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Delayed onset generalised dystonia after cyanide poisoning
Clinical Neurology and Neurosurgery
ELSEVIER
Clinical Neurology and Neurosurgery 97 (1995) 213-215
Case r e p o r t
Delayed onset generalised dystonia after cyanide poisoning Rupam Borgohain a'*, Ajay Kumar Singh a, Hari Radhakrishna a, V. Chalapathi Rao b, Surath Mohandas a aDepartment of Neurology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad- 500 482, India bDepartment of Radiology, CDR Hospital, Hyderguda, Hyderabad - 500 029, India Received 30 August 1994; revised 7 February 1995; accepted 7 February 1995
Abstract
A 27 year old female developed delayed onset of persistent generalized dystonia following a suicidal attempt with potassium cyanide. Cranial CT scan showed bilateral putaminal hypodensities which were also seen on MRI scans to be hypointense on T I and hyperintense on T2 weighted images. Multimodality evoked potentials were normal. An improvement was noted with levodopa.
Keywords." Cyanide; Dystonia; MRI; CT scan; Putaminal lesions; Poisoning
Introduction
Acute cyanide (CN) poisoning may be suicidal or accidental and is usually fatal. As very few persons survive, reports of delayed neurological sequelae [1-5], which manifest as either parkinsonism or dystonia, are rare. Chronic low level CN poisoning is due to environmental exposure to cyanogenetic glycosides in plants and manifests as either optic neuropathy [6], deafness [7], tropical ataxic myeloneuropathy [8,9] or 'konzo', an epidemic form of spastic parapare,;is [10]. A 27-year-old woman who survived acute CN il~gestion only to develop severe persistent, incapacitating, generalized dystonia, is described.
2. Case report
A 27-year-old woman was admitted with stiffness and weakness of all four limbs making her more or less bedridden for the past 5 years. These symptoms started a month after she had attempted suicide by ingesting ap-
*Corresponding author. Tel.: (+91-040) 228 899, ext. 543 (office), 842 933 (residence); Fax: (+91-040) 229 316. 0303-8467/95/$9.50 © 1995 Elsevier Science B.V. All rights reserved S S D I 0303-8467(95)00029.-1
proximately 300 mg KCN, procured from her father's place of work, a goldsmith. In the immediate aftermath she was admitted to a local hospital in a state ofhypotension and was quickly given a gastric lavage and fluid supplementation. Specific antidotal treatment was not administered. There was no history of altered sensorium or seizures. She was independently ambulant when discharged a week later. She remained asymptomatic for a month. Over the next 2 months she developed gradually progressive stiffness and weakness of all four limbs along with a lack of clarity in speech. These symptoms peaked within 2 months and remained as such till her admission. At admission, there were no remarkable features on general or systemic examination. Neurological examination revealed normal higher intellectual functions. She had severe hyperkinetic dysarthria due to dystonia with a mixture of impairment of articulatory, phonatory and prosodic elements. Mild left facial weakness, severe generalised lead pipe rigidity and bradykinesia were noted. The dominating feature was hemiplegic dystonia with bilateral involvement characterized by flexed upper limbs, extended lower limbs and normal deep tendon reflexes with flexor plantar responses. Neck and spine were rigidly extended. Upper limbs were flexed and supihated, with fingers tightly flexed and thumb strongly opposed. Lower limbs were extended at all joints with
214
R. Borgohain et al. I Clinical Neurology and Neurosurgery 97 (1995) 213-215
I
Fig. 1. Coronal Tz weightedMRI slice showingbilateral symmetrical hypointense putaminal lesions (arrows).
