Working in the 1660s, William Croone wrote on the nature of connections between nerve and muscle. A previously unknown copy of his essay, wrongly attributed to Thomas Willis, has recently come to light. Croone left the challenges of clinical neurology to his successors. The story of multiple sclerosis begins early in the nineteenth century. Despite much information on the aetiology and pathogenesis, the origins of that disease remain obscure. Here, the hypothesis is advanced - based on the epidemiology, clinical neurology, immunology and genetics of demyelinating disease, linked to European history and population genetics - that multiple sclerosis evolved from a related disorder, neuromyelitis optica (or Devic's disease). Genetic drift and stratification altered the immune response to a common pathogen and changed the disease phenotype. Against this background, the sustained epidemic of multiple sclerosis arose when cultural changes led to a subtle but crucial alteration in the age at which genetically vulnerable individuals are exposed to Epstein Barr infection.