Plasma neurofilament light levels are associated with risk of disability in multiple sclerosis

Objective: To investigate the association between plasma NfL (pNfL) levels and risk of developing sustained disability worsening. Methods: Concentrations of pNfL were determined in 4,385 persons with MS and 1,026 randomly selected population-based sex- and age-matched controls using the highly sensitive Single Molecule Array (SimoaTM) NF-light® Advantage kit. We assessed the impact of age-stratified pNfL levels above 80th, 95th and 99th of controls' percentiles on the risk of Expanded Disability Status Scale (EDSS) worsening within the following year and reaching sustained EDSS scores of 3.0, 4.0 and 6.0 and conversion to secondary progressive (SP) MS. Results: The median (interquartile range) pNfL was 7.5 (4.1) pg/ml in controls and 11.4 (9.6) pg/ml in MS (P <0.001). The median (interquartile range) duration of follow-up was 5 years (5.1). High pNfL was associated with increased adjusted rates of EDSS worsening ranging between 1.4 (95% confidence intervals (CI): 1.1-1.8) and 1...