Prospects for the use of perampanel in the treatment of epilepsy in patients with malignant gliomas of the brain

Abstract

Epilepsy occurs in 35–95% of patients with low-grade malignant cerebral gliomas and in 29–71% of patients with high-grade gliomas. Seizures can be the first manifestation of a malignant cerebral glioma or may develop in the postoperative period and during chemoradiation therapy. This necessitates the use of antiepileptic drugs that can control seizures, ensure seizure prevention, and provide secondary seizure prophylaxis without reducing the effectiveness of anticancer therapy or the patient’s quality of life. The processes of epileptogenesis and oncogenesis are closely interrelated through common developmental mechanisms, with glutamate playing a key role. Increased glutamate secretion is accompanied by elevated expression and activation of its receptors, which raises seizure susceptibility. This is associated with increased levels of brain-derived neurotrophic factor, the number of synapses between peritumoral neurons and glioma cells, and the expression of various growth factors, all of which contribute to tumor progression. In this context, special attention is given to perampanel, a glutamate receptor antagonist and third-generation antiepileptic drug, in the treatment of epilepsy in patients with malignant cerebral gliomas. It has been shown that perampanel not only effectively controls seizures in patients with malignant cerebral gliomas but also suppresses tumor progression. Perampanel can dose-dependently enhance apoptosis and disrupt cell migration in malignant glioma cell lines. A synergistic effect of perampanel in combination with temozolamide has been identified. During chemoradiation therapy, perampanel exerts a protective effect on healthy peritumoral tissues. Adverse drug reactions associated with perampanel use are infrequent and mild. Further research is needed to investigate the anticonvulsant and antitumor efficacy of perampanel for the treatment of epilepsy in patients with malignant brain tumors.

Keywords

perampanel / epilepsy / malignant cerebral gliomas / glioblastoma / antitumour activity / temozolamide

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