Gulf War illness is a multi symptom chronic illness, featuring a multitude of  symptoms that include but are not limited to fatigue, recurring neuropathic pain, memory dysfunction, cognitive disorders, balance disturbances, and depression. Gulf War illness afflicts an estimated 175,000 military personnel who were deployed to the 1991 Persian Gulf War (1). There have been a number of studies associating Gulf War illness with exposure to specific neurotoxic chemicals ( 2–4 ), including organophosphate pesticides, pyridostigmine bromide, and low-level sarin nerve gas, all of which are cholinergic stimulants that inhibit cholinesterase, the enzyme responsible for synthesizing acetylcholine, and can cause persistent brain changes ( 1,4 ). Recently Gulf War illness has been categorized into three primary variants: syndrome 1 (impaired cognition), syndrome 2 (confusion- ataxia), and syndrome 3 (central neuropathic pain) (2,3).

The neurotransmitter of most interest in Gulf War illness is acetylcholine (Ach). In the autonomic nervous system Ach plays a pivotal role in skeletal muscle movement, as well as in the regulation of smooth muscle and cardiac muscle. Ach is the most prevalent neurotransmitter in the human body and is instrumental in maintaining normal circadian sleep/wake cycles as well as modulating the sympathetic response to stress. In the central nervous system acetylcholine plays a pivotal role in learning, memory, and mood. Ach is synthesized from choline, an amino acid found in many foods and certain medical food products. Toxic chemicals that affect the structure of the CNS and functioning of the ANS will impair the synthesis of Ach in the human body hindering many of the restorative processes associated with the autonomic nervous system.

The structural changes of vital components of the central nervous system (CNS) as a result of exposure to these chemicals can lead to sustained physiologic problems and continued autonomic nervous system (ANS) dysfunction yielding more complicated and costly health issues many years after exposure. For example, in 2010 the U.S. Department of Veterans Affairs (VA) officially recognized the direct correlation of increased rate of early onset Parkinsons Disease (PD) among Vietnam veterans and exposure to Agent Orange during the Vietnam War (5). The general mismanagement of exposure to toxic chemicals among the Veteran population has dramatically increased the cost of healthcare to the VA.

Active military personnel are not the only people at risk for exposure to brain altering toxic chemicals. Victims of the 1995 Tokyo subway sarin attack showed reduced hippocampal volume and reduced volumes of insular cortex and surrounding white matter (6) similar to those veterans of the 1991 gulf war (7). The heroic first responders to the 9/11 bombings of the World Trade Center were exposed to clouds of toxic dust that ultimately affected ANS function yielding numerous health issues years later. According to the Mount Sinai study, 48 percent of rescue workers with asthma, 38 percent with sinusitis, and 43 percent with GERD were also diagnosed with at least one mental health condition (8). The early recognition of autonomic dysfunction associated with toxic exposure can help veterans and civilians manage future health problems and avoid the emotional and financial costs of managing chronic disease.

1. August 2, 2010. Binns JH , Barlow C , Bloom FE , et al (Research Advisory Committee on Gulf War Veterans’ Illnesses). Gulf War Illness and the Health of Gulf War Veterans. Washington, DC: Department of Veterans Affairs. http://www1.va.gov/rac-gwvi/ . Published 2008 .

2.  Haley RW , Kurt TL , Hom J . Is there a Gulf War Syndrome? searching for syndromes by factor analysis of symptoms . JAMA 1997 ; 277 ( 3 ): 215 – 222 .

3. Haley RW , Luk GD , Petty F . Use of structural equation modeling to test the construct validity of a case defi nition of Gulf War syndrome: invariance over developmental and validation samples, service branches and publicity . Psychiatry Res 2001 ; 102 ( 2 ): 175 – 200 .

4. Golomb BA . Acetylcholinesterase inhibitors and Gulf War illnesses . Proc Natl Acad Sci U S A 2008 ; 105 ( 11 ): 4295 – 4300 .

5. http://www.federalregister.gov/articles/2010/08/31/2010-21556/diseases-associated-with-exposure-to-certain-herbicide-agents-hairy-cell-leukemia-and-other-chronic

6. Yamasue H , Abe O , Kasai K , et al . Human brain structural change related to acute single exposure to sarin . Ann Neurol 2007 ; 61 ( 1 ): 37 – 46 .

7. Chao LL , Rothlind JC , Cardenas VA , Meyerhoff DJ , Weiner MW . Effects of lowlevel exposure to sarin and cyclosarin during the 1991 Gulf War on brain function and brain structure in U.S. veterans . Neurotoxicology 2010 ; 31 ( 5 ): 493 – 501 .

8. http://www.mssm.edu/departments-and-institutes/preventive-medicine/about-us/news/first-long-term-study-of-world-trade-center-rescue-and-recovery-workers-shows-widespread-health-problems-ten-years-after-9-11