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Objective  To assess the value of annual serum neurofilament light (NfL) measures in predicting 10‐year clinical and  MRI  outcomes in multiple sclerosis ( MS ).    Methods  We identified patients in our center's  C omprehensive  L ongitudinal  I nvestigations in   M S  at  B righam and Women's Hospital ( CLIMB ) study enrolled within 5 years of disease onset, and with annual blood samples up to 10 years ( n  = 122). Serum NfL was measured using a single molecule array ( SIMOA ) assay. An automated pipeline quantified brain T2 hyperintense lesion volume (T2 LV ) and brain parenchymal fraction ( BPF ) from year 10 high‐resolution 3T  MRI  scans. Correlations between averaged annual NfL and 10‐year clinical/ MRI  outcomes were assessed using Spearman's correlation, univariate, and multivariate linear regression models.    Results  Averaged annual NfL values were negatively associated with year 10  BPF , which included averaged year 1–5 NfL values (unadjusted  P  < 0.01; adjusted analysis  P  < 0.01), and averaged values through year 10. Linear regression analyses of averaged annual NfL values showed multiple associations with T2 LV , specifically averaged year 1–5 NfL (unadjusted  P  < 0.01; adjusted analysis  P  < 0.01). Approximately 15–20% of the  BPF  variance and T2 LV  could be predicted from early averaged annual NfL levels. Also, averaged annual NfL levels with fatigue score worsening between years 1 and 10 showed statistically significant associations. However, averaged NfL measurements were not associated with year 10  EDSS ,  SDMT  or T25 FW  in this cohort.    Interpretation  Serum NfL measured during the first few years after the clinical onset of  MS  contributed to the prediction of 10‐year  MRI  brain lesion load and atrophy.

Neurofilament light chain serum levels correlate with 10‐year MRI outcomes in multiple sclerosis