25 May 2000

Gulf War Veterans Have Brain Damage

by Kate Melville

In the June issue of Radiology, researchers report that sick Gulf War veterans when compared with healthy veterans had 20 percent less brain cells in the brain stem, 12 percent less in the right basal ganglia and 5 percent less in the left basal ganglia. That reduction is similar in magnitude to results found in patients with brain diseases like amyotrophic lateral sclerosis (ALS) and multiple sclerosis, as well as dementia and other degenerative neurological disorders, although the brain areas affected are different.

"A common question is whether these levels of brain-cell loss found in these veterans are clinically important," said Dr. Robert Haley, UT Southwestern chief of epidemiology and lead author of the study. "You need to ask yourself if you would be willing to give up 5 percent to 25 percent of the brain cells in vital parts of your brain that serve as the relay station for all automatic and subconscious functions of your brain.

"When you sustain such brain-cell losses, you get a host of subtle malfunctions of all systems of the body."

Using magnetic resonance (MR) spectroscopy - highly specialized brain scans that measure chemical levels inside the brain - UT Southwestern researchers found evidence of brain damage that causes a variety of symptoms in sick veterans, including joint pain, fatigue, dizziness and mental confusion. MR spectroscopy explores brain chemistry by using radio waves to measure intracellular concentrations of protons and estimate the concentrations of common brain chemicals.

Previous magnetic resonance imaging (MRI) on the veterans found no visible structural changes to the brain. But by using MR spectroscopy, researchers could look at brain chemical levels, which show biochemical and physiological changes to the brain.

Dr. James Fleckenstein, professor of radiology, presented initial findings from the study Nov. 30 at the Radiological Society of North America's annual meeting. Publication of the findings in the journal Radiology indicates they have now passed rigorous peer review.

"This brain disorder is quite similar to a variety of other diseases in which patients may be severely disabled, the conventional MRI scan is normal and the MR spectroscopy scan uniquely detects brain damage," Fleckenstein said.

The tests were conducted on 22 members of a Naval Reserve construction battalion, commonly known as Seabees, in the southeastern United States. The tests were also done on 18 healthy veterans from the same battalion. Investigators performing the tests were blinded to group identities.

The findings were replicated among a small sample of six Gulf War Army veterans living in Dallas who have been diagnosed with Gulf War Syndrome 2.

"Finding the same level of brain cell abnormality in the veterans from a different branch of service and a different part of the country increases the likelihood that the findings are widespread among the nation's veterans," Haley said.

In 1997 Haley and his colleagues defined three Gulf War syndromes in the Journal of the American Medical Association. Syndrome 1, commonly found in veterans who wore pesticide-containing flea collars, is characterized by impaired cognition. Syndrome 2, called confusion-ataxia, the most severe and debilitating of the syndromes, is found among veterans who said they were exposed to low-level nerve gas and experienced side effects from anti-nerve gas, or pyridostigmine (PB), tablets. Syndrome 3, characterized by central pain, is found in veterans who wore insect repellent with high concentrations of DEET and experienced side effects from the PB tablets.

The MR spectroscopy study found that veterans with Syndrome 2 had 18 percent less N-acetylaspartate (NAA) in the right basal ganglia and 26 percent less NAA in the brain stem, compared with healthy veterans of the same age, sex and educational level.

NAA is the brain chemical that indicates the number of functioning brain cells in the area being scanned. Finding less NAA in the deep brain structures of the sick veterans implies that many brain cells have either been destroyed or become too damaged to function.

The varying magnitude of loss of brain function explains why some veterans are sicker than others are, while some suffer only mild symptoms.

As a consequence of having the greatest loss of brain cells, veterans with Syndrome 2 have the highest rate of occupational disability, report the worst vertigo attacks and performed the worst on objective medical tests of brain function. Veterans with Syndromes 1 and 3 are generally still able to work, have less dizziness, performed better on the medical tests and were found to have less severe loss of brain cells on the brain scans.

On brain-function tests, sick veterans with the greatest loss of brain cells performed similarly to victims of the Tokyo subway sarin nerve gas attack.

In previous studies, Haley and his colleagues have shown that Gulf War veterans who complain of being sick have genetically lower levels of a blood enzyme, PON-Q that fights off nerve gas making them more susceptible to illness from low levels of nerve-gas exposure. In the new study, those veterans born with the lowest PON-Q levels were found to have the greatest loss of functional brain cells measured by MR spectroscopy.