Epilepsy and diffuse low-grade gliomas

Abstract

World Health Organization diffuse low-grade gliomas (DLGGs) are highly epileptogenic primary brain tumors. Here, we will discuss the incidence and predictors of epileptic seizures and of seizure control, the pathophysiological epileptogenic mechanisms, the impact of oncological treatments on epileptic seizures, and their prognostic significance. Epileptic seizures occur in more than 90% of cases at diagnosis and their predictors are male gender, age, eloquent tumor locations and the presence of competitive other symptoms. Epileptic seizures progress together with drug resistance during the course of DLGG despite treatments and predictors of uncontrolled seizures are simple partial seizures, motor seizures, long duration from seizure onset to oncological treatment, temporal lobe, insular lobe and central area involvement. Epileptogenic foci are nested within the peritumoral neocortex infiltrated by sparse glioma cells and glioma-related epileptogenic mechanisms are multifactorial and intermixed. An excessive glutamatergic excitatory neurotransmission is induced by a high extracellular glutamate concentration resulting from a decrease in glutamate uptake and from an increase in glutamate release by glioma cells and by neighbouring non-tumor cells. An impaired GABAergic signaling is induced by reduced GABAergic inhibitory pathways and functioning and by pathological changes in neuronal chloride homeostasis that switch GABAergic signaling from hyperpolarizing to depolarizing. The short seizure duration before surgery and the extent of resection are main predictors of postoperative seizure control in DLGG and a supratotal resection encompassing the epileptogenic foci in the peripheral neocortex surrounding the DLGG can improve seizure control. Last, epileptic seizure independently impacts DLGG prognosis, as both malignant progression-free survival and overall survival are longer in patients with a history of epileptic seizures.