Serum Neurofilament Light Chain for Multiple Sclerosis Relapses Too Little Too Late?

Over the past 25 years, neurofilament light chain (NfL) has emerged as a promising biomarker for multiple sclerosis (MS). NfL, a neuron-specific protein, is an integral component of the neuronal and axonal cytoskeleton in both the central nervous and peripheral nervous systems. High-sensitivity methods can detect serum NfL (sNfL) levels that are proportionate to those in the cerebral spinal fluid, making it an attractive way to investigate CNS pathology. In isolation, elevated NfL in the cerebral spinal fluid and serum signifies nonspecific neuroaxonal damage in a number of traumatic, inflammatory, and neurodegenerative diseases.(1) However, in the context of MS, sNfL can be quite useful. Elevated sNfL predicts conversion from radiographically and clinically isolated syndrome to relapsing-remitting MS.(2,3) In addition, elevated sNfL correlates with ongoing inflammatory disease including clinical relapses, gadolinium-enhancing lesions, and new T2 lesions on MRI.(4-6) Based on this, sNfL is well positioned as a lower cost, less burdensome alternative to frequent MRI as a measure of MS inflammatory disease activity. To date, the bulk of our understanding of the relationships between sNfL and MS disease outcomes is correlative. We need a better understanding of the immediate, dynamic relationships between sNfL and MS markers of inflammation.