Case report
Transient opsoclonus in organophosphate poisoning De Bleecker JL. Transient opsoclonus in organophosphate poisoning. Acta Neurol Scand 1992: 86: 529-531. 0 Munksgaard 1992.
I
Opsoclonus transiently occurred in the acute stage of combined parathion and methyl-parathion poisoning. Despite persistent cholinesterase inhibition this symptom subsided spontaneously. This observation provides strong evidence for cholinergic pathways being reversibly involved in isolated opsoclonus.
Opsoclonus is the term used to describe rapid, involuntary, irregular and chaotic eye movements that occur in various either linear or rotatory directions (1). It is a rare disorder occurring in both children and adults, associated or not with focal or generalized myoclonus and then termed the opsoclonusmyoclonus syndrome (OMS). Its most common causes are viral encephalitis, and a remote effect of neoplasms (2). Rare causes have been multiple sclerosis (3), brain stem glioma (4), ischaemic and hemorrhagic stroke (5,6), hydrocephalus (7), brain trauma (8), hyperosmolar nonketotic coma (9, lo), congenital syndromes (1 l), and toxins. The latter have included malathion (12), amitriptyline (13), chlordecone (14), DDT (15), lithium and haloperidol (16), thallium (17), toluene (18), phenytoin (19), and cocaine (20). The localization of the anatomic site of pathology in opsoclonus or OMS is still under debate. The pontine paramedian reticular formation (PPRF), midbrain, thalamus and cerebellum have all been suggested (21). We report an organophosphate-poisoned patient with transient opsoclonus in the acute stage of the intoxication. Case report
A 29-year-old man with unremarkable medical history was admitted after a suicide attempt through ingestion of an insecticide containing parathion and methyl-parathion. He was drowsy, and presented with profuse fasciculations, muscle cramps, tenes-
J. L. De Bleecker Department of Neurology, University Hospital, Ghent, Belgium
Key words: organophosphorus compound: opsoclonus; cholinergic
1
J.L. De Bleecker, Mayo Clinic and Foundation, Neuromuscular Lab, Guggenheim Building room 801, Rochester, MN 55905, USA Accepted for publication April 20, 1992
mus, increased salivation, sweating and lacrimation. The pupils were myotic and equal. Ocular movements were full. There was a slight generalized hypotonic weakness. Deep tendon reflexes were normal with flexor plantar responses. The level of consciousness gradually declined within a few minutes. He was intubated and ventilated. Gastric lavage and instillation of activated charcoal and oral mannitol were continued for several days. Intravenous atropine and pralidoxime were started. Plasma pseudocholinesterase (ChE) activity had decreased to 290 micromole/ml.min. (normal in our lab 22397655; mean 4797) and erythrocyte acetylcholinesterase (AChE) was 1559 micromole/mg.min. (normal 5204-13630; mean 9422). Eight hours later, the patient obeyed to commands. Muscarinic symptoms had nearly disappeared and fasciculation was mild. Striking opsoclonus was noted, with bursts of rapid, involuntary, conjugate eye movements that occurred most frequently in the vertical and oblique planes, without intersaccadic intervals. Their irregular rhythm varied from about 3 to 8 Hz. Eye closure did not affect them. On attempts for fixed gaze, the outbursts increased. voluntary extraocular movements could not be adequately estimated. The cranial nerves were otherwise unremarkable. There were no associated facial, palatal, truncal, diaphragm or limb movements. A symmetric paresis of 3/5 was noted in all limbs. Plantar reflexes were flexor. The neurologic condition remained unaltered for the next 24 h. EEG and brain CT scan were normal. 529
De Bleecker At the end of the second hospital day, the involuntary eye movements had disappeared. Consciousness was slightly impaired, artificial ventilation was continued, but muscarinic symptoms and fasciculations were absent. A marked external ophthalmoparesis and ptosis were observed. The patient could not lift his head from the pillow, and a severe, flaccid, predominantly proximal limb muscle paresis was noted. The deep tendon reflexes were absent, with both plantar responses flexor. Atropine and pralidoxime treatment was continued as before, and esterase activities remained depressed. On the third hospital day, a temporary recurrence of severe muscarinic symptoms and fasciculations occurred. Atropine was temporarily increased to 3 mg/h, and the muscarinic symptoms were soon relieved. Plasma ChE had further decreased to 38, erythrocyte AChE being 2105. The neurologic examination was otherwise comparable to the previous. External ophthalmoparesis, ptosis, respiratory paresis, weakness of neck flexors and proximal limb muscles, and depressed tendon reflexes persisted for more than 2 weeks. Muscarinic symptoms only briefly recurred on Day 15, apparently provoked by slightly tapering the atropine dosage. The neurologic examination was entirely normal by Day 18. Extubation was successful on day 20. Severe esterase inhibition persisted for 2 weeks, and gradually recovered thereafter. The final outcome was unremarkable. Discussion
