Researchers Strive to Solve the Mystery of Gulf War Illness

Posted in GUMC Stories

Even after participating in a 2001 Institute of Medicine panel on Gulf War illness (GWI), David Goldsmith, MSPH, Ph.D. , associate professor in the Department of Human Science at GUMC, was a self-described GWI skeptic. “There wasn’t really a clear-cut set of clinical parameters or a clinical test that would differentiate someone who clearly had a case of Gulf War illness from someone who was healthy,” he said.

Then Goldsmith learned about research by James Baraniuk, MD , a professor of medicine at GUMC.

“Because of Dr. Baraniuk’s breakthrough research, I changed my mind 180 degrees,” Goldsmith said during “Hilltop Dialogue: Georgetown Discovery Paves the Way for Diagnosis & Treatment of Gulf War Illness,” a May 29 discussion in the Rafik B. Hariri Building. “There is no question that we would not be having this discussion today had it not been for Dr. Baraniuk’s groundbreaking research and he really deserves credit for giving us a completely new insight into Gulf War illness.”

Since the Gulf War ended in 1991, more than 200,000 veterans have been fighting GWI, a mysterious chronic multisystem illness. Little is known about GWI but innovative researchers at GUMC are working to identify ways to diagnose and ultimately treat the disease, giving hope to veterans and their families.

Looking for clues

While working with the Institute of Medicine panel, Goldsmith and his colleagues focused on environmental exposures, such as solvents and pesticides, that could be responsible for GWI. However, the panel could not identify any elements that aligned neatly with the symptoms veterans reported. “There were a whole group of candidates, including inoculations, exposures to depleted uranium, oil field fires and emissions, exposures to weapons that the Iraqis had put together and were burned out in the desert, a whole variety of things,” Goldsmith said. “But none of them seemed to stack up and make clear to us from an epidemiological perspective what was a major risk factor for what at the time was called Gulf War syndrome.”

The symptoms of GWI range from mild to debilitating and include fatigue, generalized pain, unrefreshing sleep and cognitive impairment. Those with GWI also experience a worsening of their symptoms after physical or mental exertion, a clue that Baraniuk fixated on in his research. In 2012, Baraniuk and his colleagues conducted fMRI scans before and after exercise stress tests in a study with 28 Gulf War veterans and 10 control group participants.

After the stress test, 18 veterans experienced increased levels of pain and their fMRI scans indicated brain matter atrophy near regions associated with pain regulation. This group became known as the Stress Test Occurring Phantom Perception (STOPP) group. The other 10 veterans had substantial increases in their heart rate while their fMRI scans showed reduced brain matter in the brain stem, which regulates heart rate. As a result, they were called the Stress Test Associated Reversible Tachycardia (START) group. The healthy control group did not experience changes in their levels of pain or heart rate.  

“The reason that we need to pay attention to this is because the brain scans are different for those in the START group and it indicates that there are regions of the brain that control the heart rate that appear to be quite different, quite shrunken, when compared to controls and when compared to the STOPP group,” Goldsmith said.  

“Gulf War illness has been confused with a lot of other ill-defined syndromes, like chronic fatigue syndrome, for example, or fibromyalgia,” said Marc Blackman, MD, associate chief of staff for research and development at the Washington, D.C. Veterans Affairs Medical Center. “But it is now the consensus of all who have really looked at this that it is its own entity.”

Yet defining GWI remains problematic. In the absence of a consistent definition shared by the various parties who deal with the condition, including the Veterans Health Administration, Department of Defense and Department of Health and Human Services, it will be nearly impossible to determine the incidence and prevalence of GWI, Blackman said. “That’s not going to advance either our knowledge, our ability to care for or ability to research. We need a common clinical definition. So that’s one of the chief goals,” he said.

Turning research into treatment

Developing clinical applications for GWI research is another goal for the Department of Veterans Affairs, Blackman said. “If I’m interested in understanding a human condition that adversely impacts people, I want to not only understand it and publish a lot of papers and get grants and talk about it,” he said. “What I want to do more than anything is see that translated into improving the well-being of those who are adversely affected.”

The Clinical and Translational Science Award (CTSA) was designed by the National Institutes of Health to bridge the gap between medical research and clinical practices. In 2010, Georgetown University, along with Howard University, MedStar Health Research Institute, Oak Ridge National Laboratory and the Washington, D.C. Veterans Affairs Medical Center, received a CTSA which led to the formation of the Georgetown-Howard Universities Center for Clinical and Translational Science.  

“Of course, we are very proud at Georgetown to be the recipient of one of these CTSAs,” said James Giordano, PhD , chief of the Neuroethics Studies Program at the GUMC Pellegrino Center for Clinical Bioethics. “This is not only an applied, clinically focused center but also one that relies heavily upon its research infrastructure. And that research is, for the most part, cutting edge, spanning the gap between those things that are exceedingly low tech to those things that are exceedingly high tech, and doing so in a way that attempts to de-silo some of the more disciplinary frameworks so as to be able to be far more integrative in its approach.”

As a U.S. Naval officer who served on active duty with the Marine Corps during Operation Desert Shield, Giordano expressed concern for veterans struggling with GWI. “Some of these individuals are still not seeking care because of the stigma attached to psychiatric illness in the military. Others, after being discharged, fell between proverbial cracks because they were misdiagnosed or not assessed in the appropriate ways,” he said.

Future research directions

This fall, Baraniuk will repeat his previous study with a new group of Gulf War veterans to confirm his results. “He’s very much looking forward to see if he can confirm and verify these earlier findings,” Goldsmith said.

Baraniuk also received a grant from the Sergeant Sullivan Foundation to study biomarkers and will look for patterns in MRIs, blood samples and cerebrospinal fluid to differentiate between the STOPP and START groups, as well as a control group. “If the biomarkers research that he’s talking about is fruitful, this could be one of the things that could allow for much more rapid diagnosis,” Goldsmith said.

Meanwhile, there are just under 400 ongoing VA studies related to GWI. The VA is also setting up bio-repositories to store brain scans, blood samples and more. “These bio-repositories are a big part of the Gulf War plan,” Blackman said. “I am sure that a few years from today, not only will we have more knowledge but more importantly, we’ll have better outcomes.”

Kat Zambon
GUMC Communications