Neurocognitive performance in relapsing-remitting multiple sclerosis patients is associated with metabolic abnormalities of the thalamus but not the hippocampus– GABA-edited 1H MRS study

Kantorová, Ema; Hnilicová, Petra; Bogner, Wolfgang; Grendár, Marian; Großmann, Jan; Kováčová, Slavomíra; Hečková, Eva; Strasser, Bernhard; Čierný, Daniel; Zeleňák, Kamil; Kurča, Egon

doi:10.1080/01616412.2021.1956282

Cited by 11 publications

(6 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This study proves signifi cant differences in performance of SDMT between RRMSp and CON, in accordance with previous studies (4,21,22). In agreement with other authors and our previous research, SDMT is capable to discriminate between RRMSp and CON very well (23)(24)(25)(26).…”

Section: Cognitive Dysfunction Measured By Sdmt and Its Correlation W...supporting

confidence: 93%

Information-processing speed in mildly disabled relapsing-remitting multiple sclerosis patients correlates with volumetry of optic chiasma and subcortical grey matter nuclei

Kováčová¹,

Hnilicová²,

Čierný³

et al. 2022

BLL

View full text Add to dashboard Cite

INTRODUCTION: Multiple sclerosis (MS) is an infl ammatory demyelinating disease leading not only to physical disability but also to cognitive dysfunction. The aim of our study was to test cognitive functions of MS patients with mild relapsing-remitting form and to fi nd out the relationship between cognitive functions and brain volumetry. METHODS: 52 patients (RRMSp) and 23 age-related healthy participants (CON) were enrolled. Mild disability was defi ned by mean EDSS 2.4 (≤ 4.0), and by median of disease duration 5.2 years. Cognitive status was tested using Single Digit Modality Test (SDMT). Brain volumetry was processed in FreeSurfer 2.0.0. RESULTS: RRMSp patients showed signifi cantly lower SDMT score than CON. SDMT results correlated positively with volume of thalamus, putamen and nc. caudate, and negatively with optic chiasma volume. Compared with CON, RRMSp presented with signifi cantly lower volume in left and right nc. accumbent, cuneus and insular GM, right putamen, total brain cortical grey matter (GM), white matters hypointensities, and 3 rd ventricular widths. CONCLUSION: To our best knowledge, this is the fi rst study that presents results showing a correlation of lower SDMT with higher optic chiasma volume, due to its subclinical chronic demyelination. We confi rmed that GM atrophy is involved in cognitive functions in MS (Tab.

show abstract

Section: Cognitive Dysfunction Measured By Sdmt and Its Correlation W...supporting

confidence: 93%

Information-processing speed in mildly disabled relapsing-remitting multiple sclerosis patients correlates with volumetry of optic chiasma and subcortical grey matter nuclei

Kováčová¹,

Hnilicová²,

Čierný³

et al. 2022

BLL

View full text Add to dashboard Cite

show abstract

“…41,42 Previous 3T 1 H-MRS measurements of glutamate and GABA concentrations have yielded conflicting results in MS. Elevated glutamate levels have been shown in normal appearing white matter and acute white matter lesions 43,44 , but reduced levels have also been reported. 39,45,46 Similarly, regional GABA increases 39 and decreases 38,47 have been found in mixed tissue voxels. These discrepancies may be ascribed to glutamate and GABA being difficult to reliably quantify at 3T.…”

Section: Changes In Regional Glutamate and Gaba Concentrationsmentioning

confidence: 82%

Linking cortical lesions to metabolic changes in multiple sclerosis using 7T proton MR spectroscopy

