The mystery of the origin of multiple sclerosis.

Our present understanding of the aetiology and pathogenesis of multiple sclerosis is discussed in relation to the views of Sir William Gowers. He perceived that both environmental and genetic factors might be implicated in the aetiology of the disease. Evidence for the former was first reported in 1903, but has become convincing only in the past 20 years; the nature of the environmental factor remains obscure. Evidence for a genetic influence on susceptibility has accumulated since the 1930s, the most compelling coming from the recent Canadian twin study. The number and mode of operation of the genetic factors is still uncertain, but there is evidence for the implication of genetically controlled cellular immune mechanisms in the pathogenesis of the disease. The precise relationship between transient changes in immunological status and the development of new lesions has yet to be defined; magnetic resonance imaging (MRI) promises to play a significant role in this analysis because of its sensitivity in detecting abnormalities in multiple sclerosis. MRI is not in itself specific; it is probable that the similar appearances in multiple sclerosis and cerebral vascular disease both derive at least in part from the influence of astrocytic gliosis on proton content and distribution. The significance of the gliosis is uncertain. Gowers believed that the primary defect in multiple sclerosis lay in the astrocyte. Recent observations on the immunological functions of this cell in vitro suggest that it could be involved early in the pathogenesis of the lesion.