A patient comes into a neurologist's office, complaining of memory problems, fatigue, and headaches, and mentions that he was in the first Gulf War. Researchers say that should set off an alarm bell in the doctor's head, but too often that alarm is silent and the patient doesn't get the treatment he or she needs for Gulf War Syndrome.

In a new 465-page report issued in November by the Congressionally-mandated Research Advisory Committee on Gulf War Veteran's Illnesses, physicians and researchers evaluated almost two decades of studies, clinical trials, and anecdotal evidence about Gulf War Syndrome, and concluded that almost one in four of the 697,000 US veterans of the 1991 Gulf War suffer from the syndrome. The committee attributed the cause to exposure to toxic chemicals and pesticides, as well as adverse effects from the drug pyridostigmine given to troops to protect against nerve gas.

ONE IN FOUR of the 697,000 US veterans of the 1991 Persian Gulf War suffer from Gulf War syndrome, according to a new report that contradicts earlier findings by an Institute of Medicine panel.

EXPOSURE TO NERVE POISONS

They contend that pyridostigmine, pesticides, and Sarin gas — a fluorinated phosphonate — can act as nerve poisons because they are cholinesterase inhibitors. Acute exposure has toxic effects on the CNS. Lower level but chronic exposure causes an encephalopathy, with problems in balance, memory, and concentration.

The Department of Defense claims about 100,000 US troops may have been exposed to low-levels of these nerve agents as a result of large-scale US demolitions of Iraqi munitions near Khamisiyah, Iraq, in 1991, according to the report.

“There are people who have abnormal brain scans and these kind of symptoms [memory problems, fatigue, and headaches] and there's evidence of structural brain damage,” said Roberta F. White, PhD, chair of the department of environmental health at the Boston University School of Public Health and the committee's scientific director for the report. Dr. White, who has been working with Gulf War veterans, added: “Other people just have the symptoms and have the history of exposure in the Gulf War.”

In addition, the committee said, Gulf War veterans have significantly higher rates of amyotrophic lateral sclerosis (ALS) than other veterans, and troops who were downwind from the Khamisiyah demolitions have died from brain cancer at twice the rate of other Gulf War veterans. [See “ALS and Gulf War Vets” for related articles from past issues of Neurology Today.]

Dr. ROBERTA F. WHITE: “There are people who have abnormal brain scans and these kind of symptoms [memory problems, fatigue, and headaches] and theres evidence of structural brain damage.”

“Clearly there's a brain illness here and it's a real illness,” said epidemiologist Robert Haley, MD, who holds the US Armed Forces Veterans Distinguished Chair for Medical Research at the University of Texas Southwestern Medical School in Dallas, citing the committee's findings. “It's caused by damage to brain cells from a toxic combination of chemicals they were exposed to in the war.”

But 17 years later, the report authors say many questions remain, and there are few diagnostic tests, and little success in the way of treatment.

“This is a challenge for neurologists, because there's no objective diagnostic test, and there's no treatment,” Dr. Haley said. “There isn't even an ICD-9 code.”

SYNDROME IS CONTROVERSIAL

The existence of the syndrome itself is controversial. A 2006 report from the Institute of Medicine (IOM) concluded that although Gulf War veterans had a range of neurological and cognitive complaints there was no specific pattern that could constitute a unique syndrome.

Investigators on the congressional committee said much more research had come out since the IOM report, and that animal evidence was not included in the IOM review. They called for the institute to revisit its findings.

Calls for comments from the chair of the 2006 IOM committee report Lynn Goldman, MD, professor of occupational and environmental health at the Bloomberg School of Public Health at Johns Hopkins University in Baltimore, were not returned.

Jeffrey S. Sartin, MD, an infectious disease specialist who has researched Gulf War syndrome, questioned, however, how so many veterans — particularly enlisted men rather than officers — could really be diagnosed with a specific illness related to the war. There has not been a study showing any increase in mortality or hospitalization in patients who claim to have Gulf War illness, said Dr. Satin, who is affiliated with the Gundersen Clinic in La Cross, WS.

“I agree we need to study this more and, if there are treatments, study them,” he said. “The problem is that when studying a certain exposure, it's so much easier to study it early on than down the line because you get into compound variables — people get depressed in middle age, they get arthritis. I'm not enthusiastic that we'll have a hard answer in the next couple of years.”

CALLS FOR MORE RESEARCH

The new report calls for additional funding for the study of Gulf War syndrome, particularly in the areas of diagnosis and treatment. Everyone interviewed for this article said that it was frustrating not to have a specific diagnostic test, whether it be an MRI, CT scan or even a blood test that would help doctors identify the illness.

Dr. White noted that the patients themselves are often “strapping-looking people.” Too often, she said, doctors just dismiss cases when people come in and complain but nothing comes out in the lab tests and there's no straightforward diagnosis.

“People hate to diagnose things they can't treat, that's natural,” she said. “But the same is true for Alzheimer or Parkinson disease or many other things we diagnose. This is no different.”

Dr. Sartin compared the vague symptoms and obscure diagnosis to chronic fatigue syndrome, fibromyalgia, and even post-traumatic stress disorder.

“What you're getting into here is two fields that are hard to quantify – one is large scale epidemiology — how do you define an illness?” said Dr. Sartin. “The other is, how do you measure exposures? You have to recognize the limitation of these types of endeavors.”

Gulf War Syndrome Report: Findings In Brief

Among findings, the new report found:

Gulf War illness is a serious condition that affects at least one-fourth of the 697,000 US veterans who served in the 1990–1991 Gulf War.

Gulf War illness fundamentally differs from trauma and stress-related syndromes described after other wars.

Evidence strongly and consistently indicates that two Gulf War neurotoxic exposures are causally associated with Gulf War illness: 1) use of pyridostigmine bromide (PB) pills, given to protect troops from effects of nerve agents, and 2) pesticide use during deployment.

For several Gulf War exposures, an association with Gulf War illness cannot be ruled out. These include low-level exposure to nerve agents, close proximity to oil well fires, receipt of multiple vaccines, and effects of combinations of Gulf War exposures.

Other wartime exposures are not likely to have caused Gulf War illness for the majority of ill veterans.

Gulf War illness is associated with diverse biological alterations that most prominently affect the brain and nervous system.

Gulf War illness has both similarities and differences with multisymptom conditions in the general population.

Studies indicate that Gulf War veterans have significantly higher rates of amyotrophic lateral sclerosis (ALS) than other veterans, and that Gulf War veterans potentially exposed to nerve agents have died from brain cancer at elevated rates.

A copy of the complete report is available at http://sph.bu.edu/insider/racreport.

ALS and Gulf War Vets in Neurology Today

See these past articles on Gulf War syndrome and ALS among returning veterans online on the Neurology Today Web site, www.neurotodayonline.com: