MR spectroscopic evidence for glial increase but not for neuro-axonal damage in MS normal-appearing white matter

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Abstract

Quantitative single-voxel, short echo-time (TE) MR spectroscopy (MRS) was used to determine metabolite concentrations in the cerebral normal-appearing white matter (NAWM) of 76 patients with multiple sclerosis (MS), and the WM of 25 controls. In NAWM of all MS disease types (primary progressive, relapsing-remitting, and secondary progressive), the concentration ratio of total N-acetyl-aspartate (tNAA)/total creatine (tCr) was decreased compared to controls. Remarkably, this was entirely due to an increase of tCr in MS patients, whereas there was no difference in tNAA. Separate quantification of the two tNAA components yielded no significant difference in NAA (N-acetyl-aspartate), while the concentration of NAAG (N-acetyl-aspartyl- glutamate) was slightly - but significantly - elevated in MS patients. Myo-inositol (Ins) was strongly increased in MS patients, and choline-containing compounds (Cho) were mildly increased. There were no metabolite differences between disease types, and no correlations with disability scores. The results are supported by measures of spectral quality, which were identical for patients and controls. In conclusion, MS NAWM containing very little perilesional tissue is characterized by increased glial cell numbers (increase of Ins and tCr) without evidence of axonal dysfunction (normal NAA). Further studies should elucidate the mechanism underlying increased NAAG in MS NAWM.

Original languageEnglish
Pages (from-to)256-266
Number of pages11
JournalMagnetic Resonance in Medicine
Volume53
Issue number2
DOIs
Publication statusPublished - 1 Feb 2005

Cite this

@article{4f2a5e008a894a5e91966b00a10fd1e5,
title = "MR spectroscopic evidence for glial increase but not for neuro-axonal damage in MS normal-appearing white matter",
abstract = "Quantitative single-voxel, short echo-time (TE) MR spectroscopy (MRS) was used to determine metabolite concentrations in the cerebral normal-appearing white matter (NAWM) of 76 patients with multiple sclerosis (MS), and the WM of 25 controls. In NAWM of all MS disease types (primary progressive, relapsing-remitting, and secondary progressive), the concentration ratio of total N-acetyl-aspartate (tNAA)/total creatine (tCr) was decreased compared to controls. Remarkably, this was entirely due to an increase of tCr in MS patients, whereas there was no difference in tNAA. Separate quantification of the two tNAA components yielded no significant difference in NAA (N-acetyl-aspartate), while the concentration of NAAG (N-acetyl-aspartyl- glutamate) was slightly - but significantly - elevated in MS patients. Myo-inositol (Ins) was strongly increased in MS patients, and choline-containing compounds (Cho) were mildly increased. There were no metabolite differences between disease types, and no correlations with disability scores. The results are supported by measures of spectral quality, which were identical for patients and controls. In conclusion, MS NAWM containing very little perilesional tissue is characterized by increased glial cell numbers (increase of Ins and tCr) without evidence of axonal dysfunction (normal NAA). Further studies should elucidate the mechanism underlying increased NAAG in MS NAWM.",
keywords = "In vivo, Metabolite concentrations, N-acetyl-aspartate, Spectral quality, White matter disease",
author = "H. Vrenken and F. Barkhof and Uitdehaag, {B. M J} and Castelijns, {J. A.} and Polman, {C. H.} and Pouwels, {P. J W}",
year = "2005",
month = "2",
day = "1",
doi = "10.1002/mrm.20366",
language = "English",
volume = "53",
pages = "256--266",
journal = "Magnetic Resonance in Medicine",
issn = "0740-3194",
publisher = "John Wiley and Sons Inc.",
number = "2",

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TY - JOUR

T1 - MR spectroscopic evidence for glial increase but not for neuro-axonal damage in MS normal-appearing white matter

AU - Vrenken, H.

AU - Barkhof, F.

AU - Uitdehaag, B. M J

AU - Castelijns, J. A.

AU - Polman, C. H.

AU - Pouwels, P. J W

PY - 2005/2/1

Y1 - 2005/2/1

N2 - Quantitative single-voxel, short echo-time (TE) MR spectroscopy (MRS) was used to determine metabolite concentrations in the cerebral normal-appearing white matter (NAWM) of 76 patients with multiple sclerosis (MS), and the WM of 25 controls. In NAWM of all MS disease types (primary progressive, relapsing-remitting, and secondary progressive), the concentration ratio of total N-acetyl-aspartate (tNAA)/total creatine (tCr) was decreased compared to controls. Remarkably, this was entirely due to an increase of tCr in MS patients, whereas there was no difference in tNAA. Separate quantification of the two tNAA components yielded no significant difference in NAA (N-acetyl-aspartate), while the concentration of NAAG (N-acetyl-aspartyl- glutamate) was slightly - but significantly - elevated in MS patients. Myo-inositol (Ins) was strongly increased in MS patients, and choline-containing compounds (Cho) were mildly increased. There were no metabolite differences between disease types, and no correlations with disability scores. The results are supported by measures of spectral quality, which were identical for patients and controls. In conclusion, MS NAWM containing very little perilesional tissue is characterized by increased glial cell numbers (increase of Ins and tCr) without evidence of axonal dysfunction (normal NAA). Further studies should elucidate the mechanism underlying increased NAAG in MS NAWM.

AB - Quantitative single-voxel, short echo-time (TE) MR spectroscopy (MRS) was used to determine metabolite concentrations in the cerebral normal-appearing white matter (NAWM) of 76 patients with multiple sclerosis (MS), and the WM of 25 controls. In NAWM of all MS disease types (primary progressive, relapsing-remitting, and secondary progressive), the concentration ratio of total N-acetyl-aspartate (tNAA)/total creatine (tCr) was decreased compared to controls. Remarkably, this was entirely due to an increase of tCr in MS patients, whereas there was no difference in tNAA. Separate quantification of the two tNAA components yielded no significant difference in NAA (N-acetyl-aspartate), while the concentration of NAAG (N-acetyl-aspartyl- glutamate) was slightly - but significantly - elevated in MS patients. Myo-inositol (Ins) was strongly increased in MS patients, and choline-containing compounds (Cho) were mildly increased. There were no metabolite differences between disease types, and no correlations with disability scores. The results are supported by measures of spectral quality, which were identical for patients and controls. In conclusion, MS NAWM containing very little perilesional tissue is characterized by increased glial cell numbers (increase of Ins and tCr) without evidence of axonal dysfunction (normal NAA). Further studies should elucidate the mechanism underlying increased NAAG in MS NAWM.

KW - In vivo

KW - Metabolite concentrations

KW - N-acetyl-aspartate

KW - Spectral quality

KW - White matter disease

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U2 - 10.1002/mrm.20366

DO - 10.1002/mrm.20366

M3 - Article

VL - 53

SP - 256

EP - 266

JO - Magnetic Resonance in Medicine

JF - Magnetic Resonance in Medicine

SN - 0740-3194

IS - 2

ER -