One of the first studies to raise questions about possible long-term CNS effects of OPs was an uncontrolled study of industrial workers exposed in the 1950s and 1960s (Metcalf and Holmes, 1969). This case series identified long-term alterations in workers’ EEG and cognition. It provided the impetus for studies in rhesus monkeys (Burchfiel et al., 1976, described earlier) and the first controlled study of long-term CNS effects in workers accidentally exposed to sarin (Duffy et al., 1979; Burchfiel and Duffy, 1982). Researchers studied a population of 77 workers with previously documented accidental exposure at a manufacturing plant and compared them to unexposed controls from the same plant (n = 38) on EEG activity. None had been exposed within a year of the study. Exposed workers had one or more exposure incidents within the previous 6 years. At the time of exposure, they had clinical signs and depressed erythrocyte cholinesterase activity (by at least 25 percent). The EEG investigation consisted of spectral analysis of tape-recorded EEGs, visual inspection of routine clinical EEGs, and visual inspection of all-night sleep EEGs. Univariate and multivariate analysis of the EEG power spectra showed significant increase in high-frequency, beta activity (15–30 Hz) in temporal, central, and occipital regions in workers exposed to sarin compared to the control group (p < .001). There was a discrepancy between increased amounts of slow-wave activity in the delta and theta frequency bands (0–8 Hz) seen on visual inspection of EEG and the absence of such a finding by spectral analysis for the group exposed to sarin. Analysis of all-night sleep recordings showed a significant increase in the amount of REM (rapid eye movement) sleep only in the workers exposed to sarin. The clinical significance of these changes was not clear. Exposed workers also reported increased dreaming, instances of irritability, disturbed memory, and difficulty in maintaining alertness and attention (Burchfiel and Duffy, 1982), although methodological details of the symptom reporting were not provided. The increase in EEG beta activity in both monkeys (see earlier discussion) and humans years after acute exposure to sarin lends credence to a chronic CNS effect of sarin.
In the late evening of June 27, 1994, Japanese terrorists spread sarin vapor, using a heater and fan mounted on a truck, in a residential neighborhood near the center of Matsumoto, Japan (Nakajima et al., 1997). About 600 people (residents and rescue teams) developed acute symptoms of sarin exposure (i.e., the acute cholinergic syndrome); 58 were admitted to hospitals, 253 sought medical assistance, and 7 people died. Sarin was later detected in air and water samples by gas chromatograph-mass spectrometry (GC-MC) (Nakajima et al., 1998). Several case reports, case series, and a population-based epidemiologic study emerged from this attack on a civilian population. The population-based study, the first of its kind on sarin exposure, identified symptoms persisting up to 3