234 Letters to the Editor

presynaptic terminal, interfering with ACh ratory findings included: pH 6.8; serum J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.55.3.234 on 1 March 1992. Downloaded from release. methanol: 180 mmol/l. Treatment by intra- PATRICK PULLICINO venous infusion of sodium bicarbonate and NOEL BECK 4-methyl pyrazole was initiated and the _f-.P Department ofMedicine, acidosis was overcome within a few hours. St Luke's Hospital, Gwardamangia, Malta Two days later, she regained consciousness and reacted to verbal commands. On exam- In1wv Correspondence to: Dr Pullicino, Department of ination, bilateral extensor plantar response, Neurology/SUNY Buffalo, Buffalo General Hospi- tal, Buffalo, NY 14203, USA. blurred vision, rigidity, and distal postural Figure Incremental increase in the compound tremor, were noted. The right pupil was motor action potential of the left abductor digiti 1 Oh SJ. Electromyography. Neuromuscular transmis- unreactive and optic fundi examination minimi on repetitive stimulation of the ulnar sion studies. Baltimore, MD: Williams and showed bilateral oedema. CT carried out five nerve at 50 Hertz. Wilkins;1988:69. 2 Ropper AH, Widjicks EFM, Shahani BT. Elec- days after intoxication showed a bilateral, trodiagnostic abnormalities in 1 3 consec- symmetrical area of low density involving the utive patients with Guillain-Barre Syndrome. basal ganglia region (fig a). One week later, Arch Neurol 1990;47:881-7. the was 3 Ropper AH. Unusual clinical variants and signs patient well-oriented and cooperative in Guillain-Barre syndrome. Arch Neurol without apparent intellectual deterioration. 1986;43:1 150-2. Tremor and rigidity were of left predom- 4 Koski CL, Gratz E, Sutherland J, Mayer RF. inance and with ami- Clinical correlation hypokinesia persisted normal in two nerves; c) CMAP ratio from with anti-peripheral mye- mic face and monotonous proximal and distal stimulation less than 0-7 lin antibodies in Guillain-Barre syndrome. dysarthric, speech. Ann Neurol 1986;19:573-7. Sensory examination revealed symmetrical in the nerves right median and left ulnar 5 Miller RG, Kuntz NL. Nerve conduction stud- loss of superficial and proprioceptive sensa- recorded on day 21; d) A reduction of both ies in infants and children. J Child Neurol 1986;1: 19-26. tion of the lower extremities with hyper- ulnar sensory action potential amplitudes Motor conduction velocities and dis- below 80% of the lower limit of pathia. normal; d) F tal latencies were normal, but distal sensory wave latency prolongation from day 7, latencies of both sural nerves were increasing to 120% of the upper limit of decreased. normal by day 21. Putaminal necrosis after methanol Brain MRI was performed with a 0.5 T Repetitive stimulation of the left ulnar intoxication superconductive magnet three weeks after nerve was performed, with the active surface intoxication (fig b, c). The core lesion (fig b) recording electrode over the midportion of Optic neuropathy and putaminal necrosis are centred on the putamen, surrounded by a the abductor digiti minimi muscle. The the two main complications of methanol large hyperintensity (fig c), suggested major CMAP at rest was compared with the highest poisoning,' 2 generally occurring in combina- oedema. Two months later she remained CMAP on amplitude stimulation. On the tion after severe intoxication of either suicidal almost totally blind with optic atrophy on third hospital day supramaximal stimulation or accidental origin. Surviving patients usu- fundus examination. Signs of moderate bilat- at 3 Hertz gave an increment of 18%, and ally show permanent sequelae consisting of eral sensory neuropathy and extrapyramidal stimulation at 50 Hertz gave an abnormal bilateral blindness and motor dysfunction syndrome persisted. Neuropsychological incremental response of 81% (normal mean including rigidity, hypokinesis, and other evaluation was within normal limits. Repeat increment = 2-4%; upper limit of normal = Parkinsonian-like signs, occasionally asso- CT and MRI examinations showed residual 42 4%') (figure). The incremental response ciated with limb polyneuropathy. Brain bilateral putaminal cavities. decreased over the next 10 days (table). pathology has been documented in earlier Our report illustrates the usual conse- The patient was intubated. She was started studies showing the specific involvement of quences of massive methanol intoxication on on