ankle inversion and toe flexion. This was asymmetric with the left side being more involved. The hemiplegic dystonia did not permit an accurate assessment of power - this appeared to be MRC grade 2-3/5 on the left and 4/5 on the right. She had a markedly dystonic gait and needed support to walk. Routine investigations including haemoglobin estimation, total and differential leucocytic counts, peripheral smear, blood glucose, blood urea nitrogen, serum creatinine, sodium and potassium were all normal. Slit lamp examination for Kaiser-Fleischer rings were negative and serum ceruloplasmin and copper were normal; these were done as part of the routine workup for generalised dystonia. A C T scan of the brain showed bilateral putaminal lucencies. MRI of the brain showed sharply delineated hypointense lesions corresponding to the two putamina in T1 (Fig. 1) and hyperintense lesions in T2 (Fig. 2) weighted images. Visual evoked potentials, brain stem auditory evoked potentials and somatosensory evoked potentials on stimulation of the posterior tibial nerves were normal. In the absence of a response to high dose anticholinergics, she was treated with gradually increasing dosages of levodopa and carbidopa. She showed a significant improvement in the rigidity with a reduction in dystonic posturing resulting in clearer speech, ability to use her right hand for eating, and allowed her to take a few steps without support though mostly on her toes. Further progress was hampered by gastric intolerance to doses higher than 250 mg L-Dopa with 25 mg carbidopa 3 times a day.
used sodium and potassium CN salts and organic cyanides (burning of polyurethanes, ingestion of bitter almonds or apricot stones) [11]. Taken orally CN is rapidly absorbed and reacts instantaneously with cytochrome oxidase to cause a widespread histotoxic hypoxia. Death is due to respiratory arrest following medullary dysfunction [1]. The average lethal dose of KCN is only 250 mg and most cases of acute CN poisoning are fatal within the first half hour [1]. As a consequence, delayed neurological sequelae have rarely been reported [1-5]. In such instances, the brunt is borne by the basal ganglia clinically manifesting as dystonia or parkinsonism, invariably associated with lesions of putamina and pallidum. Dystonia is often correlated with isolated putaminal or pallidal lesions while combined lesions result in parkinsonism [1-5]. The bilateral putaminal lesions seen correlated well with the clinical concomitant of dystonia in this patient and are unlikely to be of ischemic-hypoxic origin as the Ammon's horns were unaffected [1]. Our patient had features of hemiplegic dystonia as described in rare cases of necrosis of the putamen by Denny-Brown [121. Chronic CN toxicity is due to presence of cyanogenetic glycosides in large amounts in certain tropical staple foods such as cassava, yam, sweet potato, corn, millet and certain beans such as small black lima beans. Tobacco smoke also contains considerable amounts of CN (150-300/lg per cigarette). Plant glycosides are hydrolysed to release CN as hydrocyanic acid (HCN) which is rapidly absorbed through the gastrointestinal tract or the lungs. Detoxification is mainly to thiocyanate (SCN). Chronic CN toxicity has been associated with a form of optic neuropathy [6] variously known as tobacco amblyopia, West Indian amblyopia, Jamaican optic neuropathy and tropical amblyopia. Chronic CN intoxication has also been associated with deafness [7], tropical ataxic
3. Discussion
Acute CN intoxication may be secondary to accidental or suicidal exposure to hydrocyanic acid, industrially
Fig. 2. Axial T 2 weightedMRI section showing symmetricalhyperintense putaminal lesions (arrows).
1~ Borgohain et al./ Clinical Neurology and Neurosurgery 97 (1995) 213-215
myeloneuropathy [8,9] ~Lnd with 'konzo', an epidemic form of spastic paraparesis [10]. Cyanide (acute), carbon monoxide and manganese intoxication are clinically similar and produce either parkinsonism or a dystonia syndrome. Manganese is concentrated in mitochondria [13], CN inhibits cytochrome oxidase, and carbon mono:dde binds to haemoglobin and cytochromes. Parkinsonism due to acute CN poisoning appears to be due to postsynaptic mechanisms [1], though presynaptic perturbations caused by structural and functional damage of nigrostriatal pathways, may also contribute [5]. Based on a response to parenteral apomorphine, Valenzuel~L et al. [2] treated a patient of acute CN toxicity with levodopa and obtained a gratifying response. This patient too, when treated with levodopa combined with carbidopa, showed an improvement. Our patient, like previously reported cases [2], had delayed onset of extrapyramidal syndrome. Unlike those cases [2-4], she showed only a minimal tendency for spontaneous recovery. A lone previous study of brain stem auditory and visual evoked potentials in acute CN toxicity reported normal findings [2] confirming the neurophysiological integrity of the auditory and visual pathways as, except for the reticular zone of the substantia nigra, there is no clinical or pathological evidence of damage to brain stem or visual pathways. We too found normal VEPs and BAEPs similarly in our patient. In addition the somatosensory evoked potentials from both the lower limbs were normal. Somatosensory evoked potentials have not been previously documented in acute CN toxicity. There have been only 12 reports [3,5] of MRI of the brain following acute CN intoxication and hyperintensity in T2 in the 2 putamina has been reported as early as 8 days [3]. Similar finclings were seen in our patient when MRI was done 6 & IL/2years after acute CN intoxication.
