Abstract

BackgroundThe purpose of this study was to explore if administration of N-acetyl-cysteine (NAC) in patients with multiple sclerosis (MS) resulted in altered cerebral blood flow (CBF) based on Arterial Spin Labeling (ASL) magnetic resonance imaging (MRI). MethodsTwenty-three patients with mild to moderate MS, (17 relapsing remitting and 6 primary progressive) were randomized to either NAC plus standard of care (N = 11), or standard of care only (N = 12). The experimental group received NAC intravenously (50 mg/kg) once per week and orally (500mg 2x/day) the other six days. Patients in both groups were evaluated initially and after 2 months (of receiving the NAC or waitlist control) with ASL MRI to measure CBF. Clinical symptom questionnaires were also completed at both time points. ResultsThe CBF data showed significant differences in several brain regions including the pons, midbrain, left temporal and frontal lobe, left thalamus, right middle frontal lobe and right temporal/hippocampus (p < 0.001) in the MS group after treatment with NAC, when compared to the control group. Self-reported scores related to cognition and attention were also significantly improved in the NAC group as compared to the control group. ConclusionsThe results of this study suggest that NAC administration alters resting CBF in MS patients, and this is associated with qualitative improvements in cognition and attention. Given these findings, large scale efficacy studies will be of value to determine the potential clinical impact of NAC over the course of illness in patients with MS, as well as the most effective dosages and differential effects across subpopulations.

Highlights

  • Multiple sclerosis (MS) is a chronic neurological disorder characterized by focal lesions of autoimmune-mediated demyelination and inflammation in the CNS

  • Patients were excluded if they had any of the following: any structural intracranial abnormalities that would prevent the analysis software from performing accurately; and any medical, neurological, or psychiatric disorder that could reasonably be expected to interfere with the assessment of multiple sclerosis (MS) symptoms, or with any of the study assessments including the resting Arterial Spin Labeling (ASL) imaging to measure cerebral blood flow (CBF)

  • There were significant improvements in the MHI cognition scores in the NAC group compared to controls (NAC increased or improved by a mean of 8.611 while control group decreased by a mean of 3.056; p < 0.05) and the PDQ attention scores (NAC decreased or improved by a mean of 1.417 while the control group increased 0.917; p < 0.05)

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Summary

Introduction

Multiple sclerosis (MS) is a chronic neurological disorder characterized by focal lesions of autoimmune-mediated demyelination and inflammation in the CNS. These interventions, if effective, may improve brain function and restore neuronal function [10]. Conclusions: The results of this study suggest that NAC administration alters resting CBF in MS patients, and this is associated with qualitative improvements in cognition and attention. Given these findings, large scale efficacy studies will be of value to determine the potential clinical impact of NAC over the course of illness in patients with MS, as well as the most effective dosages and differential effects across subpopulations

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