Physiologic Characterization of Multiple Sclerosis and Its Clinical Implications

Multiple sclerosis (MS) is a central nervous system autoimmune disorder that features cognitive impairment as a prominent symptom in almost 70% of these patients. Little remains known about the pathophysiology of this impairment. Our understanding of mechanisms that underlie MS-related cognitive impairment mainly emerge from structural magnetic resonance imaging (sMRI) studies. Clinicians also depend on sMRI for MS diagnosis, treatment choice, and disease surveillance. These sMRI techniques, however, are limited in providing information regarding MS-related physiologic or metabolic alterations, disease origin, and the extent of underlying tissue injury. Lack of such information has hindered our ability to better understand the mechanisms that underlie cognitive impairment in MS. Such limitations often have repercussions in the management of MS and are reflected as misdiagnosis and inappropriate treatment. In this dissertation, I describe a set of studies that assess physiologic and metabolic changes in MS patients using novel functional MRI techniques. These techniques permitted me to investigate how such changes contribute to the development of MS-related cognitive impairment, and to evaluate the translational ability of such physiologic metrics to clinical practice.