556 Letters to the Editor J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.59.5.556 on 1 November 1995. Downloaded from mmol/l), total bilirubin (1 59 mg/dl), >- Neuropathological studies in patients with glutamyl transferase (73 U/1), and pro- Wemicke's encephalopathy have shown thrombin time (1-37 international symmetric lesions in the paraventricular normalised ratio, normal values from 1-00 to regions of the thalamus and hypothalamus, 1*27). Examination of CSF one day after in the mamillary bodies, periaqueductal admission showed a raised CSF/serum albu- region of the midbrain, floor of the fourth min ratio (12-5), but a normal cell count (no ventricle, and midline structures of the cere- malignant cells were detected) and glucose bellum.2 Histologically, the acute lesions concentration; fluid was sterile on culture. were found in and around blood vessels. Oligoclonal IgG bands were absent in the Hypertrophic endothelial cells, demyelina- CSF. A cranial CT on admission as well as tion, loss of neuropil, proliferation of astro- bilateral carotid angiography three days after cytic and microglial cells, and relative admission were normal. Five days after preservation of neurons have been reported admission her mental state deteriorated. She in neuropathological studies. Periventricular was intubated and transferred to the neurol- haemorrhages, usually petechial in size, may ogy intensive care unit. On admission there be found in up to 20% of cases. Two she was comatose without reaction to patients were reported to have died of exten- painful stimuli. Oculocephalic responses sive haemorrhagic brainstem lesions were absent. The isocoric pupils had slight detected on necropsy.3 bilateral reaction to light. Corneal reflexes Wemicke's encephalopathy remains a were symmetrically present. An EEG clinical diagnosis, because of the insen- showed diffuse slowing. She had hypo- sitivity of neuroimaging in this setting. Initial tension requiring fluid administration, CT in our patient was normal. Hae- dopamine, and noradrenaline. She had a morrhages due to Wemicke's encephalo- (39°C) and a raised C-reactive protein pathy detected on CT or MRI are seldom concentration (13-8 mg/dl); antibiotic treat- reported in the medical literature. In one ment (imipenem plus erythromycin) was ini- report scattered haemorrhages in the thalami tiated. Repeat cranial CT was normal. and posterior diencephalon in a patient with Twenty four hours after admission at the Wernicke-Korsakoff syndrome were shown intensive care unit she acutely developed by CT.4 In a case report a small haemor- bilateral dilated areactive pupils. Immediate rhagic lesion adjacent to the body of the lat- CT showed severe intraventricular haemor- eral ventricle was discovered on MRI.5 The rhage (figure, A). Coagulation studies (pro- severe intraventricular haemorrhage due to thrombin time, partial thromboplastin time, Wernicke's encephalopathy as seen in our platelet count) determined on the same day patient raises the question of whether spon- as well as the day before intraventricular taneous bleeding of Wernicke's encephal- haemorrhage were normal. The patient had opathy was accentuated by an associated no clinical signs of cutaneous or mucous coagulopathy. At the time of ventricular bleeding. Despite immediate insertion of haemorrhage the data on clotting studies bilateral intraventricular drains the patient were normal. Moreover, the patient had not died 14 hours later. received antiplatelet agents. At necropsy the brain weighed 1440 g and HANS-WALTER PFISTER FRIEDRICH VON ROSEN showed some arteriosclerosis of the great Department ofNeurology arteries at the base of the brain. An KARL BISE aneurysm was not found in the circle of Institute for Neuropathology, Ludwig-Maximilians-University ofMunich, (a) Demonstration ofhaemorrhage by CT Willis. Coronal sections showed pronounced Germany (without contrast) in the third ventricle, ambi- haemorrhages at the walls of the third ven- ent, and quadrigeminal cistern. (b) Coronal tricle bilateral, which extended into the third Correspondence to: Professor Hans-Walter section showed a pronounced haemorrhage in ventricle, the aqueduct, and the floor of the Pfister, Ludwig-Maximilians-University, Depart- ment of Neurology, Klinikum GroBIhadern, the third ventricle (arrow). In addition, small fourth ventricle (figure, B, C). There