2024 McDonald MS Criteria Endorse Kappa Free Light Chains as CSF Biomarker
The updated 2024 McDonald diagnostic criteria for multiple sclerosis now accept kappa free light chain measurement in CSF as interchangeable with oligoclonal IgG bands for demonstrating intrathecal immunoglobulin synthesis. The recommended kappa-FLC index cutoff of 6.1 or higher provides equivalent diagnostic sensitivity and specificity. Validated turbidimetric or nephelometric assays with proficiency testing are recommended, while neurofilament light chain is reserved for prognosis and monitoring rather than diagnosis.
The original study
Positive cerebrospinal fluid in the 2024 McDonald criteria for multiple sclerosis.
- Authors
- Deisenhammer F, Hegen H, Arrambide G, Banwell BL, Coetzee T, Gnanapavan S, et al.
- Journal
- EBioMedicine
- Type
- Journal Article, Review
- PMID
- 40967951
Original 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.