness. The siblings attacks would usually last from a few minutes to half an hour. His I. Rojas-Marcos, A. Fernańdez, J.A. Caballero, A. Sua´rez, compliance was checked & metabolic causes were ruled out. MRI Brain was normal. No interictal epileptic activity was observed during A. Blanco prolonged video EEG monitoring. Hospital Juan Ramoń Jimeńez (Huelva, ES); Hospital Virgen del Five months later, seizures increased in frequency. He was brought Rocıó (Sevilla, ES) early morning to hospital in an unconscious state & had hypoglyce- Objectives: transient epileptic amnesia (TEA) is a syndrome of mia (48mg/dl) that recovered immediately on treatment. It was temporal lobe epilepsy characterized by abrupt and transient distur- apparent that his previous seizures occured in early morning or sev- bance of memory without or little involvement of other functions of eral hours after meals & post seizure confusion state was shortened if the brain. This syndrome is probably under diagnosed and is often he ate something. He gained 10 kg over last 6 months. Endocrine confused especially with transient global amnesia (TGA). Relapse of evaluation suspected insulinoma. Contrast enhanced CT revealed a symptoms, occasional automatisms or olfactory hallucinations, EEG solitary insulinoma in the head of pancreas. Surgical removal was abnormalities and response to antiepileptic treatment suggest the done & benign insulinoma was confirmed on histopathology. He has diagnosis of TEA. Furthermore some patients present memory deficits been asymptomatic for last 6 months. during interictal period that cannot be identified by standard neuro- Conclusion: 1)This case highlights the importance of considering pyschological assessment. We report a family of three siblings with hypoglycemia in atypical neurological or psychiatric episodes & TEA. To our knowledge there are previous reports of familial TGA emphasizes the role of inpatient evaluation of refractory epilepsy. 2) but not TEA. Neuroglycopenia should be considered in all patients with seizures, & Methods: we reviewed clinical records of three patients (two sis- other neuropsychiatric symptoms, especially if they do not conform to ters and one brother) who meet criteria of TEA. All of them were diagnostic criteria or respond to standard treatment. 3)Taking a full assisted at our outpatient clinic and initially diagnosed of TGA. history (including relationship of attacks to food, non-stereotyped or Neuropsychological assessment was performed including WAIS test, atypical attacks, and poor response to treatment) and clinical suspi- pyramid and palm trees test, Weschler Memory Scale, biographic cion is the key to making a diagnosis of insulinoma. Once suspected, memory test, Stroop, verbal and phonetic fluency, Boston naming test, confirming the diagnosis with a 72 h fast is relatively simple. 4) HADS. Informed consent was obtained for neuropsychological Insulinomas are a potentially curable cause of seizures but may be assessment and publication of data. No genetic study was performed. fatal if unrecognized. Early treatment can free many a patient from Results: Patient 1. A 65-years-old male presented four episodes burdensome multiple antiepileptic treatments. since the age of 48 lasting between minutes and 6 h consisting in short term memory impairment. EEG: slow and sharp waves located in both frontotemporal regions predominating in the right side. Brain P674 MRI: mild frontal atrophy. He received carbamacepin and valproate. He complaint of memory deficits. Evoked potentials and high frequency oscillations Patient 2. 68-years-old female. At 59 and 63 years she presented in the human hippocampal formation using single pulse two episodes of amnesia lasting four and six hours. EEG: left tem- cortical electrical stimulation poroparietal slow waves. Brain MRI: mild frontal atrophy. Treatment A. Sakovics, E. Toth, L. Eross, I. Ulbert, D. Fabo with oxcarbazepine and gabapentin was not tolerated. National Institute for Neuroscience (Budapest, HU); Peter Pazmany Patient 3. A 84-years-old female presented three episodes of Catholic University (Budapest, HU); Institute for Psychology, HAS amnesia since she was 70 lasting 15-30 min. EEG: slow and sharp (Budapest, HU) waves located in both temporal lobes. Brain MRI: periventricular ischemic lesions. She received treatment with carmazepine and phe- Objective: Cortical electrical stimulation (CES) is an approved ther- nytoin. Neuropsychological assessment was normal in three patients. apy for drug resistant focal epilepsies. Despite the advanced usage of Conclusions: TEA has specific features that allow its identifica- intracortical evoked potentials (iEP) the neuronal circuit mechanisms tion. TEA may have a familial presentation. Identification of the of CES are poorly understood. We examined the effect of CES under

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S179 general anesthesia in the hippocampal formation (HF) of five tem- with the exception of valproic acid and diazepam - in kindled sei- poral lobe epilepsy (TLE) patients. zures tests. Valproic acid was less effective in OHSCs than in the Methods: We used laminar multielectrodes to record local field kindled seizure tests and diazepam was more (generalized seizures) potential (LFP), multiple unit activity (MUA), current source density or less (focal seizures and afterdischarge durations) effective in this (CSD) and spectral activation of iEPs elicited by brief, singe pulse, animal model than in OHSCs. We conclude that the PAD test in subdural cortical electrical stimuli (0.1ms; 5- 15mA; 0.5Hz). High OHSCs is a suitable in vitro model of evoked seizures. The validity frequency oscillation packages, ripples, were detected by semi auto- of this model could be further examined by studying the effects of matic methods. newer AEDs. Results: Bi- or tri-phasic iEPs were elicited from the HF stimu- This research was supported by the Sander Foundation and the lating the temporo-basal areas. We observed an early, less than 5ms, DFG SFB TR3 C7. component in the high MUA regions, probably the pyramidal layers, of the subiculum. This early response was elicited from a circum- scribed region adjacent to the recording electrodes. In most of the cases the activation of the area around the hippocampal fissure, P676 concordant to the termination patterns of the perforant pathway, The antiepileptic effect of sodium valproate happened around 10-30ms. High frequency oscillation (ripple and fast during different phases of the oestrous cycle ripple) activity was measured during the initial sink in the region of in PTZ-induced seizures in rats high intensity MUA. The central frequencies of different ripples were 100, 150 and 250Hz. Ripple activity was elicited with high proba- J. Kaboutari Katadj, M. Zendehdel, S. Habibian Dehkordi bility (60-98 %). Both ripples and fast ripples were evoked both in the University of Shahrekord (Shahrekord, IR); University of Tehran subiculum and the dentate gyrus. (Shahrekord, IR) Conclusions: We conclude that CES evokes stimulus strength Objective: Catamenial epilepsy is a form of epilepsy which is related dependent response in the HF with high fidelity. The iEPs contain to the menstrual. Cyclic variation in the levels of ovarian hormones abundant amount of ripples and fast ripples. The role of differently plays a pivotal role in its pathogenesis. Sodium Valproate (VPA) is activated afferent fiber systems in the ripple genesis may be crucial one of the oldest antiepileptic drugs (AEDs) which inhibit hepatic for anti-epileptic effect of CES. The evoked ripple activity raises metabolizing enzymes. The aim of this study was to evaluate the questions about the long-term effects of CES in the temporal lobe. antiepileptic effects of VPA during different phases of the estrous cycle in rats. Methods: 72 adult female Wistar rats in 3 groups (control, 75mg/kg P675 &100 mg/kg VPA), each with 4 subgroups (proestrous, estrous, metestrous and diestrous) were used (n=6). First puberty was assessed using A new model of epilepsy based on organotypic vaginal smears and rats with 2 regular cycles were selected. VPA with hippocampal sliceculture doses 75 and 100 mg/kg was administered intraperitoneally (i.p) in the A. Wahab, K. Albus, U. Heinemann treatment groups followed by i.p injection of 80mg/kg Pentylentetrazol University of Karachi (Karachi, PK); Charite´ (Berlin, DE) (PTZ) in the treatment and control groups. After induction of seizure by PTZ, initiation time of myoclonic seizures (ITMS), initiation time of Purpose: In the hippocampus intense high frequency electrical stimula- tonic- clonic seizures (ITTS), seizures duration (SD) and mortality rate tion induces a long lasting rhythmic synchronization (primary (MR) were recorded for 30 min. Data were presented as Mean±SD, one afterdischarge). Primary afterdischarges (PADs) in organotypic hippo- way ANOVA followed by Tukey –Kramer multiple comparison post hoc campal slice cultures (OHSCs) can be reversibly blocked by test was used for analysis of data (P\0.05). carbamazepine and phenytoin at concentrations effective in the treatment Results: The results of this study showed that VPA significantly of partial and generalized tonic–clonic seizures in humans and in animal improved antiepileptic parameters including ITMS, ITTS, SD and models. In order to examine the suitability of PADs in OHSCs as an in MR, in which they were significantly more prominent during the vitro model of evoked seizures we have worked out in detail the sensi- luteal phase than the follicular phase (p\0.05). In addition, there was tivity of PADs to standard antiepileptic drugs (AEDs). no significant difference neither between proestrus and estrous nor Methods: OHSCs were prepared using interface culture method between metestrous and diestrous in each separately group of rats from eight to 11 day old Wistar rats. A PAD in CA1 was elicited by (P[0.05). stimulating the stratum radiatum with an intensity of two times that Conclusion: It seems that during follicular phase by using other anti required to elicit a maximal population spike. The effects of standard epileptic drug mid VPA can improve the antiepileptic efficacy, but AEDs on the duration and on frequency properties of PADs and the during luteal phase by decreasing the dose of VPA can decrease the tonic-like and clonic-like subdivisions of PADs were determined and likelihood of VPA side effects including reproductive disturbances. EC50 values were calculated from concentration - response curves. This research was supported by a grant from Research Council of Key finding: Carbamazepine, phenytoin, valproic acid, phenobarbi- the College of Veterinary Medicine, University of Shahrekords. tal, diazepam reduced the durations of PADs and tonic-like and clonic- like subdivisions of PADs. The effects were concentration dependent and reversible. Ethosuximide was ineffective. The effects on subdivisions of PADs differed between AEDs. Carbamazepine and phenytoin shortened P677 the tonic-like and clonic like subdivisions at similar proportions whereas phenobarbital, diazepam and valproic acid preferentially shortened the Recurrent symptomatic seizure in postischaemic stroke clonic-like subdivision. The suppressive effects of AEDs on frequency prophylaxis patients properties of tonic-like and clonic-like subdivisions were variable and D.I. Cuciureanu observed only at higher concentrations. University of Medicine and Pharmacy Gr. T. Popa (Iasi, RO) Significance: Carbamazepine and phenytoin were more effective in the PAD test in OHSCs than in the MES test and kindled seizures Background: to investigate the relationship between recurrence rate of test. The effectiveness of phenobarbital, diazepam and valproic acid symptomatic seizures in postischemic stroke patients receiving anti- in the PAD test matched their effectiveness in the MES test and - platelet/anticoagulant therapy.

123 S180 J Neurol (2012) 259 (Suppl 1):S1–S236

Method: We reviewed the clinical findings and laboratory data of approximately 93 %.. The average read length and read depth of target 212 patients with postischemic stroke symptomatic seizures, hospi- regions were about 78 bp and 60, respectively. The average number of talized in our neurological service for primary diagnoses between observed variants per sample was 50,719 SNPs and 7,488 indels, 2007 – 2010 and 1 year follow-up in outpatient’s service. All patient, respectively. For each sample, approximately 60-100 SNPs were aged 35 – 75, were investigated by clinical examination, brain com- identified in the CMT-causative (or related) genes. Of them, 15-25 puted tomography, vascular related blood tests, EEG studies, variants per sample were nonsynonymous (or splicing site) variations. cerebrovascular ultrasound and transthoracic echography searching When filtering common variants registered in the dbSNP135, 1000 possible new sources of emboli for every new seizure. All received genomes project databases, and TIARA database (for Koreans) were first line antiepileptic drugs and 104 patients received antiplatelet/ performed, only 3 or less variations were finally left in each sample. anticoagulant treatment. Conclusion: Whole exome analysis of the 25 CMT patients Results: We find 46 (22 %) patients with early-onset seizures and revealed eight causative mutations (32 %) from five genes. This rate 166 (78 %) late-onset seizures patients. Regarding the topography of detecting causative mutations seems rather high, since each sample and types of infarcts 98 (47 %) supratentorial infarcts, 28 (13 %) was tested before the study for 17p12 duplication/deletion and major watershed 48 (22 %) with subcortical involvement, 24 (11 %) lacu- CMT genes. Therefore, we suggest that the exome sequencing can be nars strokes, 14 (7 %) TIA. 38 (18 %) patients with recurrent stroke. a highly exact, rapid and economic molecular diagnostic tool for Seizure type: 72 (34 %) generalized tonico clonic, 62 (29 %) simple CMT patients who were tested for major genetic causes. partial seizures, 78 (37 %) partial seizures with secondary general- This study was supported by the PGM21 project (KHIDI) funded ization. Only 38 (18 %) patients with recurrent stroke. from Ministry of Health & Welfare, Korea. 22 (3 vs. 8) patients with early-onset seizures, 82 (30 vs. 52) late- onset seizures patients, 32 (10 vs. 21) simple partial seizures, 72 (22 vs. 40) patients with primary and secondary generalized tonico clonic P679 seizures received antiplatelet/anticoagulant treatment with lower rate of seizure recurrence. Mutations in aminoacyl-tRNA synthetase genes are rare Conclusion: Rate of seizures recurrence was lower in groups with in Korean Charcot-Marie-Tooth disease patients antiplatelet treatment, may be due to lower rate of recurrent small K. Chung, Y. Hyun, H. Lee, B. Choi silent infarcts. Kongju National University (Gongju, KR); Ewha Womans University (Seoul, KR) Objective: Aminoacyl-tRNA synthetases (ARSs) are enzymes responsible for charging tRNAs with their cognate amino acids in the Neurogenetics cytoplasm or mitochondria. Mutations in four ARS genes (GARS, YARS, AARS and KARS) have been implicated to axonal Charcot- Marie-Tooth disease (CMT). The present study was performed the P678 whole exome sequencing to identify causative mutations from 38 ARS genes in Korean 122 families. Whole exome sequencing in Korean patients Methods: This study included 122 CMT families who were pre- with Charcot-Marie-Tooth disease screened for 17p12 duplication and several CMT genes. Motor and K. Chung, K. Nakhro, B. Yoon, B. Choi sensory conduction velocities were determined on the median, ulnar, Kongju National University (Gongju, KR); Ewha Womans University peroneal, tibial, and sural nerves. In order to identify causative mutations, (Seoul, KR) whole exome sequencing was performed for all the patients. Whole exome was captured using the SeqCap EZ, v2.0 (Roche-NimbleGen), and Objectives: Charcot-Marie-Tooth disease (CMT) is one of the most next generation sequencing (NGS) was performed using the HighSeq common inherited neuropathies, and is a genetically and clinically 2000 Genome Analyzer (Illumina). heterogeneous disorder with variable inheritance modes. Since sev- Results: Mean values of the NGS showed *6.71 Gb (total reads), eral molecules have been reported to have therapeutic effect on CMT 101 bp (read length), 152.5X (read depth), 92.8 % (coverage of target depending on the underlying genetic causes, exact genetic diagnostics region more than 10X), 19,846 SNPs (coding regions), and 384 indels is becoming very important for realizing personalized therapy. (coding regions). The exome sequencing revealed more than fifty Whole-exome sequencing has recently been introduced as an avail- mutations which were implicated to CMT development. However, able method to identify rare or novel genetic defects from genetic few mutations of ARS gene were considered as the underlying cause disorders. Particularly, CMT is a model disease to apply the exome of CMT. Two novel c.598G[A (D200N) and c.794C[T (S265F) in sequencing, since more than 50 genes (loci) are involved its devel- GARS was identified in axonal CMT families. The mutations co- opment with weak genotype-phenotype correlation. segregated with affected individuals, and not found in 200 controls. Methods: The exome sequencing was performed in subject with 25 Many novel nonsynonymous mutations, but not considered as caus- unrelated CMT patients who revealed neither 17p12 duplication/ ative, were found in several ARS genes: I445V in YARS, E738K in deletion nor several major CMT genes. For each patient, the whole GARS, and K40E and N57S in KARS. exome was captured from the genomic DNA using the Human Whole Conclusion: We identified two novel GARS mutations as the exome SeqCap EZ, v2.0 (Roche-NimbleGen, and next generation consideration of underlying causes of axonal CMT. No causative sequencing (NGS) was performed using the Solexa GAIIx Genome mutation was found in YARS, AARS and KARS, as well as other Analyzer (Illumina). ARS genes. It seems that ARS genes may serve rarely genetic defects Results: We identified 8 causative heterozygous mutations from as the underlying cause of CMT in Korean patients. each different family (32 %). The detection rate seems rather high, This study was supported by the PGM21 project (KHIDI) funded since each sample was tested before the study for major genetic causes. from Ministry of health & Welfare, Korea. The mean coverage rate of targeted exon regions ([=10X) was

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S181

P680 fundal examination and retinal photography. We also assessed Nenaline myopathy with unusual oculo - muscolo - patients’ CTG repeat size, age, 6 min walk and motor impairment rating scale (MIRS). skeletal muscle phenotype due to nebulin deletion Results: We examined 59 eyes in 30 patients (1 patient had had recent C. Angelini, C. Wallgren-Petterson, W. Lehtokan, eye surgery and was unable to be examined in that eye) and 56 eyes in 28 V. Codemo, C. Semplicini, E. Pegoraro controls. 26 eyes (44 %) in 18 (60 %) myotonic dystrophy patients University of Padova (Padova, IT); Department of Medical Genetics showed evidence of epiretinal membranes (ERM) compared with just 4 (Helsinki, FI) (7 %) eyes in 4 controls (14 %); p\0.0001 and p\0.001 respectively (two tailed Fisher’s exact test). Most of these were asymptomatic at this Objectives: To describe an unusual oculo- musculo-skeletal pheno- time but three of the ERMs amongst the myotonic patients were type due to a nebulin mutation in a nemaline-2 congenital myopathy impairing vision (visual acuity 6/15) and one patient was referred for linked to chromosome 2q21. retinal peel operation. About half the patients with ERM also had retinal Case report and methods. A 50-year-old woman, now with pigmentary changes as well (compared with 4 controls). respiratory and swallowing difficulties is described. At age 3 she There was no association between the presence of ERM and dis- presented a waddling gait with slight weakness of upper and limb ability as measured by MIRS or 6 min walk test, nor with CTG repeat girdle muscles that remained stable in the following years. At age 18 length. There was a trend towards patients with ERM being older neurological examination showed height 153 cm, weight 31 kg, mild (average age 48 years vs 40 years p=0.14). dysmorphic and long face, high-arched palate, dental malocclusion; Conclusion: Epiretinal membrane is a treatable cause of visual diffuse muscular weakness, anterior thorax abnormalities, clinodac- disability in myotonic dystrophy and should be specifically looked for tyly, outcome of a T2-L1 arthrodesis, bilateral pes cavus and hammer in patients with impaired vision even when they don’t have other toes. A ‘‘ rectus lateralis ‘‘ muscle paresis with nystagmus and ani- signs of advanced disease. socoric pupils were observed. Serum enzymes (CPK, LDH, GOT, GPT, aldolase), thyroid hormones, EEG, EKG, brain CT scan and I.Q. were normal. EMG was myopathic. Muscle biopsy was performed in her and her brother and showed rods. Subsequently due to her low skeletal and respiratory muscle mass the patient at age 28 she had P682 a respiratory worsening and a sudden restrictive failure, she was Motor neuron disease as a new manifestation hospitalized for 8 months in an intensive care unit and we performed of phenotypic mutation 9185T[ C in gene MTATP6 another biopsy. With treatment the patient slowly recovered, but M. Brum, A. Romeiro, P. Santos, R. Matos, R. Guerreiro, remained thin and weak and since she uses overnight the ventilator and has difficulty in swallowing solid food. J. Pinto Marques Results: A recent genetic study demonstrated a deletion in nebulin Hospital de Setubal (Setubal, PT) gene consistent with nemaline type 2. The patient muscle biopsy Objectives: The mitochondriopathy resulting from the mutation showed with Gomori-trichrome collections of rods at the center and 9185T[ C in gene MTATP6 has an extremely variable clinical on sub-sarcolemmal location of the muscle fibers, NADH-TR and phenotype including Leigh’s syndrome, isolated demyelinating acid ATPase displayed type I fiber predominance. The rod bodies, peripheral neuropathy, neurogenic muscle weakness, ataxia and reti- were anisotropic in polarized light and by electron microscopy, rods nitis pigmentosa (NARP) and asymptomatic clinical picture. The appeared as an extension from each side of Z disc into the myofibrils mitochondrial disease can mimic motor neurone disease either clini- and showed a transverse and longitudinal periodicity of 165 to 185 A˚ cally and electrophysiologically, although this was not previously and 130 to 140 A˚ respectively. described in association with this particular mutation. Conclusion: Ocular involvement is not a common feature in ne- Methods: Male of 33 years old, caucasian. We performed anam- maline myopathy: we suggest that, to understand this unusual clinical nesis, neurological examination and diagnostic exams like MRI, phenotype it would be useful to elucidate the role of nebulin also in electromyogram and genetic study. ocular muscles. More than 140 mutations in 7 genes are responsible Results: 33 year-old male, fourth sibling of non-consanguineous for nemaline myopathy. Most nemaline families identified with parents, with family history of mitochondrial encephalopathy: mother nebulin mutations (NEM-2) so far have an autosomal recessive died at 30 years, three brothers with cognitive impairment and epi- inheritance, except possibly for the present and another family. lepsy, and an apparently healthy sister. The patient presents with mild cognitive impairment, fatigue, exercise intolerance since childhood and fasciculations, progressive muscle weakness manifesting in the P681 last year. Neurological examination presents global hypotonia, predominantly proximal flaccid tetraparesis (grade 4 +), without atrophy Epiretinal membrane: a reversible cause for visual or fasciculations, without pyramidal signs, ataxia or bulbar dysfunc- disability in myotonic dystrophy tion. The study highlights an increase of lactate and lactate/pyruvate R.H. Roxburgh, H. Kersten, N. Child, H.V. Danesh-Meyer ratio in serum, at rest and after exercise; electromyogram showed Auckland City Hospital (Auckland, NZ); University of Auckland signs of chronic neurogenic compromise suggestive of motor neurone (Auckland, NZ) disease; muscle biopsy suggestive of spinal muscular atrophy and mitochondriopathy; negative genetic study of SMN1 and detection of Myotonic dystrophy type 1 is a multisystem disorder that affects homoplasmic mutation 9185T[ C in ATP6 gene, confirming the skeletal and smooth muscle as well as the eye, heart, endocrine sys- diagnosis of mitochondriopathy. tem, and central nervous system. In the eye it commonly causes ptosis Conclusion: The mitochondriopathy with the mutation 9185T[ C and cataracts and has been associated with retinal pigmentary chan- in gene MTATP6 of mitochondrial DNA is a rarity. This case dis- ges. In a case control study of 30 patients not selected for eye tinguishes itself even more by the relative benignity and the symptoms and 28 age matched controls, we performed a compre- coexistence of clinical neurophysiological and pathological findings hensive screen of the eye including optical coherence tomography of suggestive of motor neurone disease that, although described in macula and retinal nerve fibre layer, visual acuity and colour vision, mitochondrial disease, have not yet been reported in association with pupil assessment, visual fields, slit lamp, intra ocular pressure, dilated this mutation.

123 S182 J Neurol (2012) 259 (Suppl 1):S1–S236

P683 temporal area. MRI showed mild cerebral atrophy. Nowadays she Clinical features of an ataxic patient maintains refractory partial epilepsy with gait and speech automatisms, in spite of polytherapy with VA, topiramate and with an heterozygous variant of APTX gene carbamazepine. An extensive analytical study ruled out inborn error S. França, M. Sampaio, M. Real, R. Rocha, D. Alves, M. Leaõ of metabolism. Genomic microarray showed an extensive and de Centro Hospitalar de Saõ Joaõ (Porto, PT); Centro Hospitalar Vila novo deletion of 4,1 Mb at Xp22.2-p22.12, including CDKL5 and Nova de Gaia (Vila Nova de Gaia, PT); Centro Hospitalar Saõ Joaõ another 29 genes, some of them associated with mental retardation (Porto, PT) (AP1S2, BMX, CA5B, CA5BP, CDKL5, CTPS2, GRPR). Introduction: Ataxia oculomotor apraxia type 1 (AOA1) is caused by Conclusion: There are still little data on the key clinical diagnosis mutations in the APTX gene and is the second most common form of and natural history of CDKL5 delection with encephalopathy. We autosomal recessive ataxia in Portugal. It is characterized by early- describe a case of EIEE2 caused by, to the best of our knowledge, the onset cerebellar ataxia, oculomotor apraxia (OMA), choreoathetosis, largest delection (4,1 Mb) involving CDKL5 and other 29 genes. mild mental retardation, peripheral neuropathy, hypoalbuminemia A systemic review of the literature showed that delections and hypercholesterolemia. Atypical forms have been associated with evolving CDKL5 and other contiguous genes are quite rare(less than variants of unknown pathogenic effects. 10 cases described). The review of the other reported cases lead us to ´ Case report: 17-years-old female, nonconsanguineous parents. conclude that there isnt an evident correlation between the dimension No family history of neurological disease. At 4 years-old started with of the delection and the clinical severity. oculomotor apraxia, and latter on developed cerebellar ataxia, mild mental retardation and a severe axonal sensorimotor neuropathy. With 12 years becomes unable to walk independently. The MRI P685 disclosed severe cerebellar atrophy. The serum and CSF study was Frequency of autosomal dominant mutations normal, except for alpha-fetoprotein that was slightly increased. Molecular studies for Friedreich´s ataxia, ataxia-telangectasia and in an Italian population of patients with frontotemporal AOA2 were negative. The study of AOA1 (GENDIA) reveled an lobar degeneration heterozygous mutation of APTX: c.742t[A: a missense variant that G.G. Fumagalli, A. Arighi, D. Galimberti, F. Jacini, lead to the substitution of a leucine by a methionine on aminoacid L. Ghezzi, A. Pietroboni, M. De Riz, C. Fenoglio, position 248 of the resulting protein (p.L248M, exon 5). Conclusion: The variant found in our patient was found previously M. Serpente, E. Ridolfi, N. Bresolin, E. Scarpini in 7 of 208 ataxic patients of Italian origin, and was not found in 752 University of Milan, Fondazione Ca Granda IRCCS Hospital control chromosomes. In one case the variant was found in the 2 (Milan, IT) affected brothers and in their healthy mother and in another was Background: Frontotemporal Lobar Degeneration (FTLD) recognizes present in the unaffected mother of a sporadic patient. In our case the high familial incidence. It has been shown that mutations in the genes parents are clinically asymptomatic and had no neuropathy, but the encoding for Microtubule Associated Protein Tau (MAPT), pro- heterozygous mutation is present in the mother. The clinical picture of granulin (GRN), and more recently, a hexanucleotide repeat AOA1 in a heterozygous patient for an APTX variant, already expansion in the first intron of C9ORF72 are the most frequent causes described in other patients of Mediterranean origin, lead us to spec- of autosomal dominant familial forms of FTLD. ulate if this variant can explain the clinical features of some ataxia- Aim: To describe the frequency of autosomal dominant mutations oculomotor apraxia phenotypes in which homozygosity or double in patients with FTLD. heterozygosity for autosomal recessive genes cannot be proved. Methods: All patients underwent clinical and neuropsychological examination, as well as structural and functional brain imaging. Clinical diagnoses were done according to current criteria. MAPT and P684 GRN mutations were detected by direct sequencing. The hexanucleotide expansion in C9ORF72 was determined by repeated-primed Early infantile epileptic encephalopathy type 2 caused PCR and subsequent sequencing. by a giant Xp22.2 deletion Results: We screened 125 patients with FTLD patients (51 males and S. França, M. Sampaio, M. Real, R. Rocha, D. Alves, 74 females). Clinical diagnoses were: 96 behavioural variant Fronto- M. Leaõ temporal Dementia (bvFTD) and 29 Progressive Non Fluent Aphasia Centro Hospitalar de Saõ Joaõ (Porto, PT); Centro Hospitalar de Vila (PNFA). Six patients (4.8 %) were carriers of GRN mutations leading to Nova de Gaia (Vila Nova de Gaia, PT) haploinsufficiency; one of them was diagnosed with PNFA, whereas remainders were diagnosed with bvFTD. One patient (0,8 %), diagnosed Introduction: Mutations in the human X-linked cyclin-dependent with PNFA, was a carrier of a MAPT mutation, while 5 patients, all of kinase-like 5 (CDKL5) gene have been shown to cause early infantile which diagnosed with bvFTD, were carriers of the C9ORF72 hexanu- epileptic encephalopathy-2 (EIEE2) and mental retardation with a cleotide expansion (4 %). Patients with autosomal dominant mutations Rett-like phenotype in female patients. The majority of cases are accounted for 9.6 % of the total number of cases. caused by single base mutations and larger delections involving Conclusions: Our data suggest that the presence of an autosomal CDKL5 gene and other contiguous genes is a rare subgroup of EIEE2. dominant mutation is a frequent cause of FTLD. Case report: Female, 20-years-old, referred to our neurogenetics clinic showing delayed psychomotor development without a clear period of regression, microcephaly, epilepsy and autistic spectrum P686 disorder. At three months-age presented spasms in extension and Familial Creutzfeldt-Jakob disease carrying a V180I latter partial seizures with mastigatory automatisms. A diagnosis of atypical West syndrome was made and she was started on valproic mutation with a MV129 polymorphism acid(VA) with difficult control of seizures until now. A previous EEG Y. Harigaya, K. Hirayanagi, K. Mizushima, T. Kitamoto video monitoring disclosed electroclinical seizures with bursts of Maebashi Red Cross Hospital (Maebashi, JP); Tohoku University generalized spike-wave activity followed by slow waves at the right (Sendai, JP)

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S183

Introduction: Familial Creutzfeldt-Jakob disease (fCJD) results from machine. The CAG repeat number in the HTT gene was detected by mutations in the prion protein gene (PRNP), with more than 30 iden- PCR and gel electrophoresis. tified, and accounts for about 10-15 % of prion disease cases. The point Results: The first symptoms of the proband appeared at the age of mutation of valine to isoleucine at codon 180 (V180I) of PRNP is most 51 years with memory loss, and anxiety. The patient’s father suffered common in Japan, while only 2 cases have been reported in Europe. We from dementia as well. Neurological examination found choreiform report 2 Japanese patients with fCJD carrying a V180I mutation with a hyperkinesis in the limbs, palmomental reflex on both side, non-fluent methionine/valine polymorphism at codon 129 (MV129). aphasia, damaged verbal fluency, perseveration, visuospatial distur- Case 1: A 71-year-old woman with no contributing family history bance. Mini Mental State Examination (MMSE) score was 25/30. The developed speech difficulties over 6 months, could not perform daily severity of the symptoms are slowly progressing. Brain MRI showed activities without support by 9 months. She could not follow simple mild cortical atrophy. A novel missense mutation in the PSEN2 gene commands, and became bedridden with muscle rigidity in all at the c.1163 T[C (T388M) position have been detected. The affected extremities, myoclonic jerks, and startle reactions at 15 months after amino acid is highly conserved in various species and the mutation onset. CSF analysis was positive for 14-3-3 protein and elevated leads to severe structural change in the protein. Mutation prediction neuron-specific enolase (NSE). No periodic synchronous discharges by PolyPhen2 software revealed the substitution as probably dam- (PSDs) were exhibited on an electroencephalogram (EEG). Diffusion- aging (PSIC score 0,999). Genetic testing revealed no mutations in weighted MRI (DWI) showed diffuse high signal intensity in the the PSEN1 and APP genes. In the HTT gene one allele increased 42 cerebral cortex, but not the medial occipital lobes, cerebellum, or CAG repeat number was detected. The PSEN2 gene mutation was brain stem. Single photon emission computed tomography (SPECT) found in the proband’s 57-years-old paternal aunt and was not present revealed severely decreased perfusion corresponding with the high in the proband’s sister. The aunt has normal repeat number in the DWI signal intensity. Genetic analysis revealed a V180I mutation HTT gene, the 50-year-old sister has a reduced penetrance (CAG)n with MV129 heterozygosity. She gradually developed akinetic mut- repeat number (37) on one allele. ism over 4 years and died 7 years after onset. DWI high signal Conclusion: Here we report the coexistence of a novel, putatively intensity gradually decreased with age, while cerebral atrophy with pathogenic PSEN2 gene mutation and a pathologically expanded ventricular dilatation progressed. repeat number in the HTT gene. However there are differences in the Case 2: A 92-year-old woman with no contributing family history disease pathways determinated by these two gene mutations, the had a 7-month history of depression and progressive memory dis- double hit may have an add-on effect on the clinical phenotype. turbance. She did not speak and walked only with support. TA´ MOP-4.2.1/B-09/1/KMR-2010-0001. Gegenhalten in all extremities, snout and palmomental reflex, and startle reactions were observed. CSF analysis was positive for 14-3-3 protein, with elevation of NSE and total tau protein. EEG showed no PSDs. DWI demonstrated diffuse high signal intensity in the cerebral P688 cortex and left putamen. SPECT found severe hypoperfusion, par- Visual loss in orbitofacial neurofibromatosis type 1 ticularly in the frontal lobes. The V180I mutation with MV 129 D.T. Oystreck, J. Morales, I. Chaudhry, I.A. Alorainy, heterozygosity was detected. She gradually developed akinetic mut- S.M. Elkhamary, T.M.U. Pasha, T.M. Bosley ism 2 years after onset. King Saud University (Riyadh, SA); King Khaled Eye Specialist Conclusion: Familial CJD with the V180I mutation must be Hospital (Riyadh, SA) considered in patients with late onset of rapidly progressive dementia showing characteristic DWI findings, such as extensive cortical high Objectives: On occasion, neurofibromas in neurofibromatosis type 1 intensity not including the cerebellum, brain stem, and medial may be present on the lid, brow, or face of an infant or child, a occipital lobes. circumstance commonly referred to as orbitofacial neurofibromatosis (OFNF). In this study we evaluate the causes and extent of visual loss in a group of patients with OFNF. Methods: Retrospective medical record review and re-examination P687 of selected patients from one institution, including assessment of Double hit for the neurons: the coexistence of a novel visual acuity and identification of underlying etiology of reduced vision. presenilin 2 mutation and a huntingtin gene CAG Results: Fifty patients with unilateral OFNF (23 males: 27 repeat expansion females; ages 4 to 48 at last visit) and five with bilateral OFNF (2 V. Remenyi, G. Miltenberger-Miltenyi, G. Nyiro, males: 3 females; ages 15 to 43 years) had adequate information T. Kovacs, M.J. Molnar available to assess afferent visual functioning. Nine (4 males: 5 females; ages 4 to 28 years) patients had optic pathway glioma in Semmelweis University (Budapest, HU); University of Lisbon addition to OFNF. Patients were followed as long as 27 years (mean (Lisbon, PT) 8.4 years). Thirty-nine patients (71 % of total) had visual acuity of Objectives: Alzheimer’s disease (AD) and Huntington disease (HD) 20/60 or worse on the side of OFNF involvement (or the side of worse are both neurodegenerative disorders. For early-onset familial Alz- OFNF involvement in patients with bilateral disease). One or more heimer’s disease most frequently the amyloid precursor protein gene causes of amblyopia were present in 29 of these patients, while 19 had (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2) gene muta- organic disease of the eye (e.g., glaucoma and/or retinal detachment) tions are responsible. In PSEN2 only 18 pathogenic mutations have or the afferent system (e.g., optic pathway glioma), and 12 had cor- been reported so far. Huntington disease is a progressive autosomal rectable refractive errors. dominant trinucleotide disease caused by an expanded CAG repeat in Conclusions: Visual loss in this OFNF cohort was common, typ- exon 1 of the huntingtin (HTT) gene. ically profound, and usually multifactorial. Unfortunately, some Methods: A 55 years-old female patient suffering from young causes of visual loss (including congenital glaucoma with buphthal- onset Alzheimer dementia and her two family members have been mos and retinal detachment; disconjugate gaze due in part to distorted investigated. Detailed clinical and laboratory investigation have been skull development causing strabismic amblyopia; and OPG) were performed. All exons of the PSEN1, PSEN2, and 16. and 17. exons of difficult to treat adequately and tended to cause progressive, severe APP genes were sequenced using ABI Prism 3500 sequencing visual loss. Therefore, careful observation should be made during the

123 S184 J Neurol (2012) 259 (Suppl 1):S1–S236 period of visual immaturity for possible causes of amblyopia that insidious onset after the age of 40, motor impairment (clumsiness, might be treatable such as refractive changes, occlusion of the visual choreoathetotic movements, dysarthria and slight dysphagia), axis, or congenital glaucoma. As affected individuals get older, behavioural changes (irritability and depression), and cognitive physicians must be vigilant for the progression of optic nerve disease deterioration. Brain MRI showed mild enlargement of ventricular and due to glaucoma or optic pathway glioma and to the possibility that subarachnoid spaces. Molecular analysis evidenced CAG expansions vision might be improved by refraction. (39 and 38 respectively) within the IT15 gene. Their mother, dead at 54 with diagnosis of ‘‘dementia’’, was retrospectively considered as affected in reason of the presence of choreoathetotic movements. The 17-years-old daughter of the younger sibling presented since early P689 childhood an unusual autism-like phenotype with speech and lan- Successful pre-implantation genetic diagnosis guage delay, altered social behaviour with extremely reduced in isolated sulphite oxidase deficiency due to a novel interpersonal relationship and facial hypomimia. Interestingly, motor mutation in the sulfite oxidase gene alterations were minimal, consisting in mild upper limbs rigidity and sporadic dystonic and choreiform movements of lips and hands. M.A.M. Salih, T.M. Bosley, I.A. Alorainy, K.K. Abu-Amero, Conclusion: We reported a new Italian HD pedigree with the A. Helani younger member presenting an unusual early-onset phenotype mainly King Saud University (Riyadh, SA); Saad Medical Center including psychic and behavioural alterations. Our findings provide (Al Khobar, SA) further evidences concerning the importance of the age of onset in modifying HD clinical picture, also leading to intra-familiar Objectives: To present a consanguineous family with isolated sulfite variability. oxidase deficiency (ISOD) who eventually had a normal child through preimplantation genetic diagnosis (PGD). ISOD is an autosomal recessive disorder typically causing seizures and cystic cerebral cortical degeneration shortly after birth followed by death at an early age. P691 Methods: Review of clinical records and neuroimaging on all three CPEO due to mutations in the tRNA for isolucine: two affected children and examination of the one living affected child with ISOD. additional Italian cases Results: A consanguineous Sudanese family had three children M. Ranieri, D. Ronchi, A. Bordoni, M. Rizzuti, who were biochemically diagnosed with ISOD. Another child died M.G. Moggio, M. Sciacco, A. Govoni, G. Riboldi, shortly after birth without a definitive diagnosis; a fetus was aborted S. Messina, V. Silani, S.P. Corti, N. Bresolin, G. Comi because of anencephaly; and a normal fetus aborted after chorionic University of Milan (Milan, IT) villus sampling. PGD revealed a novel two base successive deletion c.1232-1233 delTG in the sulfite oxidase gene on chromosome 12. The Objectives: Mutations in mitochondrial tRNAs affect protein syn- family finally had a healthy child after PGD and in vitro fertilization. thesis resulting in respiratory chain dysfunction and leading to Conclusions: Patients with ISOD generally develop intractable heterogeneous clinical phenotypes. Among human mitochondrial seizures within days of birth followed by what appears on neuroim- tRNA genes, tRNA(Ile) is a recognized mutational hot spot, and aging to be diffuse brain ischemia affecting predominantly cerebral associated clinical pictures often include cardio myopathy and white and grey matter, basal ganglia, and other deep grey structures. ophthalmoplegia. Molybdenum cofactor treatment has been suggested as a partial We report the case of a 66- year old man affected with chronic treatment for molybdenum cofactor deficiency, a biochemically progressive external ophthalmoplegia (CPEO) harboring a novel similar autosomal recessive syndrome, but only preimplantation mitochondrial DNA (mtDNA) mutation at nucleotide 4267 of the genetic diagnosis offers definitive diagnosis and treatment for ISOD. tRNA Ile gene (MTTI). A second patient, diagnosed with Klippel-Feil syndrome and presenting additional mild cognitive impairment, dysarthria, ptosis and ophthalmoplegia, harbors the previously described m.4316 A[G substitution in the same gene. P690 Methods: Total DNA was extracted from muscle biopsy and genes Unusual presentation of early-onset Huntington’s encoding mitochondrial tRNAs were analysed by direct sequencing disease, report of a new Italian family using the Variant Seq System (Applied Biosystems). Histological and D. Italiano, R.S. Calabro`, P. Bramanti histochemical studies were performed using standard procedures Results: Histochemical reactions performed on muscle biopsy IRCCS Centro Neurolesi Bonino-Pulejo (Messina, IT) showed ragged-red fibers in the first patient and COX negative fibers Objectives: Huntington disease (HD) is a dominantly inherited neu- in both. Southern blot analysis was negative whereas long PCR rodegenerative disorder characterized clinically by abnormal revealed some deleted molecules. involuntary movements, psychiatric disturbances and cognitive Sequence analysis of mitochondrial tRNAs disclosed two different decline. Although chorea is the main feature of adult-onset HD, substitutions: the novel m.4267A[G variant and the previously juvenile-onset HD is usually characterized by rigidity, behavioral and reported m.4316G[A transition, both affecting conserved positions cognitive disorders, oropharyngeal dysfunctions and seizures. We within tRNA(Ile) sequencing in Acc-stem and T-loop regions, report a new Italian family with HD, in which one of four affected respectively. The m.4267A[G mutation was heteroplasmic with an members exhibits a peculiar early-onset phenotype. estimated mutational load of 60 % in skeletal muscle tissue, whereas Methods: We performed clinical and genetic investigation of an the m.4316G[A mutation resulted almost homoplasmic. PCR–RFLP Italian family whose clinical picture was suggestive of HD. Pedigree analysis in muscle and other tissues is underway. The m.4316G[A analysis was compatible with an autosomal dominant pattern of variant has been recently identified in a patient with cardiomyopathy inheritance. Molecular testing has been performed by polymerase and profound hearing loss in association with another point mutation chain reaction, searching for expansions within the IT15 gene. affecting MT-ND1 gene. Results: Two affected brothers, aging 45 and 50 years old Conclusions: this study further expands the spectrum of point respectively, exhibited a similar clinical course characterized by mutations associated with sporadic CPEO, underlying the

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S185 importance of analyzing the mtDNA sequence after deletions have capacity of the patients was attributed to one of four categories: no been excluded. The occurrence of the m.4316G[A mutation in a ambulatory capacity, therapeutic ambulatory capacity, functional second independent proband supports its pathogenetic role in caus- ambulatory capacity and full ambulatory capacity. Patients were ing human disease. subjected to CT brain (to identify the presence of any intracranial lesions, hemorrhage or edema), Conventional radiography of the cervical, dorsal and lumbar spine(to detect the exact site of fracture to be further evaluated by MRI). Electrophysiological examination P692 included: sensory conduction study of the sural and superficial Fibromyalgia and celiac disease peroneal nerves, motor conduction study of the posterior tibial, deep N. Rizhova, S. Kopishinskaya, A. Gustov, A. Repin peroneal and femoral nerves, F-wave latency of the posterior tibial Nizhny Novgorod Medical Academy (Nizhny Novgorod, RU); and deep peroneal nerves, H-reflex latency and H/M ratio, mixed Nizhny Novgorod Regional Diagnostic Center (Nizhny Novgorod, somatosensory evoked potentials for the posterior tibial nerves, RU) motor evoked potentials using transcranial magnetic stimulation and needle EMG for segment pointing muscles (vastus medialis for L3, Objectives: Celiac disease (CD) is an autoimmune enteropathy trig- tibialis anterior for L4, gluteus medius for L5 and gastrocnemius for gered by the ingestion of gluten in genetically susceptible individuals. S1). CD is common, affecting 1 to 2 % of the population. CD has been Results: Results showed that age, length of the cord pathology, associated with various neurological disorders, the most common clinical examination including (sensory index scoring, motor index being neuropathy, cerebellar ataxia and migraine. Fibromyalgia is a scoring and lower extremities motor scoring), H-reflex latency and H disorder with unknown aetiology. The prevalence of fibromyalgia in maximum amplitude/M maximum amplitude, SSEP parameters and population is 2-4 %. The aim of the present study was to assess the MEP parameters were all of a predictive value in determining prevalence of fibromyalgia among celiac disease patients. ambulatory capacity outcome. Methods: We surveyed two groups of patients. They had direct Conclusion : SSEP and MEP are of prognostic value and should be interviews and full physical and neurological examinations. There performed for all patients with traumatic SCI. Needle EMG should be were 235 celiac disease patients in the first group. The diagnosis of performed in patients with complete SCI to detect the degradation of CD was confirmed endoscopically and by serum IgG antitransgluta- neuronal function below the level of the lesion. minase (TgA) and IgA antiendomysia (EmA). 110 patients who had reflux-esophagitis according to endoscopy results made up the second control group. All patients were fulfilled the 1990 American College of Rheumatology diagnostic criteria for fibromyalgia. A visual analog P694 scale for pain and a functional disability inventory were obtained on all patients. Prognostic significance of A-waves as an isolated Results: In the group of celiac disease patients we revealed higher abnormity of nerve conduction studies prevalence of fibromyalgia 22.6 % (53 patients) than in the second E. Vlckova, M. Hnojcikova, S. Bursova, J. Bednarik control group 3.6 % (4 patients). Masaryk University and University Hospital Brno (Brno, CZ) Conclusions: Fibromyalgia is comparatively frequent disorder in cases of CD. Background: A-waves represent a frequent type of late responses. They are generally considered as a non-specific electrophysiological finding and their significance remains unclear, particularly in tibial nerves. The aim of our study was to examine, if the occurrence of A-waves as the only abnormality may predict increased probability of Clinical neurophysiology the development of other electrophysiological abnormalities in corresponding nerves in the future. Patients and methods: The occurence of the A-waves was assessed P693 in patients examined in the EMG laboratory of the University Hos- pital Brno. Only individuals, whose examination was assessed as Utility of electrophysiological studies in assessing normal (or with occurence of A-waves as the only acceptable prognosis and recovery of traumatic spinal cord abnormality) and who were re-examined in our laboratory in the same injuries part of the body at least 12 months apart, were than included into the D. Mohasseb, A. Abou Alfa, M. Reda, I. Khalil, R. El Gafi study. Altogether, 74 patients (38 men, 36 women, mean age 52.7 ± 9.1 years) fulfilled these criteria, with the mean interval between the Alexandria University (Alexandria, EG) examinations of 37 ± 24 months. Objectives: Spinal cord injury (SCI) often results in significant neu- Results: At initial examination, A-waves were very rare in upper rologic dysfunction and disability. Following SCI, an accurate extremities (where they occured in 1 of 90 examined motor nerves baseline clinical assessment is important. The electrophysiological only), and were significantly more frequent in lower extremities, examinations are of considerable value in the diagnostic assessment where they´d been found in 4 % of 69 examined peroneal nerves and of spinal cord lesions, in the prediction of functional outcome, and in in 25 % of 72 examined tibial nerves (p= 0.003). At control exami- monitoring the course of neurological deficits. This is helpful for nation 12 or more months apart, clearly defined EMG abnormality in planning and selection of appropriate therapeutic approaches within a corresponding nerve was newly found in 100 % individuals with the rehabilitation program. This study aimed to assess the prognosis A-waves in the ulnar nerve (ulnar nerve lesion in the cubital canal) or and recovery of traumatic spinal cord injured patients using electro- in the peroneal nerve (polyneuropathy or L5 radiculopathy) in con- physiological procedures as compared to clinical and radiological trast to 11 and 24 % of newly found abnormalities in the individuals evaluation . without A-waves in these nerves at initial EMG examination Methods: The study was carried out on 25 patients with SCI. (p\0.001). In the tibial nerves, polyneuropathy or S1 radiculopathy Extent of injury was assessed by the American Spinal Injury Asso- developed in 62 % and 21 % of patients with and without A-waves at ciation (ASIA) Impairment Scale. Clinical assessment of ambulatory initial examination, respectively (p=0.006).