215
References [l] Uitti, R., Rajput, A., Ashenhurst, E. and Rozdilsky, B. (1985) Cyanide induced Parkinsonism: a clinicopathologic report. Neurology, 35: 921-925. [2] Valenzuela, R., Court, J. and Godoy J. (1992) Delayed cyanide induced dystonia. J. Neurol. Neurosurg. Psychiat., 55: 198-199. [3] Messing, B. (1991) Extrapyramidal disturbances after cyanide poisoning (first MRI investigation of the brain). J. Neural Transm., 33 (Suppl.): 141-147. [4] Finelli, P. (1981) Changes in the basal ganglia following cyanide poisoning. J. Comput. Assist. Tomogr., 5: 755-756. [5] Rosenberg, F., Myers, J. and Martin, W. (1989) Cyanide-induced parkinsonism: clinical, MRI and 6-fluorodopa PET studies. Neurology, 39: 142-144. [6] Victor, M. (1970) Tobacco amblyopia, cyanide poisoning and vitamin B12 deficiency: a critique of current concepts. In: Smith, J.L. (Ed.), Neuro-ophthalmology: Symposium of the University of Miami and Bascom Palmer Eye Institute, Vol. 5, Huffman Publishing Company, Hallandale, FL, pp. 33~18. [7] Osuntokun, B.O., Singh, S.P. and Martinson, F.D. (1970) Deafness in tropical nutritional ataxic neuropathy. Trop. Geogr. Med., 22: 281-288. 18] Osuntokun, B.O. (1968) An ataxic neuropathy in Nigeria: a clinical, biochemical and electrophysiological study. Brain, 91: 215248. [9] Roman, G.C., Spencer, P.S. and Schoenberg, B.S. (1985) Tropical myeloneuropathies: the hidden endemias. Neurology, 35:11581170. [10] Tylleskar, T., Howlett, W.P., Rwiza, H.T., Aquilonius, S.-M., Stalberg, E., Linden, B., Mandahl, A., Larsen, H.C., Brubaker, G.R. and Rosling, H. (1993) Konzo: a distinct disease entity with selective motor neuron damage. J. Neurol. Neurosurg. Psychiat., 56: 638-643. [111 Berlet, H., Quadbeck, G. and Ule, G. (1983) Chemische Krankheitsursachen und Nervensystem: exogene Intoxikationen. In: Ule, G. (Ed.), Pathologie des Nervensystems, Vol. 2, SpringerVerlag, Berlin-Heidelberg-New York, pp. 251-656. [12] Denny-Brown, D. (1968) Clinical symptomatology of basal ganglia diseases. In: Vinken, P.J. and Bruyn, G.W. (Eds.), Handbook of Clinical Neurology, Vol. 6, Diseases of the Basal Ganglia, North Holland Publishing Company, Amsterdam, pp. 133-172. [13] Mena, N. (1979) Manganese poisoning. In: Bruyn, G.W. and Vinken, P.J. (Eds.), Handbook of Clinical Neurology, Vol. 36, Intoxications of the Nervous System, Pt I., North Holland Publishing Company, Amsterdam, pp. 217-237.
