Choroid plexus enlargement associates with serum neurofilament and predicts relapse-free progression in multiple sclerosis

The choroid plexus (CP), a key regulator of cerebrospinal fluid production and immune cell trafficking, is increasingly recognized as a potential magnetic resonance imaging (MRI) biomarker in multiple sclerosis (MS). Serum neurofilament light chain (sNfL) serves as a sensitive blood-based indicator of neuroaxonal injury. We investigate the prognostic value of CP volume and its longitudinal change for neurodegeneration, defined by sNfL levels and disability progression. In a prospective, multicenter, longitudinal study, 891 people with MS undergo high-resolution 3T MRI, sNfL measurement, and clinical assessment over 6 years; 434 meet criteria for inclusion. CP volume correlates with sNfL after adjustment for demographic, clinical, treatment, and imaging variables. In a 2-year MRI subcohort (n = 209), CP enlargement likewise associates with sNfL. High CP volume confers a 1.8-fold increased risk of disability worsening and a 2.7-fold increased risk of progression independent of relapse activity. These findings identify CP imaging as a promising non-invasive biomarker of neuroaxonal loss and relapse-free progression.