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Gliomas present a complex challenge in neuro-oncology, often accompanied by the debilitating complication of epilepsy. Understanding the biological interaction and common pathways between gliomagenesis and epileptogenesis is crucial for improving the current understanding of tumorigenesis and also for developing effective management strategies. Shared genetic and molecular mechanisms, such as IDH mutations and dysregulated glutamate signaling, contribute to both tumor progression and seizure development. Targeting these pathways, such as through direct inhibition of mutant IDH enzymes or modulation of glutamate receptors, holds promise for improving patient outcomes. Additionally, advancements in surgical techniques, like supratotal resection guided by connectomics, offer opportunities for maximally safe tumor resection and enhanced seizure control. Advanced imaging modalities further aid in identifying epileptogenic foci and tailoring treatment approaches based on the tumor's metabolic characteristics. This review aims to explore the complex interplay between gliomagenesis, epileptogenesis, and neural circuit remodeling, offering insights into shared molecular pathways and innovative treatment strategies to improve outcomes for patients with gliomas and associated epilepsy.

Objective: Surgery is the mainstay of treatment for low-grade glioma (LGG)-related epilepsy. However, the goal of achieving both oncological radical resection and seizure freedom can be challenging. PET with [11C]methionine (MET) has been recently introduced in clinical practice for the management of patients with LGGs, not only to monitor the response to treatments, but also as a preoperative tool to define the metabolic tumor extent and to predict tumor grading, type, and prognosis. Still, its role in defining tumor-related epilepsy and postoperative seizure outcomes is limited. The aim of this preliminary study was to investigate the role of MET PET in defining preoperative seizure characteristics and short-term postoperative seizure control in a cohort of patients with newly diagnosed temporal lobe low-grade gliomas (tLGGs)., Methods: Patients with newly diagnosed and histologically proven temporal lobe grade 2/3 gliomas (2021 WHO CNS tumor classification) who underwent resection at the authors' institution between July 2011 and March 2021 were included in this retrospective study. MET PET images were acquired, fused with MRI scans, and qualitatively and semiquantitatively analyzed. Any eventual PET/MRI involvement of the temporomesial area, seizure characteristics, and 1-year seizure outcomes were reported., Results: A total of 52 patients with tLGGs met the inclusion criteria. MET PET was positive in 41 (79%) patients, with a median metabolic tumor volume of 14.56 cm3 (interquartile range [IQR] 6.5-28.2 cm3). The median maximum and mean tumor-to-background ratio (TBRmax, TBRmean) were 2.24 (IQR 1.58-2.86) and 1.53 (IQR 1.37-1.70), respectively. The metabolic tumor volume was found to be related to the presence of seizures at disease onset, but only in noncodeleted tumors (p = 0.014). Regarding patients with uncontrolled seizures at surgery, only the temporomesial area PET involvement showed a statistical correlation both in the univariate (p = 0.058) and in the multivariate analysis (p = 0.030). At 1-year follow-up, seizure control was correlated with MET PET-derived semiquantitative data. Particularly, higher TBRmax (p = 0.0192) and TBRmean (p = 0.0128) values were statistically related to uncontrolled seizures 1 year after surgery., Conclusions: This preliminary study suggests that MET PET may be used as a preoperative tool to define seizure characteristics and outcomes in patients with tLGGs. These findings need to be further validated in larger series with longer epileptological follow-ups.