Multiple sclerosis is the most common disabling neurologic disease among young people. While accounts of what most likely constituted MS date back to Viking Norse stories of the eighth century, it was the Scottish physician Robert Carswell who pathologically described the plaques of MS as “firm spots” in 1830, signifying the yet-to-be-discovered fibrous and sclerotic nature of the disease.1 Jean Cruveilhier in France described the degeneration of the white matter columns of the spinal cord derived from a patient at the Salpêtrèie Institute in Paris.2 The most exacting histopathologic description of spinal cord MS was provided by the German Carl Frommann in 1867.3 Frommann recognized the role of glial elements as a critical component of the lesion substrate (ie, gliosis). Without a doubt, however, it was Jean-Martin Charcot4 in 1868 who assembled all of the clinical, neuroanatomic, and pathological elements into the first comprehensive framework of MS (sclérose en plaques). Charcot recognized the cardinal elements of MS: the history of disease-related relapses and remissions, producing a myriad of symptoms derived from a diversity of potential lesion localizations (dissemination of disease in time and space). Siemerling and Raecke5 recognized in 1914 that MS plaques could be disseminated throughout white matter but also in the cerebral cortex, an observation now receiving greater attention by contemporary workers. In 1916, James Dawson6 refined the gross pathology of MS lesions by drawing attention to the fingerlike projections arising from the ventricular lining, an observation that would later represent a classic magnetic resonance imaging signature of MS, as demonstrated by Dr McDonald; this observation also had implications for understanding postcapillary venular trafficking of circulating mononuclear cells.