Corticosteroids have been the mainstay of treatment for the management of acute relapses in multiple sclerosis (MS) for many years. They have immunomodulatory and antiinflammatory effects that restore the integrity of the blood–brain barrier, reduce edema, and possibly facilitate remyelination and improve axonal conduction. Corticosteroid therapy has been shown to shorten the duration and severity of the relapse and accelerate recovery, but there is no convincing evidence that the overall degree of recovery is improved or that the long-term course of the disease is altered.

Adrenocorticotropic hormone (ACTH, corticotropin) was the first agent demonstrated to be helpful in recovery from acute exacerbations. Brief courses of high-dose intravenous (IV) methylprednisolone (IVMP, 500–1000 mg/day for 3–5 days) have generally supplanted ACTH because of convenience, reliability, fewer side effects, and perhaps a more consistent and rapid onset of action.

Results of the Optic Neuritis Treatment Trial have been extrapolated by many neurologists to MS-associated relapses in general. In this study, 457 patients with acute optic neuritis were randomly assigned to receive 1000 mg of IVMP per day for 3 days followed by 1 mg of oral prednisone per kilogram per day for 11 days, 1 mg of oral prednisone per kilogram per day for 14 days, or oral placebo. The advantage of studying cases of optic neuritis is that very sensitive outcome measures (e.g., visual field, contrast sensitivity, color vision, and visual acuity) can be applied.

The rate of recovery of vision was significantly faster in the IVMP-treated group, with the greatest benefits in patients with visual acuity of 20/40 or worse at entry. After 6 months there was no significant difference in visual acuity between the IVMP and placebo groups. Oral prednisone provided no benefit over placebo.

Unanticipated findings were that during the 6 to 24 months of follow-up, the risk of recurrent optic neuritis in either eye was increased with oral prednisone and that IVMP reduced by approximately 50 percent the risk of a new attack leading to the diagnosis of MS. This effect was most evident for patients at highest risk for subsequent relapse, that is, those with multiple brain lesions on MRI at entry into the study.

These results should be interpreted with the understanding that this study was not designed to assess the effect of glucocorticoids on subsequent relapses and that the IVMP group was unblinded and lacked a placebo control. Differences between the treatment groups were no longer significant after 3 years, which suggests that IVMP at best delayed but did not stop the development of MS.

Magnetic resonance imaging follow-up studies have convincingly shown the effect of steroids, as evidenced by the reduction of gadolinium-enhancing lesions. However, this effect is only short-lived, and new enhancing lesions can develop within a week following treatment.

Despite the widespread use of corticosteroids as a treatment for relapses, very little is known about the optimal treatment regimen. The main controversies relate to the relative efficacy of the type of steroid (i.e., intramuscular ACTH versus IV steroids versus oral steroids), the optimal dosage for each route of administration, and whether a short course of IV treatment should be followed by a tapering regimen of orally administered corticosteroids.

Some clinicians substitute oral corticosteroid treatment for IVMP for the management of relapses mainly because of its easier route and reduced expense of administration. Data substantiating its equivalent benefit in acute relapse have been presented but are not very persuasive. Remarkably, in various studies—all being rather small—quite different dosage regimens of oral steroids have been applied.

Other antiinflammatory drugs, the so-called nonsteroidal antiinflammatory drugs (NSAIDs), including aspirin, indomethacin, ibuprofen, and naproxen, have not been shown to be of benefit in the treatment of MS relapses.

"In the opinion of the Committee, a course of corticosteroids can be recommended for patients with exacerbations who have significant functional impact. Long-term use may be associated with significant serious side effects." —Medical Management Committee, MSIF International Medical and Scientific Board (IMSB)