That most perceptive of behavioral neurologists, Charcot (1877), observed that MS patients may show “marked enfeeblement of the memory, conceptions are formed slowly and intellectual and emotional faculties are blunted in their totality.” Despite this early recognition of potential cognitive difficulties in MS patients, for the greater part of a century clinicians held to the belief that cognitive difficulties were seldom part of the clinical picture in MS, and if present, generally confined to patients with severe physical disability. Therefore, on the basis of a clinical examination, Kurtzke (1970) estimated that cognitive difficulties affected less than 5% of patients. Even more striking were the conclusions from the influencial study of Cottrell and Wilson (1926) of 100 MS patients seen in a tertiary referral center. Noting intellectual decline in only two patients, the authors considered the problem “minimal and negligible.”

With the advent of MRI in the early 1980s, clinicians and researchers were able to visualize the brain's white matter changes with a new found clarity. The ability to detect cerebral lesions in vivo was the impetus for researchers to look for clinical correlates, be they neurological or related to mentation, and MS became attractive to researchers as the prototypical subcortical, white matter dementing process. However, first the prevalence and nature of cognitive changes had to be re-examined, using the more sensitive methods of neuropsychological testing.