Fluid biomarkers in multiple sclerosis: from current to future applications

Multiple sclerosis (MS) is an immune-mediated inflammatory and degenerative disorder of the central nervous system (CNS) with heterogeneous clinical manifestations. In the last decade, the landscape of cerebrospinal fluid (CSF) and blood biomarkers as potential key tools for MS diagnosis, prognosis and treatment monitoring has evolved considerably, alongside magnetic resonance imaging (MRI). CSF analysis has the potential not only to provide information on the underlying immunopathology of the disease and exclude differential diagnoses, but also to predict the risk of future relapses and disability accrual, guide therapeutic decisions and thus improve patient outcomes. This Series article overviews the biological framework and current applicability of fluid biomarkers for MS, exploring their potential role in the molecular characterisation of the disease. We discuss recent advances in the field of neurochemistry that enabled the detection of brain-derived proteins in blood, opening the door to much more efficient longitudinal disease monitoring. Furthermore, we identify the current challenges in the application of fluid biomarkers for MS in a real-world setting, while offering recommendations for harnessing their full potential as key paraclinical tools to improve patient management and personalise treatment.