{"doi":"10.1093/noajnl/vdaf155","title":"Glutamate to GABA ratio is elevated in patients with IDH-mutant lower-grade gliomas and seizures","abstract":"Abstract Background Patients with IDH-mutant gliomas often experience seizures that significantly affect their quality of life and outcome. Seizure activity may be the result of dysregulation of excitatory (glutamate, Glu) and inhibitory (gamma-aminobutyric acid, GABA) neurotransmitters in peritumoral tissue. A non-invasive measurement of Glu (in combination with glutamine, termed Glx) and GABA is feasible with proton magnetic resonance spectroscopy (1H-MRS). The aim of this study was to determine whether IDH-mutant glioma patients with seizures exhibit altered Glx and GABA levels compared to patients without seizures. Methods We conducted a prospective study involving 23 glioma patients (15 with, 8 without seizures), who underwent single-voxel 1H-MRS using the MEGA-PRESS sequence. 1H-MRS data were collected from volumes of tissues in the tumor/peritumoral regions and parietal cortex used as control. Metabolite ratios (Glx/Cr, GABA/Cr, Glx/GABA) were analyzed and correlated with seizure presence and other clinical-pathological parameters. Longitudinal 1H-MRS data in a subset of 10 patients were also acquired. Results At first study, the Glx/GABA ratio was significantly higher in the tumor/peritumoral tissue of patients with seizures compared to those without (P = .023). Longitudinal data confirmed this finding, showing consistently elevated Glx/GABA values in patients with seizures. Moreover, patients taking two or more antiseizure medications had significantly higher Glx/GABA ratios and lower GABA/Cr ratios in the peritumoral region. Conclusion Glioma patients with seizures have an altered balance of Glx and GABA in tumor/peritumoral tissue, supporting the hypothesis that neurotransmitter imbalances contribute to seizure activity. 1H-MRS may provide non-invasive biomarkers for identifying neurotransmitter dysregulation in glioma-related epilepsy.","journal":"Neuro-Oncology Advances","year":2025,"id":528736,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9598,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":856288,"name":"Roberta Rudà","orcid":"0000-0001-9134-1537","position":1,"is_corresponding":false},{"id":256332,"name":"Peter B. Barker","orcid":"0000-0002-6410-7793","position":2,"is_corresponding":false},{"id":1407495,"name":"Jianwei Xiang","orcid":null,"position":3,"is_corresponding":false},{"id":1407046,"name":"Luigi Antelmi","orcid":"0000-0002-4173-5412","position":4,"is_corresponding":false},{"id":1047605,"name":"Ruben Gianeri","orcid":"0000-0002-1728-2070","position":5,"is_corresponding":false},{"id":1207574,"name":"Alessia Pellerino","orcid":"0000-0003-3243-0059","position":6,"is_corresponding":false},{"id":1407047,"name":"Francesca Mo","orcid":"0000-0002-8469-7567","position":7,"is_corresponding":false},{"id":607786,"name":"Riccardo Soffietti","orcid":"0000-0002-9204-7038","position":8,"is_corresponding":false},{"id":256333,"name":"Alberto Bizzi","orcid":"0000-0002-0253-5274","position":9,"is_corresponding":false},{"id":318442,"name":"Riccardo Pascuzzo","orcid":"0000-0001-6555-1784","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:50:52.565868Z","pmid":"40893414","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}