Choroid plexus morphological and microstructural changes across inflammatory phenotypes in multiple sclerosis

Background: Growing evidence supports choroid plexus (CP) involvement in MS pathophysiology, but phase-specific associations according to recent inflammatory activity and longitudinal dynamics remain unclear. Objective: To characterize CP alterations in MS using volumetric and quantitative magnetic resonance imaging (MRI) and explore associations with neuroinflammation and neurodegeneration. Methods: We analyzed cross-sectional and 2-year longitudinal data from 101 patients with active relapsing MS (RMS), 83 with inactive progressive MS (PMS), and 100 controls, with MS groups stratified by inflammatory activity within the prior year. CP volume, quantitative T1, and magnetization transfer saturation (MTsat) were assessed alongside imaging, serum, and clinical measures, with validation in a second cohort (62 active/357 inactive MS). Results: CP volume was increased in both active RMS and inactive PMS and was associated with lower total and cortical brain volumes. Associations with brain microstructural damage were more pronounced in periventricular regions, compatible with a surface-in pattern. Similar associations were observed in controls, suggesting CP volume may reflect processes beyond MS-specific pathology, including physiological factors. Longitudinally, CP volume increased exclusively in active RMS, with faster expansion associated with thalamic atrophy. CP MTsat was associated with cortical and paramagnetic rim lesions in inactive PMS. Conclusion: CP enlargement is consistent across MS phases. Longitudinal expansion occurs in active inflammatory disease and is associated with neurodegenerative changes.