White Matter Volume and Microstructural Integrity Are Associated with Fatigue in Relapsing Multiple Sclerosis

Multiple sclerosis (MS) is a prevalent neurological disorder marked by inflammation and demyelination, with fatigue being one of the most reported and debilitating symptoms. While fatigue occurs across various neurological conditions and even in healthy individuals, the specific mechanisms contributing to fatigue in each context remain unclear. In this study, we conducted a cross-sectional analysis involving 33 people with relapsing MS (PwRMS) and 29 healthy controls who also reported fatigue. Participants underwent MRI scans, including T1-weighted and diffusion-weighted imaging, to evaluate brain structure. Additionally, the Modified Fatigue Impact Scale was utilized. To investigate the hypothesis that fatigue correlates differently with brain structures in PwRMS, we employed Bayesian LASSO and Spike-and-Slab LASSO regression models. Our findings indicated that lower white matter volume and compromised microstructural integrity in specific brain regions—such as the caudate part of cingulate gyrus, inferior frontal gyrus, and the banks of the superior temporal sulcus—were significantly associated with fatigue scores in PwRMS. These results suggest that alterations in specific brain regions may play a critical role in the clinical manifestation of fatigue in MS. Understanding these insights could help differentiate general mechanisms of fatigue from those affecting people with relapsing MS, which may guide future therapeutic strategies.