Oluwatoyin Adewuyi

Increased brain white matter axial diffusivity associated with fatigue, pain and hyperalgesia in Gulf War illness.

Background Gulf War exposures in 1990 and 1991 have caused 25% to 30% of deployed personnel to develop a syndrome of chronic fatigue, pain, hyperalgesia, cognitive and affective dysfunction. Methods Gulf War veterans (n = 31) and sedentary veteran and civilian controls (n = 20) completed fMRI scans for diffusion tensor imaging. A combination of dolorimetry, subjective reports of pain and fatigue were correlated to white matter diffusivity properties to identify tracts associated with symptom constructs. Results Gulf War Illness subjects had significantly correlated fatigue, pain, hyperalgesia, and increased axial diffusivity in the right inferior fronto-occipital fasciculus. ROC generated thresholds and subsequent binary regression analysis predicted CMI classification based upon axial diffusivity in the right inferior fronto-occipital fasciculus. These correlates were absent for controls in dichotomous regression analysis. Conclusion The right inferior fronto-occipital fasciculus may be a potential biomarker for Gulf War Illness. This tract links cortical regions involved in fatigue, pain, emotional and reward processing, and the right ventral attention network in cognition. The axonal neuropathological mechanism(s) explaining increased axial diffusivity may account for the most prominent symptoms of Gulf War Illness.

Exercise Challenge in Gulf War Illness Reveals Two Subgroups with Altered Brain Structure and Function

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.

Dyspnea in Chronic Fatigue Syndrome (CFS): comparison of two prospective cross-sectional studies.

Chronic Fatigue Syndrome (CFS) subjects have many systemic complaints including shortness of breath. Dyspnea was compared in two CFS and control cohorts to characterize pathophysiology. Cohort 1 of 257 CFS and 456 control subjects were compared using the Medical Research Council chronic Dyspnea Scale (MRC Score; range 0-5). Cohort 2 of 106 CFS and 90 controls answered a Dyspnea Severity Score (range 0-20) adapted from the MRC Score. Subsets of both cohorts completed CFS Severity Scores, fatigue, and other questionnaires. A subset had pulmonary function and total lung capacity measurements. Results show MRC Scores were equivalent between sexes in Cohort 1 CFS (1.92 [1.72-2.16]; mean [95% C.I.]) and controls (0.31 [0.23-0.39]; p<0.0001). Receiver-operator curves identified 2 as the threshold for positive MRC Scores in Cohort 1. This indicated 54% of CFS, but only 3% of controls, had significant dyspnea. In Cohort 2, Dyspnea Score threshold of 4 indicated shortness of breath in 67% of CFS and 23% of controls. Cohort 2 Dyspnea Scores were higher for CFS (7.80 [6.60-9.00]) than controls (2.40 [1.60-3.20]; p<0.0001). CFS had significantly worse fatigue and other complaints compared to controls. Pulmonary function was normal in CFS, but Borg scores and sensations of chest pain and dizziness were significantly greater during testing than controls. General linear model of Cohort 2 CFS responses linked Dyspnea with rapid heart rate, chest pain and dizziness. In conclusion, sensory hypersensitivity without airflow limitation contributed to dyspnea in CFS. Correlates of dyspnea in controls were distinct from CFS suggesting different mechanisms.