Oligoclonal IgG bands in cerebrospinal fluid. Principles for demonstration and interpretation based on findings in 1114 neurological patients.

Unconcentrated cerebrospinal fluid (CSF) and serum samples from 1114 consecutive patients were examined for presence of oligoclonal IgG bands (OB) by agarose isoelectric focusing (AIF) followed by protein transfer to nitrocellulose membrane, immunolabeling, and avidinbiotin-peroxidase staining (avidin-biotin AIF). Oligoclonal bands were demonstrated in CSF from all 58 patients with multiple sclerosis (MS), eight of 29 with aseptic nervous system infections, and 9% of 1014 with other neurological disorders (OND) considered as noninflammatory at primary clinical evaluation. Comparative examination of all specimens in another laboratory by conventional AIF after concentration of CSF revealed lower frequencies of OB in all diagnostic groups. In addition to the high sensitivity of avidinbiotin AIF, which enables detection of OB by separation of 5 microL of unconcentrated CSF even when the CSF IgG level is around the lower normal range, the procedure also has optimal specificity since IgG exclusively is detected. Avidin-biotin AIF may be the method preferred for routine examination of CSF for OB. Demonstration of OB in CSF is valuable especially in MS, where, in contrast to diagnostic aids such as evoked potentials and neuro-imaging, it establishes inflammatory type of nervous system involvements. Oligoclonal IgG bands in CSF from patients with OND reflect intrathecal immune response and should lead to investigations of infectious etiology.

Monosymptomatic sensory symptoms and cerebrospinal fluid immunoglobulin levels in relation to multiple sclerosis.

Of 53 patients with monosymptomatic paresthesiae, 55% had oligoclonal bands and 28% an elevated cerebrospinal fluid (CSF) IgG index. Over a mean observation period of 64 months, nine patients developed clinically definite multiple sclerosis (MS); all of these patients had IgG bands, illustrating the prognostic importance of this CSF aberration. Two lumbar punctures more than one year apart were performed in 31 of the patients, of whom 20 had oligoclonal bands. This abnormality was constant between the time of punctures in all subjects except one, thus behaving as in MS. Similarly, the CSF findings in the 11 patients without oligoclonal bands remained normal over the observation period. The majority of patients with oligoclonal bands had cells in their CSF producing immunoglobulin of one or more of the three main classes, while none of those without oligoclonal bands displayed immunoglobulin-producing cells in CSF. Occurrence of oligoclonal bands in CSF is common in patients with paresthesiae and increases the risk for future development of MS.

Agarose isoelectric focusing of unconcentrated CSF and radioimmunofixation for detection of oligoclonal bands in patients with multiple sclerosis and other neurological diseases.

Agarose isoelectric focusing (AIEF) of concentrated CSF was compared with AIEF of unconcentrated CSF and subsequent immunofixation with radiolabeled antihuman IgG Fc Fragment antiserum and autoradiography for the demonstration of oligoclonal bands in CSF from 287 neurological patients. Oligoclonal bands were demonstrated by AIEF in 98% of 43 patients with multiple sclerosis, 72% of 18 patients with infectious CNS diseases, and 23% of 226 patients with other neurological diseases. The corresponding figures obtained with AIEF of unconcentrated CSF and radioimmunofixation were 98%, 67% and 21%, respectively. In 15 of the patients, oligoclonal bands were demonstrated in CSF and serum by both techniques. They are both useful alternatives for the demonstration of oligoclonal bands in CSF, and the method for unconcentrated CSF can be safely applied when only small CSF volumes are available. The oligoclonal IgG pattern obtained by AIEF was not influenced by concentration of CSF by ultrafiltration and subsequent dilution to the original IgG concentration, nor by storage for 6 months.