N-acetyl Cysteine Administration Is Associated With Increased Cerebral Glucose Metabolism in Patients With Multiple Sclerosis: An Exploratory Study

Background: Multiple Sclerosis (MS) is an autoimmune disease marked by progressive neurocognitive injury. Treatment options affording neuroprotective effects remain largely experimental. The purpose of this proof of concept study was to explore the effects of N-acetyl-cysteine (NAC) on cerebral gluc...

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Main Authors: Daniel A. Monti, George Zabrecky, Thomas P. Leist, Nancy Wintering, Anthony J. Bazzan, Tingting Zhan, Andrew B. Newberg
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-02-01
Series:Frontiers in Neurology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fneur.2020.00088/full
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spelling doaj-8c2c2f9bb2ee4056b70cc1b42103811a2020-11-25T02:26:55ZengFrontiers Media S.A.Frontiers in Neurology1664-22952020-02-011110.3389/fneur.2020.00088496982N-acetyl Cysteine Administration Is Associated With Increased Cerebral Glucose Metabolism in Patients With Multiple Sclerosis: An Exploratory StudyDaniel A. Monti0George Zabrecky1Thomas P. Leist2Nancy Wintering3Anthony J. Bazzan4Tingting Zhan5Andrew B. Newberg6Andrew B. Newberg7Department of Integrative Medicine and Nutritional Sciences, Marcus Institute of Integrative Health, Thomas Jefferson University, Philadelphia, PA, United StatesDepartment of Integrative Medicine and Nutritional Sciences, Marcus Institute of Integrative Health, Thomas Jefferson University, Philadelphia, PA, United StatesDepartment of Neurology, Thomas Jefferson University, Philadelphia, PA, United StatesDepartment of Integrative Medicine and Nutritional Sciences, Marcus Institute of Integrative Health, Thomas Jefferson University, Philadelphia, PA, United StatesDepartment of Integrative Medicine and Nutritional Sciences, Marcus Institute of Integrative Health, Thomas Jefferson University, Philadelphia, PA, United StatesDivision of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, PA, United StatesDepartment of Integrative Medicine and Nutritional Sciences, Marcus Institute of Integrative Health, Thomas Jefferson University, Philadelphia, PA, United StatesDivision of Nuclear Medicine, Department of Radiology, Thomas Jefferson University, Philadelphia, PA, United StatesBackground: Multiple Sclerosis (MS) is an autoimmune disease marked by progressive neurocognitive injury. Treatment options affording neuroprotective effects remain largely experimental. The purpose of this proof of concept study was to explore the effects of N-acetyl-cysteine (NAC) on cerebral glucose metabolism (CMRGlu) and symptoms in patients with multiple sclerosis (MS).Methods: Twenty-four patients with MS were randomized to either NAC plus standard of care, or standard of care only (waitlist control). The experimental group received NAC intravenously once per week and orally the other 6 days. Patients in both groups were evaluated at baseline and after 2 months (of receiving the NAC or waitlist control period) with an integrated Position Emission Tomography (PET)/ Magnetic Resonance Imaging (MRI) scanner, using 18F Fluorodeoxyglucose (FDG) to measure cerebral glucose metabolism. Following imaging evaluation at 2 months, subjects initially attributed to the standard of care arm were eligible for treatment with NAC. Clinical and symptom questionnaires were also completed initially and after 2 months.Results: The FDG PET data showed significantly increased cerebral glucose metabolism in several brain regions including the caudate, inferior frontal gyrus, lateral temporal gyrus, and middle temporal gyrus (p < 0.05) in the MS group treated with NAC, as 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 positively affects cerebral glucose metabolism in MS patients, which is associated with qualitative, patient reported improvements in cognition and attention. Larger scale studies may help to determine the clinical impact of NAC on measures of functioning over the course of illness, as well as the most effective dosage and dosage regimen.https://www.frontiersin.org/article/10.3389/fneur.2020.00088/fullN-acetyl cysteineantioxidantmultiple sclerosiscerebral glucose metabolismpositron emission tomographycognition