123 S186 J Neurol (2012) 259 (Suppl 1):S1–S236

Conclusions: Occurence of A-waves as the only electrophysio- The purpose of this study is analysis sympathovagal balance after logical abnormality significantly increases the probability of acute spinal cord injury presented by standard statistical analysis and development of clearly defined neurophysiological abnormities in the by predictive models of autonomic function and dysfunction. future. Our findings thus confirmed the significance of A-waves as We analyzed a sample of 40 patients after acute spinal cord injury initial abnormality in any of the examined nerves including the tibial and 40 healthy persons of the controls. nerve. This study establishes analyzing of heart rate variability (HRV) by Supported by CEITEC Masaryk University Brno. linear methods in frequency domain as objective measures of normal and abnormal function of autonomic nervous system. Low frequency (LF) in the group with SCI was statistically sig- P695 nificant (P\0.001) lower than in the control group. On the other hand, the parameter of parasympathetic activity, high frequency spectrum Assessment of the vestibulo-collic reflex by using (HF) was significantly higher (P \0.001) in the group with acute auditory click and electrical stimulation with alternate injuries. Low to high frequency ratio (LF/HF) was statistically sig- current nificant lower (P \0.001) in the group with SCI. J.M. Duarte, A. Antik, A.C. Binetti, H.M. D0Onofrio, Predictive models induced by inductive machine learning by logic minimization and visual methods presented decreased, but still M.F. Otero, A.C. Bertotti present sympathetic activity and suggest that descending and Deutsches Hospital (Buenos Aires, AR); British Hospital (Buenos ascending fibers of sympathetic nervous system in isolated segment Aires, AR); Hospital de Clıńicas (Buenos Aires, AR) are undamaged although without supraspinal control. Introduction: Assessment of the vestibulo-collic reflex is used to test Finally, acute spinal cord injury leads to disturbances of modu- saccular-vestibulospinal tracts. Research work has demonstrated the latory sympathetic activity on cardiovascular system. Predictive utility of auditory clicks, galvanic stimulation, vibratory and bone models could help in evaluation and objectification of the connections percussion to test this tract. To our knowledge, electrical stimulation between central nervous system and spinal sympathetic motoneurons with alternate current has not been described. Our objective is to on one side and autonomic cardiovascular control on the other side. determine the utility of testing this reflex by using auditory clicks and electrical stimulation with alternate current. Methods: Design: case–control study. Vestibulocollic reflex was P697 tested through auditory clicks (105 dB) and electrical stimulation with Optical coherence tomography and visual-evoked alternate current on the skin over mastoid processes (5 milliamper, 1 s potentials: which is more sensitive in multiple sclerosis? duration). Biphasic inhibitory responses were observed during maximal activation of sternomastoid muscle. Analysed parameters: G. Di Maggio, M. Bianco, L. Ferrari, S. Medaglini, latency (L) of the first deflection and amplitude (A) of the waveform, M. Rodegher, B. Colombo, L. Moiola, M. Radaelli, after click stimuli (LC and AC) and electrical stimulation (LE and R. Chieffo, U. Del Carro, V. Martinelli, G. Comi, L. Leocani AE); patients with chronic vertigo were compared to asymptomatic San Raffaele Hospital (Milan, IT) persons. Statistic analysis was performed by using ANOVA difference for parametric variables and Mann–Whitney test for non- Objectives: to evaluate differences between optical coherence parametric variables. Statistical significance was set as p\0.05. Sta- tomography (OCT) and visual evoked potentials (VEP) in multiple tistics pack STATA SE 10.1. sclerosis (MS) and clinically isolated syndrome (CIS) patients. Results: 20 cases and 20 controls were tested. In cases, mean LC Methods: cross-sectional study of 40 subjects with MS (6 CIS, 30 was 10.85 ms (SD 1.74) and in controls 10.22 (SD 0.86) p 0.35. In relapsing-remitting–RRMS, 4 secondary progressive–SPMS; age cases mean AC was 20.02 microvolts and in controls, 39.23 (SD 37+9, disease duration (DD) 6.3+6.4 years, 22 females, median 21.35) p 0.08. In cases mean LE was 17.97 (SD 8.7) and in controls, Expanded Disability Status Scale (EDSS) 2.0, range 0-7.5) of whom 12.94 (SD 1.97) p 0.03: In cases mean AE was 16.1 (SD 4.02) and in 10 with history optic neuritis (ON+) in a single eye and 5 in both eyes controls, 26.87 (SD 12.17) p 0.002. 3 months before or more. All patients underwent assessment of Visual Conclusion: According to our study, electrical stimulation with Acuity (VA), VEPs (checkerboard, size 15’), global and temporal alternate current showed a statistically significant difference compar- (gRNFL and tRNFL) retinal nerve fibre layer thickness (Heidelberg ing patients with vertigo with asymptomatic persons. Such difference Spectralis OCT). Severity of VEP abnormalities was quantified with a was not observed when assessing this tract with auditory clicks. 4-graded conventional score (0 normal, 3 absent). Stimulation with alternate current is a novel technique not previously Results: In 52 eyes without previous ON, 19 % had reduced described. The difference encountered might be due to activation of gRNFL, (17 % tRNFL) vs 31 % VEPs. Both examinations were different neuronal populations of saccular-vestibulospinal tracts. abnormal in 15 %. Abnormalities only at VEPs were found in 15 % and only OCT in 4 %; VEPs or OCT were abnormal in 35 % eyes. DD was significantly correlated with tRNFL quadrant thickness P696 (Pearson’s r=-0.3, p=0.02) and not with gRNFL thickness or VEPs. RNFL thickness and VEP score were correlated with EDSS (gRNFL: Heart rate variability and predictive models Spearman rs=-0.43, p=0.001; tRNFL: rs=-0.33, p=0.01; VEP: of autonomic dysfunction after acute spinal cord injury rs=0.45, p=0.0002) and with VA (gRNFL: rs=0.30, p=0.03; tRNFL: A. Krstacic, G. Krstacic, D. Gamberger, G. Buljat rs=0.42, p=0.002; VEP: rs=-0.43, p=0.001). Clinical Hospital Centar ‘‘ Sisters of Charity’’ (Zagreb, HR); Clinic In 28 ON+ eyes, OCT gRNFL thickness was abnormal in 68 % for Cardiovascular Disease Prevention and Rehabilitation (Zagreb, (64 % tRNFL) vs 71 % VEPs; 61 % had abnormalities at both HR); Rudjer Boskovic Institute (Zagreb, HR) examinations, 11 % at VEPs only and 7 % at OCT only, 79 % had abnormal VEPs or OCT. RNFL thickness and VEP score were cor- Spinal cord injury (SCI) may cause loss of cardiovascular reflexes related with EDSS (gRNFL: rs=-0.4, p=0.04; tRNFL: rs=-0.38, mediated by sympathetic drive due to interruption supraspinal control p=0.01; VEP: rs=0.56, p=0.02) and with VA (gRNFL: rs=0.4, p=0.03; of spinal sympathetic motoneurons. tRNFL: rs=0.53, p=0.04; VEP: rs=-0.7, p=0.001).

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S187

Sensitivity of OCT and VEPs did not differ significantly (McNe- articular and vascular as well as further organ involvements. The term mar Test p[0.05) also when classifying patients as CIS/early MS of neuro-Behçet (NB) is used for BD with the central nervous system (DD\2yrs, n=11 ON-, n=4 ON+) and with longer DD ([2yrs, n=15 (CNS) involvement. In this study, the existence of the abnormal ON-, n=10 ON+). brainstem auditory evoked potentials (BAEPs) was investigated in the Conclusion: the finding of similar OCT and VEP sensitivity in patients with BD or NB and aimed to test the hypothesis that such CIS/MS patients underlines the complementary usefulness of these evoked potentials (EPs) can be used as a marker in determining the tools that, when used in combination, help increasing sensitivity in subclinical NB cases. detecting abnormalities in the visual pathways. The correlation with Methods: Fifty patients with BD and 12 patients with NB who disability, VA and DD supports the role of the two tests in monitoring applied to the Yuzuncu Yil University Medical Faculty were exam- MS patients. ined. BAEP recordings which are used to electrophysiological assesment of CNS abnormalities were bilaterally performed in the each participants. Absolute latencies of wave I,II,III,IV, and V and P698 inrerpeak latencies I-III, III-V, and I–V were calculated. Can combination of optical coherence tomography Results: Age and duration of illness were found significantly higher in group NB than group BD. The abnormality frequencies for and visual-evoked potentials help in the differential BAEP were 24 % and 45.45 % in BD and NB groups respectively. diagnosis of recurrent optic neuritis? A case report Although the abnormality ratio for BAEPs were higher in NB than M. Bianco, G. Di Maggio, D. Dalla Libera, V. Martinelli, BD, there was no statistical difference between the groups. On the G. Comi, B. Colombo, L. Leocani other hand the mean values of latency of the I, III, IV waves were relatively prolonged, and the amplitudes were higher in NB group San Raffaele Hospital (Milan, IT) than BD group, no statistically significant differences were found Objectives: To compare the relative value of VEP and OCT in a case between the groups. The most important abnormalities were absolute of isolated recurrent optic neuritis. latencies of I nd III waves, and I-III interpeak latency. Results: We report a case of a 23-year old caucasian woman, who Conclusion: BAEP abnormalities which were determined in this presented 7 years before sudden complete visual loss in her left eye study indicate that subclinical affection of the vestibular pathway and (with no dyschromatopsia or pain to eye movements). The ophthal- brainstem can occur even in some BD cases without neurological mologist ruled out an eye disease and neurological examination was involvement. EPs are effective in determining the lesions small normal. Brain MRI showed only one peritrigonal lesion and hyper- enough to escape clinical recognition or situated in clinically silent intensity of the left optic nerve, evident only in the STIR sequence. areas of the CNS. In conclusion, Behçet’s and NB patients with She was treated with steroids intravenously (i.v.) with some benefit abnormal EPs can be accepted as patients with subclinical neuro- (residual visual acuity 3/10 on her left eye).Visual evoked potentials – logical involvement and these cases must be informed about VEPs (full-field, checkerboard, size 30’ and 15’) were performed after symptoms of CNS affection and monitored closely. 3 months and were negative. After 6 years, she presented again with visual loss in her right eye (visual acuity 1/10 on her right eye). Brain MRI was unchanged and a cervical and dorsal spinal cord MRI were normal. Neurological examination was unremarkable except for P700 visual loss. A CSF examination was negative for presence of oligoclonal bands, as well as serum NMO-IgG. Repeated VEPs were Non-invasive localisation of somatosensory cortex using also normal. The fundus oculi showed a slight bilateral temporal high-resolution somatosensory-evoked potentials pallor of the optic nerve head, more evident on the left side. Spectralis with mechanical stimulation optic coherence tomography (OCT) showed a reduction of retinal A.M. Lascano, F. Grouiller, M. Genetti, L. Spinelli, nerve fiber layer (RNFL) thickness in the temporal quadrant, including the papillo-macular bundle (PMB) bilaterally, more severe M. Seeck, C. Michel and diffuse in the left eye displaying also reduced RNFL thickness in University Hospital of Geneva (Geneva, CH) the superior quadrant. The patient reported a moderate improvement Objective: To non-invasively and precisely localise the primary (residual visual acuity 8/10) after i.v. steroids therapy (1 g for 4 days). somatosensory cortex (SSC) in the individual brain and to compare A strict follow-up is ongoing. high-resolution somatosensory evoked potentials (SEPs) and func- Conclusions: The combined use of OCT and VEP in patients with tional magnetic resonance imaging (fMRI) with intracranial SEP recurrent optic neuritis may increase sensitivity in detecting lesions recordings. involving the visual pathways, by adding the ability of OCT in Methods: SEPs were elicited by non-painful air-puffs on the distal detecting axonal injury to that of VEPs in indentifying demyelinating phalanx of the first digit in a total of 50 healthy subjects (divided in lesions as delayed responses. In the present case, the presence of OCT two subgroups) and 6 patients with intractable epilepsy who later abnormalities, facing the absolute normality of VEPs, suggests an underwent intracranial monitoring with depth and subdural elec- inflammatory CNS disease with predominant axonal injury rather than trodes. In all cases, SEPs were obtained with 256-channel a classic demyelinating form. electroencephalogram (EEG) and analysed using electrical source imaging (ESI) techniques calculated with a template brain (subgroup of 31 healthy subjects) or individual MRI (subgroup of 19 healthy P699 subjects and all patients). In the patient group, electrodes covered SSC allowing recording of intracranial SEP. Direct cortical stimula- Brainstem auditory-evoked potentials in Behçet’s tion (DCS) was also applied in 5/6 patients and ESI results were disease and neuro-Behçet syndrome compared to the ESI localization obtained pre-operatively. Further- T. Tombul, T. Gulec, N. Akdeniz more, we compared localization precision of SSC of ESI versus fMRI Yuzuncu Yil University (Van, TR) in the subgroup of 19 healthy subjects and 4/7 patients. In the subgroup of 31 healthy subjects, we also evaluated the precision of air- Objectives: Behçet’s disease (BD) is a chronic systemic inflammatory puff vs versus more established electrical stimulation of the median disorder characterized mainly by mucocutaneous lesions, ocular, nerve.

123 S188 J Neurol (2012) 259 (Suppl 1):S1–S236

Results: Mechanical stimulation by air-puff rendered a more term follow-up of these participants will provide valuable information accurate localization and a lower inter-subject variability as compared on both their disease trajectory and satisfaction and effectiveness of with electrical stimulation. SEPs obtained through intracranial elec- their new medication. trodes were at the same site in 5/7 patients where DCS evoked NARCOMS is supported in part by the CMSC and its Foundation. sensory symptoms. Similar results in terms of localization were found This study was supported by Novartis Pharmaceuticals. in the subgroup of 19 healthy subjects who underwent both fMRI and ESI. Conclusion: SEP using air-puff stimulation is a painless stimulation technique that, if carried out with high-resolution ESI, allows P702 precise localisation of SSC in the individual subject. The method can Vitamin D supplementation in multiple sclerosis easily be applied to all patients, including children, who are unable to patients: considering the safety issues undergo fMRI. S.M. Nabavi, Z. Sabet, D. Morsali, M. Aminzadeh Shahed University (Tehran, IR); UCL (London, UK) ______Introduction: Many reports postulate, hypovitaminosis D is a potential risk factors of multiple sclerosis (MS).Also, there are some reports in Poster session 4 beneficial effects of vitamin D3 supplementation in patients with MS and, potentially a variety of autoimmune disease. Multiple sclerosis: miscellaneous Objective: The objective of this short report was to determine the safety of high dose (pharmacologic dose) of vit D3 in patients with MS. Design: In our clinic, we prescribed vit D3 50.000/week in a 6 months protocol for 44 definite Relapsing remitting MS with disease P701 duration from 0-1 year, mean EDSS 1. we assessed the baseline and 6 What prompts a switch in disease-modifying therapy month serum 25(OH) D levels and other markers of safety and beyond first-line therapies? intoxication(ca.p, alkaline phosphatase, PTH, urine 24 ca, Urine 24 Cr)in these group. A. Salter, T. Tyry, D. Belletti, M. Malhotra, R. Marrie, Results: Mean (±SD) serum concentration 25(OH)D Increased R. Fox, G. Cutter from 7.3±15 ng/dl in baseline up to 45.6± 34.9ng/dl in month 6. University of Alabama (Birmingham, US); Barrow Neurological Serum calcium, creatinine concentration and the 24 h urinary calcium Institute (Phoenix, US); Novartis Pharmaceuticals (Walnutport, US); concentration remained in normal range of the reference values for Novartis Pharmaceuticals (East Hanover, US); Health Sciences any participants (9.2± 4.2 and 119± 64, respectively) without any Centre (Winnipeg, CA); Mellen Center for MS, Cleveland Clinic laboratory clues of toxicity. Also any patient revealed the clinical (Cleveland, US) signs of VitD toxicity. Conclusions: The data supports the tolerability of pharmacologic Objective: To investigate the reasons patients switch disease modi- doses of vit D3(At least 50000 unit per week) and it emphasis that fying therapies (DMTs) and to identify main patient characteristics vitamin D intake beyond the physiological recommended dosage is associated with the decision. Physicians and patients could benefit safe in Multiple sclerosis patients. from a better understanding of the expectations regarding DMTs and No conflict of interest. the reasons associated with a decision to switch. Method: The North American Research Committee on MS (NARCOMS) Registry conducted a supplemental survey among registry participants who reported a DMT switch in their Spring or P703 Fall 2011 update survey. The supplemental survey focused on reasons Correlation between cognitive dysfunction, fatigue, for switching DMT, origin of the discussion of DMT change and what factors influenced the decision. Demographics and disease charac- depression and disability status in a cohort of multiple teristics were obtained from the NARCOMS database. Descriptive sclerosis statistics are presented to summarise the data. S.M. Nabavi, S. Tahbaz, Z. Behjati, F. Nourbala, Results: Of the approximately 700 potentially qualified candidates, S. Sadeghi, Z. Saeedi, A. Salahesh 300 have been sent the survey and 159 meeting the eligibility criteria Shahed University (Tehran, IR); Tehran University (Tehran, IR) have responded to date. The respondents are 85.5 % female with an average (SD) age of 50 (9.8) years, disease duration of 13.2 (7.5) years, Objective: To investigate the relationships between Depression, and a median (IQR) Patient-determined Disease Steps score of 3 (gait Fatigue and Disability with Cognitive Skills of patients with multiple disability; 1-4). Based on the interim results, the drugs most frequently sclerosis (MS) in cohort of Iranian population. switched to in 2011 were fingolimod (40.3 %), natalizumab (20.1 %) Methods: One hundred and forty-seven individuals (147 MS and glatiramer acetate (15.1 %). Reports on the previous therapy Patients) with mean age of 33 years, mean disease duration of 20.20 included all DMTs, most often glatiramer acetate (38 %) and inter- months and mean EDSS of 2.13, F/M=76/23 % were included in this feron beta 1-a IM (30 %) which also were the most widely used DMTs study. Depression was measured by the Beck Depression Inventory in the spring 2011 survey (40.8 % and 20.2 %, respectively). The (BDI), Fatigue was assessed using the Fatigue Severity Scale (FFS) discussion to switch DMT was initiated almost equally by physicians and Modified Fatigue Impact Scale (MFIS), Disability was evaluated and participants. The primary reason for choosing the new DMT was by the Expanded Disability Status Scale (EDSS) and Cognitive most frequently based on physician’s recommendation (19.5 %) and Function by the Brief Repeatable Battery of Neuropsychological patient perception of efficacy (13.2 %). Over 68 % reported their Tests (BRB-N). Data were analyzed using Pearson correlation. treatment being managed by an MS specialist. Results: As results show BDI has significantly positive correlation Conclusion: Patients report having a significant role in initiating with FSS, MFIS and negatively with two subscales of BRB (PASAT & the discussion of changing DMT, although physician recommenda- WLG). It means that higher levels of depression in patients with MS tions regarding the specific therapy are still weighed highly. Long are associated with lower cognitive performance in the tasks which

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S189 required higher-order working memory (WM) processes. In addition perception using an extensive battery of bedside and quantitative to, the FFS showed the strongest negative correlation score with BRB, sensory testing (QST) was performed in 17 patients with MS (11 men and conversely displayed significant positive correlation with MFIS. and 6 women, median age 31, range 19-56 years) and 20 healthy Also the global EDSS score were negatively correlated with BRB. volunteers (8 men and 12 women, median age 34, range 23-55 years). These results approve that the higher levels of depression, fatigue and Seven of the MS patients fulfilled the current diagnostic criteria for disability are related with less cognitive function in MS patient. central neuropathic pain (CNP-MS subgroup), while no pain was Conclusion: Depression, Fatigue and Disability (the most frequent recorded in the remaining 10 MS patients (non CNP-MS subgroup) problems found in MS patients) are clearly related with cognitive and healthy controls. The testing included both static and dynamic impairment in MS patients. QST methods. Among others, magnitude of conditioned pain modu- No conflict of interest. lation (diffuse noxious inhibitory control (DNIC)-like effect) and temporal summation (TS) using thermal stimuli were assessed. Results: Comparing to healthy controls, MS patients (irrespectively to the presence of CNP) showed the decreased perception of P704 most of the sensory modalities examined (e.g. decreased cold per- Sympathetic skin response in multiple sclerosis ception thresholds and increased warm, tactile and heat pain and clinically isolated syndrome: a case-control study perception thresholds). No significant differences in any of the static M.H. Harirchian, V. Aghamollaii, A. Tafakhori, QST parameters were observed between CNP and non-CNP MS patients with the only exception of the ‘‘paradoxical cold sensation’’, M. Ghaffarpour, A. Modabbernia, M. Mousavi i.e. a warm stimuli perceived as a cold sensation, which were Tehran University of Medical Science (Tehran, IR) reported in 2 CNP (and no non-CNP) MS patients, while ‘‘para- Objective.—To compare the sympathetic skin responses (SSRs) in doxical heat sensation’’, i.e. a cold stimuli perceived as a burning hot patients with multiple sclerosis(MS), clinically isolated syndrome painful sensation was found in about a quarter of both the CNP and CIS), and healthy controls. non-CNP MS patients. No such paradoxical sensation was observed Methods.—SSR was recorded on both hands and feet in 30 in any of the healthy controls. A trend towards less efficient temporal patients and 20 healthy controls. SSR results (latency measurements) summation of thermal stimuli was observed in MS patients, partic- were compared in patients with normal or abnormal brainstem audi- ularly in CNP-MS subgroup A significant DNIC-like effect was tory evoked potentials (BAEPs), visual evoked potentials (VEPs) and demonstrated in both groups without any significant differences somatosensory evoked potentials (SEPs). between them. Results.—Twenty-three (76.6 %) and sixteen patients (53.3 %) Conclusion: Only minor differences in sensory and pain percep- with MS had abnormal SSR recordings based on 2-standard deviation tion were observed between CNP and non-CNP MN patients. (SD) or 3-SD (from the mean of the control group) abnormality criteria, respectively. Sixty-six percent and 40 percent of patients had abnormal([2 SD) SSR in at least one hand and one foot, respectively. P706 Patients with absent SSR had more severe disease and higher Expanded Disability Status Scale (EDSS) scores. Fourteen patients The autonomic dysfunction and fatigue in initial phase had an EDSS of zero, of whom nine had abnormal SSR and others had of multiple sclerosis at least one abnormal EP study. Patients with abnormal SSR had I. Okacova, E. Vlckova, M. Hnojcikova, Y. Benesova, significantly more abnormal BAEPs and SEPs than patients with P. Stourac, P. Praksova, J. Bednarik on behalf of CEITEC, normal SSR. SSR latencies were significantly correlated with EDSS and disease duration (P\0.01). All patients had at least one abnormal Central European Institute of Technology, Masaryk electrophysiological study. ROC curve analysis showed that a cut-off University score of 7008 ms as the sum of all-4-limb SSR latencies had a 80 % sensitivity and 95 % specificity for differentiating MS patients from Introduction: Patients with relapsing-remitting multiple sclerosis in healthy controls. clinical remission may present signs or symptoms of autonomic dysfunction (AD), which seem to correlate with fatigue. The aim of the study was to examine the presence of such a changes in initial phases of the disease, i.e. in patients with clinically isolated syndrome P705 (CIS). Evaluation of sensory and pain perception Patients and methods: In this prospective study, autonomic func- and mechanisms of central modulation of pain tions and fatigue were assessed in 23 patients with clinically isolated perception in patients with multiple sclerosis syndrome, fulfilling current diagnostic criteria of multiple sclerosis (CIS; 17 women, 6 men, median age 31, range 20-51, EDSS score (a pilot study) ranged from 0.0 to 3.0) and in 25 age- and sex-matched healthy M. Hnojcikova, E. Vlckova, I. Okacova, P. Praksova, volunteers (18 women, 7 men, median age 29, range 23-48). All the S. Bursova, J. Bednarik on behalf of CEITEC—Central included individuals underwent a thorough clinical neurological European Institute of Technology, Masaryk University examination, detailed assessment of autonomic symptoms and fatigue using appropriate questionnaires and the evaluation of cardiovascular and sudomotor autonomic function using the sympathetic skin Introduction: Multiple sclerosis (MS) is considered as a suitable response (SSR), and the assessment of heart rate variability in normal model for central neuropathic pain (CNP). Knowledge of sensory and deep breathing, and its reaction to standing and Valsalva profile and function of central modulation of pain perception in CNP maneuver (i.e. so called Ewing tests) as well as using spectral analysis patients may help to reveal underlying mechanisms of CNP, which of heart rate variability (SAHRV). are still not fully understood. Results: CIS patients displayed increased fatigue and significantly Patients and methods: A detailed evaluation of sensory and pain more frequent signs and symptoms of AD in comparison with healthy perception and of mechanisms of central modulation of pain individuals. Furthermore, a clear correlation of fatique scores with the

123 S190 J Neurol (2012) 259 (Suppl 1):S1–S236 frequency of symptoms and signs of AD (as well as with abnormal- P708 ities of neurophysiological autonomic tests) was found. In accordance to Stability of marital status in NARCOMS these findings, SSR (particularly in lower extremities) has been evoked significantly less frequently (p\0.05) in CIS patients comparing to S. Cofield, B. Davis, A. Salter, T. Tyry, L. Hornung, healthy controls and a trend towards lower SSR amplitudes and longer R. Marrie, R. Fox, G. Cutter SSR latencies in upper and lower extremities was found. Furthermore, University of Alabama (Birmingham, US); Barrow Neurological significantly lower spectral power values were found in SAHRV exam- Institute (Phoenix, US); University of Manitoba (Manitoba, CA); ination in CIS patients, while the differences in cardiovascular Cleveland Clinic (Cleveland, US) parameters evaluated using the Ewing tests were insignificant. Background: Multiple Sclerosis is a chronic and disabling disease that Conclusion: Significant abnormalities of several autonomic tests affects not only the persons with MS but also their personal rela- and higher frequency of related symptoms and signs has been found tionships. Five non-North American studies have found that 73-86 % already in very early phase of multiple sclerosis (i.e. in CIS patients), of persons with MS were still married 5-15 years after diagnosis, with in spite of the fact that some of the tests used in our study (in par- one study finding declining marriage rates at 5 (86 %), 10 (78 %) and ticular Ewing tests) seem to be less sensitive for the documentation of 24 (33 %) years; while one study in the United States (US) found that such a changes. Significant correlation of AD with increased fatigue 79 % of 108 participants remained married up to 14 years after was shown. diagnosis. Objective: To estimate the marital stability in the large North American based registry, NARCOMS, and compare these results to prior studies conducted in Europe, Australia & the US. P707 Methods: Marital status (never married, married, separated, Autologous stem cell transplantation in a patient divorced, widowed, cohabitating) at enrollment and 5 years after with multiple sclerosis and multiple myeloma enrollment will be assessed for a change in status. In addition, comparison between genders in status and change in status will be G. Masi, L. De Santi, A. Bucalossi, F. Toraldo, assessed and associations with insurance status, medication usage, age P. Annunziata and disease duration will be examined. University of Siena (Siena, IT) Results: The 10,076 participants in the NARCOMS registry who Objectives: High-dose melphalan with autologous stem cell trans- reported marital status at enrollment and on at least one follow up plantation (ASCT) has been an integral part of multiple myeloma survey 5 years after enrollment were 47.5±11.0 yrs old, 15.9±9.7 yrs (MM) therapy. ASCT has been assessed in the past few years as a new since diagnosis, 75.0 % Female, with 59.6 % married at enrollment, therapeutic strategy in severe multiple sclerosis (MS). However, the 17.0 % separated and 11.4 % have never been married. At enroll- conditioning protocol preceding ASCT differs in MM and MS. In this ment, men were older than women (50.8±11.2yrs vs 46.4±10.7yrs, report, we describe the case of a 48-year-old man with relapsing- p\0.0001) and more likely to be married (64.0 % vs 58.0 %, p remitting MS developing a IgA/k MM, successfully treated with \0.0001). At least 5 years after enrollment (6.1±1.5yrs, median 5.5, ASCT after a conditioning protocol for MM. In this patient, the range 5-15), 79.5 % had no change in marital status, with no differ- transplantation was also effective for MS. ence by gender (p = 0.63). Of those that were married at enrollment, Case report: A 48-year-old man with definite relapsing-remitting MS 91 % were still married at follow-up (92 % of men, 90 % of women, treated with s.c. interferon (IFN) beta-1b for 5 years switched to intra- p = 0.11), with 6 % reporting being divorced or separated. For those muscular IFN beta-1a, started to experience increasing fatigue as well as with at least 10 years of follow up (n=4,406), 75.9 % reported the appetite losing, weight loss and transient evening fever. A blood analysis same marital status as enrollment, with 89.1 % of those married at revealed the presence of megaloblastic anaemia and serum protein enrollment still married after at least 10 years. electrophoresis showed a beta monoclonal peak and hypogammaglobu- Conclusions: At 5 years after enrollment, the North American linemia. Immunoelectrophoresis revealed increased IgA levels and, at based NARCOMS participants report a higher stability in marriage immunofixation, a gammopathy IgA/k was demonstrated. A total body status compared to other studies but with a similar 10-year percent- X-ray showed skeletal disseminated lytic lesions. The diagnosis of age, with no difference in change of status between genders. Patterns multiple myeloma IgA/k stage III A was made and further confirmed by a of change in status, as well as contributing factors to a change in bone marrow biopsy disclosing the presence of 30-40 % monoclonal status will also be presented. plasma cells. After the suspension of the immunomodulatory therapy, the NARCOMS is supported in part by the CMSC and its Foundation. patient underwent a conditioning regimen with melphalan 200 mg/m2 prior to ASCT. Suspension of the IFN beta-1a was continued and nine months after ASCT, MM was on clinical remission and the patient did not experience P709 new MS relapses. In addition, a brain magnetic resonance imaging (MRI) Safety and efficacy of repetitive deep transcranial did not reveal new T2 or gadolinium-enhancing lesions. magnetic stimulation in multiple sclerosis Discussion and conclusion: Autologous stem cell transplantation has been considered as a possible new therapeutic strategy in severe G. Gaede, M. Tiede, I. Lorenz, H. Zimmermann, forms of MS. The most common conditioning protocol used in MS is C.F. Pfueller, J. Do¨rr, J. Bellmann-Strobl, A. Ginou, the BEAM regimen including carmustine (1,3-bis[2-chloroethyl]-1- A. Zangen, S. Schippling, F. Paul nitrosourea), etoposide, cytarabine (arabinosylcytosine) and melpha- Charite´ (Berlin, DE); University Medical Centre Hamburg Eppendorf lan. At present, BEAM is considered the conditioning regimen with (Hamburg, DE); Brainsway Ltd. (Jerusalem, IL); Weizmann Institute the best efficacy and safety profile. of Science (Rehovot, IL) This report suggests that the conditioning protocol used in MM, followed by ASCT, can also be effective in MS, leading to blocking Background: Fatigue is one of the most frequent symptoms in mul- of inflammatory activity and clinical disease stabilization. However, a tiple sclerosis (MS), affecting up to 90 % of patients at onset or longer follow-up is needed to assess the long-term efficacy of this during the course of the disease. Neither are underlying mechanisms ASCT conditioning protocol in MS. understood, nor do convincing therapies exist. Repetitive transcranial

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S191 magnetic stimulation (rTMS) has proven safe and efficacious for comparison, in correlation with the different HLA background treating depression. Newly developed coils, like the novel H-Coil, (DRB1*15, which is considered MS-specific, versus the other two enable the stimulation of deeper brain regions, which are presumably which are not MS-associated), highlights the possible role of HLA- involved in the pathophysiology of fatigue or depression. haplotype in the immunopathogenic processes and the possible usage Objective: To perform a randomized, sham-controlled pilot study of such information on the therapeutic choice and follow-up of the to evaluate safety, tolerability and effect of deep rTMS on fatigue patients. in patients with multiple sclerosis. This trial is registered as Conclusion: Based on these case-observations and due to lack of NCT01106365. relative studies, we propose the hypothesis that the HLA-haplotype Methods: 26 MS-patients underwent 18 sessions of deep rTMS may be a determining factor concerning the MS-typical or ‘‘MS-like’’ over a period of 6 weeks. 10 patients underwent sham stimulation, 8 nature of CNS demyelination in AS patients. In this context, further patients stimulation of the left prefrontal cortex (PFC) (18Hz, 120 % studies are needed to verify this observation-based hypothesis. motor threshold (MT)) and 8 patients of the motor cortex (MC) (5 Hz, 90 % MT). Following the treatment period, patients were observed for further 6 weeks. The effect on fatigue was evaluated with the Fatigue Severity Scale (FSS), the Modified Fatigue Impact Scale P711 (MFIS) and a Visual Analogue Scale (VAS) of fatigue. Statistical Dynamics of saccadic parameters in multiple sclerosis analyses were performed using SPSS 19. patients with fatigue Results: Deep rTMS was well tolerated without significant adverse L.M. Pech, C. Finke, J. Schlichting, C. So¨mmer, S. Stricker, effects or adverse events. There were no differences in baseline values of both the FSS and the MFIS between the 3 groups. Regarding FSS C.J. Ploner, F. Paul, A.U. Brandt scores, PFC stimulation showed a tendency to decrease (-26.14 %± Charite´ (Berlin, DE) 37.4 %, p=0.088) and MC stimulation showed a significant decrease Objective: To investigate the potential diagnostic value of a saccadic (-26.18 %±13.99 %, p=0.042), while sham showed no difference fatigue task for the detection and quantification of fatigue in multiple (-2.12 %±44.2 %, p=0.285). Regarding VAS PFC stimulation sclerosis (MS) patients showed a highly significant decrease over time (-29.39 %±44.55 %, Background: Fatigue is one of the most frequent and most dis- p=0.006), however, MC stimulation did not (+6.28 %±97.18 %, abling symptoms in patients with MS. However, its pathophysiology p=0.144). The same held true for sham stimulation (p=0.144). remains poorly understood and objective measures to reliably quan- Changes in MFIS and MFIS subscale analyses were not significant tify fatigue are not available to date. following PFC or sham stimulation, but total MFIS scores tended to Methods: 37 MS patients (16 male/21 female, age 44±9 years) decrease under MC stimulation (-27.98 %±14.89 %, p=0.067) as did and 20 age and gender matched healthy controls were prospectively MFIS physical scores (-31.82 %±8.29 %, p=0.053). recruited. Fatigue was assessed using the Fatigue Severity Scale Conclusion: Our data illustrates that deep rTMS is safe and well (FSS). Subjects then performed a saccadic fatigue task that required tolerated in MS patients with structural brain lesions and may have a execution of uniform saccades over a period of ten minutes. We positive influence on fatigue. Effects were observed in both verum arms, analyzed the dynamics of saccadic amplitude, latency and peak PFC and MC, but not in the sham group. Recruitment is ongoing. velocities during the task using non-parametric Brunner Analyses for longitudinal data. A correlation between FSS scores and task parameters was analysed using Spearman’s Rho. Selected task P710 parameters differing between fatigued and non-fatigues patients were finally tested in a ROC analysis. The fine borders between central nervous system Results: According to FSS, 25MS patients were fatigued (defined demyelination and definite multiple sclerosis in anti- as FSS[=4) and 12 MS patients were not. Fatigued patients showed a TNFa - treated ankylosing spondylitis: could it be significantly larger decrease of saccadic peak velocity (p=0.002) and genetically predisposed? amplitude (p=0.042) during the saccadic fatigue task when compared to patients without fatigue and healthy controls. Furthermore, fatigued A. Lourbopoulos, P. Ioannidis, D. Antoniadis, patients showed a significantly larger latency compared to non-fati- N. Grigoriadis, N. Tascos gued patients and healthy controls (p=0.004) throughout the whole AHEPA University Hospital (Thessaloniki, GR) task. Peak velocity change over time (Rho=-0.47, p=0.004) and latency (Rho=0.39, p=0.019) correlated well with FSS score. Best Objectives: Multiple sclerosis (MS) rarely co-morbids with ankylos- parameter to discriminate between fatigued and non-fatigued patients ing spondylitis (AS). Few cases have been described for coexistence was peak velocity change over time (ROC, AUC=0.857). of AS and MS or an ‘‘MS-like’’ syndrome, though only one has Conclusions: The saccadic fatigue task including an analysis of clearly been associated with anti-TNFa treatment. Immune therapies saccade amplitude, peak velocity and latency is a promising approach approved for the treatment of AS such as anti-TNFa factors may for quantifying fatigue in MS patients. induce demyelination in patients without any previous history of This project was supported by research grant Exc 257 from DFG. Central Nervous System (CNS) involvement or, more rarely, unre- vealing a salient MS. Methods: we present 3 cases of AS treated with anti-TNFa factors that displayed different types of CNS involvement: MS-typical or ‘‘MS-like’’ demyelination. MS was diagnosed based on the 2010 P712 revised McDonald criteria. Cognitive performance in a cohort of MS patients Results: One case was diagnosed as MS whereas the other 2 as in comparison to healthy subjects: an assessment atypical demyelination (‘‘MS-like’’). The demyelination foci were with BRB-N from Iran possibly attributed to the concomitant immunomodulating treatment (anti-TNFa). The patients had different HLA haplotypes: HLA- S. Tahbaz, S.M. Nabavi, Z. Behjati, F. Nourbala, DRB1*15 for the MS-AS patient and HLA-DRB1*16 or DRB1*04/ S. Sadeghi, Z. Saeedi 07 in the demyelination-AS cases. Their clinical and MRI Tehran University (Tehran, IR); Shahed University (Tehran, IR)

123 S192 J Neurol (2012) 259 (Suppl 1):S1–S236

Objective: To investigate the cognitive skills of patients with multiple Objective: To study different domains of motor and cognitive fatigue sclerosis (MS), relative to healthy control participants a cohort of in mildly disabled patients with clinical isolated syndromes (CIS) and Iranian population. relapsing remitting multiple sclerosis (RR-MS) with self-reports by Methods: MS patients (n= 147) with mean age of 33 years, mean the patient and objective methods to record the decline of motor and disease duration of 20.20 months and mean EDSS of 2.13, F/M=76/ cognitive performances over time, and to study correlations of motor 23 % and healthy control subjects (n= 100) were assessed by the Brief fatigue with central motor conduction failure detected by of the triple Repeatable Battery of Neuropsychological Tests (BRBN). This stimulation technique (TST). instrument measures 5 different domains of cognitive function, Methods: 21 patients with RR-MS and 16 patients with CIS including: Selective Reminding Test (SRT), Spatial Recall Test (Expanded Disability Status Scale (EDSS) 0 – 4, median 2.0) were (SPART), Symbol Digit Modalities Test (SDMT), Paced Auditory examined: 12 min-walking test (12MW) was performed, were the Serial Addition Test (PASAT), Word List Generation (WLG). Data distance covered per minute was registered and a linear trend was were analyzed using Pearson’s and Spearman rank order correlations calculated as a measure of change of walking distance per minute. and ANCOVAs. TST (a collision technique of corticospinally mediated excitatory Results: results indicated that Age and disability level generally responses elicited by transcranial magnetic stimulation and distal and correlated negatively and significantly with task performance, proximal peripheral nerve motor potentials) to the upper limbs (to whereas a higher level of education was associated with better task abductor digiti minimi muscle) and lower limbs (to abductor hallucis performance. Relative to controls, cognitive performance of MS muscle) was used to quantify central motor conduction. Both 12MW patients was deficient in all BRBN measures except Symbol Digit and TST were also applied to normal controls to establish normal Modalities Test which is a measure of attention and processing speed. values. Rao´s neuropsychological test battery (BRB) containing cog- Conclusion: MS patients exhibit a pattern of cognitive impairment nitive tasks (learning, memory, concentration, executive functions) running across the studied cognitive domains and in comparison to and the Beck depression inventory (BDI) were carried out. Subjective healthy subjects. motor and cognitive fatigue were questioned with the ‘‘Wu¨rzburger Fatigue Inventory in MS’’ (WEIMuS). SPSS-standard software was used for statistical analysis. Results: Self-reported motor and cognitive fatigue and clinical P713 findings in the BDI were highly correlated (p \ 0.001; r = 0,9), both Comparison of self-destructive personality tendencies correlated weakly with below-average abilities in cognition (BRB) in MS patients and healthy subjects and ambulation (12MW). Central conduction failure to the lower S. Tahbaz, S.M. Nabavi, N. Ghorbani limbs quantified with TST correlated significantly with the EDSS (p\ 0.01) but not with self-reported motor fatigue or the linear trend of the Tehran University (Tehran, IR); Shahed University (Tehran, IR) 12MW. Background: Based on ‘‘teleological coherence’’ hypothesis, all of the Conclusions: In mildly disabled CIS- and RR-MS patients self systems of an organism (nervous, immune, neuroendocrine and psy- reported motor or cognitive fatigue is neither caused by pyramidal chological systems) are going to achieve a common goal: building a tract lesions or disability reflected in the EDSS, nor are these accu- distinct self-identity, and when the boundaries between self/nonself rately reflected by objective measurements of declining motor or are broken in one system (e.g. producing autoantibodies in immune cognitive performance over the tested time. Significant correlations of system), they’ll be destroyed in other systems more probably self reported motor and cognitive fatigue and the BDI may discrim- (developing self-destructive personality tendencies at the psycholog- inate a subgroup of CIS and MS patients whose subjective symptoms ical level). might be an epiphenomenon of depression or alternatively caused by Method: In this project we studied self-destructive tendencies cortical pathology. and integrative self-knowledge of MS patients (N=88) and normal subjects Study supported by: Bayer-Vital, Leverkusen, Germany (unre- (N=130) by means of following scales: Integrative-Self-Knowledge, stricted grant). mindfulness, self-control, Interpersonal problems, Self-Harm, and masochism subscale of Millon Clinical Multiaxial Inventory. Results: Results showed that MS patients were significantly higher than normal subjects in masochism, interpersonal sensitivity and P715 aggression and lower in Integrative Self-Knowledge (ISK). Then, Assessment of gait and balance in early relapsing- disharmony in one system is accompanying by disharmony in other remitting multiplescleroris systems. E. Degirmenci, L.S. Bir Conclusion: There are some therapeutic implications for this Pamukkale University (Denizli, TR) result: in order to reduce the disharmony in one system, we should improve the disharmony in other systems. So, psychological inter- Objectives: Balance and gait disorders can be the initial symptoms of ventions that promote self-interest in MS patients can improve multiple sclerosis (MS) and can be very disabling symptoms which immunological symptoms in these patients. affect about 75 % of patients during the course of the disease. Mildly No conflict of interest. disabled MS patients complaining poor balance control may not show any unequivocal clinical signs of imbalance during standard examination. In this study we aimed to evaluate the balance and gait problems in relapsing-remitting MS (RRMS) patients by Tinetti P714 Balance & Gait Test (TBGT) and Timed Get up & Go Test (TGUGT) Motor fatigue correlates with cognitive fatigue and to find the relationship with fall attacks. and depression but not with central motor conduction Methods: 60 patients with RRMS and 30 age and gender matched failure and walking speed in mildly disabled patients controls volunteered for the study. The mean age of the patients was 39.6±9.9 years and the mean EDSS score was 1.3±1.2 indicating a with clinical isolated syndromes and multiple sclerosis mild-to-moderate impairment. Statistical analyses were performed on U. Hofstadt-van Oy, U. Menge, J. Burschka, P. Oschmann three groups; the first group was consisting of RRMS with fall attacks Klinikum Bayreuth (Bayreuth, DE) (Fallers; 41.7 % of the patient group), the second group was

