Question  Can serum neurofilament light chain measurements serve as a reliable biomarker of disease Worsening for patients with Multiple Sclerosis?
Findings  In this cohort study of 607 patients with Multiple Sclerosis, serum neurofilament light chain levels increased significantly faster in those experiencing disability Worsening than in those who remained clinically Stable. Serum neurofilament light chain level was associated with brain fraction loss, whereas this was less the case for clinical outcomes such as relapses or EDSS Worsening.
Meaning  The association of serum neurofilament light chain level with changes in relevant clinical and neuroimaging outcomes in Multiple Sclerosis was confirmed, strengthening the potential of this biomarker as a measure of disease activity in Multiple Sclerosis; however, the clinically useful prognostic value of serum neurofilament light chain level for the individual patient was limited.
Importance  Blood sample–based biomarkers that are associated with clinically meaningful outcomes for patients with Multiple Sclerosis (MS) have not been developed.
Objective  To evaluate the potential of serum neurofilament light chain (sNFL) measurements as a biomarker of disease activity and progression in a longitudinal MS data set.
Design, Setting, and Participants  Single-center, ongoing, prospective observational cohort study of 607 patients with MS from the longitudinal EPIC (Expression, Proteomics, Imaging, Clinical) study at the University of California, San Francisco from July 1, 2004, through August 31, 2017. Clinical evaluations and sample collection were performed annually for 5 years, then at different time points for up to 12 years, with a median follow-up duration of 10 (interquartile range, 7-11) years. Serum NFL levels were measured using a sensitive single molecule array platform and compared with clinical and magnetic resonance imaging variables with the use of univariable and multivariable analyses.
Main Outcomes and Measures  The main outcomes were disability progression defined as clinically significant Worsening on the Expanded disability Status Scale (EDSS) score and brain fraction atrophy.
Results  Mean (SD) age of the 607 study participants at study entry was 42.5 (9.8) years; 423 (69.7%) were women; and all participants were of non-Hispanic European descent. Of 3911 samples sequentially collected, 3904 passed quality control for quantification of sNFL. Baseline sNFL levels showed significant associations with EDSS score (β, 1.080; 95% CI, 1.047-1.114; P 
(Originally posted by Stuart)

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