Neurofilament light as a prognostic marker in multiple sclerosis

Abstract

Relapsing-remitting multiple sclerosis has a variable prognosis and lacks a reliable laboratory prognostic marker. Our aim in this study was to investigate the association between neurofilament light levels in cerebrospinal fluid in early multiple sclerosis and disease severity at long-term follow-up. Neurofilament light levels in cerebrospinal fluid collected at diagnostic lumbar puncture were measured in 99 multiple sclerosis cases. Clinical data were obtained from 95 out of those at follow-up visits made 14 years (range 8-20 years) after disease onset. Significant correlations between neurofilament light levels and the multiple sclerosis severity score were found for all cases (r = 0.30, p = 0.005), for relapsing-remitting multiple sclerosis cases (r = 0.47, p < 0.001) and for cases with a recent relapse (r = 0.60, p < 0.001). In the multivariate logistic regression analysis, neurofilament light levels >386 ng/L (median value of cases with detectable levels) increased the risk for severe multiple sclerosis fivefold (odds ratio 5.2, 95% confidence interval 1.8-15). Kaplan-Meier analysis showed that conversion to secondary-progressive multiple sclerosis was more likely in cases with neurofilament light levels >386 ng/L than in those with neurofilament light levels <60 ng/L (p = 0.01) or 60-386 ng/L (p = 0.03). We conclude that elevated levels of neurofilament light in cerebrospinal fluid collected at diagnostic lumbar puncture were associated with unfavourable prognosis. These data suggest that the neurofilament light level could be used as a prognostic marker in early relapsing-remitting multiple sclerosis.

Elevated Concentrations of Neurofilament Light Chain in the Cerebrospinal Fluid of Bipolar Disorder Patients

“…Thus, the CSF concentration of NF-L mirrors the degree of acute axonal degradation. Elevated concentrations of neurofilament subunits have been described in many neurological diseases including Alzheimer's disease (Sjogren et al, 2000;Brettschneider et al, 2006), vascular dementia (Bjerke et al, 2009), amyotrophic lateral sclerosis (Zetterberg et al, 2007;Lu et al, 2012), and multiple sclerosis (Salzer et al, 2010). In multiple sclerosis, the CSF concentration of NF-L is downregulated by treatment with the anti-inflammatory drug natalizumab, indirectly implicating that increased CSF NF-L reflects inflammatory-mediated axonal damage (Gunnarsson et al, 2011).…”

Serum neurofilament is associated with progression of brain atrophy and disability in early MS

“…Immunoassays for both NfL and NfH have been extensively published and have short-term and long-term prognostic value in various neurologic disorders. [2][3][4][5] The phase II riluzole trial in participants with early multiple sclerosis (MS) was a randomized, double-blind, placebo-controlled study assessing the putative neuroprotective effect of riluzole. The primary outcome of the trial, brain atrophy, was negative.…”

Paramètres cliniques, biochimiques et d’imagerie prédictifs de I’ évolution de la sclérose en plaques

“…des protéines de neurofilaments ont été détectées dans le liquide céphalorachidien (lcR) et dans des échantillons sanguins de patients atteints de SEP et ont été récemment considérées comme l'un des plus prometteurs des potentiels biomarqueurs de la maladie dans la SEP. 80 on a constaté une progression entre les taux des neurofilaments (NFl) dans le lcR mesuré au stade précoce de la SEP et la gravité de la maladie dans un suivi à long terme (8 à 20 ans). 81 de plus, un traitement avec le natalizumab a normalisé le taux de neurofilament dans le lcR dans une des études, indiquant cette protéine comme un marqueur éventuel de la réponse au traitement. 82 la présence de bandes oligoclonales (Bo) d'immunoglobulines de type G (lgG) peut s'avérer un prédicteur sensible de la conversion des Sci à une SEP confirmée.…”