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.

Figure 1.. NfL levels in the 2 CIS groups

Results adjusted for CIS topography and disease-modifying treatment. CDMS = clinically definite multiple sclerosis; CIS = clinically isolated syndrome; NfL = neurofilament light chain.

Figure 2.. Scatterplots showing the correlations between NfL levels and brain volume changes

The graphs represent the raw data. The correlation coefficients and p values correspond to the partial correlations adjusted for age and baseline gadolinium-enhancing lesions. (A) BPF change at 1 year. (B) PBVC at 1 year. (C) BPF change at 5 years. (D) PBVC at 5 years. BPF = brain parenchymal fraction; NfL = neurofilament light chain; PBVC = percentage brain volume change.