The contribution of British neurologist Russell Walter Brain (1895-1966) to the field of neurology is difficult to overestimate and his seminal work continues to influence modern neurological education and practice. In a landmark review published in the Quarterly Review of Medicine in 1930, he gives a critically important account summarising ideas of the time thought to underlie the then called 'disseminated sclerosis', a disease he notes to be, 'after syphilis, the most frequent disease of the nervous system' in the UK. Across a century and a half, vast progress has been made in attempting to elucidate the as yet unknown cause of MS, which is unravelling to be multifactorial, highly complex and likely dependent on both genetic and environmental risk factors. Brain's observations highlight the changing epidemiology of MS over the last century which are likely to provide the platform in striving towards elucidating MS causation, notably a seemingly reduced latitudinal gradient of MS incidence, an increasing female-to-male sex ratio and an increasing disease rate in dark-skinned compared to light-skinned individuals. In this report we aim to evaluate the relevance today of what we believe to have been an important review demonstrating a perspective on MS far ahead that of its time, with a focus on Brain's ideas on the aetiology of MS; many of which have stood the test of time.