J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.65.4.604 on 1 October 1998. Downloaded from 604 J Neurol Neurosurg Psychiatry 1998;65:604–615

degeneration. The protein concentration in 2 Smedley H, Katrak M, Sikora K, et al. CSF was 208 mg/dl, there were no cells. Neurological eVects of recombinant human interferon. BMJ 1983:286;262–4. LETTERS TO Immunoelectrophoresis was normal, and 3 Rutkove SB. An unusual axonal polyneuropathy antiganglioside antibodies (GM1, GD1a, induced by low-dose interferon á-2a. Arch THE EDITOR GD1b, GT1b) were absent. Serum bio- Neurol 1997:54;907–8. chemical studies, including HIV antibody 4 Batocchi AP, Evoli A, Servidei S, et al. Myasthe- nia gravis during interferon á therapy. Neurol- determination, were negative. We ruled out ogy 1995:45;382–3. the presence of cryoglobulins. Although 5 Gorson KC, Allam G, Somovic D, et al. IFN-á was discontinued, the disease contin- Improvement following interferon-á 2A in ued to worsen; the maximal neurological chronic inflammatory demyelinating polyneu- Chronic inflammatory demyelinating ropathy. Neurology 1997:48;777–80. polyneuropathy during treatment with deficit was reached 5 months from onset. The interferon-á patient was given prednisone (60 mg/day) and progressively improved. One year later he Posteroventral pallidotomy can Interferon-á (IFN-á) is widely used for the had no symptoms and showed areflexia only ameliorate attacks of paroxysmal treatment of chronic viral hepatitis. There on neurological examination. A further EMG dystonia induced by exercise have been some reports concerning the showed appreciable improvement. development of autoimmune diseases, par- This is the first report of CIDP develop- Paroxysmal exercise induced dystonia is a ticularly thyroid disease, in patients under ment during treatment with IFN-á. CIDP is rare disorder classified as one of the paroxys- treatment with IFN.1 Disorders including an immune mediated disorder that usually mal dyskinesias.12 In this condition patients autoimmune haemolytic anaemia, pernicious responds to plasma exchange, intravenous develop dystonia, mostly involving their feet, anaemia, thrombocytopenic purpura, sys- gammaglobulin, or corticosteroids, although after prolonged exercise, usually walking or temic lupus erythematosus, Raynaud´s dis- occasionally the disease is refractory to these swimming.1–3 Treatment response is poor to ease, parotiditis, and epididymitis have been therapies. In the past, some authors have both antieplileptic drugs and drugs given for reported. Some neurological problems have reported improvement in patients with CIDP dystonia—for example, anticholinergic also been described2; although most such who were receiving IFN-á.5 The mechanism drugs, muscle relaxants, or acetazolamide.3 adverse events have involved the CNS, several by which IFN induced improvement in these We recently noted the dramatic benefit of cases of peripheral nervous system involve- patients is uncertain, although it may be unilateral pallidotomy in completely abolish- ment have been reported—namely, axonal related to complex immunomodulating ef- ing attacks of paroxysmal exercise induced polyneuropathy,3 neuralgic amyotrophy, mul- fects, possibly by reduction of proinflamma- dystonia of the contralateral foot in one tiple mononeuropathies, and myasthenia tory cytokine concentrations (tumour necro- patient. gravis.4 On the other hand, some authors have sis factor and IFN-ã) which may have a role This 47 year old woman was followed up reported that IFN-á maybeaneVective in the development of inflammatory over 2 years for a 10 year history of attacks of alternative therapy in patients with chronic demyelination.5 The relation between IFN-á dystonia aVecting her right foot, induced by inflammatory demyelinating polyneuropathy and CIDP in our patient is uncertain. exercise. At onset the attacks were mild and (CIDP) who are refractory to conventional Whether IFN-á was the cause of CIDP or were induced by walking long distances. 5 treatments. Two trials using IFN-á and whether their relation was only coincidental During an attack her right foot would invert IFN-â on patients with CIDP are currently in remains unknown. Nevertheless it seems for a few minutes making it diYcult for her to progress. We describe one patient who devel- clear that the treatment mentioned above did continue walking or stand. The attack would oped CIDP during IFN-á treatment. not prevent the development of this demyeli- subside within 2–3 minutes on resting. Two A 29 year old man who had hepatitis C for nating disease with an immunological basis. years after onset the attacks subsided and she 2 years, was started on IFN-á treatment. He IFN-á exerts complex immunomodulator was attack free for 3–4 years. Four years ago had the usual related flu-like syndrome eVects, it can improve or worsen autoinmune the attacks returned and got progressively during the first month of treatment. Previ- diseases. worse, increasing in frequency and intensity. ously he had had some migraine headache Although our findings could be coinciden- Over the past 2 years she could have an attack episodes, but no other medical problems. tal, the data suggest caution, as IFN-á on walking even 10–15 steps. The attacks in After 4 months of treatment, he progressively treatment might yield undesirable eVects the past few years not only made her right developed paraesthesias and weakness in involving autoimmune phenomena. foot to in turn as before but caused her to fall both feet. When he came to our hospital 4 Mª EUGENIA MARZO as the right leg would rise up in the air and http://jnnp.bmj.com/ months later, his condition had worsened. MAR TINTORÉ flex at the knee and hip and there would be Neurological examination disclosed tetra- ORIOL FABREGUES some involvement of the trunk causing her paresia (proximal and distal) with 4/5 XAVIER MONTALBÁN spine to twist to the left. Recently the toes of strength (Medical Research Council scale), AGUSTÍN CODINA the left foot were also noted to curl up during generalised areflexia, and hypoaesthesia both Unit of Clinical Neuroimmunology, Department of attacks. She would never lose consciousness in his hands and feet. EMG data are summa- Neurology, Hospital Vall d’Hebron, Barcelona, Spain and the attacks would last 1–2 minutes and rised in the table. Prolonged distal motor Correspondence to: Dr Xavier Montalban, Unit of then subside. They never occurred in sleep. latencies, slowed conduction velocities, tem- Clinical Neuroimmunology, Department of Neu- Interictally the neurological examination was poral dispersion of the compound muscle rology, Hospital Vall d’Hebron, Psg Vall d’Hebron 119–129, Barcelona 08915, Spain. Fax 0034 3 normal although posturing of the right foot action potentials (CMAPs), marked prolon- on September 25, 2021 by guest. Protected copyright. 4274700; email [email protected] could be induced by repeated prolonged pas- gation of F wave latencies, and a reduction of sive flexion-extension movements of the right sensory and motor CMAPs in both arms and ankle. More recently she also began to have the right sural nerve were found. These find- 1 Burman P, Karlsson A, Oberg K, et al. Autoim- occasional spontaneous attacks. Investiga- ings were consistent with a demyelinating mune thyroid disease in interferon-treated tions including repeated MRI of the head and polyradiculoneuropathy with a mild axonal patients. Lancet 1985:ii;100–1. spine were normal as were tests for Wilson’s disease and other causes of secondary dysto- Nerve conduction studies nia. Examination of CSF gave normal results and disclosed no oligoclonal bands. The Conduction velocity Amplitude (µV (sensory) Distal latency (m/s) (m/s) mV(motor)) patient was negative for the common mito- chondrial mutations. An EMG/nerve con- Sensory: duction study detected no evidence of a Right median 3.1 50 4.2 peripheral neuropathy and somatosensory Right ulnar 2.7 48 1.1 Left sural 2.8 41 8.5 evoked potentials were normal. Polymyogra- Right sural 3 43 3.3 phy confirmed cocontraction of agonists and Motor: antagonist muscle pairs in the right leg during Right median 4.4 34 2.4 an attack supporting an organic basis for the Left posterior tibial 10 39 0.8 dystonia. Surface EEG during an attack and Right common peroneal 7.9 38 3.6 interictally disclosed no abnormality. The F wave: Latency F-M Incidence (n (%)) patient was tried on a variety of treatments Right median 42.9 30 (100) including baclofen, levodopa, benzexhol, Right ulnar 36.3 31 (60) tetrabenazine, and acetazolamide without Left posterior tibial 65.5 57 (70) Right common peroneal 63.7 57 (70) benefit. DiVerent antiepileptic drugs given individually or in combination (1g sodium J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.65.4.604 on 1 October 1998. Downloaded from Letters, Correspondence, Book reviews 605 valproate with 1 g carbamazepine, and 2 m Sudden appearence of invalidating torsional dystonias were still present and clonazepam a day) also did not help. The dyskinesia-dystonia and oV fluctuations rated 10 (SD 2). Bromocriptine up to 10 failure of the medical treatment and the after the introduction of levodopa in two mg/day was not tolerated. During the next 2 frequency of up to 10 or more attacks a day dopaminomimetic drug naive patients years levodopa treatment could not be increased. His UPDRS scores was 89 at 2 made normal functioning impossible for the with stage IV Parkinson’s disease patient and therefore a surgical option was weeks before his sudden death due to appar- considered particularly as the attacks were ent cardiovascular complications with cardiac mainly unilateral. With the consent of the Hyperkinesias (dystonia, dyskinesia) are, with arrest. A postmortem examination showed patient a left posteroventral medial palli- fluctuating akinesias, the most debilitating anteroinferior myocardial infarction, and dotomy was carried out as in a previously disturbances appearing during the advanced normal brain structures with depigmentation 1 of the nigral structure. Mesencephalic struc- described technique.4 She made an unevent- course of Parkinson’s disease. The origin of tures were cut into horizontal 7 µm thick sec- ful recovery and had no neurological compli- these disturbances is controversial; as hyper- tions and stained with haematoxylin and cations. Immediately after operation the kinesias are seen after long term treatment with levodopa or dopaminoagonist drugs eosin; three Lewy bodies were found in 109 attacks of exercise induced dystonia had identified pigmented cells and cell loss was ceased completely having occurred more many researchers think that these motor fluc- tuations could be prevented by dopaminomi- about 86% compared with age matched con- than 10 times a day immediately before the 5 metic drug restriction,1 others think that trols and literature reports. operation even on walking 10–15 steps. At Patient 2 was a 72 year old man from the the end of 6 months follow up she had been hyperkinesias will appear anyway after enough years, independently of dopaminomi- same region of central Italy. He came to us attack free, apart from occasional minor metic drug restriction—that is, the supersen- akinetic and rigid, with a stooped posture and spasms of her left foot on exercise, despite sitivity of striatal structures to external minor tremor of both upper limbs, and was normal activities; anticonvulsant treatment administration of dopaminomimetic drugs is confined to a wheelchair. Utterances were fee- was gradually being withdrawn. an epiphenomenon of natural degeneration ble and incomprehensible. His total UPDRS This is the first example of the usefulness of in Parkinson’s disease.2 motor score was 93 for upper limbs, rest pallidotomy in a patient with any form of Ten years apart from one another we had tremor was only 2. He had been incapable of paroxysmal dyskinesia. Pallidotomy and the chance to observe two patients with Par- walking during the past year, and spent his more recently pallidal stimulation are cur- kinson’s disease with prevalent akinetic time on a chair, where he also slept. His rently being used as surgical techniques for symptoms who came to us already in an relatives described the progressive deteriora- advanced Parkinson’s disease in patients with advanced stage of Parkinson’s disease, classi- tion in the past 10 years, from the stooped complications of levodopa treatment.5 These fied as stage IV according to the Hoehn and posture to progressive akinesia and language procedures are particularly helpful in abolish- Yahr scale.3 These patients had never been and walking deterioration. His disturbances ing the levodopa induced dyskinesias.5 Palli- treated with dopaminomimetic agents (levo- were attributed to senescence-arthrosis, until dotomy has also been found beneficial in dopa, dopaminoagonists), or amantadine or comparison with other patients with Parkin- patients with generalised dystonia6 and re- anticholinergic drugs, and both developed son’s disease living in the same region, cently a unilateral pallidotomy was reported dyskinesias and motor fluctuations when prompted the neurological consultation. This to produce bilateral benefit in one patient levodopa was increased to the amounts com- patient was treated with increasing doses of with tardive dyskinesia.7 monly used in patients with stage III-IV Par- levodopa+benserazide after a one week trial with 125 mg thrice daily had not changed his Given the improvement in our patient a kinson’s disease treated for 6–10 years. UPDRS score. A 1.5 g daily dose of levodopa unilateral pallidotomy could be considered as Patient 1 was a 76 year old man living in (in 6 administrations) was reached in the next a treatment option in patients with stere- the inner mountainous part of central Italy. week. Oromandibular dyskinesias and leftward otyped paroxysmal attacks as occur in parox- When he came to us he was incapable of ris- torsion dystonias appeared in the same week. ysmal exercise induced dystonia and the ing from his bed; hypomimia, akinesia, flexed dystonic posture, and rigidity were rated 20 at He became able to walk unaided but tremor of other paroxysmal dyskinesias such as parox- motor examination with the unified Parkin- the upper limbs was still present, at rest and ysmal non-kinesigenic dyskinesias in which 4 during walking. His dyskinesias were uncom- 2 son’s disease rating scale (UPDRS), modest treatment is often unsatisfactory. A bilateral 4–5 Hz tremor was present at the upper fortable, although not painful, and his stooped procedure could be considered in patients limbs, left and right intensity was rated 4 at posture was only slightly modified (score 3 with bilateral attacks such as patients with the UPDRS, and utterances were feeble and from 4). His UPDRS score during treatment paroxysmal non-kinesigenic dyskinesias who incomprehensible. The total UPDRS score was 57, tremor score was 4, and dyskinesia- http://jnnp.bmj.com/ are unresponsive to drug treatment as was 126 (SD 4). dystonia score was 7 (SD 1). Treatment was bilateral pallidotomy seems to improve pa- It was possible to reconstruct his clinical then reduced to 500 mg levodopa+ tients with generalised dystonia.6 history from relatives, and apparently his benserazide with 15 mg ropinirole (increasing KP BHATIA early stooped posture and akinetic distur- in three weeks from 1.5 mg/day). With this C D MARSDEN bances had appeared at least 10 years before, treatment dyskinesias were reduced, UPDRS Department of Clinical Neurology but was considered to be due to severe score for dyskinesias was 4 in the morning, 5 in arthrosis and was treated with salicilates. the afternoon, and he was able to walk unaided D G T THOMAS Brain MRI at admission was normal. Early in the morning. His UPDRS score was 65 (SD Department of Neurosurgery, Institute of Neurology, treatment with 62.5 mg levodopa thrice 4) in the morning and 79 (SD 2) in the after- on September 25, 2021 by guest. Protected copyright. National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK daily+benserazide did not induce gastro- noon. Brain MRI was normal. intestinal intolerance but did not change his In conclusion, both patients came to us Correspondence to: Dr KP Bhatia, Institute of UPDRS score and was rapidly (4 days) with a levodopa responsive parkinsonism that Neurology, Queen Square, London WC1N 3BG. increased to 250 mg levodopa four times had appeared, according to history recon- daily+benserazide. Oromandibular dyskine- struction, at least 10 years before. Both could sias, dystonic neck and trunk leftward be considered at least in stage IV of the 1 Lance JW. Familial paroxysmal dystonic chore- 3 oathetosis and its diVerentiation from related rotations, and left leg dyskinesias were Hoehn and Yahr scale. Both had never been syndromes. Ann Neurol 1977;ii:285–93. noticed 2 days after the 1g daily levodopa treated with dopaminomimetic drugs or with 2 Demirkirin M, Jankovic J. Paroxysmal dosage was reached. Dystonic-dyskinetic other drugs currently used in the treatment of dyskinesias: clinical features and classification. movements appeared 20–30 minutes after the Parkinson’s disease. In both patients dykine- Ann Neurol 1995;38:571–9. first (7 00 am) 250 mg levodopa+benserazide sias and dystonias, accompanied by motor 3 Bhatia KP, Soland VL, Bhatt MH, et al. Parox- ysmal exercise-induced dystonia: eight new tablet, lasted through the day, and were pain- fluctuations throughout the day, appeared in sporadic cases and a review of the literature. ful, mostly in the afternoon. the first week. After that a levodopa dose able Mov Disord 1997;12:1007–12. His UPDRS scores were 72 (SD 3) from 8 to modify the akinesia and rigidity scores was 4 Laitinen LV. Pallidotomy for Parkinson’s dis- 00 am to 2 00 pm, 88 (SD 3) from 2 00 pm reached. Reduction of levodopa dosage in ease. Neurosurg Clin N Am 1995;6:105–12. to 8 00 pm. Dyskinesia-dystonia scores were patient 2 and introduction of a dopaminoag- 5 Lang AE, Lozano AM, Montgomery E, et al. Posteroventral medial pallidotomy in advanced 11 (SD 2) from 8 00 am to 10 00 pm and 13 onist improved dyskinesia but the total Parkinson’s disease. N Engl J Med 1997;337: (SD 2) from 2 00 pm to 10 00 pm. Because UPDRS score was higher than the score 1036–42. dyskinetic-dystonic movements were not tol- obtained with 1.5 g/day levodopa. 6 Jankovic J, Ondo WO, Lai E, et al. Pallidotomy erated, the daily levodopa had to be reduced These findings favour the hypothesis for dystonia [abstract]. Ann Neurol 1997;42: 446. to 62.5 mg every 3 hours (total 375 mg/day). suggesting that hyperkinetic fluctuations are 7 Wang Y, Turnbull I, Calne S, et al. Pallidotomy With this treatment UPDRS scores were 86 not dependent on prolonged dopaminomi- for tardive dyskinesia. Lancet 1997;349:777–8. (SD 4); oromandibular dyskinesias and metic drug administration but on the natural J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.65.4.604 on 1 October 1998. Downloaded from 606 Letters, Correspondence, Book reviews course of Parkinson’s disease.6 In favour of this viewpoint is the finding that MPTP exposed parkinsonian patients had severe loss of dopaminergic neurons and developed dyskinesias rapidly after starting levodopa therapy.7 Caveats about this conclusion must be placed, relative to the fact that both patients had prominently akinetic distur- bances, and thus prevalent tremorigenic par- kinsonisms might have diVerent courses with diVerent occurrences of complications during levodopa treatment. MARCO ONOFRJ CRISTINA PACI ASTRID THOMAS Department of Oncology and Neuroscience, University of Chieti, Italy Correspondence to: Professor Marco Onofrj, Cli- nica Neurologica, Ospedale Clinicizzato “SS An- nunziata”, Università “GD’Annunzio”, Via Vestini, 66100 Chieti, Italy. Telephone 0039 871 358527; fax 0039 871 562019; email [email protected] or [email protected]

