title: Tumoral epileptogenicity: how does it happen?
abstract: Gliomas are the most frequent primary brain tumors and most glioma patients have seizures. The origin and mechanisms of human glioma-related epilepsy are multifactorial and an intermix of oncologic and neuronal processes. In this brief review, we show that the infiltrated peritumoral neocortex appears to be the key structure for glioma-related epileptic activity, which depends on the interactions between the tumor per se and the surrounding brain. We shed light on the underlying mechanisms from two different "tumorocentric" and "epileptocentric" approaches, with a special emphasis on the glioma-related glutamatergic and γ-aminobutyric acid (GABA)ergic changes leading to epileptogenicity. Because gliomas use the neurotransmitter glutamate as a "tumor growth factor" to enhance glioma cell proliferation and invasion with neurotoxic, proinvasive, and proliferative effects, glutamate homeostasis is impaired, with elevated extracellular glutamate concentrations. Such excitatory effects contribute to the generation of epileptic activity in the peritumoral neocortex. GABAergic signaling is also involved both in tumor growth and in paradoxical excitatory effects mediated by alterations in neuronal and tumor cell Cl(-) homeostasis related to cotransporter changes. Local excitability may also be affected by an increase in extracellular K(+) concentration, the alkalization of peritumoral neocortex, and alterations of gap-junction functioning. Finally, the tumor itself may mechanically affect locally neuronal behavior, connections, and networks. Better understanding of glioma-related oncologic and epileptologic processes are crucial for development of combined therapeutic strategies, but so far, the surgical management of gliomas should comprise a maximally safe surgical resection encompassing peritumoral neocortex.
authors: Neurosurgery Unit, Sainte-Anne Hospital, Paris, France; Paris Descartes University, Paris, France.
authors: Johan
authors: J
authors: Pallud
authors: Laurent
authors: L
authors: Capelle
authors: Gilles
authors: G
authors: Huberfeld
mesh_terms: D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000150:complications*; D004827:Epilepsy / Q000209:etiology*; D005910:Glioma / Q000150:complications*; D006801:Humans
keywords: Chloride; Epilepsy; GABA; Glioma; Glutamate