WASHINGTON (Army News Service, May 27, 2009) -- Research completed and analyzed over the past year has narrowed the underlying causes of Gulf War Syndrome to three factors.For 18 years, researchers struggled to pinpoint the causes of Gulf War Syndrome and its wide-ranging symptoms. Then last year, a group of researchers under the U.S. Army Medical Research and Materiel Command and the Congressionally Directed Medical Research Program narrowed the primary causes to three: chemical nerve agents, pesticides, and the use of Pyridostigmine Bromide pills.A report titled Gulf War Illness and the Health of Gulf War Veterans was released by the Department of Veteran's Affairs in November 2008, consolidating all research on the syndrome to date."There is definitely something different that has happened to servicemembers during the Gulf War as opposed to what is happening to Soldiers now," said retired Col. Melissa Forsythe, program manager of the Congressionally Directed Medical Research Program."Today's Soldiers don't exhibit any of the same symptoms," Forsythe said. "We're talking about the same geographical region. So what happened to these servicemembers in 1990-91 that's not happing now' That's really the central question."Chemical nerve agents, PB, and many of the pesticides to which Gulf War veterans were exposed belong to a class of chemicals called Acetylcholinesterase inhibitors.These chemicals inactivate the enzyme Acetylcholinesterase, which is essential for breaking down the neurotransmitter chemical acetylcholine - a chemical which affects numerous bodily functions, according to the report.Forsythe believes a mixture of the three items above in combination with vaccines given to Gulf War servicemembers can't be ruled out as a possible cause for Gulf War Syndrome.The acute symptoms of excess exposure to Acetylcholinesterase inhibitors results in increased salivation and respiratory secretions, nausea, abdominal cramping, diarrhea, excess sweating, increased heart rate, and blood pressure.Other side effects can include muscle twitching, cramps, weakness, tremors, paralysis, fatigue, mental confusion, headache, poor concentration, and general weakness. At sufficient doses, exposure to Acetylcholinesterase inhibiting chemicals can result in respiratory arrest and death.Many of these side effects coincide with those of GWS.Typically, Gulf War veterans exhibit a number of symptoms including chronic headaches, widespread diffused pain that moves to different parts of the body, fatigue, gastrointestinal problems, cognitive difficulties, skin rashes, and respiratory problems, said Forsythe.Because of the wide range of symptoms, a diagnosis of GWS could be likened to finding a needle in a haystack, Forsythe said. There is no one test that will yield a definitive diagnosis for this illness that affects 25-32 percent of Gulf War veterans, she said, adding that the only way to diagnose the disease is to eliminate all other diseases with similar symptoms.Today's GWS research focuses primarily on diagnosis and treatment rather than a single cure.Studies focusing on the physical differences between ill and healthy Gulf War veterans may make a diagnosis easier and provide a much needed legitimacy to the illness."At first, servicemembers were told that the illness was all in their heads. So now, it's very validating for those servicemembers to see that there are real physical differences between themselves and the Gulf War Veterans that are not ill," said Forsythe.Other GWS studies by the CDMRP include: research looking into the over-the-counter herbal supplement Co-enzyme Q10; the drug methylpristine, which may help with cognitive problems; and plans to look at self medications that Gulf War veterans have used and whether or not those were effective. Acupuncture is also being looked at for possible funding.Currently, the only relief for GWS sufferers is to prescribe treatments for their individual symptoms, said Forsythe.Unfortunately, record keeping practices during the Gulf War were not equal to today's standards, said Forsythe. Records on the use of Pyridostigmine Bromide and pesticides in theatre are virtually nonexistent.PB had been approved, since 1955, for treatment of myasthenia gravis, a muscular disease. During the Gulf War, PB was not licensed for protection against chemical nerve agents by the U.S. Food and Drug Administration, but it was authorized by the FDA to be released to Soldiers in combat as an "investigational new drug" as a nerve agent pretreatment.PB is now FDA approved as an effective pretreatment exclusively for the nerve agent soman and it is still issued to Soldiers for that purpose.Pesticides are still used in theater, however, only a handful of those pesticides linked to GWS in the report are still in the Department of Defense's pest control inventory."Research is not necessarily fast, but is our best route in terms of helping people," said Forsythe. We know that people are out there suffering and they're trying to find their own remedies for symptoms. So our program, being focused on improving the diagnosis and treatments, is trying to get at the two prongs that can best serve those veterans who are ill."