Opsoclonus is a striking disorder of eye movements characterized by involuntary multidirectional conjugate jerking of the eyes at high frequencies without intersaccadic interval. Its most frequent causes are viral encephalopathies, often benign and self-limited, and a paraneoplastic syndrome, each occurring in both children and adults (2). The most common remote tumor in children has been neuroblastoma (22), whereas in adults a variety of neoplasms including carcinoma of the lung, thyroid gland, ovary, uterus, breasts, thymus, and lymphoma have been reported. Most paraneoplastic cases have clinically shown an OMS often combined with ataxia, and in some anti-neuronal and anti-Purkinje cell antibodies have been detected (2, 23). The precise localization of the morphological lesion underlying opsoclonus is unknown. It has been proposed that opsoclonus might result from dysfunction of the mechanism by which so-called pause cells in the PPRF inhibit horizontal and vertical saccadic-burst neurons (24). Others have questioned that point of view, and found that damage in this region produced slowing of saccades rather than opsoclonus (25). The pause neurons have been reported 530
normal at autopsy in two cases of opsoclonus associated with oat cell carcinoma of the lung (26). Radiology and pathology in the most common cases with either viral or paraneoplastic causes have been of little help. Autopsies in several patients with paraneoplastic OMS have shown loss of Purkinje cells, a finding characteristic of the paraneoplastic cerebellar syndrome in general. In the few patients with structural brain lesions either pontine (27,28), midbrain (4,7), or thalamic (6) involvement have been demonstrated. In our patient, opsoclonus has been provoked by acute anticholinesterase action of the potent organophosphate agents parathion and methyl-parathion. No associated myoclonus or cerebellar signs were observed. The opsoclonus spontaneously disappeared after 1 day, despite further decreasing cholinesterase activities in the next few days. Adaptation of the central and peripheral nervous system to severe anticholinesterase action is known (29,30). The only other case of anticholinesterase agentrelated opsoclonus has been reported by Pullicino and Aquilana in malathion poisoning (12). Hata et al. described atypical ocular bobbing in a diazinonpoisoned patient (3 1). Both patients also displayed their ocular oscillations in the acute stage of the poisoning, and they lasted for several hours to a few days. As different organophosphates were involved, a direct toxic effect can be ruled out. Rather, their common mechanism of cholinesterase inhibition seems to be responsible. These observations strongly underscore a cholinergic mechanism being involved in saccadic eye movement control. The dysfunction underlying opsoclonus can be entirely reversible, as well. After the acute episode, our patient suffered from a prolonged type of organophosphate toxicity that has been termed the “Intermediate Syndrome” because it appears in the time period after the acute cholinergic crisis and before the usual onset of the so-called Organophosphate-Induced Delayed Neurotoxicity (OPIDN) (32). The main clinical features of an intermediate syndrome are respiratory paresis, weakness in the territory of several motor cranial nerves, proximal limb muscle and neck flexor weakness, and depression of the deep tendon reflexes. It is beyond the scope of this paper to further discuss this syndrome, as it is unrelated to the reported opsoclonus. References 1. VIGNAENDRA V, LIMCL. Electro-oculographic analysis of opsoclonus: its relationship to saccadic and non-saccadic eye movements. Neurology 1977: 27: 1129-1133. 2. DIGRE KB. Opsoclonus in adults. Report of three cases and review of the literature. Arch Neurol 1986: 43: 1165-1175.
