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MR spectroscopic evidence for glial increase but not for neuro-axonal damage in MS normal-appearing white matter
H Vrenken1, F Barkhof, B M J Uitdehaag
1Department of Radiology, MR Center for MS Research, VU University Medical Center, Amsterdam, The Netherlands. H.Vrenken@vumc.nl
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.
Insights
Multiple Sclerosis (MS) brain white matter shows increased glial cells, indicated by elevated myo-inositol and creatine, without axonal damage. N-acetyl-aspartate remains normal, suggesting glial activation is key in MS.
Area of Science:
- Neuroimaging
- Biochemistry
- Neurology
Background:
- Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system.
- Understanding metabolic changes in normal-appearing white matter (NAWM) is crucial for MS pathogenesis.
- Previous studies suggest white matter alterations in MS, but specific metabolite changes in NAWM require further elucidation.
Purpose of the Study:
- To quantify metabolite concentrations in the cerebral NAWM of MS patients using MR spectroscopy (MRS).
- To investigate metabolic differences between MS patients and healthy controls.
- To explore potential correlations between metabolite changes and disease characteristics.
Main Methods:
- Quantitative single-voxel, short echo-time (TE) MR spectroscopy (MRS) was employed.
- 76 patients with various MS types and 25 healthy controls were included.
- Concentrations of total N-acetyl-aspartate (tNAA), N-acetyl-aspartate (NAA), N-acetyl-aspartyl-glutamate (NAAG), total creatine (tCr), myo-inositol (Ins), and choline-containing compounds (Cho) were measured.
Main Results:
- The ratio of tNAA/tCr was decreased in MS NAWM compared to controls, driven by increased tCr, not decreased tNAA.
- NAA levels were unchanged, while NAAG was significantly elevated in MS patients.
- Myo-inositol (Ins) was strongly increased, and choline-containing compounds (Cho) were mildly increased in MS patients.
- No significant metabolite differences were observed between MS disease subtypes or correlations with disability scores.
Conclusions:
- MS NAWM is characterized by increased glial cell markers (Ins and tCr) without evidence of axonal dysfunction (normal NAA).
- Elevated NAAG in MS NAWM warrants further investigation into its underlying mechanisms.
- These findings suggest glial activation plays a significant role in MS white matter pathology.
