ArticleNeurology2016
Neurofilament light chain level is a weak risk factor for the development of MS.
Erratum issuedOpen access · hybridAbstract read
In one paragraph
Article in Neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 60 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 1 pooled it
10.6field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- Predictors of Multiple Sclerosis After Clinically Isolated Syndrome: A Systematic Review and Meta-Analysis.European journal of neurology · 2026Pooled it
- Neurofilament light levels are associated with long-term outcomes in multiple sclerosis.Multiple sclerosis (Houndmills, Basingstoke, England) · 2020Trial
- Blood neurofilament light chain as a biomarker of MS disease activity and treatment response.Neurology · 2019Trial
- The Barcelona baseline risk score to predict long-term prognosis after a first demyelinating event: a prospective observational study.The Lancet regional health. Europe · 2025Article
- Contribution of Blood Biomarkers to Multiple Sclerosis Diagnosis.Neurology(R) neuroimmunology & neuroinflammation · 2025Article
- No Relation Between Cognitive Impairment, Physical Disability and Serum Biomarkers in a Cohort of Progressive Multiple Sclerosis Patients.Biomolecules · 2025Article
- CSF synaptic biomarkers and cognitive impairment in multiple sclerosis.Journal of neurology · 2024Article
- Emerging Trends: Neurofilament Biomarkers in Precision Neurology.Neurochemical research · 2024Review
- Cerebrospinal fluid neurofilament light chain in acute optic neuritis and its predictive ability of multiple sclerosis.Journal of neurology · 2024Article
- Determination of systemic inflammatory biomarkers in multiple sclerosis.Journal of medical biochemistry · 2024Article
- Serum levels of neurotensin, pannexin-1, and sestrin-2 and the correlations with sleep quality or/and cognitive function in the patients with chronic insomnia disorder.Frontiers in psychiatry · 2024Article
- Serum neurofilament light chain correlations in patients with a first clinical demyelinating event in the REFLEX study: aTherapeutic advances in neurological disorders · 2024Article
- Neurofilament Light Chain in Adult and Pediatric Multiple Sclerosis: A Promising Biomarker to Better Characterize Disease Activity and Personalize MS Treatment.Neurology and therapy · 2023Review
- Intrathecal kappa free light chain synthesis is associated with worse prognosis in relapsing-remitting multiple sclerosis.Journal of neurology · 2023Article
- Chitinase-3-like 1-protein in CSF: a novel biomarker for progression in patients with multiple sclerosis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2023Article
- Validity of serum neurofilament light chain as a prognostic biomarker of disease activity in multiple sclerosis.Journal of neurology · 2023Review
- Serum neurofilament light chain levels in patients with cognitive deficits and movement disorders: comparison of cerebrospinal and serum neurofilament light chain levels with other biomarkers.Frontiers in human neuroscience · 2023Article
- Biomarkers in autoimmune diseases of the central nervous system.Frontiers in immunology · 2023Review
- Serum Neurofilament Identifies Patients With Multiple Sclerosis With Severe Focal Axonal Damage in a 6-Year Longitudinal Cohort.Neurology(R) neuroimmunology & neuroinflammation · 2023Observational
- A Scoping Review on Body Fluid Biomarkers for Prognosis and Disease Activity in Patients with Multiple Sclerosis.Journal of personalized medicine · 2022Article
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
24 authors at 2 institutions in 2 countries.
Georgina ArrambideFrom 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.
Carmen EspejoFrom 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.
Herena EixarchFrom 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.
Luisa M VillarFrom 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.
José C Alvarez-CermeñoFrom 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.
Carmen PicónFrom 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.
Jens KuhleFrom 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.
Giulio DisantoFrom 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.
Ludwig KapposFrom 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.
Jaume Sastre-GarrigaFrom 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.
Deborah ParetoFrom 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.
Eva SimonFrom 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.
Manuel ComabellaFrom 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.
Jordi RíoFrom 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.
Carlos NosFrom 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.
Carmen TurFrom 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.
Joaquín CastillóFrom 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.
Angela Vidal-JordanaFrom 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.
Ingrid GalánFrom 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.
Maria J ArévaloFrom 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.
Cristina AugerFrom 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.
Alex RoviraFrom 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.
Xavier MontalbanFrom 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.
Mar TintoreFrom 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.
Vall d'Hebron Institut de Recerca · ESOspedale regionale di Lugano · CH
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo determine the prognostic value of selected biomarkers in clinically isolated syndromes (CIS) for conversion to multiple sclerosis (MS) and disability accrual.
methodsData 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.
resultsThe 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.
conclusionsNfL 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.
Indexed as
AdultBiomarkersBrainDemyelinating DiseasesDisability EvaluationDisease ProgressionEnzyme-Linked Immunosorbent AssayFemaleFollow-Up StudiesHumansLongitudinal StudiesMagnetic Resonance ImagingMaleMultivariate AnalysisNeurofilament ProteinsOrgan SizeBiomarkersneurofilament protein LNeurofilament Proteins
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