Transient opsoclonus in organophosphate poisoning 3. GRESTYMA, FINDLEY LJ, WADEP. Mechanism of rotatory eye movements in opsoclonus. Br J Ophthalmol 1980: 64: 923-925. 4. KEANEJR, DEVERAUX MW. Opsoclonus associated with
an intracranial tumor: a clinicopathologic case report. Arch Ophthalmol 1974: 92: 443-445. 5 . BODDIEHG. Ocular bobbing and opsoclonus. J Neurol Neurosurg Psychiatry 1972: 35: 739-742. 6. KEANEJR. Transient opsoclonus with thalamic hemorrhage. Arch Neurol 1980: 37: 423-424. 7. SHETTYR, ROSMANNP. Opsoclonus in hydrocephalus. Arch Ophthalmol 1972: 88: 585-589. S, ALEXANDRE A, BRICOLOA et al. Opsoclonus 8. TURAZZI and palatal myoclonus during prolonged post-traumatic coma. Eur Neurol 1977: 15: 257-263. K, SONOHM, TAMAOKA A, SAKUTAM. 9. MATSAMURA Syndrome of opsoclonus-myoclonus in hyperosmolar nonketotic coma. Ann Neurol 1985: 18: 623-624. 10. NODAS, TAKAO A, ITOHH, UMEZAKI H. Opsoclonus in hyperosmolar nonketotic coma. J Neurol Neurosurg Psychiatry 1985: 48: 1186-1187. 11. COPPETOJR, MONTEIROML. Craniofacial dysmorphism and opsoclonus. Ophtalm Ped Genet 1984: 4: 147-153. P, AQUILANA J. Opsoclonus in organophosphate 12. PULLICINO poisoning. Arch Neurol 1989: 46: 704-705. JL. Opsoclonus with amitriptyline over13. Au WJ, KELLTNER dose. Ann Neurol 1979: 6: 87. JR, SELHORST JB, HOUFFSA et al. Chlordecone 14. TAYLOR intoxication in man: I. Clinical observations. Neurology 1978:
phenytoin and diazepam. Ann Neurol 1987: 21: 216. 20. SCHARFD et al. Opsoclonus-myoclonus following the intranasal usage of cocaine. J Neurol Neurosurg Psychiatry 1989: 52: 1447-1448. 21. DROPCHO E, PAYNE R. Paraneoplastic opsoclonus22. 23.
24. 25.
26. 27.
myoclonus. Association with medullary thyroid carcinoma and review of the literature. Arch Neurol 1986: 43: 410-415. SOLOMON GE, CHUTORIAN AM. Opsoclonus and occult neuroblastoma. N Engl J Med 1968: 279: 475-477. LUQUEFA, FURNEAUX HM, FERZIGER R et al. Anti-Ri: an antibody associated with paraneoplastic opsoclonus and breast cancer. Ann Neurol 1991: 29: 241-251. ZEEDS, ROBINSON DA. A hypothetical explanation of saccadic oscillations. Ann Neurol 1979: 5: 405-414. BRONSTEIN AM, RUDGEP, GRESTY MA, D u BOULAY G, MORRISJ. Abnormalities of horizontal gaze. Clinical, oculographic and magnetic resonance imaging findings. 11. Gaze palsy and internuclear ophthalmoplegia. J Neurol Neurosurg Psychiatry 1990: 53: 200-207. RIDLEYA, KENNARDC, SCHOLTZCL et al. Omnipause neurons in two cases of opsoclonus associated with oat cell carcinoma of the lung. Brain 1987: 110: 1699-1709. ARAKIK, UEDAY, HAYAFUJI M, TAKINO T. Opsoclonus myoclonus syndrome with abnormal magnetic resonance imaging and brain stem auditory evoked potentials. Japanese J Med 1989: 28: 753-756.
