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Cited by 46Multiple Sclerosis Research StudiesPeripheral Neuropathies and DisordersPolyomavirus and related diseases

Positive cerebrospinal fluid in the 2024 McDonald criteria for multiple sclerosis

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Deisenhammer, Florian, Hegen, Harald, Arrambide, Georgina, Banwell, Brenda L., Coetzee, Tim, Gnanapavan, Sharmilee, Montalban, Xavier, Tumani, Hayrettin +2 more·2025·eBioMedicine
DOI 10.1016/j.ebiom.2025.105905PMC PMC12571584
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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.

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Authors
Deisenhammer, F., Hegen, H., Arrambide, G., Banwell, B. L., Coetzee, T., Gnanapavan, S., Montalban, X., Tumani, H., Willrich, M. A., & Freedman, M. S.
Affiliations
  • Innsbruck Medical University (AT)
  • Universitat Autònoma de Barcelona (ES)
  • Johns Hopkins University (US)
  • Queen Mary University of London (GB)
  • University Hospital Ulm (DE)
  • Mayo Clinic (US)
  • University of Ottawa (CA)
Corresponding author
Deisenhammer, Florian
ORCID
Venue
eBioMedicine
Publisher
Elsevier BV
Published
2025-10
Volume
120
Pages
105905
ISSN
2352-3964 (ISSN-L)
DOI
10.1016/j.ebiom.2025.105905
PMC
PMC12571584
OpenAlex
W4414372077
Cited by
46
References
98
Citations by year
2026: 36 · 2025: 10
FWCI
7.90
Type
journal article
Language
en
Open access
Licence
Locations
  • EBioMedicine (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Health and Human Services
  • European Committee for Treatment and Research in Multiple Sclerosis
  • National Multiple Sclerosis Society
  • National Institutes of Health
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
  • Health Sciences › Medicine › Oncology › Polyomavirus and related diseases
Keywords
multiple sclerosis, kappa free light chains, cerebrospinal fluid, oligoclonal bands, intrathecal immunoglobulin synthesis, sensitivity and specificity, neurofilament light chain, disease activity prediction, pediatric multiple sclerosis, progressive multiple sclerosis
MeSH terms
Humans, Immunoglobulin kappa-Chains, Multiple Sclerosis, Prognosis, Biomarkers, Neurofilament Proteins, Oligoclonal Bands

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