Clinically isolated syndrome and multiple sclerosis: rethinking the arsenal.

Until the end of the past century, a diagnosis of multiple sclerosis (MS) was often accompanied by a sense of apprehension, fueled primarily by the lack of available therapies and failed attempts with numerous agents. The modern era of MS therapeutics introduced in the past 20 years has helped to assuage the previous belief that little could be done to treat MS. The advent of disease-modifying treatments such as interferons and glatiramer acetate has had a notable impact on the course of MS. Numerous trials have demonstrated the clear benefit of initiating therapy in patients with a diagnosis of MS, but more importantly, they have shown that early initiation of treatment can delay progression to clinically definite MS in patients with clinically isolated syndrome who have concurrent changes on MRI. As newer agents become available, trials to assess their efficacy and tolerability are under way in an effort to expand the arsenal of available treatments. However, questions constantly resurface about the effect of treatments on disability, the safety of combination therapies, the role in neuroprotection, and other aspects. Moreover, recent attention regarding a radiologic and clinical dissociation, best illustrated by the anecdotally termed "radiologically isolated syndrome," highlights the frustrations facing clinicians when they try to predict disease course and the role of medications, if any.Despite the need for clear answers to these questions, the current practice is to initiate the available treatments early in patients with relapsing-remitting multiple sclerosis, in order to reduce the severity and frequency of clinical relapses. Treatment should also be initiated early in patients with clinically isolated syndrome because they are at high risk for developing clinically definite multiple sclerosis.