Exploring CSF neurofilament light as a biomarker for MS in clinical practice; a retrospective registry-based study

• Background: Neurofilament light (NFL) has been increasingly recognized for prognostic and therapeutic decisions. Objective: To validate the utility of cerebrospinal fluid NFL (cNFL) as a biomarker in clinical practice of relapsing-remitting multiple sclerosis (RRMS). Methods: RRMS patients (n = 757) who had cNFL analyzed as part of the diagnostic work-up in a single academic multiple sclerosis (MS) center, 2001-2018, were retrospectively identified. cNFL concentrations were determined with two different immunoassays and the ratio of means between them was used for normalization. Results: RRMS with relapse had 4.4 times higher median cNFL concentration (1134 [interquartile range (IQR) 499-2744] ng/L) than those without relapse (264 [125-537] ng/L, p < 0.001) and patients with gadolinium-enhancing lesions had 3.3 times higher median NFL (1414 [606.8-3210] ng/L) than those without (426 [IQR 221-851] ng/L, p < 0.001). The sensitivity and specificity of cNFL to detect disease activity was 75% and 98.5%, respectively. High cNFL at MS onset predicted progression to Expanded Disability Status Scale (EDSS) > 3 (p < 0.001, hazard ratios (HR) = 1.89, 95% CI = 1.44-2.65) and conversion to secondary progressive MS (SPMS, p = 0.001, HR = 2.5, 95% CI = 1.4-4.2). Conclusions: cNFL is a robust and reliable biomarker of disease activity, treatment response, and prediction of disability and conversion from RRMS to SPMS. Our data suggest that cNFL should be included in the assessment of patients at MS-onset.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Keyword

Multiple sclerosis

cerebrospinal fluid

neurofilament light protein

prognosis

therapy

cerebrospinal-fluid biomarkers

fibrillary acidic protein

multiple-sclerosis

disease-activity

neurodegenerative diseases

disability

efficacy

marker

damage

Neurosciences & Neurology

Publication and Content Type

ref (subject category)

art (subject category)