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.