Neurofilament light chain level is a weak risk factor for the development of MS

Abstract

Objective:To determine the prognostic value of selected biomarkers in clinically isolated syndromes (CIS) for conversion to multiple sclerosis (MS) and disability accrual.Methods:Data were acquired from 2 CIS cohorts. The screening phase evaluated patients developing clinically definite MS (CIS-CDMS) and patients who remained as CIS during a 2-year minimum follow-up (CIS-CIS). We determined levels of neurofascin, semaphorin 3A, fetuin A, glial fibrillary acidic protein, and neurofilament light (NfL) and heavy chains in CSF (estimated mean [95% confidence interval; CI]). We evaluated associations between biomarker levels, conversion, disability, and magnetic resonance parameters. In the replication phase, we determined NfL levels (n = 155) using a 900 ng/L cutoff. Primary endpoints in uni- and multivariate analyses were CDMS and 2010 McDonald MS.Results:The only biomarker showing significant differences in the screening was NfL (CIS-CDMS 1,553.1 [1,208.7–1,897.5] ng/L and CIS-CIS 499.0 [168.8–829.2] ng/L, p < 0.0001). The strongest associations were with brain parenchymal fraction change (rs = −0.892) and percentage brain volume change (rs = −0.842) at 5 years. NfL did not correlate with disability. In the replication phase, more NfL-positive patients, according to the cutoff, evolved to MS. Every 100-ng/L increase in NfL predicted CDMS (hazard ratio [HR] = 1.009, 95% CI 1.005–1.014) and McDonald MS (HR = 1.009, 95% CI 1.005–1.013), remaining significant for CDMS in the multivariate analysis (adjusted HR = 1.005, 95% CI 1.000–1.011). This risk was lower than the presence of oligoclonal bands or T2 lesions.Conclusions:NfL is a weak independent risk factor for MS. Its role as an axonal damage biomarker may be more relevant as suggested by its association with medium-term brain volume changes.

Neurofilaments in CSF As Diagnostic Biomarkers in Motor Neuron Disease: A Meta-Analysis

“…All of above might lead to overestimation of the test performance. It should also be noted that increased neurofilament level are not specific for ALS and have been reported in a number of other neurological diseases, including multiple sclerosis, dementia and brain trauma (Norgren et al, 2003; Skillback et al, 2014; Arrambide et al, 2016; Kirkcaldie and Collins, 2016; Xu et al, 2016). An ideal study should include other neurodegenerative disorders and ALS mimics as controls and use a pre-specified threshold.…”

Neurofilament light chain in cerebrospinal fluid and prediction of disease activity in clinically isolated syndrome and relapsing–remitting multiple sclerosis

“…The CSF levels of NFL in patients with CIS have been reported to be an independent prognostic marker for conversion from CIS to MS [23][24][25], to correlate with MS severity score during long-term follow-up in MS [6] and to decrease on treatment [8]. To our knowledge, this is the first study to demonstrate that NFL at baseline is a strong predictor of disease activity in the comprehensive form of NEDA-3 status during 2 years of follow-up in CIS and newly diagnosed MS. We also confirmed that CSF levels of NFL predicted conversion from CIS to MS.…”

Clinical usefulness of prognostic biomarkers in optic neuritis

“…CSF NFL values were examined first. NFL is considered as a biomarker of axonal damage and is associated with conversion to MS in general CIS cohorts . In our ON series, CSF NFL levels seemed to be higher in patients who converted to CDMS, although differences were not significant.…”