Gulf War Illness (GWI) is a chronic and multi-symptomatic disorder affecting 25 to 30 percent of military veterans who served in the 1990-1991 Persian Gulf War. Symptoms vary, but typically include fatigue, muscle pain, cognitive problems and more. The cause of GWI is currently unknown, although hypotheses have included: pesticides, pills containing pyridostigmine bromide, sarin, cyclosarin, and emissions from oil well fire.
In 2000, researchers made one of the most important clinical findings regarding GWI to date—veterans experience more severe symptoms and general illness exacerbation following physical, cognitive, emotional or other exertion. Now, researchers from Georgetown University Medical Center have expanded upon this discovery.
James Baraniuk and Stuart Washington used functional magnetic resonance imaging (fMRI) to show that, based on physiological changes in the brain, GWI patients can actually be characterized into two distinct groups post-physical exercise. This suggests a more complex illness that previously thought, but also better informs multiple strategies for future treatments of GWI patients.
The work builds off a previous study by the researchers in which they assessed changes in heart rate before exercise and after 5 minutes of standing post-exercise. Three distinct groups were identified and used in the current study: 1) GWI-START, who presented with a heart rate exceeding 30 bpm, but returned to normal within 24 to 48 hours after exercise; 2) GWI-POTS, those with an elevated heart rate during all periods of standing; and 3) GWI-STOPP, those who did not experience an elevated heart rate, but complained of pain reminiscent of phantom limb pain.
Washington, a post-doc fellow and lead author of the study published in Brain Communications, imaged the brains of the three subgroups of veterans with GWI before and after moderate exercise, as well as healthy control patients. The following day, the groups had a second stress test and a memory test during brain imaging.
Prior to exercise, there were no differences in fMRI scans between veterans. However, that changed after exercise with subgroups showing significantly different activation levels in multiple regions of interest in the brain. All groups of GWI veterans showed differences in brain activity compared to healthy patients—who showed no changes at all—but the type of abnormal brain activity was different between the groups.
The two veteran groups prone to racing heart rates—GWI-START and GWI-POTS—both presented with a significant decrease in brain activity in the cerebellum, the part of the brain responsible for fine motor control, cognition, pain and emotion. In contrast, the GWI-STOPP group not prone to racing heart rates had a significant increase in brain activity in a different part of the brain that is responsible for planning of body movements and is also associated with chronic pain.
According to the researchers, these results suggest brain activity can be used to distinguish the GWI-START from the GWI-STOPP phenotype. “The exercise stressor paradigm affected different neural mechanisms in the GWI phenotypes,” write the study authors. “Distinct neural networks may mediate the cognitive dysfunction, post-exertional malaise, and exertional exhaustion in these veterans.”
At the very least, the study results leave open numerous areas for future targeted research on GWI.
“Now that different regions of the brain have been associated with two subtypes of GWI, we can study these regions through imaging and other techniques to improve diagnosis and, perhaps, to study future treatments," said Baraniuk.
Photo: A Kuwaiti oil field set afire by retreating Iraqi troops burns in the distance beyond an abandoned Iraqi T-55A tank following Operation Desert Storm in 1991. Credit: Georgetown University.