Multiple sclerosis: epidemiology, genetics, classification, natural history, and clinical outcome measures.

Advances in MR imaging and randomized controlled-trial methodology have fundamentally altered the diagnosis and investigation of multiple sclerosis (MS). Further progress in epidemiology and classification will provide clues toward identification of the genetic and environmental factors that predispose to MS and dictate its course. More detailed understanding of the descriptive natural (untreated) history of the disease and development of intermediate and surrogate outcome measures, with better validity and reliability, will increase the likelihood that future clinical trials will identify beneficial treatments to reduce disability. This article reviews the current state of knowledge of MS epidemiology, genetics, disease classification, natural history, and outcome measures.