guanidine, 240 mg every six hours. Slow the basal ganglia, especially the putamen. the nervous system.2 After a short comatose improvement began by the twelfth hospital This unusual lesion site was more recently period, severe bilateral blindness and moder- day, but eye movements took over a month to confirmed in reports including brain imaging ate extrapyramidal syndrome were found in return to normal. The patient started to walk data, either with CT or MRI.3 We report a association with lower limb axonal after two months and subsequently made a new case study in which repeated CT and neuropathy. complete recovery. MRI examinations may help elucidate the The relationship between methanol- An incremental response to repetitive stim- specific putaminal damage. induced blindness and damage to the retina ulation is characteristic of impairment of A 40 year old depressive woman was and optic nerve was the first feature to be well http://jnnp.bmj.com/ presynaptic release ofacetylcholine (ACh), as admitted to hospital after attempting suicide documented in early clinical-pathological seen in the myasthenic syndrome, botulism, by methanol ingestion, having drunk nearly works. Subsequently, several necropsy stud- and also with some drugs and with certain one litre of methylated spirits several hours ies of the brain revealed symmetrical haem- types of arthropod envenomation. In the earlier. On admission, she was comatose with orrhagic necrosis of the putamen or promi- myasthenic syndrome it appears very likely generalised hypotonia, non reactive pupils nent hyperaemia in the basal ganglia' as the that an antibody, probably IgG, interferes and hyperventilation. Her vital signs were: specific neuropathological outcome of with ACh release. In botulism, the botulinus apyrexia, blood pressure 120/60, pulse rate human methanol intoxication. Selective toxin also decreases ACh release.' 1 10 bpm, respiration 30/mn. The main labo- putaminal locus of lesions was confirmed in

Although the progression of signs in our on September 30, 2021 by guest. Protected copyright. patient was similar to that seen in botulism, the normal pupils and inability to detect Clostridium botulinum or botulinus toxin were against botulism. The raised CSF protein is very atypical for botulism and the finding of abnormal motor and sensory nerve conduc- tion and F wave prolongation are strongly in favour of GBS.2 A clinical picture resembling botulism is known to occur as a variant of GBS.3 There is increasing evidence for a humoral role in GBS. Antibodies to several myelin antigens have been found in GBS and com- plement fixing antibodies to peripheral nerve myelin appear to be involved in myelin destruction.4 The titre of these antibodies is highest when neurological symptoms first occur' and the abnormal incremental Figure 1 (a) First non injected CT scan five days after intoxication. Bilaterally symmetrical, low response early in the course of our patient's density lesion in the putaminal region with central isodense zone possibly suggesting illness fits this pattern. The finding of an microhaemorrhages; (b) MRI scan: Ti weighted axial section (TR = 450ms; TE=28ms). incremental response to repetitive stimula- Bilateral putaminal lesions; (c) T2 weighted sequence ( TR = 2000ms, TE = 120ms). High signal tion in our patient with GBS suggests the intensity of the basal ganglia and the periventricular white matter suggesting major oedematous presence of an antibody directed against the participation. Letters to the Editor 235 vivo with CT and MRI examination. Initial 2 McLean DR, Jacobs H, Mielke BW. Methanol the deficits of position and vibration sense J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.55.3.234 on 1 March 1992. Downloaded from CT may be normal but evidence of promi- poisoning: a clinical and pathological study. dropped to the level of the wrist and ankle. Ann Neurol 1980;8:161-7. could walk with a cane, but there was nent putaminal destruction generally appears 3 Koopmans RA, Li DKB, Paty DW. Basal She a few days post onset. Residual bilateral ganglia lesions in methanol poisoning: MR obvious wasting of the hand and foot putaminal hypodensity is common.3 Since appearance. Comput Assist Tomogr 1988; muscles. of the putamina has not 12: 168-9. Electrophysiological assessments were symmetrical necrosis 4 Orthner H. Die methylalkohol vergiftung. Berlin: been observed after other intoxications, such SpringerVerlag. 