1 Stocchi F, Nordera G, Marsden CD. Strategies for treating patients with advanced Parkinson’s disease with disastrous fluctuations and dyski- nesias. Clin Neuropharmacol 1997;20:95–115. 2 Rajput AH, Fenton ME, Birdi S, et al.Is levodopa toxic to human substantia nigra? Mov Disord 1997;12:634–8. 3 Hoehn MM, Yahr MD. Parkinsonisms: onset, progression, and mortality: Neurology 1967;17: 427–42. 4 Fahn S, Elton RL, et al. Unified Parkinson’s dis- ease rating scale. In: Fahn S, Mardsen CD, Clane DB, et al.eds.Recent developments in Par- kinson’s disease. Vol 2. Florham Park; Macmil- lan Health Care Information, 1987:153–63, 293–304. 5 Gibb WRG, Lees AJ. Anatomy, pigmantation, ventral and dorsal subpopulations of the substantia nigra, and diVerential cell death in Thoracic MRI showing areas of abnormal signal intensity Parkinson’s disease. J Neurol Neurosurg Psy- chiatry 1991;54:388–96. in the central portion of the spinal cord at the T4–5 level. 6 Agid Y, Bonnet AM, Ruberg M, et al. Patho- (A) sagittal, T2 weighted; (B) sagittal, T1 weighted; and physiology of levodopa induced abnormal (C) axial, T1 weighted. (D) T1 weighted cervical MRI involuntary movements. In: Casey D, Chase showing a Chiari malformation type I. TN, Christensen VN, et al, eds. Dyskinesia- research and treatment. Psychopharmacology (Berl) 1985;(suppl 2):145–59. all normal. Bleeding and whole blood clotting hydromyelia (central canal dilatation) due to 7 Langstone JW, BallardP, Tetrud JW, et al. times were normal. Tests for oligoclonal changes in the CSF dynamics, especially in Chronic parkinsonism in humans due to a bands and myelin basic proteins of CSF were those who have a Chiari malformation.2 We product of peperidine-analog synthesis. Science 1983;219:979–80. negative. Thoracic cord MRI detected areas have no idea why this hydromyelia developed of abnormal signal intensity (high in the T2 at the upper thoracic level. http://jnnp.bmj.com/ weighted and low in the T1 weighted images We conclude that synchronised swimming Reversible hydromyelia in a with no enhancement by Gd-DTPA) in the rules should not encourage prolonged under- synchronised swimmer with recurrent central portion of the spinal cord at the T4–5 water performances and unnatural compul- thoracic girdle pains level (figure A, B, C). The intensities were sory figures, and that prior checks for risk linear-elliptic in the sagittal plane, and small factors such as a Chiari malformation should Synchronised swimming is considered a low and round in the axial plane, indicative of be made. injury competitive aquatic sport for all ages, hydromyelia (central canal dilatation). My- although stress related symptoms such as elography and MRI of the cervical and lumbar The lumbar puncture, myelography and follow up MRI were done at the Department of Neurology,