ELSEVIER
Clinical Neurology and Neurosurgery 97 (1995) 213-215
Case r e p o r t
Delayed onset generalised dystonia after cyanide poisoning Rupam Borgohain a'*, Ajay Kumar Singh a, Hari Radhakrishna a, V. Chalapathi Rao b, Surath Mohandas a aDepartment of Neurology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad- 500 482, India bDepartment of Radiology, CDR Hospital, Hyderguda, Hyderabad - 500 029, India Received 30 August 1994; revised 7 February 1995; accepted 7 February 1995
Abstract
A 27 year old female developed delayed onset of persistent generalized dystonia following a suicidal attempt with potassium cyanide. Cranial CT scan showed bilateral putaminal hypodensities which were also seen on MRI scans to be hypointense on T I and hyperintense on T2 weighted images. Multimodality evoked potentials were normal. An improvement was noted with levodopa.
Keywords." Cyanide; Dystonia; MRI; CT scan; Putaminal lesions; Poisoning
Introduction
Acute cyanide (CN) poisoning may be suicidal or accidental and is usually fatal. As very few persons survive, reports of delayed neurological sequelae [1-5], which manifest as either parkinsonism or dystonia, are rare. Chronic low level CN poisoning is due to environmental exposure to cyanogenetic glycosides in plants and manifests as either optic neuropathy [6], deafness [7], tropical ataxic myeloneuropathy [8,9] or 'konzo', an epidemic form of spastic parapare,;is [10]. A 27-year-old woman who survived acute CN il~gestion only to develop severe persistent, incapacitating, generalized dystonia, is described.
2. Case report
A 27-year-old woman was admitted with stiffness and weakness of all four limbs making her more or less bedridden for the past 5 years. These symptoms started a month after she had attempted suicide by ingesting ap-
*Corresponding author. Tel.: (+91-040) 228 899, ext. 543 (office), 842 933 (residence); Fax: (+91-040) 229 316. 0303-8467/95/$9.50 © 1995 Elsevier Science B.V. All rights reserved S S D I 0303-8467(95)00029.-1
proximately 300 mg KCN, procured from her father's place of work, a goldsmith. In the immediate aftermath she was admitted to a local hospital in a state ofhypotension and was quickly given a gastric lavage and fluid supplementation. Specific antidotal treatment was not administered. There was no history of altered sensorium or seizures. She was independently ambulant when discharged a week later. She remained asymptomatic for a month. Over the next 2 months she developed gradually progressive stiffness and weakness of all four limbs along with a lack of clarity in speech. These symptoms peaked within 2 months and remained as such till her admission. At admission, there were no remarkable features on general or systemic examination. Neurological examination revealed normal higher intellectual functions. She had severe hyperkinetic dysarthria due to dystonia with a mixture of impairment of articulatory, phonatory and prosodic elements. Mild left facial weakness, severe generalised lead pipe rigidity and bradykinesia were noted. The dominating feature was hemiplegic dystonia with bilateral involvement characterized by flexed upper limbs, extended lower limbs and normal deep tendon reflexes with flexor plantar responses. Neck and spine were rigidly extended. Upper limbs were flexed and supihated, with fingers tightly flexed and thumb strongly opposed. Lower limbs were extended at all joints with
214
R. Borgohain et al. I Clinical Neurology and Neurosurgery 97 (1995) 213-215
I
Fig. 1. Coronal Tz weightedMRI slice showingbilateral symmetrical hypointense putaminal lesions (arrows).
