Central nervous system pathology in Gulf War Illness due to exposure to low levels of chemical warfare agents sarin (GB) and cyclosarin (GF)

Chao LL, Abadjian L, Hlavin J, Meyerhoff DJ, Weiner MW.:

Center for Imaging of Neurodegenerative Diseases, San Francisco Veterans Affairs Medical Center, San Francisco, CA, United States; Department of Psychiatry, University of California, San Francisco, CA, United States; Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, United States.

Abstract
BACKGROUND:
More than 100,000 US troops were potentially exposed to chemical warfare agents sarin (GB) and cyclosarin (GF) when an ammunition dump at Khamisiyah, Iraq was destroyed during the 1991 Persian Gulf War (GW). We previously found reduced total gray matter (GM) volume in 40 GW veterans with suspected GB/GF exposure relative to 40 matched, unexposed GW veterans on a 1.5T MR scanner. In this study, we reexamine the relationship between GB/GF exposure and volumetric measurements of gross neuroanatomical structures in a different cohort of GW veterans on a 4T MR scanner.

METHODS:
Neuropsychological and magnetic resonance imaging (MRI) data from a cross sectional study on Gulf War Illness performed between 2005 and 2010 were used in this study. 4T MRI data were analyzed using automated image processing techniques that produced volumetric measurements of gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF).

RESULTS:
Binary comparisons of 64 GB/GF exposed veterans and 64 'matched', unexposed veterans revealed reduced GM (p=0.03) and WM (p=0.03) volumes in the exposed veterans. Behaviorally, exposed veterans committed more errors of omission (p=0.02) and tended to have slower responses (p=0.05) than unexposed veterans on the Continuous Performance Test (CPT), a measure sustained and selective attention. Regression analyses confirmed that GB/GF exposure status predicted GM (β=-0.11, p=0.02) and WM (β=-0.14, p=0.03) volumes, and number of CPT omission errors (β=0.22, p=0.02) over and above potentially confounding demographic, clinical, and psychosocial variables. There was no dose-response relationship between estimated levels of GB/GF exposure and brain volume. However, we did find an effect of Gulf War Illness/Chronic Mulitsymptom Illness on both GM and WM volume in the GB/GF exposed veterans.

CONCLUSIONS:
These findings confirm previous reports by our group and others of central nervous system pathology in GW veterans with suspected exposure to low levels of GB/GF two decades after the exposure.