N-acetyl cysteine administration affects cerebral blood flow as measured by arterial spin labeling MRI in patients with multiple sclerosis

Shiva Shahrampour, Justin Heholt, Andrew Wang, Faezeh Vedaei, Feroze B Mohamed, Mahdi Alizadeh, Ze Wang, George Zabrecky, Nancy Wintering, Anthony J Bazzan, Thomas P Leist, Daniel A Monti, Andrew B Newberg, Shiva Shahrampour, Justin Heholt, Andrew Wang, Faezeh Vedaei, Feroze B Mohamed, Mahdi Alizadeh, Ze Wang, George Zabrecky, Nancy Wintering, Anthony J Bazzan, Thomas P Leist, Daniel A Monti, Andrew B Newberg

Abstract

Background: The 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).

Methods: Twenty-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.

Results: The 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.

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.

Keywords: Antioxidant; Arterial spin labeling MRI; Cerebral blood flow; Cognition; Multiple sclerosis; N-acetyl cysteine; NAC.

Conflict of interest statement

The authors declare no conflict of interest.

© 2021 The Author(s).

Figures

Figure 1
Figure 1
Panel A (top row) shows the comparison of the pre (left) and post (right) scan of an MS patient in the NAC group demonstrating a marked increase in global CBF after two months of receiving NAC. Panel B (bottom row) shows the comparison of the pre (left) and post (right) scan of a control patient revealing a decrease in global CBF during the waitlist period.

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