1 on September 25, 2021 by guest. Protected copyright. knee or shoulder pain are common. We cord and of the brain showed no abnormali- the National Institute of Neuroscience Kohnodai report a case of recurrent thoracic girdle ties except for a Chiari malformation type I Hospital, Ichikawa, Chiba. We thank Dr Takeshi pains in a professional instructor of this sport (figure D). Only a recommendation not to Sato and his colleagues for their expert help. due to reversible hydromyelia. strain or hold her breath was given, and the TOSHIO FUKUTAKE The patient was a 40 year old woman with pains resolved spontaneously over the next 10 TAKAMICHI HATTORI 15 years experience as an instructor of days. Two months later follow up MRI of the Department of Neurology, Chiba University School of synchronised swimming. She was in good thoracic cord showed the absence of the initial Medicine, Chiba, Japan health up to 15 December 1996 when she abnormal finding. Correspondence to: Dr Toshio Fukutake, Depart- developed insidious left thoracic pains 2 days Synchronised swimming requires flexibil- ment of Neurology, Chiba University School of after an underwater exhibition performance ity, kinesthetic awareness, and aerobic condi- Medicine, 1–8–1 Inohana, Chuo-ku, Chiba 260, that was longer and more strenuous than tioning. Few acute injuries occur in the Japan. Telephone 0081 43 226 2129; fax 0081 43 226 2160. usual. The pains spontaneously disappeared participation of this sport, but overuse over the next 10 days. On 6 February 1997, injuries such as knee pain associated with the 1 Weinberg SK. Medical aspects of synchronised she again experienced similar thoracic girdle eggbeater kick and shoulder pain associated swimming. Clin Sport Med 1986;5:159–67. pains 2 days after prolonged lessons and a with sculling are becoming more common.1 2 Williams B. On the pathogenesis of syringomyelia: A review. JRSocMed1980;73: week later came to our hospital. The pain was Therefore the thoracic pain in our patient 798–806. dull and increased intermittently, in particular might have been wrongly diagnosed as having when she turned over in bed at night. On a musculoskeletal origin. examination she was alert, afibrile, and The combination of breath holding and the Barium carbonate intoxication: an normotensive. Neurological examination dis- performance of compulsory figures, such as electrophysiological study closed no abnormalities in her cranial nerve, those that involve hyperextension of the spine, motor, sensory, and autonomic functions. can markedly raise intrathoracic and intracra- Barium carbonate is an uncommon poison- There was no nuchal rigidity. Routine labora- nial pressures during prolonged underwater ing agent in India. This whitish coloured tory findings for blood, urine and CSF were performances, and may cause dangerous powder is available over the shelf from the J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.65.4.604 on 1 October 1998. Downloaded from Letters, Correspondence, Book reviews 607 chemists and is used mainly as a rodenticide potentials were normal in amplitude and acted at more than one level—that is, (rat poison). We report an unusual case of duration. The recruitment pattern was re- muscles, proximal segments of the reflex arc, barium carbonate poisoning. The nerve and duced. Visual evoked potential, EEG, and and probably ã eVerents as the tone was muscle electrophysiological studies are re- brain stem evoked potential were all normal. increased. ported for the first time in barium carbonate Nerve conduction velocity and EMG were A KAKAR intoxication. repeated on day 7 and were normal in all I ANAND A 19 year old boy presented to a hospital aspects. PK SETHI emergency department with sudden onset Most patients with barium intoxication Department of Neurology, Sir Ganga Ram Hospital, tetraplegia. He was referred to our centre as a have gastrointestinal and cardiac involvement Rajinder Nagar, New Delhi 60, India case of Guillian-Barré syndrome. The patient with tetraplegia. Barium carbonate is a rare Correspondence to: Dr Atul Kakar, 31 South Patel presented with tingling in the right upper arm, cause of hypokalaemic periodic paralysis.1 Nagar, New Delhi 110008, India. which was immediately followed by weakness Diarrhoea and arrhythmias are due to direct in all four limbs. The weakness progressed stimulatory action of barium ions on smooth 2 1 Stedwell RE, Allen KM, Binder LS. Hypokale- and involved trunk muscles also within a few and cardiac muscles. Heart failure and mic paralysis: review of etiologies, pathophysi- minutes. There was no history suggestive of hypertension may occur in a few cases. ology, presentation and therapy. Am J Emerg bulbar or facial nerve involvement. Barium blocks the potassium channels and Med 1992;10:143–8. On examination, higher mental functions, thus potassium eZux from the muscle is 2 Gosselin RE, Smith RP, Hodge HC, et al .Clini- cal toxicology of commercial products, 5th ed. cranial nerves, and sensory and cerebellar reduced whereas the sodium-potassium Baltimore: Williams and Wilkins, 1984:3;61–2. examination were normal. Examination of pump is intact. This causes increased potas- 3 Layzer RB . Periodic paralysis and the sodium- the motor system showed a power of 0/5 glo- sium in the muscle and decreased resting potassium pump. Ann Neurol 1982;11:5437– 3 52. bally. No deep tendon reflex could be elicited. membrane potential. Barium acts mainly at 4 Agarwal AK, Ahlawat SK, Gupta S, et al. Surprisingly, with complete areflexic paralysis the neuromuscular junction by this Hypokalemic paralysis secondary to acute there was increased tone in the lower limbs. A mechanism.4 The fatal dose of barium barium carbonate toxicity. Trop Doct 1995:25: diagnosis of Guillian-Barré syndrome was carbonate is 0.8 g and death occurs within 101–3. 4 5 Clinical aspect of electromyography. In: AmnoV considered, but there were some pointers 2–12 hours. MJ, ed. Electromyography in clinical practice. against this diagnosis. The onset and progres- There is only one report of an EMG study Electrodiagnostic aspect of neuromusclar disease. sion to complete tetraplegia was very rapid done in four patients with paralysis because 2nd ed. New York: Churchill Livingstone, 1987:73–101. and the weakness started from the upper of barium carbonate poisoning. It was done limbs followed by that of the lower limbs. within 1 week of admission and did not show Increased tone in the lower limbs was also not any abnormality.4 In our case nerve conduc- Central pontine myelinolysis causes consistent with the diagnosis of Guillian- tion velocity studies and EMG were done on bilateral loss of deep sensitivity and Barré syndrome. the first day and were sequentially repeated. pseudochoreoathetosis Routine blood investigations at the time of Interpreting the nerve conduction velocity admission, including serum electrolytes, were studies of day 1—namely, low amplitude of Central pontine myelinolysis is characterised normal. Nerve conduction study showed compound muscle action potentials— would as symmetric and selective destruction of normal distal latency of the compound mus- indicate axonal neuropathy but similar find- myelin sheath of the basis pontis. Central cle action potential and motor nerve conduc- ings can be found in profound muscle weak- pontine myelinolysis often results from rapid tion. Amplitude of the compound muscle ness because of neuromuscular junction increase of serum sodium after hyponatrae- action potential was low on proximal and dis- blockade or myopathy. Loss of F waves and H mia. Patients with central pontine myelinoly- tal stimulation. No conduction block, disper- reflexes on day 1 can be explained by the sis often show symptoms such as conscious sion of compound muscle action potential, or presence of lower amplitudes of compound disturbances, tetraparesis, and pseudobulbar F wave response was recordable. Sensory muscle action potentials on distal nerve palsy.1–3 We present a case of central pontine conduction studies on median and ulnar stimulation. Loss of F waves and H reflexes myelinolysis due to compensation of hyponat- nerves at both sides of the body were normal with normal distal nerve conduction velocity raemia, resulting in acute onset of pseudo- for distal latency and amplitude of sensory is suggestive of proximal demyelination or choreoathetosis and sensory disturbances. nerve action potential. No H reflex was dysfunction at the spinal cord level. Loss of H A 39 year old woman was submitted to a recordable on stimulation of posterior tibial reflexes and the F response has not been department of internal medicine of another nerves on both sides. The patient now reported previously in patients with hypoka- hospital due to a long history of alcoholism, disclosed that he had accidentally consumed laemic periodic paralysis. As H reflex latency resulting in bad general condition accompa- http://jnnp.bmj.com/ barium carbonate (15 g) on the day before depends on several factors including the cen- nied by severe anaemia, toxic gastritis, and admission. He ingested barium salt by tral delay in the cord involving conduction, acute pancreatitis. She was alert without any mistaking it for dieting food given to him by a synaptic transmission, and activation of ante- mental disturbances. Laboratory data dis- slimming centre. Ingestion was followed rior horn cells, any of these processes might closed metabolic acidosis and hyponatraemia immediately by profuse vomiting. One hour be involved in barium carbonate poisoning. of 126 mmol/l. She received bicarbonate and later, the patient had watery diarrhoea. Four The exact mechanism for their absence is still physiological saline intravenously to compen- hours later he was taken to hospital where his unclear. These responses reverted back to sate for the metabolic disturbances. Serum stomach was washed out with magnesium normal on day 7. The concentric needle sodium increased to 136 mmol/l within 3 sulphate solution. Blood investigations re- EMG study on the second day showed a days. On the third day she suddenly devel- on September 25, 2021 by guest. Protected copyright. peated 8 hours after admission showed reduced recruitment pattern which is found oped severe choreoathetotic movements. normal blood counts, blood gas analysis, and in neuropathies but has also been reported in Therefore she was transfered to our depart- renal and liver function tests. Serum potas- hypokalaemic periodic paralysis.5 ment of neurology. On the day of submission sium was 2.8 m mol/l and sodium was 140 In most cases of barium ingestion the to our department she remained alert, but she mmol/l. An ECG showed prominent U recovery from weakness occurs rapidly and had diYculties in swallowing and speaking. waves. Based on available history and investi- uneventfully.4 Oral magnesium sulphate or Examination of the cranial nerves showed gations, a diagnosis of barium carbonate sodium sulphate precipitate barium in the gut bilateral ptosis and a dissociated nystagmus induced hypokalemic periodic paralysis was and thus reduce absorption. Large amounts on the left side. We also found weakened cor- considered. The patient was moved to the of intravenous potassium are needed to neal and pharyngeal reflexes. There was a intensive care unit and monitored for ar- restore the pump electrogenesis and to general reduction of deep tendon reflexes and rhythmias. He was started on intravenous displace barium from potassium channels.1 muscle tone. Muscle strength was normal. potassium. On day 2, the patient had Hypertension caused by barium cannot be Involuntary movements were absent but completely recovered clinically (power 5/5). reversed by this treatment. Haemodialysis is a angle positioning during movements was Serum potassium was normal. Nerve con- useful therapeutic adjuvant in severe barium choreoathetotic. She was unaware of the duction studies were performed as on day 1 carbonate poisoning. Ventilatory support position of her limbs with closed eyes. We with similar results except that the amplitude may be required due to respiratory muscle instructed her to watch her limbs and she was of compound muscle action potentials were involvement.4 then able to reach her nose with the finger. in the normal range. The F waves and In summary, this is the first electrophysi- When investigating her sensitivity we found a H-reflexes were still unrecordable. Electro- ological study done on day 1 in a case of complete loss of touchíng, vibration, and myography was carried out with concentric barium carbonate poisoning with paralysis. position sense in all limbs. Pinprick sensation needles in the biceps, deltoid, and quadri- Previously involvement of neuromuscular was unremarkable in the upper limbs, ceps. It showed no abnormal insertional or junctions has been considered as a cause for whereas testing of the legs caused a painful spontaneous activity and motor unit action weakness. In our study, we found that barium burning sensation. Thermal sensation and J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.65.4.604 on 1 October 1998. Downloaded from 608 Letters, Correspondence, Book reviews

sensory evoked potentials, which, due to technical reasons, were only performed after the patient’s recovery, were normal. To our knowledge this is the first reported case of central pontine myelinolysis associ- ated with acute onset of movement disorder and isolated aVection of propioceptive sensitivity.1 The appearance of parkinsonism, dystonia, or choreoathetosis in the course of central pontine myelinolysis are often looked on as symptoms of additional manifestation of extrapontine myelinolysis. The association with manifestation of central pontine my- elinolysis remained speculative in some cases of delayed onset of movement disorders after central pontine myelinolysis.1 By contrast our patient showed an acute onset of pseudo- choreoathetosis after manifestation of central pontine myelinolysis and MRI imaging in our subject disclosed no signs of extrapontine myelinolysis. Our patient additionally showed an iso- lated loss of propioceptive sensation. Distur- bances of sensation are described as less severe symptoms of central pontine my- elinolysis. Silver et al2 described an associ- ation of sensory ataxia and aVection of vibra- tion and position sense, but with reduced pinprick sensation.2 This case may imply a further extension of the pontine lesion or a possible extrapontine lesion, not detectable on MRI.2 Defebre et al reported two cases of central pontine myelinolysis with isolated aVection of deep sensation.3 Isolated affection of the medial lemniscus of the brain stem or thalamic infarction may cause sensory ataxia and disturbances of deep sensitivity resulting in choreoathetotic movements.45 Therefore, we speculate that our patient’s pontine lesion caused sensory ataxia and subsequent pseu- dochoreoathetosis, because the movement disturbances appeared without delay after the onset of sensory defects. Moreover, the loss of propioceptive sensitivity with spared thermal and pain sensation implies an isolated altera- tion of the medial lemniscus by sparing the spinothalamic tract.4 This finding suggests a lesion with a pontine site. We found no

extrapyramidal lesion by MRI in our patient. http://jnnp.bmj.com/ In conclusion we hypothesise that the pontine lesion itself may be a possible cause of our patient’s pseudochoreoathetotic movements. JENS FEDERLEIN THOMAS POSTERT HORST PRZUNTEK THOMAS MÜLLER Department of Neurology, Ruhr-University Bochum, St. Josef Hospital, Gudrunstrasse 56, 44791 Bochum, Germany on September 25, 2021 by guest. Protected copyright. Correspondence to: Dr Thomas Müller, Depart- ment of Neurology, Ruhr-University Bochum, St Josef Hospital, Gudrunstrasse 56, 44791 Bochum, Germany.

