Contribution of CSF studies to diagnosis of multiple sclerosis

Current principles for optimal examination of CSF regarding cell counting, evaluation of blood-brain barrier (BBB) function, intra-BBB synthesis of IgG, IgA and IgM, demonstration of oligoclonal IgG bands, determination of immune complexes and levels of myelin basic protein are reviewed. The importance for clinical as well as research purposes of accurately performed examinations regarding these variables is underlined. Multiple sclerosis (MS) is characterized by elevated mononuclear cell count in about one third of the patients, elevated CSF/serum albumin ratio as evidence of BBB damage in around 10%, elevated CSF IgG index, equal to (CSF/serum IgG): (CSF/serum albumin), in about 70% and presence of oligoclonal bands demonstrable by electrophoresis or isoelectric focusing in almost every patient. These variables are recommended for the routine evaluation of CSF, especially when a diagnosis of MS is suspected. Additional tests advisable for the well-equipped laboratory include determination of CSF IgM index, which is elevated in about 50%, and of myelin basic protein level, which is frequently increased during clinical exacerbations. CSF abnormalities are registered more frequently than abnormal evoked potentials, and at a frequency similar to that found by advanced neuroimaging, but only CSF studies have the potential to disclose the inflammatory character of nervous system lesions and intra-BBB immune response which are characteristic for MS. Documentation of an intra-BBB immune response by CSF studies will thus also in the future have diagnostic implications, and continue to be highly relevant for research regarding etiology and pathogenesis of MS.