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Using Antimyelin Antibodies to Predict Multiple Sclerosis

Ninety percent of patients who are diagnosed with multiple sclerosis initially present with an isolated neurologic event (e.g., optic nerve, brainstem, or spinal cord involvement). The disease-modifying treatments for multiple sclerosis are most effective when they are employed early in the progression of the disease, but only one third of patients with an initial neurologic event progress to multiple sclerosis within the next year. Currently, no reliable immunologic or radiologic findings identify patients who are more likely to progress to multiple sclerosis. Berger and associates examined the utility of two antibody markers in the prediction of later conversion to clinically definite multiple sclerosis.

The study enrolled 119 consecutive patients presenting to an academic neurology referral center with an initial neurologic event, all of whom had magnetic resonance imaging (MRI) scans showing multiple white-matter lesions and oligoclonal bands on examination of cerebrospinal fluid. Sixteen patients were ex-cluded from analysis. All patients received 1,000 mg of intravenous methylprednisolone for three to five days at their initial presentation. Subsequent evaluation for disease progression was performed every three months for an average follow-up duration of 50.9 months. Patients with a relapsing event not caused by an obvious external trigger (fever, heat, infection, or drugs) were deemed to have clinically definite multiple sclerosis. Before steroid treatment was administered, serum samples were assayed for antibodies against two myelin-related proteins: myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP). The study cohort was 71 percent female and had an average age of 32 years at presentation.

Serum titers for both anti-MOG and anti-MBP were present in 21 percent of patients; 41 per--cent were seropositive for anti-MOG antibodies only, and 38 percent were seronegative for both anti-MOG and anti-MBP antibody markers. Progression to clinically definite multiple sclerosis occurred in 95 percent of study subjects with positive titers for both anti-MOG and anti-MBP, compared with a relapse rate of 23 percent in persons who were seronegative for both antibodies. Eighty-three percent of patients with only anti-MOG seropositivity relapsed. The mean length of time until relapse was 7.5 months in those with both antibody markers and 45.1 months in patients lacking either marker. Those with only anti-MOG antibodies had an average relapse time of 14.6 months. Compared with patients without either marker, seropositivity for anti-MOG increased the risk of relapse 32-fold, while seropositivity for both markers increased the risk 76 times. The number of white-matter lesions seen on MRI scan of the brain at initial presentation was higher in patients with both antibodies than in those without anti-MOG and anti-MBP; however, this number was not an independent predictor of disease progression in multi-variate analysis.

The authors conclude that seropositivity for antibodies against two myelin-related proteins in patients with an initial neurologic event is associated with a higher rate of conversion to clinically definite multiple sclerosis and a shorter time interval until relapse occurred.

bill zepf, m.d.

Berger T, et al. Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event. N Engl J Med July 10, 2003;349:139-45.

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