collection DOAJ
language English
format Article
sources DOAJ
author Daniel A. Monti
George Zabrecky
Thomas P. Leist
Nancy Wintering
Anthony J. Bazzan
Tingting Zhan
Andrew B. Newberg
Andrew B. Newberg
spellingShingle Daniel A. Monti
George Zabrecky
Thomas P. Leist
Nancy Wintering
Anthony J. Bazzan
Tingting Zhan
Andrew B. Newberg
Andrew B. Newberg
N-acetyl Cysteine Administration Is Associated With Increased Cerebral Glucose Metabolism in Patients With Multiple Sclerosis: An Exploratory Study
Frontiers in Neurology
N-acetyl cysteine
antioxidant
multiple sclerosis
cerebral glucose metabolism
positron emission tomography
cognition
author_facet Daniel A. Monti
George Zabrecky
Thomas P. Leist
Nancy Wintering
Anthony J. Bazzan
Tingting Zhan
Andrew B. Newberg
Andrew B. Newberg
author_sort Daniel A. Monti
title N-acetyl Cysteine Administration Is Associated With Increased Cerebral Glucose Metabolism in Patients With Multiple Sclerosis: An Exploratory Study
title_short N-acetyl Cysteine Administration Is Associated With Increased Cerebral Glucose Metabolism in Patients With Multiple Sclerosis: An Exploratory Study
title_full N-acetyl Cysteine Administration Is Associated With Increased Cerebral Glucose Metabolism in Patients With Multiple Sclerosis: An Exploratory Study
title_fullStr N-acetyl Cysteine Administration Is Associated With Increased Cerebral Glucose Metabolism in Patients With Multiple Sclerosis: An Exploratory Study
title_full_unstemmed N-acetyl Cysteine Administration Is Associated With Increased Cerebral Glucose Metabolism in Patients With Multiple Sclerosis: An Exploratory Study
title_sort n-acetyl cysteine administration is associated with increased cerebral glucose metabolism in patients with multiple sclerosis: an exploratory study
publisher Frontiers Media S.A.
series Frontiers in Neurology
issn 1664-2295
publishDate 2020-02-01
description Background: Multiple Sclerosis (MS) is an autoimmune disease marked by progressive neurocognitive injury. Treatment options affording neuroprotective effects remain largely experimental. The purpose of this proof of concept study was to explore the effects of N-acetyl-cysteine (NAC) on cerebral glucose metabolism (CMRGlu) and symptoms in patients with multiple sclerosis (MS).Methods: Twenty-four patients with MS were randomized to either NAC plus standard of care, or standard of care only (waitlist control). The experimental group received NAC intravenously once per week and orally the other 6 days. Patients in both groups were evaluated at baseline and after 2 months (of receiving the NAC or waitlist control period) with an integrated Position Emission Tomography (PET)/ Magnetic Resonance Imaging (MRI) scanner, using 18F Fluorodeoxyglucose (FDG) to measure cerebral glucose metabolism. Following imaging evaluation at 2 months, subjects initially attributed to the standard of care arm were eligible for treatment with NAC. Clinical and symptom questionnaires were also completed initially and after 2 months.Results: The FDG PET data showed significantly increased cerebral glucose metabolism in several brain regions including the caudate, inferior frontal gyrus, lateral temporal gyrus, and middle temporal gyrus (p < 0.05) in the MS group treated with NAC, as 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 positively affects cerebral glucose metabolism in MS patients, which is associated with qualitative, patient reported improvements in cognition and attention. Larger scale studies may help to determine the clinical impact of NAC on measures of functioning over the course of illness, as well as the most effective dosage and dosage regimen.
topic N-acetyl cysteine
antioxidant
multiple sclerosis
cerebral glucose metabolism
positron emission tomography
cognition
url https://www.frontiersin.org/article/10.3389/fneur.2020.00088/full
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