Asymptomatic sequelae to acute sarin poisoning in the central and autonomic nervous system 6 months after the Tokyo subway attack

Abstract Six to eight months after the Tokyo subway attack in March 1995, the neurophysiological effects of acute sarin poisoning were investigated in 18 passengers exposed to sarin (sarin cases) in the subways to ascertain the focal or functional brain deficits induced by sarin. The event-related and visual evoked potentials (P300 and VEP), brainstem auditory evoked potential, and electrocardiographic R-R interval variability (CVRR), together with the score on the posttraumatic stress disorder (PTSD) checklist, were measured in the sarin cases and the same number of control subjects matched for sex and age. None of the sarin cases had any obvious clinical abnormalities at the time of testing. The P300 and VEP (P100) latencies in the sarin cases were significantly prolonged compared with the matched controls. In the sarin cases, the CVRR was significantly related to serum cholinesterase (ChE) levels determined immediately after exposure; the PTSD score was not significantly associated with any neurophysiological data despite the high PTSD score in the sarin cases. These findings suggest that asymptomatic sequelae to sarin exposure, rather than PTSD, persist in the higher and visual nervous systems beyond the turnover period of ChE; sarin may have neurotoxic actions in addition to the inhibitory action on brain ChE.

[1]  K. Murata,et al.  Acute effects of alcohol on cognitive function and central nervous system assessed by auditory event-related potentials. , 1992, Nihon eiseigaku zasshi. Japanese journal of hygiene.

[2]  L. Wecker,et al.  Elevated choline levels in brain. A non-cholinergic component of organophosphate toxicity. , 1986, Biochemical pharmacology.

[3]  L. Kaufman,et al.  The hippocampal formation as a source of the slow endogenous potentials. , 1983, Electroencephalography and clinical neurophysiology.

[4]  J. Holmes,et al.  EEG, PSYCHOLOGICAL, AND NEUROLOGICAL ALTERATIONS IN HUMANS WITH ORGANOPHOSPHORUS EXPOSURE * , 1969, Annals of the New York Academy of Sciences.

[5]  R. McConnell,et al.  Chronic central nervous system effects of acute organophosphate pesticide intoxication , 1991, The Lancet.

[6]  J. Graham,et al.  Cardiomyopathy in Soman and Sarin intoxicated rats. , 1987, Toxicology letters.

[7]  P. Sutker,et al.  Cognitive deficits and psychopathology among former prisoners of war and combat veterans of the Korean conflict. , 1991, The American journal of psychiatry.

[8]  K. Murata,et al.  Autonomic and central nervous system effects of lead in female glass workers in China. , 1995, American journal of industrial medicine.

[9]  Philip D. Harvey,et al.  Learning and memory in combat veterans with posttraumatic stress disorder. , 1995, The American journal of psychiatry.

[10]  T Okumura,et al.  Report on 640 victims of the Tokyo subway sarin attack. , 1996, Annals of emergency medicine.

[11]  J. Davies Neurotoxic concerns of human pesticide exposures. , 1990, American journal of industrial medicine.

[12]  A. Neetens,et al.  Visual evoked potentials. , 1982, Bulletin de la Societe belge d'ophtalmologie.

[13]  J. Rohrbaugh,et al.  Endogenous potentials generated in the human hippocampal formation and amygdala by infrequent events. , 1980, Science.

[14]  H. Morita,et al.  Sarin poisoning in Matsumoto, Japan , 1995, The Lancet.

[15]  F. Duffy,et al.  Long-term effects of an organophosphate upon the human electroencephalogram. , 1979, Toxicology and applied pharmacology.

[16]  H. Akaike A new look at the statistical model identification , 1974 .

[17]  J. Vandenbroucke,et al.  QT Interval Prolongation Predicts Cardiovascular Mortality in an Apparently Healthy Population , 1991, Circulation.

[18]  S. Southwick,et al.  MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder. , 1995, The American journal of psychiatry.

[19]  K. Murata,et al.  Auditory event-related potential (P300) in relation to peripheral nerve conduction in workers exposed to lead, zinc, and copper: effects of lead on cognitive function and central nervous system. , 1992, American journal of industrial medicine.

[20]  Ashutosh Kumar Singh,et al.  Choline Transport and Metabolism in Soman‐or Sarin‐Intoxicated Brain , 1988, Journal of neurochemistry.

[21]  R. Sapolsky Why Stress Is Bad for Your Brain , 1996, Science.

[22]  K. Murata,et al.  Assessment of autonomic neurotoxicity in occupational and environmental health as determined by ECG R-R interval variability: A review , 1996 .

[23]  J. Santolucito,et al.  EEG of rhesus monkeys following prolonged low-level feeding of pesticides. , 1971, Toxicology and applied pharmacology.

[24]  F H Duffy,et al.  Persistent effects of sarin and dieldrin upon the primate electroencephalogram. , 1976, Toxicology and applied pharmacology.

[25]  S. Arlinger,et al.  Visual evoked potentials: relation to adult speechreading and cognitive function. , 1989, Journal of speech and hearing research.