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

Arrambide, G; Espejo, C; Eixarch, H; Villar, LM; Alvarez-Cermeno, JC; Picon, C; Kuhle, J; ... Tintore, M; + view all (2016) Neurofilament light chain level is a weak risk factor for the development of MS. Neurology , 87 (11) pp. 1076-1084. 10.1212/WNL.0000000000003085. Green open access

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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.

Type: Article
Title: Neurofilament light chain level is a weak risk factor for the development of MS
Open access status: An open access version is available from UCL Discovery
DOI: 10.1212/WNL.0000000000003085
Publisher version: https://doi.org/10.1212/WNL.0000000000003085
Language: English
Additional information: This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.
Keywords: Science & Technology, Life Sciences & Biomedicine, Clinical Neurology, Neurosciences & Neurology, CLINICALLY ISOLATED SYNDROME, FIBRILLARY ACIDIC PROTEIN, MULTIPLE-SCLEROSIS, N-ACETYLASPARTATE, CSF NEUROFILAMENT, AXONAL INJURY, BIOMARKERS, MARKERS, CONVERSION, DAMAGE
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neuroinflammation
URI: https://discovery.ucl.ac.uk/id/eprint/10055647
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