was MarchioninistraBe 15, 81377 Munich, Germany. http://jnnp.bmj.com/ areas of haemorrhagic discolouration in corti- destruction of the mamillary bodies by callsubcortical regions secondary to agonal haemorrhage. In addition to petechial haem- 1 Naidoo DP, Bramdev A, Cooper K. Wemicke's raised intracranial pressure are shown. (c) A encephalopathy and alcohol-related disease. necrotising haemorrhagic lesion in the floor of orrhage, microscopy showed prominent and Postgrad Med J 1991;67:978-81. the fourth ventricle (arrow), small areas of dilated capillaries, reactive astrocytes in the 2 Victor M, Adams RD, Collins GH. The haemorrhagic necrosis in cortical regions sec- periventricular regions around the third and Wernicke-Korsakoff syndrome and related disor- ondary to agonal raised intracranial pressure, fourth ventricles and aqueduct, and mild ders due to alcoholism and malnutrition. 2nd in ed. Philadelphia; Davis, 1989:1-117. and subarachnoid haemorrhage, especially neuronal loss. 3 Harper C. Wemicke's encephalopathy: a more the basal cisterns and the leptomeninges of the The clinical diagnosis of Wemicke's common disease than realised. A neuro- cerebellar vermis secondary to intraventricular pathological study of 51 cases. .7 Neurol encephalopathy is often overlooked' and was on September 23, 2021 by guest. Protected copyright. haemorrhage. Neurosurg Psychiatry 1979;42:226-31. not suspected in our non-alcoholic patient 4 Roche SW, Lane RJM, Wade JPH. Thalamic during her lifetime. Her mental abnormali- hemorrhages in Wemicke-Korsakoff syn- and cystectomy with construction of an ileal ties had aroused clinical suspicion of carci- drome demonstrated by computed tomogra- nomatous meningitis, paraneoplastic phy. Ann Neurol 1988;23:312. conduit were performed. Two and a half 5 Schroth G, Wichmann W, Valavanis A. Blood- weeks before admission the patient devel- disorder, cerebral vasculitis, or sinus throm- brain barrier disruption in acute Wemicke oped a rectovaginal fistula; the rectum and bosis. A recent necropsy study showed that encephalopathy: MR findings. 7 Comput sigmoid colon were resected and an end 80% of patients with the Wemicke- Assist Tomogr 1991;15:1059-61. colostomy and another ileal conduit were Korsakoff syndrome were not diagnosed constructed. Oesophagogastroscopy, per- during life (Harper et al, 1986, cited in formed because of vomiting four days before Naidoo et all). Apart from patients with a admission, showed candidiasis of the history of chronic alcoholism, Wemicke's in association with oesophagus. Neurological examination encephalopathy can be found in other med- malignant hyperpyrexia showed that the patient was disoriented in ical settings-for example, malnutrition, time, had a right sided abducens paresis, prolonged intravenous feeding, cancer, gas- We report a case of neuromyotonia in a horizontal gaze evoked nystagmus to the left, tric plication, and acquired immuno- patient with malignant hyperpyrexia. and a vertical gaze evoked nystagmus deficiency syndrome. ' 2 The extensive The patient, a 19 year old woman, has upward. The tendon reflexes were normal. abdominal surgery and vomiting before had several discrete episodes of muscular She had no paresis of the extremities, but admission may have led to decreased food stiffness over her lifetime and several years slight dysmetria of the arms and legs. There uptake and thiamine deficiency in our of twitching in the hand and calf muscle. were no sensory abnormalities. Routine patient. Parenteral nutrition in the intensive Episodes of calf muscle contracture and pain laboratory tests were normal except for care unit probably aggravated Wernicke's had occurred from the age of 5 with two serum glucose (243 mg/dl), (2-4 encephalopathy. severe episodes at the ages of 5 and 16. Letters to the Editor 557 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.59.5.556 on 1 November 1995. Downloaded from associ- P K NEWMAN University Department ofClinical Neurology, Some of the episodes may have been Neurology Department, Institute ofNeurology, ated with fever. A third severe episode Middlesbrough General Hospital, Queen Square, occurred at the age of 19 two weeks after Ayresome Green Lane, London WClN 3BG, UK normal vaginal delivery of a healthy child. Middlesbrough, Cleveland, developed rapid onset of spasms affect- 1 Smith CAD, Cough AC, Leigh