Letters to the Editor 255

Electrophysiological and biomechanical data before and after repetitive magnetic stimulation in 12 ventional pharmacotherapy often induces J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.58.2.255 on 1 February 1995. Downloaded from patients with (median range) side effects including loss of muscle strength, drowsiness, dizziness, and nausea. Maximum voluntary contraction (Nm) Stretch reflex Threshold of amplitude stretch reflex A double blind and sham stimulation con- Dorsi Plantar (% M,,,) (/s) trolled study of the effect of repetitive mag- netic stimulation on spasticity is under way. Before treatment 15 5 (0-23-0) 19-0 (1 7-32-0) 1-23 (0-10-4) 22 (6 0-88 0) J0RGEN F NIELSEN After treatment 20-0 (1 4-48 0)** 26-0 (3-2-44 0)** 0-88 (0O002-10O5)* 33 (12-0-88O0)* BENNY KLEMAR HANS JACOB HANSEN *p<0-05; **p <001. Department ofNeurology, Aarhus University Hospital, Aarhus, Denmark THOMAS SINKJAER Centerfor Sensory-Motor Interaction, values in 12 patients with clinical definite icantly by 1-0 (3-(-1)) AU (p = 0 03); pre- Department ofMedical Informatics and Image multiple sclerosis.' All had spasticity of the treatment and post-treatment group values Analysis, Aalborg University, Denmark lower extremities, a preserved capability of were 6-5 (11-4) AU and 6-5 (11-2) AU. Correspondence to: Dr J F Nielsen, Department continuous walking for at least 30 meters, Electrophysiological measures of spasticity of Neurology, Aarhus University Hospital, and a clinical stable condition during the six improved. The table shows a significant N0rrebrogade 44, 8000 Aarhus C, Denmark. of the stretch months before study. Eight patients had not decrease of EMG amplitude 1 Poser CM, Paty DW, Scheinberg L, been treated recently for spasticity and four reflex of 28% (p = 0 04) and an increase in McDonald IW, Davis FA, Ebers GC, et al. patients stopped drug treatment one week the threshold of the stretch reflex of 50% New diagnosis criteria for multiple sclerosis: The stimulus (p = 0 03). Maximum voluntary contrac- guidelines for research protocols. Ann before the study. magnetic Neurol 1983;13:227-31. has a biphasic waveform with a pulse width tion of plantar and dorsiflexion of the foot 2 Ashworth B. Preliminary trial of carisoprodol of 400 ,ps, a rise time of 200 ,us, and a maxi- strengthened significantly, by 27% and 29% in multiple sclerosis. Practitioner 1964;192: mum magnetic field of 2-1 Tesla. The oil respectively (p = 0-008 and p = 0 009). 540-2. stimu- 3 Sinkjaer T, Toft E, Andreassen S, cooled coil was placed in the midline at the No major side effects of magnetic Homemann BC. Muscle stiffness in human midthoracic level with the caudal part of the lation were found. All patients reported a ankle dorsiflexors: intrinsic and reflex com- coil positioned at the eighth thoracic verte- tight feeling as if wearing a narrow ring ponents. J Neurophysiol 1988;60: 1110-21. The were stimulated in a around the midthoracic level during stimu- 4 Sinkjaer T, Toft E, Larsen K, Andreassen S, bra. patients Hansen HJ. Nonreflex and reflex mediated relaxed supine position for 30 minutes with lation. One patient had a single episode of ankle joint stiffness in multiple sclerosis stimulation for eight seconds at 12 Hz fol- brief dizziness but otherwise magnetic stim- patients with spasticity. Muscle Nerve lowed by 22 seconds of rest. The range of ulation was well tolerated. By contrast, con- 1993;16:69-76. stimulation intensity was 40-65% of maxi- mal stimulator intensity. At the start of the study and 24 hours after the last magnetic stimulation clinical, electrophysiological, and biomechanical performances were reg- the istered. The same physician evaluated Patients with clinically definite multi- had a duration of disease of at least one spasticity at both knee and ankle joints by year, an upper age limit below 45 at onset, total ple sclerosis, white matter abnormali- an Ashworth's score (0-4)2 with a ties on MRI, and normal CSF: if not and the presence of multiple white matter maximum score of 32 arbitrary units (AU) multiple sclerosis, what is it? lesions on MRI and they were given repeat as well as the patellar and Achilles tendon CSF and MRI examinations between reflexes according to conventional clinical January