K, IMAIT, YAMADA T, KOJIMA 28. HATTORIT, HIRAYAMA
S . Pontine lesion in opsoclonus myoclonus syndrome shown by MRI. J Neurol Neurosurg Psychiatry 1988: 51: 1572-
28: 626-630. 15. GARCINR, GINSBOURG M, GODLEWSKI ST et al. Intoxi-
1575. 29. VANDONGEN CJ, WOLTHUIS OL. On the development of
cation par le DDT: Syndrome mkningo-enckphalique aigu rkgressif avec des dtcharges cloniques diffuses et mouvements dksordonnts “en salves’’ des globes oculaires. Rev Neurol
behavioral tolerance to organophosphates. I. Behavioral and biochemical aspects. Pharmacol Biochem Behav 1989: 34:
1965: 113: 559-565. 16. COHENWS, COHENNH. Lithium carbonate, haloperidol and reversible brain damage. JAMA 1974: 230: 1283-1287. M, SEZLINGER D, SNYDERR. Thallotoxicosis 17. MACCARID
with coma and abnormal eye movement (opsoclonus). Clinical and EEG correlations. Electroencephalogr Clin Neurophysiol 1976: 38: 98-99. 18. LAZARRB, HO SU, MELEN0 etal. Multifocal nervous system damage caused by toluene abuse. Neurology 1983: 33: 1337-1340. 19. DEHAENE I, VAN VLEYMENB. Opsoclonus induced by
473-481. 30. GUPTA RC, PATTERSON G, DETTBARN W-D. Mechanisms of toxicity and tolerance to diisopropylphosphorofluoridateat
the neuromuscular junction of the rat. Toxicol Appl PharmaCOI 1986: 84: 541-550. 3 1. HATAS, BERNSTEIN E, DAVIS LE. Atypical ocular bobbing in acute organophosphate poisoning. Arch Neurol 1986: 43: 185-186. 32. SENANAYAKE N, KARALLIEDDE N. Neurotoxic effects of organophosphorus insecticides. An intermediate syndrome. N Engl J Med 1987: 316: 761-763.
53 1
Transient opsoclonus in organophosphate poisoning De Bleecker JL. Transient opsoclonus in organophosphate poisoning. Acta Neurol Scand 1992: 86: 529-531. 0 Munksgaard 1992.
I
Opsoclonus transiently occurred in the acute stage of combined parathion and methyl-parathion poisoning. Despite persistent cholinesterase inhibition this symptom subsided spontaneously. This observation provides strong evidence for cholinergic pathways being reversibly involved in isolated opsoclonus.
Opsoclonus is the term used to describe rapid, involuntary, irregular and chaotic eye movements that occur in various either linear or rotatory directions (1). It is a rare disorder occurring in both children and adults, associated or not with focal or generalized myoclonus and then termed the opsoclonusmyoclonus syndrome (OMS). Its most common causes are viral encephalitis, and a remote effect of neoplasms (2). Rare causes have been multiple sclerosis (3), brain stem glioma (4), ischaemic and hemorrhagic stroke (5,6), hydrocephalus (7), brain trauma (8), hyperosmolar nonketotic coma (9, lo), congenital syndromes (1 l), and toxins. The latter have included malathion (12), amitriptyline (13), chlordecone (14), DDT (15), lithium and haloperidol (16), thallium (17), toluene (18), phenytoin (19), and cocaine (20). The localization of the anatomic site of pathology in opsoclonus or OMS is still under debate. The pontine paramedian reticular formation (PPRF), midbrain, thalamus and cerebellum have all been suggested (21). We report an organophosphate-poisoned patient with transient opsoclonus in the acute stage of the intoxication. Case report
A 29-year-old man with unremarkable medical history was admitted after a suicide attempt through ingestion of an insecticide containing parathion and methyl-parathion. He was drowsy, and presented with profuse fasciculations, muscle cramps, tenes-
J. L. De Bleecker Department of Neurology, University Hospital, Ghent, Belgium
Key words: organophosphorus compound: opsoclonus; cholinergic
1
J.L. De Bleecker, Mayo Clinic and Foundation, Neuromuscular Lab, Guggenheim Building room 801, Rochester, MN 55905, USA Accepted for publication April 20, 1992
