Cognitive Impairment and Brain Reorganization in MS: Underlying Mechanisms and the Role of Neurorehabilitation.

Multiple sclerosis (MS) is a chronic, immune-mediated, inflammatory, and degenerative disease of the central nervous system (CNS) that affects both white and gray matter. Various mechanisms throughout its course, mainly regarding gray matter lesions and brain atrophy, result in cognitive network dysfunction and can cause clinically significant cognitive impairment in roughly half the persons living with MS. Altered cognition is responsible for many negative aspects of patients' lives, independently of physical disability, such as higher unemployment and divorce rates, reduced social activities, and an overall decrease in quality of life. Despite its devastating impact it is not included in clinical ratings and decision making in the way it should be. It is interesting that only half the persons with MS exhibit cognitive dysfunction, as this implies that the other half remain cognitively intact. It appears that a dynamic balance between brain destruction and brain reorganization is taking place. This balance acts in favor of keeping brain systems functioning effectively, but this is not so in all cases, and the effect does not last forever. When these systems collapse, functional brain reorganization is not effective anymore, and clinically apparent impairments are evident. It is therefore important to reveal which factors could make provision for the subpopulation of patients in whom cognitive impairment occurs. Even if we manage to detect this subpopulation earlier, effective pharmaceutical treatments will still be lacking. Nevertheless, recent evidence shows that cognitive rehabilitation and neuromodulation, using non-invasive techniques such as transcranial magnetic or direct current stimulation, could be effective in cognitively impaired patients with MS. In this Mini Review, we discuss the mechanisms underlying cognitive impairment in MS. We also focus on mechanisms of reorganization of cognitive networks, which occur throughout the disease course. Finally, we review theoretical and practical issues of neurorehabilitation and neuromodulation for cognition in MS as well as factors that influence them and prevent them from being widely applied in clinical settings.