Age at disability milestones in multiple sclerosis

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Abstract
Many efforts have been devoted to the description of the prognosis of multiple sclerosis and its possible influential factors in terms of time to reach disability milestones. By contrast, the age at which patients with multiple sclerosis reach these milestones has not yet stirred much interest. We have tested the hypothesis whether the prognosis of multiple sclerosis depends on the current age of patients and the initial course of the disease. We have assessed disease onset and course, and assignment of scores of irreversible disability in 1844 patients with multiple sclerosis. We have used three scores on the Kurtzke Disability Status Scale as benchmarks of disability accumulation: DSS 4 (limited walking but without aid), DSS 6 (walking with unilateral aid) and DSS 7 (wheelchair-bound). We used Kaplan–Meier analyses to estimate the age of the patients at assignment of disability milestones. The possible influence of the initial course of multiple sclerosis and of other clinical variables early assessable in the disease on these outcome measures was also studied, using the Kaplan–Meier curves for univariate analyses and Cox models for multivariate analyses. For the 1844 patients, median ages at time of assignment of irreversible disability were 44.3 years (95% CI 43.3–45.2) for a score of DSS 4, 54.7 years (95% CI 53.5–55.8) for DSS 6 and 63.1 years (95% CI 61.0–65.1) for DSS 7. These results were essentially similar whether the initial course of multiple sclerosis was exacerbating-remitting or progressive, and whatever the initial symptomatology. Females reached disability milestones at an older age than males. The most influential clinical factor was age at clinical onset of multiple sclerosis: the younger the onset, the younger the age at assignment of disability milestones. Therefore, prognosis in multiple sclerosis appears, at least to some extent, as age-dependent and not substantially affected by the initial course, be it exacerbating-remitting or progressive. Aside acute focal recurrent inflammation and diffuse chronic neurodegeneration, accelerated ageing-related mechanisms may operate in the central nervous system of multiple sclerosis patients.