1 Tison FX, Ferrer X, Julien J. Delayed onset movement disorders as a complication of central pontine myelinolysis. Mov Disord 1991;6:171–3. 2 Silver NC, Barker GJ, MacManus DG, et al. Decreased magnetisation transfer ratio due to demyelination: a case of central pontine myelinolysis. J Neurol Neurosurg Psychiatry 1996;61:208–9. 3 Defebvre L, Rogelet P, Destée A, et al. Regressive dystonia and cerebellar ataxia: two T2 weighted MRI (A) sagittal, and (B) axial scan after acute onset of pseudochoreoathetosis: high unusual symptoms in central pontine my- signal in the central part of the pons. elinolysis. J Neurol 1995;242:450–4. 4 Roh JK, Lee YS. Bilateral medial medullary inf- arction manifested as sensory ataxia: a case sensitivity of her face were normal. We weeks the subject’s symptoms had nearly dis- report and review of the literature. J Korean excluded tabes dorsalis and vitamin B12 appeared. Only a slight reduction of the Med Sci 1996;11:193–6. deficiency by laboratory tests. Cranial CT vibration sense in all limbs persisted. Control 5 Lee MS, KimDY, Kim JT, et al. Abrupt onset of was normal. T2 weighted MRI showed a MRI after 4 weeks disclosed an unchanged transient pseudochoreoathetosis associated with proprioceptive sensory loss as a result of a hyperintense lesion within the pons but no size of the patient’s pontine lesion. At that thalamic infarction. Mov Disord 1998;13: extrapontine myelinolysis (figure). Within 4 time nerve conduction velocities and somato- 184–6. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.65.4.604 on 1 October 1998. Downloaded from Letters, Correspondence, Book reviews 609

Successful treatment of peripheral of antinuclear antibodies was 1:960; most of at least two cases, a diVerential response to paraneoplastic neurological syndromes them were identified as anti-Scl-70. High immunotherapy of peripheral and central 23 in small cell cancer titre (1:6000) antineuronal antibodies were syndromes was found in the same patients. seen on immunofluorescence of fresh frozen In one case,2 a patient with paraneoplastic Immune mediated paraneoplastic neurologi- sections of rat cerebellum. Anti-Hu appeared Lambert-Eaton myasthenic syndrome and cal syndromes often become manifest before as a prominent band in a western blot of subacute cerebellar degeneration due to an the underlying malignancy is detected. As a recombinant Hu protein. initially undetected small cell lung cancer, rule, these syndromes do not improve with As treatment with 3,4-diaminopyridine chemotherapy had a beneficial eVect on antineoplastic treatment.1 We report on a (10 mg every 4 hours) improved the muscle Lambert-Eaton myasthenic syndrome, but case of a patient with small cell cancer with weakness but had no eVect on constipation not on subacute cerebellar degeneration. In peripheral neurological syndromes that re- and the sensory disorder, these symptoms the second case,3 the same combination of sponded favourably to combination chemo- were thought to indicate anti-Hu syndrome. peripheral syndromes was caused by a therapy. Four cycles of chemotherapy (ACO-I non-Hodgkin’s lymphoma. Immunosuppres- At the time of admission the patient, a 66 scheme), however, improved all neurological sion improved neuromuscular, but not cer- year old woman, had had a combination of syndromes. Muscle pain and leg hypo- ebellar symptoms. peripheral neurological symptoms for 3 aesthesia disappeared, and muscle strength Paraneoplastic autoantibodies seem to months: (a) muscle weakness and muscle was fully restored so that the patient was able arise from immunological cross reactions pain of the legs so that she could not walk to walk unattended for long distances. The between tumour antigens and normal target unattended; (b) a numbness of both legs from features of Lambert-Eaton myasthenic proteins. They may take part in the immune the foot to the middle of the thigh; (c) dryness syndrome were also no longer detectable by response to malignancies, or simply be an of the eyes and mouth; and (d) severe consti- EMG. Constipation was alleviated. All types epiphenomenon of an immune process trig- pation. of autoantibodies declined considerably. The gered by the neoplasm.4 The prognosis of Clinical examination showed a load de- antinuclear antibodies titre was reduced to patients who mount a humoral antitumour pendent, proximally accentuated symmetric 1:32; immunoprecipitation for antivoltage response is usually better than that of patients muscle weakness and hypoaesthesia of the gated calcium channel antibodies yielded without response.5 The immune process legs. The patient was unable to stand or walk 22.7 pM, which is within the normal range. characterised by production of paraneoplas- without support. The deep tendon reflexes of Antineuronal antibodies were barely tic autoantibodies, however, is a two edged the arms were decreased on both sides and detected on sections of rat cerebellum at a sword. The neurological disorders often leg reflexes could not be elicited. No patho- serum dilution of 1:32. The anti-Hu signal associated with some paraneoplastic autoan- logical reflexes were detectable. Analysis of was also clearly reduced on a western blot. tibodies are so severe that they require imme- CSF yielded normal values for protein The clinical, physiological, and laboratory diate treatment, even before a tumour is content, cell number, and glucose. Besides a findings before and after chemotherapy— detected. In such cases, immunosuppressive slightly increased erythrocyte sedimentation that is, six months after admission—are treatments bear the risk of supporting rate (35 mm in the first hour), standard summarised in the table. Combination tumour growth by inhibiting the ongoing laboratory values showed no abnormalities. chemotherapy brought about a considerable immune attack against the neoplasm without Abdominal auscultation and CT were unre- and unexpected improvement of two periph- interfering with the metabolism of the malig- vealing. eral neurological syndromes (Lambert- nant cells. Therefore, all eVorts should be Electrophysiological investigation (somato- Eaton myasthenic syndrome and anti-Hu directed at identifying the underlying malig- sensory evoked potentials of the tibial and syndrome with gastrointestinal pseudo- nancy. As soon as the presence of a tumour is median nerves, EMG, and electroneurogra- obstruction, muscle pain, and sensory defi- confirmed, chemotherapy should be initiated phy) showed delayed latencies and a reduced cits) and a concomitant decrease in autoan- to control its growth and to suppress autoan- amplitude of P40 (tibial SEP), N10, and N13 tibody titres in a patient with small cell tibody production, at least outside the CNS. potentials (median SEP) and polyphasic cancer. muscle action potentials. Nerve conductance The results of treatment for paraneoplastic The skillful technical assistance of Mrs S Weiser is velocities were on the border of the normal neurological syndromes are still discourag- gratefully acknowledged. We thank Drs P Eichhorn range for the motor peroneal and tibial nerves ing, despite widespread use of chemotherapy and M Wick for determination of antinuclear as well as for the sensory sural nerve. Stimu- combining antineoplastic and immunosup- antibodies, Dr J Posner for determination of anti-Hu, Dr J Dalmau for critically reading the lation of the ulnar nerve with 20 Hz yielded pressive activity. The reasons for the frequent manuscript, and Ms J Benson for copy editing it. an increment of 60%. Besides a polyneuropa- failures may be irreversible loss of neurons This work was supported by the Friedrich Baur- http://jnnp.bmj.com/ thy syndrome, the results of the electrophysi- due to autoimmune attack and the diVeren- Foundation, Munich. ological examinations suggested Lambert- tial susceptibility of autoreactive B and T VIKTOR ARBUSOW Eaton myasthenic syndrome. cells inside and outside the blood-brain Department of Neurology, Ludwig-Maximilians Computed tomography showed a small barrier to the infusion of immunosuppressive University Munich, Klinikum Groâhadern, D-81366 metastasis of an undetectable primary tumour drugs. Autoimmune paraneoplastic syn- Munich, Germany in a mediastinal para-aortal lymph node, dromes involving the CNS are probably RAYMOND D VOLTZ which was immediately resected and histologi- caused by intrathecal autoreactive lym- Department of Neurology, Memorial Sloan-Kettering cally identified to be small cell cancer. phocytes, which may be less accessible to Cancer Center, 1275 York Avenue, New York, NY 10021, USA

As an autoimmune paraneoplastic origin of inhibiting drugs than immune cells outside on September 25, 2021 by guest. Protected copyright. the neurological symptoms, particularly the blood-brain barrier. This hypothesis is MICHAEL STRUPP Lambert-Eaton myasthenic syndrome, was supported by the case presented here and by Department of Neurology, Ludwig-Maximilians suspected, we measured autoantibodies reports of the diVerential response of central University Munich, Klinikum Groâhadern, D-81366 against presynaptic voltage gated calcium and peripheral syndromes to treatment.23 Munich, Germany channels by immunoprecipitating 125I- By contrast with the refractory central syn- PETER SCHULZ conotoxin binding proteins. The antivoltage dromes, tumour treatment for Lambert- Department of Oto-Rhino-Laryngology, gated calcium channel titre of 105 pM was Eaton myasthenic syndrome has been shown Ludwig-Maximilians University Munich, Klinikum positive, although not extremely so. The titre to have beneficial eVects in many patients. In Groâhadern, D-81366 Munich, Germany Table 1 Clinical, electrophysiological, and immunological variables before and after chemotherapy in Correspondence to: Dr V Arbusow, Department of a patient with small cell cancer Neurology, University of Munich, Klinikum Groâhadern, Marchioninistrasse 15, D-81377 München, Germany. Telephone 0049 89 7095 3 Months after 2585; fax 0049 89 7095 8883; email Time of admission chemotherapy [email protected] Tumour diameter 3 cm Not detected Titre of ANAs 1:960 1:32 IgG titre on rat cerebellum 1:6000 1:32 1 Voltz RD, Posner JB, Dalmau J, et al. Paraneo- Anti-Hu Band in western blot Declined plastic encephalomyelitis: an update of the Pseudo-obstruction Present Absent eVects of the anti-Hu immune response on the nervous system and tumour. Ability to walk unattended No Yes J Neurol Neurosurg Psychiatry 1997;63:133–6. Numbness of legs Present Absent 2 Blumenfeld AM, Recht LD, Chad DA. Coexist- Antibodies against VGCC 105 pM 22.7 pM ence of Lambert-Eaton myasthenic syndrome Electromyography at 20 Hz Increment 60% No increment and subacute cerebellar degeneration: diVeren- tial eVects of treatment. Neurology 1991;41: ANA=antinuclear antibody; VGCC=voltage gated calcium channel. 1682–5. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.65.4.604 on 1 October 1998. Downloaded from 610 Letters, Correspondence, Book reviews

