Abstract
OBJECTIVE: The claustrum is a small, thin structure of predominantly gray matter with broad connectivity and enigmatic function. Little is known regarding the impact of claustrum pathology in multiple sclerosis (MS). METHODS: This study assessed whether claustrum volume was reduced in MS and whether reductions were associated with specific disability domains. We compared the impact of claustrum volume reductions on neurological disability versus the well-studied thalamus. Data from the 15,793 participants in the MS PATHS study were used for primary analyses. A second cohort of 71 people with MS and healthy controls from our center was used for validation. RESULTS: Claustrum and thalamic volumes were reduced to a similar degree across MS types. Claustrum volume, like thalamic volume, was associated with disability measures of walking speed, upper extremity dexterity, and cognition. Partial correlation analyses supported that both claustrum and thalamic volumes independently contribute to disability. Interestingly, claustrum volume outperformed thalamic volume as a predictor of future disability progression. INTERPRETATION: This study suggests that damage and resulting atrophy to the claustrum may be an important component of MS-related disability.