TWO promising biomarkers, the kappa free light chains (kFLC) index and central vein sign (CVS), have been incorporated into the revised 2024 McDonald criteria, offering improved diagnostic precision for multiple sclerosis (MS) and radiologically isolated syndrome (RIS).
The revisions, announced at the most recent European Committee for Treatment and Research in Multiple Sclerosis meeting, mark a significant evolution in the diagnostic framework for MS. Notably, the optic nerve has been added as a fifth topographical site for dissemination in space, and MS diagnosis may now be established in RIS patients when biomarker evidence is added to at least two of the five dissemination sites.
The kFLC index, used to assess intrathecal immunoglobulin synthesis, is now positioned alongside oligoclonal band (OCB) detection. This addition enables a more sensitive evaluation of central nervous system immune activity in MS. The CVS, on the other hand, is a radiological feature visible on MRI that distinguishes MS-specific lesions by identifying veins at the center of white matter lesions. Its inclusion enhances lesion specificity and helps differentiate MS from other mimicking conditions.
This review provides a comprehensive summary of the clinical and diagnostic utility of the kFLC index and CVS in both MS and RIS. Their integration into the McDonald criteria reflects mounting evidence supporting their value in clinical practice. By refining diagnostic accuracy earlier in the disease course, these biomarkers may enable faster intervention and tailored management strategies for at-risk individuals.
As the field advances, the adoption of these markers into established criteria highlights the importance of biomarker-driven approaches in neuroinflammatory disease diagnostics. Their use could represent a shift toward greater specificity and timeliness in identifying MS, particularly in patients who do not yet meet traditional diagnostic thresholds.
Reference:
Levraut M et al. The Kappa Free Light Chains Index and Central Vein Sign: Two New Biomarkers for Multiple Sclerosis Diagnosis. Neurol Ther. 2025;14(3):711-731.
