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In vivo evidence of differential frontal cortex metabolic abnormalities in progressive and relapsing-remitting multiple sclerosis

Swanberg, Kelley M LU orcid ; Prinsen, Hetty ; DeStefano, Katherine ; Bailey, Mary ; Kurada, Abhinav V ; Pitt, David ; Fulbright, Robert K and Juchem, Christoph (2021) In NMR in Biomedicine 34(11).
Abstract

The pathophysiology of progressive multiple sclerosis remains elusive, significantly limiting available disease-modifying therapies. Proton MRS (1 H-MRS) enables in vivo measurement of small molecules implicated in multiple sclerosis, but its application to key metabolites glutamate, γ-aminobutyric acid (GABA), and glutathione has been sparse. We employed, at 7 T, a previously validated 1 H-MRS protocol to measure glutamate, GABA, and glutathione, as well as glutamine, N-acetyl aspartate, choline, and myoinositol, in the frontal cortex of individuals with relapsing-remitting (N = 26) or progressive (N = 21) multiple sclerosis or healthy control adults (N = 25) in a cross-sectional analysis. Only individuals with progressive multiple... (More)

The pathophysiology of progressive multiple sclerosis remains elusive, significantly limiting available disease-modifying therapies. Proton MRS (1 H-MRS) enables in vivo measurement of small molecules implicated in multiple sclerosis, but its application to key metabolites glutamate, γ-aminobutyric acid (GABA), and glutathione has been sparse. We employed, at 7 T, a previously validated 1 H-MRS protocol to measure glutamate, GABA, and glutathione, as well as glutamine, N-acetyl aspartate, choline, and myoinositol, in the frontal cortex of individuals with relapsing-remitting (N = 26) or progressive (N = 21) multiple sclerosis or healthy control adults (N = 25) in a cross-sectional analysis. Only individuals with progressive multiple sclerosis demonstrated reduced glutamate (F2,65  = 3.424, p = 0.04; 12.40 ± 0.62 mM versus control 13.17 ± 0.95 mM, p = 0.03) but not glutamine (F2,65  = 0.352, p = 0.7; 4.71 ± 0.35 mM versus control 4.84 ± 0.42 mM), reduced GABA (F2,65  = 3.89, p = 0.03; 1.29 ± 0.23 mM versus control 1.47 ± 0.25 mM, p = 0.05), and possibly reduced glutathione (F2,65  = 0.352, p = 0.056; 2.23 ± 0.46 mM versus control 2.51 ± 0.48 mM, p < 0.1). As a group, multiple sclerosis patients demonstrated significant negative correlations between disease duration and glutamate or GABA (ρ = -0.4, p = 0.02) but not glutamine or glutathione. Alone, only relapsing-remitting multiple sclerosis patients exhibited a significant negative correlation between disease duration and GABA (ρ = -0.5, p = 0.03). Taken together, these results indicate that frontal cortex metabolism is differentially disturbed in progressive and relapsing-remitting multiple sclerosis.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Adult, Aged, Aspartic Acid/analogs & derivatives, Choline/metabolism, Female, Frontal Lobe/metabolism, Glutamine/metabolism, Glutathione/metabolism, Gray Matter/metabolism, Humans, Inositol/metabolism, Magnetic Resonance Spectroscopy, Male, Metabolome, Middle Aged, Multiple Sclerosis, Relapsing-Remitting/diagnosis, Neurotransmitter Agents/metabolism, Young Adult, gamma-Aminobutyric Acid/metabolism
in
NMR in Biomedicine
volume
34
issue
11
article number
e4590
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:85111349883
  • pmid:34318959
ISSN
0952-3480
DOI
10.1002/nbm.4590
language
English
LU publication?
no
additional info
© 2021 John Wiley & Sons, Ltd.
id
1c4b14f2-840f-4091-ae22-2c4ef364e71c
date added to LUP
2023-09-18 14:59:46
date last changed
2024-04-19 01:21:13
@article{1c4b14f2-840f-4091-ae22-2c4ef364e71c,
  abstract     = {{<p>The pathophysiology of progressive multiple sclerosis remains elusive, significantly limiting available disease-modifying therapies. Proton MRS (1 H-MRS) enables in vivo measurement of small molecules implicated in multiple sclerosis, but its application to key metabolites glutamate, γ-aminobutyric acid (GABA), and glutathione has been sparse. We employed, at 7 T, a previously validated 1 H-MRS protocol to measure glutamate, GABA, and glutathione, as well as glutamine, N-acetyl aspartate, choline, and myoinositol, in the frontal cortex of individuals with relapsing-remitting (N = 26) or progressive (N = 21) multiple sclerosis or healthy control adults (N = 25) in a cross-sectional analysis. Only individuals with progressive multiple sclerosis demonstrated reduced glutamate (F2,65  = 3.424, p = 0.04; 12.40 ± 0.62 mM versus control 13.17 ± 0.95 mM, p = 0.03) but not glutamine (F2,65  = 0.352, p = 0.7; 4.71 ± 0.35 mM versus control 4.84 ± 0.42 mM), reduced GABA (F2,65  = 3.89, p = 0.03; 1.29 ± 0.23 mM versus control 1.47 ± 0.25 mM, p = 0.05), and possibly reduced glutathione (F2,65  = 0.352, p = 0.056; 2.23 ± 0.46 mM versus control 2.51 ± 0.48 mM, p &lt; 0.1). As a group, multiple sclerosis patients demonstrated significant negative correlations between disease duration and glutamate or GABA (ρ = -0.4, p = 0.02) but not glutamine or glutathione. Alone, only relapsing-remitting multiple sclerosis patients exhibited a significant negative correlation between disease duration and GABA (ρ = -0.5, p = 0.03). Taken together, these results indicate that frontal cortex metabolism is differentially disturbed in progressive and relapsing-remitting multiple sclerosis.</p>}},
  author       = {{Swanberg, Kelley M and Prinsen, Hetty and DeStefano, Katherine and Bailey, Mary and Kurada, Abhinav V and Pitt, David and Fulbright, Robert K and Juchem, Christoph}},
  issn         = {{0952-3480}},
  keywords     = {{Adult; Aged; Aspartic Acid/analogs & derivatives; Choline/metabolism; Female; Frontal Lobe/metabolism; Glutamine/metabolism; Glutathione/metabolism; Gray Matter/metabolism; Humans; Inositol/metabolism; Magnetic Resonance Spectroscopy; Male; Metabolome; Middle Aged; Multiple Sclerosis, Relapsing-Remitting/diagnosis; Neurotransmitter Agents/metabolism; Young Adult; gamma-Aminobutyric Acid/metabolism}},
  language     = {{eng}},
  number       = {{11}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{NMR in Biomedicine}},
  title        = {{In vivo evidence of differential frontal cortex metabolic abnormalities in progressive and relapsing-remitting multiple sclerosis}},
  url          = {{http://dx.doi.org/10.1002/nbm.4590}},
  doi          = {{10.1002/nbm.4590}},
  volume       = {{34}},
  year         = {{2021}},
}