Gulf War Syndrome May Alter Brain Chemistry - Brief Article - Statistical Data Included

Family Pratice News,  Feb 1, 2000  by Betsy Bates

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CHIGAGO -- Distinct brain chemistry abnormalities and a genetic vulnerability to the effects of toxic substances have been identified in veterans with Gulf War syndrome.

Together, the findings begin to put to rest questions about whether the illnesses suffered by Gulf War veterans are real, investigators maintained during the annual meeting of the Radiological Society of North America.

"The evidence that there is a Gulf War disease verges on overwhelming," said Dr. James L. Fleckenstein, associate professor of neuroradiology at the University of Texas Southwestern Medical Center at Dallas.

Furthermore, the detection of injured neurons in certain portions of the brain points the way to potential cures, said Dr. Robert W. Haley, associate professor of epidemiology at the university.

"We have really strong clues about where to go for (targeting) treatment. There are probably a hundred different medications out there that might be used to treat this," said Dr. Haley, principal investigator of the study of 22 veterans identified with Gulf War syndrome' and 18 control subjects who also fought in the Gulf but did not become ill.

Magnetic resonance spectroscopy (MRS), which measures brain chemicals, detected diminished levels of N-acetyl-aspartate (NAA) in the left and right basal ganglia of veterans with any of three identified Gulf War syndromes. (See box below.)

These levels were 10%-25% below the NAA levels that were detected in the basal ganglia of healthy veterans, a highly statistically significant result that was then duplicated in six more veterans with Gulf War syndrome who were from a different part of the country.

A significant depletion of NAA in the brain stem was also seen in patients with Gulf War syndromes 2 and 3.

Elevated choline levels, which are seen in depressed patients, were not observed in symptomatic veterans, a notable point since some skeptics have suggested that veterans' symptoms could be due to stress or a major depressive disorder.

In a prior study of the same veterans, Dr. Haley and his associates showed that some veterans with Gulf War syndrome also had significantly reduced activity of PON 1 arylesterase, an enzyme that protects against the effects of chemical toxicity in the brain.

Brain levels of this enzyme are genetically determined, implying that the veterans who had become ill may have had a predisposed sensitivity to the chemicals that they were exposed to during their tours in the Persian Gulf.

Dr. Fleckenstein cited previous research that symptomatic veterans were 8-32 times more likely to have been exposed to chemicals found in government-issued insect repellant, flea collars, and nerve gas tablets, as well as nerve gas itself, compared with unaffected veterans.

Dr. Fleckenstein called on the U.S. government to pursue research into brain chemical evidence of Gulf War syndrome, especially in determining the standard deviation (accuracy) of the test.

Until such a large-scale study is done and potentially therapeutic drugs are identified, there is little point in MRS testing of all symptomatic veterans, he said.

Further, the military may want to test troops for levels of PON 1 arylesterase before issuing drugs or chemical products, he added.

Dr. Haley noted that most physicians in veterans' hospitals and the Pentagon initially viewed Gulf War syndrome as a disease but began to doubt that conclusion when soldiers' physical examinations, brain scans, magnetic resonance imaging scans, and ECGs were normal.

Advances in MRS technology look beyond the brain's architecture to its chemical makeup, which is profoundly altered in the sickest veterans, he said.

From the Pentagon, Dr. Michael Kilpatrick, medical advisor to the special assistant for Gulf War illnesses, told this newspaper that he found the MRS study results to be "very intriguing" but still preliminary.

Although MRS is an accepted test for indicating neuron loss in illnesses such as schizophrenia, Parkinson's disease, and multiple sclerosis, a normal range has not been well established, Dr. Kilpatrick commented.

He added that he was less than hopeful for a potential cure once neurons are lost, as demonstrated by NAA depletion.

The government is spending $131 million in a "hard effort to get some answers" as to why 104,000 veterans of the Gulf War have reported symptoms of some kind, he said. New technology, MRS as well as single photon emission computed tomography and PET scanning, may help determine organic explanations for Gulf War illnesses.

Dr. Kilpatrick encouraged physicians seeing Gulf War veterans for fatigue, bone and joint pain, and/or neurocognitive symptoms to consider enrolling them in one of two treatment protocols being coordinated through Veterans' Affairs hospitals (800-827-1000).

More than 1,000 veterans will participate in an exercise and biofeedback study and 450 veterans with positive Mycoplasma fermentans incognitus assays will be randomly assigned to receive doxycycline or placebo. Results are expected in about 2 years.