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Neurofilament light chain level is a weak risk factor for the development of MS.
Arrambide, Georgina; Espejo, Carmen; Eixarch, Herena; Villar, Luisa M; Alvarez-Cermeño, José C; Picón, Carmen; Kuhle, Jens; Disanto, Giulio; Kappos, Ludwig; Sastre-Garriga, Jaume; Pareto, Deborah; Simon, Eva; Comabella, Manuel; Río, Jordi; Nos, Carlos; Tur, Carmen; Castilló, Joaquín; Vidal-Jordana, Angela; Galán, Ingrid; Arévalo, Maria J; Auger, Cristina; Rovira, Alex; Montalban, Xavier; Tintore, Mar.
Affiliation
  • Arrambide G; From 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
  • Espejo C; From 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
  • Eixarch H; From 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
  • Villar LM; From 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
  • Alvarez-Cermeño JC; From 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
  • Picón C; From 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
  • Kuhle J; From 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
  • Disanto G; From 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
  • Kappos L; From 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
  • Sastre-Garriga J; From 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
  • Pareto D; From 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
  • Simon E; From 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
  • Comabella M; From 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
  • Río J; From 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
  • Nos C; From 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
  • Tur C; From 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
  • Castilló J; From 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
  • Vidal-Jordana A; From 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
  • Galán I; From 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
  • Arévalo MJ; From 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
  • Auger C; From 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
  • Rovira A; From 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
  • Montalban X; From 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
  • Tintore M; From 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
Neurology ; 87(11): 1076-84, 2016 Sep 13.
Article in En | MEDLINE | ID: mdl-27521440
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Demyelinating Diseases / Neurofilament Proteins Type of study: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Adult / Female / Humans / Male Language: En Journal: Neurology Year: 2016 Document type: Article Publication country: EEUU / ESTADOS UNIDOS / ESTADOS UNIDOS DA AMERICA / EUA / UNITED STATES / UNITED STATES OF AMERICA / US / USA
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Demyelinating Diseases / Neurofilament Proteins Type of study: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Adult / Female / Humans / Male Language: En Journal: Neurology Year: 2016 Document type: Article Publication country: EEUU / ESTADOS UNIDOS / ESTADOS UNIDOS DA AMERICA / EUA / UNITED STATES / UNITED STATES OF AMERICA / US / USA