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

Georgina Arrambide, Carmen Espejo, Herena Eixarch, Luisa M. Villar, José C. Alvarez-Cermeño, Carmen Picón, Jens Kuhle, Giulio Disanto, Ludwig Kappos, Jaume Sastre-Garriga, Deborah Pareto, Eva Simon, Manuel Comabella, Jordi Río, Carlos Nos, Carmen Tur, Joaquín Castilló, Angela Vidal-Jordana, Ingrid Galán, Maria J. ArévaloCristina Auger, Alex Rovira, Xavier Montalban, Mar Tintore

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Abstract

© 2016 American Academy of Neurology. 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 (r s -0.892) and percentage brain volume change (r s -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.
Original languageEnglish
Pages (from-to)1076-1084
JournalNeurology
Volume87
Issue number11
DOIs
Publication statusPublished - 13 Sep 2016

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    Arrambide, G., Espejo, C., Eixarch, H., Villar, L. M., Alvarez-Cermeño, J. C., Picón, C., Kuhle, J., Disanto, G., Kappos, L., Sastre-Garriga, J., Pareto, D., Simon, E., Comabella, M., Río, J., Nos, C., Tur, C., Castilló, J., Vidal-Jordana, A., Galán, I., ... Tintore, M. (2016). Neurofilament light chain level is a weak risk factor for the development of MS. Neurology, 87(11), 1076-1084. https://doi.org/10.1212/WNL.0000000000003085