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S193 consisting of RRMS without any fall attacks (Non-fallers 58.3 % of P717 the patient group) and the third group was consisting of healthy Validation of Brief International Cognitive Assessment subjects. Results: Statistical analyses showed that both TBGT and for Multiple Sclerosis (BICAMS) TGUGT scores were significantly lower in RRMS patients than the J. Blahova Dusankova, T. Kalincik, E. Havrdova, control group. In addition, the TBGT scores were significantly R.H.B. Benedict lower in fallers group than the non-fallers group of the RRMS Charles University, General Teaching Hospital (Prague, CZ); Jacobs patients. Neurological Institute, Buffalo General Hospital (Buffalo, US) Conclusion: These tests showed the existence of evident fall risk in patients with RRMS even in the early stages of the disease and our Background: Cognitive impairment is a common and disabling results suggest that these scales taking nearly 5-minutes, which are symptom of multiple sclerosis (MS), with prevalence rates ranging very easy to perform, may be used to estimate risk of fall in early from 43 % to 70 % at both the earlier and later stages of the disease. RRMS patients. Traditionally, cognitive function has not been included in standard clinical assessment, and cognitive tests are widely perceived to be complicated, time-consuming, and expensive to perform. Objective: Our aim was to examine validity and accuracy of the BICAMS - brief cognitive assessment for MS - that was recently P716 recommended by an expert committee and constructed to maximize Familial multiple sclerosis: a clinical, ophthalmic international use. and radiological study Methods: We tested 367 MS patients and 134 healthy controls. C. Oreja-Guevara, L. Rodriguez de Antonio, N. Martin, Mean patient age was 34.4 ± 9.5 years, with completed 14.1 ± 2.9 years of education, 65 % (n=250) women and 35 % (n= 117) men. B. Manzano, E. Diez-Tejedor, S. Noval The mean EDSS score was 3.1 ± 1.5 and the mean disease duration University Hospital la Paz (Madrid, ES) was 8.1 ±6.8 years. Most patients (n=250 or 68.1 %) had relapsing- Introduction: Susceptibility to multiple sclerosis is determined by remitting rather than secondary-progressive (n=94 or 25.6 %), pro- environmental and genetic factors. Some studies found more benign gressive-relapsing (n=14 or 3.8 %), or primary-progressive (n=9 or MS and less progressive forms in familial multiple sclerosis than in 2.5 %) course. Mean control age of 33.8 ± 8.8 years and 14.4 ± 2.5 sporadic cases. years of education. The majority of the controls were women (n=95 Objective: To search for patterns of concordance in clinical, or 71 %). All participants underwent the validated 90-minute neu- radiological and ophthalmic manifestations among patients with ropsychological battery, MACFIMS (Minimal Assessment of familial MS. Cognitive Function in MS), which also comprises the 3-tests of the Methods: Descriptive retrospective study. Members of the same BICAMS battery (Symbol Digit Modalities Test, Brief Visuospatial family who were diagnosed of MS were invited to participate. Memory Test-Revised, California Verbal Learning Test, second Patients were considered familial MS if they had in their family at edition). least one relative of first or second degree diagnosed with MS. Results: The most accurate BICAMS criterion of cognitive deficit Neurological exploration were performed every six months. Radio- was that of at least 1 of the overall 3 tests outside the normal range -28 logical studies were performed at baseline. The ophthalmologic (accuracy = 90 %, p=10 ). Sensitivity and specificity of BICAMS to examination included visual acuity, colour and contrast sensitivity patients with cognitive deficit diagnosed with MACFIMS was 94 % tests, anterior and posterior pole examinations and RNFL thickness and 86 %, respectively. While MACFIMS evaluated 55 % of the MS measurement. patients as having cognitive deficit, BICAMS detected 58 % of the Results: Seventeen patients who belonged to eight different MS patients. BICAMS showed changed employment status compa- families were recruited. Six pairs were siblings and five subjects had rable to MACFIMS. a second grade familiar relationship. There is a concordance for age Conclusion: We conclude that the BICAMS is a valid approach to at onset, however the onset symptoms were very different. The routine neuropsychological assessment of MS patients. BICAMS is relapse rate is significant different between parents and children and optimized for small centers, with one or few staff, who may not have siblings (p\0.03). There is no concordance for disease severity neuropsychological training. within any of the considered family groups (p\0.05). Very similar Supported by the Czech Ministry of Education, Research Program focal brain abnormalities occur in the baseline MRI within the same MSM 0021620849. family. Seven patients had suffered optic neuritis (41.2 %) and there were isolated cases of fourth nerve palsy, internuclear ophthalmoplegia, P718 pars planitis and nystagmus. Ocular manifestations were similar in two families. All cases had a visual acuity of at least 2/3, 19 out of 20 Interrelation between visual impairment and cognitive correctly identified Ishihara plates and a mean of 25.36 out of 70 performance in multiple sclerosis letters (2.5 % Sloan chart) in each eye. Optic nerve atrophy was found L. Wieder, L.M. Pech, K. Klumbies, H. Zimmermann, mainly in patients with a history of optic neuritis or in those with the K. Deuschle, J. Bellmann-Strobl, K. Ruprecht, A.U. Brandt, longest time from diagnosis. Conclusion: Although similar brain MRI abnormalities occur F. Paul in familial MS at onset, clinical characteristics and evolution were Charite´ (Berlin, DE) very different. No specific patterns of ocular manifestations were Objectives: Cognitive impairment affects 50 to 70 % of multiple found. This study supports the presence of other critical non- sclerosis (MS) patients. Established screening procedures focus on inherited factors responsible of the clinical evolution of the cognitive domains such as memory, learning, attention and executive patients within the same family and the low concordance in function. Visual impairment affects about clinical neurological and ophthalmic manifestations between 80 % of MS patients in the course of disease. Currently under- relatives. represented in routine scoring, it is under debate to include further

123 S194 J Neurol (2012) 259 (Suppl 1):S1–S236 tests for cognitive and visual function in the Multiple Sclerosis type psoriasis was prominent (83 %). Arthritis was diagnosed in 3 Functional Composite (MSFC). The aim of our study on the one hand patients (25 %). The mean EDSS score was 2.75±1.9. MRI lesions’ was to reveal a possible impact of visual deficits on cognitive test distribution and morphology were typical for MS in 11 patients. Only performance. On the other hand, complex visual tests like contrast 1 patient had a single tumor-like lesion at MS onset. CSF oligoclonal sensitivity require cognitive abilities and might thus be influenced by bands were positive in 6 patients (50 %). 3 patients reported cognitive impairment themselves. improvement in psoriasis symptoms after the onset of MS and 3 Methods: 125 patients with clinically isolated syndrome or MS aggravation (2 of them treated with IFN-B 1b). 4 out of 10 patients were prospectively recruited. All patients received cognitive evalua- reported psoriatic lesions improvement during MS relapse (40 %). 2 tion with the Paced Auditory Serial Addition Test (PASAT), the patients presented with CIS during or right after the completion of Symbol Digit Modalities Test (SDMT) and the Faces Symbol Test treatment with Etanercept and one had MS onset during treatment (FST). Visual assessments included retinal nerve fibre layer (RNFL) with Ustekinumab. 10 patients had one 1st or 2nd degree relative with thickness measurements by optical coherence tomography, functional autoimmune disorder (50 % psoriasis). acuity contrast testing (FACT) and visual acuity. PASAT was per- Conclusion: No significant increase in the incidence of psoriasis formed as cognitive test without visual components and SDMT and was found among MS patients. Psoriasis was found to precede MS in FST as cognitive tests with visual components. all cases, with a higher incidence of arthritis than usually reported (5- To estimate effect sizes we performed linear regression models 10 %). High familial autoimmunity prevalence was also found. Pso- using means from monocular measurement. We confirmed these riasis improvement during MS relapses was reported in 4 patients. results with generalized estimating equations models (GEE) Disease severity, lesion distribution and morphology did not differ accounting for intra-patient inter-eye correlations. from MS patients without psoriasis. Results: In linear regression models PASAT predicted 19.6 % (p\ 0.001) and RNFL thickness 6.3 % (p = 0.002) of FST results (total R2 = 0.259). PASAT predicted 26.2 % (p \ 0.001) and RNFL thickness 2.6 % (p = 0.043) of SDMT results (total R2 = 0.287). PASAT pre- P720 dicted 6.6 % (p = 0.014) and RNFL thickness 9.7 % (p = 0.002) of A case of progressive multifocal leucoencefalopathy contrast sensitivity (total R2 = 0.163). Significance levels were con- after discontinuation of natalizumab: when could we let firmed using GEE. the guard down? Conclusion: Cognitive function as expressed by PASAT and visual impairment expressed by RNFL thickness both influence L. Moiola, F. Sangalli, M. Radaelli, V. Barcella, results in vision dependent cognitive tests and, importantly, also S. Gerevini, V. Martinelli, A. Ghezzi, G. Comi contrast sensitivity assessments. We presume that cognitive function San Raffaele Hospital (Milan, IT); Sant’Antonio Abate Hospital and visual function can hardly be measured independently. Clinicians (Milan, IT) should be aware that changes in cognitive function might influence Objective: To report on a case of progressive multifocal leukoen- visual performance and vice versa. cephalopathy (PML) after natalizumab treatment discontinuation. This project was supported by research grant Exc 257 from DFG. Case report: She is a 24-years-old woman who developed a very active multiple sclerosis in 1999 when she was 12. Between 2000 and 2004 she was treated with immunomodulants and she underwent 3 P719 cycles of Mithoxantrone for a cumulative dose of 45 mg. Then for continuous clinical and MRI activity she started natalizumab treat- Psoriasis coexistent with multiple sclerosis: a case series ment in May 2007. During this therapy she did not have any disease E. Andreadou, S. Katsavos, S. Papachilleos, activity and she had a very good quality of life. In September 2010 M.E. Evangelopoulos, K. Kilidireas, A. Rombos, she was tested for anti-JCV antibodies resulting positive. In October E. Stamboulis 2010 the treatment was interrupted after 44 doses due to her high risk of developing PML In facts she had all risk factors: duration of Athens National and Kapodistrian University (Athens, GR) treatment, previous use of IS and JCV antibodies seropositivity. She Objectives: Previous reports suggest an increased risk of psoriasis in was asymptomatic until middle of January 2011 when she developed Multiple Sclerosis (MS) patients. We aimed to evaluate the preva- seizures and changes in personality. She was admitted to hospital and lence of psoriasis in MS patients and to identify any special the first MRI showed a right frontal subcortical lesion extending to characteristics in the subgroup of patients carrying both diseases, in lateral ventriculus with enhancement compatible with PML and initial respect of the natural history and the clinical, laboratory and imaging IRIS. She undergone two lumbar punctures and qualitative PCR findings of MS. showed a mild positivity for JCV in both samples. Then at the middle Methods: We retrospectively reviewed the records of all patients of February she was admitted to our neurological department were the examined at the Unit of Demyelinating Diseases of the 1st Neurology neurological examination revealed only dysphoric and hypocritic Department of Athens University, during the period 2010-2011. All behavior (EDSS 2,0 and Karnoksfki Score 80); she underwent a third patients fulfilled the 2005 revised McDonald criteria for definite MS lumbar puncture and a quantitative PCR assay was negative. MRI or clinically isolated syndrome (CIS). Clinical data collected were age scan showed an extension of the frontal lesion with increased T1 at disease onset, disease duration, initial symptoms, disease subtype, hypointensity and gadolinium enhancement as well as reactivation of family history of autoimmunity, medication and Expanded Disability many MS lesions. The patient was treated with monthly iv steroid Status Scale (EDSS) score at the time of examination. Cerebrospinal courses. Both clinical condition (EDSS 1,0 and Karnoksfki Score fluid (CSF) and Magnetic Resonance Imaging (MRI) data were 100) and neuroradiological features improved. recorded. Conclusions: We report this case to emphasize the importance of Results: We identified a subgroup of 12 patients with MS and close clinical and neuroradiological follow up after natalizumab dis- psoriasis (9 women, 3 men) within a total group of 417 patients continuation since an indolent PML could develop during the phase of (2.88 %). 6 patients had relapsing–remitting MS (RRMS), 4 CIS, 1 immunoreconstitution. Moreover we remark the relevance of strati- primary progressive and 1 secondary progressive MS. The onset of fying the risk of PML especially in patients with long duration of psoriasis preceded that of MS in all cases by 3 to 45 years. Plaque treatment and previous use of immunosuppressant drugs.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S195

P721 test (PASAT) and symbol digits modalities test (SDMT)in patients Fatigue characteristics in multiple sclerosis patients with multiple sclerosis. Methods: Our batch was composed of 111 patients diagnosed with living in the northeastern Iran (a low prevalence zone) different forms of multiple sclerosis. For every patient we performed R. Jajvandyan, S.M Nabavi, S. Oryan, H. Khani neurological examination (EDSS) and cognitive assessment using Islamic Azad University (Tehran, IR); Shahed University (Tehran, MMSE, MoCA, PASAT and SDMT tests. IR); Tarbiat Moallem University (Tehran, IR); North Khorasan We made statistical correlation between EDSS score and cognitive University (Tehran, IR) tests score (Pearson method) and we compare cognitive tests using Background: We assessed the fatigue severity, its impact and asso- multiple comparisons methods. ciation with other demographic and clinical parameters among Iranian Results: 76 out of 111 are female (68.5 %), medium age is 38.09 MS patients aged 315 years in North Khorasan state of Iran which the year, medium EDSS is 3.3. 77.5 % patients were diagnosed with prevalence of MS was estimated around 13 in 100000. relapsing remitting MS, 16.2 % were diagnosed with secondary Methods: Fatigue was evaluated by the three validated question- progressive MS, 5.4 % were diagnosed with primary progressive naires including; Visual Analog Scale for Fatigue (VAS-F), Fatigue MS and 6.3 % were at the beginning of the disease (clinically Severity Scale (FSS), Modified Fatigue Impact Scale (MFIS). isolated syndrome). 23 patients obtained a MMSE score under 26 Results: 106 MS patients completed the questionnaires. The mean points, and 47 patients obtained a MoCA score under 26 but with a age was 32.67±10.43 years (ranging 16-61 years, 75 female (70.8 %), MMSE score over 26 points (for 70 out of 111 patients we can clinical course of disease in 80 was RRMS (75.5 %),in 9 PPMS diagnose dementia or mild cognitive impairment, so 63.06 % were (8.5 %), and 17 SPMS (16.0 %). The Mean disease duration was cognitively affected). We have obtained a statistically significant 5.29±6.01 years. 95 patients (89.6 %) were receiving immune mod- negative correlation between EDSS and MMSE score (r= -0.44, ulating agents, Mean EDSS was 2.5±2.72. p=0.0001), MoCA score (r= -0.45, p=0.0001), PASAT score (r=- Results: The mean FSS score was 4.85±1.54. FSS score among 0.47, p=0.0001), and SDMT score (r=-0.56, p=0.0001). MMSE male patients (5.03±1.59) and female patients (4.77±1.56) was not score correlated statistically significant with MoCA, PASAT and statistically significant (p=0.445). The mean total FSS score in SDMT score with positive r, and p=0.0001. PASAT and SDMT tests patients with PPMS (6.45±0.47) and SPMS (5.91±0.99) was higher were specific for cognitively impaired group at t student test than RRMS (4.44±1.53). Based on the FSS score, 72 (67.9 %) of (p=0.001). patients reported severe fatigue (FSS score[= 4). patients with severe Conclusion: Our results showed similar values for cognitive dis- fatigue were more likely to be older (p=0.001), male, effete and ability in MS patients as this is reported in literature. There isn’t a rule jobless with education level lower than high school (p=0.011) than that patients who are physically disabled are in the same time cog- those with mild/moderate fatigue. Regarding to disease characteris- nitively disabled, but our study showed this. EDSS score is more tics, patients with severe fatigue were more likely to be older at the prone to measure physical disability, so it is necessary to have a onset of disease (p=0.029), with higher EDSS score (p\0.0001) than sensitive and validated tool to measure cognitive disability in MS. those with mild/moderate fatigue. The fatigue severity also differed The results of our study emphasized that MoCa scale is a sensitive significantly between MS different disease subtypes. All of patients method to measure cognitive disability in MS patients. with primary or secondary progressive MS had reported severe fatigue. The mean total MFIS score in MS patients was 32.89±22.49 P723 (range 0-83) The mean VAS-F score in patients was 5.4±2.62 (range Cognitive deterioration in patients with initial 1-10) we found a high correlation between three fatigue scores and EDSS score Interestingly, patients who were bedridden, showed the relapsing-remitting multiple sclerosis most severe fatigue based on FSS, VAS-F, MFIS and its subscales. K. Genov, M. Dimitrova Conclusions: Due to high prevalence of fatigue in MS patients and Military Medical Academy (Sofia, BG) impact of fatigue on daily activities, fatigue should be evaluated routinely and pharmacologic and non pharmacologic treatments are Objectives: To assess the cognitive abilities in patients with initial recommended for MS care plan to improve the quality of life in relapsing-remitting multiple sclerosis(RRMS) and to find a possible patients. correlation between them and clinical and magnetic resonance No conflict of interest. tomography(MRT) changes. Methods: Patients with initial RRMS and healthy control subjects were assessed simultaneously in three test sessions over a period of 2 years by using a short repeated battery of neuropsychological tests. P722 Patients were also assessed with MRT and an analysis of T2 Cognitive impairment in multiple sclerosis: methods lesions(T2LV), gadolinium-enhanced lesions and cortical atrophy of the brain was done. Forty five patients with initial RRMS (mean age - of assessment 36,9 ±8,9 years, average duration of the disease - 2,9± 1,7 years, S. Petrescu, P. Ionescu, G. Vanghelie, E. Sandu, EDSS - 1,7±0,7) and twenty five healthy control subjects were N. Munjev, C. Panea, M. Manea assessed. The Emergency University Elias Hospital (Bucharest, RO); Al. Results: Twelve patients(30,6 %) had cognitive impairment at the Obregia Hospital (Bucharest, RO) beginning of the trial. After the two years, cognitive functions had deteriorated in 27,3 % of all patients, in contrast EDSS progression Objectives: Our aim was to asses cognitive disability using mini was found in only two patients. The most sensible test for finding a mental state examination test (MMSE) a validated test to quantify cognitive deterioration over a period of time is Symbol-Digital dementia and Montreal cognitive assessment test (MoCA)a non val- Modalities Test (SDMT). The only sign which could be used for idated test which can quantify mild cognitive impairment and to make prognosis of the deterioration is the presence of moderate cognitive correlation with expanded disability status scale (EDSS) score (vali- disability at the beginning of the trial (p = 0,03). Among the MRT dated scale for physical disability), and to compare these methods changes, only T2LV showed mild to moderate relations with some with specific cognitive tests such as passed auditory serial additional cognitive tests.

123 S196 J Neurol (2012) 259 (Suppl 1):S1–S236

Conclusion: Cognitive deterioration could be expected in only one different brain pathways during different cognitive tasks. In this third of patients with initial RRMS and short duration of the disease study, we aimed to examine whether this profile of increased activity over the period of 2 years. SDMT is appropriate for monitoring and is developed across different or specific stages of information pro- assessment of MS- related cognitive impairments. cessing during the performance of a cognitive test in MS patients. To address this issue, we combined event-related potentials (ERPs) and individual magnetic resonance imaging (MRI) in order to increase the spatial–temporal resolution which could be used to identify brain P724 regions involved in information processing. Natalizumab-aggravated psoriasis: a case report Methods: Thirty-three subjects (15 relapsing remitting patients J. Millań-Pascual, L. Turpıń-Fenoll, M.T. Ortega-Leoń, with low EDSS disability and 18 controls) completed a visual Stroop M. Pacheco-Jimeńez, P. Del Saz-Saucedo, B. Espadafor- task while data were recorded from 64 EEG channels. First, analyses of ERP were computed separately for each condition of the Stroop Lo´pez, A. Vadillo-Bermejo test. The cortical sources of these activities were estimated using two Complejo Hospitalario Mancha Centro (Alca´zar de San Juan, ES) modeling (wMNE and sLORETA) techniques. Second, the spatio- Background: Several factors, included different drugs, are known to temporal reconstructions of ERP sources were estimated using the trigger psoriasis, a chronic and immune-mediated disease. The cor- individual anatomy (MRI) of each participant. relation between drugs and psoriasis comprises the initiation of de Results: Results in the control group showed the activation of large novo psoriasis, the exacerbation of pre-existing psoriatic lesions and distributed networks with a well defined temporal course which was the development of treatment-resistant psoriasis. Although multiple similar for different conditions of the Stroop test. For the condition with sclerosis (MS) therapy, such as interferon beta, can trigger psoriasis, it higher cognitive conflict, the dorsolateral prefrontal cortex showed a remains unclear if other drugs like natalizumab (NTZ) also can. significant increase of activity during early (120-250 ms) and late (400- Case report: We report a 31 years old woman who developed skin 450 ms) periods. In comparison with the controls, MS patients showed an limited psoriasis at 17, with mainly topical treatment but two short increased activity in different brain networks mainly involving the periods (\ 6 months) of methotrexate. At 29 MS diagnosis was made associative visual cortex as well as parietal and frontal regions. However, according to typical clinical and radiological findings. A first immuno- the time course of activity in some of these brain regions was delayed in modulatory treatment with interferon beta for 9 months did not affect MS patients compared to the control group. disease course with relapses and disability progression so NTZ was Discussion: The existence of cortical reorganization in early stages proposed. Maybe due to steroid treatment in the several preceding of MS appears to limit the impact of lesions through compensatory relapses she hadn’t psoriastic lesions at NTZ onset. After six infusions mechanisms by calling on cognitive resources from other brain areas and with an appropriate respond of the course of MS (no relapses, no new adjacent to those which are essential to perform the Stroop test. The T2 lesions, no T1 gadolinium lesions), the patient suffered a severe present study combining ERP and MRI information in a multimodal psoriasis disseminated eruption. Topical treatment did not improve the strategy indicated that MS patients overactivated specific brain areas skin lesions and due to the aggressive MS course, NTZ was decided not to in order to perform the task as controls but also that this overacti- stop and ultraviolet-B therapy was initiated. Eight months and NTZ vation pattern in some brain regions is absent or delayed during infusions later MS course remained stable, without evidence of clinical or specific stages of information processing. MRI activity, but psoriatic lesions also were. This work has been supported in part by European Commission Discussion: Psoriasis is a very complex disease with an unpre- (7th Framework Programme) through to Marie Curie postdoctoral dictable activity and an important impact on the quality of live. Its fellowship (IEF) to Dr. Javier Gonzalez-Rosa. pathophysiology resembles MS and indeed some drugs like fumarates have been proposed to treat both. Both diseases can be triggered by drugs, immune-related or not, but in psoriasis’ case only few drugs P726 like beta-blockers have an undoubted causal relationship. To our knowledge there is no other reported case of psoriasis aggravated by Peduncular hallucinosis related with multiple sclerosis: natalizumab. Because the increasing use of monoclonal antibody in a case report autoimmune disease we have to take into account its potential dele- O. Kamisli, Y. Kaplan, S. Kamisli, C. Ozcan terious effect, even when a coincidental relation is also possible. In Inonu University, (Malatya, TR) our patient is no possible withdraw natalizumab to try improving and demonstrating a casual relationship but the aggressive course and Introduction: Peduncular hallucinosis (PH) is a rare syndrome char- drug-resistance support this hypothesis. More research is needed for acterized by visual hallucinations. Patients are usually aware that the the distinction between drug-induced and drug-trigger psoriasis or if images are not real. PH is associated with intrinsic lesions of the there is only a casual association and its exact mechanism. midbrain, since its first description in 1922 by Lhermitte. We present a case of PH secondary to Multiple sclerosis who has brainstem lesions. To our knowledge, this is the second report of PH associated with multiple sclerosis. P725 Case report: A 46-year-old woman was admitted to our outpatient Brain reorganisation and temporal activation patterns clinic. She has diagnosis of relapsing remitting multiple sclerosis in early multiple sclerosis patients revealed since 2001. She had transient vivid, colorful visual hallucinations lasting 4-5 min since 3 months. These phenomena consisted of long by estimation of EEG cortical sources and individual yellow hair in her fingers and also humans with bags on their heads. In MRI these episodes the patient insisted that the images were not real. J.J. Gonzalez-Rosa, A. Inuggi, G. Riccitelli, M.A. Rocca, Physical examination was normal. She has right hemiparesia and M. Filippi, G. Comi, L. Leocani ataxia in neurological examination. The blood count, detailed biochemical and serological tests were normal. Routine chest graphy and INSPE, University-IRCCS Hospital San Raffaele (Milan, IT) EEG were also normal. Cranial MRI indicated multiple demyelinating Objectives: It has been reported that multiple sclerosis (MS) patients, lesions in periventricular area and left thalamus, left lateral pons and when compared with controls, show increased activity within left cerebral pedicul.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S197

Discussion: PH has been reported in various diseases of thalamus, Objectives: Transcondylar approach is a new approach used for substantia nigra, midbrain, pons and basal diencephalon. This phe- detection of chronic cerebro-spinal venous insufficiency (CCSVI) and nomena may accompany with many neurological disorders, such as venous reflux in intracranial venous system in patients with multiple epilepsy, migraine, narcolepsy, tumors, cerebeller metastasis and sclerosis. The aim of the study was to assess the capability of the cerebrovascular diseases. To our knowledge PH related with multiple transcondylar approach to detect a flow in deep brain veins and sclerosis has been reported only once in the literature. The clinical venous sinuses. manifestations of PH are probably mistaken with psychosis or are not Materials and methods: Brain magnetic resonance imaging and investigated in detail. In fact visual hallucinations do not generally transcranial duplex sonography (TCCS) from transtemporal and have a strong localizing value, but it will be any subtle sign of transcondylar approaches using the new technology – Fusion Imaging brainstem pathologies. Therefore patients with acute visual halluci- – were performed in 6 volunteers and 5 patients with multiple nations should be carefully examined. sclerosis. Results: The root mean square error\0.5 cm and the accuracy of the system\1 mm, measured using a registration pen, were detected P727 in all subjects. All arteries of the circle of Willis, deep middle cerebral Spatial mapping of brain lesions and cognition vein, basal vein of Rosenthal, superior and inferior petrosal sinuses, cavernous and transversal sinuses and confluens sinuum were detec- in multiple sclerosis ted from transtemporal approach in all subjects. However, the internal F. Rossi, A. Giorgio, M. Battaglini, M. Stromillo, carotid artery siphon was detected in only 3 (27.3 %) subjects and E. Portaccio, B. Goretti, M. Amato, N. De Stefano middle cerebral artery in 1 (9 %) subject from transcondylar University of Siena (Siena, IT); University of Florence (Florence, IT) approach. The blood flow signal from cavernous, inferior or superior petrosal sinuses and deep brain veins was not detected in any subject Objective: To assess the relationship between cognition and brain even using the Fusion Imaging. Bidirectional Doppler signal from the white matter (WM) lesion distribution and frequency, measured on region of cavernous sinus was evaluated as the artefact. MRI-based lesion probability map (LPM), in patients with relapsing- Conclusion: The study results showed that TCCS transcondylar remitting (RR) multiple sclerosis (MS). approach cannot be used for standard detection of intracranial venous Methods: We studied 142 patients with RRMS (107 female/35 reflux. male, age: 39.4±9.1 years, disease duration: 11.0±9.8 years, EDSS: 1.8±1.2). Brief Repeatable Neuropsychological Battery (BRB) was administered at the time of brain MRI scan. According to the number ([1) of failed tests, the MS population was divided into cognitively P729 preserved (CP) and cognitively impaired (CI). T2-lesion masks were Model of MS multicentre multinational research used to create LPM for different patient groups. Significance of vo- as a translational tool in neurology xelwise analyses, performed with FSL, was set at p\0.05, cluster- corrected for multiple comparisons. C. Santos, L. Thome, P. Lima on behalf of Grupo de Results: CI group had a greater T2-lesion volume (LV) than CP group modelagem de estudos multicentricos (14.2±11.0, vs 8.02±9.1, p=0.001). On LPM analysis, the highest lesion frequency was found in the forceps major (FM) (61 %) in CI patients and Objective: Propose a model and algorithm of multicenter study in the posterior corona radiata (PCR) in CP patients (37 %).FM and the applied to multiple sclerosis (MS) as a translational tool to improve body of the corpus callosum (CC) were the WM regions where the lesion research in Latin America. Although Brasil since 2006 ranks 15th frequency was higher in CI than in CP patients. In addition, an association among the countries publishing in indexed peer-reviewed journals, of higher lesion frequency in FM, superior longitudinal fasciculus (SLF) many Latin American countries have been prolific and cooperative and in the body of the CC was found with increasing number of failed research is in demand. Populational, longitudinal studies of multi- tests. Body of CC and FM were still significant after correction for T2- center design, supported by a consistent information system (IS) with LV. Among the different tests of the BRB, SDMT showed a significant standardized data collection through the internet, will be a transla- relationship with lesion frequency. In particular, lower SDMT scores tional tool to build Latin American multinational databanks for rare correlated with higher lesion frequency in the body of the CC, forceps diseases as MS. minor, FM and inferior-fronto occipital fasciculus. Methods: Concepts of translational science integrating Admin- Conclusion: This study showed a significant relationship between istration, Medicine, Software Engineering and Law were applied in lesion location across the brain and the degree of CI. Indeed, patients both scope definition (preliminary research) and the work break- with CI have a particularly high frequency of lesion occurrence in down structure. The application of modeling techniques resulted in commissural (interhemispheric) fiber tracts such as the FM and the the organizational model and the project structure. The IS was body of the CC. The presence of lesions in these areas of the WM modeled in accordance with the research protocol and the organi- may cause a multiple disconnection syndrome between different zational scheme. bilateral areas of the cognitive network. Results: The MultiEM Project was structured in four stages: 1) Local, collection of multiple sclerosis patient’s clinical and demographic data and software validation in a single center design. 2) State Multicenter, validation of the organizational model. 3) P728 National, expansion of the project scope to encompass national Can the intracranial venous reflux be detected multicenter research and 4) Multinational. The IS allows the from the transcondylar approach? The results inclusion of patients with CIS as well as the results of disability scales and complementary exams applied to MS definition. Data of of the fusion imaging study definite MS undergo statistical analysis. Designed for scalability and E. Hurtikova, M. Kuliha, M. Roubec, J. Havelka, R. Herzig, flexibility, the IS will absorb the new diagnostic criteria, exams and D. Skoloudik disability scales as they become accepted in practice. Steps are listed University Hospital Ostrava (Ostrava, CZ); Palacky University and for the four stages, as well as description of the actors activities and University Hospital Olomouc (Ostrava, CZ) hierarchy.

123 S198 J Neurol (2012) 259 (Suppl 1):S1–S236

Conclusions: This model can help integrate multiple diverse Materials and methods: We prospectively analyzed patients with researchers within different countries; decrease the language barriers; lacunar syndrome treated with intravenous rtPA. As control group we accelerate transference of knowledge from basic sciences to medical consecutively selected patients with lacunar syndrome adjusted by treatments. Generalization of this model to studies of chronic diseases age, baseline NIHSS and prior mRS. We analyzed the functional may be a useful tool for clinical trials. outcome at three months and bleeding complications. Results: We included 39 patients treated with rtPA and 216 controls. The final diagnosis of LS was achieved in 163 patients (63.9 %). Cerebrovascular disorders IV A good outcome (mRS \3) was presented in 181 patients (71 %). Factors associated with good prognosis were younger age, initial severity and final diagnosis of LS. Treatment with rtPA did not reach statistical significance. Three patients had a hemorrhagic transfor- P730 mation (TH1), in all cases with good final prognosis. Multivariate Acute stroke thrombolysis unit may be associated analysis showed no association between good prognosis and rtPA. with more favourable performance measures However, there was a better evolution in patients with LACI and B. Koyuncu, A. Onalan, O.G. Tuncer, S.T. Ozkan, NIHSS[ 6 (64 patients) in which rtPA was associated with good prognosis in 50 % of cases vs 25 % in untreated patients, p = 0.039. E. Altindag, R. Tolun, Y. Krespi Conclusions: The use of rtPA is safe in patients with lacunar Istanbul Bilim University (Istanbul, TR); Florance Nightingale syndrome and is associated with a higher percentage of good prog- Hospital, Sisli (Istanbul, TR) nosis in patients with higher initial severity. Background: Stroke units facilitate implementation of thrombolytic therapy. In Istanbul, stroke units and thrombolytic therapy are not well organized. The objective of this study was to examine the per- P732 formance measures and quality of a referral unit, especially designed to deliver thrombolytic therapy. Basilar artery thrombosis in a child treated Methods: Istanbul Bilim University Acute Stroke Thrombolysis Unit with intravenous t-PA and endovascular mechanical is a specialized referral center integrated with emergency medical sys- thrombectomy tem (EMS) where only thrombolytic therapy candidates are admitted. D. Kondziella, J. Fink, L. Sonneborg, A.P. Born, Hospitals and EMS can have direct access to the treating neurologist in- duty by a single telephone number. The referred patients are received by M. Holtmannspo¨tter thrombolysis team at the emergency room (ER) and brought to the CT Rigshospitalet, University Hospital (Copenhagen, DK); Roskilde which is located together with the ER, at the ground floor near the Hospital (Roskilde, DK) entrance of ambulances. Thrombolytic therapy is started in the CT Basilar artery occlusion (BAO) in children is rare. BAO is associated room. In this study data of patients, who underwent CT-based intrave- with a high mortality and morbidity if recanalization of the basilar nous (IV) thrombolytic therapy at the first 4.5 h were analyzed and artery is not achieved before extensive brainstem damage has compared with results of the SITS Stroke Database. occurred. An 11-year old boy presented with a clinical and radio- Results: Between January and December 2011, 125 patients were logical top-of-the-basilar syndrome. Intravenous tissue plasminogen admitted, 87 % was referred from other hospitals. Thirty one patients activator (t-PA) was administered and the patient immediately (24.8 %), 19 males, with a mean age of 61 (min: 37, Max: 89) had IV referred to the regional stroke center. Mechanical thrombectomy thrombolytic therapy. Median of door to imaging time (DIT), door to using a Solitaire stent resulted in clot removal and recanalization of needle time (DNT) and onset to needle time (ONT) were 18 (SITS: the basilar artery 4 h after stroke onset. The patient made a full 25), 40 (SITS:67) and 220 (SITS: 149) minutes, respectively. Three clinical recovery. To our knowledge this is the first report on BAO in month mortality and functional independence (mRS 0-2) were com- a child treated with bridging therapy, the combination of intravenous parable to SITS data. Symptomatic intracranial hemorrhage (sICH) thrombolysis and endovascular thrombectomy. according to SITS - MOST criteria rates was 3.6 % (95 % CI: 06-17,7) (SITS: 1,7 %(95 % CI: 1,4- 2)). Conclusion: Our data indicate that a ‘‘thrombolysis unit’’ paradigm can significantly lower DIT and DNT and increase the probability of P733 thrombolysis per admission. Because of high proportion of referrals, ONT can be long and may lead to higher rates of sICH. More data is First case report of mechanical thrombectomy for acute needed to confirm the safety of thrombolytic therapy in such units. ischaemic stroke in ovarian hyperstimulation syndrome in pregnancy C. Tham, Y.L. Tan, K.E. Lee P731 National Neuroscience Institute (Singapore, SG) Efficacy and safety of intravenous rt-PA in patients Background: Ovarian hyperstimulation syndrome (OHSS) is a rare with lacunar clinical syndrome but serious complication of hormonal treatment for ovulation induc- M. Lo´pez Cuinã, M. Ley Nacher, L. Planellas, tion in patients undergoing assisted reproduction. The increased I. Navalpotro, E. Muinõ, A. Ois, A. Rodriguez, J. Roquer capillary permeability due to excess vascular endothelial growth Hospital del Mar (Barcelona, ES) factor production results in hemoconcentration and a prothrombotic state, leading to arterial and venous occlusions. Objectives: The use of rtPA in patients with lacunar stroke (LS) is still Methods: We present a case report of a 38 year old woman who controversial. Assuring the diagnosis of LS in these patients is diffi- had undergone in vitro fertilization and had developed OHSS in the cult in the early hours. The aim of our study was to evaluate the third week of her pregnancy. A week later, she developed an acute prognosis and safety of rtPA in patients with lacunar syndrome. left hemiplegia, left sided neglect, dysarthria and right gaze pref-

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S199 erence. Magnetic resonance imaging done within two hours of P735 stroke onset showed an acute right middle cerebral artery territory Factors affecting blood glucose level in hyperacute infarct and acute thrombotic occlusion of the distal right internal carotid artery. ischaemic stroke. Is mismatch a contributing factor? The patient was deemed not a suitable candidate for intravenous S. Gur Ozmen, B. Aksay Koyuncu, S. Tavukcu Ozkan, thrombolysis in view of her pregnancy. Decision was made for R. Tolun, Y. Krespi mechanical thrombectomy instead, which was performed within four Istanbul Science University (Istanbul, TR); Sisli Florence Nightingale hours of stroke onset. A balloon guiding catheter was placed in the Hospital (Istanbul, TR) proximal right internal carotid artery and a microcatheter was introduced through the guiding catheter and negotiated past the thrombus. Background: Hyperglycemia is detected in nearly 50 % of acute A device was then introduced through the microcatheter and deployed stroke patients admitted to the emergency room, most of whom don’t across the clot. A total of 2 passes were made to remove the clot. At have diabetes mellitus (DM). In hyperglycemia of acute critical ill- the end of the procedure, a repeat angiogram showed complete re- ness, intravenous insulin is actually considered the mainstay of canalisation of the right internal carotid artery and right middle therapy but its safety in acute ischemic stroke patients is not well cerebral artery. known. Patients with severe stroke and salvageable brain tissue at Results: The patient underwent rehabilitation with physiotherapy admission can have higher glycemic levels and potentially be at risk and occupational therapy and her neurological status improved. By of iatrogenic hypoglycemia or on the contrary benefit the most from the time she was discharged from hospital three weeks later, she was insulin therapy. In this study we examined the relationship between able to ambulate independently, had no more dysarthria or neglect the existence of MR diffusion/perfusion mismatch and admission and only had mild left arm weakness. She had a successful delivery of blood glucose level (ABGL) in patients admitted in the first 12 h after a healthy baby at 38 weeks gestation. onset. Conclusion: A search of the literature revealed 14 case reports of Method: Data of patients prospectively and consecutively regis- strokes occurring in patients with OHSS. Of these, one patient had tered to Florence Nightingale Stroke Unit acute stroke database received intra-arterial recombinant tissue plasminogen activator and between the years of 2006-2009 were used for the analysis. At MRI the rest had received conventional therapy. To our knowledge, this is PWI/DWI mismatch was considered as present if estimated at least to the first reported case of the successful use of mechanical throm- be approximately 20 % by eyeballing the lesions. The ABGL was bectomy to treat acute ischemic stroke in OHSS. This may be a safer categorized as [140 mg/dl vs \=140 mg/dl. Correlation between option for use in pregnancy. mismatch and ABGL was analyzed with multivariate logistic regression analysis. Age, gender, DM history, Hba1c level, treatment for DM, index proximal vessel occlusion (iPVO) and other potential correlates of blood glucose level (onset to door time, NIHSS, level of consciousness, stroke type and stroke etiology) were included in the P734 analyses. Sex-related differences in stroke outcome Results: The sample consisted of 212 patients (124 men and 88 at a University of Maiduguri teaching hospital, women) with a mean age of 70 (SD: 13). Mean ABG level was 137 northeastern Nigeria (SD: 44). One hundred and six individuals (55 %) had mismatch and one hundred and twenty-six individuals 67 ( %) had iPVO. Mismatch M.M. Watila, Y.W. Nyandaiti, A. Ibrahim, I.D. Gezawa, (adjusted OR 2,452, 95 %CI 1,022-5,879) was associated with high S.A. Bwala ABGL. Lower level of consciousness, cardioembolic etiology, higher University of Maiduguri Teaching Hospital (Maiduguri, NG) Hba1c level and anti-diabetic usage were the other independent pre- Objectives: Studies have reported sex differences in stroke risk factor, dictors of high ABGL. presentation, morbidity and mortality. This study aims to determine Conclusion: Our findings indicated that hyperacute ischemic the effect of sex on morbidity and 30-day fatality in patients with stroke patients with PWI/DWI mismatch which is considered as acute stroke. potentially harboring salvageable penumbral brain tissue are more Methods: Ninety-one patients were recruited for the study. We likely to present with hyperglycemia, and this is independent of documented sex differences in stroke presentation, stroke severity iPVO. The safety of parenteral insulin therapy should be specifically on admission and discharge, and 30-day in-hospital fatality. Con- investigated in this subpopulation. tinuous variables were assessed using the student t-test. While outcome measures were analysed using the logistic regression analysis. P736 Results: Women were less likely to be formally educated (P = The Clock Drawing test as an independent predictor 0.024). Men were more likely to have lacunar strokes (P = 0.048), to smoke (P = 0.046) and take alcohol (P = 0.027). Men had a higher of functional and clinical outcomes in stroke patients diastolic blood pressure at presentation (P = 0.046), even though they A.S. Champod, G.A. Eskes, G.J. Gubitz, C. Christian, were more likely to be on antihypertensive medications pre-stroke (P Y. Reidy, L. Radu, S.J. Phillips = 0.036). Women were more likely to present with coma on pre- Dalhousie University (Halifax, CA) sentation (P = 0.003), and suffer urinary tract infections (P = 0.023). Women were also more likely to have a severe stroke on admission Objectives: The Clock Drawing Test (CDT) is commonly used as a (Barthel’s ADL \ 45, odds ratio OR = 5.30; 95 % CI, 1.10 to 25.62 cognitive screening tool for the assessment of dementia. The utility of and mRS[4, OR = 5.38; 95 % CI, 1.53 to 18.96), poorer activity of this instrument in other populations with focal neurological damage is daily living (ADL) status on discharge (OR = 4.40; 95 % CI, 1.45 to not well documented. The purpose of the present study was to 13.35) and a higher in-hospital fatality (OR = 2.19; 95 % CI, 0.72 to examine the utility of the CDT (Draw version) in stroke patients in 6.65). predicting a variety of neurological, functional, and clinical outcomes Conclusions: Sex differences in outcome exist in this study and at 12 months post-stroke. women appear to have a poorer stroke outcome, more studies are Methods: 598 consecutive acute ischaemic and haemorrhagic needed to assess sex differences in response to therapy. stroke patients admitted to an acute stroke unit were enrolled in the

