How do you interpret conflicting findings on CSF immunoglobulin tests for work up of multiple sclerosis and its mimics?

Although the specific role of cerebrospinal fluid (CSF) testing has evolved in the successive revisions of the McDonald criteria, it remains an important part of the evaluation of suspected multiple sclerosis (MS), both to provide support for the diagnosis of MS and to look for findings that suggest an alternative diagnosis. In the 2024 McDonald criteria, detection of intrathecal IgG production can substitute for demonstration of dissemination in time. The optimal test for intrathecal IgG production is CSF-specific oligoclonal bands (OCBs) by isoelectric focusing and immunoblotting, but it is labor-intensive, requires specialized technical expertise to perform and interpret, and has a qualitative readout. Substantial evidence supports that ...

There is approximately 90% concordance between the presence of oligoclonal bands in the CSF and an elevated kappa free light chain index.

According to the 2024 McDonald Criteria, the presence of either OCB or an elevated kappa free light chain index counts as positive CSF.

The MS immunological "signature" for MS is the presence of at least 2 unique CSF-specific oligoclonal bands (OCB), not seen in a parallel serum profile (though I prefer at least 3); a raised IgG Index, fewer than 50 lymphocytes, and a minimally elevated protein. If an established test is available for KFLC, then OCB is unnecessary. IgG Index CANNOT be used to replace either KFLC or OCB as it is both less sensitive and specific for MS. If OCBs are hard to interpret (e.g., faint bands) or the KFLC index is minimally elevated, then a raised IgG Index, with the other features above regarding cell count and protein, can help steer the diagnosis to MS.