Elevated basal glutamate and unchanged glutamine and GABA in refractory epilepsy: Microdialysis study of 79 patients at the yale epilepsy surgery program

ObjectiveAberrant glutamate and γ‐aminobutyric acid (GABA) neurotransmission contribute to seizure generation and the epileptic state. However, whether levels of these neurochemicals are abnormal in epileptic patients is unknown. Here, we report on interictal levels of glutamate, glutamine, and GABA in epilepsy patients at seizure onset and nonepileptic sites, cortical lesions, and from patients with poorly localized neocortical epilepsies. MethodsSubjects (n = 79) were medically refractory epilepsy patients undergoing intracranial electroencephalogram evaluation. Microdialysis probes (n = 125) coupled to depth electrodes were implanted within suspected seizure onset sites and microdialysis samples were obtained during interictal periods. Glutamate, glutamine, and GABA were measured using high‐performance liquid chromatography. Probe locations were subsequently classified by consensus of expert epileptologists. ResultsGlutamate levels were elevated in epileptogenic (p = 0.03; n = 7), nonlocalized (p < 0.001), and lesional cortical sites (p < 0.001) when compared to nonepileptogenic cortex. Glutamate was also elevated in epileptogenic (p < 0.001) compared to nonepileptogenic hippocampus. There were no statistical differences in GABA or glutamine, although GABA levels showed high variability across patients and groups. InterpretationOur findings indicate that chronically elevated extracellular glutamate is a common pathological feature among epilepsies with differ...
Source: Annals of Neurology - Category: Neurology Authors: Tags: Research Article Source Type: research