fMRI reveals 2 Gulf War Illness phenotypes

In an unanticipated finding, George Washington University researchers discovered two distinct phenotypes of Gulf War Illness. An exercise challenge showed one subgroup with orthostatic tachycardia and a second with exercise-induced hyperalgesia, according to a study published online June 14 in PLOS One.   

Almost 30 percent of the 700,000 military personnel who served in the Persian Gulf War are afflicted with Gulf War Illness (GWI), a multifaceted syndrome characterized by cognitive impairment, widespread pain, interoceptive complaints and autonomic dysfunction.

Rakib U. Rayhan, from the division of rheumatology, immunology and allergy at George Washington University Medical Center in Washington, D.C., and colleagues hypothesized that stress tests would alter symptoms in Gulf War veterans but not in controls, which would allow them to determine underlying central mechanisms and regions of dysfunction.

The researchers enrolled 28 Gulf War veterans and 10 controls. Participants underwent an fMRI scan prior to and after a bicycle exercise challenge.

The data showed two clinical GWI subgroups. Ten veterans met the criteria for the Stress Test Associated Reversible Tachycardia (START) phenotype. fMRI showed the increased heart rate was accompanied by atrophy in the brain stem, which regulates heart rate.

The remaining 18 veterans comprised the Stress Test Occurring Phantom Perception (STOPP) subtype, and showed signs of exercise-induced hyperalgesia. This post-exercise increase in pain levels was accompanied by a loss of brain matter in adjacent regions associated with pain regulation as shown via fMRI.

In addition, fMRI during a cognitive task performed prior to exercise showed increased compensatory use of the cerebellum, a trait seen in neurodegenerative disorders. Veterans lost the ability to use this compensatory area after exercise.

The controls did not show signs of changes in cognition, brain structure and symptoms.

"The use of other brain areas to compensate for a damaged area is seen in other disorders, such as Alzheimer's disease, which is why we believe our data show that these veterans are suffering from central nervous system dysfunction," Rayhan said in a press release.

"Our findings help explain and validate what these veterans have long said about their illness," he continued.

The findings also indicate that exercise may provide a means of diagnostic verification and division into subtypes.