Neurofilament light chain levels in MS At the doorstep of clinical application

In addition to the mysteries and autobiographies that some of you may be packing for a late summer vacation or long weekend, consider including the current issue of N2. Each article has a plot that will leave you on edge, and here, I will introduce some of them. It is well known that the presentation of MS is diverse, with some patients presenting early with very mild disease and others presenting late with extensive damage from silent disease. Until now, the best biomarker of disease activity and treatment effects has been the MRI. However, MRI has several limitations, including availability, cost, interscan variability, limited sensitivity for predicting disease progression, and the need to include the spinal cord for comprehensive assessment. Serum neurofilament light chain (NfL), a neuroaxonal intermediate protein, is a promising biomarker candidate. Elevated serum levels of NfL in patients with MS substantially decrease when the disease is controlled by treatment, and this may have prognostic value. In this issue of N2, Thebault et al.(1) assessed the NfL levels in serum and CSF, along with MRI and clinical measures, in patients with MS at baseline and 1 and 3 years after immunoablative chemotherapy followed by autologous hematopoietic stem cell transplantation (IAHSCT). The authors found that at baseline, NfL levels in patients with MS were significantly elevated compared with those of controls and that after IAHSCT, NfL levels in patients with MS decreased and became not significantly different from the levels of controls. These and other findings related to the associations between NfL levels and clinical and MRI outcomes are discussed by the authors and in an editorial comment by Leppert and Kuhle(2) suggesting that blood NfL testing is at the doorstep of clinical application.