Neurofilament light chain level is a weak risk factor for the development of MS
Arrambide, Georgina (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Espejo, Carmen (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Eixarch, Herena (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Villar, Luisa M. (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Alvarez-Cermeño, José C. (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Picón, Carmen (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Kuhle, Jens (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Disanto, Giulio (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Kappos, Ludwig (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Sastre-Garriga, Jaume (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Pareto, Deborah (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Simon, Eva (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Comabella, Manuel (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Río, Jordi (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Nos, Carlos (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Tur, Carmen (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Castilló, Joaquín (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Vidal-Jordana, Angela (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Galan, Ingrid (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Arévalo, María Jesús (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Auger, Cristina (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Rovira, Alex (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Montalban, Xavier (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Tintoré, Mar (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

Fecha:	2016
Resumen:	To determine the prognostic value of selected biomarkers in clinically isolated syndromes (CIS) for conversion to multiple sclerosis (MS) and disability accrual. 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. 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 = −0. 892) and percentage brain volume change (r = −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. 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.
Ayudas:	Instituto de Salud Carlos III RD07-0060 Instituto de Salud Carlos III RD12-0032 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-0793 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-1082 Ministerio de Economía y Competitividad PI08-0788 Ministerio de Economía y Competitividad PI12-01313 Ministerio de Economía y Competitividad ISCIII/CP07-00146 Ministerio de Economía y Competitividad ISCIII/CP13-00028 Ministerio de Economía y Competitividad ISCIII/CD09-0363 Ministerio de Economía y Competitividad ISCIII/CM10-00032
Nota:	Altres ajuts: T Jens Kuhle was supported by an ECTRIMS Research Fellowship Programme and by the Forschungsfonds of the University of Basel, Switzerland.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	Neurology, Vol. 87 (september 2016) , p. 1076-1084, ISSN 1526-632X

DOI: 10.1212/WNL.0000000000003085
PMID: 27521440

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