The Effect of Corticosteroids for Acute Optic Neuritis on the Subsequent Development of Multiple Sclerosis

Optic neuritis is often the first clinical manifestation of multiple sclerosis, but little is known about the effect of corticosteroid treatment for optic neuritis on the subsequent risk of multiple sclerosis. We conducted a multicenter study in which 389 patients with acute optic neuritis (and without known multiple sclerosis) were randomly assigned to receive intravenous methylprednisolone (250 mg every six hours) for 3 days followed by oral prednisone (1 mg per kilogram of body weight) for 11 days, oral prednisone (1 mg per kilogram) alone for 14 days, or placebo for 14 days. Neurologic status was assessed over a period of two to four years. The patients in the first group were hospitalized for three days; the others were treated as outpatients. Definite multiple sclerosis developed within the first two years in 7.5 percent of the intravenous-methylprednisolone group (134 patients), 14.7 percent of the oral-prednisone group (129 patients), and 16.7 percent of the placebo group (126 patients). The adjusted rate ratio for the development of definite multiple sclerosis within two years in the intravenous-methylprednisolone group was 0.34 (95 percent confidence interval, 0.16 to 0.74) as compared with the placebo group and 0.38 (95 percent confidence interval, 0.17 to 0.83) as compared with the oral-prednisone group. The beneficial effect of the intravenous-steroid regimen appeared to lessen after the first two years of follow-up. Signal abnormalities on magnetic resonance imaging (MRI) of the brain were a strong indication of risk for the development of definite multiple sclerosis (adjusted rate ratio in patients with three or more lesions, 5.53; 95 percent confidence interval, 2.41 to 12.66). The beneficial effect of treatment was most apparent in patients with abnormal MRI scans at entry. In patients with acute optic neuritis, treatment with a three-day course of high-dose intravenous methylprednisolone (followed by a short course of prednisone) reduces the rate of development of multiple sclerosis over a two-year period., Optic neuritis is frequently the first manifestation of multiple sclerosis¹. Even when optic neuritis occurs without other clinical signs of multiple sclerosis (“isolated optic neuritis”), magnetic resonance imaging (MRI) of the brain often demonstrates signal abnormalities of white matter,²–⁵ and analysis of cerebrospinal fluid often shows oligoclonal bands⁶–⁸. Within 2 years of an attack of optic neuritis, the risk of multiple sclerosis is approximately 20 percent,⁸–¹² and within 15 years it is in the range of 45 to 80 percent⁸–¹¹. The Optic Neuritis Treatment Trial, a multicenter, randomized clinical trial of corticosteroid treatment…