Objective Phenotypes in Gulf War Illness with Chronic Fatigue Syndrome
Tuesday, February 24, 2015
Exhibit Hall A3 (Convention Center)
Jianing Shi, PhD, Rakib Rayhan, MS, James N Baraniuk, MD, Richard G Baraniuk, PhD
Rationale: Gulf War Illness (GWI), Chronic Fatigue Syndrome (CFS), fibromyalgia (FM), and allied disorders share subjective complaints such as pain and fatigue. Proposed causes include sarin exposure (GWI), TH2 cytokine deviation and virus infections (CFS), central sensitization of nociceptive pathways (FM), and psychiatric dysfunction. Mechanistically-based objective markers are required to assess these illnesses.

Methods: Ten Control and 28 GWI subjects who met GWI (Fukuda, 1998) plus CFS (Fukuda, 1994) criteria had submaximal exercise stress tests on DAY 1 and DAY 2. Blood oxygenation level dependent (BOLD) brain imaging during N-back working memory tests were performed before and after stress testing. Two GWI subgroups were identified by exercise-induced autonomic dysfunction. START (Stress Test Activated Reversible Tachycardia; n=10) developed postural tachycardia after exercise that lasted 36 hr, brain stem atrophy, and activation of the cerebellar vermis for cognitive compensation (Rayhan, 2013). STOPP (Stress Test Originated Phantom Pain; n=18) had basal ganglia and insula activation for cognitive compensation. BOLD signals were further analyzed by 2-level general linear modeling and functional connectivity analysis to discriminate between START and STOPP.

Results: BOLD on DAY 2 during the high cognitive load test revealed activated dorsal anterior cingulate cortex (dACC) and left premotor cortex in Controls. STOPP activated dACC, right caudate head, and left superior parietal lobe. START had no regions of significant activation. 

Conclusions: This testing paradigm revealed two objectively defined GWI phenotypes. Studies in progress may reveal distinct phenotypes in CFS, FM, and other functional disorders commonly encountered by allergists in practice.