123 S200 J Neurol (2012) 259 (Suppl 1):S1–S236 study. On admission, patients were administered a neuropsycho- Objectives: The aim of the current study was to design a new simpler logical screening battery including the CDT. At 12 months post- form of National Institutes of Health Stroke Scale (NIHSS) for use in stroke, neurological, functional, and clinical measures were col- emergency settings, and compare its predictive ability with original lected such as the degree of disability and dependence (with the NIHSS score for mortality. Modified Rankin Scale or MRS), the performance in activities of Methods: A series of 152 consecutive patients with first ever daily living (with Barthels Index or BI), the reintegration into nor- ischemic stroke admitted to a university affiliated hospital were mal activities (with Reintegration to Normal Living index or RNL) enrolled. NIHSS score on admission was estimated and the predictive and the progression of dementia (with Global Deterioration Scale or ability of NIHSS items for mortality at 28 days was evaluated by GDS). logistic regression. Stepwise discriminant analysis was performed on Results: Hierarchical linear regression was used to study the total NIHSS items to obtain a discriminant function with the best dis- score on the CDT at admission as a predictor of functional and criminative ability for mortality. Further, receiver operating clinical outcomes at 12 months post-stroke. The CDT at admission characteristics (ROC) curves were depicted to compare the new was found to be an independent predictor of all outcomes measured determined discriminant function with the original NIHSS score. (i.e., MRS (p\0.001), BI (p\0.001), RNL (p\0.001), and GDL (p Results: Cumulative rate of mortality was 11.8 % for 28-day \ 0.001)) above and beyond patients’ demographic and neurological follow-up period. Among NIHSS items, scores of visual field, limb factors including gender, age, and localization of lesion. ataxia and extinction neglect were not associated with mortality Conclusion: The CDT at admission has good predictive value of a (P[0.05). On the contrary, level of consciousness-commands, lan- variety of functional and clinical outcomes at 12 months post-stroke. guage and gaze were determined as independent indicators of These findings combined with its quick administration time and ease mortality (P\0.05), and their coefficients on discriminant function of interpretation suggest that the CDT may be a useful measure in the were equal to 0.65, 0.44 and 0.30, respectively. In addition, area under assessment of stroke patients for discharge and rehabilitation the ROC curve of the calculated discriminant function was not sta- planning. tistically different from NIHSS score (P[0.05). Conclusions: The suggested discriminant function, comprising NIHSS items of level of consciousness-commands, language and P737 gaze, can predict 28-day mortality after stroke in a similar way to the original NIHSS score and can provide a baseline for stroke severity in N-terminal pro-brain natriuretic peptide emergency settings. and short-term mortality after stroke This study was performed in partial fulfillment of the requirements M. Ghabaee, M. Pourashraf, A. Meysami, S. Parviz, for completing residency training of Dr. Zeynali Kahaki in neurology H. Sadeghian, A. Hadad Saraei, S. Mohebbi, Z. Zeinali at Tehran University of Medical Sciences (TUMS). Kahaki Tehran University (Tehran, IR) Background: N-terminal pro-brain natriuretic peptide (NT-proBNP) P739 levels are frequently elevated in the setting of acute ischemic stroke. The effect of middle cerebral artery blood flow This study investigated whether the baseline NT-proBNP level on parameters for clinical outcome in acute ischaemic admission can predict short-term mortality after ischemic stroke. Methods: 100 patients with acute ischemic stroke underwent a stroke thorough clinical and paraclinical evaluation including serum NT- M. Baydemir, G. Tekgo¨l Uzuner, N. Uzuner proBNP measurement. Osmangazi University (Eskisehir, TR) Results: 7 % of patients died within a week after the stroke onset. The NT-proBNP levels were significantly higher among the Aim: We aimed to investigate whether there is an association between patients who died than among the survivors (p=0.002). The optimal blood flow parameters of middle cerebral artery measured with NT-proBNP cut-off point for predicting mortality was 1330 pg/ml, transcranial Doppler which is an easy, low-cost, noninvasive, with a sensitivity of 100 % and a specificity of 70 %. Multivariate repeatable and bedside applicable examination and prognosis during analysis demonstrated that NT-proBNP concentration was an acute, subacute and chronic periods in patients with acute ischemia on independent predictor of short-term post-stroke mortality middle cerebral artery territory. (p=0.027). Materials and methods: Sixty-two patients with acute ischemia on Conclusions: An increased NT-proBNP level was significantly and middle cerebral artery territory, applied within first 12 h after start of independently correlated with short-term mortality in patients after symptom and meet the study criteria were included. The middle ischemic stroke. cerebral artery blood flow parameters were measured with transcra- This work was conducted as research project No. 88-02-54-8949 nial Doppler during acute period. Also, stroke severity and prognosis financially supported by a grant from Tehran University of Medical were determined on detailed neurologic examination with GCS, NI- Sciences. HSS and mRANKIN values during acute, subacute and chronic periods. Results: Transcranial Doppler was performed within mean 6.0±2.9 h during acute period. When we look at blood flow velocity parameters with transcranial Doppler during acute period, pulsatility P738 index on the lesion side was 1.4±0.5. Based on the detailed neuro- A simple risk score for early stroke mortality derived logic examination during acute period, mean arrival GCS was from national institutes of health stroke scale: 13.3±2.4 and mean arrival NIHSS was 12.3±6.4. Mean NIHSS and a discriminant analysis mRS were found 11.2±9.3 and 3.1±1.9 on neurological examination during subacute period, respectively. Mean NIHSS and mRS were A. Zandieh, Z. Zeynali Kahaki, H. Sadeghian, found 9.1±11.0 and 2.5±2.2 on neurological examination during M. Pourashraf, S. Parviz, M. Ghaffarpour, M. Ghabaee chronic period, respectively. There were significantly negative asso- Iranian Center of Neurological Research (Tehran, IR) ciation between pulsatility index measured at the side of lesion during

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S201 acute period and arrival GCS (p=0.002) and significantly positive P741 association between pulsatility index and arrival NIHSS (p=0.001). In Epileptic seizures after stroke - clinical and imaging addition, significant positive associations were found between the pulsatility index on the side of lesion during acute period with NIHSS peculiarities (p=0,001 ve p=0,006, respectively) and mRANKIN (P=0,001 ve I. Macavei, I. Huza, A. Macavei, E. Iftenie p=0,004, respectively) values measured during subacute and chronic University of Medicine and Pharmacy (Targu Mures, RO); Clinical periods County Emergency Hospital (Targu Mures, RO) Conclusion: In this study, we concluded that important informa- Objectives: Analysis of the incidence of epileptic seizures, predictive tion about prognosis on acute, subacute and chronic periods can be risk factors and some clinical and imaging considerations in patients obtained with pulsatility index measurement which is not affected by who experienced epileptic seizures at the onset of a stroke. measuring fondness among the blood flow parameters measured with Methods: This is a retrospective study which included 1062 transcranial Doppler that as a simple examination method on acute patients admitted to the 1st Neurology Clinic Targu-Mures, dur- stroke. ing 01.01.2011-31.12.2011, with a diagnosis of acute stroke. From the total of 1062 patients, 47 patients have experienced epileptic seizures at the onset of stroke. We have excluded from P740 the study patients with a history of epilepsy, with transient High incidence of embolic potential in acute stroke ischemic attacks, those with subarachnoid hemorrhage or with cerebral thrombosis. All patients have been investigated using patients with middle cerebral artery occlusion even computed tomography (CT), electroencephalogram (EEG) test without cardioembolic sources and magnetic resonance in some particular cases. Severity of J.S. Lee, S.J. Lee, D.H. Shin, J.M. Hong, I.S. Joo stroke was evaluated by using National Institutes of Health Stroke Ajou University (Suwon, KR) Scale (NIHSS). Results: 4.42 % of the patients have had epileptic seizures at the Objectives: Various methods including mechanical thrombectomy onset of stroke. From the total of 47 patients with acute stroke and and intracranial stenting were recently introduced to recanalize epileptic seizures, 37 patients had an ischemic stroke (78.73 %) and occluded intracranial arteries. Most acute middle cerebral artery 10 patients had a hemorrhagic stroke (21.27 %). Among these, 29 (MCA) occlusion results from cardioembolism (CE) and atheroscle- patients experienced early-onset seizures (61.7 %) and 18 patients rosis (AS). Ideally, mechanical thrombectomy is believed to be more experienced late-onset seizures (38.3 %). Regarding the type of proper on CE while intracranial stenting is thought to be better for seizures, 57.4 % were secondarily generalized tonic–clonic seizures, AS. However, it is difficult to differentiate CE and AS in acute MCA 36.17 % were focal motor seizures and only 6.39 % were sensitive occlusion. seizures. Cortical cerebral lesions were more frequently associated Methods: Consecutive 81 patients with acute ischemic stroke due with seizures (78.3 %). The incidence of seizures was greater in to MCA stem occlusion, whose initial NIHSS score was 5 or higher patients with cardioembolic stroke (64.86 %), followed by those with and who had intravenous (IV) thrombolytics, intra-arterial (IA) atherothrombotic stroke (19.5 %), haemodynamic stroke (5.4 %) and treatment or both, were enrolled. Among TOAST classification, lacunar stroke (5.4 %). In terms of NIHSS, 13 patients (27.65 %) had patients with CE and AS were grouped. Characteristics of CT and mild neurological deficit (NIHSS\5 points), 33 patients (70.21) had transfemoral cerebral angiography, and responses of IV and IA moderate neurological deficit (NIHSS=16-25 points) and only one treatment were compared between the groups. patient (2.12 %) had a severe neurological deficit (NIHSS[25 Results: CE (n=48) was more frequent in patients with acute points). Epileptic seizures occurred more frequently in patients with MCA occlusion who needs IV or IA treatments than AS (n=21). Age important cerebral lesions located in the anterior cerebral circulation and sex were not significantly different between groups. Initial NI- (65.95 %). HSS score was higher in CE than AS group (15.33±3.24 vs Conclusion: Seizures were more common in patients with ische- 12.71±4.45, p=0.008). On CT imaging, the frequency of dense mic stroke and in those with cortical lesions. There was an association MCA sign (68.8 % vs 55.0 %, p=0.280) and higher ASPECTS score between stroke mechanism, particularly the cardioembolic one, and ([=8) (40.4 % vs 50.0 %, p=0.485) was not different between CE the incidence of seizures. It is still not sure if stroke severity is an and AS groups. However, the frequency of higher calcification independent risk factor, although it is associated with an increase of burden ([=3) (8.3 % vs 30.0 %, 0.022) and relevant artery stenosis acute epileptic seizures. (0 % vs 10.0 %, p=0.026) was significantly lower in CE than in AS group. On transfemoral cerebral angiography, the frequency of full leptomeningeal collateral was not different between CE and AS groups (32.4 % vs 37.5 %, p=0.720). However, the frequency of P742 partial or full recanalization following IV thrombolytic therapy was Predictors of functional outcomes in endovascular significantly higher in CE than in AS group (52.9 % vs 16.7 %, recanalisation of acute symptomatic carotid artery p=0.011). After IA treatment, the frequency of full revascularization of MCA stem recorded by AOL grading was marginally higher in occlusions CE than in AS group (77.1 % vs 57.0 %, p=0.093). Interestingly, N.S. Ranawat, S.A. Chaudhary, A.I. Qureshi full revascularization according to AOL grading was observed in University of Minnesota Medical Center (Minneapolis, US) more than half patients in AS group. Background: Treatment of occluded carotid arteries in patient’s with Conclusion: CT and transfemoral cerebral angiography did not acute symptoms has not been clearly defined. With bypass surgery not supply sufficient information to differentiate the etiology of being a viable option as shown in the EC/IC bypass & COSS trials, occluded MCA. With or without cardioembolic sources, most alternative treatments need to be evaluated. patients in acute MCA stem occlusion had embolic potential so that Objective: To review functional outcomes in patients undergoing mechanical thrombectomy can be a first-line option for IA endovascular recanalization (EVR) of occluded carotid arteries with treatment. ipsilateral acute stroke or TIA symptoms.

123 S202 J Neurol (2012) 259 (Suppl 1):S1–S236

Method: From a prospectively maintained institutional database, group 26.8±6.2 %). There was no significant difference in the degree we reviewed records of all patients undergoing EVR for acute stroke of neurologic deficit in two groups. Mean cerebral blood flow velocity between July 1999 to May 2010. All patients with ICA occlusions increased in both groups to 59.4 % (the first group - to 31.9 %, the were analyzed. Data collected included pertinent stroke risk factors, second group to 42 %). Intracranial pressure decreased in both clinical and neuroimaging findings, site of occlusion (tandem or non- groups, but it was statistically significant only for patients with brain tandem) and methods of intervention. edema. Primary end points: Arterial recanalization defined as Thrombol- Tympanic temperature decreased to 34.6±0.86 C, axillary tem- ysis in Myocardial Infarction (TIMI) score [= 2 Post-procedure perature decreased to 36.1±0.28 C. The temperature gradient was parenchymal hematomas (PH) 1 Post-procedure hemorrhagic trans- 2.56±1.3 C. formations (HT) Good functional outcome defined as a modified Conclusion: Craniocerebral hypothermia caused the decreasing of Rankin Scale (mRS) \= 2 at 3 months. the neurological deficit degree and the increasing of the cerebral 128 patients with symptomatic occlusions were identified The blood flow velocity of the patients with the acute ischemic stroke. We mean ± SD age of this cohort was 63.5 ± 11.3 yrs The mean± SD have the temperature gradient between tympanic and axillary tem- NIHSS was 12.8. One patient had no documented NIHSS. The perature. Craniocerebral hypothermia decreased intracranial pressure mean± SD Alberta Stroke Program Early CT Scores was of patients with brain edema. 8.4±1.5. 107 patients (83.5 %) had successful recanalization (TIMI [= 2) of their occlusions. 51(39.8 %) had complete recanalization (TIMI 3). 63 patients (49.2 %) had the pre-defined favorable outcome (mRS \=2) at 90 days follow up. P744 28 (21.8 %) patients died (mRS=6) 40 patients (31.3 %) suffered Vascular risk factors and aetiology comparison from post-procedure intracranial hemorrhages: 13 (32.5 %) were PH 27 (67.5 %) were HT 13 (32.5 %) of these had a favorable outcome between cancer and non-cancer patients with acute (mRS \=2) 27 fared poorly (mRS [=3) 16 (40 %) died. ischaemic stroke Multivariate analysis showed that a high pre- procedure NIHSS & A.M. Carrilho Romeiro, P. Santos, M. Brum, A. Valadas, low post- procedure TIMI scores predicted poor outcomes. EVR is a R. Guerreiro, J. Pinto Marques viable option to medical or surgical therapy in acute symptomatic Centro Hospitalar de Setu´bal - Hospital Saõ Bernardo (Setu´bal, PT) carotid artery occlusions. It needs to be evaluated against existing therapies in a blinded randomized controlled trial in future. Objectives: Recent data suggest that classical vascular risk factors appear to be similar between cancer and non-cancer patients. However, in cancer patients there are several clinical conditions that appear to increase the risk of stroke. Our goal was to compare ischemic stroke in cancer and P743 non-cancer patients according to vascular risk factors, etiology and out- The change in cerebral blood flow characteristics come at discharge and one year later. and degree of neurological deficit in acute ischaemic Methods: Retrospective case–control study conducted in patients admitted to a stroke unit between January 2007 and November 2011. stroke patients with the use of craniocerebral Cases had a concomitant diagnosis of cancer and acute ischemic hypothermia stroke, controls of only stroke. Age, gender, vascular risk factors and I.A. Sharinova, O.A. Shevelev, I.E. Kalenova, M.V. Tardov etiology (based on TOAST criteria) were compared between groups. Presidental Hospital N1 (Moscow, RU); Peoples‘ Friendship Outcome at discharge was assessed by NIH Stroke Scale (NIHSS) and University of Russia (Moscow, RU); Otolaryngological Research modified Rankin Scale (mRS) scores. Patients without imaging evi- Institute (Moscow, RU) dence of acute ischemic stroke were excluded. Results: Forty-six cases were identified; 60.9 % were men with a Objective: To explore the influence of the craniocerebral hypothermia median age of 72 years (31-87 years); 18 patients (39.13 %) had evi- on the neurologic deficit degree and cerebral blood flow character- dence of active cancer. Gastrointestinal cancer (26.1 %) was the most istics of the patients with the acute ischemic stroke. common; 121 controls were included matched for gender and age. Materials and Methods: 25 patients with acute ischemic stroke Classic vascular risk factors, between groups: arterial hypertension were treated with the craniocerebral hypothermia. Including criteria [69.57 % vs 80.17 %, p=0.21], dyslipidemia [41.30 % vs 53.72 %, was acute ischemic stroke (first 72 h). Excluding criteria was p=0.21], atrial fibrillation [28.26 % vs 25.62 %, p=0.88] and diabetes bradycardia. mellitus [17.40 % vs 30.58 %, p=0.13], were not significantly different. We used: Previous thrombotic events were more frequent in the cancer cohort - the therapeutic hypothermia helmet device (THHD) for the [8.70 % vs 0 %, p\0.01]. Etiology of stroke among cases and controls craniocerebral hypothermia. were cardioembolism [32.61 % vs 39.67 %, p=0.51], small-vessel - the ultrasound Doppler analyzer for the recording of the cerebral occlusion [17,4 % vs 22,31 %, p=0.63], stroke of undetermined etiol- blood flow parameters ogy [23.91 % vs 13.22 %, p=0.15]. Other determined etiology subtype Patients were examined with the help of the National Institutes of was more frequent in the cancer patients when compared to controls Health Stroke Scale (NIHSS), blood pressure (BP) measurement, and [13.04 % vs 0.83 %, p\0.01]. At admission, median NIHSS score of temperature monitoring (tympanic, axillary, THHD temperature). cases and controls was 9 vs 8 [p=0.53]. At discharge, cancer and control Intracranial pressure was calculated with the help of the transcranial patients had median NIHSS scores of 6 and median mRS score of 3 vs 4, ultrasound Doppler parameters and BP data. [p=0.71].Longer hospitalization [5.5 days vs 4 days, p\0,01], was Patients were divided into 2 groups: characteristic of cancer patients. Mortality rate was higher in cancer 1. Patients with the stroke onset time first 48 h: 18 patients, 7 patients at discharge [15.22 % vs 3.31 %, p=0.02] and one year later women and 11 men, mean age 69.6±11.4, NIHSS 14.1±5.9. [17.40 % vs 4.96 %, p=0.02]. 2. Patients with the stroke onset time 49-72 h: 7 patients, 4 women Conclusion: Despite the similarity concerning classical vascular and 3 men mean age 73.75±7.8, NIHSS 11.0±7.16. risk factors, acute ischemic stroke in cancer patients seems to be more Results: Significant regress of the neurological deficit degree was frequently associated with a hypercoagulable state and has a poorer recorded in both groups (the first group 40.9±17.4 %, the second outcome.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S203

P745 Cerebrospinal fluid did not show any sign of inflammation. Echo- Patients with different TIA subtypes: stroke risk cardiographically there was no source for cardiac embolism, no heart valve colonisation and no persistent foramen ovale. On fol- reduction following urgent assessment and treatment low-up and after rehabilitation one patient remained apallic, two O. Fartushna patients had minor neurologic deficits (mild hemiparesis and dys- Bogomolets National Medical University (Kiev, UA) arthria; mild cognitive impairment) and another patient recovered Patients with transient ischaemic attacks (TIA) have higher level of completely. stroke risk. According to different authors, it happens more than in Conclusion: Cerebral fat embolism mostly presents as an altered 10 % in the first 48h. That’s why, improved methods of effective level of consciousness, sometimes with focal neurologic symptoms therapy of patients with TIA are very important. and epileptic seizures. In our cases MRI was the most sensitive means The aim is to evaluate the role of comprehensive urgent assess- to diagnose CFE. It showed the typical pattern of disseminated sub- ment and emergency therapeutic approach as a secondary prevention cortical microinfarcts on T2-weighted sequences and on diffusion- of an acute ischemic stroke in patients with TIA. weighted sequences. Our cases show that the clinical examination Methods: The clinical, Doppler ultrasound, MRI, transthoracic alone is not very conclusive to provide the diagnosis of CFE. echocardiography examination of 187 patients aged 25 to 83 years Whenever a patient shows an unexplained coma after traumatic injury (average-57.5±0.9 years) was performed. We used the classic or orthopaedic surgery a diffusion-weighted MRI is necessary to find 24-hour definition of TIA. The cases were reviewed by two neurol- the typical pattern of disseminated hyperintense lesions in the white ogists to establish the correlation between the diagnoses. TIAs were matter that are associated with CFE. divided into 4 subtypes according to the TOAST criteria. The patients were divided into 2 groups, depending on the applied assessment and therapy: 1- traditional assessment and therapy(n=91), 2- urgent assessment P747 and emergency complex therapeutic approach (n=96) according the Risk factors, recurrence and return to work in various last ESO Guidelines for management of ischemic stroke and TIA. Development of stroke was considered the primary endpoint. stroke subtypes: insights from Hyderabad Stroke Observation period was two years. Registry, India Results: Stroke developed in 27 (29.6 %) cases which received S. Kaul, U. Rani, V. Bandaru, S. Alladi traditional therapy and in 16 (16.7 %) cases - the proposed assess- Nizam’s Institute of Medical Sciences (Hyderabad, IN) ment and therapeutic range (OR(95 %CI)=0.59(0.35-0.63), ARR=0.126, p=0.035). The probability of stroke has been the Objective: Limited data from India is available on recurrence and highest with patients with TIA and new ischemic lesion on MRI return to work in patients of stroke. This project was aimed to study (OR(95 %CI)=6.7(3.4-8.3)). The preventive effect of urgent assess- the risk factors, recurrence and outcome including return to work in ment and therapy was the most effective in patients with small various stroke subtypes. vassal disease (ARR=0.03, p=0.049) and cardioembolic (ARR=0.05, Methods: The Hyderabad Stroke Registry was initiated in January p=0.086) TIA subtypes. Correlation analysis revealed a high corre- 2001 in the form of an observational project aimed at consecutively lation between the time from TIA onset to treatment (r=0,429, p\ collecting the clinical, imageological, laboratory and outcome data of 0.001) and stroke. cases of acute stroke. Conclusions: The urgent assessment, well-timed determination of Result: The total number of patients recruited till 30th April 2010 the leading TIA mechanisms and emergency therapeutic approach was 2744, out of whom 2174(79.22 %) were ischemic and significantly reduced the stroke risk in patients with TIA, especially 570(20.77 %) were hemorrhagic strokes. Factors significantly asso- in patients with small vassal disease and cardioembolic subtypes of ciated with ischemic stroke were older age (p=0.05), diabetes TIA. (p=0.0001), smoking (p=.0127), hyperlipidemia (p=.0001), recurrence and ischemic heart disease (p=.0001), whereas history of hypertension (p=.0155), alcohol use (p=0.0001), and high hospital mortality (p =.0001) was more common in hemorrhagic stroke. There P746 was no significant difference in the risk factors between small and Symptomatic cerebral fat embolism large artery strokes. History of previous stroke was noted in 40/570 J. Dunkel, C. Roth, A. Ferbert (7.5 %) of hemorrhagic strokes and 420/2174(20.4 %) of ischemic strokes. Previous stroke had occurred in 19.8 % (35/176) of extra- Klinikum Kassel (Kassel, DE) cranial large artery atherosclerosis; 20.6 % (127/616) of intracranial Objectives: Symptomatic cerebral fat embolism (CFE) is a rare atherosclerosis; 24.3 %(57/234) of cardioembolic strokes; 17.9 % complication after traumatic injury or orthopaedic surgery and is (74/412) of small artery disease, 12.7 %(11/86) of stroke of other diagnostically challenging. determined etiology; 17.36 % (99/570) of stroke of unknown etiology Methods: We report about four patients of our department who and in 22.5 % (18/80) of strokes with multiple mechanisms. The 30 could be diagnosed with cerebral fat embolism over the last three day case fatality was 19 % (83/439) in hemorrhagic and 5.1 %(80/ years. 1563) in ischemic stroke. At 90 days, 1106/2174 (50.8 %) of ischemic Results: Our patients (51 years, female; 81 years, female; 85 years, stroke and 213/570 (37.2 %) of hemorrhagic stroke had returned to male; 88 years, female) had all undergone orthopaedic surgery with their previous work with varying degrees of disability. Among all endoprosthetic hip replacement. The day after surgery all four patients subtypes, maximum number of patients i.e 219/297(83.8 %) achiev- showed a disturbance of consciousness, from somnolence to coma. ing good outcome (MRS =\ 2), was seen in patients having a small We also found disturbance of oculomotor and pyramidal trac signs. artery stroke. The initial computed tomography (CT) did not show any signs of Conclusion: At least one half to one third of all stroke patients infarction. The magnetic resonance imaging (MRI) showed multiple returned to their previous work at 90 days after the stroke. Best small, scattered, nonconfluent hyperintense intracerebral lesions in the outcome was noted in the strokes due to small artery disease. All centrum semiovale and periventricular white matter in all patients. stroke subtypes were noted to have a high frequency of recurrence.

123 S204 J Neurol (2012) 259 (Suppl 1):S1–S236

P748 related to the procedure. Of the 18 survivors, 12 were men (66.6 %) Aetiological spectrum and outcome of paediatric stroke and mean age was 45years. Among these 14(77.7 %) had mRS\=2, 4(22.3 %) had mRS [2 and one patient had recurrent stroke. at a tertiary referral centre in South India Conclusion: SPG stimulation initiated within 24 h from stroke onset S. Kaul, A. Murty appears to be safe and efficacious. The long term outcome of the stim- Nizam’s Institute of Medical Sciences (Hyderabad, IN) ulated patients after 3 years showed that most of the surviving patients Objective: Pediatric stroke is not uncommon, and with newer inves- were functionally independent and only one patient had recurrence. The tigatory modalities, an etiology is found more often than before. Since ISS is currently being evaluated in a multinational, randomized, double the available literature in this field is limited, this study was done to blind, sham controlled pivotal trial (ImpACT-24). investigate the risk factors, the mechanism of stroke, and outcome in *CAUTION — Investigational device. Limited by Federal (or the pediatric population. United States) law to Methods: All stroke patients attending the stroke clinic of the investigational use. Nizam’s Institute of Medical Sciences, Hyderabad, India, between Aug 2006-June 2011 were included. Inclusion criteria were 1)age\18 years, 2) any ischemic or hemorrhagic stroke including venous sinus P750 thrombosis. Data collected and analyzed included demographic, Role of perfusion CT in the emergent evaluation clinical, biochemical, radiological investigations and outcomes at 3- 6 of seizures mimicking acute stroke at onset months. L. Llull, A. Renu, N. Sola`, C. Gaig, A. Chamorro, S. Amaro Results: Pediatric stroke formed about 2 % of all strokes. The Hospital Clinic Barcelona (Barcelona, ES) mean age of presentation was 11.8 years. Ischemic strokes formed 63.3 %, venous thrombosis 28.7 % and intracranial bleeds were 8 % Introduction: The clinical presentation of acute seizures may mimick of the total group. The gender distribution was 58.5 % females and acute stroke at onset, especially in the case of partial status epilep- 41.5 % males. Arteriopathy was most common cause of ischemic ticus, thus challenging the identification of patients that could benefit stroke, anemia for venous thrombosis whereas vascular malforma- from acute reperfusion therapies or from antiepileptic drugs. We tions were associated with hemorrhagic stroke. Overall mortality in report five patients admitted to the emergency room with the suspect the total group was 4 %, and favorable outcome using modified of acute stroke and final diagnosis of partial status epilepticus in Rankin score was 76.8 %. whom a perfusion CT (PCT) was crucial in the initial assessment. Conclusion: The demographic profile of pediatric stroke in this Methods: Five patients with vascular risk factors (only one with study is different from that reported from other Asian countries, with previous history of seizures) were admitted to the emergency room mean age at presentation higher, fewer incidences of hemorrhagic suffering from acute hemispheric syndrome. A PCT was performed at subtypes and more venous thrombosis cases. Our patients had better hospital admission to rule out ischemic stroke. outcome compared to that reported from other Asian countries. Results: Plain CT did not show acute ischemic lesions and the vascular study was negative for significative arterial occlusions. In one patient it disclosed a left cortical-subcortical parietal lesion suggestive of subacute hematoma and in another a chronic temporal ischemic lesion. In P749 all the patients, PCT showed signs of a focal cerebral hyperperfusion in Long-term outcome of Neuropath IS System the symptomatic hemisphere consisting in increased regional cerebral in ischaemic stroke patients from South India blood flow, increased regional cerebral blood volume and shortened time-to-peak. Suspecting status epilepticus, reperfusion therapies were S. Kaul, M. Panigrahi, V. Bandaru, J. Rani, S. Alladi prevented and anticonvulsant treatment was administered with good Nizam’s Institute of Medical Sciences (Hyderabad, IN) clinical response and. An electroencephalogram, performed within 24 h Background: The Ischemic Stroke System (ISS) is a novel device of clinical onset and after anticonvulsant therapy initiation disclosed designed to deliver stimulation to the sphenopalatine ganglion (SPG). lateralized or focal slow activity in two patients, interictal focal epilep- The SPG sends parasympathetic innervation to the anterior cerebral tiform discharges in two, and partial status epilepticus in one. A control circulation. In rat stroke models, SPG stimulation results in increased neuroimage was performed in all subjects and showed a chronic ischemic cerebral blood flow, reduced infarct volume and improved neuro- lesion in two and a cortical focal hematoma in one. All patients recovered logical outcome. Thirty five patients from Nizam’s Institute of completely within 48 h. Medical Sciences, Hyderabad (India), were enrolled (mean age 50.1 Conclusion: PCT could be an adjuvant and complementary tool to years, men 24(68.5 %), mean baseline NIHSS 12.5 and mean treat- EEG in the early diagnosis of acute focal neurological deficits secondary ment time from stroke onset 19h). Patients treated with the ISS had to seizures, and therefore allowing an early initiation of antiepileptic better outcome at 90 days as measured by the improvement in mRS treatment and avoid unnecessary use of reperfusion therapies. and NIHSS compared to the NINDS study. Objective: The purpose of this study is to present the long term follow up of the 35 patients implanted with this device from a Uni- P751 versity hospital in South India. Botulinum toxin A related changes of cortical activity Methods: Patients with anterior AIS, baseline NIHSS 7-20 and in patients suffering from severe hand paralysis ability to initiate treatment within 24h from stroke onset, were implanted and treated with the ISS. All patients were implanted with arm spasticity following ischaemic stroke between 2006 and 2008. Long term follow up assessment after a T. Veverka, P. Hlusˇtı´k, Z. Toma´sˇova´, P. Hok, P. Otruba, minimum period of 3 years was done. M. Kra´l, Z. Tu¨do¨s, J. Zapletalova´, R. Herzig, A. Krobot, Results: Out of 35 patients enrolled, 9 (25.7 %) patients were lost P. Kanovsky´ to follow up as on 31st December, 2011. The mean follow up duration Palacky´ University and University Hospital (Olomouc, CZ) of the remaining patients was 5 years (range 40-65months). Out of 26 patients 8(30.7 %) had died. Two patients died within 90 days of Objectives: Investigations were performed to localize and analyze the implantation whereas 6 died after 1 year. None of the deaths were botulinum toxin (BoNT-A) related changes of cerebral cortex

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S205 activation in chronic stroke patients suffering from severe hand Muscle disorders paralysis with arm spasticity. Effects on task- related cerebral activation were evaluated by functional magnetic resonance imaging (fMRI). Methods: 14 patients (5 males, 9 females, mean age 55.3 years) P753 suffering from upper limb post-stroke spasticity were investigated. The Peripheral nerves involvement in patients change of arm spasticity was assessed by using the modified Ashworth with myotonic dystrophy type 1 scale (MAS). FMRI sessions were performed before (W0), four weeks S. Peric, A. Nikolic, A. Kacar, I. Basta, I. Marjanovic, (W4) and 11 weeks (W11) after BoNT-A application. Patients were scanned while performing imaginary movement with the impaired hand. D. Lavrnic, Z. Stevic, V. Rakocevic-Stojanovic Group fMRI analysis included patient age as a covariate. Neurology Clinic, Clinical Center of Serbia (Belgrade, RS); Results: BoNT-A treatment was effective in alleviation of arm University of Belgrade (Belgrade, RS) spasticity. Mean MAS was at Week 0: 2.5 (SD 0.53), at Week 4: 1.45 Background: Myotonic dystrophy type 1 (DM1) is the most common (SD 0.38), at Week 11: 2.32 (SD 0.44). form of muscular dystrophy in adults. DM1 is an autosomal dominant Task-related fMRI prior to the treatment showed extensive acti- multisystem disease. Central and also peripheral nervous system are vation of bilateral frontoparietal sensorimotor cortical areas, anterior reported to be affected in DM1. cingulate gyrus, pallidum, thalamus and cerebellum. Aim: Electrophysiological evaluation of frequency, type and Effective BoNT-A treatment (W4) resulted in partial reduction of possible causes of peripheral neuropathy (PNP) in a cohort of patients active network volume in most of the observed areas, whereas BoNT- with DM1. free data (W11) revealed further volume reduction in the sensori- Patients and method: This retrospective study comprised 111 motor network. patients genetically diagnosed with DM1. Patients with glucose On direct comparison, significant activation decreases associated intolerance, diabetes mellitus and thyroid dysfunction were excluded with BoNT-A treatment were located in areas outside the classical from the study and remaining 89 patients were analyzed (51.7 % sensorimotor system, namely, ipsilesional lateral occipital cortex, males, age 41.0±9.1 years, duration of disease 14.7±9.3 years). supramarginal gyrus and precuneus cortex. On comparison of W4 and Nerve conduction study (NCS) was performed on right sural and W11, no activation increases were found, instead, activation further motor part of peroneal nerve using criteria from the Report of the decreased in ipsilesional insular cortex, contralesional superior frontal American Academy of Neurology from 2005. gyrus and bilateral frontal pole. Results: NCS of peroneal nerve showed reduced velocity in 25 Conclusion: Whole brain activation patterns during BoNT-A (28.1 %) patients and reduced amplitude of a compound muscle treatment of post-stroke arm spasticity and further follow up docu- action potential (CMAP) in 9 (10.1 %). NCS of sural nerve revealed ment predominantly gradual changes both within and outside the reduced velocity in 5 (5.6 %) patients, while amplitude of sensory classical sensorimotor system. nerve action potential (SNAP) was normal in all examined patients. In This work was supported by the IGA Ministry of Health Czech summary, 30 (33.7 %) patients had at least one electrophysiological Republic grant number NS9920-4/2008. sign of PNP. Patients with peripheral nerve impairment were elder (p\0.05), and had longer duration (p\0.01) and more severe form of disease (p\0.05). They also had higher level of serum triglycerides P752 (p\0.01) and cholesterol (p\0.01) and higher BMI (p\0.05) in Early experience of using pH-weighted MRI to detect comparison to those without PNP. Conclusion: NCS showed signs of peripheral neuropathy in 34 % the ischaemic penumbra at 1.5 Tesla of patients with DM1, mostly due to motor and demyelinating W. Yang, Z. Shen, G. Xiao, R. Wu impairment. Presence of PNP was in association with DM1 itself Shantou University (Shantou, CN) (duration and severity of disease) and also with dyslipidemia and BMI. We suppose that alternative splicing of certain peripheral nerve In acute stroke, anaerobic glycolysis lead to accumulation of lactic protein(s) may lead to PNP in DM1 which is secondary worsen by acid, which decrease the intracellular pH. Lactic acid is osmolyte and metabolic impairment frequently described in DM1. therefore directly contribute to the formation of cerebral edema and neurons apoptosis. The development of diffusion and perfusion MRI has improved our understanding of acute ischemic tissue damage, and is increasingly used to help guide stroke treatment. The classic definition of the ischemic penumbra is a hypoperfused region in which P754 metabolism is impaired, but still sufficient to maintain cellular Are brain and muscle independently involved in DM1? polarization. And thrombolytic therapy can restore blood flow and C. Ferrati, V. Romeo, M. Fanin, A. Nascimbeni, improve patient outcome, so detecting the ischemic penumbra is R. Manara, M. Ermani, E. Pegoraro, C. Angelini important. But it often remains unclear whether a PWI–DWI mis- University of Padova (Padova, IT); University Hospital of Padova match corresponds to benign oligemia or a true penumbra. We (Padova, IT); IRCSS San Camillo Venice (Venice, IT) hypothesized that pH-weighted MRI (pHWI) can subdivide the PWI– DWI mismatch into these regions. Twenty human who suffered from Objectives: The aim of this study is to determine the degree of stroke was studied using multiparametric MRI. We find that 15 involvement in brain and skeletal muscle in a series of 24 molecu- pHWI/DWI match, and other 5 pHWI/DWI mismatch, pHWI larly-defined DM1 patients in order to highlight possible correlations abnormality is smaller than the PWI, and larger than the DWI. These or their independent involvement. data suggest that the outer boundary of the hypoperfused area Cerebral and muscle impairment in myotonic dystrophy type 1 showing a decrease in pH without DWI abnormality may correspond (DM1) is well documented but there are few reports on their corre- to the outer boundary of the ischemic penumbra, while the hypop- lation in the same patients. erfused region at normal pH may correspond to benign oligemia. Methods: Twenty four DM1 patients were recruited for our study. These first results show that pHWI can provide information com- Age at study, age at disease onset and disease duration were recorded. plementary to PWI and DWI in the delineation of ischemic tissue. Molecular characterization of CTG(n) expansion was done in

123 S206 J Neurol (2012) 259 (Suppl 1):S1–S236 genomic DNA from blood. Neuromuscular assessment in DM1 P756 patients was performed by Muscular Impairment Rating Scale High prevalence of vitamin D deficiency in myotonic (MIRS). A morphometric study of muscle biopsies included the quantitative evaluation of fibre atrophy/hypertrophy factor of both dystrophies fibre types. All patients underwent brain MRI; MRI imaging was E. Bugiardini, E. Passeri, V.A. Sansone, B. Ambrosi, classified by the Age Related White Matter Changes (ARWMC) score S. Corbetta, L.V. Renna, R. Cardani, G. Meola in order to quantify the pattern of distribution of White Matter University of Milan (San Donato, IT); Fondazione Malattie Hyperintense Lesions (WMHLs). Miotoniche (San Donato, IT) Results: Morphometric analysis of muscle showed an increased atrophy factor(AF) for both type I or type II fibres, AF was increased Objectives: Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are especially for type I fibres in 14/24 cases. 20/24 patients had abnormal progressive multisystem genetic disorders that share a similar path- MRI imaging, showing scattered supratentorial, bilateral, symmetrical ogenetic mechanism and clinical manifestations. Growing interest has focal or diffuse WMHLs, with a typical temporo-insular diffuse been focused on endocrine and metabolic alterations but only few subcortical pattern in most patients. studies concern bone density and calcium metabolism. A hyperostotic A more severe muscle impairment both at clinical and histopa- potential and an association between myotonic dystrophy and thological level was observed in patients harbouring larger CTG hyperparathyroidism have been previously showed (Rodriguez JR expansion. No significant correlation were found between atrophy et al. 1991; Schneider C et al. 2000); however no studies have been factors and MRI total lesion load of WMHL. performed to assess vitamin D metabolism. Vitamin D plays an Conclusion: We conclude that greater expansion size is confirmed important role in different tissues, including skeletal muscle, and it as a risk factor for more extensive cerebral and muscle impairment, seems to be related to cardiovascular risk and diabetes (Holick MF, however our study indicates that muscle and brain are independently 2007; Ceglia L, 2008). The aim of the study was to evaluate the involved. vitamin D status in DM1 and DM2 patients and its association with disease stage and bone density. Methods: We enrolled 31 DM1 (age 44,2±11,9) and 13 DM2 (age 56,9±9,1) male patients. Patients under 18 and over 65 years were excluded. Muscle strength assessment was made by manual muscle P755 testing (MRC score) on 15 muscles on the right and left and con- Anticipation in families with myotonic dystrophy type 1 sidering a total score of 150 for normal muscle strength. Stage of the and type 2 disease of DM1 patients was defined using Muscular Impairment A. Shopova, T. Chamova, V. Guergeltcheva, I. Tournev Rating Scale (MIRS). University Hospital Alexandrovska (Sofia, BG) Vitamin D status was evaluated by measurement of 25-hydroxyvitamin D [25(OH)D] on plasma. Bone mineral density was Myotonic dystrophy type 1 (DM1) is caused by expansion of a CTG evaluated by DEXA at both lumbar and femoral segments. Patients trinucleotide repeat in the non-coding region of DMPK. Expansion were divided into four different groups based on vitamin D level: of the CCTG repeat in intron 1 of ZNF9 causes proximal myotonic normal status [25(OH)D [30 ng/ml]; vitamin D insufficiency myopathy (PROMM, DM2). Anticipation is a known phenomenon [25(OH)D \30 ng/ml]; vitamin D deficiency [25(OH)D \20 ng/ml]; in DM1 most often when the mother transmits the disease. Clinical vitamin D severe deficiency [25(OH)D \10 ng/ml]. features have been reported to worsen from generation to generation Results: We found a vitamin D insufficiency in 90 % of patients in families that participated in the original characterization of DM2. (mean value±SD; DM1: 12,2±8,1 ng/mL; DM2: 13,7±5,5 ng/mL) Data suggested that this was caused by anticipation, however there and a severe deficiency in 41,9 % of DM1 patients and in 30,8 % of is no evidence of a congenital or childhood form of myotonic dys- DM2 patients. No significant differences in muscle strength and in trophy type-2. Furthermore, the lack of correlation between disease stage of disease were found among the groups of patients with dif- severity and CCTG repeat length in DM2 points that intergenera- ferent level of vitamin D (ANOVA p[0,05). Bone mineral density tional changes in repeat length would not be expected to reliably was normal in almost all cases, except for the presence of osteopenia worsen disease severity. The aim of the presentation was to inves- in 3 DM1 and 2 DM2 patients. tigate the anticipation in families with DM1 and PROMM. During Conclusion: There is a high prevalence of severe vitamin D the period of three years, among the patients with DM1 and DM2 deficiency in myotonic dystrophies patients regardless of disease that we have investigated, we selected 10 families with affected stage or muscular function. Despite bone mineralization seems not to members in several generations and in that way represent more be impaired it is useful to evaluate and manage vitamin D status for clearly the phenomenon of anticipation. Seven of the families with its role in muscle function and in cardiovascular disease. DM1 and PROMM were not only clinically verified but also genetically confirmed with defined number of the CTG repeats and CCTG expansion. We based our analysis of anticipation on the age P757 of disease onset and the severity of some symptoms as cardiac abnormalities, posterior iridescent cataracts, muscle weakness and Genetics of limb-girdle muscular dystrophies in Saudi wasting, myotonia, cognitive impairment and central nervous sys- Arabia tem changes, such as cortical atrophy and white matter S. Bohlega, D. Monies, M. Al Muhaizea, I. Al Homoud, abnormalities. Anticipation was assumed if the offspring had these H. Al Hindi, A. Alazami, S. Majid, B. Meyer symptoms earlier and more severe in life than his or her affected King Faisal Specialist Hospital (Riyadh, SA) parent. In our study seven of the DM1 families show anticipation. In four of them there was a correlation between the age of onset and the Objectives: The limb-girdle muscular dystrophies (LGMDs) consti- severity of the disease and the number of the CTG repeats even with tute a genetically heterogeneous group of progressive skeletal muscle congenital form of the disease, while in the PROMM families disorders, involving the pelvic or shoulder-girdle musculature. The anticipation was not represented. Our findings confirm the occur- autosomal recessive (AR) from of the disease alone demonstrates a rence of anticipation in parent-offspring pairs only from families cumulative prevalence of approximately 1:15,000 and is most likely with DM1. more prevalent in Saudi Arabia as a consequence of high cousin

