Early metabolic alterations in the normal‑appearing grey and white matter of patients with clinically isolated syndrome suggestive of multiple sclerosis: A proton MR spectroscopic study

Tzanetakos,Dimitrios; Kyrozis,Andreas; Karavasilis,Efstratios; Velonakis,Georgios; Tzartos,John S.; Toulas,Panagiotis; Sotirli,Stefania Alexia; Evdokimidis,Ioannis; Tsivgoulis,Georgios; Potagas,Constantin; Kilidireas,Costantinos; Andreadou,Elisabeth

doi:10.3892/etm.2023.12048

July-2023 Volume 26 Issue 1

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July-2023 Volume 26 Issue 1

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Article Open Access

Early metabolic alterations in the normal‑appearing grey and white matter of patients with clinically isolated syndrome suggestive of multiple sclerosis: A proton MR spectroscopic study

Authors:
- Dimitrios Tzanetakos
- Andreas Kyrozis
- Efstratios Karavasilis
- Georgios Velonakis
- John S. Tzartos
- Panagiotis Toulas
- Stefania Alexia Sotirli
- Ioannis Evdokimidis
- Georgios Tsivgoulis
- Constantin Potagas
- Costantinos Kilidireas
- Elisabeth Andreadou
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Affiliations: Second Department of Neurology, ‘Attikon’ University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece, First Department of Neurology, Eginition Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece, Research Unit of Radiology, Second Department of Radiology, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece, Second Department of Neurology, ‘Attikon’ University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece, MS Center and Other Neurodegenerative diseases, Metropolitan General Hospital, 15562 Holargos, Athens, Greece, First Department of Neurology, Eginition Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece

Copyright: © Tzanetakos et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Article Number: 349
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Published online on: May 30, 2023

https://doi.org/10.3892/etm.2023.12048
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Abstract

Proton magnetic resonance spectroscopy (¹H‑MRS) is an advanced method of examining metabolic profiles. The present study aimed to assess in vivo metabolite levels in areas of normal‑appearing grey (thalamus) and white matter (centrum semiovale) using ¹H‑MRS in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis and compare them to healthy controls (HCs). Data from 35 patients with CIS (CIS group), of which 23 were untreated (CIS‑untreated group) and 12 were treated (CIS‑treated group) with disease‑modifying‑therapies (DMTs) at the time of ¹H‑MRS, and from 28 age‑ and sex‑matched HCs were collected using a 3.0 T MRI and single‑voxel ¹H‑MRS (point resolved spectroscopy sequence; repetition time, 2,000 msec; time to echo, 35 msec). Concentrations and ratios of total N‑acetyl aspartate (tNAA), total creatine (tCr), total choline (tCho), myoinositol, glutamate (Glu), glutamine (Gln), Glu + Gln (Glx) and glutathione (Glth) were estimated in the thalamic‑voxel (th) and centrum semiovale‑voxel (cs). For the CIS group, the median duration from the first clinical attack to ¹H‑MRS was 102 days (interquartile range, 89.5.‑131.5). Compared with HCs, significantly lower Glx(cs) (P=0.014) and ratios of tCho/tCr(th) (P=0.026), Glu/tCr(cs) (P=0.040), Glx/tCr(cs) (P=0.004), Glx/tNAA(th) (P=0.043) and Glx/tNAA(cs) (P=0.015) were observed in the CIS group. No differences in tNAA levels were observed between the CIS and the HC groups; however, tNAA(cs) was higher in the CIS‑treated than in the CIS‑untreated group (P=0.028). Compared with those in HC group, decreased Glu(cs) (P=0.019) and Glx(cs) levels (P=0.014) and lower ratios for tCho/tCr(th) (P=0.015), Gln/tCr(th) (P=0.004), Glu/tCr(cs) (P=0.021), Glx/tCr(th) (P=0.041), Glx/tCr(cs) (P=0.003), Glx/tNAA(th) (P=0.030) and Glx/tNAA(cs) (P=0.015) were found in the CIS‑untreated group. The present findings showed alterations in the normal‑appearing grey and white matter of patients with CIS; moreover, the present results suggested an early indirect treatment effect of DMTs on the brain metabolic profile of these patients.

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Early metabolic alterations in the normal‑appearing grey and white matter of patients with clinically isolated syndrome suggestive of multiple sclerosis: A proton MR spectroscopic study

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