ArticleAnnals of neurology2014
In vivo evidence of glutamate toxicity in multiple sclerosis.
Article in Annals of neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.
- Memantine for Multiple Sclerosis: A Systematic Review and Meta-Analysis of Randomized Trials.Frontiers in neurology · 2020Pooled it
- NAA is a Marker of Disability in Secondary-Progressive MS: A Proton MR Spectroscopic Imaging Study.AJNR. American journal of neuroradiology · 2020Trial
- Impaired myelination in multiple sclerosis organoids: p21 links oligodendrocyte dysfunction to disease subtype.Frontiers in cellular neuroscience · 2026Article
- Modulating glutamate neurotransmission inFrontiers in immunology · 2026Review
- Ultrafast J-resolved magnetic resonance spectroscopic imaging for high-resolution metabolic brain imaging.Nature biomedical engineering · 2025Article
- Demyelination-induced glutamatergic imbalance mediates hippocampal Hyperexcitability.Neurobiology of disease · 2025Article
- Should We Consider Neurodegeneration by Itself or in a Triangulation with Neuroinflammation and Demyelination? The Example of Multiple Sclerosis and Beyond.International journal of molecular sciences · 2024Review
- Inhibiting AMPA receptor signaling in oligodendrocytes rescues synapse loss in a model of autoimmune demyelination.iScience · 2024Article
- Association of Cortical Lesions With Regional Glutamate, GABA,Neurology · 2024Article
- Re-emergence of T lymphocyte-mediated synaptopathy in progressive multiple sclerosis.Frontiers in immunology · 2024Article
- Observational
- MicroRNA-92a-CPEB3 axis protects neurons against inflammatory neurodegeneration.Science advances · 2023Article
- Smouldering Lesion in MS: Microglia, Lymphocytes and Pathobiochemical Mechanisms.International journal of molecular sciences · 2023Review
- 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.Experimental and therapeutic medicine · 2023Article
- Glia Connect Inflammation and Neurodegeneration in Multiple Sclerosis.Neuroscience bulletin · 2023Review
- Imaging Methods Applicable in the Diagnostics of Alzheimer's Disease, Considering the Involvement of Insulin Resistance.International journal of molecular sciences · 2023Review
- CEST MRI and MALDI imaging reveal metabolic alterations in the cervical lymph nodes of EAE mice.Journal of neuroinflammation · 2022Article
- Are Neurophysiological Biomarkers Able to Discriminate Multiple Sclerosis Clinical Subtypes?Biomedicines · 2022Article
- Article
- Relaxation-Compensated Chemical Exchange Saturation Transfer MRI in the Brain at 7T: Application in Relapsing-Remitting Multiple Sclerosis.Frontiers in neurology · 2022Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveThere is increasing evidence that altered glutamate (Glu) homeostasis is involved in the pathophysiology of multiple sclerosis (MS). The aim of this study was to evaluate the in vivo effects of excess brain Glu on neuroaxonal integrity measured by N-acetylaspartate (NAA), brain volume, and clinical outcomes in a large, prospectively followed cohort of MS subjects.
methodsWe used multivoxel spectroscopy at 3T to longitudinally estimate Glu and NAA concentrations from large areas of normal-appearing white and gray matter (NAWM and GM) in MS patients (n = 343) with a mean follow-up time of 5 years. Using linear mixed-effects models, Glu was examined as a predictor of NAA decline, annualized percentage brain volume change, and evolution of clinical outcomes (Multiple Sclerosis Functional Composite [MSFC], Paced Auditory Serial Addition Test-3 [PASAT], and Expanded Disability Status Scale). Glu/NAA ratio was tested as a predictor of brain volume loss and clinical outcomes.
resultsBaseline Glu[NAWM] was predictive of accelerated longitudinal decline in NAA[GM] (-0.06mM change in NAA[GM] /yr for each unit increase in Glu; p = 0.004). The sustained elevation of Glu[NAWM] was predictive of a loss of 0.28mM/yr in NAA[NAWM] (p < 0.001) and 0.15mM/yr in NAA[GM] (p = 0.056). Each 10% increase in Glu/NAA[NAWM] was associated with a loss of 0.33% brain volume/yr (p = 0.001), 0.009 standard deviations/yr in MSFC z-score (p < 0.001), and 0.17 points/yr on the PASAT (p < 0.001).
interpretationThese results indicate that higher Glu concentrations increase the rate of NAA decline, and higher Glu/NAA[NAWM] ratio increases the rate of decline of brain volume, MSFC, and PASAT. This provides evidence of a relationship between brain Glu and markers of disease progression in MS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.