Brainstem atrophy in Gulf War Illness.

• The GWI developed after 1990–1991 Gulf War has no validated definition or validated diagnostic marker. • Neuroimaging studies in GWI have been limited by small sample sizes, inconsistent GWI definition. • Using automated brain MRI volumetric measurement in a large GWI cohort, this study identified subcortical atrophy in GWI. • A greatest brainstem abnormality in GWI veterans was detected. Further investigations into the brainstem substructures are needed. • The brainstem atrophy in correlation with GWI core symptoms demonstrated a key role of the brainstem structures in GWI. Gulf War Illness (GWI) is a condition that affects about 30 % of veterans who served in the 1990-91 Persian Gulf War. Given its broad symptomatic manifestation, including chronic pain, fatigue, neurological, gastrointestinal, respiratory, and skin problems, it is of interest to examine whether GWI is associated with changes in the brain. Existing neuroimaging studies, however, have been limited by small sample sizes, inconsistent GWI diagnosis criteria, and potential comorbidity confounds. Using a large cohort of US veterans with GWI, we assessed regional brain volumes for their associations with GWI, and quantified the relationships between any regional volumetric changes and GWI symptoms. Structural magnetic resonance imaging (MRI) scans from 111 veterans with GWI (Age = 49 ± 6, 88 % Male) and 59 healthy controls (age = 51 ± 9, 78 % male) were collected at the California War Related Illness and Injury Study Center (WRIISC-CA) and from a multicenter study of the Parkinson's Progression Marker Initiative (PPMI), respectively. Individual MRI volumes were segmented and parcellated using FreeSurfer. Regional volumes of 19 subcortical, 68 cortical, and 3 brainstem structures were evaluated in the GWI cohort relative to healthy controls. The relationships between regional volumes and GWI symptoms were also assessed. We found significant subcortical atrophy, but no cortical differences, in the GWI group relative to controls, with the largest effect detected in the brainstem, followed by the ventral diencephalon and the thalamus. In a subsample of 58 veterans with GWI who completed the Chronic Fatigue Scale (CFS) inventory of Centers for Disease Control and Prevention (CDC), smaller brainstem volumes were significantly correlated with increased severities of fatigue and depressive symptoms. The findings suggest that brainstem volume may be selectively affected by GWI, and that the resulting atrophy could in turn mediate or moderate GWI-related symptoms such as fatigue and depression. Consequently, the brain stem should be carefully considered in future research focusing on GWI pathology. [ABSTRACT FROM AUTHOR]