and April 1993, together with a score of 16 Clinical overdiagnosis of multiple sclerosis grading (0-4) with a maximum may occur in as many as 10% of patients variety of tests screening for mitochondrial AU. according to Hendon and Brooks.' Whereas encephalomyopathy, , For the electrophysiological and biome- diagnosis has been facilitated by the use of Lyme disease, AIDS, coagulopathy, vas- chanical measurements the patients were MRI,23 the detection of focal disease scat- culitis, sarcoidosis, and cardiac embolic seated in a chair with the foot strapped to a tered throughout the CNS in young adults sources. pedal rotated by a strong motor.3 Spasticity The MRI characteristics of multiple scle- the is not specific for multiple sclerosis (table). was electrophysiologically evaluated by We therefore estimated the proportion of rosis are "multiple small lesions mainly threshold and amplitude of the stretch diagnostic mistakes still found in our large involving white matter with asymmetric dis- http://jnnp.bmj.com/ reflex by EMG of the soleus muscle and cohort of clinically diagnosed patients with tribution that have optimal specificity if the expressed as a percentage of the supramaxi- following three features are present: size > 6 The multiple sclerosis. mal direct muscle response (M,,,,). Four hundred and five new patients were mm, abutting ventricular bodies, infratento- short latency stretch reflex was elicited by studied between 1988 and 1992. Three rial location".4 rotating the platform at different stretch cohort We defined the MRI as: (a) "typical" from 7-5 to 120'/s.4 hundred and fifty two patients of our velocities in the range met the Poser criteria for "clinically definite and (b) "compatible" when not all the Stretches and releases of 4° were delivered multiple sclerosis" and 184 had a complete three features for optimal specificity were with a duration of 500 ms and were applied present. CSF examination. Of these 184 patients, on September 27, 2021 by guest. Protected copyright. randomly with an interval of 4 0 (SD 0 2)s. In 16 of these 18 cases, the MRI was was 166 had positive immunological findings for The amplitude of the stretch reflex multiple sclerosis. The remaining 18 had no typical for multiple sclerosis, but four had measured at a stretch velocity of 900/s. a final diagnosis that was not multiple Maximum voluntary contraction of dorsi CSF abnormalities. These eighteen patients and plantar flexion of the foot was mea- sured as the highest value the patient could maintain for one second out of three attempts. The patients self scored the ease Differential diagnosis of brain MRI mimicking multiple sclerosis of daily activities (0-10) with a score of 5 as the preset level. Group values and delta dif- Multiple sclerosis-variants: Charcot type, Devic type, Schilder type, Marburg type, isolated syndromes ference values between the pretreatment Normal aging* Alzheimer's disease* and post-treatment condition are given as Migraine median values and ranges. Differences were Subcortical arteriosclerotic encephalopathy or Binswanger's disease* tested by Wilcoxon signed rank test with a Multiple metastases Vasculitis: Sjogren's syndrome, polyarteritis nodosa, systemic erythematosus, Beqhet's disease, giant 5% limit of statistical significance. cell arteritis Self score of ease of daily day activities Sarcoidosis improved significantly (p = 0-01) by 2 (4-0) Leucodystrophies AU pretreatment and post-treatment group Encephalitis: Viral: HTLV-I myelopathy, progressive multifocal leucoencephalopathy (Papova), subacute sclerosing values were 5 (5-5) AU and 7 (9-5) AU. panencephalitis (measles), acute disseminated encephalomyelitis The clinical score of spasticity decreased Bacterial: tuberculosis significantly by 1-5 (8-(-1)) AU (p = 0-03); Spirochaetal: syphilis, neuroborreliosis, or Lyme disease Chronic demyelinating inflammatory polyneuropathy pretreatment and post-treatment group val- Subacute combined degeneration of the spinal cord ues were 9-5 (17-1) AU and 5-5 (10-2) AU. The score of hyper-reflexia decreased signif- *Excluded by age. 256 Letters to the Editor sclerosis. In two more cases the neuroradi- biopsy of a salivary gland confirmed the J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.58.2.255 