Consensus statement on CSF standards in diagnosis of MS

Freedman MS, Thompson EJ, Deisenhammer F, et al. Recommended standard of cerebrospinal fluid analysis in the diagnosis of multiple sclerosis. A Consensus statement. Arch Neurol 2005; 62:865-870.

general points
1. The IgG index or any other quantitative IgG anaysis is not equivalent to qualitative analysis using isoelectric focusing with immunofixation, as opposed to the previous recommendation that equated the IgG index with qualitative analysis.

There is complete agreement that isoelectric focusing (IEF) on agarose gels followed by immunoblotting should be the gold standard for detecting oligoclonal bands. Other methods such as polyacrylamide gels combined with IEF and silver staining of proteins might have proved useful IN THE PAST but they LACK SPECIFICITY for IgG and are not supported by consensus. Direct silver staining techniques demonstrate reduced sensitivity and specificity.

Some techniques also stain kappa and gamma light chains (both free and bound) that discern faint bands better against polyclonal background. Light chain staining will also be positive in rare cases where OCB's are caused by the presence of IgA or IgM which will not appear on gels stained only for IgG. These add little to routine MS diagnosis.

Serum free chains are usually removed by kidney (free chains). Intrathecal IgG is usuallyy associated with kappa chains.

Sensitivity of using IEF with immunoblotting is in excess of 95 %. A negative test is an indication to rethink the diagnosis. The presence of only one band in CSF not in serum may indicate the need to retest as many patients will convert. There is a high negative predictive power of negative CSF in clinically isolated syndrome (CIS) such that a negative CSF exam indicates a low likelihood of developing MS. There are five patterns accepted (1- no bands in CSF or serum 2- OCB in CSF not in serum 3-- OCBs in CSF, identical bands in serum (still there is CSF IgG synthesis) 4-- same as 3 except with leaky BBB suggesting systemic oligoclonal band production 5-- Monoclonal bands in CSF and sera, suggestive of a monoclonal IgG protein present).

Q albumen (albumen quotient) can be used to assess CSF leakiness. Controls should be run with each sample to make sure that OCB's in positive controls are not overdeveloped and negative controls are not underdeveloped.

Patients deserve to have CSF analyzed at a lab that utilizes accepted standards.