Glutamate to GABA ratio is elevated in patients with IDH-mutant lower-grade gliomas and seizures

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.

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.

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.

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.