1950. performed on day 6, 17, 28, and 57 after CT findings may be of special diagnostic 5 Berkovic KJ, Karpati G, Carpenter S, Lang AE. ingestion. Motor and sensory conduction value.3 MRI findings in our case suggest the Progressive dystonia with bilateral putaminal studies were performed using standard tech- hypodensities. Arch Neurol 1987;44:1 184-7. usefulness of this method for accurate delim- ;.iques of supramaximal percutaneous stim- itation of lesion boundaries, especially with ulation and surface recording. F response partial recovery technique, as well as for latencies were recorded as the minimal laten- evaluating the extent and importance of cies following median and peroneal nerve oedema on spin-echo images. stimulation. Electromyography was per- The mechanism of methanol toxicity formed using standard concentric needle seems to be indirect, related to the effect of electrode. Somatosensory cortical evoked formic acid generated from methanol by Reversible myeloneuropathy resulting responses, referred to Fz, were recorded from alcohol dehydrogenase. Accordingly, studies from podophyllin intoxication: an 2-5 cm behind the vertex (Cz') following in monkeys have shown that ocular toxicity electrophysiological foliow up posterior tibial nerve stimulation at the could be prevented by 4-methyl pyrazole, an ankles and from a point just posterior to C3 alcohol dehydrogenase inhibitor. Several (C3') on the 10-20 system, following median reports have insisted on the relationship Podophyllin used mainly as a vegetable nerve stimulation at the wrists. Erb's point between symptoms of poisoning or neuro- cathartic has been known for over 100 years. and spinal recording (Cv2) were also made logical sequelae and the degree of metabolic In 1942, Kaplan introduced the use oftopical but are not shown. Stimuli sufficient to cause acidosis and level ofblood formate. The main podophyllin in the management of con- a small muscle twitch were delivered at 3 Hz unresolved issue remains that of the mechan- dyloma acuminatum.' Although widely used, and two trials of 500 responses were aver- ism of the putaminal damage, and, specifi- however, there are scant reports concerning aged. Sensory nerve action potential ampli- cally, the significance of this part of the the toxic effect of this compound and it is not tudes of median and sural nerves reduced striatal complex being selectively involved. generally appreciated that podophyllin may progressively from 18 and 13 pV, respect- Orthner4 proposed that the putaminal necro- produce systemic and neurological toxicity. ively, to no response on day 6 to day 28. sis resulted from decreased venous outflow The earliest systemic toxicity includes nau- Compound muscle action potential ampli- through the veins of Rosenthal. Another sea, vomiting and watery diarrhoea. Bone tudes ofthenar and extensor digitorum brevis suggestion was that formic acid may achieve marrow suppression and disturbance of muscle decreased from 11 and 5 mV, respec- higher concentrations within the putamen hepatic function may appear in the first week. tively, to 8 and 0-5 mV from day 6 to day 57. than in other brain structures.2 Having Neurological toxicity can produce peripheral Conduction velocity of peroneal nerve over observed some similarity between optic neuropathy with or without encephalopathy. the leg segment decreased from 32:5 m/s to lesions and brain white matter changes in Autonomic neuropathy and ataxia have also 23-9 m/s. F response latencies were pro- their cases, Sharpe et al' proposed that been described.2 Previously, ataxia has been longed or responses blocked at wrist and methanol could provoke a specific histotoxic attributed to the central nervous system ankle stimulation. EMG showed mildly anoxia with myelinoclastic effect. However, toxicity of podophyllin;' 2 however, a patient decreased recruitment patterns without white matter damage is not the rule in most with severe sensory ataxia was reported by spontaneous activity on day 6 and moderate cases of methanol intoxication. Rather, as Gorin et al3 who described the first case of denervation with fibrillation potentials in the previously emphasised, the necrotic process podophyllin intoxication resulting in pro- distal muscle on day 57, but the proximal appears to involve primarily the grey matter found loss of proprioception. They ascribed muscle revealed normal patterns of recruit- of the putamen. ataxic gait and