Quantitative magnetic resonance brain imaging in US army veterans of the 1991 Gulf War potentially exposed to sarin and cyclosarin.
BACKGROUND
In March 1991, a munitions storage complex at Khamisiyah, Iraq was destroyed, potentially exposing more than 100,000 US troops to low levels of the organophosphate nerve agents sarin and cyclosarin. Little is known about the neurophysiological effects of low-dose exposure to sarin/cyclosarin in humans, although some research has indicated subtle but persistent neurobehavioral and neurochemical changes in individuals exposed to sarin/cyclosarin at levels insufficient to produce obvious clinical symptoms. However, the neuroanatomical correlates of these changes are unclear. The current study examined the association between modeled estimates of sarin/cyclosarin exposure levels and volumetric measurements of gross neuroanatomical structures in 1991 Gulf War veterans with varying degrees of possible low-level sarin/cyclosarin exposure.


METHODS
Twenty-six GW-deployed veterans recruited from the Devens Cohort Study participated. Magnetic resonance images of the brain were acquired and analyzed using morphometric techniques, producing volumetric measurements of white matter, gray matter, right and left lateral ventricles, and cerebrospinal fluid. Volumetric data were analyzed using exposure estimates obtained from refined models of the 1991 Khamisiyah presumed exposure hazard area.


RESULTS
Binary comparisons of sarin/cyclosarin 'exposed' (N=13) and 'unexposed' (N=13) veterans revealed no differences in volumetric measurements of discrete brain tissues. However, linear trend analyses showed a significant association between higher levels of estimated sarin/cyclosarin exposure and both reduced white matter (adjusted parameter estimate=-4.64, p<0.0001) and increased right lateral ventricle (adjusted parameter estimate=.11, p=0.0288) and left lateral ventricle (adjusted parameter estimate=.13, p<0.0001) volumes.


CONCLUSIONS
These findings suggest subtle but persistent central nervous system pathology in Gulf War veterans potentially exposed to low levels of sarin/cyclosarin and argue for further investigation of the long-term effects of low-dose sarin/cyclosarin exposures in humans.
Heaton
Kristin J
KJ
Boston Environmental Hazards Research Center, VA Boston Healthcare System, Boston, MA, USA. kristin.heaton@us.army.mil
Palumbo
Carole L
CL
Proctor
Susan P
SP
Killiany
Ronald J
RJ
Yurgelun-Todd
Deborah A
DA
White
Roberta F
RF
D000328:Adult; D000704:Analysis of Variance; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D002619:Chemical Warfare Agents / Q000633:toxicity*; D015331:Cohort Studies; D005260:Female; D047830:Gulf War; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009943:Organophosphorus Compounds / Q000633:toxicity*; D012189:Retrospective Studies; D012524:Sarin / Q000633:toxicity*; D014481:United States; D014728:Veterans
D002619:Chemical Warfare Agents; D009943:Organophosphorus Compounds; D012524:Sarin; C053914:cyclohexyl methylphosphonofluoridate