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S207 marriages. Thus far 20 genes have been implicated in the cause of this P759 hereditary disease worldwide. Expression of chemokines and their receptors in muscle Methods: We studied the clinical, pathological and genetic finding in 40 native Saudi Arabian families affected with LGMD. The disease tissues from Duchenne muscular dystrophy patients onset, progression and phenotypes were variable even within families B. De Paepe, K.K. Creus, J.-J. Martin, J.L. De Bleecker affected with similar sub-type in addition moderate intra-familial Ghent University Hospital (Ghent, BE); Antwerp University Hospital variability was noted in majority of patients. (Antwerp, BE) Result: Sarcoglycanopathy was the most prevalent subtype and Objectives: In Duchenne muscular dystrophy (DMD), skeletal muscle accounted for 36 % of all families studied alpha subtype (LGMD2D) infiltration by immune cells is correlated to disease severity and is was the commonest followed by Gamma LGMD2C then Beta prognostic for disease progression, yet, the precise mechanisms LGMD2E. Dysferlinopathy-Miyoshi distal myopathy (LGMD2B) was behind inflammatory muscle tissue damage remain poorly under- the second commonest genotype and seen in 24 % of the families stood. We studied chemotactic cytokines or chemokines, which are studied. Calpainopathy (LGMD2A) was found in 12 % of families. key factors in the recruitment and activation of immune cells, in Novel mutations were seen in 2 families (8 %) with FKTY with peculiar DMD muscle. clinical muscular weakness and appearance consistent with LGMD2M Methods: Chemokines and chemokine receptors were visualized phenotype. In 20 % of the cases, no identified mutations could be found in skeletal muscle from 9 patients using immunohistochemistry, even with the sequencing of all genes responsible for LGMDs. immunofluorescence and in situ hybridization. When our result compared with other ethnic group, there were few Results: CXCL1,2,3,8,11 were absent from normal but induced in common mutations among Saudis with more homogenous phenotypic DMD myofibers. Some, but not all, were regenerating or necrotic presentations within each sub-group. muscle fibers. CXCL11,12 and CCL2 were upregulated on DMD Conclusion: In Saudi Arabia, LGMD is the most prevalent blood vessel endothelium. CD68+ macrophages express high levels of genetically inherited muscle disorder with variable presentation and CXCL8, CCL2 and CCL5. In contrast, chemokine expression in there is no clear phenotype, genotype correlation among the various infiltrating T-cells, B-cells and DCs was low or lacking. subtypes of LGMDs. Conclusion: Based on the spatial distribution and the selective Research Advisory Council Project # 2070005 expression pattern of distinctive chemokines, diverse functions in DMD muscle inflammation are suspected. On the one hand, chemokines are probably involved in inflammatory cell recruitment and P758 macrophage cytotoxicity. On the other hand, certain chemokines may Late-onset Pompe disease presenting as asymptomatic be beneficial in muscle damage control. hyperCKemia and early respiratory impairment J.J. Vilchez, N. Muelas, T. Sevilla, L. Bataller, R. Sivera, P760 P. Martin University Hospital La FE (Valencia, ES) Lymphotoxin beta: an important cytokine in inflammatory myopathy Alfa-glucosidae (AGA) enzyme replacement therapy (ERT) for Pompe disease (PD) has pose new challenges. Early diagnoses would be K.K. Creus, B. De Paepe, J. Weis, J.L. De Bleecker desirable to a start therapy as soon as possible and hinder functional Ghent University Hospital (Ghent, BE); Aachen University Hospital impairment. On the other hand it has been reported that AGA defi- (Aachen, DE) ciency can remain as asymptomatic hyper-Ckemia for decades, making Objectives: It has been established that Lymphotoxin beta (LTbeta) is unnecessary the use of a costly and hazardous treatment. We have been a key factor in lymphoneogenesis, but it may also regulate the diverse observing two young-adult PDpatients diagnosed as asymptomatic inflammatory mechanisms behind the idiopathic inflammatory myo- hyperCKemia that showed significant respiratory decline shortly after pathies (IM). the diagnosis, demanding immediate medical intervention. Methods: We studied LTbeta and its receptor (LTbetaR) in IM, A male and a female aged 32 and 27 years-old were found to suffer comparing with normal and disease controls, and using immunohis- from persistent asymptomatic hyperCKemia (700 to 1500 U/L) for tochemistry, Western blotting and in situ hybridisation. approximately five year. The diagnosis of Pompe disease was estab- Results: LTbeta is found in myonuclei of normal controls, but is lished by enzymatic dried blood tests (DBS) in case 1 and muscle strongly upregulated in regenerating muscle fibres in all myopathies. biopsy the second one. A genetic mutational investigation was con- Denervated myofibres are LTbeta negative. Normal-appearing myo- firmatory in both cases. Strength on manual muscle testing and fibres in IM and muscular dystrophies express LTbeta possibly conventional functional tests (6MWT, 10 meter walking, and reflecting early myofibre damage, representing a hitherto undescribed ascending-descending 4 steps) were maintained in normal range dur- pathologic hallmark. We showed LTbeta in several inflammatory cell ing fallow-up. MRI appeared with limited lumbar paravertebral types in IM, with highest levels observed in B-cells. muscle changes in patient 1 an totally normal in patient 2. Respiratory Discussion: Our data point to multiple actions of LTbeta both in functional impairment was observed in both cases: reduction standing- normal and in diseased muscle. The LTbeta expression observed in lying FVC [ 25 % and decreased PIMAX. Nocturnal pulsioxymetry normal appearing muscle fibres could facilitate the attraction of studies were abnormal and assisted ventilation was settled to both inflammatory cells, activating the inflammatory cascade in muscle. patients. Enzyme replacement therapy was indicated as well. Late-onset PD is characterized by a broad variability in clinical expression and rate of progression making it difficult to draw P761 guidelines over ERT onset. Our observation stresses the importance MRI evaluation of respiratory function in patients of AGA testing in asymptomatic hyper-CKemia and the need for close respiratory surveillance in pre-symptomatic PD. with the late-onset form of Pompe disease This work has been supported by a grant of the Spanish Instituo O. Musumeci, M. Gaeta, E. Barca, A. Mileto, A. Toscano Carlos II: FIS PI11/01330. University of Messina (Messina, IT)

123 S208 J Neurol (2012) 259 (Suppl 1):S1–S236

Pompe disease is an inherited disorder due to deficiency of the regards to detection of serum anti-AChR antibody (p: 0.3, OR 1.17 lysosomal enzyme, alfa glucosidase. IR 95 % 0.31-4.36). In contrast to other neuromuscular diseases, where respiratory Conclusions: The data presented here, derived from a retrospective insufficiency occurs after loss of ambulation, respiratory symptoms in analysis of MG patients, show that positivity for serological and Pompe disease can be one of the first clinical manifestations of the electrophysiologic findings are not mutually exclusive, with a sig- disease, and patients may present respiratory impairment despite still nificant number of cases presenting discordant findings. Additionally, ambulating. Diaphragm weakness with sleep disorder breathing and patients with a more focal presentation of MG tended to present lower respiratory failure also seem to be an inevitable part of the Pompe sensitivity to the RNS test in comparison with those with the gen- disease course. Respiratory failure in patients with Pompe disease can eralized form. range from insidious to acute onset and t is the most common cause of early death in patient’s with Pompe disease, as well as in other patients with primary neuromuscular disease. The dual-echo dual-flip angle spoiled gradient recalled is a new MRI technique which allows to accurately quantify and display the muscle fat P763 fraction (MFF). We recently showed that it provides an accurate fat Evolution of thymoma-associated Myasthenia gravis quantification when compared to muscle biopsy findings in different A. Nacu, V. Lisnic, L. Munteanu, C. Grosu neuromuscular disorders. We evaluated the MFF of all respiratory State Medical and Pharmaceutical University (Chisinau, MD); muscles in 9 ambulant late onset Pompe disease patients. We correlated Institute of Neurology and Neurosurgery (Chisinau, MD) the MRI data with the pulmonary function evaluated by percentage of function vital capacity (FVC) in sitting and supine position. Myasthenia gravis (MG) is the most common autoimmune disease We found a statistically significant correlation between degree of affecting the neuromuscular junction, characterized by painless fati- diaphragm atrophy and pulmonary dysfunction especially in upright gable muscle weakness. position. The role of the thymus in the pathogenesis of MG is not entirely Our data suggests that MRI study of respiratory muscles could be a clear, but 75 % of patients with MG have some degree of thymus useful tool to evaluate the impairment of respiratory function and to abnormality (hyperplasia or thymoma). follow the disease progression in patients with Pompe disease Objective: To study the clinical, serological, electrophysiological evolution of thymoma-associated myasthenia gravis. Methods: Between January 2008 and December 2011, sixty one patients (39 females and 22 males) with confirmed MG were studied. P762 Clinical, serological, electrophysiological, mediastinal CT scan, sur- Electrophysiological and immunological aspects gical and medical treatment was performed on included cases. Eleven in Myasthenia gravis: a retrospective study of 100 patients were tested for antibodies to AchR. Results: Clinical staging at diagnosis (MG Task Force Foundation) Brazilian patients was as follows: gr I - 8 (13 %); gr II – 28 (46 %); gr III – 19 (31 %), and P.J. Lorenzoni, R.H. Scola, C.S.K. Kay, L. Filla, gr IV – 6 (10 %). Mediastinal CT revealed a thymoma in 33 (54 %) A.P.P.Miranda, L.C. Werneck cases, thymic hyperplasia - in 17 (28 %) cases, normal thymus - in 11 University Federal do Parana´ (Curitiba, BR) (18 %) cases. Antibodies to AchR were positive in eight cases. TE was performed in 35 cases (57 %). The following results were Objective: Myasthenia Gravis (MG) is a rare autoimmune neuro- obtained by means of microscopic examination: thymoma - 29 muscular junction disorder characterized by weakness and (83 %), thymic hyperplasia - 5 (14,3 %) cases, and normal thymus – 1 fatigability. The diagnosis is based mainly on clinical history and (3 %) cases. neurological examination. Once suspected, laboratory confirmation After a follow-up from 1 to 17 years of thymoma-associated may be obtained using pharmacological, electrophysiological and myasthenia gravis patients 7(24 %) improved their clinical status serological (immunological) tests. To analyze features of electro- [1 (3,5 %) became asymptomatic, without any treatment; 6(20 %) physiological and immunological tests used to confirm the diagnosis obtained a reduction in medications]; 9(31 %) had a stable disease in a large sample of MG patients. without clinical changes; 10(35 %) experienced a worsening in their Methods: The study retrospectively analyzed the chart records of clinical picture, requiring more medications. The recurrence of the patients diagnosed with MG followed up in our department from thymoma was registered in one case (3,5 %). Two cases of death January 1999 to May 2011. Diagnostic parameters included clinical (7 %). aspects and paraclinical data, namely sequential Repetitive Nerve Conclusions: This data suggests that evolution of patients with Stimulation (RNS) test and the presence of serum anti acetylcholine thymoma present a less favorable outcome. receptor (AChR) antibodies. RNS tracings were considered positive for a defect in neuromuscular transmission when a decrement greater than 10 % was detected. P764 Results: Medical records of one hundred patients with a diagnosis of MG analyzed, including 87 % with the generalized clinical Epidemiology of Autoimmune Myasthenia Gravis form. RNS test was performed in 97 %, 84.5 % presenting the in Argentina typical findings pointing to a defect in neuromuscular transmission. C.G. Mazia, M.O. Melcom, V.L. Salutto Serum AChR antibody was measured in 48 % of the patients, University of Buenos Aires, Centro de Asistencia Docencia e 68.7 % had positive results. In this group of seropositive patients Investigacion en Miastenia (Buenos Aires, AR); Fundation for 75.7 % also had a positive RNS test. Among patients with ocular Neuroepidemiology Research (Junin, AR) presentation, 46.1 % had a positive RNS test, 46.1 % had anti- AChR antibody positive and just 15.3 % presented both tests posi- Background: Myasthenia Gravis (MG) prevalence was estimated tive. Differences regarding positivity of RNS test between between 1.5 to 17.9/100, 000/inhabitants worldwide. An increasing generalized and ocular MG were significant (p: 0.004, OR 6.38 IR incidence ranged from 3.0 to 30.0 per million population was reported 95 % 1.88-21.63). The same, however, was not demonstrated in in the last years.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S209

Few data from Latin America and the Caribbean are available. P766 Epidemiological studies from Argentina are not disposable. Clinico—immunological study in patients with ocular Objective: To determine the prevalence, incidence and clinical features of Myasthenia Gravis in a well-defined population from Argentina. and generalised form of Myasthenia gravis Methods: Two-phase case-finding strategy was used to perform a V. Borislavova, S. Cherninkova, I. Tournev MG epidemiological study of residents from Anãtuya. This 30.000 University Hospital Aleksandrovska (Sofia, BG) inhabitants town is located at 28S/62W in northwest of Argentina. Objective: Follow out the dynamics of the clinical symptoms in Point of prevalence day was October 14, 2011. myasthenia gravis patients with pure ocular and generalized form Diagnosis of definite or probable MG was established based on the according to the kind and titer of the antibodies in the sera. presence of two or more of the following findings: fluctuating Methods: A total of 63 patients with myasthenia gravis were weakness, high titers of acetylcholine receptor antibodies, decre- included in this study. A blood test was performed to all of them in mental response on repetitive nerve stimulation and favorable order to verify the type and the titer of antibodies in the sera, as well response to acetylcholine esterase inhibitors. as electromyography, computed thomography of mediastinum, full Results: Twelve MG patients were identified. Eleven fulfilled the neuro-ophthalmological examination and hormonal tests for evalua- criteria for definite diagnosis and one for probable disease. Female/ tion of the thyroid grand function. male ratio:3/1. Prevalence rate was: 37.5/100,000. Incidence rate was Results: In 63 of the evaluated patients with myasthenia gravis, the 5.5/100,000 persons-year. presence of anti – acetylcholine receptor antibodies (AChR) has been Higher prevalence was observed in patients under 40 years-old determined in 43 individuals (68,2 %). Thirteen of them (30,2 %) than in patients over 40 years-old (83 vs. 17 %).Ethnicity of the have pure ocular form of myasthenia gravis and 31 (72,1 %) have studied population was composed mostly for mestizos. generalized form. In the patients with pure ocular form of myasthenia Mean age at prevalence day was 37 years-old. Mean age at clinical gravis, the not high anti-AChR antibodies titer as well as the lack of onset was 23 years-old. Mean age at diagnosis was 25.5 years-old. thymic hyperplasia is pointed to a tendency for a more favourable Mean disease duration: 14.1 years (median= 6) clinical course of the disease for a 2-year follow up period. Among Time elapsed between onset of symptoms and diagnosis: 2.6 yrs the patients without anti- AChR antibodies in the sera – 31,7 % we (3mo-11yrs). found equal frequency of ocular and generalized form of the disease. Maximum severity according MGFA Clinical Classification was In five individuals among the patients without anti-AChR antibodies Grade V in 2 patients (17 %); grade IV in 4 (33 %); grade III in 4 in the sera we found another kind of antibodies, anti – muscle – (33 %); grade II in 1 (8 %) and grade I in 1 patient (8 %). specific kinase (MuSK), in total 7,9 % of the group. The clinical Conclusion: The prevalence and incidence of myasthenia gravis picture in these patients is distinguished with a tendency for more observed and in this study are amongst the higher rates reported serious symptoms, especially bulbar weakness and not pronounced or previously. This may be explained by improvements in the diagnosis, missing neuro-ophthalmological symptoms. Among the patients with better knowledge of the disease and potential environmental factors. generalized form and a high anti-AChR titer we found a high percentage of thymic hyperplasia 41,9 %, while among the patients with pure ocular form and not a high anti-AChR titer, thymic hyperplasia have 21,4 %. In 10 patients (15,8 %) we found Hashimoto thyroiditis P765 as other autoimmune disease, on clinical course of which symptoms Myasthenia gravis associated with thymolipoma of myasthenia gravis have been manifested. J.H. Cho, H.S. Yoo, S.M. Kim, I.N. Sunwoo, S.H. Kim Conclusion: Immunological examinations for evaluating the kind National Health Insurance Corporation Ilsan Hospital (Goyang-si, and titer of sera antibodies in patients with myasthenia gravis might KR); Yonsei University (Seoul, KR); Yonsei University Wonju be of use as a prognostic sign for the clinical course of the disease. (Wonju-si, KR) High frequency of anti-MuSK antibodies in seronegative patients suggests that may be there are also other rare antibodies in their sera, Purpose: Thymolipomas are unusual, benign and slow growing that might have significance for the clinical course of the disease. mediastinal tumors. Most of them are discovered incidentally. Thymolipoma may be rarely associated with myasthenia gravis. Methods: We analyzed the clinical data from patients of myasthenia gravis associated thymolipoma retrospectively. Pathologically confirmed thymolipoma had a mixture of thymic and mature adipose P767 tissue in a mediastinal mass at microscopic evaluation. Response of refractory generalised Myasthenia gravis Results: There were four female and three male patients, whose ages at MG onset ranged from 42 to 59 years, with a mean age of 45.4 years. to treatment with rituximab: first report from Kingdom The mean age at thymectomy and diagnosis of thymolipoma is 47.4 of Bahrain years. Anti-AchR antibody was elevated in three of six patient. Chest CT I.A. Alsharoqi, H. Shaath do not reveal thymic tumor in any of the cases. One had thymic hyper- Salmaniya Medical Complex (Manama, BH) plasia and another had enlarged mediastinal fat tissue. And three patients had normal chest CT. All patients had generalized myasthenia gravis at Objective: Myasthenia gravis (MG) is the most frequently encoun- the time of symptom presentation. The MGFA clinical classification of tered neuromuscular disorder of an autoimmune pathology. Current patients was various from IIa to V at the time of thymectomy. Despite therapies available, which are mainly immune modulators or sup- thymectomy, all patients had to receive the treatment with immunosup- pressors, include acetyl cholinesterase inhibitors, corticosteroids, pressant including corticosteroid. azathioprine, methotrexate, cyclophosphamide, mycophenolate mo- Conclusions: We report patients with myasthenia gravis. It is uncer- fetil, intravenous immunoglobulin (IVIg), plasmapheresis and tain that thymolipoma is associated with generalized symptoms of thymectomy. Many of these therapies carry significant side effects myasthenia gravis because thymectomy is performed only in patients and in many instance not a satisfactory improvement. with generalized myasthenia gravis. Thymectomy may not be enough in Methods: We report two patients with generalized MG who pre- myasthenia gravis with thymolipoma because all these patients have to sented with a rapid down spiral clinical course. Both female patients receive immunosuppressant after the thymectomy. were in myasthenic crisis with severe bulbar weakness and being on

123 S210 J Neurol (2012) 259 (Suppl 1):S1–S236 mechanical ventilation with quadriparesis and facial diplegia and Neurorehabilitation opthalmoplegai. Both were seropositive, however, they were Musk negative. One of them had malignant thymoma grade 4. Both patients received IVIg, plasmapheresis and were on mycophenolate mofetil in addition to corticosteroid but with poor response. P769 Results: we initiated Rituximab with a mean follow-up of 2.5 Biomechanical study of hand function disorders years (375 mg/m2, days 1, 8, 15, 28 during the first month and then in patients with cervical spine cord injury one dose every 6 months). The response was remarkable. In 3 weeks I. Morozov, S. Belousov, N. Rukina they were off ventilator and they were then fully independent. After N. Nov. Research Institute of Traum and Orth (Nizhny Novgorod, 2.5 years of follow-up, both patients stopped acetyl cholinesterase RU) inhibitors and corticosteroids. One of the patients died from the complication of malignant thymoma. Hand dysfunction is one of the most serious impairments as Conclusion: Rituximab, an anti-CD20 monoclonal antibody is an power and precision grips of the hand are critical in completing effective therapy for refractory MG including patients with malig- activities of self care, mobility and walking with support for the nant thymoma being well tolerated by patients. This is the first patients with cervical spine injuries. Hand grips are only possible report from Bahrain regarding the use of Rituximab in Arab patient. due to certain muscle synergy which is lost as a result of spinal cord We also frequently use for other immune related neurological injury. Muscle imbalance changes the load on different parts of hand disorders. which is to be considered when working out adequate rehabilitation programs. Key issue of rehabilitation for spinal cord injuries is to determine muscle imbalance and restore hand function to enable early rehabilitation. P768 Cylindrical grip of 40 patients with cervical spinal injury was New quantitative MRI indexes useful to investigate studied. The tests were performed before and after treatment, as muscle diseases well as in the course of follow-up care in 6, 12 months and 5 years C. Angelini, M. Fanin, E. Peterle after the injury. We found the following disorders in load distribution on different parts of hand during cylindrical grip: increase University of Padova (Padova, IT) in load on finger I, decrease in pressure on fingers II-V, and on Objectives: We propose new types of quantitative measurement to thenar especially. The study shows that indices of load distribution evaluate muscle atrophy: the quadriceps index (QI) and the left vastus on different parts of hand in case of any type of spinal cord lateralis index (VLI), measuring by MRI their area. conductivity disorder, differ from the norm and are higher in case Methods. We have used T1 sequences on thigh muscle MRI, at of conductivity disorder of type A and B. The study did not reveal about 15 cm from the head of the femur (second slide of MRI in lower that load on different parts of hand depends on the degree of extremities). In these sequences we measured the muscle area of the cervical spinal injury (segments from C5 to T1) and period after left quadriceps femoris and of the left vastus lateralis. These mea- the injury. surement were carried out in 11 patients with various types of Assessing the character of load distribution on parts of hand in myopathies i.e. two cases of lipid storage myopathies, 1 amyotrophic dynamics, the result of patient rehabilitation with cervical spinal lateral sclerosis, 1 facio-scapulo-humeral dystrophy, 1 myofibrillar injury is prognosticated. If the load on parts of hand, which did not myopathy, 1 metabolic myopathy, 2 patients with LGMD2A, 1 participate in flexing earlier, or re-distribution of load on different patient with LGMD1F, 1 localized myositis ossificans, 1 aspecific parts of hand, is coming closer to the norm this means that hand myopathy. Muscle biopsies of these patients were further investigated function can be potentially restored. Diagnostic forecast accuracy for by morphometry and molecular markers of atrophy or autophagy i.e. hand function restoration of patients with cervical spinal injury was MURF, LC3. 91 %. The method can be used for hand function assessment in Results: We performed the measurement of muscle area of quadriceps dynamics (sensitivity 89 %), using strain-gauge indices (specificity femoris (Q.I) in 11 patients, that resulted in average 3711 mm2 ± SD 792. 98 %). In this group of patients we have identified two subgroups, one including Methodological approach to movement disorders diagnostics of 5 patients with a high degree of muscle atrophy (highly atrophic group), such patients is absence. Dynamics of severe functional disorders is whose values ranged from 2400 to 3400 mm2 (mean 2966), and one very difficult to diagnose using traditional examination methods including 6 patients with a low degree of atrophy (low atrophic group), and as a result the prognosis of function restoration is often mis- whose values ranged from 3700 to 5000 mm2 (mean 4332). takably pessimistic. Functional hand abilities of patients with The measurement of muscle area of vastus lateralis in 11 patients cervical spinal injuries should be extensively assessed using was in average 963 mm2 ± 303. In the atrophic sub-group the values existing biomechanical methods as well as develop new highly ranged from 400 to 900 mm2 (mean 658.7), while in the normal sub- sensitive techniques. group the values ranged from 900 to 1400 mm2 (mean 1217.8). Conclusion: Both the quadriceps and the vastus lateralis indexes appear useful to evaluate muscle atrophy in LGMDs, ALS and metabolic myopathies: a high degree of atrophy of QI was found in P770 calpainopathy, motor neuron disease and Limb Girdle Muscular What component of the sensory modality assessment Dystrophy type 1F, the measurement of the VLM appeared less specific since it includes a larger area. Both these quantitative indexes and rehabilitation technique is the best predictor obtained by muscle MRI, could be used as clinical outcomes of of diagnosis in low-awareness state patients? treatment in neuromuscular disorders in order to follow up and study A. Kempny, L. da Conceiçaõ Teixeira, H. Gill-Thwaites, natural history or the effect of various type of treatments (steroids, K. Yelden, S. Duport, D. Playford carnitine, etc.). A promising field of investigation appears the correlation of imaging indexes with other atrophy parameters obtained in Institute of Neuropalliative Rehabilitation (London, UK) muscle biopsy, i.e. with the cross sectional area or fibers or with Objectives: Sensory Modality Assessment and Rehabilitation Tech- molecular markers of atrophy and autophagy. nique (SMART) is a standardised scale for assessment of patients in

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S211 low awareness state (Vegetative State-VS and Minimally Conscious status was assessed using NIHSS scale. On Day 1 the mean score in State - MCS). It is based on assessment of sensory response (visual, group 1 was 11,4 ± 1,8. It was similar in group 2 (mean - 11,0 ± 1,7). auditory, tactile, gustatory, olfactory), motor function and functional Most of the patients in both groups were able to care for their basic communication. Each component is scored on a 5- point hierarchical needs (65 - 85 according to the Barthell scale) by Day 21 (time of scale with 1 point for no response and 5 points for a differentiating discharge from the hospital): 67.7 % of patients group 1 and 50 % of response. patients in group 2. NIHSS scores in group 1 became 4,8 ± 1,7 and in The aim of this study was to investigate the value of individual group 2 - 5,3 ± 1,3. component of SMART in predicting final diagnosis. Conclusion: Gradual verticalization contributes to slow and safe Method: We included 25 consecutive patients (mean age 47.2± adaptation of the body for muscular exertion preserving basic func- 15.4 years, 17 males, 10 after traumatic brain injury and 15 with tions of the lower extremities. It also helps patients to recover ischemic injury) admitted to the Royal Hospital for Neuro – disability functionally and improve after-stroke outcomes. between 12.2006 and 11.2008. The median time after ictus was 6 months. Patients were admitted in an undefined status (VS/MCS) for rehabilitation and afterwards diagnoses confirmed as either VS or MCS. SMART assessment was performed on admission and during P772 the course of rehabilitation (8.5±4.3 months) in order to determine Balance in Thai elderly after 4 weeks traditional thai the final diagnosis. dance: a pilot study Result: 12 patients were diagnosed to have MCS and 13 VS. On M. Laohhosri, J. Kanpittaya, T. Janyachareun univariate regression analysis, age, time from injury and type of Khon Kaen University (Khon Kaen, TH) injury were found not to be related to the outcome. SMART total score was found to be a strong predictor of final diagnosis (OR 1.4, Objective: Public health was developed continuously. That seemed to P=0.015). On ROC curve analysis a cut-off value of [14 points (35 increase in the number of elderly. However, elderly people had high maximal) was found to predict final diagnosis to MCS with 100 % risk of chronic diseases, loss of competency in daily living and easy to sensitivity and 54 % specificity. When analysing the components of fall. Exercise is the important way to protect disability, against SMART motor function was found to be the strongest predictor of chronic diseases and prevent fall. The aim of this study was to outcome and outperformed all other components (OR 29.0, P=0.002). investigate the effects of traditional Thai dance on balance in Thai On ROC curve analysis a cut off value of [3 (of max 5 points) elderly, that was a pilot study. predicted the outcome with 92 % sensitivity and 85 % specificity Methods: Ten female elderly was 66.6 ± 4.4 years of age average. (AUC=0.89). Each subject had baseline characteristics, Berg balance scale (BBS), Conclusion: The motor component of SMART predicts a final Time up and go test (TUGT) before (0 week) and immediately after diagnosis of MCS with high sensitivity and specificity. Further studies traditional Thai dance program was completed (4 weeks). should focus on more detailed assessment of motor function. Results: BBS of subjects before and after were 52.6± 2.2 and 54.3±1.6 score, and TUGT before and after were 9.1±0.6 and 7.6± 0.7 s, respectively. BBS of subjects were significant difference (p\0.01, 95 %CI = 0.74 to 2.65), when the results of the before and P771 immediately after program completion were compared. Furthermore, Using tilt table and functional beds for early TUGT of subjects showed significant difference (p\0.01, 95 %CI = rehabilitation after stroke -1.93 to -1.02), between before and after 4 weeks of traditional Thai L. Bikbulatova, G. Izhbuldina, E. Sabirova, L. Akhmadeeva dance. Conclusion: In conclusion, the result of this study imply the effects Bashkirian State Medical University (Ufa, RU); Municipal Clinical of traditional Thai dance on the improve of balance. Thus, it may be Hospital No. 18 (Ufa, RU) applied in individuals or elderly. However, the present study was Tilt tables are used for prevention and elimination of complications conducted in small number of subjects, that should expand the caused by the patient’s prolonged bed rest. Verticalization means the number of subjects in the future. patient’s slow rising from the supine position to the vertical position. The objective of the study was to evaluate the effectiveness of early rehabilitation of patients after stroke by using passive verticalization. P773 Methods. Thirty in-patients aged 51- 64 years (mean 58.3 years, SD = 3.1 years) unable to move around by themselves during the Improved walking speed in prolonged-release acute stage of stroke were the subjects of our study. It was a non- fampridine timed-walk responders may translate randomized controlled study with 2 groups of patients: group 1 to improvements in functional walking ability included 18 subjects verticalized using the tilt table «Lojer Tilt». P. van Asch Group 2 (control group) consisted of 12 patients whose postural Fitness and Physiotherapy Centre (Kontich, BE) changes were made by means of functional beds. Physical exertion was indicated for all patients at 1, 2, 3 and 5 days after onset of the Objectives: Functional walking scales have been used to assess par- disease. Monitoring of blood pressure and heart rate was done ticipation in activities of daily living (ADL) and may help with the simultaneously. To assess severity of neurologic symptoms we used interpretation of patients’ limitations. Recently, walking speed (WS) the National Institute of Health Stroke Scale (NIHSS). For compre- cut-offs corresponding to Modified Functional Walking Categories hensive assessment of the patient’s self-care ability on admission to (FWCs) were defined in MS patients (Kempen et al. 2011 Mult Scler). the hospital (1st day), on the seventh day and on discharge from the The objective of this post hoc analysis of 2 phase 3 trials (MS-F203/ hospital (21st day) the Barthell scale was used. MS-F204) was to evaluate changes in FWC in MS patients treated Results. On the first day of the passive verticalization, there was a with prolonged-release (PR) fampridine tablets (dalfampridine decrease in blood pressure over 20 mm Hg in most patients (44.4 %) extended release in the US). of group 1. On the second day - in 22.2 % of patients. All patients had Methods: Patients with MS who could complete the Timed strict restrictions on life activity in the beginning (mean - 31.7±8.4 by 25-foot Walk (T25FW) in 8-45s were randomised to placebo Barthell scale in group 1 and 31.5±7.7 in group 2). Neurological (n=190) or PR-fampridine 10 mg (n=343) twice daily. WS was

123 S212 J Neurol (2012) 259 (Suppl 1):S1–S236 assessed using the T25FW 4 times pre-treatment, 4 times during ACC with the right cerebellum and inferior temporal gyrus (ITG). A double-blind treatment, and once post-treatment. A consistent ‘‘treatment x time’’ interaction was found in the right IPL and right Timed-walk Responder (TWR) walked faster on the T25FW on at ITG. In the TG only, significant correlations (p\0.001) were found least 3 of 4 on-treatment versus the fastest of any of 5 off-treatment between improvement of PASAT performance and RS FC of the ACC visits. Mean baseline (BL; average of pre-treatment assessments) with the right MFG (r=0.88) and IPL (r=0.76). and on-treatment WS were used to group placebo patients, Conclusions: In MS, cognitive rehabilitation modulates RS FC of PR-fampridine Timed-walk non-responders (TWnR), and PR-fam- brain regions subserving the trained functions. fMRI might be useful pridine TWRs into 5 of Kempen’s FWCs: limited household walker to monitor rehabilitative strategies in MS. (LHW: \0.48 m/s), unlimited household walker (UHW: [=0.48 to \1.04 m/s), most-limited community walker (MLCW: [=1.04 to \1.35 m/s), least-limited community walker (LLCW: [=1.35 to \1.63 m/s), and unlimited community walker (UCW: [=1.63 m/s). P775 Results: The median EDSS was 6.0; 69 % of patients had pro- Therapeutic rehabilitation of patient with NMO- gressive MS. At BL, 46 (24.2 %), 62 (29.0 %), 35 (27.1 %) patients were LHW; 144 (75.8 %), 148 (69.2 %), 94 (72.9 %) patients were positive relapsing longitudinal myelitis: case report UHW; and 0, 4 (1.9 %), and 0 patients were MLCW in the placebo of two diversing cases (n=190), TWnR (n=214), and TWR (n=129) groups, respectively. No S-H. Pelidou, A. Ploumis, D. Varvarousis, A. Beris, patients were LLCW or UCW at BL. More TWRs (34.1 %) improved A. Kyritsis by 1 FWC than TWnRs (10.3 %) or placebo (10.5 %) patients. University of Ioannina (Ioannina, GR) Among LHW at BL, more TWRs (51.4 %) than TWnR (16.1 %) or placebo (19.6 %) patients improved to UHW. Among UHW at BL, Objective: The purpose of this study is to describe the difference in more TWRs (27.7 %) than TWnRs (7.4 %) or placebo (7.6 %) timely diagnosis and proper rehabilitation process of two paraplegic patients improved to MLCW. Among UHW at BL, 2.1 %, 4.1 %, and patients with longitudinal myelitis. 0 % of placebo, TWnRs, and TWRs worsened. One TWR improved Methods: This a retrospective chart review of two patients (39 from UHW to UCW during treatment. and 32 year-old) with longitudinal myelitis and positive neuro- Conclusions: This post hoc analysis showed that a consistent myelitis optica (NMO)-antibodies. The disease started after a T25FW response to PR-fampridine was associated with improve- febrile episode and presented as spastic paraplegia with neuro- ments on some FWCs and adds to previous data that showed a genic bowel and bladder 3 and 7 years before, respectively. CSF consistent response to PR-fampridine was associated with overall analysis was evident for inflammation and MRI showed cord improved subjective walking ability. edema from cervical to lumbar area. Steroids and azathioprine Original studies were funded by Acorda Therapeutics and these were administered as soon as possible (e.g. 5 months later) for analyses by Biogen Idec; editorial assistance was provided by the first patient and at the time of NMO-positivity during a severe Samantha Forster of UBC Scientific Solutions, which was supported ON attack (e.g. 5 years from the onset of symptomatology) for by Biogen Idec. the second patient. In-patient physical therapy included exercises with tilt table and body weight suspension treadmill walking for the first patient while the second patient was advised home-based self exercises. P774 Results. The first patient was competent of bowel and bladder Cognitive rehabilitation modulates the functional sphincters within one month while the second patient still conducts connectivity of the anterior cingulate cortex in patients intermittent bladder catheterization and a bowel program. In two with multiple sclerosis months following initiation of the disease, the first patient was able to bear full body weight and walk with aid to full functionality L. Parisi, M.A. Rocca, P. Valsasina, L. Panicari, today. The second patient is ASIA C chair-bound paraplegic and has F. Mattioli, M. Filippi a baclofen pump for severe spasticity. Both had relapses of the Vita-Salute San Raffaele University (Milan, IT); Spedali Civili of disease, which were treated appropriately with steroids and contin- Brescia (Brescia, IT) uously immunosuppression therapy, which did not leave new deficits. Objective: We investigated how resting state (RS) functional con- Conclusions. Early diagnosis and properly oriented therapeutic nectivity (FC) of the anterior cingulate cortex (ACC) is modulated by rehabilitation (including intense physical therapy program, close cognitive rehabilitation in relapsing remitting multiple sclerosis observation for relapses and immunosuppression for long time (RRMS) patients. recessions) of patients with NMO longitudinal myelitis leads to Methods: A neuropsychological assessment and RS fMRI at successful outcome. baseline and after 12 weeks were obtained from 20 RRMS patients, who were assigned randomly to undergo treatment (n=10) (treatment group - TG), which entailed computer-assisted cognitive rehabilitation of attention/information processing and executive functions for P776 3days/week, or not to receive any cognitive rehabilitation (n=10) (control group - CG). Voxel-wise changes of ACC RS FC were Obstacle-crossing ability in independent ambulatory assessed using SPM8. patients with spinal cord injury Results: In both groups, at the two study time points, the ACC W. Pramodhyakul, S. Amatachaya, P. Wuttanapun, activity was correlated with that of the bilateral middle and inferior W. Siritaratiwat, W. Eungpinichpong frontal gyrus, basal ganglia, posterior cingulate cortex, cerebellum (lobule X and Crus1), precuneus, middle temporal gyrus, and inferior Khon Kaen University (Khon Kaen, TH) parietal lobule (IPL). At follow up, compared to baseline, the TG Background: Obstacle crossing is one of many complex tasks asso- showed an increased FC of the ACC with the right middle frontal ciated with ambulation in an everyday environment. Fail on obstacle gyrus (MFG) and IPL, while the CG showed a decreased FC of the crossing can lead to a trip and subsequent fall. Independent

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S213 ambulatory patients with spinal cord injury (SCI) encounter high risk Conclusions: MSFC seems to be more sensitive than the EDSS in of fall. Knowledge regarding ability on obstacle crossing in these patient’s perceived functional improvement at the end of FKT, patients is crucial to improve their gait safety. especially in those with greater functional impairment. So FKT is able Objectives: To describe obstacle crossing ability in independent to improve not only the physical aspect of the disease but that MS ambulatory participants with SCI who walked with and without people may perceive this intervention as beneficial for their whole walking devices, and to compare balance control between the par- concept of health. ticipants who pass and fail on obstacle crossing. Materials and methods: Thirty-three participants (21 walked with a walking device, and 12 walked without a walking device) were investigated their ability to walk over small obstacles in six sizes and P778 balance control by using Timed Up and Go Test (TUGT). Descriptive Combined neurorehabilitative approach of botulinum statistics were applied to explain findings of the study. Ability of toxin type A, transcranial direct stimulation balance control of participants who passed and failed on obstacle and electric stimulation with finger-equipped electrode crossing was compared using Mann–Whitney U test. Levels of significant differences were set at 0.05. for post-stroke spastic upper limb hemiparesis Results: Eleven from 21 participants who walked with walking J. Inobe devices (52.38 %) failed on obstacle crossing. In contrast, every Inobe Hospital (Oita, JP) participant who walked without walking devices passed to walk over Object: Electric stimulation (ES) has been recognized as an effective an obstacle. Participants who passed on obstacle crossing required method to improve motor function to paralyzed patients with stroke. It is time to complete the TUGT significantly less than that of those who important for ES to synchronize with voluntary movement. Recently, we failed on obstacle crossing (p\0.05). have developed a new ES treatment system, using a finger-equipped Conclusion: Participants with SCI who walked with a walking electrode (FEE), for patients with severe paresis. It consists of an elec- device encountered a high risk injury when walking over small trode fitted on a finger, much like a finger cap. By touching the patient’s obstacles. Physiotherapists need to emphasize on the improvement of paretic upper extremity (UE), the therapist applies the ES and thus can balance control in order to promote ability of obstacle crossing and control its timing. Previous studies have shown that transcranial direct minimize the risk of injury of the patient after discharge. stimulation (tDCS) can enhance the motor performance of the hands and botulinum toxin type A (BoNTA) has been used for the control of focal spastic hypertonia in patients with upper motor neuron disturbance. In P777 this study, we investigated the effectiveness of FEE combined with tDCS Impact of intensive inpatient rehabilitation on quality and botulinum toxin type A (BoNTA) for chronic spastic UE hemiparesis after stroke. of life in multiple sclerosis. Correlation with selected Method: Four patients (three males, one female) with chronic demographical and clinical parameters stroke participated. All had severe UE weakness. BoNTA was D. Ungaro, N. Riva, I.R. Zarbo, A. Nuara, F. Martinelli injected into spastic muscles of UE, and all patients received 22 Boneschi, M. Comola, G. Comi, V. Martinelli, P. Rossi sessions of 30-min cathodal tDCS above the contralateral hemisphere and 120-min training of UE using FEE by the therapist. Before and Scientific Institute San Raffaele INSPE (Milan, IT) after the treatment, UE motor function was evaluated by Fugl-Meyer Background: Multiple Sclerosis (MS) is one of the most common Assessment (FMA). causes of severe physical disability in young people. Health-related Results: All patients improved UE function. The mean FMA score quality of life (hrqol) is a complex concept in which evaluation of increased from 20 to 26. physical, emotional and social domains of health are included. In Conclusion: Our results indicate that the ES with FEE combined patients with MS hrqol has shown to be worse than in other chronic with tDCS and BoNTA is a useful neurorehabilitative approach for diseases, probably due to the relatively younger age of patients’ chronic spastic UE hemiparesis after stroke. population. In literature is well known how intensive rehabilitation has a positive impact on edss score, fatigue, msfc, fim and barthel index, but it’s still not well established if the hospitalization due to rehabilitation is able to determine a positive impact on hrqol. P779 Objective: Aim of this study is to estimate intensive inpatient New gait analysis method using the laser rangefinder rehabilitation is able to determine an improvement in quality of life in for patients with cerebral ataxia people with MS and to investigate correlations with selected demo- V. Ondar, S. Prokopenko, A. Lyapin, M. Lavrenova graphic and clinical parameters. Krasnoyarsk State Medical University Prof. V.F. Vojno-Yasenetsky Methods: We recruited 110 ms patients who underwent a pro- (Krasnoyarsk, RU) gramme of intensive rehabilitation in our neurorehabilitation unit. We recorded hrqol with a specific disease oriented questionnaire as 450 thousand strokes occur annually in Russia; about 50 % of these the msqol at the beginning of rehabilitative hospitalization and strokes are lacunar or vertebro-basilar. Atactic disorders arise in third 1 month after; we correlate this data with edss, pasat score, sex, of these patients. For definition of movement disorders severity it disease duration and course of the disease (relapsing-remitting or is necessary an objective method of the gait analysis. The known progressive). methods are expensive and difficult for using. Results: There is a positive correlation between the improvement Aim: diagnosing the walking changes after a stroke in vertebro- of the overall score of the questionnaire of quality of life and level of basilar by using a new method with the help laser range finder. cognitive impairment and between mental subscore of MsQuol and Methods: we used model laser range finder Dimetix DLS BH 15. fatigue. The same positive correlation was found also between the The footwear of the patient was with electronic contacts. During a overall score of quality of life questionnaire and the MSFC, while the phase of a double support the range finder measured distance to the EDSS did not correlate in any way with the improvement of quality of investigated patient. The data on distance measurement were regis- life questionnaire. tered in spreadsheets Microsoft Exel.

