Exposure to sarin may have caused brain damage in U.S. troops

On March 4th 1991, four days after the end of the Persian Gulf War, ground troops from the U.S. 37th Engineering Battalion destroyed large caches of weapons found at the Khamisiyah Ammunitions Storage Facility, a site approximately 25 square kilometres in size, located some 350km south east of Baghdad.

The U.S. Department of Defense initially denied that its troops may have been exposed to nerve agents during the demolitions at Khamisiyah, but following an inspection of the site by the United Nations Special Commission (UNSCOM) in 1997, it emerged that the munitions destroyed on that day included more than six thousand 155 artillery shells filled with mustard gas and more than two thousand 122 mm rockets containing the nerve agent sarin and a related compound called cyclosarin.

After the discovery that the destroyed weapons had in fact contained nerve agents, the Department of Defense carried out a number of special investigations. The investigations involved producing mathematical computer models based on the meteorological conditions, the number and type of weapons destroyed and the positions of U.S. Army units, which were used to estimate the size and movements of the gas plume produced and the levels of nerve agents to which U.S. troops may have been exposed. It was estimated that some 8.4 metric tonnes of sarin were released during the demolition of the munitions dump, and that more than 100,000 troops may have been exposed to sarin in the week following the demolition. (An independent investigation carried out by the British Ministry of Defence concluded that British personnel were not affected by the nerve agents released at Khamisiyah.)

Sarin (o-isopropyl methylphosphonoflouridate) is a synthetic organophosphate compound whose chemical structure is similar to some common insecticides. At room temperature, it is a colourless, odourless and highly volatile liquid. The name sarin is derived from the names of the German chemists (Schrader, Ambros, Rudiger and van der Linde) who, in 1938, discovered the compound while trying to synthesize stronger pesticides. Sarin inhibits an enzyme called cholinesterase, which normally breaks down acetylcholine, the neurochemical transmitter released by motor neurons onto muscles during voluntary movement, and by the nerve fibres of the autonomic nervous system that control involuntary movements such as breathing. Sarin therefore prevents the breakdown of acetylcholine after it has been released by neurons into synapses, thus prolonging the actions of the neurotransmitter. Specifically, sarin prevents hydrolysis of acetylcholine by forming a covalent bond with a serine residue in the active site of the cholinesterase enzyme.

The symptoms produced by exposure to sarin are produced by the effects of the compound on the central and peripheral nervous system. These initially include a runny nose, constriction of the pupils and constriction of the muscle in the chest. These symptoms are soon followed by nausea, vomiting, difficulty in breathing, impairment of various cognitive functions and loss of control over bodily functions. The victim then becomes comatose and suffocates following a series of convulsive spasms. Someone who has absorbed a non-lethal dose can be treated with atropine, an alkaloid compound derived from deadly nightshade (Atropa belladona), which reversibly inhibits acetylcholine receptors. If this treatment is not administered almost immediately, permanent neurological damage may occur.

Although sarin's mechanism of action is known, the short- and long-term effects of the compound on the central nervous system are still not understood. A new study now provides some evidence of abnormalities in the brains of U. S. troops exposed to low levels of the nerve agent during the 1991 Gulf War. Roberta White, of Boston VA Medical Center, and her colleagues used quantitative magnetic resonance imaging to examine the brains of 26 Gulf War veterans, 13 of whom are believed to have been exposed to low levels of the nerve agent following the demolition of the weapons caches at Khamisiyah. It is one of only a small number of studies in which neuroimaging techniques have been used to investigate possible effects of exposure to sarin on brain anatomy. The results obtained from troops whose units were located within the hazard area around Khamisiyah in the days following the demolition were compared to those from troops whose units were outside the hazard area. White's group measured the volumes of various brain structures, and correlated the measurements with estimates of levels of exposure to sarin. This showed that troops exposed to sarin had reduced volumes of white matter and enlarged lateral ventricles in both cerebral hemispheres. These changes were rather subtle - those troops exposed to sarin had about 5% less white matter than those who weren't - but were found to be directly correlated to the extent of exposure to sarin.

The preliminary data obtained by White's group were published in the June issue of the journal NeuroToxicology. Similar results were also obtained in a recent study of individuals exposed to sarin released in the Tokyo subway system by the Aum Shinrikyo sect in 1995. This study found that, compared to controls, those exposed to the nerve agent had smaller volumes of white matter in the region surrounding the insular cortex. Earlier studies showed that Gulf War veterans believed to have been exposed to sarin performed very poorly on visuospatial and psychomotor tasks compared to unexposed troops. Impaired visuospatial and psychomotor skills were also observed in individuals who were exposed to sarin in the Tokyo subway system. Other studies performed in rats showed that sarin causes neuronal cell loss in the cerebral cortex, hippocampus and cerebellum, but much more research into the long-term effects of exposure to sarin should be carried out.

Of the 700,000 U.S. troops who served in the 1991 Gulf War, at least 150,000 have complained of an undiagnosed illness whose symptoms include persistent fatigue, headaches, joint pain and nausea. The Department of Defense long denied that such a condition existed, and instead suggested that the symptoms were psychological in basis. But it now seems clear that the condition - which has variously been referred to as chronic multisyndrome illness complex, Gulf War Syndrome, or the Gulf War Illnesses - does indeed have a physiological basis. And the animal studies suggest that the onset of symptoms of exposure to sarin can be delayed, that the symptoms persist for years, and that they worsen with time. The myriad symptoms are unlikely to have a single cause, and instead may be due to a number of things, including exposure to a combination of hazardous and potentially neurotoxic substances, such as depleted uranium and other nerve agents. A recent study shows that the number of closed head injuries caused by improvised explosive devices, which may go unnoticed for years, may far outnumber the penetrative wounds caused by the devices; they could also be a contributing factor to the Gulf War Illnesses.

It is therefore difficult to extricate the effects of sarin from those other substances, and from other known (and unknown) causes of neurological damage. And although the findings of White's group are inconclusive, they do suggest that exposure to sarin may also contribute to the symptoms of the so-called Gulf War Illnesses. They also suggest that exposure to low levels of sarin may lead to neurological damage without any noticeable clinical symptoms. However, one needs to bear in mind that White's group could not determine precisely the levels of sarin to which the participants were exposed; they used estimates based on the plume models developed by the Department of Defense. Nevertheless, the little we do know about the effects of exposure to sarin has serious implications for those troops who served in the 1991 Gulf War. And we mustn't forget that the Iraqi people have also been exposed to many, if not all, of the same substances to which U.S. troops have been exposed.

Reference:

Heaton, K. J., et al. (2007). Quantitative magnetic resonance brain imaging in U. S. Army veterans of the 1991 Gulf War potentially exposed to sarin and cyclosarin. NeuroToxicology doi: 10.1016/j.neuro.2007.03.006. [Abstract]