Effects of low-level exposure to sarin and cyclosarin during the 1991 Gulf War on brain function and brain structure in US veterans

Abstract

Background: Potentially more than 100,000 US troops may have been exposed to the organophosphate chemical warfare agents sarin (GB) and cyclosarin (GF) when a munitions dump at Khamisiyah, Iraq was destroyed during the Gulf War (GW) in 1991. Although little is known about the long-term neurobehavioral or neurophysiological effects of low-dose exposure to GB/GF in humans, recent studies of GW veterans from the Devens Cohort suggest decrements in certain cognitive domains and atrophy in brain white matter occur individuals with higher estimated levels of presumed GB/GF exposure. The goal of the current study is to determine the generalizability of these findings in another cohort of GW veterans with suspected GB/GF exposure.

Methods: Neurobehavioral and imaging data collected in a study on Gulf War Illness between 2002 and 2007 were used in this study. We focused on the data of 40 GW-deployed veterans categorized as having been exposed to GB/GF at Khamisiyah, Iraq and 40 matched controls. Magnetic resonance images (MRI) of the brain were analyzed using automated and semi-automated image processing techniques that produced volumetric measurements of gray matter (GM), white matter (WM), cerebrospinal fluid (CSF) and hippocampus.

Results: GW veterans with suspected GB/GF exposure had reduced total GM and hippocampal volumes compared to their unexposed peers (p< or =0.01). Although there were no group differences in measures of cognitive function or total WM volume, there were significant, positive correlations between total WM volume and measures of executive function and visuospatial abilities in veterans with suspected GB/GF exposure.

Conclusions: These findings suggest that low-level exposure to GB/GF can have deleterious effects on brain structure and brain function more than decade later.

Figure. 1

Examples of SPMP8 segmentation of high resolution T1-weighted MRI in a 40 year-old unexposed male GW veteran (A) and a 45 year-old GW veteran with suspected GB/GF exposure. The images at the far left show the coronal T1-weighted images. The images to the right show the SPM8 classification of GM, WM, and CSF.

Figure 2

Regional GM density reduction in GB/GF exposed GW veterans. Regions showing reduced gray matter (GM) density in veterans with suspected GB/GF exposure compared with unexposed veterans are rendered onto the image of a single unexposed GW veteran (voxel threshold: p= 0.001, uncorrected).