PN, Summers She TS5 SAZ, UK BA, Harding AE, Maraganore DM, et al. ing her legs and arms which progressed so M C BATESON Debrisoquine hydroxylase gene polymor- that she had difficulty breathing and swal- Bishop Auckland General Hospital, phism and susceptibility to Parkinson's dis- lowing. She was also vomiting. Examination Cockton Hill Rd, ease. Lancet 1992;339:1375-7. Bishop Auckland, 2 Armstrong M, Daly AK, Cholerton S, showed a temperature of 42°C with tachy- County Durham, Bateman DN, Idle JR. Mutant debrisoquine cardia and tachypnoea and generalised BL14 6AD, UK hydroxylation genes in Parkinson's disease. muscular spasm. Her kinase was Lancet 1992;339: 1017-8. to Dr Newman. raised at 740 IU/l and investigation for an Correspondence 3 Kurth MC, Kurth JH. Variant cytochrome P450 CYP2D6 allelic frequencies in infective source including blood cultures 1 Nelson TE, Flewellen EH. The malignant Parkinson's disease. Am J Med Genet 1993; was negative. A chest radiograph was nor- syndrome. N Engl J Med 1983; 48: 166-8. mal and autoantibodies were negative. She 309:416-8. 4 Plante-Bordeneuve V, Bandmann 0, Wenning 2 Newsom-Davis J, Mills KR. Immunological G, Quinn NP, Daniel SE, Harding AE. responded well to treatment with intra- associations of acquired neuromyotonia. CYP2D6 debrisoquine hydroxylase gene venous within one week and had Brain 1993;116:453-69. polymorphism in multiple system atrophy. no permanent neurological sequelae. 3 Foster PS, Denborough MA. The effect of cal- Mov Disord 1995;10:277-8. channel antagonists and BAY K 8644 Further admissions to a general medical cium 5 Armstrong M, Idle JR, Daly AK. A polymor- on fluxes of malignant hyperthermia phic cfo I site in exon 6 of the human unit occurred two weeks after starting susceptible muscle. Int J Biochem 1993;25: cytochrome P450 CYP2D6 gene detected by phenytoin, with rash, fever and generalised 495-504. the polymerase chain reaction. Hum Genet muscle stiffness, and two months later just 1993;91 :616-7. 6 Tsuneoka Y, Matsuo Y, Iwahashi K, Takeuchi after starting trimethoprim for a urinary H, Ichikawa Y. A novel cytochrome infection, with rash and muscle stiffness P450IID6 mutant gene associated with only. No further episodes have since Parkinson's disease. Y Biochem 1993;114: occurred during treatment with carba- Arg296 to Cys296 polymorphism in exon 263-6. is 7 Iwahashi K, Miyatake R, Tsuneoka Y, Matsuo mazepine. In addition to the episodes of 6 of cytochrome P-450-2D6 (CYP2D6) Y, Ichikawa Y, Hosokawa K, et al. A novel fever and muscle stiffness she has several not associated with multiple system cytochrome P-450IID6 (CYPIID6) mutant years of twitching of the hand and calf mus- atrophy gene associated with multiple system atro- phy. J Neurol Neurosurg Psychiatry 1995; cles. No muscle spasm due to exertion or 58:263-4. cold was described. Neurological examina- An allelic association between mutant alleles 8 Quinn NP. Multiple system atrophy. In: Fahn tion showed hypertrophy of both calves and of the cytochrome P-450-2D6 (CYP2D6) S, Marsden CD, eds. Movement disorders 3. continuous twitching of the calves and fore- and Parkinson's disease has been shown by Oxford: Butterworths International Medical Reviews, 1994:262-81. arms. Two sisters and her parents had no several groups'-3. The analysed lie neuromuscular symptoms; none had ever in exon 4 and 5 of the CYP2D6 gene, received a . homozygotes showing the poor metaboliser Sensory and motor nerve conduction phenotype. Analysis of these mutant alleles studies and EMG were performed. The among patients with multiple system atro- Ataxic hemiparesis with bilateral leg sensory (superficial peroneal and median) phy showed no difference in the frequency ataxia from pontine infarct and motor (posterior tibial and median) dis- of these alleles from that in control subjects.4 tal latencies and conduction velocities were A further polymorphism causing an Ataxic hemiparesis is a syndrome charac- normal. The sensory nerve action potential amino acid change from Arg296 to Cys296 terised by weakness and cerebellar-like amplitudes were normal as were the com- at the HhaI site in exon 6 of the CYP2D6 ataxia on the same side of the body.' A pound muscle action potential (CMAP) gene has been described.56 The frequency of lesion resulting in ataxic hemiparesis must amplitudes recorded from the abductor pol- this