mus, increased salivation, sweating and lacrimation. The pupils were myotic and equal. Ocular movements were full. There was a slight generalized hypotonic weakness. Deep tendon reflexes were normal with flexor plantar responses. The level of consciousness gradually declined within a few minutes. He was intubated and ventilated. Gastric lavage and instillation of activated charcoal and oral mannitol were continued for several days. Intravenous atropine and pralidoxime were started. Plasma pseudocholinesterase (ChE) activity had decreased to 290 micromole/ml.min. (normal in our lab 22397655; mean 4797) and erythrocyte acetylcholinesterase (AChE) was 1559 micromole/mg.min. (normal 5204-13630; mean 9422). Eight hours later, the patient obeyed to commands. Muscarinic symptoms had nearly disappeared and fasciculation was mild. Striking opsoclonus was noted, with bursts of rapid, involuntary, conjugate eye movements that occurred most frequently in the vertical and oblique planes, without intersaccadic intervals. Their irregular rhythm varied from about 3 to 8 Hz. Eye closure did not affect them. On attempts for fixed gaze, the outbursts increased. voluntary extraocular movements could not be adequately estimated. The cranial nerves were otherwise unremarkable. There were no associated facial, palatal, truncal, diaphragm or limb movements. A symmetric paresis of 3/5 was noted in all limbs. Plantar reflexes were flexor. The neurologic condition remained unaltered for the next 24 h. EEG and brain CT scan were normal. 529
De Bleecker At the end of the second hospital day, the involuntary eye movements had disappeared. Consciousness was slightly impaired, artificial ventilation was continued, but muscarinic symptoms and fasciculations were absent. A marked external ophthalmoparesis and ptosis were observed. The patient could not lift his head from the pillow, and a severe, flaccid, predominantly proximal limb muscle paresis was noted. The deep tendon reflexes were absent, with both plantar responses flexor. Atropine and pralidoxime treatment was continued as before, and esterase activities remained depressed. On the third hospital day, a temporary recurrence of severe muscarinic symptoms and fasciculations occurred. Atropine was temporarily increased to 3 mg/h, and the muscarinic symptoms were soon relieved. Plasma ChE had further decreased to 38, erythrocyte AChE being 2105. The neurologic examination was otherwise comparable to the previous. External ophthalmoparesis, ptosis, respiratory paresis, weakness of neck flexors and proximal limb muscles, and depressed tendon reflexes persisted for more than 2 weeks. Muscarinic symptoms only briefly recurred on Day 15, apparently provoked by slightly tapering the atropine dosage. The neurologic examination was entirely normal by Day 18. Extubation was successful on day 20. Severe esterase inhibition persisted for 2 weeks, and gradually recovered thereafter. The final outcome was unremarkable. Discussion
Opsoclonus is a striking disorder of eye movements characterized by involuntary multidirectional conjugate jerking of the eyes at high frequencies without intersaccadic interval. Its most frequent causes are viral encephalopathies, often benign and self-limited, and a paraneoplastic syndrome, each occurring in both children and adults (2). The most common remote tumor in children has been neuroblastoma (22), whereas in adults a variety of neoplasms including carcinoma of the lung, thyroid gland, ovary, uterus, breasts, thymus, and lymphoma have been reported. Most paraneoplastic cases have clinically shown an OMS often combined with ataxia, and in some anti-neuronal and anti-Purkinje cell antibodies have been detected (2, 23). The precise localization of the morphological lesion underlying opsoclonus is unknown. It has been proposed that opsoclonus might result from dysfunction of the mechanism by which so-called pause cells in the PPRF inhibit horizontal and vertical saccadic-burst neurons (24). Others have questioned that point of view, and found that damage in this region produced slowing of saccades rather than opsoclonus (25). The pause neurons have been reported 530
