ABSTRACT
In the last edition of this handbook, this chapter concluded with the statement that epidemiology is inferential-its role is to provide etiologic clues, but it cannot prove nor refute causality. Multiple sclerosis (MS) is a complex trait that appears to be determined by both genetic and environmental factors. It exhibits a changing incidence over time in an uneven geographic distribution. The evidence of these spatial and temporal trends from migrant studies affirms the etiological relevance of environmental factors, although their nature remains mysterious and is undoubtedly complex. A best summarizing guess at the causality of the disease was proffered, supposing that all MS patients possess one of the range of genotypes that confer susceptibility, that different genotypes are associated with different phenotypes, and that about one-third of those susceptible will develop the disease while the remaining two-thirds will noteither because they possess inhibitory or protective genes or because they do not come into contact with the necessary triggering factors in their internal or external environments.