3 Goldstein JM, Waxman SG, Vollmer TL. Suba- and signs might be a predictor of increased Comparison of side of onset with presence cute cerebellar degeneration and Lambert- vulnerability. If initial right sided symptom of psychosis disclosed more patients with Eaton myasthenic syndrome associated with antibodies to voltage-gated calcium channels: predominance did indeed predict the subse- right sided onset of parkinsonian symptoms diVerential eVect of immunosuppressive quent development of psychotic phenomena having psychotic symptoms, although this therapy on central and peripheral defects. J (independent of cognitive decline, age, and was not significant (÷2=3.0, df=1 p<0.09; Neurol Neurosurg Psychiatry 1994;57:1138–9. medication) this might be clinically useful in 4 Drlicek M, Bianchi G, Bogliun G, et al. table). Presence of psychosis was significantly Antibodies of the anti-Yo and anti-Ri type in identifying a patient subgroup in whom associated with presence of cognitive decline. the absence of paraneoplastic neurological particular care is required in titrating medi- Eighteen out of 38 in the cognitively impaired syndromes: a long-term survey of ovarian can- cation. cer patients. J Neurol 1997;244:85–9. group were psychotic by comparison with 12 5 Winter SF, Sekido Y, Minna JD, et al. Antibod- A retrospective review of all case notes of out of 62 in the cognitively intact group ies against autologous tumor cell proteins in patients with Parkinson’s disease, identified (÷2=13.5, df=1, p<0.003). Presence of psy- patients with small-cell lung cancer: association by their presence on the specialist Parkinson’s with improved survival. J Natl Cancer Inst chosis was also associated with duration of 1993;85:2012–8. disease nurse register in a district general illness (t test=2.69, df=36, p<0.02). There hospital, was carried out (a) to evaluate the were no significant diVerences between the presence of psychotic symptoms using a psychotic symptom group and the other A preliminary investigation of laterality checklist, (b) to record asymmetry of parkin- patient groups in age, age at onset of in Parkinson’s disease and susceptibility sonism both currently and at onset, and (c)to symptoms, and dosage of current medication. to psychosis record handedness. Psychotic symptoms (de- Comparative dosage of levodopa and sel- lusions and hallucinations) were only noted egiline are shown in the table. Benzhexol, when they occurred outside an acute confu- Cerebral disease with more prominent left bromocriptine, pergolide, and orphenadrine sided cerebral involvement may be more sional state. All patients had been diagnosed were taken by 10, 14, 13, and seven patients closely associated with psychotic phenomena; by one of two consultant neurologists. The respectively, and showed no diVerences be- a comprehensive review of cerebral laterality level of medication, both current and while tween the groups. Furthermore there were no in relation to psychosis has suggested that a having psychotic symptoms, cognitive assess- special, although unclear, pathophysiology ment, number of years of illness, and significant diVerences in the dose of current may be at work.1 demographic variables were also recorded. medication and the dose noted when under- A review of patients with treated Parkin- Patients who had had a psychotic episode going a psychotic episode. son’s disease found an overall incidence of were compared with the remainder with Cognitive decline was associated with psychiatric side eVects of 20% (range 10–50) respect to asymmetry of symptoms at onset of increasing age but was not related to age of in 908 patients treated in major studies.2 illness, age, duration of illness, medication onset or dosage of medication. When patients Psychoses—that is, hallucinations and levels and demographic variables. This was with cognitive decline (n=38) were removed delusions—occurred with a frequency of 4% repeated with a subgroup of patients with no from the analysis, right sided onset of and were more likely to occur with concur- cognitive deficit. Logistic regression analysis symptoms was significantly related to the rent dementia, increasing age and use of (forward stepwise) was carried out with psy- presence of psychosis (÷2=5.0, df=1, p<0.03) higher dose of levodopa. It is assumed that chosis as the dependent variable. in the remainder. In this subsample there the main precipitant of psychotic phenomena The case notes of 100 patients were were no significant diVerences between left in Parkinson’s disease is dopaminergic excess reviewed. There were 51 men and 49 women and right side onset for age, duration of secondary to treatment. Cognitive impair- in the sample. Fifty one patients were right illness, or dosage of diVerent medication. ment, which has been reported to occur in as handed, four were left handed, and in 45 Logistic regression analysis of the total many as 29% of patients with Parkinson’s handedness was unknown. Dementia was sample, with psychosis as the dependent vari- disease, associated with increased age and noted in 30 patients, with “memory diYcul- able, confirmed the association between psy- older age at onset, may also increase vulner- ties” recorded in a further eight. Hallucina- chosis and cognitive decline (t=3.89, ability to psychosis. tions were recorded in 28 patients and p<0.003) and increased duration of illness Asymmetry in Parkinson’s disease is said to delusions in six. The patients with hallucina- (t=2.64, p<0.02). There were no other remain unchanged over time,3 and patients tions or delusions were classified as the significant contributing variables, although with unilateral onset of Parkinson’s disease psychosis group (n=30), and those with side of onset was the strongest associated manifestations have greater degeneration of dementia and memory diYculties as the cog- variable remaining (t=1.69, p<0.09). How- the contralateral substantia nigra at postmor- nitively impaired group (n=38), for analysis. ever, when the logistic regression was re- 4 tem examination. If predominantly left sided Details of illness, for the whole sample and peated with the subsample without cognitive http://jnnp.bmj.com/ pathology increases the vulnerability to psy- separated into psychotic and non-psychotic decline, right sided onset was the only chotic phenomena then initial right sided subgroup, side of onset, and the demographic variable significantly associated with psy- predominance of parkinsonian symptoms data, are shown in the table. chotic symptoms (t=2.30, p<0.03). Patients’ characteristics and the presence of psychosis Our results show only a trend, in the sam- ple as a whole, linking right sided symptoms Psychosis at onset and the subsequent development of psychosis; perhaps unsurprising in view of the Total sample Ye s N o p Value confounding eVect of cognitive impairment. In the cognitively intact subsample there was on September 25, 2021 by guest. Protected copyright. Patients (n) 100 30 70 Age (y): a significant association with right sided onset Mean 71 71.8 71 NS of symptoms of Parkinson’s disease. This SD 6.8 4.5 7.5 suggests that damage to left hemispheric Age at onset: structures involved in Parkinson’s disease is Mean 64 61.6 64.7 NS associated with a predisposition to psychosis. SD 8.9 8.2 9.1 Duration of illness (y): Our results do not support an iatrogenic Mean 7 10 6.3 <0.02 dopaminergic excess as a cause of psychosis; SD 5.7 7.1 4.6 this may be because of subsequent dosage Dose of levodopa (mg/day): adjustment, or the explanation may lie in Mean 455 506 433 NS asymmetric upregulation of dopaminergic SD 353 320 367 Dose of selegeline (mg/day): receptors and supersensitivity to dopaminer- Mean 3.8 2.8 4.1 NS gic therapy at equivalent doses of medication. SD 5.7 4.3 6.1 The limitations of using retrospective data Side of onset total (n=100): are well recognised and the possibility of mild Right 431627NS cognitive dysfunction not being detected in Left 45 9 36 Side of onset cognitively unimpaired (n=62): the cognitively intact group needs to be Right 25 7 18 <0.03 recognised. However, this preliminary study Left 32 2 30 provides support for our a priori hypothesis EPS at onset (n=95): that right sided predominance of neurologi- Tremor 55 13 42 NS cal deficit at the onset of Parkinson’s disease Rigidity 19 4 15 Akinesia 21 10 11 predicts the subsequent development of psy- chosis. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.65.4.604 on 1 October 1998. Downloaded from Letters, Correspondence, Book reviews 611

We thank Dr Margaret Barrie and Dr Rodney Results of thrombophilia screening Walker for the permission to review case-notes of patients under their care. We thank Vanessa Botwright, specialist Parkinson’s disease nurse, for Test Result Laboratory normal range access to her case register. Prothrombin gene (20210A) mutation Heterozygous SUKHWINDER S SHERGILL Factor V Leiden mutation Negative Department of Psychological Medicine, Institute of Antithrombin III activity (%) 70 80–155 Psychiatry, London, UK Antithrombin III (4 months later) (%) 85 80–155 ZUZANA WALKER Protein C activity (%) 66 65–165 CORNELIUS LE KATONA Protein S free antigen (%) 79 70–115 Protein S total antigen (%) 87 65–115 Department of Academic Psychiatry, University Activated protein C resistance ratio 3.05 >2.3 College London Medical School, London, UK IgG anticardiolipin antibodies (GPL U/ml) 4.1 0.0–14.1 Correspondence to: Dr SS Shergill, Clinical Re- IgM anticardiolipin antibodies (MPL U/ml) 1.3 0.0–1.6 MPL U/ml search Fellow, Department of Psychological Medi- Russell’s viper venom test ratio 1.16 0.9–1.1 cine, Institute of Psychiatry, De Crespigny Park, 50/50 Russell’s viper venom ratio 1.01 0.9–1.1 London SE5 8AF, UK. Platelet neutralisation ratio 1.16 Correction (%) 0.0 0.0–12 1 Flor-Henry P. Cerebral basis of psychopathology. Bristol: John Wright, 1983. 2 Goodwin FK. Psychiatric side eVects of levo- cells/mm3 and a protein concentration of Thrombotic tendencies arise when concen- dopa in man. JAMA 1971;218:1915–20. 3 Lee CS, Schulzer M, Mak E, et al. Patterns of 1.5 g/l with normal glucose. A repeat brain CT trations are less than 60% of normal. The ini- asymmetry do not change over the course of with contrast showed diVuse swelling in the tial concentration was probably secondary to idiopathic Parkinson’s disease. Neurology 1995; posterior fossa, with supratentorial and in- the acute thrombosis or treatment with 45:435–9. 4 Kempster PA, Gibb WR, Stern GM, et al. fratentorial haemorrhages and high attenua- heparin. Repeat testing after 4 months Assymetry of substantia nigra neuronal loss in tion around many of the venous sinuses. Brain showed normal concentrations, hence we Parkinson’s disease and it’s relevance to the MRI disclosed extensive thrombosis of the think that antithrombin deficiency is unlikely mechanism of levodopa related motor func- superior sagittal sinus, the straight sinus, and tions. J Neurol Neurosurg Psychiatry 1989;52: to be implicated in this patient’s CVT. There 72–6. both transverse and sigmoid sinuses. There were no other risk factors for venous was haemorrhage in the left cerebellar hemi- thrombosis in our patient, unlike the recently sphere and haemorrhagic infarcts in the left reported patient with sagittal sinus thrombo- Cerebral venous sinus thrombosis parietal and both cerebellar hemispheres. sis, who was taking the oral contraceptive associated with 20210A mutation of the Full blood count and biochemistry were pill.9 prothrombin gene normal. The erythrocyte sedimentation rate Activated protein C resistance due to the was 24 mm in the first hour and C reactive factor V Leiden mutation is the most Predisposing factors can be identified in up to protein was 24.1 mg/l (normal<8). Autoanti- common hereditary thrombophilia associated 80% of patients who develop cerebral venous bodies including antinuclear antibodies were with CVT,3–6 although in most cases it is also thombosis (CVT).1 In many patients risk fac- negative. Treponemal pallidum haemaggluti- associated with an acquired prothrombotic tors are acquired but 10 to 15% of patients nation test and rapid plasmin reagin tests 3 may have inherited tendencies to thrombosis. were negative. The prothrombin time and tendency, such as the oral contraceptive pill. Deficiencies of protein C, protein S, or activated partial thromboplastin time were In a recent study of 40 patients with CVT, antithrombin are reported in large series. The normal. A thrombophilia screen was per- Activated protein C resistance with the recently identified factor V Leiden mutation formed 24 hours after starting heparin (table). Leiden mutation was found in four patients, (FVR506Q) giving rise to activated protein C Initial antithrombin activity was reduced at protein C deficiency in one, and protein S 3 resistance is one of the most prevalent genetic 70% but was normal when repeated 4 deficiency in another. Isolated hereditary mutations currently identified (10% to 15% months after the initial presentation; how- thrombophilias as a cause of CVT seem to be of the white population),2 and it is now ever, the patient was found to be hetero- rare in the absence of other factors, with only known to be an important risk factor for cer- zygous for the 20210A prothrombin gene the patient with protein S deficiency in the ebral venous thrombosis.3–6 All of these mutation. This was identified using the series of Deschiens et al3 and other occasional thrombophilic tendencies, and particularly polymerase chain reaction (PCR) of exon 14 cases45having no other predisposing factor. the factor V Leiden mutation, are com- and the 3’-untranslated region of the pro- The identification of an inherited throm- pounded by other factors such as the oral thrombin gene, followed by restriction diges- bophilia in a patient with CVT should not, http://jnnp.bmj.com/ contraceptive pill, pregnancy, pueperium, or tion by Hind III. The mutant allele then therefore, preclude a search for other provok- immobility. appeared as an extra DNA fragment on agar- ing factors. To the list of inherited throm- Prothrombin is a precursor of the serine ose gel electrophoresis. The presence of the bophilias should now be added the newly protease thrombin and is a key enzyme in the 20210A allele was subsequently confirmed identified 20210A prothrombin gene muta- process of haemostasis. Recently, a single by DNA sequencing. tion. nucleotide substitution (G to A) at position He was treated with intravenous heparin 20210 in the 3’ untranslated region of the (APTT ratio 2 to 3) with the gradual M W KELLETT P J MARTIN gene encoding prothrombin has been introduction of warfarin which he will T P ENEVOLDSON identified.7 Its heterozygous state, 20210A, is continue for life. His condition gradually on September 25, 2021 by guest. Protected copyright. The Walton Centre for Neurology and Neurosurgery, a risk factor for the development of deep vein improved; he had mild residual pyramidal Rice Lane, Liverpool, UK thromboses,78and it has recently been impli- signs, but no significant disability, and no cated in the development of superior sagittal further seizures. C BRAMMER sinus thrombosis in a woman taking the oral The substitution of G to A at position C M TOH contraceptive pill.9 We report the develop- 20210 of the prothrombin gene is a recently Department of Haematology, Royal Liverpool University Hospital, Prescot Street, Liverpool, UK ment of extensive cerebral venous thrombosis recognised risk factor for venous thrombosis. in a patient, without other risk factors, who It has been found in 18% of selected patients Correspondence to: Dr MW Kellett, The Walton was found to be heterozygous for this newly with a family history of venous thrombosis, Centre for Neurology and Neurosurgery, Rice Lane, Liverpool L9 1AE, UK. Telephone 0044 151 identified genetic mutation. 6% to 7% of unselected patients with deep 529 4324; fax 0044 151 525 3857; email A 46 year old man had headaches for 2 vein thrombosis, but only 1% to 2% of [email protected] weeks which became acutely worse and were controls,78 making it the second most com- associated with vomiting and dizziness. His mon hereditary thrombophilia after the factor conscious level fluctuated but was progres- V Leiden mutation.2 Prothrombin is encoded 1 Bousser M-G, Ross Russell R. Cerebral venous thrombosis. London: WB Saunders, 1997. sively deteriorating. He had a generalised by a 21 kb gene located on chromosome 2 Dahlback B, Hillarp A, Rosen S, et al. tonic-clonic seizure and a history of a sponta- 11p11 to q12. Patients with the mutation Resistance to activated protein C, the FV:Q506 neous deep vein thrombosis. There was no (20210A) have higher plasma prothrombin allele, and venous thrombosis. Ann Haematol family history of thromboses. concentrations than controls with the normal 1996;72:166–76. 3 Deschiens M, Conard J, Horrellou M, et al. He was obtunded with bilateral papil- genotype (20210G), suggesting that hyper- Coagulation studies, factor V Leiden and anti- loedema. There were no focal signs except for coaguability is due to hyperactivity of the cardioloipin antibodies in 40 cases of cerebral a right extensor plantar. Unenhanced brain common coagulation pathway resulting in venous thrombosis. Stroke 1996;27:1724–30. 7 4 Dulli DA, Luzzio CC, Williams EC, et al. CT was normal but a lumbar puncture increased thrombin production. Cerebral venous thrombosis and activated pro- disclosed a pressure of 34 cm of CSF with Our patient had reduced antithrombin tein C resistance [comments]. Stroke 1996;27: 28 000 red blood cells, 40 white blood concentrations at 70% on initial testing. 1731–3. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.65.4.604 on 1 October 1998. Downloaded from 612 Letters, Correspondence, Book reviews

