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

Tanuja Chitnis, Cindy Gonzalez, Brian C Healy, Shrishti Saxena, Mattia Rosso, Christian Barro, Zuzanna Michalak, Anu Paul, Pia Kivisakk, Camilo Diaz-Cruz, Neda Sattarnezhad, Isabelle V Pierre, Bonnie I Glanz, Davorka Tomic, Harald Kropshofer, Dieter Häring, David Leppert, Ludwig Kappos, Rohit Bakshi, Howard L Weiner, Jens Kuhle, Tanuja Chitnis, Cindy Gonzalez, Brian C Healy, Shrishti Saxena, Mattia Rosso, Christian Barro, Zuzanna Michalak, Anu Paul, Pia Kivisakk, Camilo Diaz-Cruz, Neda Sattarnezhad, Isabelle V Pierre, Bonnie I Glanz, Davorka Tomic, Harald Kropshofer, Dieter Häring, David Leppert, Ludwig Kappos, Rohit Bakshi, Howard L Weiner, Jens Kuhle

Abstract

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 Comprehensive Longitudinal Investigations in MS at Brigham 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 (T2LV) 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 T2LV, specifically averaged year 1-5 NfL (unadjusted P < 0.01; adjusted analysis P < 0.01). Approximately 15-20% of the BPF variance and T2LV 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 T25FW 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.

Figures

Figure 1
Figure 1
Boxplot of NfL distribution for each year. (A) Boxplot distributions of NfL during each sample year (N subjects=122), using the log scale. (B) Spaghetti plot of the arithmetic mean observed trajectories per each subject

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