Glutathione as a Predictor of Neuropsychological Impairment in Patients with Relapsing Remitting, Secondary Progressive, and Primary Progressive Multiple Sclerosis

iii Abstract Multiple sclerosis (MS) has long been characterized as an inflammatory disease of the central nervous system (CNS); however, recent research has suggested that neurodegenerative processes such as oxidative stress may be the primary force driving disease progression and associated neuropsychological impairment in this population. Recent work by our research group identified GSH, an important cerebral antioxidant, as a marker of oxidative stress-mediated neurodegeneration in patients with secondary progressive (SP) MS. However, the present study featured the first comparison of cerebral GSH concentrations among patients with RR, PP, and SP subtypes of MS and healthy controls. The primary aims of this study were to examine differences in GSH concentrations among subtypes of MS and to investigate whether reductions in GSH concentrations occurred in conjunction with neuropsychological impairments in processing speed, memory, and executive function. Results indicated that relative to RR patients, progressive (PP and SP) patients exhibited the largest reductions in GSH concentrations, with no significant differences between PP and SP patients. A similar pattern of outcomes was observed on the neuropsychological measures, with reductions in GSH being accompanied by a worsening of impairment in processing speed and a broadening of impairment to include deficits in learning and memory. These results support the hypothesis that even in the absence of inflammatory processes underlying acute clinical exacerbations, diffuse oxidative stress signals an ongoing neurodegenerative process that likely contributes to disease progression and cognitive decline over the course of the disease.