ankle inversion and toe flexion. This was asymmetric with the left side being more involved. The hemiplegic dystonia did not permit an accurate assessment of power - this appeared to be MRC grade 2-3/5 on the left and 4/5 on the right. She had a markedly dystonic gait and needed support to walk. Routine investigations including haemoglobin estimation, total and differential leucocytic counts, peripheral smear, blood glucose, blood urea nitrogen, serum creatinine, sodium and potassium were all normal. Slit lamp examination for Kaiser-Fleischer rings were negative and serum ceruloplasmin and copper were normal; these were done as part of the routine workup for generalised dystonia. A C T scan of the brain showed bilateral putaminal lucencies. MRI of the brain showed sharply delineated hypointense lesions corresponding to the two putamina in T1 (Fig. 1) and hyperintense lesions in T2 (Fig. 2) weighted images. Visual evoked potentials, brain stem auditory evoked potentials and somatosensory evoked potentials on stimulation of the posterior tibial nerves were normal. In the absence of a response to high dose anticholinergics, she was treated with gradually increasing dosages of levodopa and carbidopa. She showed a significant improvement in the rigidity with a reduction in dystonic posturing resulting in clearer speech, ability to use her right hand for eating, and allowed her to take a few steps without support though mostly on her toes. Further progress was hampered by gastric intolerance to doses higher than 250 mg L-Dopa with 25 mg carbidopa 3 times a day.
used sodium and potassium CN salts and organic cyanides (burning of polyurethanes, ingestion of bitter almonds or apricot stones) [11]. Taken orally CN is rapidly absorbed and reacts instantaneously with cytochrome oxidase to cause a widespread histotoxic hypoxia. Death is due to respiratory arrest following medullary dysfunction [1]. The average lethal dose of KCN is only 250 mg and most cases of acute CN poisoning are fatal within the first half hour [1]. As a consequence, delayed neurological sequelae have rarely been reported [1-5]. In such instances, the brunt is borne by the basal ganglia clinically manifesting as dystonia or parkinsonism, invariably associated with lesions of putamina and pallidum. Dystonia is often correlated with isolated putaminal or pallidal lesions while combined lesions result in parkinsonism [1-5]. The bilateral putaminal lesions seen correlated well with the clinical concomitant of dystonia in this patient and are unlikely to be of ischemic-hypoxic origin as the Ammon's horns were unaffected [1]. Our patient had features of hemiplegic dystonia as described in rare cases of necrosis of the putamen by Denny-Brown [121. Chronic CN toxicity is due to presence of cyanogenetic glycosides in large amounts in certain tropical staple foods such as cassava, yam, sweet potato, corn, millet and certain beans such as small black lima beans. Tobacco smoke also contains considerable amounts of CN (150-300/lg per cigarette). Plant glycosides are hydrolysed to release CN as hydrocyanic acid (HCN) which is rapidly absorbed through the gastrointestinal tract or the lungs. Detoxification is mainly to thiocyanate (SCN). Chronic CN toxicity has been associated with a form of optic neuropathy [6] variously known as tobacco amblyopia, West Indian amblyopia, Jamaican optic neuropathy and tropical amblyopia. Chronic CN intoxication has also been associated with deafness [7], tropical ataxic
3. Discussion
Acute CN intoxication may be secondary to accidental or suicidal exposure to hydrocyanic acid, industrially
Fig. 2. Axial T 2 weightedMRI section showing symmetricalhyperintense putaminal lesions (arrows).
1~ Borgohain et al./ Clinical Neurology and Neurosurgery 97 (1995) 213-215
myeloneuropathy [8,9] ~Lnd with 'konzo', an epidemic form of spastic paraparesis [10]. Cyanide (acute), carbon monoxide and manganese intoxication are clinically similar and produce either parkinsonism or a dystonia syndrome. Manganese is concentrated in mitochondria [13], CN inhibits cytochrome oxidase, and carbon mono:dde binds to haemoglobin and cytochromes. Parkinsonism due to acute CN poisoning appears to be due to postsynaptic mechanisms [1], though presynaptic perturbations caused by structural and functional damage of nigrostriatal pathways, may also contribute [5]. Based on a response to parenteral apomorphine, Valenzuel~L et al. [2] treated a patient of acute CN toxicity with levodopa and obtained a gratifying response. This patient too, when treated with levodopa combined with carbidopa, showed an improvement. Our patient, like previously reported cases [2], had delayed onset of extrapyramidal syndrome. Unlike those cases [2-4], she showed only a minimal tendency for spontaneous recovery. A lone previous study of brain stem auditory and visual evoked potentials in acute CN toxicity reported normal findings [2] confirming the neurophysiological integrity of the auditory and visual pathways as, except for the reticular zone of the substantia nigra, there is no clinical or pathological evidence of damage to brain stem or visual pathways. We too found normal VEPs and BAEPs similarly in our patient. In addition the somatosensory evoked potentials from both the lower limbs were normal. Somatosensory evoked potentials have not been previously documented in acute CN toxicity. There have been only 12 reports [3,5] of MRI of the brain following acute CN intoxication and hyperintensity in T2 in the 2 putamina has been reported as early as 8 days [3]. Similar finclings were seen in our patient when MRI was done 6 & IL/2years after acute CN intoxication.