5 Martinelli I, Land G, Merati G, et al. Factor V gene mutation is a risk factor for cerebral venous thrombosis. Thromb Haemost 1996;75: 393–4. 6 Zuba M, Toulon P, Marnet L, et al. Factor V Leiden mutation in cerebral venous thrombo- sis. Stroke 1996;27:1721–3. 7 Poort SR, Rosendaal FR, Reitsma PH, et al.A common genetic variation in the 3’- untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996;88:3698–703. 8 Hillarp A, Zoller B, Svensson P, et al. The 20210A allele of the prothrombin gene is a common risk factor among Swedish outpa- tients with verified deep vein thrombosis. Thromb Haemost 1997;78:900–2. 9 Bloem BR, van Putten MJAM, van der Meer FJM, et al. Superior sagittal sinus thrombosis in a patient heterozygous for the novel 20210A allele of the prothrombin gene. Thromb Hae- most 1998;79:235.

Pseudo-Argyll Robertson pupil of patients with spinocerebellar ataxia type 1 (SCA1)

A pseudo-Argyll Robertson pupil is a neuro- logical sign indicating a normal near reflex but the absence of a light reflex (light-near dissociation), a lack of miosis, and pupil irregularity. It has been reported in patients with diabetes mellitus, multiple sclerosis, Light-near dissociation in the left eye of the sister. (A) The light reflex was absent. (B) A steady gaze Wernicke’s encephalopathy, sarcoidosis, tu- on the marker in front of her nose induced the convergence and accomodation reflexes. mours, and haemorrhage.1 Although the appearance of pseudo-Argyll Robertson pupil Patient 2 was a 20 year old man, the reduced in the Argyll Robertson pupil, is very similar to Holmes-Adie pupil, the first brother of patient 1. He consulted our clinic mydriasis was seen in our patients. A patient is distinguishable from the second by the for examination, although he had not experi- with similar pupillary abnormalities (pseudo- location of lesions and pharmacological enced any neurological problems. He re- Argyll Robertson pupil) has been reported by response. The responsible lesion in pseudo- ceived dialysis three times a week because he Olsen et al.3 The causative disorder of the Argyll Robertson pupil is in the central had renal failure due to pyelonephritis. On patient reported by Olsen et al3 was congeni- region, whereas that of Holmes-Adie pupil is examination, he presented pupillary abnor- tal oculomotor paralysis. They attributed the peripheral. Dilute pilocarpine constricts the malities which were similar to those of patient pupillary abnormalities to the aberrant regen- pupils of patients with Holmes-Adie pupil, 1 (mydriasis; 6.5 mm, light-near dissocia- eration of the oculomotor nerve. In Holmes- butitisnoteVective in patients with pseudo- tion). Although the light reflex was absent, Adie pupil, the reaction to a parasympatho- Argyll Robertson pupil. We present a patient the near reflex was normal. His upward gaze mimetic agent (0.2% pilocarpine) can usually with spinocerebellar ataxia type 1 (SCA1) was slightly limited. Fasciculation was noted be confirmed. Our patient 1, however, did not and her asymptomatic younger brother who on his tongue. The distal portion of the upper respond to 0.2% pilocarpine. Therefore, both exhibited pseudo-Argyll Robertson limbs was slightly weak and the deep tendon there was no denervation supersensitivity in pupil. reflexes in the limbs were slightly accentu- the post-ganglionic parasympathetic nerve Patient 1 was a 21 year old woman who ated. Babinski’s sign was positive in both feet,

fibre after the ciliary ganglion. The most http://jnnp.bmj.com/ complained of gait instability in 1996. There- although there were no signs of spastic or plausible explanation for the mydriasis in our after, she noticed diYculties in speech and in ataxic movement in his limbs and in his gait. patients is the dysfunction of the pre- the fine movement of her hands. Her mother Their father showed no abnormalities on ganglionic parasympathetic nerve fibre con- had had gait disturbance since her 20s and neurological examination. necting the ciliary ganglion and the Edinger- died of pneumonia at the age of 35. The con- Blood was collected for molecular studies Westphal nucleus. It is conceivable that the dition of our patient deteriorated gradually, with informed consent from both patients near reflex is maintained through a diVerent and she was admitted to our hospital in April, and their father. Total DNA was extracted by pathway. Dacso 1 have divided the 1997. Neurological examination showed bi- the phenol/chloroform method from periph- et al Edinger-Westphal nucleus into the rostral lateral mydriasis (7.0 mm in diameter) and eral blood leucocytes. To detect CAG expan- and caudal portion, with the rostral portion light-near dissociation (figure). Although the sion in the SCA1 region, we performed a on September 25, 2021 by guest. Protected copyright. relating to the light reflex and the caudal por- light reflex was absent, the near reflex was polymerase chain reaction (PCR) with Rep-2 normal. The extraocular movements were (5' CAACATGGGCAGTCTGAG 3') and tion relating to the near reflex. Patients with SCA1 present mydriasis and saccadic and the upper gaze of both eyes was Rep-1 (5' AACTGGAAATGTGGGCG- 4 2 occasionally the absence of a light reflex. slightly limited. Optokinetic nystagmus was TAC 3') according to Orr et al. The products absent. Her tongue showed atrophy and However, light-near dissociation has not been of PCR were separated by electrophoresis 5 fasciculation. The distal muscles of the limbs (2% agarose) with ethidium bromide stain- reported in any of these patients. Gilman et al were slightly weak, although muscle tone was ing. Patients 1 and 2 showed the CAG repeat have reported a postmortem case of SCA1 in normal. The deep tendon reflexes were expansion in the SCA1 gene. A sequencing which they found neuronal loss and a marked augmented in her upper and lower limbs. analysis for patient 1 indicated a CAG repeat gliosis of the periaqueductal grey matter as Babinski’s and Chaddock’s signs were posi- number of 60/27 (Dr Igarashi, Niigata well as a neuronal loss of the Edinger- tive on both sides. The sensory system was University). Westphal nucleus. These pathological normal. Her speech was ataxic; slight limb Pupillary reactions are divided into light changes may cause light-near dissociation. ataxia was detected in the limbs; and her gait reflexes and near reflexes. The light reflex Future detailed examinations of the pupillary was wide based and ataxic. Blood and urine pathway reaches the Edinger-Westphal nu- abnormalities in SCA1 patients are eagerly laboratory findings were normal. Her pupils cleus through the pretectal nucleus . The near anticipated. reacted to 1% pilocarpine, but not to 0.2% reflex consists of both the convergence reflex KAZUNORI MABUCHI pilocarpine. Brain MRI showed remarkable and the accommodation reflex. Their path- HIROAKI YOSHIKAWA atrophy of the cerebellum and a slight atrophy ways are diVerent from that of the light reflex MASAHARU TAKAMORI of the pontine tegmentum. 99mTechnetium- until they reach the Edinger-Westphal nu- Department of Neurology, Kanazawa University hexamethylpropyleneamine oxime (99mTc- cleus. Therefore, it may be that the lesion for School of Medicine, Kanazawa, Ishikawa, Japan HMPAO) SPECT disclosed a hypoperfusion light-near dissociation is located between the HIDEHIRO YOKOJI of the cerebellar vermis, pons, and basal gan- pretectal nucleus and the Edinger-Westphal Department of Neurology, Noto General Hospital, glia. nucleus. Although the pupillary diameter is Japan J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.65.4.604 on 1 October 1998. Downloaded from Letters, Correspondence, Book reviews 613

