Dynamics of choroid plexus volume is associated with the presence and development of fatigue in multiple sclerosis

BACKGROUND: Immune-mediated processes are implicated in the pathogenesis of fatigue, a common symptom in multiple sclerosis (MS). The choroid plexus (CP) regulates central nervous system (CNS) immune homeostasis and undergoes volumetric modifications possibly contributing to MS-related fatigue. We explored the association between MS-related CP volume changes and fatigue dynamics. METHOD: Eighty-five patients with MS and 68 healthy controls (HC) underwent brain 3T MRI, neurological evaluation and Modified Fatigue Impact Scale (MFIS) at two timepoints (median follow-up=1.4 years). Normalised brain and regional grey matter (GM) volumes were obtained using FSL-SIENAx, FIRST, SIENA and tensor-based morphometry. CP volumes were quantified with in-house methods, and longitudinal changes were analysed using linear mixed models. RESULTS: At baseline, 25 (29%) patients with MS had fatigue (f-MS) (MFIS ≥38). Compared with HC, patients with MS had significantly higher brain T2-lesion volume, lower brain, deep GM, cortical volumes and higher CP volume (false discovery rate (FDR)-p ≤0.024). Compared with non-fatigued (nf-MS) patients, f-MS were older, more disabled (FDR-p ≤0.002) and showed numerically higher CP volume (FDR-p=0.076). At follow-up, 41 (68%) nf-MS remained non-fatigued (nf-FU-MS) and 19 (32%) developed fatigue (f-FU-MS). Patients with MS showed higher brain and deep GM atrophy rates versus HC (FDR-p ≤0.048), whereas clinical, lesional and brain volumetric changes were not significantly different among MS groups (FDR-p ≥0.287). CP volume significantly increased in all MS groups compared with HC (FDR-p ≤0.043), with greater enlargement in f-FU-MS versus nf-FU-MS (FDR-p=0.048). CONCLUSIONS: Larger CP and greater enlargement are associated with the presence and development of fatigue in MS, likely reflecting dynamic inflammatory states within the CNS, supporting the immunological contribution to MS-related fatigue.