Association of Cortical Lesions With Regional Glutamate, GABA, N -Acetylaspartate, and Myoinositol Levels in Patients With Multiple Sclerosis.

Autor:	Madsen MA; From the Danish Research Centre for Magnetic Resonance (M.A.M., M.P., V.W., H.L., H.R.S.), Copenhagen University Hospital - Amager and Hvidovre; Department of Health Technology (H.L.), Technical University of Denmark, Kgs. Lyngby; Danish Multiple Sclerosis Center (M.B., J.R.C., F.S.), Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Glostrup; Department of Neurology (H.R.S.), Copenhagen University Hospital - Bispebjerg and Frederiksberg; and Department of Clinical Medicine (F.S., H.R.S.), Faculty of Health and Medical Sciences, University of Copenhagen, Denmark., Považan M; From the Danish Research Centre for Magnetic Resonance (M.A.M., M.P., V.W., H.L., H.R.S.), Copenhagen University Hospital - Amager and Hvidovre; Department of Health Technology (H.L.), Technical University of Denmark, Kgs. Lyngby; Danish Multiple Sclerosis Center (M.B., J.R.C., F.S.), Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Glostrup; Department of Neurology (H.R.S.), Copenhagen University Hospital - Bispebjerg and Frederiksberg; and Department of Clinical Medicine (F.S., H.R.S.), Faculty of Health and Medical Sciences, University of Copenhagen, Denmark., Wiggermann V; From the Danish Research Centre for Magnetic Resonance (M.A.M., M.P., V.W., H.L., H.R.S.), Copenhagen University Hospital - Amager and Hvidovre; Department of Health Technology (H.L.), Technical University of Denmark, Kgs. Lyngby; Danish Multiple Sclerosis Center (M.B., J.R.C., F.S.), Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Glostrup; Department of Neurology (H.R.S.), Copenhagen University Hospital - Bispebjerg and Frederiksberg; and Department of Clinical Medicine (F.S., H.R.S.), Faculty of Health and Medical Sciences, University of Copenhagen, Denmark., Lundell H; From the Danish Research Centre for Magnetic Resonance (M.A.M., M.P., V.W., H.L., H.R.S.), Copenhagen University Hospital - Amager and Hvidovre; Department of Health Technology (H.L.), Technical University of Denmark, Kgs. Lyngby; Danish Multiple Sclerosis Center (M.B., J.R.C., F.S.), Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Glostrup; Department of Neurology (H.R.S.), Copenhagen University Hospital - Bispebjerg and Frederiksberg; and Department of Clinical Medicine (F.S., H.R.S.), Faculty of Health and Medical Sciences, University of Copenhagen, Denmark., Blinkenberg M; From the Danish Research Centre for Magnetic Resonance (M.A.M., M.P., V.W., H.L., H.R.S.), Copenhagen University Hospital - Amager and Hvidovre; Department of Health Technology (H.L.), Technical University of Denmark, Kgs. Lyngby; Danish Multiple Sclerosis Center (M.B., J.R.C., F.S.), Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Glostrup; Department of Neurology (H.R.S.), Copenhagen University Hospital - Bispebjerg and Frederiksberg; and Department of Clinical Medicine (F.S., H.R.S.), Faculty of Health and Medical Sciences, University of Copenhagen, Denmark., Romme Christensen J; From the Danish Research Centre for Magnetic Resonance (M.A.M., M.P., V.W., H.L., H.R.S.), Copenhagen University Hospital - Amager and Hvidovre; Department of Health Technology (H.L.), Technical University of Denmark, Kgs. Lyngby; Danish Multiple Sclerosis Center (M.B., J.R.C., F.S.), Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Glostrup; Department of Neurology (H.R.S.), Copenhagen University Hospital - Bispebjerg and Frederiksberg; and Department of Clinical Medicine (F.S., H.R.S.), Faculty of Health and Medical Sciences, University of Copenhagen, Denmark., Sellebjerg F; From the Danish Research Centre for Magnetic Resonance (M.A.M., M.P., V.W., H.L., H.R.S.), Copenhagen University Hospital - Amager and Hvidovre; Department of Health Technology (H.L.), Technical