123 S214 J Neurol (2012) 259 (Suppl 1):S1–S236

We measured gait of the 30 clinically middle age healthy people Purpose: Acid–base balance is the very important part of human at the age from 42 till 70 years. They had no neurologic and ortho- homeostasis. Alteration in tissue pH can be an indicator of many pedic diseases, disorders. Also we measured 30 patients with cerebral diseases, such as tumor. It is believed that due to the deregulating ataxia. cellular energetic and elevated metabolism, the extracellular pH in Results: The relative step length and gait variability in the healthy tumor is acidic, that is one of the typical characteristics of tumors. group corresponded to the standard well-known values. Gait of Amide proton transfer (APT) imaging, a variant of Chemical patients with a syndrome of a cerebral ataxia was characterized by exchange saturation transfer imaging, was proved to be pH dependent. reduction of the length of a step and increase of the speed of a step. To the present APT imaging technology, a steady state of chemical Conclusion: this method allows to estimate relative length and exchange is needed, and the specific absorption rate (SAR) limit duration of a step. The proposed method can be used in neurological precludes its use. In order to minimize the SAR and extend the pH- practice, as a complex for the objective gait parameters screening. weighted imaging in clinical practice, we establish a new algorithm in the unsteady state. Our earlier experiments with pH phantom prove that we can detect the pH value at 1.5 Tesla. And now we are carrying out pioneering work at 1.5 Tesla. P780 Materials and methods: A new sequence with 3.5 p.p.m. and -3.5 Musical cues during motor dexterity training influences p.p.m. radiofrequency offset was used to obtain metabolic magnetic structural brain plasticity in healthy subjects resonance imaging of volunteers with brain tumor at 1.5 Tesla. This M.A. Rocca, G. Riccitelli, L. Panicari, M.C. Di Fabio, sequence was developed based on the source code of the magnetization transfer sequence. Imaging parameters was set as follows: saturation E. Gobbetti, R. Gatti, P. Valsasina, A. Falini, G. Comi, time before each spin-echo sequence=16ms, flip angle=300, TR=400 M. Filippi ms, TE=9 ms, imaging matrix size=128*128, and acquisition band- Vita-Salute San Raffaele University (Milan, IT) width=31.25 kHz. All of the data were transferred to Matlab (The Mathworks, Natick, MA, USA) and processed by software written in- Objective: To assess, in healthy controls (HC), the structural changes house. Other routine MR images were acquired for reference. of gray matter (GM) and white matter (WM) following a manual Results: This imaging technology can accurately delineate the dexterity training, with and without musical cue and their association tumor core as Gd-T1w image does. The peripheral edema of high- with improvement of motor function. grade tumor is significantly reduced. The normal-appearing matter of Methods: Forty-five right-handed HC, without any musical expe- brain is distinguishable. But the signal-to-noise ratio is lower than rience, performed a 2-week motor training, consisting of 10 daily routine MRI and artifacts caused by field inhomogeneity are heavy, sessions of 30 min each, where they executed with their right hand a which need to be optimized in post processing. pre-defined sequence on a computer modified keyboard, following a Conclusion: This imaging technology can delineate the heteroge- rhythmical metronome cue. Subjects were randomized into three neous areas of brain tumor at 1.5 Tesla, such as separating the mass of groups: ‘‘Metronome’’ group (MG) heard no additional musical cue, solid tumor and infiltration from the surrounding edema without ‘‘Rhythm group’’ (RG) heard a musical cue at the same rhythm of the gadolinium enhanced. This finding may provide metabolic imaging metronome, and ‘‘Over-rhythm group’’ (OG) heard a musical cue at a marker as a complement for conventional imaging, and has its higher rhythm. Manual dexterity was evaluated with the 9HPT. All potential advantages in predicting the nature of tumor. Of course, subjects underwent structural magnetic MRI at baseline (T0 - before more evaluations are needed to optimize the technology, such as the training) and after 2 weeks (W2 - at the end of the training). saturation time, the flip angle and the numbers of RF pulse. Longitudinal morphologic changes of GM volumes were evaluated National Natural Science Foundation of China (30930027). using ‘‘Tensor-based morphometry’’ (TBM). Longitudinal modification of WM architecture were assessed on diffusion tensor MRI scans using ‘‘Tract-based spatial statistics’’ (TBSS). Results: 9HPT performance improved in the three study groups. P782 WM diffusivity parameters did not change after training. All groups The distinctive headache of the clivus syndrome showed a positive correlation between the improvement of 9HPT and the changes of GM volume in the right precentral gyrus, left cere- as an initial presentation of a prostate carcinoma bellum, and left supramarginal gyrus (p\0.001; r ranging from -0.55 R. Manso-Calderoń, R. Sańchez-Escribano, S. Prieto to 0.50). When considering each group separately, the OG showed a University Hospital (Salamanca, ES); Hospital Nuestra Senõra de significant correlation between improvement of 9HPT and GM Sonsoles (A´ vila, ES) changes in the left precentral gyrus and right middle frontal gyrus (r Objectives: The clivus syndrome is characterized by vertex headache, ranging from -0.66 to 0.75). which is exacerbated by neck flexion. Lower cranial nerve (VI-XII) Conclusions: In HC, a musical stimulation during motor training dysfunction usually occurs later. Though exceedingly rare, metastases improves motor performance and influences structural plasticity of involving the clivus should be considered in these cases. The meta- the GM. The complexity of the task is associated with more prostatic lesion might be a late and single expression of the primary nounced changes of GM structure. tumour. To our knowledge, the distinctive headache of the clivus syndrome as an initial presentation of a prostate carcinoma, without any cranial nerve palsy associated, has not been previously reported in Neuro-oncology the literature. Methods: A 78-year-old man complained of episodic tightness in vertex, without nausea, photophobia or phonophobia. This pain P781 appeared six months ago, lasted minutes to hours and was exacerbated Noninvasive pH imaging in human brain tumour at 1.5 by neck flexion. Acetaminophen and nonsteroidal antiinflammatory Tesla drugs didn´t improve the headache. Neurologic examination was normal. Z.Z. Dai, M.B. Wei, Z.W. Shen, G. Xiao, R.H. Wu Results: Brain magnetic resonance imaging (MRI) showed in right Shantou University (Shantou, CN) clivus a low intensity area on T1 and T2 weighted sequences with

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S215 modest enhancement, which suggested a tumour of the clivus. Lab- in segment 10 of the left lung, with a conglomeration of multiple oratory values revealed elevated prostate specific antigen (PSA) 3029 lymph nodes. Abdominal ultrasonography did not find a tumor. The ng/mL, alkaline phosphatase (ALP) 286 U/l and parathyroid hormone patient received steroid treatment, but the paresis remained unchan- (PTH) 310 mg/mL. Thoraco-abdominopelvic computed tomography ged. He was transferred to the department of pulmonology for (CT) demonstrated: a) multiple bilateral lung nodules; b) pathological bronchoscopic biopsy. paratracheal, subcarinal, hilar, mediastinal, iliac and retroperitoneal Conclusion: A lesion in the ,,hand knob’’ area was confirmed as a lymph nodes, which measured in diameter between 8-24 mm; c) a cause of the isolated paresis of the upper limb. As a rarity, it was not prostatic mass, large (45x41x51 mm) and heterogeneous with evi- caused by vascular damage, but was secondary to a metastasis, and dence of extracapsular spread to left seminale vesicle, and d) multiple the first symptom of the malignancy. Neurological investigations lytic lesions in the vertebral bodies, pelvis and ribs. A prostate biopsy revealed a malignant lung cancer. was taken. The diagnosis was bilateral prostate carcinoma, Gleason score 7, T3bN1M1 (extension to seminale vesicle, lymphadenopathy, pulmonary and bone metastases). The patient was treated with an active competitive non-steroidal androgen receptor antagonist (bica- P784 lutamide), an injectable gonadotropin releasing hormone agonist (goserelin acetate), bisphosphonates (zoledronic acid) and steroids. Case report of a patient with epileptic seizure provoked His headache improved. The patient is still alive after one year. by bone metastasis of chronic lymphoid leukaemia Conclusion: Base of skull metastases cause headache associated and Merkel cell carcinoma with well-described clinical features. Varied syndromes are named A. Folyovich, A. Majoros, G. Panczel, Z. Papai, G. Rudas, according to the site of metastasic involvement. When metastases are suspected, the diagnosis may be confirmed using axial CT imaging G. Barna, K.A. Beres-Molnar, E. Horvath, K. Vadasdi, with bone windows or MRI. The prognosis of patients with clival G. Liszkay metastases is poor. Szent Jańos Hospital (Budapest, HU); National Institute of Oncology (Budapest, HU); Military Hospital (Budapest, HU); Semmelweis University (Budapest, HU) Objective: Merkel-cell carcinoma (MCC) is a rare primary neuroen- P783 docrine cutaneous tumor, rarely metastasing to the brain. Chronic Isolated paresis of the upper limb due to lesion lymphoid leukemia (CLL) is a disease predisposing to MCC (high in the hand knob area caused by brain metastasis risk of Merkel-cell polyomavirus DNA-positive Merkel-cell carci- A. Folyovich, V. Varga, G. Varallyay, L. Kozak, M. Bakos, noma). According to previous reports, headache and focal neurological deficits suggest disease progression to brain. E. Scheidl, K. Vadasdi, K.A. Beres-Molnar, E. Horvath Methods: The 62-year-old female patient had a history of CLL that Szent Jańos Hospital (Budapest, HU); Semmelweis University was diagnosed 10 years earlier and was non-progressive under (Budapest, HU) treatment. A lesion with the appearance of an atheroma was removed Objectives: The so-called ,,hand knob’’ area is a well-defined area of from the right upper arm 2 years earlier. The lesion recurred and was the precentral gyrus, whose damage causes isolated paresis of the reoperated. Histology with immunohistochemistry confirmed the upper limb. The cause of this rare lesion is usually a lacunar infarc- diagnosis of MCC. Sentinel lymph node biopsy did not show infiltrate tion. Monoparesis raises the suspicion of peripheral neuropathy, from MCC, but progression of CLL. The patient had right axillary presenting a challenge in differential diagnosis. block dissection. Combined chemotherapy was discontinued because Methods: The 70-year-old male patient had a history of deep of bone marrow depression, postoperative radiotherapy was per- vein thrombosis of the lower limb on several occasions, long-term formed, chemotherapy of CLL was continued. The patient’s condition anticoagulation, hypertension, hypercholesterolemia, aorta and LAD deteriorated. A right axillary conglomerate soft tissue mass infiltrating stenosis. He was admitted to the department of neurology with the right lateral thoracic wall and pathologic upper mediastinal and isolated paresis of the left upper limb. He had wrist drop and was parasternal lymph nodes appeared. She was admitted to the neurology unable to grasp. He did not complain of any sensory deficit or department with her first GM seizure. numbness. Results: The patient had no focal neurological signs. Laboratory tests Results: He had postthrombotic syndrome of the left lower limb showed lymphocytosis, thrombocytopenia and anaemia. In blood smear and a systolic murmur over the aortic area. He had wrist drop on the there were Gumprecht’s shadows. On the cranial CT there was no sign left, and was unable to pronate the left hand and pinch grip with of mass lesion. The Cranial MRI/MRA showed bone metastases in the fingers I and II. Grip strength was diminished on the left. No reflex right parietal and left frontal areas, compressing the brain. EEG revealed asymmetry, pathological reflexes, sensory deficit was present. Fun- signs of right hemispheric lesion, without signs of irritation. CSF was doscopy did not show venous congestion. Neuropsychology tests clear and transparent. CSF glucose content was only 50.1 % of serum revealed an impairment in Luria’s motor sequencing test. Laboratory glucose level. CSF immunology showed intact blood-liquor barrier values showed only slightly elevated fasting glucose. Contrast- (BLB). Intrathecal IgG synthesis was not detected, but oligoclonal enhanced cranial CT showed an irregularly shaped lesion in the right gammopathy (OGP) was found. Flow cytometry of CSF did not reveal frontal, temporal and parietal area, with contrast enhancement and metastasis of MCC. CLL was only present in peripheral blood, where perifocal edema. Cranial MRI confirmed the finding of the CT, 50 % of the cells showed a corresponding phenotype. No operation was including a contrast-enhancing metastasis in the hand knob area of the performed, chemotherapy was continued. right precentral gyrus. EMG/ENG did not show peripheral nerve Conclusion: The case history of the patient is unique even among damage. Ultrasonography of cervical vessels did not show athero- rare cases of MCC metastasing to the brain. She had a history of sclerotic plaques, flow disturbance. Biplanar radiography of the proven CLL. The seizure was not elicited by cerebral metastasis, but cervical spine showed degenerative changes. Thorax radiography did by bone metastases compressing the brain. Even with the use of not show a tumor. Chest CT (plain and contrast-enhanced) showed an modern laboratory technique, only progression of MCC to the CNS irregularly shaped lesion with in homogenous contrast enhancement was suspected.

123 S216 J Neurol (2012) 259 (Suppl 1):S1–S236

P785 channel antibody (0.06 nmol/L; normal: \0.02 nmol/L), and the B-Cell lymphoblastic leukaemia/lymphoma presenting N-type calcium channel antibody (0.24 nmol/L; normal value:\0.03 nmol/L). After the first cycle of systemic chemotherapy with cisplatin as a seventh cranial nerve palsy. A case report and etoposide on 5.12.11 his mental status improved, and the patient D. Blas-Boria, P. Garciarena, J. de Groot, I Tremont- became seizure-free. There was no need to use steroids, intravenous Lukats, M.R. Gilbert immunoglobulin, or plasma exchange. His peripheral findings are due University of Puerto Rico (San Juan de Puerto Rico, US); University to a moderate axonal sensorimotor polineuropathy. of Texas (Houston, US) Conclusion: This case report highlights the diagnostic challenge posed by a paraneoplastic syndrome when there is no diagnosis or Objective: To report a VII cranial nerve palsy as initial presentation of history of cancer. A high suspicion index is important especially when B-cell lymphoblastic leukemia/lymphoma (B-CLLL). viral studies are negative. This case also illustrates how treatment of Method: A 27-year-old woman, healthy, had 7-week history of right- the underlying cancer can reverse the paraneoplastic condition. We sided facial weakness and paresthesias. Initially she was evaluated at an are closely following this patient to intervene with other treatments if outside facility for right facial tingling and numbness involving the necessary. lower lip and difficulty in closing her right eye and lower facial droop. She was diagnosed with Bell’s palsy, and treated with Acyclovir and oral prednisone without clinical improvement. Five weeks later, she was referred to MD Anderson for persistent leukocytosis. P787 Results: A bone marrow biopsy showed B-CLLL. Multiple cere- Lung tumour cells secrete factors that enhance brain brospinal fluid analyses were negative for malignant cells. MRI endothelial cell adhesion expression demonstrated enhancement of the right cranial nerve VII and VIII complex, extra-axial nodular enhancement in the right middle cranial N.J. Gutowski, S. Rai, J.L. Whatmore fossa, and lymphomatous infiltration in the right angle of mandible. Royal Devon and Exeter Foundation Hospital (Exeter, UK); The patient began high dose steroids, chemotherapy with PEG- Peninsula Medical School (Exeter, UK) Asparaginase, Rituximab, Mesna, Cyclophosphamide, Doxorubicine, Objectives: Lung tumours frequently metastasise to the brain; this and Vincristine, plus intrathecal Methotrexate twice a week and a involves specific adhesive interactions between the tumour cells and single course of intrathecal Cytarabine. Ten days later she was dis- cerebral endothelial cells. The process is facilitated by the expres- charged home with slight improvement of her right facial palsy, sion of various adhesion molecules on the surface of endothelial remaining on systemic chemotherapy. cells and their interaction with respective ligands on the tumour Conclusion: This is the first reported case we know of precursor cells. We have previously identified the release of vascular endo- B-CLLL presenting with multiple cranial neuropathy. This illustrates thelial growth factor (VEGF) and tumour necrosis factor-alpha the importance in differentiating between Bell palsy and multiple (TNF-alpha) by two non-small cell lung cancer (NSCLC) cell lines - cranial neuropathies, which may indicate an alternative diagnosis. A549 and SKMES-1, and now demonstrate the effects of these factors on the expression of adhesion molecules in cerebral endothelial cells. Methods: Adhesion molecule expression: Surface expression of P786 E-selectin, inter-cellular adhesion molecule (ICAM-1) and vascular Calcium channel- binding antibodies in a man cell adhesion molecule (VCAM-1) on human cerebral microvascular with encephalitis, peripheral neuropathy, and a tonsil endothelial (hCMEC) cells were analysed by a cell surface based enzyme-linked immunosorbent assay (ELISA). After 24 h of seeding neuroendocrine tumour onto 96-well plates, hCMEC cells were starved overnight and treated D. Blas-Boria, P. Garciarena, S. Tummala, for 4 h (E-selectin) and 24 h (ICAM-1 and VCAM-1) with 0.2, 10 I. Tremont-Lukats and 20ng/ml of VEGF and 100, 500 and 2500pg/ml of TNF-alpha. University of Puerto Rico (San Juan de Puerto Rico, US); University Following treatments, expression of adhesion molecules was mea- of Texas (Houston, US) sured by ELISA. Adhesion under flow: A549 and SKMES-1 lung tumour cells (1 x Objective: To report a patient with paraneoplastic encephalitis due to 106 cells/ml) were flowed over VEGF (0.2ng/ml) and TNF-alpha calcium channel antibodies; to highlight the confusion with viral (100pg/ml) treated hCMEC cells at a shear stress of 1 dyn/cm2. encephalitis before a cancer diagnosis. Methods: A 48-year-old man Adherent cells were analysed by microscopy techniques. was healthy and normal until 1.5.2011 when he had a first time tonic– Results: Compared to control levels (100 %), 0.2, 10 and 20ng/ml clonic seizure, followed by partial complex status. Initial MRI of of VEGF significantly increased adhesion molecule expression: after brain was normal, and a lumbar puncture (LP) showed mononuclear 4 h, E-selectin to 178.2 + 41.6 %, 135.7 + 24.3 % and 173.8 + pleocytosis, normal protein, and was negative for an infectious agent. 12.3 %; after 24 h ICAM-1 and VCAM-1 to (114.3 + 11.4 %, 120 + On exam, the patient was delirious. He received empiric treatment 17.3 % and 145 + 28.6 %) and (242.3 + 140.3 %, 273 + 115.9 % and with acyclovir x 14 d, and was discharged to a rehabilitation facility 378.3 + 137.5 %) respectively. TNF-alpha concentrations of 100, 500 with cognitive deficits. Six months later, he was diagnosed with and 2500pg/ml also enhanced E-selectin expression to 243.3 + poorly differentiated neuroendocrine carcinoma of the right tonsil. 101.2 %, 260.6 + 49.6 % and 260.6 + 65.8 %, ICAM-1 expression to A PET/CT scan showed an FDG-avid mass in right tonsil and met- 162 + 42.2 %, 202.7 + 65.2 % and 236.7 + 38.5 % and VCAM-1 to abolically active nodes in the right upper neck. The tumor cells 483.3 + 179.3 %, 588.3 + 276.4 % and 1026.3 + 60.4 %. stained positive for AE1/AE3, synaptophysin, chromogranin, CD56, Flow adhesion assay results demonstrated that VEGF and TNF- and TTF-1 and negative for CD20, CD3, CDX2, PAX5, and PSA. alpha treatment increases the number of lung tumour cells attaching to Results: Mini-Mental State Exam (MMSE) score: 26, with 0/3 in the brain endothelial monolayer. recall, 1/5 in attention. Vibration and position senses were decreased Conclusion: Factors released from lung tumour cells like VEGF in both feet, with hyporeflexia. A second MRI of brain was normal, and TNF-alpha increase expression of endothelial adhesion molecules the LP showed a protein of 65 mg/dl with no cells, and the serum and and possibly enhance tumour cell adhesion to cerebral endothelial CSF paraneoplastic panels were positive for the P/Q-type calcium cells.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S217

P788 Results: Brain tumors without occludin expression revealed a Rare paraneoplastic neurologic syndrome associated significantly higher PTBE volume (p = 0.002). Although the difference of PTBE volume between positive and negative tumors in with occult breast cancer various pathology of brain tumors was not significant statistically, A. Sousa, P. Barata, J. Morgado, A. Calado, P. Custo´dio, occludin-positive meningiomas demonstrated a high PTBE volume J. Pena comparable to occludin-negative meningiomas (p = 0.016). Centro Hospitalar Lisboa Central (Lisbon, PT) Conclusion: These results advocate that occludin provokes PTBE in brain tumours and PTBE in meningiomas is predisposed to Objectives: To report the case of a patient who presented with an occludin expression. Therefore, therapeutic block of occludin func- unusual paraneoplastic neurologic syndrome (PNS) associated with tion may be a tool of edema decrease in brain tumours. occult breast cancer that had a good recovery after the oncologic systemic treatment. Methods: Case retrieved from the Neurology and Oncology’ files with review of clinical aspects and diagnostic workup. Results: A 42 years old, pre-menopausal woman was admitted to P790 the Emergency room for acute left facial paresis. 15 days before, she Disseminated leptomeningeal hemangioblastomatosis had noticed left leg weakness with hypoesthesia without any chan- J. Marques, J. Passos, M. Casimiro, A. Azevedo ges in sphincters function. Neurologic examination revealed left Instituto Portugueˆs de Oncologia de Lisboa Francisco Gentil (Lisbon, central-like facial paresis and left tongue deviation, an upward PT); Centro Hospitalar de Lisboa Ocidental (Lisbon, PT) vertical nystagmus, moderate spastic paraparesis in addition to dystonic posturing of the left foot, lower limb hyperreflexia and Introduction: Disseminated Leptomeningeal Hemangioblastomatosis bilateral extensor plantar reflex. T2-weighted brain MRI showed (DLH) is an extremely rare form of recurrence of hemangiobastoma. small non specific white matter lesions (periventricular, right corona It is hypothesized that the overexpression of VEGF may act as a radiata and bilateral frontal subcortical) without enhancement. Spine promoter of this aggressive form of recurrence. Bevacizumab, a MRI and somatosensory evoked potentials were normal. After ruling out VEGF-inhibitor, may thus have a role in the treatment of DLH. other neurologic causes, PNS was suspected. No anti-onconeural protein Clinical Case: We report a case of a 72 year-old male patient, antibodies were found. Positron emission tomography detected an submitted to resection of a cerebellar hemangioblastoma 17 years ago increased metabolism in both mammary glandules, more intense in the (without clinical criteria for Von Hippel-Lindau Disease). He had a right one, and homolateral thoracic retro-pectoral adenopathy. Right local recurrence 13 years later, for which he was submitted to breast MRI demonstrated a retroareolar suspicious nodule with axillary resection of the new mass and ventriculoperitoneal shunt (VPS) involvement and the biopsy confirmed an invasive breast ductal carci- placement. He remained clinically stable with left abducens nerve noma. After breast oncologic surgery all neurologic symptoms were paresis and right hemiataxia. Two years ago, he presented with progressively diminished. A week later, the patient was readmitted at the worsening axial ataxia with bilateral abducens nerve paresis. Brain Hospital with a fatigable bilateral eyelid ptosis. Repetitive nerve stimu- MRI showed an extensive leptomeningeal (mainly intraventricular) lation and single-fiber EMG were normal and antiacetylcholine receptor and intramedullary dissemination. A second (systemic) neoplasm was antibodies were negative. Intravenous immunoglobulin therapy was excluded, and the CSF was negative for neoplastic cells. The patient performed, without immediate results. Two weeks later, there was only a was treated with Bevacizumab 10 mg/kg every 14 days, and later 15 slight improvement in eyelid ptosis, but a recrudescence of lower spastic mg/kg every 21 days. Before he could begin this treatment there was a paraparesis. After the beginning of adjuvant chemotherapy, a marked VPS dysfunction, with excessive diurnal hypersomnia and gait improvement was observed. apraxia. He transiently improved after the 7th cycle of bevacizumab, Conclusion: This case illustrates the importance for physicians to but remained clinically stable afterwards with mild confusion and maintain a high index of suspicion for paraneoplastic syndromes in hypersomnia, memory loss, left hemiparesis and gait apraxia. Given patients presenting with unusual neurological symptoms with no obvious the clinical stability, treatment was continued until the 16th admin- cause. It also shows how systemic oncology treatment can improve the istration, when his neurological status worsened and he became paraneoplastic symptoms mainly in the beginning of the disease. totally dependent to daily living activities. He survived 20 months after the diagnosis of DLH. Discussion: We report the rare occurrence of DLH, treated with bevacizumab, with prolonged clinical and radiological stability. P789 Given the rarity of this entity, the most adequate treatment remains to Relevance of occludin to the development be determined, but a phase II study regarding bevacizumab in of the peritumoural oedema in the brain tumours recurring or unresectable hemangioblastomas is underway. C.H. Kim, J.H. Cheong, J.M. Kim Hanyang University, Guri Hospital (Guri, KR) Infection Objectives: Most brain tumours accompany peritumoral edema (PTBE), which is influenced by various factors. PTBE can be developed because brain tumours have a leaky endothelial tight junctions (TJs). TJs comprise protein such as, occludin and claudin. P791 We investigated the relationship between PTBE volume and occludin Differential diagnosis of ischaemic and inflammatory expression in brain tumours. myelopathy – a retrospective study Methods: Sixty-one patients who underwent surgery provided specimens. The expression of occludin in each specimen was M. Sokolova, J. Malisova, O. Zapletalova, D. Skoloudik evaluated by Western blot analysis. PTBE volume was calculated by University Hospital Ostrava (Ostrava, CZ) using preoperative magnetic resonance imaging, and then, corre- Differential diagnosis between ischemic and inflammatory myelopa- lated to occludin expression in each pathology of brain tumour thy is in early stage of disease problematic. The aim of the statistically. retrospective study was to compare the findings in cerebrospinal fluid,

123 S218 J Neurol (2012) 259 (Suppl 1):S1–S236 in blood, magnetic resonance imaging (MRI) findings and clinical Conclusions: VZV usually involves the dorsal root ganglion and course of disease in patients hospitalized in Department of Neurology the respective dermatomes. Our case suggests the involvement with ischemic or inflammatory myelopathy during 4 years. of simultaneous involvement of central and peripheral nervous sys- Methods: Patients with diagnosis of ischemic myelopathy and tems and extends the range of phenotypes associated with VZV inflammatory myelopathy were retrospectively studied. Values of infection. C-reactive protein (CRP), blood count, findings in cerebrospinal fluid, spinal MRI and risk factors of atherosclerosis were statistically evaluated to find differences between patients with ischemic and inflammatory myelopathy. P793 Results: Thirty patients (16 males, age range 13 – 78 years, mean Stroke secondary to neurosyphilitic vasculitis age 48.2 ± 18 years) were included to the study. Diagnosis of inflammatory myelopathy was done in 20 patients (8 males, mean in an HIV/AIDS patient age 46.4 ±15.7); ischemic myelopathy was detected in 10 patients M. Rickard, S. Iyadurai (6 males, mean age 53,4±23.0 years). Totally, 89 % of patients with Saint Louis University (St. Louis, US) ischemic myelopathy but only 35 % of patients with inflammatory Objective: To describe a case of CNS Syphilis as a cause of large- myelopathy was admitted to the hospital within 24 h after symptoms vessel stroke in a newly-diagnosed HIV/AIDS patient. onset. No significant differences were detected in CRP value or Background: Occlusive vessel disease in young patients is usually blood count. Patients with inflammatory myelopathy have signifi- secondary to hypercoagulability risk factors. However, CNS infec- cantly higher level of proteins in cerebrospinal fluids (1.09 vs. 0.39 tions (including viral, bacterial, fungal, spirochete) can also present g/l, p=0.02) and non-significantly higher number of white blood 3 with similar findings. If not correctly identified and treated, such cells (199 vs. 37 per mm ,p[0.05). Typical MRI finding was in infections lead to significant morbidity and mortality. CNS syphilis 42 % patients with inflammatory myelopathy and in only 22 % of has been associated with perivascular inflammation, cerebrovascular patients with ischemic myelopathy. Diabetes mellitus, myocardial thrombosis, vessel occlusion, ischemia and infarction. Here we report infarction and arterial hypertension in medical history were signif- the successful and timely treatment of a young patient who presented icantly more frequent in patients with ischemic myelopathy with a large vessel stroke, with eventual diagnosis of CNS syphilis. (p\0.05) Methods: Case Report. Conclusions: Combination of MRI findings, cerebrospinal fluid Results: A 33-year old man with recent diagnosis of HIV/AIDS findings and patients history can help in differential diagnosis presented to the emergency department with a 2-month history of between ischemic and inflammatory myelopathy. personality change, depression, and new-onset syncope. Examination revealed fluctuating mental state, left-sided weakness, left hemi- neglect and right-gaze deviation. MRI brain revealed a right MCA P792 distribution infarct. MRA revealed complete occlusion of the right Foot drop and urinary retention following disseminated MCA, and stenosis of the right proximal ICA. Laboratory examination revealed a low CD4 count of 42, HIV viral load of *1 million Varicella zoster infection copies, positive serum RPR, elevated ESR (141 mm/hr) and CRP S. Damodaram, S. Iyadurai (3.4). CSF studies revealed 2 WBC, 10 RBC, normal glucose, and Saint Louis University (St. Louis, US) elevated protein. CSF VDRL and FTA tests were positive. A diagnosis of neurosyphilitic vasculitis was made. Upon treatment with Objective: To report a rare case of varicella zoster virus (VZV) Penicillin G for 14 days, the patient’s symptoms improved infection with involvement of both central and peripheral nervous significantly. systems, in an immunocompromised host. Conclusion: Here we present a case of a young man without Background: VZV usually causes root-limited sensory-cutaneous any hypercoagulability risk factors, with HIV/AIDS, with occlusive dysfunction. Motor dysfunction secondary to vasculitis/vasculopathy large vessel infarcts secondary to syphilitic infection. Our case has been rarely reported. However, nerves of the lower limb and the highlights the need for detailed evaluation of etiologies underlying sacral spinal cord are usually spared. large vessel strokes (including CSF), when such unusual stroke Methods: Case Report findings are present, so that appropriate and early treatment can be Results: A 73-year old woman with 5-year history of chronic initiated. lymphocytic leukemia, prior history of chickenpox and oral herpes infections, was seen with complaints of 2-week history of ‘‘foot drop’’. A month prior, she noticed a rash on the left forehead followed by a similar rash in areas involving the trunk and right axilla. No significant pain was reported. A week later she developed right leg P794 pain beginning in the buttock region extending to lateral thigh and leg Typical clinical presentation and broad spectrum on right and had difficulty walking. She also reported that she was not of MRI findings in general paresis due to neurosyphilis able to empty her bladder. Examination revealed multiple healing erythematous lesions in face, trunk, arms, and in the right leg and in a HIV-negative patient weakness in peroneal-innervated muscles on the right. Urinary R.S. Scalco, R.B. Soder, L.O. Rosa, L.C.P. Marrone, retention was confirmed by increased post-void residual volumes. J.V.L. Martinez, J. Becker Lumbar puncture revealed a white count of 275, elevated VZV IgG Pontificia Universidade Cato´lica do Rio Grande do Sul (Porto and HSV-IgG, EBV PCR positivity. MRI of the thoracic and lumbar Alegre, BR) spine was unremarkable. Right peroneal motor and superficial peroneal sensory were absent on the right. PCR performed on material Objectives: review and a case report of clinical and Magnetic from the facial lesion was positive for VZV and the patient was Resonance Imaging (MRI) abnormalities suggesting neurosyphilis started on acyclovir and gabapentin. Urinary retention was treated infection. with intermittent catheterization. Methods: case report.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S219

Results: A previously health 38-year-old female presented with a greater in the HIV-uninfected than -infected group (57.1 % vs. 3-month history of cognitive and behavioral abnormalities associated 32.1 %, resp.) (32.1 %); and more HIV-infected children scored in with aphasia and sensory ataxia. Her symptoms were progressively the borderline intellectual function or below range (35.7 % vs. worsening over the last month associated with severe disability. 17.9 %, resp.); these differences were not statistically significant. Neurological physical examination showed spasticity, sensory ataxia, Children with advanced HIV infection (CD4 cell count \ 100 aphasia, tetraparesis, behavioral abnormalities and exaggerated deep cells/ll) had lower IQ scores and verbal performance than children tendon reflex. Lumbar puncture showed positive VDRL (1/32) and with less-advanced HIV infection, but these differences were not positive FTA. Abs. Serum VDRL was found to be reactive (1/64). statistically significant. Verbal test scores were negatively correlated HIV testing was negative. Axial and coronal T2-weighted brain MRI with HIV viral load (R=- 0.424, p=0.024). images showed severe cortical atrophy, significantly worse in fron- Conclusions: HIV infection was associated with lower IQ scores in totemporal lobes and mesiotemporal structures. Axial FLAIR images Peruvian children. The comparison group of HIV-uninfected children, demonstrated patchy subcortical hyperintensities in bilateral fronto- who were exposed to HIV in uterus, strengthened our ability to temporal lobes, extending to anterior and mesial temporal lobe exclude many potential confounding demographic and socioeconomic structures. Axial and sagittal FLAIR images revealed hyperintensities factors. The associations between lower cognitive functioning and involving bilateral periventricular white matter and corpus callosum. advanced HIV infection are not surprising, but emphasize the need for Treatment for neurosyphilis was started and she was discharged when cognitive therapies for HIV-infected children in developing countries. partially improved. Support by Fogarty International Program and Washington Conclusion: It is important to rule out neurosyphilis even in University. patients without HIV infection. Clinical abnormalities and MRI scan of this case strongly suggest neurosyphilis. MRI findings may help in the differential diagnosis of behavioral abnormalities and general paresis. Cortical atrophy is the commonest manifestation in neuro- P796 syphilis general paresis, with important involvement of the frontotemporal lobes and mesiotemporal structures. Additionally, on Clinical isolated syndrome? Brainstem encephalitis T2-weighted images, neurosyphilis general paresis is characterized by caused by Lyme borreliosis: a case report patchy subcortical hyperintensities in frontal and temporal lobes, J. Laskovska, U. Hofstadt-van Oy, S. Schimanski, which might be related to gliosis. M. Strotzer, P. Oschmann Klinikum Bayreuth (Bayreuth, DE) Early diagnosis of clinical isolated syndromes (CIS) as first mani- P795 festation of multiple sclerosis is crucial to initiate early Intellectual quotient score comparison between immunomodulatory therapy, but diagnostic procedures like magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) HIV-infected and HIV exposed children at a national analysis are mandatory to diagnose alternate causes of inflammatory institute of child health, Lima, Peru central nervous system disease. Lyme disease caused by infection P.C. Martıńez, S.M. Montano, L. Kolevick, J. Flores, with Borrelia burgdorferi is endemic in northern hemisphere tem- V. Granados, J. Rodriguez, G. Sal y Rosas, J.R. Zunt perate regions and may cause encephalomyelitis which can be diagnosed by analysis of specific immune responses in serum and Instituto Nacional De Ciencias Neurolo´gicas (Lima, PE); United CSF. States Medical Research Unit (Callao, PE); Instituto Nacional De Case report: A 39 year old man developed a painless gradually Salud Del Ninõ (Lima, PE); Washington University (Seattle, US) increasing hemihypaesthesia, a week later double vision and unstable Objectives: Pediatric HIV (human immunodeficiency virus) enceph- gait. The patient never noted a tick bite or erythema and was pre- alopathy includes motor and cognitive deficits and can result in poor viously healthy. On admission unilateral sixth nerve palsy, a school performance, borderline intelligence or mental retardation. We contralateral hemisensory deficit and Babinski sign and slight sen- compared intellectual quotient (IQ) in HIV-infected and -uninfected sory ataxia were found. MRI demonstrated a single gadolinium children in Peru and examined the relationship between verbal and enhancing lesion in the pontomesencephalic junction, no other executive function with clinical stage of HIV infection (CDC clas- cerebral or spinal lesions were found. The CSF displayed a lym- sification), HIV viral load, CD4 cell count and other potential risk phocytic pleiocytosis of 21 cells/ll, and oligoclonal bands. factors. Antibody-serum indices (ASI) for measles, rubella and varicella Methods: We evaluated 28 HIV-infected children and 28 HIV- zoster virus were negative. CIS was suspected and a steroid pulse uninfected children matched for age and gender. The majority of initiated with no clinical response. Further analysis of serum and HIV-uninfected children were exposed to HIV during pregnancy but CSF revealed Borrelia-IgG and IgM with an IgG-ASI of 3.76 and did not become infected. Neuropsychologic testing included the intensive banding of the CSF for several Borrelia antigens (p100, Wechsler-Revised (WPPSI-R) for children between 3 - 7 years and 3 VlsE, p58, p41, p39, OspC, p18). A brainstem encephalitis due to months, and the Wechsler Third Edition (WISC-III) for children older borreliosis was diagnosed and i.v. Ceftriaxon given for 14 days. than 7 years and 4 months. Clinical records were reviewed to obtain Symptoms resolved completely, the CSF displayed no further plei- medical history, clinical and demographic data. T-test and Pearson’s ocytosis or oligoclonal bands six weeks later. On follow up for six correlation (R) were used to compare groups. IQ score was catego- months no clinical or MRI relapse was noted. rized as average or above (score[90), low average (score 80-89), or Conclusion: Isolated brainstem encephalitis due to infection with borderline intellectual function or below (score \ 80). Borrelia burgdorferi was reported in the literature very rarely. Results: The average IQ score among HIV-infected children was Because symptoms of Lyme disease can vary widely and can be lower than in HIV-uninfected children (84.6 vs. 91.7, p =0.05). This successfully treated with antibiotics, a serum and CSF analysis with difference was driven by the verbal sub test (81.2 vs. 90.3, p =0.05). search for specific antibodies against Borrelia is indicated even in The percentage of children with an average IQ score or higher was oligosymptomatic cases of so called CIS.

123 S220 J Neurol (2012) 259 (Suppl 1):S1–S236

P797 progressing left hemiparesis and two tonic–clonic seizures. There What’s happening to my wife? Psychological was no history of fever, headache or other neurological complaints. Apart from a chronic lympho-thrombocytopenia and a recent aug- impairment as isolated manifestation of deep cerebral mentation in LDH, blood workup didn’t reveal major changes, venous thrombosis in aseptic meningitis including ACE activity. The MRI showed 3 round T2-hyperintense A. Galiana-Ivars, S. Fernańdez-Meneńdez, B. Cabezas- lesions in the brain parenchyma with vasogenic oedema, localized Delamare, L. Redondo-Robles, A. Are´s-Luque mass effect, ring enhancement and restriction in diffusion, raising SACYL (Leoń, ES) differential diagnosis between sarcoid granulomas and abscesses. During the following day, the patient deteriorated rapidly with Objectives: Vascular complications are increasingly uncommon pro- progressing drowsiness, appearance of fever and development of cesses in the context of central nervous system infectious diseases due leukocytosis and elevated C-reactive protein. CSF cytochemical to early diagnosis and initiation of antibiotic treatment. The devel- parameters were normal. One blood culture was positive for Listeria opment of neuroimaging techniques has contributed significantly to monocytogenes, supporting the hypothesis of brain abscesses. The their early recognition and treatment and has improved their patient completed 45 days of Ampicillin (associated with Genta- prognosis. micin during the first week) with significant clinical and radiological Methods: A 47 year old woman was evaluated at the Emergency improvement. He was discharged with a moderate left hemiparesis Room because her husband found her with strange behavior, apathy without other neurological deficits. and language impoverishment over the last 48 h. Her past medical Literature Review: Listerial infection presenting with multiple history was unremarkable otherwise iron deficiency anemia secondary brain abscesses is rare (less than 30 cases reported). It is associated to uterine fibroids, without other medical or surgical history of interest with general medical conditions and therapies compromising the or usual treatment. The neurological examination showed fever, neck immune system. Despite sarcoidosis may confer susceptibility to stiffness, apathy and monosyllabic but adequate response to questions other CNS infections (JC virus, Cryptococcus), we found only two from the clinicians. No focal neurological deficit was seen and no reports of a single Listerial brain abscess associated with this disease. other findings stand out. Ancillary tests showed a severe microcytic Conclusion: As far as we know, this is the first reported case of anemia and a turbid cerebrospinal fluid with pleocytosis (448 poly- multiple Listerial brain abscesses in a patient with sarcoidosis. The morphonuclear leukocytes/mm3), hyperproteinorrachia (358 mg/dL) dysfunction of cell-mediated immunity (including lymphocytopenia and discrete glucose consumption. Bacterial meningoencephalitis was caused by bone marrow involvement, hypersplenism and redistribu- suspected and empirical antibiotic treatment was initiated. Magnetic tion of cells to sarcoidosis granulomas) and the corticosteroid resonance imaging showed signs suggestive of incomplete deep treatment may have contributed as susceptibility factors to this venous system thrombosis, with edema in the corpus callosum, cau- infection. date nucleus and thalamus. Oral anticoagulation was started at that moment. No pathogenic microorganisms were isolated on cultures and serologies and PCR examination for neurotropic viruses were negative. At discharge the patient had severe apathy and delayed, P799 immediate and working memory deficits. Two months later the Imported leprosy with neural involvement: a case patient was almost recovered, with patent improvement in resonance report imaging findings. M. Pedraza, P. Mulero, A. Hernańdez-Lain, C. Cruz, Results and conclusion: Deep cerebral venous thrombosis is a serious complication, probably under diagnosed, of central nervous M. Pin˜ero, A.L. Guerrero, C. Hinojosa, A. Cabello system infections. Behavioral symptoms can be its main clinical University Hospital (Valladolid, ES); Hospital 12 de Octubre presentation. We advocate the importance of high yield neuroimaging (Madrid, ES) in cases of meningitis with atypical neurological manifestations. Objectives: Leprosy is a common cause of peripheral neuropathy, especially in developing countries. As skin lesions may be absent or atypical, we should take into account that it is the most frequently treatable form of peripheral neuropathy worldwide. We aim to report P798 an imported case with a predominantly neural form, emphasizing on Multiple brain abscesses caused by Listeria its challenging diagnosis and response to therapy. Methods: A 19 year-old male who immigrated from Mauritania 4 monocytogenes in a sarcoidosis patient treated years before presented with a 2-year history of progressive sensory with corticosteroids loss and motor involvement in distal limbs. Neurological exam A.S. Aleixo Correia, J. Silvestre, S. Calado, R. Miguel, revealed normal cranial nerves, asymmetric weakness in upper limbs, P. Soares, J. Vale, P. Alegria especially in left ulnar-innervated intrinsic hand muscles with atrophy. There was mild distal weakness in lower limbs, diminished light Hospital Egas Moniz (Lisbon, PT); CEDOC, Universidade Nova de touch sensation in both hands, a burn injury in left hand, and areflexia Lisboa (Lisbon, PT); Hospital Beatriz Aˆ ngelo (Loures, PT) throughout left upper extremity and hyporeflexia otherwise. Nerve Objectives: To report a rare presentation of infection by Listeria thickening or enlargement was not detected. We found no skin lesions monocytogenes with multiple brain abscesses in a sarcoidosis patient in face or limbs, but two hypopigmented patches in trunk, with no under corticotherapy. preserved sensation. In nerve conduction study moderate to severe Methods: We present the clinico-radiological evolution of the case diffuse motor and sensory dysfunction with mixed demyelinating and and review the MEDLINE literature on CNS abscesses due to axonal features. A sural nerve biopsy was performed revealing peri- Listeria. vascular inflammation, diffuse lymphocytic infiltration in Results: Case Report: A 41-year-old man with a long standing endoneurium and perineurium, and many rods in macrophages, corticosteroid-dependent systemic sarcoidosis (lung, skin, liver, positive with Fite-Faraco staining. spleen and bone marrow) without neurological involvement, under Results: Our case report can be classified as a Multi Bacillary 60 mg/day of prednisolone, was admitted with a three-day history of leprosy, according to World Health Association (WHO), and an

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S221 intermediate form according to Ridley-Jopling system. Due to a P801 rapidly progressing nerve involvement and atypical skin lesions a Pseudo-Horner’s syndrome nerve biopsy was required for the diagnosis. Treatment was immediately initiated using a multibacilar approach (Dapsone 100 mg and J. Pinto, J. Carvalho, C. Nunes, C. Paiva, R. Veiga, R. Pais Clofazimine 50 mg daily plus Rifampicin 600 mg and Clofazimine Centro Hospitalar de Coimbra (Coimbra, PT) 300 mg monthly), with neither adverse effects nor leprosy reactions. Horner´s Syndrome or occulosympathoparesis, is a costellation of The patient experienced a strength and sensitive improvement except signs resulting from an interruption of the sympathetic innervation of for the left ulnar atrophy at baseline. the eye and ocular adnexa. Classicaly, the clinical findings include Conclusion: Leprosy is to be considered in patients from endemic ptosis, pupillary miosis and facial anhidrosis. They can be subtle, areas with nervous peripheral system involvement. In the small pro- hiding other pathologies that do not result from an interruption of portion of patients with suspected leprosy and no anesthetic patches, a sympathetic innervation. nerve biopsy may be required. Diagnosis and early treatment prevents We describe the clinical picture of a seventy-four year old further nerve damage and lead to clinical improvement, unless nerve female admitted in the Neurology’s department with a clinical damage is already present. picture characterized by a right eye ptosis, ipsilateral miosis and enophthalmia, with normal pupil reaction, associated with eyelid heaviness, predominantly in the morning, and significant weight loss with six months’ evolution. In the past medical history we could observe a dorsal herpes zoster infection coined with the beginning Neuro-ophthalmology of the clinical picture. The complementary exams, in order to advise on the possible aetiology of the picture, were brain and cervical CT- angiography, brain MRI and chest CT. They were normal, excluding P800 the possibilities of Pancoast tumor, carotid dissection and cavernous sinus injury, which had initially been placed. Subsequent Ophthal- Pourfour du Petit syndrome due to nodular thyroid mology observation revealed the presence of iridolenticular hyperplasia synechiae in the right eye and angular blepharitis, interpreted as R. Manso sequelae of probable herpetic infection. After local cortico and an- University Hospital (Salamanca, ES) tibiotherapy associated with local synechiolisis with mydriatics, there was progressive clinical improvement and partial withering Objectives: The classical signs of Pourfour du Petit syndrome away of the mentioned signs. (PDPS) are exactly the opposite of those of Horner Syndrome (HS) The diagnosis initially placed of Horner´s Syndrome, proved to be and comprise mydriasis, lid retraction and exophthalmos. It is pro- fallacious. The sequelae of an old ocular herpetic infection simulated duced by stimulation of the ipsilateral sympathetic cervical chain an Horner. We emphasize the importance of a detailed medical his- and has the same causes as HS. Some cases have been reported tory and a careful examination guided by it, in the presence of following intracranial aneurysms, non-penetrating injuries of the anisocoria with normal pupillary reaction, the differentiation between cervical sympathetic chain and brachial plexus, post-traumatic a physiological anisocoria and Horner’s Syndrome. syringomyelia, severe cranioencephalic trauma, aortic malformation, thoracic tumors (first rib condrosarcoma, esophagus carcinoma and lung carcinoma), and maxillofacial surgery (parotidectomy, mandible tumor resection). We report a patient with PDSP due to P802 nodular thyroid hyperplasia. A man who sees static Methods: A 38 year-old men presented with episodes of right F. van der Toorn, T. Schreuder blurred vision, without headache or ocular pain. Looking in a mirror, he could see a protrusion of his right eye and that his right pupil was Department of Neurology (Heerlen, NL) larger than the left. On neurologic examination, the patient exhibited Background: Persistent visual aura without infarction is rare. Visual a difference in pupillary widths, 4 mm in light and 2 mm in darkness. aura symptoms persisting[1 h are uncommon, and infarction should Cocaine (10 %) testing revealed no dilation lag. The position of the be ruled out when these symptoms do not resolve. If imaging is right upper lid was 2 mm higher than that of the left upper lid, the normal, the terms ‘persistent aura without infarction’ or ‘persistent right eye with proptosis. Direct, consensual light reaction and visual disturbance (PVD)’ are applied. This condition is often the pupillary near reaction were normal for both eyes. The optic discs refractory to treatment. showed no oedema. Visual acuity, near and distant, was 20/25 in both Case report: A 65-year-old man presented with a 3-month history eyes. The eye movements were adequate in all directions. There was of visual disturbance (VD). At first he had short spells of VD with no abnormal sweating response. The rest of the neurological exami- hundreds of black and white dots in his entire visual field, like ‘visual nation was normal. snow’ or ‘static’ for 10-15 min, but since a couple of weeks it was Results: Laboratory data including thyroid function tests were persistent. He had headache attacks that evolved into a continuous within the normal limits. The chest x ray and computerized tomog- headache with periodic exacerbations. Neurological and ophthalmo- raphy (CT) also were normal. A magnetic resonance imaging (MRI) logic examination was completely normal. study was unremarkable. A cervical ecography demonstrated two Computed Tomography (CT)of the brain was normal. Laboratory thyroid nodules in the right lobe, which measure 2 cm each one. The results, including testing for paraneoplastic antibodies, were nor- patient was treated with total thyroidectomy one year later. mal. He was treated with aspirin, a calcium channel blocker, The pathology exam was reported as a nodular thyroid hyperplasia. acetazolamide, and lamotrigine without effect on his visual symp- The ophthalmic signs persisted but had improved. toms. His headache, however resolved almost completely. Conclusion: PDPS often could remain unrecognised, especially Conclusion: Persistent (visual) aura symptoms should prompt when the signs are minor or transient. Awareness of PDPS could suspicion of migrainous infarction. If there is no evidence of infarc- support earlier detection of sympathetic disorders and the underlying tion on imaging, and aura symptoms persist [1 week persistent aura etiology. without infarction is diagnosed. Persistent VD can last for days-years

123 S222 J Neurol (2012) 259 (Suppl 1):S1–S236 and doesn’t respond as well as headache does to different types of the subjects by putting a foot board against their soles. VOR was migraine- prophylactic drugs. analyzed using electronystagmography. The oxygenated cerebral hemoglobin changes before and after the somatosensory stimulation were calculated using NIRS. Result(s): The rapid phase eye velocity (RPEV) elicited by caloric P803 stimulation was suppressed by somatosensory stimulation. The High hyperopia and demyelinating disease: is there any amount of oxygenated hemoglobin increased on the parieto-tempo- association or just a coincidence? ral(parieto-insular vestibular cortex?) lobe bilaterally by the active- G. Genç, T. Akin, S.. Demirkaya somatosensory stimulation, but it was dominant ipsilaterally. Conclusion(s): 1. Omnipause neurons(OPNs) are thought to Maresal Cakmak Military Hospital (Erzurum, TR); Gulhane Medical control a number of oculomotor behaviors, especially in rapid-phase Faculty (Ankara, TR) VOR. OPNs inhibition originates from the superior colliculus (SC). Introduction: Hyperopia is a defect of vision causing difficulty The excitatory effects from the SC are concealed by inhibitory input focusing on near objects. Coexistence of high hyperopia and demy- from OPNs and the SC activation is disclosed when this inhibition is elinating disease of central nervous system (CNS) have been not removed by a pause in OPN activity at the beginning of RPEV. The reported in the literature. We aimed to present a patient with demy- RPEV from the SC to burster-driving neuron may be augmented by elinating disease and high hyperopia, and discuss if there is any vestibular signals. It is suggested that the active-somatosensory association. input may enhance the activity of SC, OPN, and inhibit the RPEV w?>Case report: A 20 year-old man was admitted to our hospital via the central vestibular cortex. 2. The present study suggests that with the complaints of weakness of left lower limb, gait imbalance for NIRS is useful for confirming the existence of neural linkage in one year and visual impairment, since his birth. Neurologic exami- cerebral cortex between the vestibular cortex and somatosensory nation revealed marked dysarthria, right central facial paralysis, input. ataxic gait, bilateral Babinski sign. Brain MRI revealed hyperintense lesions in the supratentorial periventricular lesions on the T2 weighted images, cortical atrophy, thinning of the corpus callosum and reduction in the size of bilateral bulbus oculi. After ophthal- P805 mology consultation high hyperopia (right 15.25 D, left 16.00 D) was Deformable anatomic templates embed information diagnosed. He was given high dose methylpredniolone therapy for 5 on eye movement disorders into brain images days, but no improvement was observed. He was given physiotherapy V. Kumar, L.A. Hayman, A. Wong, R. Tang, J. Schiffman and is still going on physiotherapy. M.D. Anderson Cancer Center (Houston, US); Anatom-e (Houston, Conclusion: Despite the frequent occurrence of visual impairment US); University of Toronto (Toronto, CA); University of Texas in demyelinating disease such as multiple sclerosis, it should be kept (Houston, US) in mind that visual impairment can result from ophthalmologic pathologies such as hyperopia or myopia. Therefore neurologists Objective: This study evaluated the ability of a computer anatomical should perform the ophthalmological exam very carefully to make the atlas, Deformable Anatomical Template (DAT) to predict the type of diagnosis correctly. The concurrence of both conditions in the same eye movement disorder based on the location of the lesion. patient may be coincidentally, or some reports may put forth the Methods: Each of the three neuro-ophthalmology authors (RT, relationship in the future. AW, JS) contributed 10 cases of eye movement disorders which had positive neuroimaging studies. The anatomic distribution of abnormalities included: 7 cortical lesions (3 frontal eye fields, 2 parietal eye fields, 2 middle temporal), 6 cisternal lesions (3 cranial nerve III and 3 P804 cranial nerve VIII), 5 cerebellar (2 vermian, 1 fastigeal nucleus, 2 A study of vestibular-somatosensory interaction flocculus) and 12 brainstem lesions. The neuroradiology authors (VK, with a near-infrared spectoroscopy LAH) manually fit an annotated set of DAT onto each case and H. Yamamoto, M. Iida recorded the predicted movement disorder. Results: DAT was successfully overlaid on each of the 18 clinical Tokai University (Isehara, JP) cases with abnormalities outside of the brainstem. DAT generated Objective: The aim of the present study with a near-infrared spec- correct predictions of defective eye movements in all these cases. troscopy(NIRS) is to evaluate the correlation of the vestibule-ocular Overlay of DAT onto the brainstem lesions in the 12 cases approxi- reflex(VOR) and the somatosensory input. mated the lesion locations well enough to predict the type of defective Method(s): The present subjects consisted of five healthy young eye movements. adults with no known neuro-otological disorders. A holder of NIRS Conclusion: This study validated the DAT anatomical atlas and system was installed in the parieto-temporal region of both sides of alignment process for localizing the expected position of cortical, the subjects. Caloric stimulation was achieved in the subjects by cisternal and cerebellar lesions. It also approximated the location of irrigating the left external ear canals with 5ml of cold water(4 C) for small brainstem areas and provided useful information on possible 5 s, while the subjects lay in a supine position with eyes closed. consequences of all lesions. DAT provides a greater understanding of During the nystagmus, active-somatosensory stimulation was given to eye movement disorders.

