Multiple sclerosis: Advances in diagnosis, biomarkers, and disease management

Multiple sclerosis (MS) care has advanced rapidly across diagnosis, biomarkers, and disease-modifying therapy. The 2024 revision of the McDonald criteria enables earlier and more biologically grounded diagnosis through the cerebrospinal fluid (CSF) kappa free light chain (KFLC) index, the central vein sign (CVS), and paramagnetic rim lesions (PRLs), and applies uniform criteria across adults and children. Our understanding of disease subtypes is also evolving. In parallel, fluid biomarkers-particularly serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP)-together with high-throughput CSF proteomics are showing promise as tools for detecting inflammatory activity, smoldering neuroinflammation, and treatment response, although assay standardization and prospective validation are still needed before most are ready for routine clinical use. The therapeutic pipeline has expanded beyond relapsing disease toward the unmet need of progressive MS, with extended anti-CD20 strategies, Bruton's tyrosine kinase (BTK) inhibitors, CD40 ligand (CD40L) blockade, vidofludimus calcium, and chimeric antigen receptor (CAR) T-cell therapies at varying stages of clinical development, from late-phase trials to early proof-of-concept studies, alongside renewed efforts in remyelination and repair. This review summarizes these developments and considers how convergent progress in diagnostics, biomarkers, and mechanistically diverse therapies is changing the approach to disability accrual in MS, and what obstacles remain.