Altered in vivo brain GABA and glutamate levels are associated with multiple sclerosis central fatigue. Issue 137 (April 2021)

• Record Type: Journal Article
• Authors: Arm, Jameen; Oeltzschner, Georg; Al-iedani, Oun; Lea, Rod; Lechner-Scott, Jeannette; Ramadan, Saadallah
• Is Part Of: European journal of radiology. Issue 137(2021)
• Publication Date: 2021-04
• Subjects: ARCS audio recorded cognitive screen -- EDSS expanded disability status scale -- GABA γ-aminobutyric acid -- GABA+ GABA & co-edited contributions from macromolecules and homocarnosine -- Glx glutamine/glutamate -- HC healthy control -- MRS magnetic resonance spectroscopy -- MEGA-PRESS Mescher-Garwood point resolved spectroscopy -- MFIS modified fatigue impact scale -- MSSS multiple sclerosis severity score -- NAA N-acetylaspartate -- PFC prefrontal cortex -- RRMS relapse remitting multiple sclerosis -- SDMT symbol digit modalities test -- SMC sensorimotor cortex -- WMLL white matter lesion load; Magnetic resonance imaging -- Mescher-Garwood point resolved spectroscopy -- Magnetic resonance spectroscopy -- Neurometabolites -- MS fatigue; Medical radiology -- Periodicals; Radiology -- Periodicals; Radiologie médicale -- Périodiques; Medical radiology; Periodicals; 616.075705
• DOI: 10.1016/j.ejrad.2021.109610
• Languages: English
• ISSNs: 0720-048X

Abstract

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.