For over a century following the early clinic-pathologic descriptions of MS by Charcot and others, the major treatments for MS purely addressed the various symptoms caused by the disease. ACTH therapy in MS was first studied in 1969 and showed faster recovery from acute clinical relapses. This treatment was ultimately abandoned as its benefit was in proportion to elevation of endogenous glucocorticoids, an effect that is more easily obtained by oral or intravenous administration of these drugs. In the 1990s and early 2000s, the major medications became subcutaneous or intramuscular injectable forms of interferon or a compound called glatiramer acetate, a synthetic mixture of polypeptides that has immunomodulatory effects. In 2006, the intravenous monoclonal antibody natalizumab became available and was shown to be quite efficacious, but its use was limited by risk of opportunistic infection with JC virus causing PML. Beginning in 2010, a number of oral disease modifying oral medications became available. In addition, additional monoclonal antibody therapies have been developed in recent years.
The availability of a broad range of therapeutic options has transformed the clinical course of MS for most patients, with fewer relapses and an uncertain but apparent reduction of chronic disability. Key to the successful long-term treatment of MS is appropriate balancing of the risks, benefits, adherence, convenience, and cost of available therapies for the individual patient. In general, there are few circumstances where disease- modifying treatment is mandated immediately, and we allow enough time for the patient to consider the alternatives and sometimes encourage serial examinations and MRI to determine the course of illness. In addition, it should be acknowledged that the correlation between the number of relapses and the ultimate disability is not perfect across patients.
In addition to the available treatments discussed below, a current list of clinical trials is maintained by the National Multiple Sclerosis Society: http://www.nationalmssociety.org/research/clinical-trials/clinical-trials-in-ms/index .aspx
Glucocorticoids Under the influence of corticosteroids, recovery from an acute attack, including an attack of optic neuritis, appears to be hastened. However, a substantial group of patients with acute exacerbations fails to respond; in others, benefit is not apparent for a month or longer after the course of treatment has been completed and is difficult to distinguish from the natural course of disease. Apart from a transient effect on the duration of a relapse, chronic administration of steroids generally does not have a significant effect on the ultimate course of this disease or that they prevent recurrences. Although this strategy should only apply to a minority of patients, it is of interest that a study of intravenous methylprednisolone administered at 1 g/d for 5 days per month over 5 years showed a reduction in disability as well as in the degree of brain atrophy and total volume of hypodense lesions on T1-weighted MRI (Zivadinov et al).
As to the dosage of corticosteroids for an acute attack, it seems that initially a high dose is more effective but this has been disputed, as noted below. A randomized trial comparing oral and intravenous methylprednisolone in acute relapses of MS demonstrated no clear advantage of the intravenous regimen (Barnes et al), but many MS experts dispute this finding. The administration of adrenocorticotropic hormone (ACTH), which was popular during the 1970s, has largely been abandoned, although a newer formulation has become available again recently.