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Diagnosing multiple sclerosis, especially helpful in patients with equivocal clinical or radiological findings
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease characterized by visual, motor, and sensory disturbances. The diagnosis of MS is dependent on clinical, radiological, and laboratory findings. The detection of increased intrathecal immunoglobulin (Ig) synthesis is the basis for current diagnostic laboratory tests for MS. These tests include the cerebrospinal fluid (CSF) IgG index and CSF oligoclonal band detection.
CSF IgG index: 0.00-0.85
CSF IgG: 0.0-8.1 mg/dL
CSF albumin: 0.0-27.0 mg/dL
0-4 months: 100-334 mg/dL
5-8 months: 164-588 mg/dL
9-14 months: 246-904 mg/dL
15-23 months: 313-1,170 mg/dL
2-3 years: 295-1,156 mg/dL
4-6 years: 386-1,470 mg/dL
7-9 years: 462-1,682 mg/dL
10-12 years: 503-1,719 mg/dL
13-15 years: 509-1,580 mg/dL
16-17 years: 487-1,327 mg/dL
> or =18 years: 767-1,590 mg/dL
Serum albumin: 3,200-4,800 mg/dL
CSF IgG/albumin: 0.0-0.21
Serum IgG/albumin: 0.00-0.40
CSF IgG synthesis rate: 0-12 mg/24 hours
Oligoclonal banding (OCB): > or =4 cerebrospinal fluid (CSF)-specific bands are consistent with multiple sclerosis (MS).
CSF IgG index: >0.85 is consistent with MS.
Abnormal CSF IgG indexes and OCB patterns have been reported in 70% to 80% of MS patients. If both tests are performed, at least 1 of the tests has been reported to be positive in >90% of multiple sclerosis patients. A newer methodology for OCB detection, isoelectric focusing, is utilized in this test and has been reported to be more sensitive (90%-95%).
The presence of OCB or elevated CSF IgG index is unrelated to disease activity.
Increased intrathecal Ig synthesis may occur in other inflammatory central nervous system diseases and, therefore, these assays are not specific for multiple sclerosis (specificity=95%).
In early 2003, we compared the IEF oligoclonal banding (OCB) assay to our previous high-resolution agarose OCB assay, as well as the cerebrospinal fluid (CSF) IgG index. The IEF assay requires a smaller specimen volume and is easier to interpret than the agarose assay. Concordant normal samples usually had 0 bands by IEF, but 1 band by agarose. The concordant positive samples had an average of 11 bands by IEF and 2 bands on agarose. Among 19 cases of definite multiple sclerosis (MS), the IEF assay had a sensitivity of 95%, the agarose assay had a sensitivity of 63%, and the CSF index had a sensitivity of 74%. Among 57 consecutive non-MS cases, the IEF assay had a specificity of 95% and the agarose and CSF index assays had specificities of 97%. These data indicate a 32% increase in sensitivity and a 2% decrease in specificity for the IEF OCB assay.
1. Andersson M, Alvarez-Cermeno J, Bernardi G, et al: Cerebrospinal fluid in the diagnosis of multiple sclerosis: a consensus report. J Neurol Neurosurg Psychiatry 1994 Aug;57(8):897-902
2. Tourtellotte WW, Walsh MJ, Baumhefner RW, et al: The current status of multiple sclerosis intra-blood-brain-barrier IgG synthesis. Ann NY Acad Sci 1984;436:52-67