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S223

Author Index

Abete, M...... O332, O335 Ambrosi, B...... P756 Barata, P...... P788 Abolfazli, R...... P474 Ambrosoni, E...... P510 Barber, A...... P663 Abou Alfa, A...... P693 Amini, G...... P615 Barca, E...... P761 Abramenko, Y...... P629 Aminzadeh, M...... P702 Barcella, V...... P464, P720 Abreu, V.H...... O235 Ances, B.M...... P395 Barker, R...... P409 Absinta, M...... O193, O197, Andersen, H...... O271 Barkhof, F...... O218, O220, O290, O281, O290, O331 Ando, Y...... P515 P337, P349, P471 Abu-Amero, K.K...... P689 Andreadou, E...... P371, P600, P719 Barna, G...... P784 Acunã-Castroviejo, D...... P539 Angelini, C...... P680, P754, P768 Baroń,J...... O333, O335, P621 Adamec, I...... P582 Angelova, P...... P537 Barone, P...... 47 Adobbati, L...... P483 Ann Marrie, R...... P701 Barraza, G...... O321 Aghamolaee, V...... P593, P704 Annovazzi, P...... O216 Barraza-Sandoval, G...... P521 Agosta, F...... O204, O205, O230, O237, Annunziata, P...... P358, P482, P707 Barreiro-Pe´rez, M...... P617 O302, O326, O327, O329, Anoosheh, L...... P598 Barreto, R...... O268 P381, P545,P553, P554, P555, P659 Anprasertporn, P...... O213 Barros, P...... P505 Agrawal, C.S...... P673 Antel, J...... P348 Bartenstein, P...... P398 Aguiar de Sousa, D...... P636 Antik, A...... P695 Bartkova, A...... P374, P608 Ahmed, N...... O265 Antochi, F...... P384, P385, P495, P603 Bartolozzi, M...... P403 Ajena, D...... P512 Antoń,S...... P657 Ba´rtova´,P...... P408 Ajtay, A...... P619 Antonenko, K...... P607 Barun, B...... P582 Akdeniz, N...... P699 Antoniadis, D...... P710 Baruzzi, A...... O270 Akgun, B...... P380 Arai, M...... P630 Bassetti, C...... 147, O249, P425, P426 Akhmadeeva, L...... P771 Arce, N...... P431 Bassi, M.T...... P381, P553, P660 Akhtar Shomar, M.S...... O200 Are´s-Luque, A...... P440, P797 Basta, I...... P753 Akin, T...... P803 Arias, E...... P528 Bataller, L...... P758 Aksay-Koyuncu, B...... P484, P735 Arighi, A...... P660, P685 Batla, A...... O207 Aktas, O...... P358 Arinõ,H...... P521 Battaglini, M...... O290, P403, P727 Al Hindi, H...... P757 Arnold, D.L...... O288, O289, Battaglini, P.P...... P456 Al Homoud, I...... P757 P338, P340, P341, P459 Bauer, D...... O263 Al Muhaizea, M...... P757 Arnold, R...... O260, O261, P465 Baumgartner, C...... O224, O225 Al-Rawi, M.S...... P393 Asadi, M...... P598 Bayas, A...... P353 Al-Tamami, J...... P443 Asano, S...... O287 Baybas, S...... P360 Alazami, A...... P757 Ash, E...... P645 Baydemir, M...... P739 Alberti, D...... P512 Ashkenasi, A...... O251 Becker, J...... P549, P794 Albrecht, H...... P476 Atassi, N...... O301 Becker-Bense, S...... P396 Albus, K...... P675 Atea, C...... O335 Becser Andersen, N...... P666 Alcaˆntara, J...... P361 Aubourg, P...... 108 Bednarik, J...... O272, P640, Aldape, K...... O284 Auger, F...... O325 P694, P705, P706 Alegria, P...... P798 Aygu¨l,R...... P424, P623 Be´go-Le-Bagousse, G...... P462 Aleixo Correia, A.S...... P798 Aylloń,B...... O332, P621 Behjati, Z...... P703, P712 Alexopoulos, H...... P469 Azevedo, A...... P790 Bekmezci, Y...... P618 Alhusaini, S...... O226 Babo-Rebelo, M...... O236 Belachew, S...... O261, P465 Alladi, S...... P747, P749 Bahnasy, W...... P430 Beleza, P...... P447 Allen, J.C ...... P413 Bahri, M...... O236 Belic, A...... P456 Almeida, I...... P560 Bajenaru, O.. P384, P385, P495, P498, P603 Belletti, D...... P701 Alonso, M.E...... P661 Bajko, Z...... P523 Bellmann-Strobl, J...... P709, P718 Alorainy, I.A...... P688, P689 Bakay, R.A.E...... O231 Beloradkova, J...... O272 Alsharoqi, I.A...... P767 Bakhtiary, M...... P427 Belousov, S...... P769 Altieri, A...... P442 Baklavajyan, M...... P567 Belova, A...... P579 Altindag, E...... P367, P484, P618, P730 Bakos, M...... P783 Bender, A...... O312 A´ lvarez, M.J...... P433 Balakrishnan, R...... 160 Benedetti, S...... O304, P553 Alvarez, V...... O199, O264 Balasa, R...... P523 Benedict, R.H.B...... P717 Alves, D...... O241, O277, P386, Balgera, R...... O216 Benesova, Y...... P706 P387, P568, P683, P684 Balint, B...... P564 Beniczky, S.A...... P666 Alves, I...... O268 Baloyannis, S...... P532 Benito-Martıń,E.M...... P617 Alves, L...... P654 Balteau, E...... O239 Bense-Becker, S...... P398 Amaral-Silva, A...... P361 Balthazar, M...... P531 Benussi, L...... O327, P541 Amaravadi, L...... P342 Bandaru, V...... P747, P749 Benuzzi, F...... P649 Amaro, S...... P750 Banfi, P...... P510 Benyakov, O...... O233 Amatachaya, S...... P776 Baquer, N...... P451, P570 Benzinger, T.L.S...... O234, O324, P395 Amato, L ...... P356 Bar-Or, A...... O217, P337, P459 Berardelli, A...... O243 Amato, M. . O193, O197, O216, P403, P727 Baranı´kova´,Z...... P404 Beratis, I...... P655

123 S224 J Neurol (2012) 259 (Suppl 1):S1–S236

Bereczki, D...... P619 Brandt, A.U...... O211, P711, P718 Capello, E...... O216 Beres-Molnar, K.A...... P783, P784 Brandt, T...... P392 Capobianco, M...... O216 Beretta, E...... O281 Bravo, G...... P525 Cappa, S.F...... O237, O326, O327, Bergamaschi, R...... O216 Brayne, C...... P409 O329, P541, P659 Bergvall, N...... P345, P346 Breen, D...... P409 Caputi, N...... P650 Berilgen, M.S...... P380 Bregman, N...... P645 Caputo, D...... P555 Beris, A...... P775 Brescia Morra, V ...... P356 Cardani, R...... O275, P756 Berman, M...... P467 Bresolin, N...... O327, P541, P544, P552, Cardoso, F...... O273, P511 Bernati, T...... P652 P602, P660, P685, P691 Carita, P...... P462 Bertini, E...... O304 Bresson, D...... P364 Carlino, M...... P528 Bertotti, A.C...... P695 Brichant, J...... O236, O239 Carod-Artal, F.J...... O330 Besharat, M...... P599 Briggs, A...... P462 Carrascal, Y...... P431 Bhatia, K...... 104, O207 Brinar, V...... O288, P338, Carrasco, S...... P433 Bhattacharya, P...... O295, P565 P340, P341 Carrilho Romeiro, A.M...... P744 Bianchi, A...... O216 Britton, J ...... P601 Carter, S...... O235 Bianchi-Marzoli, S...... O212 Broccoli, V...... 106 Carvalho, J...... P801 Bianco, M...... P697, P698 Brooks, D.J...... 113 Carvalho, R...... P616 Biasotta, A...... O334 Brozman, M...... O265 Casado, V...... O333 Bibani, R ...... P601 Brozova, H...... O229 Casimiro, M...... P790 Bichev, S...... P499 Bruijn, L...... O301 Caso, F...... O237 Bijarnia, M...... P336, P347 Brum, M...... P682, P744 Castan˜o Leon, A...... P493 Bikbulatova, L...... P771 Brunetti, A ...... P356 Castellani, C...... P382 Binetti, A.C...... P695 Bruno, G...... O327 Castellotti, B...... O292 Binetti, G...... O327, P541 Bruno, M...... O236, O239 Castro, A...... P467 Bir, L.S...... P715 Brynedal, B...... P585 Catteruccia, M...... O304 Biskup, S...... O277 Bryukhovetskiy, A...... O314 Cavallaro, T...... P507, P512 Bista, P...... P461 Bryukhovetskiy, I...... O314 Cazzagon, M...... O281 Bizzi, A...... O304 Bucalossi, A...... P707 Cemberci, C...... P625 Blahova Dusankova, J...... P717 Bu¨chner, B...... P443 Cendes, F...... P531 Blahuta, J...... P408 Bugalho, P...... P654 Cerami, C...... P541 Blake, D...... O240 Bugiardini, E...... O275, P756 Ceravolo, R...... P411, P416 Blanco, A...... P672 Buljat, G...... P696 Cerma´k,P...... P408 Blas-Boria, D...... P785, P786 Bulman, D...... O276 Cermakova, R...... P656 Blazey, T.M...... O234, O324, P395 Burnand, B...... O199 Cervantes-Arslanian, A.M...... O310 Bloomgren, G...... O260 Burns, J.D...... O310 Cesar, S...... P558, P671 Boegle, R...... P396 Burschka, J...... P714 Chabriat, H...... P364 Bohlega, S...... P757 Bursova, S...... O272, P640, Chamorro, A...... P750 Bojar, M...... P404 P694, P705 Chamova, T...... P499, P755 Boll, M.-C...... P661 Buskova, J...... O246 Champod, A.S...... P736 Bologna, M...... O243 Butzkueven, H...... O261, P465 Chand, P...... P423, P535 Boly, M...... O236, O239 Bwala, S.A...... P734 Chard, D...... O290 Bonakis, A...... O328, P647, P648, P655 Caballero, J.A...... P672 Charland-Vernille, V...... O239, O253 Bondy, M...... O282 Cabello, A...... P799 Chattopadhyay, M...... P546 Bonhomme, V...... O236, O239 Cabezas-Delamare, B...... P440, P797 Chaudhary, S.A...... P742 Bonnet, C...... 102 Cabrera, S.A.S...... O249 Chaudhry, I...... P688 Bonsi, R...... P541 Cabrera, S.G...... O249 Chen, L.M...... P562 Bonuccelli, U...... P411, P416 Cacabelos, P...... P437 Chen, R.W...... P388 Boonaurana, U...... P610 Caceres, M...... P420 Chen, W...... P394 Borasio, G.D...... P557 Cagnin, A...... O327 Chen, Y...... P376, P377, P390 Bordet, R...... O325 Cai, L...... P463 Cheng, L...... O253 Bordoni, A...... P691 Caiazzo, M...... 106 Cheong, J.H...... P789 Borislavova, V...... P766 Calabrese, D...... P507 Cherdak, M.A...... P529 Borisova, N...... P450 Calabresi, P...... O219, P337, P612 Cherenko, T...... P486 Born, A.P...... P732 Calabro`, R.S...... P534, P690 Cherninkova, S...... P499, P766 Bosco, A...... O216 Calado, A...... O257, P788 Chiapparini, L...... O304, P550 Boscoe, A...... P338 Calado, S...... P798 Chiasserini, D...... P612 Bo¨sel, J...... P513 Callejo, E...... O332 Chico Ponce de Leo´n,F...... P661 Boskovic, M...... P582 Calvo, A...... O302, P545, P554 Chieffo, R...... P697 Bosley, T.M...... P688, P689 Calvocoressi, L...... O282 Child, N...... P681 Bot, M...... O231 Campagnolo, D...... O262 Chin, P...... P350 Boveroux, P...... O236, O239 Campiotti, L...... P510 Chinnery, P...... O240 Boycott, K.M...... O276 Campos, B...... P531 Chio`,A...... O300, O301, Bozic, C...... O260, P466 Cantoni, C...... P602 O302, P545, P554 Bracchi, P...... O282 Canu, E...... O237, O326, P545, Chmielewski, A...... O215 Braine, M...... P508 P553, P554, P659 Cho, A.-H...... P363 Bramanti, P...... P534, P690 Cao, Z...... P394 Cho, B.H...... P611

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S225

Cho, J.H...... P765 Contardi, S...... P509 Datta, A...... P524 Cho, K...... P490 Cooper, M...... P631 Davaki, P...... P371, P600 Cho, K.H...... P611 Copetti, M...... O194, O205, O230, Davidovic, K...... O204, O230 Choi, B.-O...... P500, P501, P678, P679 O237, O331, P555, P587 Davis, B...... P708 Choi, K.H...... P611 Corbetta, S...... P756 Dawson, K.T. . . . . O258, O259, P457, P458, Choi, S.M...... P611 Cordici, F...... P534 P459, P460 Choraõ,R...... P665 Cordonnier, C...... O325 De Bleecker, J.L...... P759, P760 Christian, C...... P736 Cornelisse, P...... P470 De Federicis, L.S...... P651 Christiansen, I...... O271 Corra`,B...... P483 De Feo, D...... O331, P622 Christodoulou, K...... P506 Corrales, M.J...... P433 De Freitas, M...... O273, P511 Christou, Y.P...... P506 Correia, F...... P370 De Groot, J...... P785 Chung, K...... P500, P501, P678, P679 Correia, P...... P673 De la Cruz, C...... O335 Ciammola, A...... P442 Corros-Vicente, C...... P617 De la Hera-Galarza, J.M ...... P617 Ciccarelli, O...... O290 Corteguera, M...... P437 De Leucio, A...... O290 Ciccolella, M...... O304 Cortes-Santiago, N...... O283 De Paepe, B...... P759, P760 Cihelkova, S...... P404 Cortet Rudelli, C...... O252 De Reuck, J...... O325 Ciobanu, O...... P488, P498 Corti, P...... P429, P669, P691 De Riz, M...... O216, P602, P660, P685 Cioni, C...... P482 Corti, S...... P544, P552 De Rossi, N...... O216 Claro, S...... P487 Cortijo, E...... O330 De Santi, L...... P358, P482, P707 Claus, E.B...... O282 Corzo, C...... P487 De Se`ze,J...... O262 Clerici, F...... O327, P541 Cossburn, M...... O192, P584 De Stefano, N...... O220, O290, P403, Clot, P...... P463 Costa, A...... P538, P665 P471, P727 Cmejla, R...... 100 Costa, S...... P657 De Vera, A...... O219, P348 Coan, A...... P531 Coupand, S...... O276 Deecke, L...... P434 Coarelli, G...... O216 Coutinho, P...... P505 Degirmenci, E...... P715 Codeluppi, L...... P509 Couture, L...... O234 Deguchi, K...... O278 Codemo, V...... P680 Cree, B...... O262 Degueldre, C...... O236 Coeytaux, A...... P422 Cremer, M...... P348 Dei Cas, P...... P646 Cofield, S...... P708 Creus, K.K...... P759, P760 DelBo,R...... P544 Cohen, C...... P525 Cruccu, G...... O334 Del Carro, U...... P444, P697 Cohen, J...... O218, O288, O289, P338, Cruto, C...... P370 Del Prete, E...... P411 P340, P341, P349 Cruz, C...... O333, P799 Del Real, M.A...... P432 Colapietro, P...... O292 Cruz-Ramos, J...... P539 Del Saz-Saucedo, P...... P724 Coles, A.J...... O288, O289, P338, Csiba, L...... O265 Delanty, N...... O226 P340, P341 Cubina, G...... O227 Delgueldre, C...... O239 Colic, G...... P578 Cuciureanu, A...... P620 Dell’ Anno, M.T...... 106 Collins, J...... O300 Cuciureanu, D.I...... P620, P677 Della-Pace, I.D...... P453 Collins, W...... P349 Cudkowicz, M...... O301 Demarin, V...... O265 Colliot, O...... 111 Cumming, P...... P398 Demir, C.F...... P380 Colombo, B...... O194, O195, O203, Cunningham, H.L...... O285 Demir, R...... P424, P623 O291, O331, P400, P401, P485, Cursi, M...... O318 Demirkaya, S...... P803 P622, P627, P638, Custo´dio, P...... P788 Depireux, P...... P438 P697, P698 Cutter, G...... P344, P701, P708 Dera, T...... P392 Colombo, K...... O313 Cyran, C.A.M...... P396 Deramecourt, V...... O325 Colosimo, C...... O243 Czerny, D...... O267 Deretzi, G...... P588 Comi, G...... O193, O194, O195, O197, Czlonkowska, A...... O208, O256, O263, Derevyanko, H...... P641 O203, O204, O205, O212, O216, O265, P421 Deuschle, K...... P718 O218, O220, O221, O230, O237, O263, D’Onofrio, H.M...... P695 Devonshire, V...... P472 O281, O291, O302, O316, O318, D’Angelo, G...... P395 Dharmasaroja, P...... P610 O326, O327, O329, O331, P336, D’Amico, A...... O304 Di,H...... O253, P397 P347, P348, P349, P381, P382, da Conceiçaõ Teixeira, L...... P770 Di Donato, O ...... P356 P400, P401, P402, P405, P406, Dai, H.Y...... P561 Di Fabio, M.C...... O316, P780 P444, P464, P471, P485, P503, Dai, Z...... P391, P781 Di Giacomo, D...... P650, P651 P544, P545, P552, P553, P554, Daifu, M...... O222 Di Maggio, G...... P697, P698 P555, P586, P587, P622, P627, Dalakas, M.C...... P469 Di Piero, V...... P612 P638, P659, P691, P697, P698, Dalla Costa, G.. . . O203, O291, P622, P638 Di Stasi, V...... O270 P720, P725, P777, P780 Dalla Libera, D...... O203, O291, P485, Di Stefano, G...... O334 Comola, M...... O221, P777 P622, P638, P698 Diaconu, N...... P569, P604 Compston, A...... O288, O289, P338, Damasceno, B...... P531 Dichgans, M...... O266 P340, P341 Damjanovic, D...... P406 Dieterich, M. . . . . O210, P392, P396, P398 Confaloni, A...... O327 Damodaram, S...... P423, P792 Diez-Tejedor, E...... P716 Confavreux, C...... O263, O288, O289, Danesh-Meyer, H.V...... P681 Dill, P...... P524 P338, P340, P341 Danos, Z...... P619 Dimitriadis, K...... P443 Connin, S...... P646 Darańyi, M...... P619 Dimitrov, N...... O286, P492 Conrad, C...... O283, O284 Darmun, E...... P594 Dimitrova, M...... P723 Constantinescu, C.S ...... P601 Daskalov, M...... P516 Ding, J...... P412

123 S226 J Neurol (2012) 259 (Suppl 1):S1–S236

Ding, Y...... O279, O279 Fabo, D...... P639, P674 Fitzsimons, M...... O226 Dityatev, A...... 106 Fabrizi, G...... P507, P512 Florczak-Rzepka, M...... P365, P366 Dobrachinski, F...... P453 Fadaii, F...... P533 Flores, J...... P795 Doerr, J...... O211 Fadel, W...... P430, P430 Flores, S...... P431 Doherty, C...... O226 Faghihzadeh, S...... P596 Flo´rez-Munõz,J.P...... P617 Dolati, P...... O200, O214, O269, O320 Falautano, M...... O326 Flossdorf, P...... P491 Dollfuß, P...... O225 Falcone, M...... P552 Fogdell-Hahn, A...... P585 Domıńguez, J...... P432, P433 Falini, A...... O193, O194, O195, O197, Folyovich, A...... P619, P783, P784 Domke, S...... P476 O212, O237, O281, O302, Formenti, A...... O221 Donadio, V...... O270, O319, P643 O316, O326, O329, O331, P381, Fortin, K...... P472 Donadoni, C...... P552 P382, P400, P401, P402, P503, Fox, E.J. . . .O288, O289, P338, P340, P341 Dornˇa´k,T...... P608 P553, P554, P586, P627, P659, P780 Fox, R...... O258, O259, O262, P457, Do¨rr,J...... P709 Fan, D...... O303 P458, P701, P708 Doventas, Y...... P360 Fan, W...... P412 Franca, S...... O241, O277, P568, Drecun, M...... P514 Fanin, M...... P754, P768 P683, P684 Drislane, F.W...... P670 Faravelli, I...... P552 Franceschi, M...... O327, P541, P659 Drory, V...... O301 Fa¨rkkila¨,M...... O309 Francis, G...... O219, P344, P348, P350 Drulovic, J...... P405, P406 Farnikova, K...... O242 Franco, E...... P420 Duarte, J.M...... P695 Farrell, K...... P409 Frauscher, B...... O247 Dubois, M-F...... P525 Fartushna, O...... P745 Frederiksen, J...... O290 Dubovy, P...... O272 Fattori, F...... O304 Fredrikson, S...... P345, P346 Duda, P...... O262 Fazan, V.P...... P519, P520 Freedman, M...... O220, O263, P471 Due, B.R...... O217 Fazekas, F...... 112, O266 Freing, A...... O211 Duek, V...... P547 Fazio, R...... P503 Frosini, D...... P411, P416 Duncan, N...... P531 Fedotova, T...... O311 Fueyo, J...... O283, O284 Dunkel, J...... P746 Feeney, J...... P583 Fujimura, H...... P441 Duport, S...... P770 Feinstein, A...... P472 Fujimura-Kiyono, C...... P543 Durgaryan, A...... O306 Fekete, K...... O265 Fukazawa, H...... P542 Durieux, N...... O325 Felipe, J...... P519 Fuller, G...... O283, O284 Durso, R...... O209 Fenoglio, C. . O327, P541, P544, P602, P685 Fumagalli, G.G...... P660, P685 Duru, C...... P410, P414 Ferbert, A...... P746 Fu¨rbaß, F...... O224, O225 Dusek, L...... O272 Fernandes, J...... P616 Furlan, R...... O291 Dziezyc,_ K...... P421 Fernańdez, A...... P672 Furuya, K...... O287 Echevarrıá, J.R...... P431 Fernańdez, M...... P355, P431 Gabelic, T...... P582 Eckert, B...... P344, P345 Fernańdez, R. . . . . O332, O333, O335, P621 Gabriel, J...... P538, P665 Economou, A...... P647, P648 Fernańdez-Buey, N...... O333 Gabriele, M...... O334 Edwards, M.J...... O207 Fernańdez-Garcıá,E...... P617 Gabrusiewicz, K.R...... O283 Ehlken, B...... P475 Fernańdez-Meneńdez, S...... P440, P797 Gaede, G...... O211, P709 Ehrmann, L...... O247 Ferrari, L...... P697 Gaeta, M...... P761 El Gafi, R...... P693 Ferrari, M...... P381, P553 Gaig, C...... O247, O248, P750 Elam, M...... O319 Ferrari, S...... P512 Gainetdinov, R...... 106 Eliasova, I...... 101 Ferrati, C...... P754 Galantucci, S...... O230, O302 Elkhamary, S.M...... P688 Ferre`,L...... P464 Galassi, G...... P509 Elkins, J...... P339, P342 Ferreira, A.P.O...... P454 Galbiati, S...... O313 Elovaara, I...... P580 Ferreira, C...... P616 Galiana-Ivars, A...... P440, P797 Emami, S...... P474 Ferro, M.T...... O216 Galimberti, D...... O327, P541, P544, Emich-Widera, E...... O298 Feuerecker, R...... O210, P398 P602, P660, P685 Enzinger, C...... O266, O290 Fierstra, J...... O215 Gallardo, L...... O330, O332, O335 Eraksoy, M...... O280 Fighera, M.R...... P453, P454 Gallardo, M.J...... P433 Erdei, K...... P619 Figueiredo, R...... P386 Gallone, S...... P541 Ergecer, S...... P527 Filippi, M. . .110, O193, O194, O195, O197, Galo, S...... P487 Erikh, I...... O233 O204, O205, O212, O230, O237, O281, Galoyan, A...... O306 Ermani, M...... P754 O290, O291, O302, O316, O326, Gamberger, D...... P696 Eross, L...... P674 O327, O329, O331, P381, P382, P400, Gantenbein, A...... P642 Ertekin, A...... P424, P623 P401, P402, P405, P406, P503, P545, Gao, B...... P426 Eskenazi, R...... P661 P553, P554, P555, P586, P587, P627, Gao, H...... O253 Eskes, G.A...... P736 P659, P725, P774, P780 Garcıá,A...... P621 Espadafor-Lo´pez, B...... P724 Filla, L...... P449, P762 Garcia, M.K...... O307 Espiritu-Picar, R...... O307 Filosto, M...... P512 Garcıá-Sańchez, M.I...... P581 Espunã,M...... P521 Fink, J...... P732 Garcia-Santiago, R...... P440 Eungpinichpong, W...... P776 Fink, K...... P585 Garcıá-Torres, M...... P581 Eusebi, P...... P612 Finke, C...... P711 Garciarena, P...... P785, P786 Evangelopoulos, M.E. . . . P371, P600, P719 Finta, L...... P639 Ga¨rtner, B...... O266 Evans, J...... P409 Fiorino, A...... O193, O197 Gasecki, D...... P613 Fabbrini, G...... O243 Fischer, D...... P524 Gasperini, C...... O290, P403 Faber, H...... O196 Fitzhenry, D...... P548 Gateva, A...... P537

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S227

Gatti, R...... O316, O318, P382, P780 Granados, V...... P795 Hartung, H.P. . . . O218, O262, O288, O289, Gavan, C...... P488 Granmayeh, SH ...... P599 P338, P340, P341, P349, P358 Gellera, C...... O292 Grant, L...... P548 Hasegawa, K...... P494 Gemignani, F...... P507 Gra¨ske, J...... O317, P373 Hasegawa, Y...... P494 Genç,G...... P575, P576, P803 Gratii, C...... P604 Hashida, H...... P530 Genetti, M...... P700 Green, D.M...... O310 Hattori, M...... P494 Genov, K...... O286, P723 Greenberg, S...... P339 Hauser, S...... P337 Gensicke, H...... P524 Grigoriadis, N...... P357, P710 Havelka, J...... P728 Georgescu, C...... P644 Grigorova, O...... O228 Havrdova, E...... O258, O259, O288, Georgescu, D...... P644 Grill, E...... O312 O289, O293, P338, Georgescu, L.A...... P644 Grimaldi, L...... O263 P339, P340, P341, Georgoulopoulou, E...... P509 Grioni, D...... P669 P457, P458, P597, P717 Geraghty, M...... O276 Gritsch, G...... O224 Hayman, L.A...... P805 Geraldes, R...... P636 Gromadzka, G...... O208 He,M...... O253, P397 Gerevini, S...... P444, P720 Groot, M.T...... P343 Herman, M...... P608 Gezawa, I.D...... P734 Grosu, A...... P604 Heck, S...... P443 Ghabaee, M...... P737, P738 Grosu, C...... P763 Hedderly, T...... O240 Ghaffarpour, M...... P596, P704, P738 Grosu, O...... P569 Heide, W...... P566 Ghareguzli, K...... P596 Grouiller, F...... P700 Heimberger, A...... O284 Ghezzi, A...... O193, O197, O216, P720 Grznarova, M...... P658 Heinemann, U...... P675 Ghezzi, L...... P541, P660, P685 Grzywacz, A...... O208 Heisen, M...... P343 Ghidoni, R...... O327, P541 Gschliesser, V...... O247 Helani, A...... P689 Ghodsi, S.M...... P383 Guadamuz, A...... P661 Hennerici, M...... O266 Gholami, K...... P474 Guaita, M...... O247 Hennessy, B...... O220, P471 Ghorbani, N...... P713 Gubina, G...... P668 Henriksson, F...... P346 Giambattistelli, F...... O319 Gubitz, G.J...... P736 Henriksson, F...... P345 Giannoccaro, M...... O270, O319, P643 Guergueltcheva, V...... P499, P755 Henriques, I...... O257 Gil-Neciga, E...... P420 Guerreiro, R...... P682, P744 Hentschke, C...... P352 Giladi, N...... P645 Guerrero, A.L...... O330, O332, O333, Heńykova´,E...... P415 Gilbert, M...... O283, P785 O335, P431, P621, P799 Hermanrud, C...... P585 Gill-Thwaites, H...... P770 Guichard, J.-P...... P364 Hernańdez, A...... P432 Ginou, A...... P709 Guimara˜es,P...... P538, P664, P665 Hernańdez-Lain, A...... P799 Giorgio, A...... O290, P403, P727 Gul, H...... P517, P624, P625 Herrero, S...... O330, O332, O333, Giovannoni, G...... O288, P341, P459 Gulec, T...... P699 O335, P621 Gkekas, G...... P559 Gumienny, Z...... P566 Herzig, R...... O267, P374, P408, Glanzman, R...... P337 Gunda, B...... P619 P608, P728, P751 Gluszkiewicz, M...... O256 Gungor-Tuncer, O...... P484 Herzog, J...... O312 Go,M...... P591 Gupta, A...... P673 Hesse, M.D...... P491 Goate, A.M...... O324 Gur Ozmen, S...... P735 Hettle, R...... P345 Gobbetti, E...... O316, P780 Gurgu, R...... P635 Heuschmann, P...... O266 Gobbi, C...... P473 Gustov, A...... P692 Heydenreich, N...... O294 Godefroy, O...... P410, P414 Gutowski, N.J...... P787 Hidalgo, H...... O249, P425, P642 Gold, R...... 146, O262, P336 Haas, C...... O315 Hideyama, T...... O305 P339, P347, P459 Habek, M...... P340, P582 Higashida, K...... P542 Goldman, L...... P663 Haberlova`,J...... P572 Hill, M...... O320 Goldstein, L...... O198 Habib, N...... P594 Hillert, J...... P585 Golubovic, S...... P577, P578 Habibian Dehkordi, S...... P676 Hinojosa, C...... P799 Gomes, I...... P549 Hackmann, O...... P407 Hirayanagi, K...... P686 Go´mez, A.B...... P621 Hadad Saraei, A...... P737 Hirose, Y...... P543 Gomez, F...... O236 Haering, D...... P350 Hlavac, V...... 103 Gomez-Manzano, C...... O283, O284 Haghjoo, S...... P372 Hlusˇtı´k,P...... P359, P415, P608, P751 Gonullu¨,S...... P368 Hagiwara, M...... O222 Hnojcikova, M...... O272, P640, Gonzalez Perez, O...... P389 Hahn, F...... O196 P694, P705, P706 Gonzalez-Rosa, J.J...... P725 Hakiki, B...... P403 Hos¸bul, T...... P576 Gorbach, T...... O227, P668 Halac, E...... P528 Hodor, A...... P426 Goretti, B...... P727 Haldre, S...... O255 Hofstadt-van Oy, U...... P439, P658, Gosal, D...... P508 Haller, S...... O220 P714, P796 Gosseries, O...... O236, O239, O253 Han, S.-J...... P363 Ho¨gl,B...... O247 Gottlieb, C...... O276 Hara, M...... P428 Hohlfeld, R...... O219 Gottschalk, R...... P336, P347 Harbo, T...... O271 Hok, P...... P359, P751 Gottwald, K...... P475 Hard, M...... P341 Holdbrook, F...... O218, P349 Govoni, A...... P544, P552, P691 Hardiman, O...... O301 Holtmannspo¨tter, M...... P732 Gow, D...... P508 Harding, K...... O192, P583, P584 Holzhausen, M...... O266 Graf, J...... P358 Harigaya, Y...... P686 Hong, J.M...... O299, P740 Graf, T...... P479 Harirchian, M.H...... P593, P704 Hong, S.S...... P590 Graham, J...... P525 Hartmann, M...... O224, O225 Honore´,J...... P652

123 S228 J Neurol (2012) 259 (Suppl 1):S1–S236

Hooftman, L...... P477 Jakobsen, J...... O271 Karabacak, K...... P575 Horakova, D...... O293 Janelidze, M...... P653 Karacostas, D...... P526 Hornung, L...... P708 Jang, S.H...... P614 Karadas, O...... P517, P624, P625, P626 Horsfield, M.A...... O194, P401, P406 Janousek, J...... P663 Karaer, H...... P634 Horvath, E...... P783, P784 Jansen, N...... P398 Karalis, F...... P436 Hoskovcova, M...... 103 Januel, J.-M...... O199 Karlinski, M...... O256, O265 Hosokawa, T...... P543 Janyachareun, T...... P772 Karlsson, T...... O319 Hossain, M.B...... O283 Jarius, S...... P564 Kassar, D...... P423, P535 Hosseini, A...... P474 Jarkovsky, J...... O272 Kassavetis, P...... O207 Hoster, E...... P557 Jatuzis, D...... O265 Kato, T...... P632 Houdayer, E...... O318 Javadi, M.R...... P474 Katsarava, Z...... P475, P502 Houlden, D...... O320 Jecmenica Lukic M...... O205, O230 Katsavos, S...... P600, P719 Howe, A...... O250 Jech, R...... O206, O229 Katsioulis, E...... P588 Hrbać,T...... O267 Jeffery, D...... O262 Kaufhold, F...... O211 Hu,X...... O253, P397 Jeffrey, R...... P508 Kaufman, M...... O262 Huang, R...... P460 Jelıńkova´,M...... P408 Kaul, S...... P747, P748, P749 Hughes, R.A.C...... P507 Jennum, P...... 149, 150 Kawabata, K...... P494 Hui, B...... O215 Jensen, L.T...... P666 Kawahara, N...... O287 Hurtikova, E...... P609, P728 Jeon, S...... P490 Kay, C.S.K...... P449, P762 Hutchinson, M.. . . O258, O259, P457, P458 Jesus, S...... P420 Kayamori, R...... P428 Hutyra, M...... P374 Ji,Y...... O303 Keil, A...... P336, P347 Huza, I...... P741 Jinoch, P...... P404 Keller, J...... O229 Hwang, S.H...... P590 Jodl, S...... O263 Kemlink, D...... O246 Hyun, J.W...... P500, P501 Johnson, S...... P355 Kempcke, R...... P354, P468 Hyun, Y...... P679 Jonszta, T...... O267 Kempny, A...... P770 Iakovlev, N...... P629 Joo, I.S...... O299, P740 Ke´ri,A...... P619 Iannaccone, S...... O302, P545, P554 Josephs, E...... O209 Kerr, D...... O301 Ibrahim, A...... P734 Joshi, D...... O245 Kersten, H...... P681 Ibrahim, W...... P430 Jox, R...... O312, P557 Kersten, S...... O315 Iftenie, E...... P741 Jugas, P...... O242 Kessler, C...... O266 Iida, M...... P804 Jung, H.-K...... P500, P501 Khairalla, G...... P571 Imai, K...... P632 Jung, H.J...... P611 Khalil, I...... P693 Imani, A...... P599 Jung, M...... P404 Khandker Parvez, A...... O243 Inada, M...... P515 Jung, S...... P590 Khani, H...... P721 Inan, R...... P517 Jungehu¨lsing, G.J...... O266 Khatri, B...... O218, P349 Incensi, A...... O270, P643 Kaboutari Katadj, J...... P676 Khodadadeh, S...... P598 Inghilleri, M...... O334 Kacar, A...... P753 Kiferle, L...... P411, P416 Ingram, G...... O192, P584 Kahn, A...... P502 Kijima, C...... P496, P605 Ingwersen, J...... P358 Kahn, N...... O243 Kilidireas, K...... P719 Inobe, J...... P778 Kaiserova, M...... O242, P415, P419 Kim, B...... P591 Inoue, K...... O278, P441 Kale, R ...... P451, P570 Kim, B.-S...... P363 Inuggi, A...... P725 Kalenova, I.E...... P743 Kim, B.C...... P611 Ioannidis, P...... P526, P710 Kalfakis, N...... O328, P647, Kim, B.J...... P592 Ionescu, P...... P722 P648, P655 Kim, C.H...... P789 Iranzo, A...... O247, O248 Kalincik, T...... O293, P717 Kim, D.E...... P611 Irina, B...... P645 Kallweit, U...... O249, P425, P642 Kim, J...... P490, P551 Isaji, T...... P428 Kamenov, Z...... P537 Kim, J.M...... P789 Isak, B...... O334 Kaminska, A...... P365, P366 Kim, J.T...... P611 Ishida, S...... P543 Kamisli, O...... P368, P634, P726 Kim, K.T...... P637 Ishikawa, H...... P542 Kamisli, S...... P368, P726 Kim, M.K...... P489, P611 Ishizawa, E...... P418 Kamondi, A...... P639 Kim, M.S...... P362, P614 Issard, D...... O220, P471 Kang, D...... P455, P490 Kim, S.H...... P500, P501, P765 Italiano, D...... P690 Kang, S.Y...... P590 Kim, S.M...... P551, P591, P592, P765 Ito, D...... P494 Kannari, K...... P418 Kim, S.Y...... P589 Ito, Y...... P632 Kanovsky, P...... O242, O244, P374, Kim, Y.J...... P500 Iwaki, A...... O278 P415, P419, P608, P751 Kimura, F...... P543 Iwanicki, T...... O298 Kanpittaya, J...... P772 King, M...... O240 Iwata, M...... P504, P530 Kantor, D...... O254, P351 Kiourtidis, D...... P369, P588 Iyadurai, S...... O213, P423, P535, Kaplan, M...... P380 Kita, M...... O258, O259, P457, P458 P792, P793 Kaplan, Y...... P368, P634, P726 Kitamoto, T...... P686 Izhbuldina, G...... P771 Kappos, L...... 144, O218, O219, O220, Kitchener, N...... P571 Izquierdo-Ayuso, G...... P581 O261, O262, O263, P336, Kitraki, E...... P452 Jacini, F...... P660, P685 P337, P344, P347, P348, Klefer, G...... P566 Jaiswal, D...... P467 P349, P350, P459, Klein, A.-M...... O312 Jajvandyan, R...... P721 P465, P470, P471 Klein, P...... P663 Jaka, O...... O274 Kaps, M...... O266 Kleinschnitz, C...... O294, O296, P478

