PET-MRI effects of N-acetylcysteine in patients with multiple sclerosis

The purpose of this study was to explore if administration of N-acetylcysteine (NAC) in patients with multiple sclerosis (MS) resulted in altered neurophysiological function as determined by the combination of functional connectivity (FC) based on resting Blood Oxygen Level Dependent (BOLD) fMRI and cerebral glucose metabolism using Fluorodeoxyglucose Positron Emission Tomography (FDG PET) and whether those changes were associated with improvements in symptoms.

Thirty-six patients with mild to moderate MS were randomized to either NAC plus standard of care, or standard of care only. The experimental group received NAC intravenously (50 mg/kg) once per week and orally (500 mg 2x/day) the other six days. Patients in both groups were evaluated initially and after 4 ± 2 months on an integrated PET-MRI platform with resting BOLD fMRI and FDG PET. Clinical symptom questionnaires were also completed at both time points.

The FC data showed significant differences in several brain regions including the inferior frontal gyrus, inferior temporal gyrus, inferior parietal gyrus, insula, cerebellum, and brain stem in the MS group after treatment with NAC. FDG PET demonstrated increased cerebral glucose metabolism in several of these structures including the inferior frontal gyrus and inferior temporal gyrus. Self-reported scores related to cognition and attention significantly correlated with these neurophysiological changes in the NAC group compared to controls.

The results of this study suggest that NAC administration alters resting functional connectivity along with cerebral glucose metabolism in MS patients, and this is associated with qualitative improvements in cognition and attention.