ArticleJournal of neurology, neurosurgery, and psychiatry2025
Blood biomarkers for predicting disability worsening in progressive multiple sclerosis: a multinational, individual participant-level analysis.
Abstract readMulticenter Study
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Article in Journal of neurology, neurosurgery, and psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14citing papers in PubMed
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Who cites it
14 citing papers in PubMed.
- Dynamic Changes in Serum Glial Fibrillary Acidic Protein Levels Predicts Early Neurological Deterioration After Intravenous Thrombolysis in Minor Stroke.Annals of clinical and translational neurology · 2026Article
- Impact of age, BMI, and renal function adjustment on interpretation of serum NfL and GFAP in multiple sclerosis progression: a scoping review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Article
- Blood Neurofilament Light Chain and Glial Fibrillary Acidic Protein as Candidate Biomarkers inNeurology. Genetics · 2026Article
- Evaluation of Dried Plasma Spot-Based Quantification of Glial Fibrillary Acidic Protein as a Disease-Associated Biomarker in Neuromyelitis Optica Spectrum Disorder.Annals of clinical and translational neurology · 2026Article
- From measurement to biomarker trajectories: platform-agnostic Z score analysis of serum NfL and GFAP in ocrelizumab-treated multiple sclerosis.Journal of neurology · 2026Article
- Intrathecal immunoglobulin production in the diagnosis, prognosis, and monitoring of autoimmune diseases of the central nervous system.Journal of translational autoimmunity · 2026Review
- A framework for blood biomarker discovery in MS.Multiple sclerosis (Houndmills, Basingstoke, England) · 2026Review
- Opioid Signaling in Multiple Sclerosis: Emerging Targets for Repair.International journal of molecular sciences · 2026Review
- Development of a Diagnostic Autoantibody Assay to a Consensus Motif for the Risk Prediction of Epstein-Barr Virus-Related Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2026Article
- The predictive value of serum neurofilament light chain in achieving no evidence of disease activity-3 (NEDA-3) status in treatment-naïve patients with multiple sclerosis.Journal of neurology · 2026Article
- Article
- Beyond biomarker validation: defining when serum neurofilament light chain should influence management in multiple sclerosis.Frontiers in immunology · 2026Review
- Brain age gap in multiple sclerosis: associated with disability but independent of serum biomarkers.Therapeutic advances in neurological disorders · 2026Article
- Multiple sclerosis: 2026 update.Free neuropathology · 2026Review
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Authors and funding
76 authors.
Ahmed AbdelhakDepartment of Neurology, University of California San Francisco (UCSF), San Francisco, California, USA Ahmed.Abdelhak@ucsf.edu.ORCID 0000-0001-9731-4169
Franziska BachhuberDepartment of Neurology, University of Ulm, Ulm, Germany.
Kiarra NingDepartment of Neurology, University of California San Francisco (UCSF), San Francisco, California, USA.
Pascal BenkertDepartment of Clinical Research, University Hospital Basel, Basel, Switzerland.
W John BoscardinDepartments of Medicine and Epidemiology & Biostatistics, University of California at San Francisco (UCSF), San Francisco, California, USA.
Aleksandra Maleska MaceskiDepartment of Neurology, University Hospital Basel, Basel, BS, Switzerland.
Sabine SchaedelinDepartment of Clinical Research, University Hospital Basel, Basel, Switzerland.
Lutz AchtnichtsDepartment of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland.
Sebastian FinkenerDepartment of Neurology, Cantonal Hospital Aarau, Aarau, Switzerland.
Patrice H LaliveDepartment of Clinical Neurosciences, Division of Neurology, Unit of Neuroimmunology and Multiple Sclerosis, Geneva, Switzerland.
Marjolaine UginetDepartment of Clinical Neurosciences, Division of Neurology, Unit of Neuroimmunology and Multiple Sclerosis, Geneva, Switzerland.
Caroline PotService of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland.
Renaud Du PasquierService of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland.
Robert HoepnerDepartment of Neurology, Bern University Hospital and University of Bern, Bern, Switzerland.ORCID 0000-0002-0115-7021
Andrew ChanDepartment of Neurology, Bern University Hospital and University of Bern, Bern, Switzerland.
Claudio GobbiNeurology Clinic Lugano, Neurocenter of Southern Switzerland, Lugano, Switzerland.
Chiara ZeccaNeurology Clinic Lugano, Neurocenter of Southern Switzerland, Lugano, Switzerland.ORCID 0000-0002-9990-3431
Stefanie MüllerDepartment of Neurology, University teaching and research hospital St. Gallen, St. Gallen, Switzerland.
