Positive cerebrospinal fluid in the 2024 McDonald criteria for multiple sclerosis

Florian Deisenhammer1, Harald Hegen1, Georgina Arrambide2

  • 1Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.

Ebiomedicine
|September 18, 2025
PubMed

Insights

The 2024 McDonald criteria for Multiple Sclerosis (MS) now include kappa free light chains (κ-FLC) as an alternative to oligoclonal IgG bands (OCB) for diagnosing MS. κ-FLC offers comparable diagnostic accuracy and potential prognostic value.

Area of Science:

  • Neurology
  • Immunology
  • Clinical Diagnostics

Background:

  • The 2024 McDonald diagnostic criteria for Multiple Sclerosis (MS) have been updated.
  • Intrathecal immunoglobulin synthesis is a key diagnostic marker for MS.

Purpose of the Study:

  • To evaluate the role of kappa free light chains (κ-FLC) in cerebrospinal fluid (CSF) as a diagnostic marker for MS.
  • To compare the diagnostic performance of κ-FLC with oligoclonal IgG bands (OCB).
  • To assess the prognostic utility of κ-FLC and Neurofilament light (NfL) in MS.

Main Methods:

  • Analysis of diagnostic sensitivity and specificity of κ-FLC detection in CSF.
  • Comparison of κ-FLC results with OCB findings.
  • Calculation and evaluation of the κ-FLC index for MS diagnosis.
  • Review of available assays and proficiency testing for κ-FLC measurement.

Main Results:

  • κ-FLC detection in CSF demonstrates diagnostic sensitivity and specificity equal to OCB for MS.
  • A κ-FLC index value of ≥6.1 is recommended for optimal MS diagnosis.
  • Concordance between κ-FLC and OCB is approximately 90%, with combined testing useful in rare cases.
  • Higher κ-FLC index values may predict increased MS disease activity, suggesting prognostic value.
  • Neurofilament light (NfL) is not recommended for MS diagnosis but may aid prognosis and monitoring.

Conclusions:

  • κ-FLC detection in CSF is a reliable and interchangeable alternative to OCB for diagnosing MS according to the 2024 McDonald criteria.
  • Validated assays and proficiency testing are crucial for accurate κ-FLC measurement.
  • The κ-FLC index holds potential for both diagnosis and prognosis in pediatric and adult MS patients across various disease courses.