Beyond MRI: The Role of Serum Biomarkers in Multiple Sclerosis

The idea behind precision medicine is simple: no two patients with multiple sclerosis (MS) have the same disease, so no two should receive the same care by default. Putting that idea into practice is harder. MS varies widely in how it presents, how it progresses, and how it responds to therapy. For years, clinicians have relied largely on relapses and MRI to guide decisions. New tools in biomarkers, imaging, and genetics promise a more complete picture of each patient's disease, but questions remain about which of these tools are ready for the clinic.

In NeurologyLive^®'s Roundtable series Precision Medicine in Multiple Sclerosis: Advances & Unanswered Questions, produced in collaboration with Cleveland Clinic Neurological Institute, three clinicians from Cleveland Clinic's Mellen Center for Multiple Sclerosis Treatment and Research take on those questions. The panelists are Robert Bermel, MD, director of the Mellen Center; Marisa McGinley, DO, staff neurologist at the Mellen Center; and Rebecca Cebull, CNP, certified nurse practitioner at the Mellen Center. They draw on their clinical experience to assess how close the field is to delivering truly individualized care.

In the second episode, the panel turns to fluid biomarkers, including serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (GFAP). Bermel notes that highly sensitive assays now allow clinicians to measure markers of central nervous system damage with remarkable precision. The harder problem is interpretive: without a full understanding of progressive MS biology, it is difficult to know what to measure. In his practice, sNfL is most useful in specific situations, such as patients who cannot undergo MRI. MRI remains the mainstay of monitoring. McGinley adds that unlike an MRI, a single sNfL result is rarely actionable on its own. Clinicians still need a better understanding of population-level and individual reference ranges.

Cebull describes the reassurance that a blood-based test can offer patients who worry about subclinical disease activity between annual scans. She cautions that it remains unclear how an elevated level should inform treatment decisions. She also highlights older patients with progressive disease whose MRIs look the same year after year even as they continue to decline clinically. Current biomarkers leave this group "in the dark." The panelists agree that the field's biggest need is a marker of neurodegeneration that tracks with real-world progression and points to a biological pathway that therapy could target.