The clinical course of multiple sclerosis.

Knowledge of the epidemiology and natural history of multiple sclerosis (MS) is essential for practitioners and patients to make informed decisions about their care. This knowledge, in turn, depends upon the findings from reliable studies (i.e., those which adhere to the highest methodological standards). For a clinically variable disease such as MS, these standards include case ascertainment using a population-based design; a large-sized sample of patients, who are followed for a long time-period in order to provide adequate statistical power; a regular assessment of patients that is prospective, frequent, and standardized; and the application of rigorous statistical techniques, taking into account confounding factors such as the use of disease modifying therapy or the age at clinical onset. In this chapter we review the available epidemiologic and natural history data as it relates clinical issues such as the likelihood of incomplete recovery from a first attack; the likelihood and time course of a second attack; the likelihood and time course of disease progression and the accumulation of irreversible disability; the disease prognosis based both upon the clinical nature and presentation of the first episode and upon the initial disease course; and the impact of disease on mortality. In addition, these studies provide insight to the pathophysiologic mechanisms underlying the course and prognosis of MS. Studies of the Lyon cohort have been particularly helpful in this regard and observations from this cohort have led to the hypothesis that, in large part, the accumulation of disability in MS is an age-related process, which is independent of the clinical subtype of MS (i.e., relapsing-remitting, primary progressive, secondary progressive, or relapsing progressive). And finally, we consider briefly the impact of various life events (e.g., pregnancy, infection, vaccination, trauma, and stress) on the clinical course of disease.