Quality versus quantity: which is better for cerebrospinal fluid IgG?

An article in this issue (1 ) reopens an old question: Is qualitative or quantitative testing of immunoglobulins in cerebrospinal fluid (CSF) more diagnostically useful? The short answer is that each has pros and cons. In the diagnosis of multiple sclerosis, it can be misleading to perform only quantitative analysis, but it is much less problematic to perform only qualitative analysis (2 ). To detect IgG synthesis within the brain/CSF, a recent International Consensus has reaffirmed that qualitative is better than quantitative analysis and has gone further to state that there must be isoelectric focusing followed by immunofixation (Freedman et al., submitted for publication). The study of “free” light chains (Bence Jones proteins) has been rekindled by the report by Fischer et al. (1 ) in this issue, in which the authors examine commercially available antibodies in the hope that they will provide a better test for intrathecal antibody synthesis. Several specific issues can be considered as individual questions, although some may be rhetorical. I will examine clinical aspects before chemical issues. Is the assertion by Consensus neurologists, that isoelectric focusing is equivalent to the IgG index (3 ), correct? Yes and no. The latter (quantitative) test is not sufficient to make the diagnosis because it is only 75% sensitive vs 95% for the focusing (qualitative) test (3 ). How often should we repeat the lumbar puncture to get the correct diagnosis? It would be best to get the right answer on the first (and thus the only) occasion. However, there are some circumstances when a second puncture may be clinically indicated, and these relate to / immunofixation after IgG isoelectric focusing (4 ). If a single band is found (although this is not an oligoclonal pattern), more than one-half these patients will progress to a full oligoclonal pattern (5 ). Is there a 2-h “rush” to get an answer? Probably not, as the authors point out (1 ) that their method takes 1.5–2 h vs 4–5 h for isoelectric focusing. Multiple sclerosis is compatible with normal longevity; therefore, a clinician has ample time to get a better answer.