Interventions for the prevention of brain atrophy in multiple sclerosis : current status

The assessment of brain volume changes on serial magnetic resonance imaging (MRI) scans can provide an objective measure of the neurodegenerative component of multiple sclerosis (MS) pathology. Results from placebo-controlled and crossover clinical trials indicate that immunomodulating (e.g. recombinant interferon-beta [IFNbeta]-1a [Rebif] and IFNbeta-1b [Betaferon] and glatiramer acetate [Copaxone]) and immunosuppressive (e.g. cladribine and alemtuzumab) treatments for relapsing-remitting (RR) and secondary progressive MS lack substantial efficacy in preventing the development of brain atrophy, despite the marked effects of these treatments on clinical and MRI outcomes of disease activity. A modest but significant treatment effect on brain atrophy has been reported for patients with RRMS only in one trial of IFNbeta-1a (Avonex) and in another study of long-term corticosteroid therapy.Failure to find a significant treatment benefit in preventing brain atrophy might be the result of inadequate trial designs, including their relatively short durations, which may not be adequate to reveal beneficial effects in a chronic disease like MS. Alternatively, such a failure might indicate that treatments proven to be effective in reducing MS-related inflammation are unable to act with the same efficacy on the most severe and disabling pathological substrates of the disease. The modest correlation between MRI enhancement frequency and brain atrophy observed in the placebo groups of several trials also fits with the concept that the suppression of inflammatory activity in MS is not fully and rapidly associated with a similar effect on the global neurodegenerative process of the disease.