Gulf War illness symptoms persist, new imaging shows

By Russell Rian

Using a new imaging technique, researchers at UT Southwestern have discovered that brain dysfunction in veterans with Gulf War illness persisted or worsened more than a decade after being initially diagnosed.

Dr. Robert W. Haley
Dr. Robert W. Haley

The findings, reported in the journal Radiology, advance research initiated at the medical center that was the first to pinpoint damage to the brains of veterans with Gulf War illness and link the illness to chemical exposure.

 “Here we confirmed that abnormal blood flow continued or worsened over the 11-year span since first being diagnosed, which indicates the damage is ongoing and lasts long term,” said Dr. Robert W. Haley, Chief of Epidemiology and senior author of the study. “We also developed a special MRI procedure that better diagnoses and distinguishes between the three main types of Gulf War illness.”

In a separate but related study reported in the journal Neuroepidemiology, Dr. Haley and associates from the Research Triangle Institute International confirmed the three primary variants of Gulf War illness, finding overall symptoms nearly four times more prevalent in those deployed than in non-deployed veterans.

“This is a critical paper because it validates the definition of Gulf War illness that underlies all of our genetic and neuroimaging studies,” Dr. Haley said. “It is also important that the paper comes primarily from RTI, an independent institution standing behind the disease definition that we have been advocating for 15 years. It is also our first paper validating our work that is based on a very large, population-representative sample of Gulf War veterans.”

Previous research at UT Southwestern identified three patterns of symptoms in ill veterans: impaired cognition, confusion and balance disturbances, and central nerve pain. In the Radiology study, veterans with the latter two patterns had an abnormal increase in blood flow in the brain after being given physostigmine, which briefly stimulates certain brain receptors thought to have been damaged by war-related chemical exposure. Veterans in the control group showed the normal decrease in cerebral blood flow when given the medicine. 

Researchers then used a specialized MRI technique called arterial spin labeling (ASL) to track blood flow in the brain in an effort to identify areas functioning abnormally. The new technique also eliminates radiation exposure and shortens testing time.

“ASL scanning after administering this medication is particularly well suited to diagnosing Gulf War illness, because it picks up brain abnormalities too subtle for regular MRI scans to detect,” said Dr. Richard Briggs, Professor of Radiology and Internal Medicine, and the chief MRI physicist on the research team. “This allows us to make the diagnosis without radiation exposure in a single two-hour scanning session, where it took us all afternoon on two separate days with our previous approach using nuclear medicine scans with radioactive tracers.”

Having an objective diagnostic test allows researchers to identify affected veterans for future clinical trials of possible treatments. It also is critical for ongoing genomic studies to see why some people are affected by chemical exposures and others are not, Dr. Haley said.

Gulf War syndrome, which includes symptoms such as fatigue, depression, and memory and concentration loss, affects an estimated 25 percent of the 700,000 military personnel deployed in the 1991 Gulf War, according to the paper.

Dr. Haley and colleagues, who first defined Gulf War syndrome in 1997, have continued to study the same group of test subjects since 1995. Previous studies revealed that veterans with Gulf War illness had lower levels of a protective blood enzyme called paraoxonase, which usually fights off the toxins such as sarin. Veterans who served in the same geographical area and did not get sick had higher levels of this enzyme.  Confirmatory studies in large, random samples of Gulf War veterans were recently completed and are being analyzed.

Other UT Southwestern researchers involved in the Radiology study include Dr. Jeffrey Spence, Assistant Professor of Clinical Sciences and Internal Medicine; Dr. C. Munro Cullum, Professor of Psychiatry and Neurology and Neurotherapeutics; Dr. Melanie Biggs, Associate Professor of Psychiatry; Dr. Andrea Hester, Assistant Professor of Psychiatry; and researchers from UT Arlington, UT Dallas School of Behavioral and Brain Sciences and Center for BrainHealth and the University of Central Arkansas.

The study was funded by a federal research contract administered by the Department of Veterans Affairs Medical Center, Dallas; and grants from the U.S. Army Medical Research and Materiel Command and the National Institutes of Health. 

Dr. Haley holds the U.S. Armed Forces Veterans Distinguished Chair for Medical Research, Honoring America's Gulf War Veterans.