Research progress in glioma-related epilepsy (Review)

Abstract

Epilepsy is a frequently occurring complication in patients with gliomas that substantially impairs their quality of life. The onset of epilepsy in patients with gliomas is driven by multiple mechanisms, including tumour-induced compression of the peripheral neural network, the release of neurotransmitters and inflammatory factors by tumour cells, alterations in the tumour microenvironment, and changes in gene expression. Collectively, these factors contribute to the abnormal excitability of local neurons, ultimately triggering seizures. Seizures occur in approximately 30 to 90% of patients with glioma, with a higher incidence observed in those with low-grade gliomas. The type and frequency of seizures are closely associated with tumour characteristics, such as tumour type, location, and growth rate. The current treatment strategies for glioma-related epilepsy (GRE) primarily involve antiepileptic drugs (AEDs) and tumour-directed therapies. While AEDs are effective in managing seizures, they show limited efficacy in some patients. Efforts have increasingly focused on identifying biomarkers and elucidating the molecular mechanisms underlying GRE, with the aim of developing more targeted and effective treatment approaches. The present review provides a comprehensive overview of the latest advancements in GRE research.

Keywords: anticonvulsants; antiepileptic drugs; epilepsy; glioma; seizure; treatment.

Figure 1

Underlying mechanisms in GRE. The mechanisms underlying GRE are multifactorial and involve tumour-related changes and the TME. (A) GRE is affected by the tumour characteristics, including its location, size, and growth rate. (B) Gliomas disrupt the BBB and cause neuroinflammation to induce seizures. (C) Excitation-inhibition imbalance of glutamate and GABA in the TME induces neuronal excitation and seizures. (D) Abnormal Na⁺ and K⁺ concentrations in the TME reduce seizure thresholds. (E) The aberrant expression of enzymes and proteins in the TME drives GRE through changes in the surrounding neuronal environment. (F) Gliomas can form neurogliomal synapses, promote excitatory synapses and hyperexcitable circuit formation, thereby mediating seizures. GRE, glioma-related epilepsy; TME, tumour microenvironment; BBB, blood-brain barrier; VGLUT, vesicular glutamate transporter; EAAT, excitatory amino acid transporter; IDH, isocitrate dehydrogenase; α-KG, α-ketoglutarate; BCAA, branched-chain amino acids; BCAT1, branched chain amino acid transaminase 1; SLC7A11/xCT, solute carrier family 7 member 11; GABA, gamma-aminobutyric acid; GAT, GABA transporter; NKCC1, Na⁺-K⁺-2Cl^- co-transporter 1; KCC2, K⁺-Cl^- co-transporter 2; PTEN, phosphatase and tensin homologue; TP53, tumour protein 53; NF1, neurofibromin 1; MGMT, methylguanine methyltransferase; ADK, adenosine kinase; ADA, adenosine deaminase; IDHmut, IDH-mutated; D-2HG, D-2-hydroxyglutarate; mTOR, mammalian target of rapamycin. The figure was created using BioRender (https://www.biorender.com/).