Ask Baylor College of Medicine professor of neurology Yadollah Harati, MD, what causes the deadly neurodegenerative disease amyotrophic lateral sclerosis (ALS), and he shrugs his shoulders.

"We really don?t know," said Harati, who has studied the disease and treated patients with ALS for nearly 30 years. "It could be environmental factors. It could be a genetic susceptibility or immune system abnormalities. Despite experimental support for some of these possibilities in animals, nothing has been scientifically proven in humans."

Finding the disease?s underlying cause has frustrated patients and doctors searching for a cure. A new study linking veterans of the Gulf War to ALS raises intriguing questions about who is more at risk for the disease.

According to the study in the Sept. 23, 2003, issue of the journal Neurology, Gulf War veterans deployed to the Gulf Region have nearly double the risk of developing ALS, also known as Lou Gehrig?s disease.

In the study, sponsored by the Department of Veterans Affairs, researchers identified 40 Gulf War veterans with ALS out of the total of approximately 700,000 who participated in Desert Storm. They compared the incidence of the disease in this group of military personnel to the incidence of the disease in the 1.8 million veterans who were not sent to the 1990 Gulf War. The incidence of ALS in veterans deployed to the Gulf was twice as high as the incidence of the disease among those who did not go to the Gulf. An estimated one in 150,000 people are diagnosed with ALS every year.

A second study published in the Sept. 23, 2003 issue of Neurology by Robert W. Haley, MD, professor of medicine and chief of the epidemiology division at The University of Texas Southwestern Medical Center at Dallas, showed similar results in younger patients. The study identified 20 ALS patients under 45 years of age who were deployed to the Gulf Region, an incidence that is two to three times greater than that in the general population.

"I was surprised by both studies," said Harati, a co-author on the VA study and formerly the chief of neurology at the Houston Veteran Affairs Medical Center. "The results show a convincing association between Gulf War veterans and ALS."

What is ALS?

ALS is a progressive degenerative neurologic disorder that is generally fatal within five years of diagnosis. The disease kills motor neurons (nerve cells), which act as power stations for the body?s muscles. When a power station shuts off or dies, the muscle degenerates.

"The tragedy of this disease is that most other functions of the body are normal, like cognition," Harati said. "Patients with the disease witness their own gradual demise."

After Haley?s initial research linked ALS to veterans with Gulf War syndrome, the VA launched a much larger study in 1999, when Gulf War veterans requested an investigation of the situation. Jack Feussner, MD, the third author on the study and then head of research at the VA, promised the veterans that the VA would conduct a scientific study on this matter.

The VA enlisted the help of Harati and five prominent ALS experts to verify the diagnosis of ALS in Gulf War veterans. Two doctors confirmed each diagnosis of ALS. If the doctors did not agree on the severity of ALS, they discussed the case with the rest of the experts via conference call to reach a consensus. Harati credits Feussner?s leadership in initiating and completing the study.

"The VA was dedicated to conducting a thorough scientific study on whether or not there was an association between ALS and Gulf War veterans," Harati said. "They spared no expense in tracking down veterans with ALS and confirming their diagnosis, even if it meant flying doctors out to that person?s home."

Twice the risk

After discovering that Gulf War veterans had twice the risk for developing ALS, the VA made the controversial decision to announce the results in December 2001 in a New York Times article rather than waiting to publish it in a scientific journal. Soon afterwards, for humanitarian reasons, the VA declared that ALS was a service-connected disability in Gulf War veterans, even though its officials were still awaiting the scientific review of the results.

The news gave comfort and relief to some, "but doesn?t answer other questions about Gulf War syndrome and doesn?t tell us what causes ALS," Harati said. "Hypotheses have included military stress, nerve gas like sarin, and vaccinations, but at this moment they all are just speculation."

Harati and Donna White, PhD an instructor of neurology and a neuroepidemiologist at the Houston VA Medical Center, are currently studying the incidence of ALS in Texas veterans of all wars. Early results show that veterans of other wars maybe at slightly higher risk for ALS than the general population. They expect to publish their results in 2004.

"Maybe the ultimate cause of ALS is multifactorial," Harati said. "But I have a suspicion that the answer is right under our noses."

Harati emphasized that despite the new data linking Gulf War veterans to ALS, the disease is still extremely rare and the risk for developing it, even among veterans, is low.