normal at autopsy in two cases of opsoclonus associated with oat cell carcinoma of the lung (26). Radiology and pathology in the most common cases with either viral or paraneoplastic causes have been of little help. Autopsies in several patients with paraneoplastic OMS have shown loss of Purkinje cells, a finding characteristic of the paraneoplastic cerebellar syndrome in general. In the few patients with structural brain lesions either pontine (27,28), midbrain (4,7), or thalamic (6) involvement have been demonstrated. In our patient, opsoclonus has been provoked by acute anticholinesterase action of the potent organophosphate agents parathion and methyl-parathion. No associated myoclonus or cerebellar signs were observed. The opsoclonus spontaneously disappeared after 1 day, despite further decreasing cholinesterase activities in the next few days. Adaptation of the central and peripheral nervous system to severe anticholinesterase action is known (29,30). The only other case of anticholinesterase agentrelated opsoclonus has been reported by Pullicino and Aquilana in malathion poisoning (12). Hata et al. described atypical ocular bobbing in a diazinonpoisoned patient (3 1). Both patients also displayed their ocular oscillations in the acute stage of the poisoning, and they lasted for several hours to a few days. As different organophosphates were involved, a direct toxic effect can be ruled out. Rather, their common mechanism of cholinesterase inhibition seems to be responsible. These observations strongly underscore a cholinergic mechanism being involved in saccadic eye movement control. The dysfunction underlying opsoclonus can be entirely reversible, as well. After the acute episode, our patient suffered from a prolonged type of organophosphate toxicity that has been termed the “Intermediate Syndrome” because it appears in the time period after the acute cholinergic crisis and before the usual onset of the so-called Organophosphate-Induced Delayed Neurotoxicity (OPIDN) (32). The main clinical features of an intermediate syndrome are respiratory paresis, weakness in the territory of several motor cranial nerves, proximal limb muscle and neck flexor weakness, and depression of the deep tendon reflexes. It is beyond the scope of this paper to further discuss this syndrome, as it is unrelated to the reported opsoclonus. References 1. VIGNAENDRA V, LIMCL. Electro-oculographic analysis of opsoclonus: its relationship to saccadic and non-saccadic eye movements. Neurology 1977: 27: 1129-1133. 2. DIGRE KB. Opsoclonus in adults. Report of three cases and review of the literature. Arch Neurol 1986: 43: 1165-1175.
Transient opsoclonus in organophosphate poisoning 3. GRESTYMA, FINDLEY LJ, WADEP. Mechanism of rotatory eye movements in opsoclonus. Br J Ophthalmol 1980: 64: 923-925. 4. KEANEJR, DEVERAUX MW. Opsoclonus associated with
an intracranial tumor: a clinicopathologic case report. Arch Ophthalmol 1974: 92: 443-445. 5 . BODDIEHG. Ocular bobbing and opsoclonus. J Neurol Neurosurg Psychiatry 1972: 35: 739-742. 6. KEANEJR. Transient opsoclonus with thalamic hemorrhage. Arch Neurol 1980: 37: 423-424. 7. SHETTYR, ROSMANNP. Opsoclonus in hydrocephalus. Arch Ophthalmol 1972: 88: 585-589. S, ALEXANDRE A, BRICOLOA et al. Opsoclonus 8. TURAZZI and palatal myoclonus during prolonged post-traumatic coma. Eur Neurol 1977: 15: 257-263. K, SONOHM, TAMAOKA A, SAKUTAM. 9. MATSAMURA Syndrome of opsoclonus-myoclonus in hyperosmolar nonketotic coma. Ann Neurol 1985: 18: 623-624. 10. NODAS, TAKAO A, ITOHH, UMEZAKI H. Opsoclonus in hyperosmolar nonketotic coma. J Neurol Neurosurg Psychiatry 1985: 48: 1186-1187. 11. COPPETOJR, MONTEIROML. Craniofacial dysmorphism and opsoclonus. Ophtalm Ped Genet 1984: 4: 147-153. P, AQUILANA J. Opsoclonus in organophosphate 12. PULLICINO poisoning. Arch Neurol 1989: 46: 704-705. JL. Opsoclonus with amitriptyline over13. Au WJ, KELLTNER dose. Ann Neurol 1979: 6: 87. JR, SELHORST JB, HOUFFSA et al. Chlordecone 14. TAYLOR intoxication in man: I. Clinical observations. Neurology 1978:
phenytoin and diazepam. Ann Neurol 1987: 21: 216. 20. SCHARFD et al. Opsoclonus-myoclonus following the intranasal usage of cocaine. J Neurol Neurosurg Psychiatry 1989: 52: 1447-1448. 21. DROPCHO E, PAYNE R. Paraneoplastic opsoclonus22. 23.
