Corticosteroid Treatment of Multiple Sclerosis Relapses
Short courses of high-dose corticosteroids have been routinely used to treat acute MS relapses for many years. The first therapeutic advance in this area began with the use of adrenocorticotropic hormone (ACTH) to stimulate the synthesis of corticosteroids.¹ A number of studies support the concept that steroids accelerate recovery.^2–5

There is limited evidence that steroid therapy may reduce tissue damage and improve the degree of recovery, at least as determined by magnetization transfer imaging.⁶ However, most studies have found little difference in the ultimate degree of clinical recovery following a relapse.^5,7 Despite the suggestion⁷ that the risk of a subsequent relapse may be reduced, other studies do not support this, nor do they support any delay in time to the next relapse.^5,8The most commonly used dosage regimen is 500–1,000mg of IVMP daily for three to five days, with or without a subsequent tapering dose of oral steroids for one to three weeks.^3,9 Within this range, the number of days of treatment may vary depending on the type and severity of relapse and the clinician’s judgment with respect to the individual patient. Although it is not clear at this time whether lower or higher doses might be more useful, 1,000mg daily can be recommended as suitable for most patients. Intravenous steroids can be administered either as a single dose per day or in divided doses. It is unclear which (if either) of these approaches is more effective. In the Optic Neuritis Treatment Trial (ONTT)³ divided dosage (250mg IVMP q6h) was used. Once-daily administration saturates steroid carriers and might lead to greater effect, but the clinical significance of these different dosing regimens is unknown. Also, the use of single or multiple infusions potentially has economic implications. Although existing data are inconclusive, the consensus of the Steroid Task Force is that a single daily dose is just as effective, more practical, and probably less costly than divided doses.

The need for an oral taper—usually of oral prednisone—and its optimal duration, if used, is uncertain. Existing data do not favor one approach over the other, and there is no real consensus as to their use. Tapers may ease the transition from taking steroids, and because of this some physicians use them routinely, but unlike the situation in systemic lupus erythematosus (SLE) it is unlikely that a taper makes any difference to overall outcome in MS. A taper should not be used if a patient previously experienced significant side effects to low-dose steroids, or if there are other reasons for withholding it, such as co-existing diabetes that might be affected adversely by steroids. Tapers have not generally been used in major clinical trials.

The question of how soon after the onset of a relapse steroid treatment should be initiated is related to two separate issues: whether to treat a specific relapse immediately and how late into a relapse it is effective to treat. Timing depends on the nature of the relapse. For example, optic neuritis is generally treated with a three-day course of steroids, as used in the ONTT, whereas more severe relapses are treated with five- or even seven-day courses. In general, we recommend that the clinician treat a major relapse (one that is potentially disabling) as soon as possible, but taking a ‘wait and see’ approach may be appropriate in many circumstances, especially when treating minor relapses (those that are purely sensory or cause no increase in disability). Although the steroid most often used to treat relapses is IVMP, other options may also be appropriate. For example, comparable doses of IV dexamethasone could be substituted for IVMP. Although comparative trials have not been performed, dexamethasone is a reasonable alternative if MP is unavailable, or for other reasons such as a previous allergic reaction to MP. Patients on dexamethasone may experience fewer overall side effects due to its relative lack of mineralocorticosteroid effects and consequently lower sodium retention than seen with other steroids. Dexamethasone and MP have different affinities for glucocorticoid and mineralocorticoid receptors, which may result in differences in clinical efficacy. However, such differences are likely to be minor, and MP is therefore recommended as the drug of choice.

There has recently been a renewed level of interest in using intramuscular or subcutaneous ACTH, the original treatment for relapse management.1 Although ACTH may have some theoretical advantages, it is more expensive than corticosteroids, generally has more side effects, and gives less consistent results. It may have a place in rare situations, such as when IV infusion is impractical, or in cases where its positive effects on bone via stimulation of dehydroepiandrosterone (DHEA) and mineralocorticoids may be desirable.