Positive cerebrospinal fluid in the 2024 McDonald criteria for multiple sclerosis
- PMID: 40967951
- DOI: 10.1016/j.ebiom.2025.105905
Positive cerebrospinal fluid in the 2024 McDonald criteria for multiple sclerosis
Abstract
The 2024 McDonald diagnostic criteria for Multiple Sclerosis (MS) introduce kappa free light chains (κ-FLC) detection in cerebrospinal fluid (CSF) which can be used interchangeably with oligoclonal IgG bands (OCB) to demonstrate intrathecal immunoglobulin synthesis. Diagnostic sensitivity and specificity of κ-FLC is equal to OCB on a 95% confidence level. In rare cases determination of both, κ-FLC and OCB should be considered as the concordance rate is around 90%. We recommend calculating the κ-FLC index with values of ≥6.1 performing best for diagnosing MS. Validated turbidimetric or nephelometric assays should be applied for which proficiency testing programs are available. There is some prognostic use of the κ-FLC index with higher values predicting higher disease activity. Neurofilament light (NfL) should not be used for diagnostic purposes although it might be useful for prognosis and disease monitoring. All recommendations apply to paediatric and adult relapsing as well as progressive onset MS.
Keywords: Cerebrospinal fluid; Criteria; Diagnosis; Free light chains; Multiple sclerosis.
Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.
Conflict of interest statement
Declaration of interests Florian Deisenhammer has participated in meetings sponsored by or received honoraria for acting as an advisor/speaker for Alexion, Almirall, Biogen, BMS, Sanofi, Horizon, Janssen, Laurea Group, Medwhizz, Merck, Novartis Pharma, Neuraxpharm, Roche, Sandoz, and Teva. His institution has received research grants from Biogen, Novartis Pharma, and Sanofi. He is review editor of Frontiers Neurology. Harald Hegen has participated in meetings sponsored by, received speaker honoraria or travel funding from Amgen, Bayer, Biogen, Bristol Myers Squibb, Janssen, Merck, Novartis, Sanofi-Genzyme, Siemens, Teva; and received honoraria for acting as consultant for Biogen, Bristol Myers Squibb, Novartis, Roche, Sanofi-Genzyme, and Teva. Georgina Arrambide has received compensation for consulting services, speaking honoraria or participation in advisory boards from Roche, Horizon Therapeutics, and Bristol Myers Squibb; and travel support for scientific meetings from Novartis, Roche, ECTRIMS, and EAN. G.A. serves as editor for Europe of the Multiple Sclerosis Journal – Experimental, Translational and Clinical journal; and as a member of the editorial and scientific committee of Acta Neurológica Colombiana; is a member of the International Women in Multiple Sclerosis (iWiMS) network executive committee, the European Biomarkers in Multiple Sclerosis (BioMS-eu) steering committee, the MOGAD Eugene Devic European Network (MEDEN) steering group, and the Platform Adaptive Trial for remyelination and neuroprotection in mUltiple Sclerosis (PLATYPUS) steering committee. Brenda Banwell has served as a consultant to Novartis, Sanofi, Teva Neuroscience, and Biogen in the design of clinical trials for pediatric multiple sclerosis. She has served as a central imaging reviewer for clinical trials by Novartis and Roche and received grant funding from the National Institutes of Health, National Multiple Sclerosis Society, and Multiple Sclerosis Canada. Timothy Coetzee is CEO of the National MS Society, a sponsor of the International Advisory Committee on Clinical Trials in MS. Sharmilee Gnanapavan has received support for conference attendances and speak fees/honoraria from CMSC, Jansen Cilag, MS Academy, Novartis, Sanofi Genzyme and Roche. She has also received Grant support from Sanofi Genzyme, Merck and Takeda. Xavier Montalban's institution has received compensation for lecture honoraria and travel expenses, participation in scientific meetings, clinical trial steering committee membership, or clinical advisory board participation in recent years from Abbvie, Actelion, Alexion, Bial PD, Biogen, Bristol-Myers Squibb/Celgene, EMD Serono, Genzyme, Hoffmann-La Roche, Immunic Therapeutics, Janssen Pharmaceuticals, Medday, Merck, Mylan, Nervgen, Neuraxpharm, Novartis, Peervoice, Samsung-Biosys, Sandoz, Sanofi-Genzyme, Teva Pharmaceutical, TG Therapeutics, Excemed, Medscape, ECTRIMS, MSIF, and NMSS or any of their affiliates. Hayrettin Tumani reports honoraria for acting as a consultant/speaker and/or for attending events sponsored by Alexion, Bayer, Biogen, Bristol-Myers Squibb, Celgene, Diamed, Fresenius, Fujirebio, GlaxoSmithKline, Horizon, Janssen-Cilag, Merck, Novartis, Roche, Sanofi-Genzyme, Siemens, Teva, and Viatris. Maria Alice Vieira Willrich discloses the following relationships/activities/interests: research support from Sebia Inc., Binding Site, and Siemens for research studies; royalties from Binding Site for the intellectual property “Quantifying Monoclonal Therapeutic Antibodies by LC-MS/MS”; advisory board service for Myeloma360 in 2021; honoraria from ADLM for the 2024 annual scientific meeting; support from ADLM for attendance of annual scientific meetings and from the College of American Pathologists from 2018 to 2023; a patent issued for “Quantifying Monoclonal Therapeutic Antibodies by LC-MS/MS”; membership and vice chair position in the Diagnostic Immunology and Flow Cytometry Committee at the College of American Pathologists from 2018 to 2023; division chair for infectious diseases and immunology at ADLM; and associate editor for the Clinical Chemistry Journal. Mark S. Freedman received research support from Sanofi-Genzyme Canada; speaking fees from Hoffman La-Roche, Novartis, EMD Inc.; and honoraria and consulting fees from Amgen, Astra Zeneca, EMD Inc./EMD Serono/Merck Serono, Find Therapeutics, Hoffman La-Roche, Novartis, Sandoz, Sanofi-Genzyme, Sentrex, Teva Canada Innovation. He also has received compensation for service on advisory boards and corporate boards from Amgen, Astra Zeneca, Autolus, Bayer Healthcare, Celestra Health, EMD Inc./Merck Serono, Find Therapeutics, Hoffman La-Roche, Neurogenesis, Novartis, Sanofi-Genzyme, Sentrex, Setpoint Medical; and compensation for service on data safety monitoring boards from Abata Therapeutics, Celltrion, Hoffman La-Roche, and Moderna.
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