polymorphism, which is not associated involve both the corticospinal fibres and the licis brevis and abductor hallucis. The with the poor metaboliser phenotype,5 was afferent or efferent cerebellar fibres in loca- CMAP waveforms were followed by after 26% among normal white subjects,5 but only tions where the tracts are in close proximity. discharges lasting for up to 50 seconds, 9% in Japanese control subjects.6 Recently, The afferent and efferent cerebellar fibres which made accurate estimation of F wave an association with the Arg296 to Cys296 form a loop extending from the cerebral cor- Concentric needle polymorphism was suggested in a small tex the pons and middle cerebellar latencies impossible. through http://jnnp.bmj.com/ EMG of tibialis anterior and medial gas- series of 10 Japanese patients with multiple peduncle to the cerebellar cortex and then trocnemius showed repetitive spontaneous system atrophy and it was suggested that extending from the dentate nucleus through discharges of motor unit potentials at all this polymorphism may be a useful marker the superior cerebellar peduncle, red sites sampled. This activity occurred irregu- for susceptibility to this disease.7 nucleus, and thalamus back to the cerebral larly in rhythmical 0-5-1-5 second bursts at We examined the frequency of this poly- cortex. Ataxic hemiparesis has been associ- high rates (50-200/s). morphism in a larger series of 74 white ated with lesions in the corona radiata, thal- This patient has electrophysiologically patients with multiple system atrophy. The amus, midbrain, and pons. Fisher and Cole established spontaneous and stimulus diagnosis was clinical in 598 and pathologi- first reported that a paramedian infarct of induced neuromyotonia without neuropathy cally established in a further 15, in whom the basis pontis located at the junction of the on September 23, 2021 by guest. Protected copyright. with episodes of hyperpyrexia consistent frozen brain samples were analysed. The upper one third of the pons with the lower with malignant hyperthermia.' Patients with method for the detection of the polymor- two thirds could produce a contralateral neuromyotonia may have increased sweat- phism has been described elsewhere.6 Our ataxic hemiparesis.' One of the major ques- ing and feel unwell but we think that malig- results show a similar frequency of the tions concerning pontine ataxic hemiparesis nant hyperthermia has not previously been mutant allele (48 of 148 total alleles) among is why the limb ataxia is seen only contralat- described. The underlying deficit in neu- the patients with multiple system atrophy eral to the lesion and not bilaterally.' 2 The romyotonia is likely to lie in the nerve cell to the published frequency among white corticopontine fibres terminate by synapsing membrane, and some patients may have control subjects (32% v 26%; X2 = 0-97, with the pontine nuclei and most fibres then abnormalities.2 P = 0 32). cross the midline to enter the contralateral Malignant hyperthermia has been associ- We conclude that, at least in white sub- middle cerebellar peduncle. A basis pontis ated with muscle membrane disorders, and jects, the HhaI polymorphism in exon 6 of infarct might thus be expected to produce abnormalities in muscle ion channels have the CYP2D6 gene is not associated with bilateral limb ataxia because it would involve been described.' We suggest an anomalous multiple system atrophy and is therefore not ipsilateral pontine nuclei and corticopontine ion channel common to muscle and nerve a useful marker for susceptibility to multiple fibres as well as pontocerebellar fibres that as a possible mechanism for the association system atrophy. have crossed from the contralateral side. We in this patient. report a case of a mid-pontine paramedian T D GRIFFITHS Financial support from the Deutsche infarct with caudolateral extension resulting Neurology Department, Forschungsgemeinschaft (DFG) and the Middlesbrough General Hospital Parkinson's Disease Society is gratefully acknowl- in ataxic hemiparesis with bilateral leg S CONNOLLY edged. ataxia. Department of Clinical Neurophysiology, 0 BANDMANN An 80 year old white man with a history Massachussetts General Hospital, G K WENNING 32 Fruit Street, N P QUINN of coronary artery disease suddenly noticed Boston, MA 02114, USA A E HARDING left sided weakness. On examination, he had