Abstract
Nearly 30% of the approximately 700,000 military personnel who served in Operation Desert Storm (1990–1991) have developed Gulf War Illness, a condition that presents with symptoms such as cognitive impairment, autonomic dysfunction, debilitating fatigue and chronic widespread pain that implicate the central nervous system. A hallmark complaint of subjects with Gulf War Illness is post-exertional malaise; defined as an exacerbation of symptoms following physical and/or mental effort. To study the causal relationship between exercise, the brain, and changes in symptoms, 28 Gulf War veterans and 10 controls completed an fMRI scan before and after two exercise stress tests to investigate serial changes in pain, autonomic function, and working memory. Exercise induced two clinical Gulf War Illness subgroups. One subgroup presented with orthostatic tachycardia (n = 10). This phenotype correlated with brainstem atrophy, baseline working memory compensation in the cerebellar vermis, and subsequent loss of compensation after exercise. The other subgroup developed exercise induced hyperalgesia (n = 18) that was associated with cortical atrophy and baseline working memory compensation in the basal ganglia. Alterations in cognition, brain structure, and symptoms were absent in controls. Our novel findings may provide an understanding of the relationship between the brain and post-exertional malaise in Gulf War Illness.
Highlights
Gulf War Illness (GWI) has affected 25% to 30% of the approximately 700,000 military personnel who served in the 1990–1991 Persian Gulf War [1]
Phenotype Identification There were no significant differences in demographic variables or Gulf War – related exposures between GWI and control subjects (Table A in File S1)
Supine and standing heart rate (HR), systolic (SBP) and diastolic blood pressure (DBP) and their associated postural changes were equivalent between GWI and controls (Figure 1 and Table C in File S1)
Summary
Gulf War Illness (GWI) has affected 25% to 30% of the approximately 700,000 military personnel who served in the 1990–1991 Persian Gulf War [1]. There are no validated clinical markers for GWI to account for inter-individual variations in symptom severity or differences from controls. Ambiguity is increased by the use of multiple epidemiologically derived criteria and non-standardized symptom assessments [1,3–5]. GWI shares subjective symptoms with other idiopathic illnesses that include chronic fatigue syndrome (CFS) and fibromyalgia [5,12]. Similar to CFS and fibromyalgia, GWI subjects complain of exertional malaise with severe exacerbations of baseline symptoms following a physiological stressor [12–15]. Exercise is a useful model to study symptom alterations in CFS, fibromyalgia and GWI [15–17]. The causal relationships between exercise, the brain, and deteriorating disease status are unknown
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