on 1 February 1995. Downloaded from ologist used the expression "compatible". diagnosis of primary Sjogren's syndrome. For these two patients, the final diagnoses In our study, we attempt to estimate the were Lyme disease and vasculitis. Hence, proportion of diagnostic mistakes in our six of 18 patients with normal CSF had a cohort of "clinically definite" multiple final diagnosis other than multiple sclerosis. sclerosis with normal CSF, and to develop a The methodological details along with the rational approach to the diagnostic proce- clinical and laboratory characteristics of our dure leading to alternative, less common, patients will be the subject of a full paper. diagnoses. Detailed reinvestigation of these Here we describe the six patients with an patients proved that, when we considered alternative diagnosis. all patients with multiple sclerosis with CSF Case 1 was a 42 year old woman who examination, about 3-2% of them turned had right and a mild deficit of out to have some diagnosis other than mul- the seventh cranial nerve in February 1989. tiple sclerosis, but when we evaluated only Symptoms improved a month after steroid patients with normal CSF the diagnoses treatment. In March 1991 she experienced had to be revised in 33%. Even when the paraesthesia and mild hypoaesthesia in her MRI picture is typical of multiple sclerosis, left leg, which remitted spontaneously in 10 it is possible to find alternative diagnoses days. An antinuclear antibody test was posi- and a firm distinction based on MRI alone tive. A skin rash developed after her inclu- is often not possible. Especially in a busy sion in our study and biopsy of this clinical service-admittedly this is a self confirmed the diagnosis of systemic vasculitis. criticism-the level of alertness should be Case 2, a 50 year old woman, experi- raised. enced multiple episodes of diplopia and Currently, having a treatment such as between January 1986 and interferon-fl- lb which seems to alter SDS-PA GE of the recombinant Yo-protei'n. September 1989 remitting in a few days favourably the course of multiple sclerosis5 (A) Lane 1: molecular size marker; lane 2: without treatment. In June 1990 she devel- emphasises the importance of making an homnogenates of transformed cells before oped weakness in her lower limbs with early and correct diagnosis of multiple scle- I.sopropyl-p-D-thiogalactopyranoside induction; severe ataxia, lasting two months and par- rosis so that treatment is given appropriately lane 3: homogenates of transformed cells after tially improving after steroid treatment. before the disease has progressed too far. Izsopropyl-p-D-thiogalactopyranioside induction; Repeated MRI was typical. In December Assessment of a patient suspected of hav- lane 4: recomnbinant protei.n fused to the mnaltose bi'nding protein purified on an amylose resi'n 1992 a progressive worsening of gait distur- ing multiple sclerosis requires (a) expertise column. The molecular weight of the fuision bance began. The MRI performed showed in performing and interpreting MRI, com- protei'n i's 62 kDa, consistent with the size severe olivopontocerebellar atrophy. Some bined with (b) a CSF study which, if nor- expectedfromn the DNA sequence. This protei.n punctate hyperintense areas in the white mal, leads to (c) detailed tests for gi.ves triple bands (double bands under 62 kDa) matter were still present. A diagnosis of alternative, less frequent, diagnoses with that are thought to be its phosphorylated olivopontocerebellar atrophy was made on particular attention to vascular disorders in products. (B) Lane 1: molecular size marker; clinical and MRI findings. young adults. lane 2: Imnmunoblot of the recombi'nant Yo- Case 3, a 46 year old woman, had several C FIESCHI protein that reacted with the patient's serumn. C GASPERINI episodes of left facial paraesthesia and G RISTORI between June 1972 and June S BASTIANELLO 1986. In September 1989 she developed F GIRMENIA V LEUZZI weakness in her left side and in March 1992 C BUTTINELLI she experienced vertigo and ataxia. All M RASURA antigen epitope is important for detecting episodes were mild, lasting a few days and Department of Neurosciences, the origin of a cancer; therefore, we con- remitting without treatment. University