Validity of serum neurofilament light chain as a prognostic biomarker of disease activity in multiple sclerosis

Abstract

Multiple sclerosis (MS) is a chronic demyelinating and neuroinflammatory disease of the human central nervous system with complex pathoetiology, heterogeneous presentations and an unpredictable course of disease progression. There remains an urgent need to identify and validate a biomarker that can reliably predict the initiation and progression of MS as well as identify patient responses to disease-modifying treatments/therapies (DMTs). Studies exploring biomarkers in MS and other neurodegenerative diseases currently focus mainly on cerebrospinal fluid (CSF) analyses, which are invasive and impractical to perform on a repeated basis. Recent studies, replacing CSF with peripheral blood samples, have revealed that the elevation of serum neurofilament light chain (sNfL) in the clinical stages of MS is, potentially, an ideal prognostic biomarker for predicting disease progression and for possibly guiding treatment decisions. However, there are unresolved factors (the definition of abnormal values of sNfL concentration, the standardisation of measurement and the amount of change in sNfL concentration that is significant) that are preventing its use as a biomarker in routine clinical practice for MS. This updated review critiques these recent findings and highlights areas for focussed work to facilitate the use of sNfL as a prognostic biomarker in MS management.

Keywords: Assay standardisation; Axonal injury; Blood-based biomarker; Cerebrospinal fluid; MS prognosis; Neurodegeneration; Neurofilament; Neuroinflammation; Treatment response.