Patrick RothDepartment of Neurology, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
Cristina GranzieraDepartment of Neurology, University Hospital Basel, Basel, BS, Switzerland.ORCID 0000-0002-4917-8761
Tanuja ChitnisDepartment of Neurology, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA.
Evan MadillDepartment of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Howard L WeinerDepartment of Neurology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Ari J GreenDepartment of Neurology, University of California San Francisco (UCSF), San Francisco, California, USA.
Stephen L HauserDepartment of Neurology, University of California San Francisco (UCSF), San Francisco, California, USA.
Bruce Ac CreeDepartment of Neurology, University of California San Francisco (UCSF), San Francisco, California, USA.
Tania KümpfelInstitute of Clinical Neuroimmunology, University Hospital Munich, Ludwig Maximilian University Munich, Munich, Germany.ORCID 0000-0001-7509-5268
Joachim HavlaInstitute of Clinical Neuroimmunology, University Hospital Munich, Ludwig Maximilian University Munich, Munich, Germany.ORCID 0000-0002-4386-1340
Thomas SkripuletzDepartment of Neurology, Hannover Medical School, Hannover, Germany.ORCID 0000-0001-8550-335X
Stefan GingeleDepartment of Neurology, Hannover Medical School, Hannover, Germany.ORCID 0000-0002-6055-5695
Makbule SenelDepartment of Neurology, University of Ulm, Ulm, Germany.ORCID 0000-0002-2737-7495
Ioannis VardakasDepartment of Neurology, University of Ulm, Ulm, Germany.
Daniela TaranuDepartment of Neurology, University of Ulm, Ulm, Germany.
Ulf ZiemannDepartment of Neurology & Stroke, Hertie Institute for Clinical Brain Research, Eberhard-Karls-University Tübingen, Tübingen, Germany.
Markus C KowarikDepartment of Neurology & Stroke, Hertie Institute for Clinical Brain Research, Eberhard-Karls-University Tübingen, Tübingen, Germany.
Ingo KleiterDepartment of Neurology, St. Josef Hospital, Ruhr University Bochum, Bochum, Germany.ORCID 0000-0002-8249-4408
Muna-Miriam HoshiMarianne-Strauß-Klinik, Behandlungszentrum Kempfenhausen für Multiple Sklerose Kranke, Berg, Germany.
Uwe K ZettlDepartment of Neurology, University of Rostock, Rostock, Germany.
Axel HaarmannDepartment of Neurology, University Hospital of Würzburg, Würzburg, Germany.
Simon ThebaultThe Montreal Neurological Institute and Department of Neurology and Neurosurgery, McGill University and McGill University Health Centre (MUHC), Montreal, Quebec, Canada.
Mark S FreedmanDepartment of Medicine, The Ottawa Hospital & The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.ORCID 0000-0003-1255-9701
Hailey P BergmanDepartment of Medicine, The Ottawa Hospital & The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
Ellen IacobaeusDepartment of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
Mohsen KhademiDepartment of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
Diana FerraroNeurology Unit, Department of Neurosciences, Azienda Ospedaliero-Universitaria of Modena, Modena, Italy.ORCID 0000-0003-4818-3806
Martina CardiDepartment of Biomedical, Metabolic and Neurosciences, University of Modena and Reggio Emilia, Faculty of Medicine and Surgery, Modena, Emilia-Romagna, Italy.
Sara MariottoDepartment of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.ORCID 0000-0002-7806-3103
Manuel ComabellaServei de Neurologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.ORCID 0000-0002-2373-6657
Xavier MontalbanServei de Neurologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
Andreu VilasecaServei de Neurologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
Eva M StrijbisDepartment of Neurology, MS Center Amsterdam, Amsterdam University Medical Center, Amsterdam, The Netherlands.ORCID 0000-0001-6705-5864
Mark Hj WesselsDepartment of Neurology, MS Center Amsterdam, Amsterdam University Medical Center, Amsterdam, The Netherlands.ORCID 0000-0003-2324-0499
Joep KillesteinDepartment of Neurology, MS Center Amsterdam, Amsterdam University Medical Center, Amsterdam, The Netherlands.
Bernhard HemmerDepartment of Neurology, TUM University Hospital, Technical University of Munich, Munich, Germany.ORCID 0000-0001-5985-6784
Friederike HeldDepartment of Neurology, TUM University Hospital, Technical University of Munich, Munich, Germany.