215
References [l] Uitti, R., Rajput, A., Ashenhurst, E. and Rozdilsky, B. (1985) Cyanide induced Parkinsonism: a clinicopathologic report. Neurology, 35: 921-925. [2] Valenzuela, R., Court, J. and Godoy J. (1992) Delayed cyanide induced dystonia. J. Neurol. Neurosurg. Psychiat., 55: 198-199. [3] Messing, B. (1991) Extrapyramidal disturbances after cyanide poisoning (first MRI investigation of the brain). J. Neural Transm., 33 (Suppl.): 141-147. [4] Finelli, P. (1981) Changes in the basal ganglia following cyanide poisoning. J. Comput. Assist. Tomogr., 5: 755-756. [5] Rosenberg, F., Myers, J. and Martin, W. (1989) Cyanide-induced parkinsonism: clinical, MRI and 6-fluorodopa PET studies. Neurology, 39: 142-144. [6] Victor, M. (1970) Tobacco amblyopia, cyanide poisoning and vitamin B12 deficiency: a critique of current concepts. In: Smith, J.L. (Ed.), Neuro-ophthalmology: Symposium of the University of Miami and Bascom Palmer Eye Institute, Vol. 5, Huffman Publishing Company, Hallandale, FL, pp. 33~18. [7] Osuntokun, B.O., Singh, S.P. and Martinson, F.D. (1970) Deafness in tropical nutritional ataxic neuropathy. Trop. Geogr. Med., 22: 281-288. 18] Osuntokun, B.O. (1968) An ataxic neuropathy in Nigeria: a clinical, biochemical and electrophysiological study. Brain, 91: 215248. [9] Roman, G.C., Spencer, P.S. and Schoenberg, B.S. (1985) Tropical myeloneuropathies: the hidden endemias. Neurology, 35:11581170. [10] Tylleskar, T., Howlett, W.P., Rwiza, H.T., Aquilonius, S.-M., Stalberg, E., Linden, B., Mandahl, A., Larsen, H.C., Brubaker, G.R. and Rosling, H. (1993) Konzo: a distinct disease entity with selective motor neuron damage. J. Neurol. Neurosurg. Psychiat., 56: 638-643. [111 Berlet, H., Quadbeck, G. and Ule, G. (1983) Chemische Krankheitsursachen und Nervensystem: exogene Intoxikationen. In: Ule, G. (Ed.), Pathologie des Nervensystems, Vol. 2, SpringerVerlag, Berlin-Heidelberg-New York, pp. 251-656. [12] Denny-Brown, D. (1968) Clinical symptomatology of basal ganglia diseases. In: Vinken, P.J. and Bruyn, G.W. (Eds.), Handbook of Clinical Neurology, Vol. 6, Diseases of the Basal Ganglia, North Holland Publishing Company, Amsterdam, pp. 133-172. [13] Mena, N. (1979) Manganese poisoning. In: Bruyn, G.W. and Vinken, P.J. (Eds.), Handbook of Clinical Neurology, Vol. 36, Intoxications of the Nervous System, Pt I., North Holland Publishing Company, Amsterdam, pp. 217-237.