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http://purl.uniprot.org/citations/27521440http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/27521440http://www.w3.org/2000/01/rdf-schema#comment"

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."xsd:string
http://purl.uniprot.org/citations/27521440http://purl.org/dc/terms/identifier"doi:10.1212/wnl.0000000000003085"xsd:string
http://purl.uniprot.org/citations/27521440http://purl.uniprot.org/core/author"Castillo J."xsd:string
http://purl.uniprot.org/citations/27521440http://purl.uniprot.org/core/author"Simon E."xsd:string
http://purl.uniprot.org/citations/27521440http://purl.uniprot.org/core/author"Comabella M."xsd:string
http://purl.uniprot.org/citations/27521440http://purl.uniprot.org/core/author"Montalban X."xsd:string
http://purl.uniprot.org/citations/27521440http://purl.uniprot.org/core/author"Kappos L."xsd:string
http://purl.uniprot.org/citations/27521440http://purl.uniprot.org/core/author"Alvarez-Cermeno J.C."xsd:string
http://purl.uniprot.org/citations/27521440http://purl.uniprot.org/core/author"Nos C."xsd:string
http://purl.uniprot.org/citations/27521440http://purl.uniprot.org/core/author"Rovira A."xsd:string
http://purl.uniprot.org/citations/27521440http://purl.uniprot.org/core/author"Rio J."xsd:string
http://purl.uniprot.org/citations/27521440http://purl.uniprot.org/core/author"Eixarch H."xsd:string
http://purl.uniprot.org/citations/27521440http://purl.uniprot.org/core/author"Villar L.M."xsd:string
http://purl.uniprot.org/citations/27521440http://purl.uniprot.org/core/author"Espejo C."xsd:string
http://purl.uniprot.org/citations/27521440http://purl.uniprot.org/core/author"Tintore M."xsd:string
http://purl.uniprot.org/citations/27521440http://purl.uniprot.org/core/author"Sastre-Garriga J."xsd:string
http://purl.uniprot.org/citations/27521440http://purl.uniprot.org/core/author"Auger C."xsd:string
http://purl.uniprot.org/citations/27521440http://purl.uniprot.org/core/author"Kuhle J."xsd:string
http://purl.uniprot.org/citations/27521440http://purl.uniprot.org/core/author"Disanto G."xsd:string
http://purl.uniprot.org/citations/27521440http://purl.uniprot.org/core/author"Vidal-Jordana A."xsd:string
http://purl.uniprot.org/citations/27521440http://purl.uniprot.org/core/author"Tur C."xsd:string
http://purl.uniprot.org/citations/27521440http://purl.uniprot.org/core/author"Picon C."xsd:string
http://purl.uniprot.org/citations/27521440http://purl.uniprot.org/core/author"Arrambide G."xsd:string
http://purl.uniprot.org/citations/27521440http://purl.uniprot.org/core/author"Arevalo M.J."xsd:string
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