University of Denmark, Kgs. Lyngby; Danish Multiple Sclerosis Center (M.B., J.R.C., F.S.), Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Glostrup; Department of Neurology (H.R.S.), Copenhagen University Hospital - Bispebjerg and Frederiksberg; and Department of Clinical Medicine (F.S., H.R.S.), Faculty of Health and Medical Sciences, University of Copenhagen, Denmark., Siebner HR; From the Danish Research Centre for Magnetic Resonance (M.A.M., M.P., V.W., H.L., H.R.S.), Copenhagen University Hospital - Amager and Hvidovre; Department of Health Technology (H.L.), Technical University of Denmark, Kgs. Lyngby; Danish Multiple Sclerosis Center (M.B., J.R.C., F.S.), Department of Neurology, Copenhagen University Hospital - Rigshospitalet, Glostrup; Department of Neurology (H.R.S.), Copenhagen University Hospital - Bispebjerg and Frederiksberg; and Department of Clinical Medicine (F.S., H.R.S.), Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
Jazyk:	angličtina
Zdroj:	Neurology [Neurology] 2024 Jul; Vol. 103 (1), pp. e209543. Date of Electronic Publication: 2024 Jun 13.
DOI:	10.1212/WNL.0000000000209543
Abstrakt:	Background and Objectives: Cortical lesions contribute to disability in multiple sclerosis (MS), but their impact on regional neurotransmitter levels remains to be clarified. We tested the hypothesis that cortical lesions are associated with regional glutamate and gamma-aminobutyric acid (GABA) concentrations within the affected cortical region. Methods: In this cross-sectional study, we used structural 7T MRI to segment cortical lesions and 7T proton MR-spectroscopy of the bilateral sensorimotor hand areas to quantify regional GABA, glutamate, N -acetylaspartate, and myoinositol concentrations in patients with MS (inclusion criteria: diagnosis of relapsing-remitting [RR] or secondary progressive MS [SPMS]; age 18-80 years) and age and sex-matched healthy controls. Data were collected at a single center between August 2018 and September 2020. Linear mixed-effects models were used to test for associations between metabolite concentrations and cortical lesion volumes within the same MR-spectroscopy voxel. Results: Forty-seven patients with MS (34 RRMS, 13 SPMS; 45.1 ± 12.5 years; 31 women) and 23 healthy controls (44.4 ± 13 years, 15 women) were studied. In patients, higher regional glutamate and lower regional GABA concentrations were associated with larger cortical lesion volume within the MR-spectroscopy voxel [glutamate: 0.61 (95% CI 0.19-1.03) log(mm 3 ), p = 0.005, GABA: -0.71 (-1.24 to -0.18) log(mm 3 ), p = 0.01]. In addition, lower N -acetylaspartate levels [-0.37 (-0.67 to -0.07) log(mm 3 ), p = 0.016] and higher myoinositol levels [0.48 (0.03-0.93) log(mm 3 ), p = 0.037] were associated with a larger regional cortical lesion volume. Furthermore, glutamate concentrations were reduced in patients with SPMS compared with healthy participants [-0.75 (-1.3 to -0.19) mM, p = 0.005] and patients with RRMS [-0.55 (-1.07 to -0.02) mM, p = 0.04]. N -acetylaspartate levels were lower in both patients with RRMS [-0.81 (-1.39 to -0.24) mM, p = 0.003] and SPMS [-1.31 (-2.07 to -0.54) mM, p < 0.001] when compared with healthy controls. Creatine-normalized N -acetylaspartate levels were associated with performance in the 9-hole peg test of the contralateral hand [-0.004 (-0.007 to -0.002) log(s), p = 0.002], and reduced mean creatine-normalized glutamate was associated with increased Expanded Disability Status Scale (R = -0.39, p = 0.02). Discussion: Cortical lesions are associated with local increases in glutamate and a reduction in GABA concentration within the lesional or perilesional tissue. Further studies are needed to investigate the causal relationship between cortical lesions and changes in neurotransmitter concentrations.
Databáze:	MEDLINE
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