Brainstem atrophy is associated with fatigue in myelin oligodendrocyte glycoprotein antibody-associated disease

Background: Fatigue is a common symptom in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), but its underlying mechanisms are not well understood. Objective: To investigate MRI volumetric changes associated with fatigue in MOGAD patients. Methods: Forty-three MOGAD patients and 29 healthy controls (HC) were recruited from January 2020 to December 2022. Brain volumes, including the brainstem and its subregions (midbrain, superior cerebellar peduncle [SCP], pons, and medulla), were analyzed using FreeSurfer v7.1. Volumetric measures were compared between groups, adjusted for age, sex, and intracranial volume. Correlations between Fatigue Severity Scale (FSS) scores and brain volumes were examined, and predictors of fatigue severity were further explored using multiple linear regression analysis. Results: Fatigue was present in 30.2 % of MOGAD patients. Fatigued patients had significantly reduced medulla volume compared to HC (p = 0.004) and exhibited higher Expanded Disability Status Scale scores, greater depression, and poorer sleep quality, and lower quality of life compared to non-fatigued patients. Higher fatigue scores correlated with smaller brainstem volumes, including the medulla (r = –0.368, p = 0.019), pons (r = –0.331, p = 0.037), and SCP (r = –0.338, p = 0.033). In multiple regression analysis, reduced medulla (B = –0.014, p = 0.019) and SCP volumes (B = –0.188, p = 0.008) were significant predictors of fatigue, while other clinical factors were not. Conclusions: Fatigue in MOGAD is associated with reduced brainstem volumes, particularly in the medulla, suggesting a role of the brainstem in the pathophysiology of fatigue.