MASAYUKI TAKAHIRA daily) for 5 months at which time medica- Could zopiclone have contributed to the Department of Ophthalmology, Kanazawa University tions were stopped. She was next seen in pathogenesis of the syndrome? At first sight School of Medicine, Kanazawa, Ishikawa, Japan 1996 when she was admitted with an acute this would seem unlikely; It is a cyclopyr- Correspondence to: Dr Hiroaki Yoshikawa, Depart- confusional state which was thought to be rolone with a pharmacological profile similar ment of Neurology, School of Medicine, Kanazawa alcohol related. Brain CT was again normal, to that of short acting benzodiazepines, its University, 13–1 Takaramachi, Kanazawa, Ishikawa and an EEG showed diVuse beta activity actions mediated through increased GABA 920–8640, Japan. Telephone 0081 76 265 2292; fax 0081 76 234–4253. consistent with her benzodiazepine use. At activity in the brain. Hence, it has muscle the time of discharge she was taking zopi- relaxant eVects, as well as sedative, anxiolytic, clone (7.5 mg nightly) in addition to and anticonvulsant properties.4 However, 1 Dacso CC, Bortz DL. Significance of the Argyll nitrazepam, but no neuroleptic medication GABA is an important neurotransmitter in Robertson pupil in clinical medicine. Am J Med was used. the basal ganglia, present in striatopallidal, 1989;86:199–202. 2 Orr HT, Chung MY, Banfi S, et al. Expansion of At the time of her acute admission, investi- striatonigral, pallidothalamic, pallidosubtha- an unstable trinucleotide CAG repeat in gations disclosed a mild neutrophil leucocy- lamic, and nigrothalamic fibres. In movement spinocerebellar ataxia type 1. Nat Genet 1993; tosis (10.1×109/l), hypernatraemia (152 disorders, it has been postulated that within 4:221–6. the basal ganglia-thalamocortical motor cir- 3 Olsen T, Jakobsen J. Abnormal pupillary func- mmol/l), hypoalbuminaemia (22 g/l), and tion in third nerve regeneration (the pseudo- raised erythrocyte sedimentation rate (90 cuit there are two separate projection systems Argyll Robertson pupil). A case report. Acta mm/h) and C-reactive protein (157 mg/l). from the putamen: a direct pathway of Ophthalmol Scand Suppl 1984;62:163–7. Creatine kinase was raised (maximum 978 GABA/Substance P neurons to motor por- 4 Abe T, Abe K, Aoki M, et al. Ocular changes in patients with spinocerebellar degeneration and U/l, first measured 7 days after presentation; tions of the internal segment of the globus repeated trinucleotide expansion of spinocer- normal<190 U/l; 100% MM isoenzyme) as pallidus and substantia nigra pars reticulata, ebellar ataxia type 1 gene. Arch Ophthalmol was lactate dehydrogenase (maximum 839 providing positive feedback to precentral 1997;115:231–6. motor fields; and an indirect pathway of 5 Gilman S, Sima AAF, Junck L, et al. Spinocer- U/l, normal<450 U/l). Cultures of blood, ebellar ataxia type 1 with multiple system urine, faeces, and CSF were negative. Brain GABA/enkephalinergic neurons influencing degeneration and glial cytoplasmic inclusions. CT was normal; MRI showed widespread basal ganglia output through a sequence of 1996; :241–55. Ann Neurol 39 ischaemic changes in the cerebral deep white connections involving the external segment of matter but the basal ganglia were spared and the globus pallidus and the subthalamic “Non-neuroleptic malignant” syndrome no lesions were visible in the brainstem. nucleus, providing a negative feedback to 5 Analysis of CSF showed a moderately raised precentral cortex. Shifts in the balance of We report on a patient with the clinical and protein (0.57 g/l) but was normal in all other activity within these pathways may alter biochemical features of the so-called neu- respects; CSF polymerase chain reaction was globus pallidus/substantia nigra pars reticu- roleptic malignant syndrome, occurring more negative for various infectious agents (herpes lata output and hence result in hypokinesia or than a decade after her last exposure to phe- simplex virus, varicella zoster virus, adenovi- hyperkinesia; for example, hypokinesia is nothiazines, but while taking the cyclopyr- rus, enterovirus, mumps, Mycoplasma). thought to result from increased pallidotha- rolone zopiclone. We consider possible Toxicology screen was negative for phenothi- lamic inhibition and enhanced conduction in mechanisms underpinning the development azines and enquiries with both her consultant the indirect pathway, whereas reduced con- of this clinical syndrome in the light of these psychiatrist and general practitioner aVorded duction through the direct pathway, second- findings and current models of basal ganglia no evidence for recent neuroleptic prescrip- ary to reduced pallidothalamic inhibition, 5 dysfunction. tion. Before the availability of this infor- results in hyperkinesia. For this model, it is of A 62 year old woman was found collapsed mation, a working diagnosis of neuroleptic note that a selective loss of indirect pathway at home. On admission to hospital she was GABA/enkephalin neurons is found in Hunt- malignant syndrome had been made, based 6 alert, eye opening and moving limbs sponta- on the presence of the appropriate clinical ington’s disease, and that GABAmimetics neously, but her aVect was flat and she was 1 (progabide) have been reported to iron out features. Despite appropriate medical man- 7 unable to give any account of herself. She was agement, the rigidity had persisted for 10 on-oV fluctuations in Parkinson’s disease. ° pyrexial (38.9 C) and clinically dehydrated days and therefore, as soon as the diagnosis of Hence, in the light of this model, we suggest with a pulse rate of 110/min and a blood neuroleptic malignant syndrome was consid- that our patient may have had increased brain pressure of 90/60 mm Hg. She was mute and ered, the patient was treated with bromocrip- GABA activity as a result of zopiclone (with or without nitrazepam) treatment, resulting akinetic with a jaw tremor, but there was no tine, initially 1 mg twice daily rising to a muscle tenderness. There was profound axial in increased pallidothalamic inhibition and

maximum of 2.5 mg twice daily. Over the first http://jnnp.bmj.com/ and limb rigidity with opisthotonos, making it enhanced conduction in the indirect pathway, three days on this regime, the rigidity impossible to assess power. Psychiatric review and thus producing profound hypokinesia in improved dramatically, tone returning to found no evidence for a catatonic psychotic the absence of recent neuroleptic treatment. normal. Neurological examination at this state. She was rehydrated with IV crystal- time was normal; particularly, there were no A J LARNER loids, but on the day after admission had an abnormal brainstem signs, although there SARAH C SMITH episode of tachycardia (pulse rate 140/min) SIMON F FARMER and profound hypotension (BP unrecord- was some evidence of mild cognitive impair- ment. Department of Neurology, St Mary’s Hospital, able) which responded to IV colloids. After Praed Street, London, UK The neuroleptic malignant syndrome, first this, she was noted to be less rousable, and 2 Correspondence to: Dr A J Larner, National Hospi-

named by Delay and Deniker, is character- on September 25, 2021 by guest. Protected copyright. her level of consciousness continued to tal for Neurology and Neurosurgery, Queen Square, fluctuate between alert and unrousable for ised by hyperpyrexia, hypertonus, fluctuating London, WC1N 3BG, UK. Fax 0171 829 8720. the next three days. level of consciousness, and autonomic distur- Through relatives, friends, and her previ- bances; the presence of these features is ous medical notes, a history of alcohol thought to be essential to establish the 1 Guzé BH, Baxter LR. Neuroleptic malignant 1 dependence came to light, dating back to diagnosis. Most cases have been associated syndrome. N Engl J Med 1985;313:163–6. with neuroleptic use, although levodopa 2 Delay J, Deniker P. Drug-induced extrapyrami- 1984; she had been admitted on at least three dal syndromes. In: Vinken PJ, Bruyn GW, eds. occasions in the past for alcohol detoxifica- withdrawal may also precipitate a similar Handbook of clinical neurology. Vol 6. Diseases of tion, but continued to indulge in occasional state. Loss of dopaminergic drive in the basal the basal ganglia. Amsterdam: North-Holland, binges and was on long term nitrazepam (10 ganglia has been suggested as a common fea- 1968:248–66. ture in both of these situations. Similar 3 Stauder KH. Die todliche katatonia. Archiv fur mg nightly) because of diYculty sleeping. Psychiatrie und Nervenkrankheiten 1934;102: However, there was no history of recent binge phenomena, labelled as acute lethal catatonia 614–34. drinking, or of attempted withdrawal from or fatal catatonia, were reported in the 4 Goa KL, Heel RC. Zopiclone: a review of its benzodiazepine. Also, in 1984 the patient had pre-neuroleptic era.3 Hence, current neu- pharmacodynamic and pharmacokinetic prop- roleptic use is not an absolute requirement erties and therapeutic eYcacy as a hypnotic. presented with paranoid delusions and audi- Drugs 1986;32:48–65. tory hallucinations which were thought to be for the occurrence of this clinical syndrome, 5 DeLong MR. Primate models of movement dis- due to a psychosis secondary to alcohol with- as also shown in the reported case. It remains orders of basal ganglia origin. Trends Neurosci drawal; brain CT at this time was normal. She possible that medication may act as a trigger 1990;13:281–5. 6 Reiner A, Albin RL, Anderson KD, et al.DiVer- was then seen by a psychiatrist and the diag- for some independent process, for which ential loss of striatal projection neurons in nosis was revised to schizophrenia; she was concurrent organic brain disease is recog- Huntington disease. Proc Natl Acad Sci USA treated initially with trifluoperazine (5 mg nised to be a predisposing factor.1 Perhaps 1988;85:5733–7. twice daily). previous neuroleptic use may also sensitise 7 Bergmann KJ, Limongi JCP, Lowe YH, et al. Potentiation of the dopa eVect in parkinsonism for less than 1 month, then with pimozide the basal ganglia in some way to the develop- by a direct GABA receptor agonist. Lancet (6 mg daily) and procyclidine (5 mg thrice ment of these features. 1984;i:559. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.65.4.604 on 1 October 1998. Downloaded from 614 Letters, Correspondence, Book reviews