24. 25.
26. 27.
myoclonus. Association with medullary thyroid carcinoma and review of the literature. Arch Neurol 1986: 43: 410-415. SOLOMON GE, CHUTORIAN AM. Opsoclonus and occult neuroblastoma. N Engl J Med 1968: 279: 475-477. LUQUEFA, FURNEAUX HM, FERZIGER R et al. Anti-Ri: an antibody associated with paraneoplastic opsoclonus and breast cancer. Ann Neurol 1991: 29: 241-251. ZEEDS, ROBINSON DA. A hypothetical explanation of saccadic oscillations. Ann Neurol 1979: 5: 405-414. BRONSTEIN AM, RUDGEP, GRESTY MA, D u BOULAY G, MORRISJ. Abnormalities of horizontal gaze. Clinical, oculographic and magnetic resonance imaging findings. 11. Gaze palsy and internuclear ophthalmoplegia. J Neurol Neurosurg Psychiatry 1990: 53: 200-207. RIDLEYA, KENNARDC, SCHOLTZCL et al. Omnipause neurons in two cases of opsoclonus associated with oat cell carcinoma of the lung. Brain 1987: 110: 1699-1709. ARAKIK, UEDAY, HAYAFUJI M, TAKINO T. Opsoclonus myoclonus syndrome with abnormal magnetic resonance imaging and brain stem auditory evoked potentials. Japanese J Med 1989: 28: 753-756.
K, IMAIT, YAMADA T, KOJIMA 28. HATTORIT, HIRAYAMA
S . Pontine lesion in opsoclonus myoclonus syndrome shown by MRI. J Neurol Neurosurg Psychiatry 1988: 51: 1572-
28: 626-630. 15. GARCINR, GINSBOURG M, GODLEWSKI ST et al. Intoxi-
1575. 29. VANDONGEN CJ, WOLTHUIS OL. On the development of
cation par le DDT: Syndrome mkningo-enckphalique aigu rkgressif avec des dtcharges cloniques diffuses et mouvements dksordonnts “en salves’’ des globes oculaires. Rev Neurol
behavioral tolerance to organophosphates. I. Behavioral and biochemical aspects. Pharmacol Biochem Behav 1989: 34:
1965: 113: 559-565. 16. COHENWS, COHENNH. Lithium carbonate, haloperidol and reversible brain damage. JAMA 1974: 230: 1283-1287. M, SEZLINGER D, SNYDERR. Thallotoxicosis 17. MACCARID
with coma and abnormal eye movement (opsoclonus). Clinical and EEG correlations. Electroencephalogr Clin Neurophysiol 1976: 38: 98-99. 18. LAZARRB, HO SU, MELEN0 etal. Multifocal nervous system damage caused by toluene abuse. Neurology 1983: 33: 1337-1340. 19. DEHAENE I, VAN VLEYMENB. Opsoclonus induced by
473-481. 30. GUPTA RC, PATTERSON G, DETTBARN W-D. Mechanisms of toxicity and tolerance to diisopropylphosphorofluoridateat
the neuromuscular junction of the rat. Toxicol Appl PharmaCOI 1986: 84: 541-550. 3 1. HATAS, BERNSTEIN E, DAVIS LE. Atypical ocular bobbing in acute organophosphate poisoning. Arch Neurol 1986: 43: 185-186. 32. SENANAYAKE N, KARALLIEDDE N. Neurotoxic effects of organophosphorus insecticides. An intermediate syndrome. N Engl J Med 1987: 316: 761-763.
53 1