ofRome "La Sapienza ", Italy structed recombinant Yo protein (r-Yo) and Echocardiography showed an aneurysm established an enzyme linked immunosor- of the atrial septum. Correspondence to: Professor Cesare Fieschi, bent assay (ELISA) system that uses this Case 4 was a 40 year old man who Dipartimento Scienze Neurologiche, Universita' protein as the antigen. With this system, we reported dysarthria and weakness in his left "La Sapienza" di Roma, Viale Universita' 30, found a fallopian tube adenocarcinoma by 00185 Roma, Italia. http://jnnp.bmj.com/ limbs, lasting about three weeks in testing for antibody to r-Yo in a patient with September 1986. In April 1991 he devel- 1 Hendon RM, Brooks B. Misdiagnosis of mul- PCD that could not be detected by conven- tiple sclerosis. Semin Neurol 1990;5:94-8. tional methods. We measured the oped severe weakness in his right limbs, 2 Offenbacher H, Fazekas F, Schmidt R, et al. antibody remitting in two months. Steroid treatment Assessment of MRI criteria for a diagnosis titre in serum samples taken serially during was efficacious in both episodes. A repeated of MS. Neurology 1993;43:905-9. various types of treatment. CSF in 1993 showed 3 Namet H, Yu 0, Mauss Y, et al. An evalua- The details of this patient's case have examination February tion of the significance of areas of intense high concentrations of lactate, without any signal in the MR brain images of patients been reported elsewhere. Briefly, a 70 year other abnormalities. A diagnosis of mito- with multiple sclerosis. Magn Reson Imaging old woman developed cerebellar ataxia that 1993;11:311-7. worsened and she became bed- chondrial encephalomyopathy was made rapidly, on September 27, 2021 by guest. Protected copyright. 4 Fazekas F, Offenbacher H, Fuchs S, et al. ridden within two weeks. An extensive after skeletal muscle biopsy. Criteria for an increased specificity of MRI Case 5 was a 26 year old woman who interpretation in elderly subjects with sus- malignancy survey showed no evidence of reported right facial anaesthesia and dys- pected multiple sclerosis. Neurology 1988; tumour. An immunohistochemical investi- which lasted a 38:1822-5. gation showed that the IgG in her serum phagia in September 1991, 5 IFNB Multiple sclerosis study group. week with spontaneous remission. In Interferon beta-lb is effective in relapsing and in her CSF bound to the cytoplasm of December 1991 she developed mild ataxia remitting multiple sclerosis. I. Clinical Purkinje and other neuronal cells and reacted and paraesthesia in her right side; MRI was results of a multicenter, randomized, dou- with the 58 kDa band on immunoblots of ble-blind, placebo-controlled trial. Neurology cerebellar To determine compatible with multiple sclerosis. Steroid 1993;43:655-61. homogenates. treatment was started with complete remis- whether this antibody really does recognise sion in 30 days. A further CSF examination the Yo antigen, we produced r-Yo for use as after inclusion in the present study showed the antigen in immunoblotting or ELISA. a positive reaction for antibodies to Borrelia Recombinant Yo protein was produced burgdorferi. Long term course of change in anti-Yo using the nucleotide sequence reported by Case 6 was a 36 year old man who expe- antibody content in paraneoplastic Sakai et al."4 As the common epitope has rienced vertigo and mild deficit of the sev- cerebellar degeneration the leucine-zipper motif,' we designed a enth cranial nerve in July 1991, lasting a primer pair, nucleotide numbers 1 to 20 for few days with spontaneous remission; MRI Female patients with paraneoplastic cere- the 5' site and 497 to 519 for the 3' site. was compatible with multiple sclerosis. In bellar degeneration (PCD) associated with The reverse transcription polymerase chain September 1991 he developed vertigo, right breast or gynaecological cancers often have reaction (RT-PCR) was performed with facial hypoaesthesia and mild ataxia. In our a characteristic antineuronal autoantibody RNA derived from adult human cerebellum screening for alternative diagnoses we found (anti-Yo antibody).' To determine whether as the tempateTThF-I RT-PCR product- autoantibodies to Ro (SS-A)/La (SS-B); the anti-Yo antibody recognises the same with the leucine-zipper motif then was