Multiple sclerosis diagnosis

No single clinical feature or diagnostic test is adequate for the accurate diagnosis of multiple sclerosis (MS). Therefore, clinical information is integrated with paraclinical studies. Diagnosing MS after a single, acute remitting clinically isolated syndrome (CIS) is very risky. 50–70% of patients with a CIS suggestive of MS will have multifocal MRI abnormalities characteristic of MS. The presence of these MRI abnormalities increases the risk of developing MS in 1–3 years (with greater prognostic significance than CSF- OCB). The more MRI lesions, the higher the risk.

The following definitions are used in the classification system that follows:

1. attack (exacerbation, relapse): neurologic disturbance lasting > 24 hrs35 typical of MS when clinicopathological studies determine that the cause is demyelinating or inflammatory lesions

2. remission: ≥ 30 days should separate the onset of the first attack from the onset of a second 3. historical information: reporting of symptoms by the patient (confirmation by observer desirable), adequate to locate a lesion of MS, and has no other explanation (i.e., manifestations must not be attributable to another condition)

4. clinical evidence (signs): neuro dysfunction recorded by a competent examiner

5. paraclinical evidence: tests or procedures demonstrating CNS lesion which has not produced signs; e.g. Uhthoff phenomenon or sign (worsening of symptoms with hot bath or shower), BAER, imaging procedures (CT, MRI), expert urological assessment

6. typical of MS: signs & symptoms (S/S) known to occur frequently in MS. Thus excludes gray mat- ter lesions, peripheral nervous system lesions, and non-specific complaints such as H/A, depres- sion, convulsive seizures, etc.

7. separate lesions: S/S cannot be explained on basis of single lesion (optic neuritis of both eyes simultaneously or within 15 days represents single lesion)

8. laboratory support: in this study, the only considerations were CSF oligoclonal bands (CSF-OCB) (see below) (OCB must not be present in serum) or increased CSF IgG production (CSF-IgG) (se- rum IgG must be normal). This assumes that syphilis, SSPE, sarcoidosis, etc. have been ruled out.

Multiple sclerosis MRI.

CSF analysis can support the diagnosis in some cases, but cannot document dissemination of lesions in time or space. The CSF in MS is clear and colorless. The OP is normal. Total CSF protein is < 55 mg/ dl in ≈ 75% of patients, and < 108 mg/dl in 99.7% (values near 100 should prompt a search for an alternative diagnosis). The WBC count is≤5cells/mcl in 70% of patients, and only 1% have a count > 20 cells/mcl (high values may be seen in the acute myelitis).

In ≈ 90% of patients with MS, CSF-IgG is increased relative to other CSF proteins, and a characteristic pattern occurs. Agarose gel electrophoresis shows a few IgG bands in the gamma region (oligoclonal bands) that are not present in the serum (higher resolution isoelectric focusing can demonstrate 10–15 bands). CSF-OCB are not specific for MS and can occur in CNS infections and less commonly with strokes or tumors. The predictive value of the absence of IgG in a patient with suspected MS has not been satisfactorily elucidated.

Recommended criteria have been published, most of which pertain to specifics of laboratory analysis.

1. qualitative assessment of IgG is the most informative analysis and is best performed using IEF with some form of immunodetection (blotting or fixation)

2. analysis should be performed on unconcentrated CSF and must be compared to simultaneously run serum sample in the same assay

3. runs should use the same amount of IgG from serum and CSF

4. each run should contain positive and negative controls

5. quantitative analysis should be made in terms of one of the 5 recognized staining patterns for OCB

6. an individual experienced in the techniques should report the results

7. all other tests performed on the CSF (including WBC, protein & glucose, lactate) should be taken into consideration

8. evaluation using light chains for immunodetection may be helpful in certain cases to resolve equivocal oligoclonal IgG patterns

9. if clinical suspicion is high but CSF results are equivocal, negative or show only a single band, consider

repeating the LP

10. to measure IgG levels, nonlinear formulas that consider integrity of the blood-CSF barrier should be used (e.g. the ratio of CSF to serum albumin (AKA Qalb) is a measure of leakiness)

11. labs analyzing CSF should have internal as well as external quality assessment controls

12. quantitative IgG is a complementary test, but is not a substitute for qualitative IgG testing, which has the highest sensitivity and specificity.