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Neurology. 2016 Sep 13;87(11):1076-84. doi: 10.1212/WNL.0000000000003085. Epub 2016 Aug 12.

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

Author information

  • 1From Servei de Neurologia-Neuroimmunologia (G.A., C.E., H.E., J.S.-G., E.S., M.C., J.R., C.N., C.T., J.C., A.V.-J., I.G., M.J.A., X.M., M.T.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Barcelona; Universitat Autònoma de Barcelona (G.A., C.E., H.E., J.S.-G., E.S., M.C., J.R., C.N., C.T., J.C., A.V.-J., I.G., X.M., M.T.), Bellaterra; Departments of Neurology and Immunology (L.M.V., J.C.A.-C., C.P.), Multiple Sclerosis Unit, Hospital Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain; Department of Neurology (J.K., L.K.), University Hospital Basel; Neurocentre of Southern Switzerland (G.D.), Ospedale Civico, Lugano, Switzerland; and Magnetic Resonance Unit (IDI) (D.P., C.A., A.R.), Hospital Universitari Vall d'Hebron, Barcelona, Spain.
  • 2From Servei de Neurologia-Neuroimmunologia (G.A., C.E., H.E., J.S.-G., E.S., M.C., J.R., C.N., C.T., J.C., A.V.-J., I.G., M.J.A., X.M., M.T.), Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Vall d'Hebron Institut de Recerca, Hospital Universitari Vall d'Hebron, Barcelona; Universitat Autònoma de Barcelona (G.A., C.E., H.E., J.S.-G., E.S., M.C., J.R., C.N., C.T., J.C., A.V.-J., I.G., X.M., M.T.), Bellaterra; Departments of Neurology and Immunology (L.M.V., J.C.A.-C., C.P.), Multiple Sclerosis Unit, Hospital Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain; Department of Neurology (J.K., L.K.), University Hospital Basel; Neurocentre of Southern Switzerland (G.D.), Ospedale Civico, Lugano, Switzerland; and Magnetic Resonance Unit (IDI) (D.P., C.A., A.R.), Hospital Universitari Vall d'Hebron, Barcelona, Spain. mtintore@cem-cat.org carmen.espejo@vhir.org.

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.

PMID:
27521440
PMCID:
PMC5027802
DOI:
10.1212/WNL.0000000000003085
[PubMed - in process]
Free PMC Article
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