Cholinergic Autonomic Dysfunction in Veterans With Gulf War Illness Confirmation in a Population-Based Sample

Background: The authors of prior small studies raised the hypothesis that symptomsin veterans of the 1991 Gulf War, such as chronic diarrhea, dizziness, fatigue, and sexual dysfunction, are due to cholinergic autonomic dysfunction. Objective: To perform a confirmatory test of this prestated hypothesis in a larger, representative sample of Gulf War veterans. Design: Nested case-control study. Setting: Clinical and Translational Research Center, University of Texas Southwestern Medical Center, Dallas. Participants: Representative samples of Gulf War veterans meeting a validated case definition of Gulf War illness with 3 variants (called syndromes 1-3) and a control group, all selected randomly from the US Military Health Survey. Main Outcome Measures: Validated domain scales from the Autonomic Symptom Profile questionnaire, the Composite Autonomic Severity Score, and high-frequency heart rate variability from a 24-hour electrocardiogram. Results: The Autonomic Symptom Profile scales were significantly elevated in all 3 syndrome groups (P < .001), primarily due to elevation of the orthostatic intolerance, secretomotor, upper gastrointestinal dysmotility, sleep dysfunction, urinary, and autonomic diarrhea symptom domains. The Composite Autonomic Severity Score was also higher in the 3 syndrome groups (P = .045), especially in syndrome 2, primarily due to a significant reduction in sudomotor function as measured by the Quantitative Sudomotor Axon Reflex Test, most significantly in the foot; the score was intermediate in the ankle and upper leg and was nonsignificant in the arm, indicating a peripheral nerve length-related deficit. The normal increase in high-frequency heart rate variability at night was absent or blunted in all 3 syndrome groups (P < .001). Conclusion: Autonomic symptoms are associated with objective, predominantly cholinergic autonomic deficits in the population of Gulf War veterans. JAMA Neurol. 2013;70(2):191-200. Published online November 26, 2012. doi:10.1001/jamaneurol.2013.596