ArticleNeuro-oncology2022
IDH-mutated gliomas promote epileptogenesis through d-2-hydroxyglutarate-dependent mTOR hyperactivation.
Article in Neuro-oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 68 citations in OpenAlex.
- Tumor-related epilepsy and preoperative cognitive performance in glioma: a preliminary study.Journal of neuro-oncology · 2026Article
- [Journal of neuro-oncology · 2026Article
- Seizure-Related Deterioration in Treated Glioma: A Narrative Review of Nonconvulsive Status Epilepticus, Peri-Ictal Pseudoprogression, Treatment-Related Change, and True Progression.Diagnostics (Basel, Switzerland) · 2026Review
- A malignant symbiosis: The neuro-metabolic symphony rewires the tumor microenvironment.Neoplasia (New York, N.Y.) · 2026Review
- Postoperative Seizure Prophylaxis in Intracranial Tumors: Evaluating the Role of Anti-Seizure Medication in Seizure-Naïve Patients.Current neurology and neuroscience reports · 2026Review
- Metabolic Landscape and Emerging Therapeutic Potential in Pediatric and Adult Gliomas.International journal of molecular sciences · 2026Review
- Review of glioblastoma and systemic comorbidities.Frontiers in oncology · 2026Review
- Impact of healthcare disparities on the treatment and survival of patients with high-grade gliomas in Colombia: a multicenter inverse probability-weighted cohort analysis.Journal of neuro-oncology · 2025Article
- Article
- Small cell lung cancer induces synaptic scaling to alter neuronal excitability.Communications biology · 2025Article
- Review
- State of the art: glioma-associated epilepsy-bridging tumor biology and epileptogenesis.Neurological research and practice · 2025Review
- Tumor-related epilepsy in glioma: A multidisciplinary overview.Epilepsia · 2025Review
- Perioperative IDH inhibition in treatment-naive IDH-mutant glioma: a pilot trial.Nature medicine · 2025Article
- Early seizure freedom with [Epilepsia · 2025Article
- Research progress in glioma-related epilepsy (Review).Biomedical reports · 2025Article
- The excitatory milieu in glioma: Mechanisms and therapeutic avenues.Neuro-oncology · 2025Review
- The molecular landscape of glioblastoma-associated epilepsy.Journal of molecular medicine (Berlin, Germany) · 2025Review
- The role of vorasidenib in the treatment of isocitrate dehydrogenase-mutant glioma.Neuro-oncology · 2025Review
- Study protocol of short versus long-term levetiracetam in brain tumors (LIBRA): a phase 3 randomized controlled trial.BMC cancer · 2025Article
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundUncontrolled seizures in patients with gliomas have a significant impact on quality of life and morbidity, yet the mechanisms through which these tumors cause seizures remain unknown. Here, we hypothesize that the active metabolite d-2-hydroxyglutarate (d-2-HG) produced by the IDH-mutant enzyme leads to metabolic disruptions in surrounding cortical neurons that consequently promote seizures.
methodsWe use a complementary study of in vitro neuron-glial cultures and electrographically sorted human cortical tissue from patients with IDH-mutant gliomas to test this hypothesis. We utilize micro-electrode arrays for in vitro electrophysiological studies in combination with pharmacological manipulations and biochemical studies to better elucidate the impact of d-2-HG on cortical metabolism and neuronal spiking activity.
resultsWe demonstrate that d-2-HG leads to increased neuronal spiking activity and promotes a distinct metabolic profile in surrounding neurons, evidenced by distinct metabolomic shifts and increased LDHA expression, as well as upregulation of mTOR signaling. The increases in neuronal activity are induced by mTOR activation and reversed with mTOR inhibition.
conclusionTogether, our data suggest that metabolic disruptions in the surrounding cortex due to d-2-HG may be a driving event for epileptogenesis in patients with IDH-mutant gliomas.
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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.