Jameen Arm1, Georg Oeltzschner2, Oun Al-Iedani1, Rod Lea3, Jeannette Lechner-Scott4, Saadallah Ramadan5. 1. School of Health Sciences, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, 2308, Australia; Hunter Medical Research Institute, 1 Kookaburra Circuit, New Lambton, NSW, 2305, Australia. 2. The Russell H. Morgan Department of Radiology and Radiological Science, the Johns Hopkins University School of Medicine, Baltimore, MD, USA; F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore MD, USA. 3. Hunter Medical Research Institute, 1 Kookaburra Circuit, New Lambton, NSW, 2305, Australia; Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Queensland University of Technology, Brisbane, Australia. 4. Hunter Medical Research Institute, 1 Kookaburra Circuit, New Lambton, NSW, 2305, Australia; Department of Neurology, John Hunter Hospital, New Lambton Heights, Newcastle, 2305, Australia; School of Medicine and Public Health, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, 2308, Australia. 5. School of Health Sciences, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW, 2308, Australia; Hunter Medical Research Institute, 1 Kookaburra Circuit, New Lambton, NSW, 2305, Australia. Electronic address: Saadallah.ramadan@newcastle.edu.au.
Abstract
PURPOSE: Fatigue is a common symptom in patients with multiple sclerosis (MS) with unknown pathophysiology. Dysfunction of the GABAergic/glutamatergic pathways involving inhibitory and excitatory neurotransmitters such as γ-aminobutyric acid (GABA) and glutamine + glutamate pool (Glx) have been implicated in several neurological disorders. This study is aimed to evaluate the potential role of GABA and Glx in the origin of central fatigue in relapse remitting MS (RRMS) patients. METHODS: 24 RRMS patients and 16 age- and sex-matched healthy controls (HC) were scanned using Mescher-Garwood point resolved spectroscopy (MEGA-PRESS) with a 3 T system to quantify GABA+ and Glx from prefrontal (PFC) and sensorimotor (SMC) cortices. Self-reported fatigue status was measured on all participants using the Modified Fatigue Impact Scale (MFIS). RESULTS: RRMS patients had higher fatigue scores relative to HC (p ≤ 0.05). Compared to HC, Glx levels in RRMS patients were significantly decreased in SMC (p = 0.04). Significant correlations were found between fatigue scores and GABA+ (r = -0.531, p = 0.008) and Glx (r = 0.511, p = 0.018) in PFC. Physical fatigue was negatively correlated with GABA+ in SMC and PFC (r = -0.428 and -0.472 respectively, p ≤ 0.04) and positively with PFC Glx (r = 0.480, p = 0.028). CONCLUSION: The associations between fatigue and GABA + and Glx suggest that there might be dysregulation of GABAergic/glutamatergic neurotransmission in the pathophysiological mechanism of central fatigue in MS. Crown
PURPOSE: Fatigue is a common symptom in patients with multiple sclerosis (MS) with unknown pathophysiology. Dysfunction of the GABAergic/glutamatergic pathways involving inhibitory and excitatory neurotransmitters such as γ-aminobutyric acid (GABA) and glutamine + glutamate pool (Glx) have been implicated in several neurological disorders. This study is aimed to evaluate the potential role of GABA and Glx in the origin of central fatigue in relapse remitting MS (RRMS) patients. METHODS: 24 RRMS patients and 16 age- and sex-matched healthy controls (HC) were scanned using Mescher-Garwood point resolved spectroscopy (MEGA-PRESS) with a 3 T system to quantify GABA+ and Glx from prefrontal (PFC) and sensorimotor (SMC) cortices. Self-reported fatigue status was measured on all participants using the Modified Fatigue Impact Scale (MFIS). RESULTS: RRMS patients had higher fatigue scores relative to HC (p ≤ 0.05). Compared to HC, Glx levels in RRMS patients were significantly decreased in SMC (p = 0.04). Significant correlations were found between fatigue scores and GABA+ (r = -0.531, p = 0.008) and Glx (r = 0.511, p = 0.018) in PFC. Physical fatigue was negatively correlated with GABA+ in SMC and PFC (r = -0.428 and -0.472 respectively, p ≤ 0.04) and positively with PFC Glx (r = 0.480, p = 0.028). CONCLUSION: The associations between fatigue and GABA + and Glx suggest that there might be dysregulation of GABAergic/glutamatergic neurotransmission in the pathophysiological mechanism of central fatigue in MS. Crown
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