aimless limb movement to loss ment throughout follow up. A series of CT and MRI findings are compatible with of position sense resulting from dorsal cortical evoked potentials of median and ischaemic necrotic lesions. From an anatom- radiculopathy. posterior tibial nerves is shown in the ical point of view, the arterial supply of the In our country, powder of roots and figure. putamen is provided by the lateral lenticulo- rhizome of Podophyllum peltatum is an expen- Our patient presented acutely with symp- striate arteries, originating from the proximal sive herb used for treatment of liver diseases toms and signs of spinal cord and peripheral http://jnnp.bmj.com/ middle cerebral artery. The lesion site in our and soft tissue pain. We describe a 51 year old nerve disease soon after exposure to podo- case, as in most similar reports in the woman whose systemic and neurological phyllin. Electrophysiological studies corre- literature, is restricted to the putamen, symptoms appeared rapidly soon after ingest- lated well with clinical features which pre- whereas, in usual deep MCA infarcts, the ing Podophyllum peltatum for relief of soft dominantly involve the sensory system. From caudate nucleus is generally involved, what- tissue rheumatism. One hour later, she devel- the initial series of assessments, ataxia was ever the mechanism, haemodynamic or oped headache followed by nausea and best ascribed to dysfunction of the posterior occlusive. watery diarrhoea. The next day, she could not column. However, as her symptoms pro- the residual disturbance of the poste- Finally, bilateral putaminal necrosis has sit or stand without support. Incoordination gressed on September 30, 2021 by guest. Protected copyright. also been reported in other conditions such of all her limbs and rapidly spreading numb- rior column played a minor role and neuro- as Wilson's disease, striatal degenerations, ness rendered her severely ataxic. On the pathy appeared to have largely contributed to anoxic strokes and Leigh's disease.5This part fourth day after ingestion, she was admitted her ataxia. of the basal ganglia may be particularly to our hospital for further evaluation. On One interesting aspect of electrophysiology susceptible to various pathological processes. admission, her vital signs and general phys- is the dramatic improvement of central con- Moreover, massive bilateral oedema has been ical examination were unremarkable. Her duction accompanied by deterioration of shown on MRI (fig c) and strongly suggests mental status and cranial nerves were nor- peripheral nerve function. The rapid disruption of the blood-brain barrier, possi- mal. Tendon reflexes could not be elicited. improvement of abnormalities of cortical bly facilitating the diffusion of toxic formate There was mild muscle weakness, predom- evoked potentials is of considerable interest molecules into the adjacent putamen. inantly distal. Plantar responses were flexor. and suggests remyelination of the affected J PELLETIER Proprioception and vibration sense were lost axons in the posterior column once the M H HABIB R KHALIL at the level of the elbow and inguinal region. exposure to podophyllin ended. Regarding Department of Neurology Fine touch sensation was impaired below T8 the pathology of the peripheral nerves, G SALAMON level. In contrast, cutaneous sensation was sequential electrodiagnosis suggests axonal Department of Neuroradiology was marked degeneration with sensory predominance. D BARTOLI minimally involved. There dys- Department of Radiology metria and truncal ataxia which was The clinical and electrophysiological fea- P JEAN increased by obliteration of vision. Neither tures of our patient are similar to those of Toxicology Clinic, orthostatic hypotension nor other autonomic nitrous oxide abuse,4 except for the acute as University Hospital of chronic onset. It is well known Marseilles, France dysfunctions were observed. opposed to Routine blood, urine and stool chemistry, that the pathology of nitrous oxide abuse is as well as serology, immunology and CSF demyelination of posterior and/or lateral col- 1 Sharpe JA, Hostovsky M, Bilbao JM, Rewcasde tests were normal. umn with axonal neuropathy.4The pathology NB. Methanol optic neuropathy: a histo- our was similar to that of nitrous pathological study. Neurology (Ny) 1982;32: Two months later, there was a marked of patient 1093-1100. improvement of kinaesthetic sensibility and oxide abuse.