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Previous Volume 329:1764-1769 December 9, 1993 Number 24 Next

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ABSTRACT

Background 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.

Methods 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.

Results 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.

Conclusions 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.

Source Information

From the Jaeb Center for Health Research, Tampa, Fla. (R.W.B.); the Departments of Ophthalmology (R.W.B.), Neurology (R.W.B.), and Epidemiology and Biostatistics (R.W.B., C.H.B.), University of South Florida, Tampa; the Biostatistics Center, George Washington University, Rockville, Md. (P.A.C.); the Kellogg Eye Center, University of Michigan, Ann Arbor (J.D.T.); the Division of Visual Science, Michigan State University, East Lansing (D.I.K.); the Department of Ophthalmology, New York University, New York (M.J.K.); and the Department of Neurology, University of British Columbia, Vancouver, Canada (D.W.P.). The major participants in the Optic Neuritis Study Group are listed in the Appendix.

Address reprint requests to Dr. Beck at the Jaeb Center for Health Research, 3010 E. 138 Ave., Suite 13, Tampa, FL 33613.

Full Text of this Article

Related Letters:

Corticosteroids, Optic Neuritis, and Multiple Sclerosis
Olek M. J., Khan O. A., Hart R. G., Beck R. W.
Extract | Full Text  
N Engl J Med 1994; 330:1238-1239, Apr 28, 1994. Correspondence

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• Panitch, H. S (1996). Investigational drug therapies for treatment of multiple sclerosis. Mult Scler 2: 66-77 [Abstract]  
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• Miller, D. (1996). Guidelines for MRI monitoring of the treatment of multiple sclerosis: recommendations of the US Multiple Sclerosis Society's task force. Mult Scler 1: 335-338 [Abstract]  
• Kappos, L. (1996). Combinations of drugs. Mult Scler 1: 400-403 [Abstract]  
• Vollmer, T. L. (1996). Multiple Sclerosis: New Approaches to Immunotherapy. Neuroscientist 2: 127-136 [Abstract]  
• Rudick, R., Medendorp, S., Namey, M, Boyle, S, Fischer, J (1995). Multiple sclerosis progression in a natural history study: Predictive value of cerebrospinal fluid free kappa light chains. Mult Scler 1: 150-155 [Abstract]  
• Levin, L. A. (1995). Ophthalmology. JAMA 273: 1703-1705 [Abstract]  
• Crockard, A., Treacy, M., Droogan, A., McNeill, T., Hawkins, S. (1995). Transient immunomodulation by intravenous methylprednisolone treatment of multiple sclerosis. Mult Scler 1: 20-24 [Abstract]  
• Whitaker, J., McFarland, H., Rudge, P, Reingold, S. (1995). Outcomes assessment in multiple sclerosis clinical trials: a critical analysis. Mult Scler 1: 37-47 [Abstract]  
• Beck, R. W., Optic Neuritis Study Group, (1995). The Optic Neuritis Treatment Trial: Three-Year Follow-up Results. Arch Ophthalmol 113: 136-137 [Abstract]  
• Beck, R. W., Optic Neuritis Study Group, (1994). Optic Neuritis Treatment Trial Study-Reply. Arch Ophthalmol 112: 1274-1275 [Abstract]  
• O'Brien, T. P., Goldberg, M. F. (1994). Ophthalmology. JAMA 271: 1695-1696 [Abstract]  
• Slavin, M. L., Burde, R. M. (1994). Prepublication Blackout in the Optic Neuritis Treatment Trial. Arch Ophthalmol 112: 581-581 [Abstract]  
• Olek, M. J., Khan, O. A., Hart, R. G., Beck, R. W. (1994). Corticosteroids, Optic Neuritis, and Multiple Sclerosis. NEJM 330: 1238-1239 [Full Text]  
• Miller, A., Bourdette, D., Ritvo, P., Stuart, W., Vollmer, T. (1994). The Neurologist's Perspective: What Do We Know and Where Do We Go?. Neurorehabil Neural Repair 8: 105-111 [Abstract]  
• Trobe, J. D. (1994). High-Dose Corticosteroid Regimen Retards Development of Multiple Sclerosis in Optic Neuritis Treatment Trial. Arch Ophthalmol 112: 35-36 [Abstract]  
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