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Multiple Sclerosis Panel

Since cerebrospinal fluid (CSF) is an ultrafiltrate of plasma, it has much lower concentrations of the highest molecular weight proteins such as IgG, IgA and IgM. Elevated CSF IgG levels can either be the result of diffusion of plasma IgG across an altered blood brain barrier or intrathecal synthesis. Patients with multiple sclerosis and other demyelinating disorders often have elevated CSF IgG concentrations due to intrathecal synthesis. Analysis of cerebrospinal (CSF) IgG is helpful in diagnosing multiple sclerosis and other demyelinating diseases.

About 50% of multiple sclerosis patients have elevated CSF protein levels and about 75% have increased gamma globulins. Several tests have been devised to determine if the elevated gamma globulin is the result of intrathecal IgG synthesis. The percent of IgG present is more useful than the absolute concentration, because it compensates for increased blood brain permeability. The first ratio devised was the CSF IgG to CSF total protein ratio. Normally the ratio is less than 0.12. This calculation had poor sensitivity for detection of multiple sclerosis. A more sensitive indicator was the calculation of the CSF IgG to CSF albumin ratio. Normally, it should be 0.066 to 0.270.An elevated ratio is seen in approximately 80% of multiple sclerosis patients. A further refinement has been the calculation of the CSF IgG index, which has even higher sensitivity for detecting intrathecal IgG synthesis. This index is elevated in 85% of patients with multiple sclerosis. It is calculated as follows:

CSF IgG Index= CSF IgG x serum albumin/CSF albumin x serum IgG

Although these ratios are useful clinically, they do not quantify the CNS IgG production rate. The CSF IgG synthesis rate is calculated as follows:

5 [ {CSF IgG - (Serum IgG/369)} – { (CSF albumin - serum albumin/230) } x 0.43 (serum IgG/serum albumin) ]

Protein concentrations are expressed in mg/dL. The numbers 369 and 230 are the average normal serum: CSF ratios for IgG and albumin, respectively. 0.43 is the molecular weight ratio of albumin: IgG and 5 is the daily CSF production expressed in dL. The reference interval is –9.9 to +3.3 mg per day. Negative values are considered normal. Multiple sclerosis patients usually have a synthesis rate >8.0. This calculation is more complex and does not provide any more clinical information than the CSF IgG index. Therefore, it is not routinely performed as part of the multiple sclerosis panel.

One of the best methods to detect intrathecal IgG synthesis has been to examine CSF for the presence of oligoclonal bands after separation of proteins by electrophoresis. IgG in normal CSF migrates as a faint diffuse zone, but in demyelinating diseases, IgG migrates as discrete oligoclonal bands.

During the summer of 2003, the FDA approved a new method for the detection of oligoclonal bands that uses isoelectric focusing plus immunofixation (IEF) instead of electrophoresis. The Consortium of Multiple Sclerosis Centers has endorsed IEF because of its increased sensitivity (>95%). With IEF, oligoclonal bands may be detected while the total CSF IgG concentration is still within the normal range. Saint Luke’s Regional Laboratories began using this method in September 2003.

In order for the pathologist to interpret the results, a red top tube of blood must accompany all CSF specimens submitted for a multiple sclerosis profile. Serum and CSF should be tested in parallel. Four different patterns are observed.


Bands Observed

Associated Diseases


Polyclonal pattern (no discrete bands) in both serum & CSF

Rare Multiple sclerosis


CNS vasculitis

Paraneoplastic syndromes



Same number of OCB in serum & CSF


CNS vasculitis

Paraneoplastic syndromes


CNS infections

Neoplastic meningitis

Behcet Disease

Rasmussen Disease

Hashimoto encephalitis

Lymphoproliferative disorders

Hepatitis C


OCB in both serum & CSF. CSF has at least 2 more bands than serum

Multiple sclerosis

Most CNS infections


More than 2 OCB in CSF & polyclonal pattern in serum

Most Multiple sclerosis

Patterns 3 and 4 are reported as positive for OCB. Although a single band difference between CSF and serum is not diagnostic of multiple sclerosis, more than one half of these patients will progress to a full oligoclonal pattern.

Reference ranges are:


Reference Range


9.0 - 32.0 mg/dL

Gamma Globulins

1.1 - 5.5 mg/dL

IgG/Albumin ratio

0.066 - 0.270

IgG index

0.0 - 0.7 mg/dL

Oligoclonal bands


Specimen requirement is 3 mL of cerebrospinal fluid and one SST tube of blood.

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