The initial cognitive studies in MS were concerned with establishing the prevalence and nature of the deficits. Once these objectives had largely been attained, attention could be directed at other areas such as the pathogenesis, natural history, clinical significance and treatment of cognitive difficulties. This chapter will review the findings relating to one of these aspects, namely the natural history of cognitive decline in MS, and attempt to answer the following questions. How early in the illness does cognitive dysfunction become apparent? How do these changes progress over the years or, indeed, do they progress? With MS frequently running a relapsing–remitting course characterized by disease exacerbations and variable degrees of recovery, how do these changes affect cognition?

The onset of cognitive dysfunction

Canter (1951) had shown that a general decline in intellect occurred within four years of developing MS. However, it was unclear whether cognitive decline coincided with the onset of neurological symptoms or at some point thereafter. In addition, the limited scope of his psychometric battery and the paucity of objective measures of neurological disease curtails the study's conclusions.

Clinically isolated syndromes of the type seen in multiple sclerosis

In order to assess how early cognitive abnormalities become apparent, research has been directed at patients with clinically isolated syndromes (CIS) of the type seen in MS. These syndromes may present as optic neuritis, brainstem or spinal cord syndromes (Ch. 1).