ABSTRACT
Approximately 85% of multiple sclerosis (MS) patients present with a relapsing-remitting course, in which there are acute relapses followed by partial or complete recovery.[1] By definition, clinical manifestations are stable between relapses. In most patients, the course eventually evolves into gradual progression with or without superimposed relapses, minor remissions and plateaus, termed secondary progressive MS.[1] The transition from relapsing-remitting MS to secondary progressive MS is typically rather insidious and occurs over several years. Secondary progressive MS has been distinguished from primary progressive MS, in which patients exhibit gradual worsening from disease onset without relapses (see chapter 35).[2] In primary progressive MS, the patients tend to have an older age of onset, and relatively more men are affected. Magnetic resonance imaging (MRI) demonstrates fewer and less distinct cerebral lesions, a paucity of new lesions over time despite increasing disability, and less gadolinium enhancement.[3]
At the onset of MS, factors predictive of the development of progressive disease include male sex, older age at onset, motor symptoms, polyregional onset, and incomplete remission after first relapse.[4] After 5 years, a high neurologic deficit, the number of affected functional systems, the degree of remission from the last relapse, and the occurrence of polyregional symptoms with the last relapse predict development of progressive disease. However, the predictive ability of these factors, either individually or in combination, is weak. Also, absence of these poor prognostic factors is a weak predictor of a good prognosis. Rather, there is a steady increase in the proportion of patients who convert from relapsing-remitting MS to secondary progressive MS with increasing disease duration.[5] After 10 years, over 50% of patients with initially relapsing-remitting disease develop secondary progressive MS. After 25 years, 90% of patients have converted to secondary progressive MS. Secondary progressive MS is the phase of MS in which significant disability tends to accumulate. The median times from onset of a progressive course to reach a particular Kurtzke expanded disability status score (EDSS) were 1.40 years to a score of 3, 4.50 years to a score of 6, and 24.08 years to a score of 8.