Secondary hyperkalaemic paralysis al which was not considered in the article, and can be diYcult to verify by clinical CORRESPONDENCE In their report describing a case of hyperka- history alone. The use of anabolic steroids is laemic paralysis associated with renal failure very prevalent among body builders with the and use of spironolactone, Evers et al1 provide lateral thigh being a common site of adminis- an illustration of the results obtained from tration. Direct injection could have trauma- conduction studies performed on the pa- tised the nerve, and may also explain the lack Corpora amylacea in hippocampal tient’s median sensory nerve. Utilising the of any improvement with time. It is also noted sclerosis calibration markers, the average amplitude of in the illustration of the unaVected leg, that a the sensory action potential (SAP) measures small dimple is present in the skin at a site I read with pleasure the short report of Van 10.6 µV before haemodialysis and 27.2 µV where the distal motor branch may be Paesschen et al.1 This finding perhaps may afterward. However, these measurements are vulnerable, although this is significantly more raise some interest again in corpora amylacea recorded in table 1 as being 20.0 µV and 24.0 distal than the biopsy site in our patient. This as well as in the pathology of temporal lobe µV, respectively. may, however, be an indicator of previous epilepsy. As I studied corpora amylacea for An increase in SAP amplitude after nor- injections to the lateral thigh. about 25 years I call the attention of the malisation of serum potassium concentration authors to the first—but important—finding would oVer additional support the authors’ PETER L SILBERT of Ramsey who published in her article in suggestion that the pathological process Department of Neurology, Royal Perth Hospital, Perth, Western Australia 19652 a case of a 35 year old man who had causing weakness in secondary hyperkalae- intractable temporal lobe epilepsy. Surgical mic paralysis probably originates at the level ROD MOORE intervention was performed with temporal of nerve rather than muscle. Sports Medicine, St John of God Hospital, Murdoch, lobe resection including 3 cm of hippocam- R F GLEDHILL Perth, Western Australia pus. The pathologist’s report stated that the Department of Neurology, MEDUNSA and BRIAN DAWSON tissue seemed histologically normal except Ga-Rankuwa Hospital, South Africa for a few areas of pyknosis and shrinkage of Department of Human Movement, University of Correspondence to: Professor R F Gledhill, Depart- Western Australia, Perth, Western Australia neurons and a decrease in the number of ment of Neurology, PO Box 108, Medunsa 0204, neurons in the hippocampus. The presence South Africa. Telephone 0027 12 521 4136/4209; Correspondence to: Dr P Silbert, Department of of corpora amylacea without gliosis was fax 0027 12 521 4758/560 0086. Neurology, Royal Perth Hospital, GPO Box X2213, Perth, Western Australia. Telephone 0061 8 9224 noted and was especially prominent in the 2593; fax 0061 8 93817848; email: psilbert@ hippocampus. The diagnosis was “mild 1 Evers S, Engelien A, Karsch V, et al. Secondary opera.iinet.net.au presenile cortical atrophy of the temporal hyperkalaemic paralysis. J Neurol Neurosurg lobe with corpora amylacea in the hippocam- Psychiatry 1998;64:249–52. pus.” 1 Padua L, D’Aloya E, LoMonaco M, et al. I studied the occurrence of corpora Mononeuropathy of a distal branch of the Evers replies: femoral nerve in a body building champion. amylacea in 1407 cases of various diseases J The figures in table 1 were indeed incorrect Neurol Neurosurg Psychiatry 1997;63:669–71. with special reference to the so called predi- and the correct figures from the original data lection sites of corpora amylacea, and I are 8 µV before haemodialysis and 24 µV after sometimes found large numbers of corpora The authors reply: haemodialysis. amylacea in the hippocampal area and other We are grateful for the response of Silbert et regions with and without special pathology, SEVERS al. In our paper1 we described an isolated even in young people. The conditions which Department of Neurology, University of Münster, mononeuropathy of a distal branch of the favour the development of corpora amylacea Albert Schweitzer Strasse 33, D 48129 Münster, femoral nerve and hypothesised that stretch- vary greatly (aging, chronic vascular— Germany ing and compression of the nerve had hypoxic—diseases, ALS, multiple sclerosis, probably occurred during strenuous exercise. dementias, etc) as well as various pathoge- We agree with the possibility of a traumatic Traumatic distal femoral neuropathy netic mechanisms promoting formation, nerve lesion due to needle injection and we which included chronic hypoxia, neuronal We read with interest the recent report by have knowledge of some cases of this kind of degeneration, external hydrocephalus—as a 1 nerve injury in body builders, but in the case Padua et al on a body building champion consequence of local cortical atrophy— with an isolated mononeuropathy of a distal reported in the article, we specifically asked http://jnnp.bmj.com/ diabetes mellitus, and other processes which branch of the femoral nerve, having recently the patient if drug injections had been carried induce stress states expressed by strong HSP out in the thigh. He replied that he had never 3–7 seen a similar patient, with a diVerent cause. 60 positivity in our investigations (see for A 39 year old sports physiologist under- used this kind of drug administration. appropriate references). So the corpora amy- went a resting muscle biopsy using the Berg- Moreover, our patient did not refer to any lacea formation really is an epiphenomenon strom technique, for research purposes. He pain in the thigh, whereas in the case of in diVerent diseases, as Van Paesschen et al had previously undergone eight of these Silbert et al an “intense cramp” was felt by the state. biopsies on the other leg without adverse subject. Concerning the figure, detailed clini- eVect, and this biopsy was performed by an cal examination of both thighs had been per-

L LEEL-O˜SSY experienced operator. Under lignocaine an- formed and no suspected “dumping” was on September 25, 2021 by guest. Protected copyright. Departments of Neuropathology, Neurology, aesthesia the biopsy needle was inserted. As seen. We think that the eVect in the figure Neurosurgery, and Psychiatry, University Hospital could rather be due to the hypertrophy of a Tatabánya and Miskolc, Hungary manual suction was applied followed imme- diately by closing the biopsy needle, the sub- nearby muscle and as noted it is distal to the ject had an intense feeling of cramp (that had site of the femoral nerve branch. not been noticed with previous biopsies). The For these reasons, the hypothesis of needle 1 Van Paesschen W, Révész T, Duncan JS. site of the biopsy was 5 cm lateral to the mid- injury was not considered in the article, but Corpora amylacea in hippocampal sclerosis. J point between the patella and the anterior we agree that in the case of nerve lesion in Neurol Neurosurg Psychiatry 1997;63:513–15. body builders, a needle injury (for anabolic 2 Ramsey HJ. Ultrastructure of corpora amylacea. superior iliac spine. Over subsequent months J Neuropathol Exp Neurol 1965;24:25–39. wasting of the distal lateral vastus lateralis drug injection) must always be suspected. 3 Leel-Ox ssy L. The origin and the pathological muscle was noted. An EMG 3 months after significance of the corpus amylaceum. Acta LUCA PADUA Neuropathologica (Berl) Suppl II, 1981:396–99. injury showed increased insertional activity, 4 Leel-Ox ssy L. The structure and the pathological fibrillation potentials, and positive sharp PIETRO TONALI significance of the corpus amylaceum. (Hung.) waves with no activation of motor unit poten- Ist Neurologia In: Leel-Ox ssy L, ed. Selected chapters in tials in the distal fibres of the vastus lateralis neuropsychiatry. Budapest: Statistics Publishing ROBERTO PADUA Co, 1989:189–202. muscle. A further EMG 6 months after the Ist Ortopedia, Università Cattolica 5 Leel-Ox ssy L. Pathological significance and biopsy showed evidence of reinnervation. characteristics of corpus amylaceum. Neuropa- In our patient, the distal mononeuropathy LUCA PADUA thology (Japan) 1991;11:105–14. 6 Leel-Ox ssy L. The occurrence of corpus amy- was traumatic, and clearly related to the nee- AFaR Osp Fatebenefratelli, Isola Tiberina, Roma, Italy laceum (polyglucosan body) in diabetes melli- dle biopsy. A distal motor branch of the tus. Neuropathology (Japan) 1995;15:108–11. femoral nerve as identified in the anatomical 7 Leel-Ox ssy L. Statistical evaluation and patho- studies of Padua 1 was traumatised by the 1 Padua L, D’Aloya E, LoMonaco M, et al. logical significance of the incidence of corpus et al Mononeuropathy of a distal branch of the anylaceum. Clinical Neuroscience (Hung) 1997; biopsy. It does raise the possibility of an alter- femoral nerve in a body building champion. J 50:90–102. native mechanism for the patient of Padua et Neurol Neurosurg Psychiatry 1997;63:669–71. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.65.4.604 on 1 October 1998. Downloaded from Letters, Correspondence, Book reviews 615

linear accelerator has shown that it is possible important point of all, and I repeat it here: “.. to achieve good results with this technique the most important question in designing or BOOK REVIEWS and some of these are also published here. In choosing a scale is how well it is suited to the the United Kingdom we are beginning to task at hand in terms of validity, eYciency, identify a much wider range of applications sensitivity and specificity ... ”. If only every for this technique and, in the not too distant researcher would read, remember, and act on future, we should expect a whole range of this one statement then neurological research Radiosurgery. Volume Two. Edited by reports of its use in malignant brain tumours, would advance greatly. DOUGLAS KONDZIOLKA. (Pp 268, Sw Fr 258). recurrences, melanomas, and other meta- The book is then primarily structured Published by S Karger AG, Switzerland, static lesions. However, for the moment the around diseases. This is useful to anyone 1998. ISBN 3-8055-6547-X. literature is rather sparse and it remains to be interested in a specific disease, but means that seen whether the technique in future will also many non-specific areas of measurement are It has sometimes been said, perhaps unfairly, become the treatment of choice for these not covered. The chapters cover most of the that radiosurgery has been a treatment look- rather dismal conditions. common and important neurological dis- ing for a successful application. This volume, The place of radiotherapy in general, and eases: multiple sclerosis; amyotrophic lateral the second in the series on radiosurgery, stereotactic techniques in particular, for sclerosis; head injury; stroke; movement attempts, in some parts more successfully benign lesions, such as acoustic neuromas disorders including Parkinson’s disease; epi- than others, to refute that suggestion. The and meningiomas, in my view remains lepsy; and dementia. Many of the chapters technique was first established by Lexsell, uncertain despite some rather encouraging follow a similar layout, but there are excep- using a collimated cobalt source (“the gamma results published here. At this stage it is per- tions. Most seem to be written by people who knife”). In the United Kingdom, the Stere- haps sensible to proceed with caution until have direct experience of the scales, and otactic Radiosurgery Centre in SheYeld has the long term eVects are clearer. With regard indeed there is much original and useful data been treating patients since 1985. The to the future, the rapid advances in imaging relating to the assessment of progression in published results for treatment of arteriov- techniques using MRI, the various new vari- motor neuron disease in that chapter. There enous malformations have been good and its ants of CT, and the PET machine, oVer the are two more general chapters. The first cov- place in the non-operative management of tantalising possibility of being able to ers paediatric developmental scales, and I cerebral arteriovenous malformations is now identify both the anatomical and functional think that this is the only similar book to secure. Radiosurgery has now become the pathology to be targeted for treatment. With cover this area. The second covers the treatment of choice for appropriately sized the merging of these exciting new technolo- measurement of the outcome from rehabilita- and located malformations. However, in- gies it may at last be possible to make some tion. The best chapters are those covering creasingly refined techniques of endarterial real progress in improving the outcomes for multiple sclerosis, amyotrophic lateral sclero- obliteration for vascular lesions have also CNS tumours. sis, movement disorders, and dementia. The been developing apace in parallel, and it DAVID HARDY chapter on stroke is much less comprehen- seems likely that the combined use of both sive, and contains some errors in references techniques will in future make it increasingly (for example, to the Hamrin ctivity Index), rare for us to have to undertake surgery for Handbook of Neurologic Rating Scales. and the chapter on head injury stands out as these often demanding lesions. Edited by ROBERT M HERNDON (Pp 276, containing much less useful information. The main drawback of the “gamma knife” US$125). Published by Demos Vermande, The book gives considerable useful infor- technique of radiosurgery has been the enor- New York, 1997. ISBN 1-888799-07-2. mation about many of the scales mentioned, mous capital outlay required for the equip- and certainly would help anyone who was ment. In the United Kingdom there is only This well produced book joins a small group unfamiliar with the field. The references are one machine and this has perhaps inhibited a of books which actually show some of the reasonable, although sometimes inaccurate wider application of the technique in the measures now used in clinical research. and quite often statements are made without management of intracranial malignancy. The There are many, many measures, and each reference, which can be irritating especially as greater availability of machines in the United book can only show a selection. This book references do exist to support most state- States, and the commercial pressures to would be helpful to anyone who is interested ments. Overall this book is good, and retain the appropriate return on investment, in learning about measures of disease severity complements the other books available well. has led to a wider range of applications in the and outcome, although it might not be the It will be especially helpful to those interested

United States and the results of some of these best in any particular circumstance. in the current “hot” diseases, multiple sclero- http://jnnp.bmj.com/ are published in this book. The development Everyone should read the introduction to sis, amyotrophic lateral sclerosis, and Parkin- of fractionated stereotactic radiotherapy this book, written by Dr Herndon. It is full of son’s disease. using relocatable stereotactic frame and a common sense. It also emphasises the most DERICK WHITE on September 25, 2021 by guest. Protected copyright.