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S229

Klempir, J...... 100 Kuehlmeyer, K...... P557 Lelard, T...... P414 Kleopa, K...... P506 Kuhle, J...... P470 Lenti, L...... P619 Klopstock, T...... P443 Kuliha, M...... O267, P608, P609, P728 Leo, D...... 106 Klosova´,J...... P359 Kulke, S...... P548 Leocani, L...... O221, O291, O318, Kluge, T...... O224, O225 Kumar, N...... O245 P382, P697, P698, P725 Klumbies, K...... P718 Kumar, P...... P451, P570 Leoń-Durań,D...... P617 Knop, M...... O196 Kumar, V...... P805 Leppert, D...... P337 Knorn, P...... P476 Kurian, M...... O240 Lerario, A...... P442 Kobayashi, A...... O265 Kurosawa, K...... O278 Levin, Y...... O250 Kobayashi, H...... P630 Kurt, S...... P634 Ley Nacher, M...... P731 Kobayashi, K...... O222 Kutukcu, Y...... P624 Leys, D...... O325 Kobayashi, M...... P504 Kwak, S...... O305 Lheo´,A...... P657 Kobys, T...... P480 Kwarciany, M...... P613 Li,D...... P337 Kocher, M...... P608 Kwon, K.H...... P590 Li,L...... P377 Kockum, I...... P585 Kwon, M...... P490 Li,X...... O279 Koenig, E...... O312 Kwon, S...... P490, P590 Liebetrau, U...... P407 Kofidou, E...... P357 Kyriakides, T...... P506 Liguori, R...... O270, O319, P643 Kofler, M...... O322 Kyrosis, A...... P775 Lima, J...... O285 Ko¨hler, A...... P439 Kyrozis, A...... O328, P647, P648, P655 Lima, P...... P729 Kolarikova, K...... P597 La Cesa, S...... O334 Limmroth, V...... P407 Kolev, N...... P516 La Mantia, L...... O216 Lin, J.P...... O240 Kolevick, L...... P795 Labiano Fontcuberta, A...... P493 Lin, T...... P497 Kon, S...... P417 Labunskiy, D...... O311 Linden Junior, E...... P549 Kondziella, D...... P732 Lacima, G...... P521 Link, J...... P585 Kong, L.M...... P388, P562 Lagoudaki, R...... P357 Linnebank, M...... O249 Konstantinova, V...... P516 Laguna, G...... P431 Lioutas, V.A...... O310 Kontaxis, T...... O328, P647, P648 Lake, S.L. . .O288, O289, P338, P340, P341 Lisnic, V...... P763 Kontogeorgi, E...... P469 Laki, Z...... P619 Liszkay, G...... P784 Kopishinskaya, S...... P692 Laloux, P...... P438 Litwin, T...... O208 Kopp, D...... O238 Lambert-Rodriguez, J.L ...... P617 Liu, D...... O283 Kopyta, I...... O298 Lang, F...... O284 Liu, H.M...... P388 Kordi, M.R...... P598 Langhauser, F...... O294 Liu, Y...... O279, P394 Kornyeyeva, E...... O218, P349 Langova´,K...... O267 Liuzzi, R ...... P356 Koros, C...... O328, P452 Lanzillo, R ...... P356 Lizrova Preiningerova, J...... P597 Korv, J...... O265 Laohhosri, M...... P772 Ljubisavljevic, J...... P481 Koskiniemi, M...... O309 Lascano, A.M...... P422, P700 Ljubisavljevic, S...... P481 Kostalova, M...... 101 Laskovska, J...... P796 Llull, L...... P750 Kostalova, P...... P609 Lassen, L...... O271 Lobanova, I...... P480 Kostic, V.S...... O204, O205, O230 Lassman, H...... O194 Locatelli, F...... O313 Kothari, S...... 158 Lassuthova`,P...... P572 Loeterman, J...... P546 Koukouni, V...... P559 Laureys, S...... O236, O239, O253, P397 Logroscino, G...... O300 Koutlas, E...... P588 Lauria, G...... P550 Longoni, G...... O195, O205, P381, P400 Kovacs, K.L...... P619 Lauwick, S...... O236, O239 Lopes, J...... P664 Kovacs, T...... P687 Lavrenova, M...... P779 Lopes, T...... P531 Kovarova, I...... P341 Lavrnic, D...... P753 Lo´pez, A...... P432, P433 Kowalczyk, K...... P613 Lawrence, S...... O276 Lo´pez Cuinã,M...... P731 Koyuncu, B...... P367, P618, P730 Laza, C...... P384, P385, P495, P603 Lopez de Muniain, A...... O274 Kozak, L...... P783 Leao, M...... O241, O277, P386, Lo´pez-Armas, G...... P539 Kozlowski, O...... O252 P387, P568, P683, P684 Lorenz, I...... P709 Kraft, P...... O296 Ledoux, D...... O236, O239 Lorenzoni, P.J...... P449, P762 Krajca, J...... O267 Lee, B.H...... P362, P614 Lourbopoulos, A...... P357, P526, P710 Kral, M...... P374, P608, P751 Lee, H...... P679 Lourenço,S...... P487 Krasensky, J...... O293 Lee, J.H...... P501, P611 Low, E...... P546 Kraus, J...... P572 Lee, J.S...... O299, P740 Lukashev, M...... P461 Kresojevic, N...... O204 Lee, K...... P591, P592 Lukic, S...... P662 Krespi, R...... P527 Lee, K.E...... P733 Lundkvist, M...... P585 Krespi, Y...... O265, P367, P484, Lee, P...... P467 Luppe, S...... O192 P527, P618, P730, P735 Lee, S...... O260 Lus, G...... O216 Kreutzfeldt, M...... P355 Lee, S.H...... P611 Luü¨s, S.-M...... O255 Krikmann, U¨ ...... O255 Lee, S.J...... O299, P614, P740 Luxen, A...... O239 Krobot, A...... P751 Lehr, L...... O220, P471 Lyapin, A...... P779 Krommyda, M...... P369, P588 Leht, L...... O255 Lynch, T...... O240 Krstacic, A...... P696 Lehtokan, W...... P680 Ma,Y...... O279, O279, O279 Krstacic, G...... P696 Leinonen, M...... P443 Maa, E...... O201 Krupicka, R...... 103 Leis, A.A...... O322 Macavei, A...... P741 Krystkowiak, P...... P410, P414 Lekomtseva, Y...... O227, P668 Macavei, I...... P741

123 S230 J Neurol (2012) 259 (Suppl 1):S1–S236

Machado, A´ ...... O202, P540, P616 Martinez, J.V.L...... P794 Midha, R...... O320 MacManus, D...... O259 Martıńez, P.C...... P795 Miguel, B...... P432, P433 Maeurer, M...... P352 Martinez, Y...... P661 Miguel, R...... P798 Maffioli, M...... P510 Martıńez-Quiterio, V...... O321 Mikami, H...... P542 Maghsoodi, N...... P598 Martino, G...... 107 Mikulicova, L...... O242 Magli, V ...... P356 Martus, P...... O266 Mikulik, R...... O265 Magnani, G...... O237, O326, Martyn, D...... P548 Mikulis, D.J...... O215 O327, O329, P659 Marzban, M...... P427 Milani, N...... P550 Magri, F...... P544, P552 Marziniak, M...... P479 Milesi, J...... O212 Magzhanov, R...... P450 Masi, G...... P707 Mileto, A...... P761 Mahli, M...... O315 Masoumi, A...... P546 Milivojevic, I...... P582 Mai, C...... O315 Mastrokosta, A...... P369 Millań-Pascual, J...... P581, P724 Maia, B...... P361 Matarazzo, M...... P493 Miller, A...... O263 Maiovis, P...... P526 Matej, R...... O244 Miller, D...... O258, O259, P457, P458 Majerova, V...... 100 Matevosyan, M...... O306 Miller, T...... O289 Majid, S...... P757 Matilde, L...... P507 Milne, G.L...... P460 Majoros, A...... P619, P784 Matos, R...... P682 Milonas, I...... P436 Malentacchi, G...... P403 Matsi, S...... O328, P647, P648, P655 Miltenberger-Miltenyi, G...... P687 Malhotra, M...... P701 Matsui, M...... O222 Minasyan, A...... P567 Malisova, J...... P791 Matsumura, T...... P441 Mintun, M.A...... O234, O324 Malucchi, S...... O216 Matsuno, A...... O287 Miozzo, M...... O292 Manara, R...... P754 Mattioli, F...... P774 Mir, P...... P420 Mancini, M ...... P356 Maune, S...... P407 Miradouro, R...... P487 Mandell, D.M...... O215 Maurage, C.-A...... O325 Miranda, A.P.P...... P449, P762 Mandrioli, J...... P509 Maürer, M...... P476 Mirsaev, T...... P450 Manea, M...... P722 Maxted, J ...... P601 Mitsueda-Ono, T...... O222 Manoucherihnnia, A ...... P601 Maya Morales, G...... P389 Mitsuma, A...... P515 Mansmann, U...... O312 Mayordomo, F...... O274 Mitsuma, N...... P494 Manso, R...... P800 Mazia, C.G...... P764 Mitsumoto, H...... O301 Manso-Calderoń,R...... P437, P782 Mazurek, M...... P563 Miyazaki, Y...... O222 Manukyan, G...... P567 Mazzucchi, S...... P416 Mizuma, A...... P496 Manzano, B...... P716 McCrone, P...... O198 Mizushima, K...... P686 Maquet, P...... O239 McKee, D...... P435 Modabbernia, A...... P704 Marchesi, C...... P550 McMillan, H.J...... O276 Modak, A...... O209 Marco, J...... O333 Medaglini, S...... P697 Modreanu, R...... O206 Marcone, A...... O237, O326, O327, Medici-Olaso, C...... O321 Modugno, N...... O243 P541, P659 Meergans, M...... P354 Moggio, M.G...... P691 Mare´,R...... P447 Mehling, M...... P336 Mohammadi, F...... P593 Maresˇ,J...... P415 Mehrabian, S...... P537 Mohasseb, D...... P693 Margolin, D.H...... O288, O289, Meier, T...... P443 Mohebbi, S...... P737 P338, P340, P341 Mekyska, J...... 101 Moilanen, E...... P580 Mariani, C...... O327, P541 Melcom, M.O...... P764 Moiola, L...... O193, O197,O216, Mariani, V...... P510 Menge, U...... P714 P464, P697, P720 Marini, C...... P612 Menguy-Vacheron, F...... P463 Moldovanu, E...... P620 Mariotti, C...... O292 Mensˇ´ıkova´,K...... O244, P415, P419 Moldovanu, I...... P569 Marjanovic, I...... P753 Meola, G...... O275, P756 Molinari, M...... P649 Markulan, O...... P486 Mercier, F...... P344 Molnar, M.J...... P687 Markvardsen, L.H...... O271 Mergeani, A...... P384, P385, P495, P603 Momcilovic-Kostadinovic, D...... P429, Marques, J...... P790 Merkler, D...... P355 P574, P669 Marques Jr., W...... P511 Merle, P.E...... P410 Momjian-Mayor, I...... P422 Marrie, R...... P708 Merlen, E...... O252 Monaco, S...... P512 Marrone, C.D...... P549 Merlini, A...... P444 Monies, D...... P757 Marrone, L.C.P...... P794 Mesaros, S...... O194, P401, P405, P406 Montalban, X. 143, O218, O262, P348, P349 Marrosu, M...... P336, P347 Mesquita, T...... P361 Montano, S.M...... P795 Marshall, A...... P508 Messina, M.J...... P444 Montes de Oca Dominguez, T...... P389 Marsili, L...... O243 Messina, R...... O212, O331, P622, P627 Moore, O...... P645 Marti, M.J...... O206, O321 Messina, S...... P691 Moore, P...... P583, P584 Martı´,P...... O274 Meswani, P...... P548 Mora, J.S...... O301 Martin, J.-J...... P759 Methner, A...... P546 Morais, H...... P505 Martin, N...... P716 Meyer, B...... P757 Morales, J...... P688 Martin, P...... P758 Meyer, S...... P373 Moreira, I...... P560 Martıń-Fernańdez, M...... P617 Meysami, A...... P737 Morgadinho, A...... P399 Martinelli, V...... O203, O291, P402, Michel, C...... P700 Morgado, J...... O257, P445, P788 P444, P464, P586, P622, P638, Michel, P...... O264 Mori, E...... P536 P697, P698, P720, P777 Michita, S...... P556 Morita, A...... O287 Martinelli Boneschi, F...... P777 Middleton, L...... P506 Mormont, E...... P438

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S231

Moroni, I...... O304 Nizzardo, M...... P552 Ozturk, B...... P625, P626 Morozov, I...... P769 Noble, A...... O198 Ozturk, M...... P360 Morris, H...... O240 No´brega, C...... O257 Pikrylova´ Vranova´,H...... P415 Morris, J.C...... O234, O324, P395 Noirhomme, Q...... O236 Pace, A...... O262 Morrish, W...... O214, O269 Nojima, S...... P630 Pacheco-Jimeńez, M...... P724 Morsali, D...... P702 Nolte, M.W...... O294 Padron Lopez, I...... P389 Mota, B.C...... P454 Nomura, M...... P542 Padua, L...... P507 Motataianu, A...... P523 Nordberg, A...... O235 Paes, D...... P466 Moullart, V...... P410 Norrving, B...... O266 Pagani, E...... O194, O195, P400, Mousavi, M...... P704 Northoff, G...... P531 P401, P405, P553, P586 Mrackova, M...... 101 Nourbala, F...... P703, P712 Pais, R...... P801 Muelas, N...... O274, P758 Nousiopoulou, E...... P357 Paiva, C...... P801 Muengtaweepongsa, M.D., S...... P610 Novakovic, N...... P577 Paiva-Nunes, A...... P361 Muinõ,E...... P731 Noval, S...... P716 Palace, J...... P336, P347 Muir, K...... 109 Novas, M...... O258, P457, P458, P460 Pall, H...... O240 Mulder, M...... P477 Novas, R...... P519 Palmeri, B...... O216 Mulero, P...... O330, O332, O333, Nowak, D...... O312 Palmour, N...... P557 O335, P621, P799 Nowak, T...... O298 Panchani, R...... P673 Mu¨ller, F...... O312 Nuara, A...... O221, O318, P777 Panczel, G...... P784 Munjev, N...... P722 Numata, Y...... O278 Pandey, A...... O295, P565 Munõz, I.. . O330, O332, O333, O335, P621 Nunes, C...... P801 Panea, C...... P635, P722 Munteanu, L...... P763 Nunes, J...... P399 Panicari, L...... O316, P774, P780 Muradyan, N...... P516 Nyandaiti, Y.W...... P734 Panigrahi, M...... P749 Murata, M...... O232 Nyiro, G...... P687 Pantaleoni, C...... O304 Murphy, J...... P345 Nyka, W...... P613 Pantzaris, M ...... O323 Murty, A...... P748 O’Connor, P...... O219, O263, Panzara, M...... O288, O289, P338, Musumeci, O...... P761 P337, P348, P462 P340, P341 Myalovitska, O...... P480 O’Gorman, J...... P460 Papachilleos, S...... P600, P719 Nabavi, S.M...... P596, P598, P599, O’Neill, G...... P342 Papacostas, S ...... O323 P702, P703, P712, P713, P721 Oberwahrenbrock, T...... O211 Papadopoulos, D...... P469 Naber, S...... O317 Oberye, J...... P477 Papageorgiou, E...... P559 Nacmias, B...... O327 Obuhovica, L...... P667 Papageorgiou, S.G. O328, P647, P648, P655 Nacu, A...... P763 Odabasi, Z...... P624, P625, P626 Papai, Z...... P784 Nakagomi, T...... O287 Ogura, A...... P632 Papathanasiou, A...... P371 Nakai, N...... P494 Oguri, T...... P515 Papathanasiou, E ...... O323 Nakajima, H...... P543 Ois, A...... P731 Papp, A...... P639 Nakano, I...... O301 Okacova, I...... P640, P705, P706 Paquereau, J...... O252 Nakaya, Y...... O222 Okada, Y...... O232 Parees, I...... O207 Nakhro, K...... P678 Okudan, Z...... P484 Pareja, P...... P431 Nalysnyk, L...... O300 Oliveira, F...... P520 Pareyson, D...... O292, P507, P550 Nam, T.S...... P611 Olsen, N.K...... O271 Paris, L...... P370 Naoki, K...... P556 Olsson, T...... O263 Parisi, L...... P382, P774 Nardi, K...... P612 Onalan, A...... P730 Park, H.M...... P637 Nardini, M...... P552 Ondar, V...... P779 Park, J.H...... P500, P590 Narkiewicz, K...... P613 Ono, S...... P542 Park, K...... P551, P591, P592 Nascimbeni, A...... P754 Orefice, G ...... P356 Park, M.S...... P362, P611, P614 Nascimento, O...... O273, P511 Oreja-Guevara, C...... P716 Park, S.K...... P637 Naseri, M...... P596 Ortega-Leoń, M.T...... P724 Parnetti, L...... P612 Nassar, H...... P430 Oryan, S...... P721 Parviz, S...... P737, P738 Natarajan, A...... O260, O262 Osaka, H...... O278 Pasha, T.M.U...... P688 Natarajan, R...... P580 Oschmann, P...... P439, P658, P714, P796 Pashapour, A...... P633 Navalpotro, I...... P731 Oshinsky, M...... P631 Pashapour, P...... P633 Nemec, M...... O272 Ossowska, A...... O223 Pashapour, S...... P633 Nessler, R...... P520 Ota´hal, D...... O267 Pasquier, F...... O325 Nestorov, I...... P460 Otero, M.F...... P695 Passafiume, D...... P651 Nevsimalova, S...... O246 Otruba, P...... P751 Passeri, E...... P756 Newton, H.B...... O285 Ovecka, J...... O242 Passos, J...... P790 Nichelli, P.F...... P649 Owen, M...... O240 Pastare, D...... P667 Nickel, J...... O238 Oyama, Y...... P417 Pastore, A...... O304 Nicolaou, P...... P506 Oystreck, D.T...... P688 Pastore, V...... O313 Niemczyk, G...... P475, P476, P478, P479 Oyuela, P...... P340 Patel, S.N...... P475 Nikolic, A...... P753 Ozcan, C...... P368, P726 Patnaik, R...... O295, P565 Nischwitz, S...... O196 O¨ zdemir, G...... P424, P623 Patti, F...... O216 Nishi, R...... P494 Ozdemir, H...... P380 Paul, F...... O211, P709, P711, P718 Nisida, S...... P632 O¨ zel, L...... P424, P623 Paul, S...... O295, P565 Nixon, R...... P344 Ozkan, S.T...... P367, P730 Pavan, G...... P485

123 S232 J Neurol (2012) 259 (Suppl 1):S1–S236

Pavelova, E...... P663 Ploumis, A...... P775 Raunio, M...... P580 Pavlic, G...... P604 Poalelungi, A...... P498 Raycheva, M...... O228, P499, P537 Pavlova, R...... O228 Poewe, W...... 46,O247 Real, M...... P683, P684 Pavlovic, D...... P481 Pollak, P...... P422 Rebocho, L...... P487 Peall, K...... O240 Polman, C...... O219, 220, P471 Recla, M...... O313 Pech, L.M...... P711, P718 Poluektov, M...... O250 Reda, M...... P693 Pedraza, M...... O330, O332, O333, Popescu, D...... P384, P385, P495, P603 Redondo-Robles, L...... P440, P797 O335, P621, P799 Portaccio, E...... P403, P727 Regev, K...... P645 Pedrosa, R...... P445 Posavec, V...... P582 Rego, I...... P370 Pegenius, G...... O319 Potic, A...... P429, P574, P669 Regula, J...... P564 Pegoraro, E...... P680, P754 Potic, J...... P429, P669 Rehberg-Weber, K...... P475, P476, Pelidou, S.-H...... P775 Po¨tzl, U...... P439 P478, P479 Pellegrini, F...... O261, P465 Poublanc, J...... O215 Reich, E...... P528 Pelletier, J...... O218, P349 Pourashraf, M...... P737, P738 Reichmann, H...... 45 Pena, J...... P445, P788 Prada, F...... P550 Reidy, Y...... P736 Penãs, M.L...... O330 Prakash, K.M...... P413 Reifschneider, G...... P476 Penev, L...... P499 Praksova, P...... P640, P705, P706 Reilly, M.M...... P507 Pensato, V...... O292 Pramodhyakul, W...... P776 Reiner, P...... P364 Pepe, A...... O334 Preiss, M...... P656 Reiter, R...... P539 Perdigao, S...... P558, P671 Prelle, A...... P555 Rektorova, I...... 101 Pereira, F...... P531 Previtali, S...... P503 Relvas, R...... O257 Pereira, J.P...... P370 Preziosa, P...... O194, P401, P402, Remenyi, V...... P687 Peric, S...... P753 P405, P587 Renna, L...... O275, P756 Perini, M...... P555 Prieto, S...... P782 Renu, A...... P750 Perko, H...... O224, O225 Prihodova, I...... O246 Repin, A...... P692 Pershyna, I.V...... P606 Procha´zka, V...... O267, P608 Rey, R.C...... P547 Peterle, E...... P768 Prokopenko, S...... P779 Rezaeezadeh, H...... P596 Petrescu, S...... P722 Protti, A...... O216 Ribeiro, A.C...... P399 Petrolini, M...... O212 Provinciali, L...... O216 Ribeiro, L.R...... P453 Petrou, P...... P369, P588 Prozorovski, T...... P358 Ribeiro, O...... P654 Petrova, M...... O228 Psaltaki, M...... O328 Ribeiro da Silva, M...... L.P387 Peuckert, S...... P407 Psychoyios, K...... P559 Riboldi, G...... P544, P552, P691 Pezzoli, G...... 106 Pupe, C...... O273, P511 Riccitelli, G...... O195, O316, P402, Pfefferle, J...... O282 Purrucker, J.C...... P513 P586, P587, P725, P780 Pfeiffer, A...... P546 Putaala, J...... O266 Richards, S...... P341 Pfeilschifter, W...... O296 Pu¨tz,B...... O196 Richman, S...... O260, P466 Pfueller, C.F...... P709 Putzki, N...... P595 Richter, H...... P639 Phan-Ba, R...... O239 Pyrzowski, J...... O223 Rickard, M...... P793 Phillips, C...... O239 Quattrone, A...... P507 Ridolfi, E...... P541, P602, P685 Phillips, G...... P339 Qureshi, A.I...... P742 Ridsdale, L...... O198 Phillips, J.T...... O258, O259, P457, P458 R.Waterham, H...... P429 Riester, K...... P342 Phillips, S.J...... P736 Racine, E...... P557 Rimoldi, M...... O292 Piccio, L...... P602 Radaelli, M...... P464, P586, P697, P720 Riva, N...... O302, P545, P554, Pickersgill, T...... O192, P584 Radice, D...... P507 P555, P777 Picmausova, J...... 100 Radmilovic, M...... P582 Rivas, S...... P467 Piemonte, F...... O304 Radu, L...... P736 Rizhova, N...... P692 Pietilaïnen-Nickleń,J...... O309 Radue, E...... O219 Rizzo, F...... O275, P552 Pietroboni, A...... P602, P660, P685 Raffelseder, V...... O247 Rizzo, M...... O288, P338 Pievani, M...... O205 Raghupathi, K...... P457 Rizzuti, M...... P691 Pin˜ero, M...... P799 Rai, S...... P787 Robberecht, W...... O301 Pinho, J...... O202 Raichle, M.E...... O234 Roberto, D...... O327 Pinschewer, D...... P355 Rainero, I...... O327, P541 Robertson, N.P...... O192, P583, P584 Pinto, J...... P801 Rakocevic-Stojanovic, V...... P753 Rocca, M.A...... O193, O194, O195, Pinto Marques, J...... P682, P744 Rakusa, M...... P456 O197, O212, O281, O290, Pires-Barata, S...... P487 Ramalheira, J...... P664 O316, O331, P382, P400, P401, Piscopo, P...... O327 Rambo, L.M...... P453 P402, P405, P406, P503, Piscosquito, G...... P550 Ramirez, J.O...... O249 P586, P587, P627, P725, P774, P780 Pisko, J...... O246 Ramos Gonzalez, A...... P493 Rocco, A...... P365, P366 Pizza, F...... O270 Rampen, A...... P518 Rocha, R.. . .O241, O277, P568, P683, P684 Plafadeli, A...... P469 Ranawat, N.S...... P742 Rocha, S...... O202, P447, P540, P616 Planellas, L...... P731 Rango, M...... P660 Rodegher, M...... O195, O216, P400, Plavina, T...... O260, P466, P467 Rani, J...... P749 P444, P697 Playford, D...... P770 Rani, U...... P747 Rodrigues, F...... P454 Plenevaux, A...... O236 Ranieri, M...... P544, P552, P691 Rodrigues, M...... P447 Ploner, C.J...... P711 Ranjan, R...... P673 Rodriguez, A...... P731 Ploscutanu, N...... P635 Rata, A...... P495 Rodriguez, G.E...... P547

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S233

Rodriguez, J...... P795 Saeedi, Z...... P703, P712 Schildkraut, J...... O282 Rodriguez de Antonio, L...... P716 Saengsuwan, J...... P573 Schimanski, S...... P796 Rodriguez-Sua´rez, M.L ...... P617 Saenz, A...... O274 Schindler, C...... P524 Rojas de Dios, J...... P389 Saj, A...... P652 Schippling, S...... O211, P709 Rojas-Marcos, I...... P672 Sakoda, S...... P441 Schlain, B...... P467 Rojek, A...... P613 Sakovics, A...... P639, P674 Schlesinger, I...... O233 Rolfs, A...... O266 Sal y Rosas, G...... P795 Schlichting, J...... P711 Rombos, A...... P600, P719 Sala, S...... O329 Schmidt, R...... O266 Romeiro, A...... P682 Salahesh, A...... P703 Schmidt, R...... P396 Romeo, V...... P754 Salamero, M...... O247 Schnakers, C...... O253 Rominger, A...... P398 Salani, S...... P552 Schneble, H.-M...... P364 Ronan, L...... O226 Salehi, M...... P615 Schniepp, R...... O210 Ronchi, D...... P552, P691 Salemi, G...... O216 Schomer, A.C ...... P670 Ronnevi, L-O ...... O301 Salgado, H.C...... P520 Scho¨nenberger, S...... P513 Ropele, S...... O266 Salih, M.A.M...... P689 Schreuder, T...... P802 Roque, R...... P361 Salsano, E...... O292, P550 Schro¨ter, F...... P358 Roquer, J...... P731 Salter, A...... P701, P708 Schuh, K...... P352, P353 Roriz, J...... P505 Salutto, V.L...... P764 Schultheiß, T...... P468 Rosa, L.O...... P794 Salvatore, E P356 Schwab, S...... P476 Rosa, M.I...... P547 Salvi, F...... P555 Schwartz, M...... O320 Rosales-Corral, S...... P539 Salzano, M...... O304 Sciacco, M...... P691 Rosebush, P...... P563 Samavati, S...... P427 Scola, E. . . O237, O302, O326, O329, P659 Rosen, D...... O209 Samochowiec, J...... O208 Scola, R.H...... P449, P762 Rossetti, A...... O199, O264 Sampaio, M...... O241, O277, P386, Secades-Gonza´lez, S...... P617 Rossi, F...... P403, P727 P387, P568, P683, P684 Seeck, M...... P700 Rossi, M...... P382 Sanak, D...... P374 Seed, P...... O198 Rossi, P...... O221, P777 Sańchez, A...... O332, P621 Seeman, P...... P572 Roth, C...... P746 Sańchez-Escribano, R...... P782 Seferyan, T...... O306 Roth, J...... 100 Sańdor, P...... P642 Seidensticker, F...... P443 Rotta, F.T...... P549 Sandrock, A...... O260 Seidl, Z...... O293 Roubec, M...... O267, P608, P609, P728 Sandu, E...... P722 Seitz, R.J...... O238 Rousseaux, M...... O252, P646, P652 Sandu, R...... O297 Selmaj, K. .O217, O219, O288, O289, P338, Roussel, M...... P414 Sangalli, D...... P483 P339, P340, P341, P459 Routsis, C...... O328, P647, P648, P655 Sangalli, F...... P464, P720 Semplicini, C...... P680 Rovelli, A...... P429, P669 Sanglagi, B...... P598 Serpente, M...... O327, P541, P602, P685 Rovira, A...... O290 Sanli Turk, A...... P360 Serranova´,T...... O206 Roxburgh, R.H...... P681 Sansone, V.A...... P756 Sessa, M...... P381, P553 Royes, L.F.F...... P453, P454 Santamaria, J...... 148, O247, O248 Sevilla, T...... O274, P758 Rozhkova, Z...... P480 Santangelo, M...... P403 Sfangos, K...... P600 Ruano, L...... O268 Santoro, L...... P507 Sfikas, N...... O219, P348 Rudas, G...... P784 Santos, C...... P505, P729 Shaath, H...... P767 Rudolf, J...... P369 Santos, E...... P560 Shahov, B...... P579 Rudolph, G...... P443 Santos, P...... P682, P744 Shahsavarzadeh, T...... P372 Ruiz, L...... O330 Sarchielli, P...... P612 Shakouri, M...... P383 Ruiz, M...... O333, O335 Sari, A...... P380 Shalenkov, I...... P579 Rukina, N...... P769 Sarro, L...... O204, P659 Sharinova, I.A...... P743 Rulseh, A.M...... O229 Satoshi, H...... P556 Sharma, N...... P565 Rummey, C...... P443 Savoiardo, M...... P550 Sharpe, J.A...... O215 Ruprecht, K...... P718 Savov, A...... P492 Shasia, R...... P593 Rusina, R...... O229 Sawaya, R...... O284 Shatil, E...... P656 Russell, H...... P460 Sawicka, M...... O223 Shayegannejad, V...... P596 Rusz, J...... 100 Scaioli, V...... P550 Shefner, J...... O301 Rutschmann, A...... P434 Scalco, R.S...... P453, P454, P549, P794 Sheikh, S.I...... P459, P460 Ruttanathantong, K...... P573 Scanlon, C...... O226 Shen, Z...... P390, P394, P497, P752 Ruzicka, E...... 100, 103, O206 Scanlon, J...... O260 Shen, Z.W ...... P561, P781 Ruzickova, H...... 100 Scarale, A...... O205, P553 Sheridan, J...... P342 Ryan, S...... P461 Scarlato, M...... P381, P553 Shevelev, O.A...... P743 Sa´,J...... P636 Scarpini, E...... O327, P541, P544, Shigemasa, H...... P556 Sˇanˇa´k,D...... P608 P602, P660, P685 Shimizu, Y...... P504 Saadat, S...... P383 Scekic, J...... P514 Shin, D.H...... O299, P490, P740 Saadatnia, M...... P372, P615 Schabus, M...... O236, O239 Shon, Y.-M...... P363 Sabet, Z...... P702 Scheidl, E...... P783 Shopova, A...... P755 Sabirova, E...... P771 Schenone, A...... P507 Sica, R.E...... P547 Sacko, A...... P410 Schestatsky, P...... P549 Sieger, T...... O206 Sadeghi, S...... P599, P703, P712 Schicklmaier, P...... P476 Sieminski, M...... O223 Sadeghian, H...... P737, P738 Schiffman, J...... P805 Sierens, D...... O231

123 S234 J Neurol (2012) 259 (Suppl 1):S1–S236

Sierra, L...... O332, P621 Stecher, S...... P460 Tavernarakis, A...... P469 Siever, A...... P336, P347 Stefanova, I...... P392 Tavukcu Ozkan, S...... P735 Silani, V...... O301, O302, P442, Steinbach, K...... P355 Tavy, D...... P518 P483, P545, P554, P691 Steiner, T...... P365, P366 Tedim Cruz, V...... O268 Silva, A.R...... P519 Stella, F...... P531 Teixeira, F...... P560 Silva, E...... P531 Stephan, T...... O210, P392, P396 Tekgo¨l Uzuner, G...... P628, P739 Silva, M...... P538, P568 Stetkarova, I...... O322 Tench, C...... P601 Silva Cunha, J.P...... P393 Stevanovic, I...... P481 Teramoto, S...... O305 Silvestre, J...... P798 Stevic, Z...... P753 Terecoasa, E...... P488, P498 Silvestrini, M...... P612 Stewen, J...... P566 Tevzadze, N...... P653 Simeone, J...... O300 Stites, T...... O218, P349 Tham, C...... P733 Simon, B...... P631 Stojanovic, I...... P481 Theochari, E...... P435 Simone, C...... P552 Stoll, G...... O294, O296 Theotokis, P...... P357 Simu, M...... P644 Stosic-Opincal, T...... P405, P406 Thome, L...... P729 Sindrup, S...... O271 Stourac, P...... P595, P706 Thompson, A...... 145 Sirchia, S...... O292 Straube, A...... O312 Tichalas, A...... P588 Siritaratiwat, W...... P573, P776 Strazzer, S...... O281, O313 Ticho, B...... O262, P466 Sison, J...... O282 Stricker, S...... P711 Ticozzi, N...... P483 Sivera, R...... P758 Strnad, M...... P415 Tiede, M...... P709 Skelina, S...... O228 Stromillo, M...... P403, P727 Tillard, A...... P646 Skibova, J...... O246 Strotzer, M...... P658, P796 Tinbergen, J...... P337 Sˇkoloudı´k,D...... O267, P374, P408, Strygin, K...... O250 Tintore´,M...... O290 P608, P609, P728, P791 Sturcova, Z...... 103 Tiu, C...... P488, P498 Skupch, A...... O225 Su,Y...... O234, O324, P463 Tiu, I...... P498 Skvorc, A...... P582 Sua´rez, A...... P420, P672 Toda, T...... O232 Slyusar, T...... P629 Suarez, M...... P657 Todorova, G...... P537 Smekal, Z...... 101 Subramanyam, M...... O260, P466, P467 Todorova-Dimitrova, E...... O286, P492 Smiljkovic, T...... P429, P669 Suk, S.H...... P590 Tolosa, E...... O247 Smith, M...... O240 Sun, P.Z...... P497 Tolun, R...... P367, P484, P527, Soares, P...... P798 Sung, J...... P591, P592 P618, P730, P735 Soddu, A...... O236 Sunwoo, I.N...... P551, P765 Toma´sˇova´,Z...... P751 Soder, R.B...... P794 Sussman, J...... P508 Tombul, T...... P699 Soghoyan, A...... P567 Sutherland, G...... O269 Tomic, A...... O205, O230 Sokolova, M...... P791 Suzuki, I...... O287 Tomic, D...... P336, P347 Sokolovic, D...... P481 Suzuki, M...... P504, P542 Tondelli, M...... P509 Sola, C...... P649 Svetel, M...... O204, O205, O230 Tonguk, L...... P630 Sola, N...... O247, P750 Svigelj, V...... O265 Topaloglu, P...... O280 Sola, P...... O216 Sweetser, M.T...... P457 Toraldo, F...... P707 Solari, A...... P507 Syed, S...... P446 Toribio, E...... O330 So¨mmer, C...... P711 Szabo, Z...... 103 Torkamandi, H...... P474 Sommer, C...... P502 Tabano, S...... O292 Torres, C...... P437, P528 Song, H...... P490 Taborska´,K...... P404 Toscano, A...... P761 Sonka, K...... O246 Taborsky, M...... P374 Toth, E...... P674 Sonneborg, L...... P732 Tafakhori, A...... P704 Touloumi, O...... P357 Sorbi, S...... O327 Tafakhri, A...... P593 Tournev, I...... P499, P755, P766 Sormani, M...... P403 Tahbaz, S...... P703, P712, P713 Toyoda, T...... O287 Soukup, T...... P408 Taheraghdam, A...... P633 Tozzi, G...... O304 Sousa, A...... P445, P788 Tajmirriahi, M...... P372, P615 Traykov, L...... O228, P537 Sousa, F...... O202, P447, P540 Takada, H...... P417 Traykova, M...... P537 Sousa, R...... O277 Takagi, K...... P630 Traynor, B...... O300 Souza, M.A...... P454 Takagi, M...... P536 Tremont-Lukats, I ...... P785, P786 Soysal, A...... P360 Takagi, S...... P605 Treur, M.J...... P343 Spagnolo, F...... O203 Takahashi, W...... P496, P605 Triantafyllou, A...... P436 Spandou, E...... P357 Takanashi, J...... O278 Tripathi, M...... 161 Sparing, R...... P491 Takeuchi, M...... P504 Trojano, M...... O216, O261, P465 Spasic, M...... P662 Takizawa, S...... P496, P605 Trufﬁnet, P...... O263 Spinelli, E...... O326 Tambour, M...... P345, P346 Truini, A...... O334 Spinelli, L...... P700 Tan, D-X...... P539 Tsapanou, A. . . . . O328, P647, P648, P655 Sprecher, E...... O233 Tan, E.K...... P413 Tsiptsios, D...... P588 Sriphetcharawut, S...... P573 Tan, Y.L ...... P733 Tsiptsios, I...... P369, P588 Staedler, C...... P473 Tang, R...... P805 Tsironis, T...... P369, P588 Stamboulis, E...... P719 Tani, H...... P543 Tso, M...... O269 Stankova, T...... P537 Tanislav, C...... O266 Tsukie, T...... P542 Stankovic, I...... O204 Tardov, M.V...... P743 Tuckova´,L...... O244, P419 Stapf, C...... P364 Tascos, N...... P357, P436, P710 Tu¨do¨s,Z...... P751 Stebbins, G.T...... O231 Tatlisumak, T...... O266 Tufekcioglu, Z...... P527

123 J Neurol (2012) 259 (Suppl 1):S1–S236 S235

Tummala, S...... P786 Velcheva, I...... P492 Wernsdo¨rfer, C...... P476 Tuncer, O...... P367, P527, P618, P730 Velon, A...... P538 Whatmore, J.L...... P787 Turconi, A...... O281 Vence, L...... O284 Whelan, C...... O226 Turk Boru, U...... P517, P625 Verdun di Cantogno, E.. . O220, P470, P471 White, C...... O240 Turpault, S...... P463 Veretzioti, A...... P469 White, L.A...... O300 Turpı´n-Fenoll, L...... P581, P724 Verhagen Metman, L...... O231 Whittington, M...... P668 Twyman, C...... O289, P340 Verheggen, B.G...... P343 Wiedau-Pazos, M...... P546 Tyblova, M...... O293 Vermersch, P...... O263 Wieder, L...... P718 Tyry, T...... P701, P708 Veverka, T...... P374, P608, P751 Wiemels, J...... O282 U¨ c¸eyler, N...... P502 Vicent, A...... P449 Wiendl, H...... O261, P465 Uchiyama, S...... P504, P530 Viglietta, V...... O258, O259, Wildeman, S...... P525 Uchiyama, Y...... P530 P457, P458 Wildemann, B...... P564 Ueda, K...... P441 Viken, J...... P666 Williams, J.R...... O301 Uhl, V...... P425, P642 Vila Real, M...... O241, O277, P568 Windhagen, S...... P476 Uitdehaag, B...... O220, P470, P471 Vila-Cha˜,N...... P370 Wingerath, B...... P358 Ulas, U...... P624, P626 Vilchez, J...... O274 Wirtz, P...... P518 Ulbert, I...... P674 Vilchez, JJ ...... P758 Woldeamanuel, Y.W...... O308 Ulmanova, O...... 103 Vilchez, R...... O274 Wolf, S...... P658 Ulvi, H...... P375, P424, P522, P623 Vilionskis, A...... O265 Wolf-Ostermann, K...... O317, P373 Umans, K...... P339 Villa, C...... P541, P602 Wolinsky, J...... O263 Ungaro, D...... P777 Villa, F...... O313 Wong, A...... P805 Uotila, L...... O309 Virtanen, O...... O309 Wong, J...... O214, O269 Uribe, F...... O330 Visioli, F...... P507 Woodall, A...... P508 Uyar, T...... O280 Vita, G...... P507 Worch, A...... P373 Uziel, G...... O292, O304 Vitols, E...... P667 Worthylake, T...... O276 Uzuner, N...... P628, P739 Vlassenko, A.G...... O234, O324, P395 Wrensch, M...... O282 Vacca, G ...... P356 Vlckova, E...... O272, P640, P694, Wu,J...... P379 Vadasdi, K...... P783, P784 P705, P706 Wu, R...... P391, P394, P455, P497, Vadillo-Bermejo, A...... P724 Vollmer, T.L...... O217 P561, P752, P781 Valadas, A...... P744 Volna, J...... O293 Wuerfel, J...... O211 Vale, J...... P798 Volonte`, M.A...... O203 Wuttanapun, P...... P776 Valencia, C...... P432, P433 Volterrani, D...... P411, P416 Wydra, G...... O315 Valenzuela, H...... P431 von Rosenstiel, P...... O218, P336, Xiao, G...... P391, P497, P752, P781 Valldeoriola, F...... O206 P347, P349, P350 Xiao, Y...... P390, P561 Valls-Sole´,J...... O206, O321, P521 Voortman, G...... P477 Xiong, C...... O324 Valsasina, P...... O193, O237, O281, Vujisic, S...... P514 Xiong, G...... P398 O316, O329, P381, P402, Vymazal, J...... O229 Xiromerisiou, G...... P369 P406, P503, P555, Wahab, A...... P675 Xuan, Y...... P455 P627, P774, P780 Wahlgren, N.-G...... O265 Xydakis, I...... P559 Valzania, F...... P509 Waite, A...... O240 Yakhno, N.N...... P529 Van Asch, P...... P773 Wallgren-Petterson, C...... P680 Yamada, S...... P494 Van den Berg, L.H...... O301 Wallin, G...... O319 Yamamoto, H...... P804 Van den Munckhof, P...... O231 Wandinger, K...... P439, P564 Yamamoto, M...... P428, P461 Van den Tweel, E...... P477 Wang, F...... P397 Yamamoto, T...... O278 Van der Hel, W.S...... P343 Wang, K...... O303 Yamano, T...... P542 Van der Toorn, F...... P802 Wang, M.-J...... P363 Yamashita, T...... O305 Van Lokven, T...... P354 Wang, Q...... O279, O279 Yamazaki, K...... P630 Vandermeeren, Y...... P438 Wa¨ngler, B...... P398 Yan, G...... P455 Vaneckova, M...... O293 Wardle, K...... P435 Yang, M...... O258, P458 Vanelli, F...... P411 Wardle, M...... O240 Yang, W...... P390, P752 Vanghelie, D...... P635 Warner, T...... O240 Yang, Y...... O279, O279, O279 Vanghelie, G...... P722 Wassilew, N...... P422 Yang, Z...... P394 Vanhaudenhuyse, A...... O236, O239 Watanabe, K...... O222 Yapici, Z...... O280 Varallyay, G...... P783 Watanabe, T...... P542 Yasuda, T...... P632 Varga, V...... P783 Watila, M.M...... P734 Yasui, K...... P494, P542 Varvarousis, D...... P775 Weber, F...... O196 Yawalkar, N...... P473 Vasileva, E...... P516 Weber, M...... O301 Yelden, K...... P770 Vasiliades, M ...... O323 Weber, P...... O196 Yerro, Y...... P414 Vastagh, I...... P619 Wei, L...... O303 Yiðiter, R...... P375, P522 Vastik, M...... O242, O244, P415, P419 Wei, M...... P391, P497, P781 Ying, L...... O253 Veggiotti, P...... O193, O197 Weiner, H...... O288, O289, P338, Yokoi, S...... P494 Vegso, P...... P639 P340, P341 Yong, M.H ...... P413 Veiga, A...... P538 Weinstock-Guttman, B...... O262 Yoo, B.G...... P489 Veiga, R...... P399, P801 Weis, J...... P439, P760 Yoo, H.S...... P765 Veira, C...... O268 Wells, C...... P337 Yoon, B...... P591, P592, P678 Velasco-Alonso, E...... P617 Werneck, L.C...... P449, P762 Yoshida, M...... P441

123 S236 J Neurol (2012) 259 (Suppl 1):S1–S236

Yousry, T...... O259 Zapletalova, O...... P791 Zhou, G...... P395 Yu,D...... O253, P397 Zarbo, I.R...... P777 Zhou, M...... O282 Yu,S...... P376, P377, P379 Zecca, C...... P473 Zhukova, M...... O314 Yuan, H...... P457 Zeinali Kahaki, Z...... P737 Ziabary, S.M...... O200 Yung, W.A...... O283, O284 Zeller, D...... P502 Zidar, I...... P456 Yutani, S...... P496, P605 Zendehdel, M...... P676 Zidar, J...... P456 Zadro, I...... P582 Zeng, W...... P461 Ziemssen, T...... P354, P468 Zafeiropoulou, E...... P469 Zeynali Kahaki, Z...... P738 Zimmermann, H...... O211, P709, P718 Zaiferte, O...... P667 Zhang, A...... O261, P459, P465, P466 Zinman, L...... O301 Zak, I...... O298 Zhang, H.D...... P388 Zipp, F...... O217 Zakestidis, C...... P369 Zhang, P...... P561 Zisimopoulou, V...... P469 Zakrzewska, A...... O223 Zhang, R...... O258, O259, P458 Zlatareva, D...... P499 Zamba-Papanicolaou, E...... P506 Zhang, Y.D...... P378 Zubalova, L...... P567 Zandieh, A...... P738 Zhang-Auberson, L...... O219 Zulaika, M...... O274 Zanetta, C...... P552 Zhao, J...... P376, P377, P379 Zunt, J.R...... P795 Zangen, A...... O221, P709 Zhao, Y...... P377, P379 Zurita Santamaria, J...... P493 Zanini, S...... O318 Zheng, H.Y...... P562 Zapletalova´,J...... P608, P751 Zheng, W.B...... P388, P562

123