Finn SellebjergDanish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.ORCID 0000-0002-1333-9623
Helene Højsgaard ChowDanish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.ORCID 0000-0003-2032-2755
Roberto Alvarez-LafuenteGrupo de Investigación de Esclerosis Múltiple, Instituto de Investigación Sanitaria San Carlos (IdISSC)/Hospital Clínico San Carlos, Madrid, Spain.ORCID 0000-0002-3132-1486
Maria Inmaculada Domínguez-MozoGrupo de Investigación de Esclerosis Múltiple, Instituto de Investigación Sanitaria San Carlos (IdISSC)/Hospital Clínico San Carlos, Madrid, Spain.
Harald HegenDepartment of Neurology, Innbruck Medical University, Innsbruck, Austria.ORCID 0000-0002-2833-6337
Klaus BerekDepartment of Neurology, Innbruck Medical University, Innsbruck, Austria.
Florian DeisenhammerDepartment of Neurology, Innbruck Medical University, Innsbruck, Austria.ORCID 0000-0003-4541-8841
Eric ThouvenotDepartment of Neurology, University Hospital of Nîmes, Nîmes, France.
Hanane AgherbiDepartment of Neurology, University Hospital of Nîmes, Nîmes, France.
Konrad RejdakDepartment of Neurology, Medical University of Lublin, Lublin, Poland.
Magda GąsiorDepartment of Neurology, Medical University of Lublin, Lublin, Poland.
Dimitrios TzanetakosSecond Department of Neurology, National & Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece.
John S TzartosSecond Department of Neurology, National & Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece.
Maria Pia SormaniDepartment of Health Sciences (DISSAL), University of Genoa, Genoa, Italy.ORCID 0000-0001-6892-104X
Irena Dujmovic BasuroskiDepartment of Neurology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
Georgina ArrambideServei de Neurologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.ORCID 0000-0002-2657-5510
Michael KhalilDepartment of Neurology, Medical University of Graz, Graz, Austria.ORCID 0000-0002-5350-3328
Fredrik PiehlDepartment of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.ORCID 0000-0001-8329-5219
Charlotte E TeunissenDepartment of Neurodegeneration, Amsterdam Neurosciences, Amsterdam, The Netherlands.
Jens KuhleDepartment of Neurology, University Hospital Basel, Basel, BS, Switzerland.ORCID 0000-0002-6963-8892
Hayrettin TumaniDepartment of Neurology, University of Ulm, Ulm, Germany.ORCID 0000-0002-1647-6201
Funding
The Role of B cells in the Origin and Progression of Multiple SclerosisR35NS111644 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STEPHEN L HAUSER · 2019 to 2026
$9.1MNINDS NIH HHS R35 NS111644
Abstract
BACKGROUND AND
objectivesBiologically informative markers like glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) may help predict confirmed disability worsening (CDW) in multiple sclerosis (MS). However, data on the prognostic value of their blood concentrations in progressive MS (PMS) are limited, and there are substantial discrepancies in the published literature. This international collaboration uses individual participant data to define the prognostic value of serum GFAP and NfL in people with PMS (pwPMS).
methodsData were collected from BioMS-eu network centres and collaborating cohorts. pwPMS with primary progressive MS (PPMS) or secondary progressive MS (SPMS) with at least one GFAP value and at least three follow-up expanded disability status scale (EDSS) scores were included. The prognostic value of serum GFAP and NfL age- and sex-adjusted Z-scores for future CDW was evaluated using Cox regression models, accounting for sex, age, baseline disease duration and EDSS, and dominant treatment during follow-up.
results1058 participants and 7530 encounters were included (median age 53 years (IQR: 44 to 59), 57% female, follow-up 4.6 years (2.9 to 8.4)) with median baseline GFAP of 0.74 (-0.10 to 1.55) and NfL of 0.64 (-0.36 to 1.51). 723 CDW events were recorded. Each GFAP Z-score increase was associated with ~10% higher CDW risk (adjusted HR (aHR) 1.107 (1.001 to 1.225), p=0.049). Results were mainly driven by SPMS participants (n=613, aHR 1.242 (1.073 to 1.438), p=0.004). Higher NfL Z-scores predicted CDW only in PPMS participants (1.236 (1.092 to 1.399), p=0.001).
conclusionsGFAP was a prognostic indicator for future CDW in pwPMS, especially in pwSPMS. On the other hand, NfL was predictive of CDW only in pwPPMS.
Indexed as
Glial Fibrillary Acidic ProteinMultiple Sclerosis, Chronic ProgressiveNeurofilament ProteinsAdultBiomarkersDisability EvaluationDisease ProgressionFemaleHumansMaleMiddle AgedPrognosisBiomarkersGFAP protein, humanGlial Fibrillary Acidic Proteinneurofilament protein LNeurofilament ProteinsMULTIPLE SCLEROSISPrognosis
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