Pascuzzo Riccardo, Rudà Roberta, Barker Peter B, Xiang Jianwei, Antelmi Luigi, Gianeri Ruben, Pellerino Alessia, Mo Francesca, Soffietti Riccardo, Bizzi Alberto
Neuroradiology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Division of Neuro-Oncology, Department of Neuroscience, University of Turin, Turin, Italy.
Neurooncol Adv. 2025 Aug 20;7(1):vdaf155. doi: 10.1093/noajnl/vdaf155. eCollection 2025 Jan-Dec.
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 (H-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.
We conducted a prospective study involving 23 glioma patients (15 with, 8 without seizures), who underwent single-voxel H-MRS using the MEGA-PRESS sequence. H-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 H-MRS data in a subset of 10 patients were also acquired.
At first study, the Glx/GABA ratio was significantly higher in the tumor/peritumoral tissue of patients with seizures compared to those without ( = .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.
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. H-MRS may provide non-invasive biomarkers for identifying neurotransmitter dysregulation in glioma-related epilepsy.
异柠檬酸脱氢酶（IDH）突变型胶质瘤患者常出现癫痫发作，这严重影响他们的生活质量和预后。癫痫活动可能是肿瘤周围组织中兴奋性（谷氨酸，Glu）和抑制性（γ-氨基丁酸，GABA）神经递质失调的结果。利用质子磁共振波谱（H-MRS）对Glu（与谷氨酰胺合称，称为Glx）和GABA进行无创测量是可行的。本研究的目的是确定与无癫痫发作的患者相比，有癫痫发作的IDH突变型胶质瘤患者的Glx和GABA水平是否发生改变。
我们进行了一项前瞻性研究，纳入23例胶质瘤患者（15例有癫痫发作，8例无癫痫发作），这些患者使用MEGA-PRESS序列进行单体素H-MRS检查。从肿瘤/肿瘤周围区域以及用作对照的顶叶皮质的组织体积中收集H-MRS数据。分析代谢物比率（Glx/Cr、GABA/Cr、Glx/GABA），并将其与癫痫发作情况及其他临床病理参数相关联。还获取了10例患者亚组的纵向H-MRS数据。
在首次研究时，有癫痫发作的患者肿瘤/肿瘤周围组织中的Glx/GABA比率显著高于无癫痫发作的患者（P = 0.023）。纵向数据证实了这一发现，显示有癫痫发作的患者Glx/GABA值持续升高。此外，服用两种或更多抗癫痫药物的患者肿瘤周围区域的Glx/GABA比率显著更高，而GABA/Cr比率更低。
有癫痫发作的胶质瘤患者肿瘤/肿瘤周围组织中Glx和GABA的平衡发生改变，支持神经递质失衡导致癫痫活动的假说。H-MRS可能为识别胶质瘤相关癫痫中的神经递质失调提供无创生物标志物。
