High serum neurofilament light chain levels correlate with brain atrophy and physical disability in multiple sclerosis.

Background and purpose: Serum neurofilament light chain (sNfL) is a promising biomarker of neuroaxonal damage in persons with multiple sclerosis (pwMS). In cross‐sectional studies, sNfL has been associated with disease activity and brain magnetic resonance imaging (MRI) changes; however, it is still unclear to what extent in particular high sNfL levels impact on subsequent disease evolution. Methods: sNfL was quantified by an ultrasensitive single molecule array (Simoa) in 199 pwMS (median age = 34.2 years, 64.3% female) and 49 controls. All pwMS underwent 3‐T MRI to assess global and compartmental normalized brain volumes, T2‐lesion load, and cortical mean thickness. Follow‐up data and serum samples were available in 144 pwMS (median follow‐up time = 3.8 years). Linear and binary logistic models were used to estimate the independent contribution of sNfL for changes in MRI and Expanded Disability Status Scale (EDSS). Age‐corrected sNfL z‐scores from a normative database of healthy controls were used for sensitivity analyses. Results: High sNfL levels at baseline were associated with atrophy measures of the whole brain (standardized beta coefficient βj = −0.352, p < 0.001), white matter (βj = −0.229, p = 0.007), thalamus (βj = −0.372, p = 0.004), and putamen (βj = −1.687, p = 0.012). pwMS with high levels of sNfL at baseline and follow‐up had a greater risk of EDSS worsening (p = 0.007). Conclusions: Already single time point elevation of sNfL has a distinct effect on brain volume changes over a short‐term period, and repeated high levels of sNfL indicate accumulating physical disability. Serial assessment of sNfL may provide added value in the clinical management of pwMS. [ABSTRACT FROM AUTHOR]