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Review
. 2024 Aug 16;25(16):8953.
doi: 10.3390/ijms25168953.

Gliomagenesis, Epileptogenesis, and Remodeling of Neural Circuits: Relevance for Novel Treatment Strategies in Low- and High-Grade Gliomas

Alessandro Grimi  1   2 , Beatrice C Bono  1   2 , Serena M Lazzarin  2 , Simona Marcheselli  2 , Federico Pessina  1   2 , Marco Riva  1   2
Affiliations
Review

Gliomagenesis, Epileptogenesis, and Remodeling of Neural Circuits: Relevance for Novel Treatment Strategies in Low- and High-Grade Gliomas

Alessandro Grimi et al. Int J Mol Sci. .

Abstract

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.

Keywords: epilepsy; epileptogenesis; glioma; gliomagenesis; neurosurgery.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Shared pathways between gliomagenesis and epileptogenesis.
Figure 2
Figure 2
Presurgical imaging (FLAIR, T1-w+c MRI, and MET–PET) of a right frontal IDH wild-type glioblastoma (WHO grade 4) surgically treated at our institution. The patient had uncontrolled seizures before surgery and underwent a supratotal resection guided by neuromonitoring (SSEP, MEP, DES, and ECoG) (A). After two years, the patient is still seizure-free, and there has not been a recurrence of the disease (B).
Figure 3
Figure 3
Mechanisms of action of AEDs with anti-tumorigenic effects.
See this image and copyright information in PMC

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