Madsen,

Považan,

Wiggermann

et al. 2023

Preprint

View full text Add to dashboard Cite

Importance: Cortical lesions contribute to disability in multiple sclerosis (MS) but their impact on regional neurotransmitter levels remains to be clarified. Objective: To test the hypothesis that cortical lesions in MS alter the regional concentrations of the main excitatory and inhibitory neurotransmitters, glutamate and gamma-aminobutyric acid (GABA), in the affected cortex. Design: Prospective, cross-sectional, observational proton MR-spectroscopy (1H-MRS) and structural MRI study at 7T. Setting: Data were collected at a single center between August 2018 and September 2020. Participants: A volunteer sample of 57 MS patients and 38 healthy participants were screened for participation in the study. 50 MS patients and 28 healthy participants were included. In the final cohort, three patients and five healthy participants were excluded due to drop out (n=6) or insufficient data-quality (n=2). Exposures: Two-voxel 7T 1H-MRS covering the right and left sensorimotor hand areas (SM1-HAND) and high-resolution structural brain 7T MRI. Main outcome: Regional concentrations of glutamate and GABA in SM1-HAND and their relation to cortical lesion volume within the MRS voxel. Results: Data from 34 relapsing remitting (RR) and 13 secondary progressive (SP)MS patients (mean +/- standard deviation, 45.1 +/- 12.5 years, 31 female) along with 23 age- and sex-matched healthy participants (44.4 +/- 13 years, 15 female) entered data-analyses. Patient data were pooled to assess the relationship between cortical lesion volume and neurotransmitter levels. Larger cortical lesion volume within SM1-HAND was associated with higher regional glutamate (0.61 +/- 0.21 log(mm3), P=0.005) and lower regional GABA (-0.71 +/- 0.27 log(mm3), P=0.01) concentration. Between-group comparison showed that glutamate concentration within the SM1-voxel was reduced in SPMS patients compared to healthy participants (-0.75 +/- 0.24 mM, P=0.004) and RRMS patients (-0.55 +/- 0.22 mM, P=0.04), while regional GABA levels did not differ among groups. Conclusion: Our results link cortical lesion load in SM1-HAND with regional glutamate and GABA levels in patients with RRMS and SPMS, showing a shift in balance between regional excitatory and inhibitory neurotransmitters towards increased excitation with increasing cortical lesion volume. Between-group comparisons provide preliminary evidence that a progressive disease course may be associated with a decrease in cortical glutamate levels.

show abstract

“…Glutamine is synthesized from glutamate and ammonia by the catalytic action of glutamine synthetase (GS) in glial cells of the brain, while it is also taken into neurons and generates glutamate and ammonia by the catalytic action of glutaminase. The glutamate-glutamine cycle is closely linked to cellular energy metabolism 56 , and ratios between neurotransmitters (GABA, glutamine and glutamate) have been used in MRS studies to probe neurological disease mechanisms and progression 59,60 . Specifically, ratios among glutamine, glutamate and aspartate have been implicated in memory function 61 , schizophrenia, depression, alcoholism and motivated performance via NAc 62 .…”

Section: Resultsmentioning

confidence: 99%

Untargeted Pixel-by-Pixel Imaging of Metabolite Ratio Pairs as a Novel Tool for Biomedical Discovery in Mass Spectrometry Imaging

Cheng,

Miller,

Southwell

et al. 2024

Preprint

View full text Add to dashboard Cite

Mass spectrometry imaging (MSI) is a powerful technology that can be employed to define the spatial distribution and relative abundance of structurally identified and yet-undefined metabolites across a tissue cryosection. While numerous software packages enable pixel-by-pixel imaging of individual metabolite distributions, the research community lacks a discovery tool that provides spatial imaging of all metabolite abundance ratio pairs. Importantly, the recognition of correlating metabolite pairs offers a strategy to discover unanticipated molecules that contribute to or regulate a shared metabolic pathway, uncover hidden metabolic heterogeneity across cells and tissue subregions, and offers a single timepoint indicator of flux through a particular metabolic pathway of interest. Here, we describe the development and implementation of an untargeted R package workflow for pixel-by-pixel imaging of ratios for all metabolites detected in an MSI experiment. Considering untargeted MSI studies of murine brain and embryogenesis, we demonstrate that ratio imaging offers the opportunity to minimize systematic data variation introduced during sample handling or due to instrument drift, markedly enhances spatial image resolution, and can serve to reveal previously unrecognized tissue regions that are metabotype-distinct. Furthermore, ratio imaging facilitates the discovery of novel regional biomarkers, and can provide anatomical information regarding the spatial distribution of metabolite-linked biochemical pathways. The algorithm described herein is generic and can be applied to any MSI dataset containing spatial information for metabolites, peptides or proteins. Importantly, this software package offers a powerful add-on tool that can significantly enhance knowledge obtained from currently employed spatial metabolite profiling technologies.

show abstract

Neurocognitive performance in relapsing-remitting multiple sclerosis patients is associated with metabolic abnormalities of the thalamus but not the hippocampus– GABA-edited 1H MRS study

Cited by 11 publications

References 41 publications

Information-processing speed in mildly disabled relapsing-remitting multiple sclerosis patients correlates with volumetry of optic chiasma and subcortical grey matter nuclei

Information-processing speed in mildly disabled relapsing-remitting multiple sclerosis patients correlates with volumetry of optic chiasma and subcortical grey matter nuclei

Linking cortical lesions to metabolic changes in multiple sclerosis using 7T proton MR spectroscopy

Untargeted Pixel-by-Pixel Imaging of Metabolite Ratio Pairs as a Novel Tool for Biomedical Discovery in Mass Spectrometry Imaging

Contact Info

Product

Resources

About