The history of multiple sclerosis: the changing frame of the disease over the centuries.

For centuries, it was recognised that there was a condition characterised by episodic and progressive neurological deterioration, classified as 'paraplegia'. Some early cases of 'paraplegia' have been described in sufficient detail to recognise a condition resembling what we now call multiple sclerosis and these cast an interesting light on the approach to therapy before the disease had a name. Multiple sclerosis was differentiated and 'framed' as a separate identifiable entity by von Frerichs, Vulpian, Charcot and others in the mid-nineteenth century. Once framed by its pathology, clinical picture, course and prognosis, cases were diagnosed by others around the world. As knowledge of the disease increased, theories of cause and approaches to treatment increased so that a review in 1935 covered 158 treatments used in MS. There were subsequent waves of therapies including anticoagulants, antibiotics, histamine desensitisation, various diets, vaccines and anti-cancer agents, as well as numerous claims of 'cures'. After the 1960s the methodology for carrying out randomised clinical trials became better defined, aided by improved disease classification and disability scales. As data accumulated, theories were tested to account for observations of genetic influences, environmental factors, geographical variations, infections and immunological changes. The development of multiple sclerosis societies advanced research and public education and changed attitudes towards the disease. At the same time, attitudes of physicians towards management of people with multiple sclerosis changed. In the last fifty years, the major advances have been in basic research to elucidate the mechanisms and processes underlying the disease, the development of imaging techniques (MRI) and the development of immunomodulatory drugs which, for the first time, are altering the outcome of the disease. We have now entered the therapeutic era of multiple sclerosis, with continual major advances bringing hope and benefit to people with multiple sclerosis.