Abstract
BACKGROUND: The choroid plexus (CP) is increasingly recognised as a contributor to chronic inflammation in multiple sclerosis (MS). While CP enlargement is reported in early MS, its role in secondary progressive MS (SPMS) is poorly understood. OBJECTIVE: We aimed to quantify CP volume in SPMS and compare it to relapsing-remitting MS (RRMS) and clinically isolated syndrome (CIS), and to assess associations with disease severity and progression. METHODS: CP volumes were manually segmented and normalised to intracranial volume. Age correction was applied using a healthy control cohort. Cross-sectional and longitudinal analyses evaluated relationships with ventricular volume, lesion burden, and brain atrophy. RESULTS: CP volume increased significantly across MS phenotypes: SPMS patients showed 26% higher CP volume than CIS (p=0.010) and 17% higher than RRMS (p=0.034). CP enlargement in SPMS was independent of ventricular size, indicating distinct underlying mechanisms. While lesion burden was the primary determinant of brain atrophy in SPMS, longitudinal data revealed significant associations between CP volume, chronic lesion expansion (r(2)=0.31), and brain volume loss (r(2)=0.52). CONCLUSION: CP enlargement is a progressive feature of MS, not driven by ventricular expansion. In SPMS, it may reflect ongoing inflammation contributing to tissue damage, supporting its role as a biomarker.