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Elevated basal glutamate and unchanged glutamine and GABA in refractory epilepsy: Microdialysis study of 79 patients at the yale epilepsy surgery program
Author(s) -
Çavuş Idil,
Romanyshyn Jonathan C.,
Kennard Jeremy T.,
Farooque Pue,
Williamson Anne,
Eid Tore,
Spencer Susan S.,
Duckrow Robert,
Dziura James,
Spencer Dennis D.
Publication year - 2016
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.24673
Subject(s) - glutamine , microdialysis , glutamate receptor , ictal , epilepsy , gabaergic , epilepsy surgery , electrocorticography , medicine , neuroscience , psychology , chemistry , amino acid , biochemistry , central nervous system , inhibitory postsynaptic potential , receptor
Objective Aberrant 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. Methods Subjects (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. Results Glutamate 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. Interpretation Our findings indicate that chronically elevated extracellular glutamate is a common pathological feature among epilepsies with different etiology. Contrary to our predictions, GABA and glutamine levels were not decreased in any of the measured areas. Whereas variability in GABA levels may in part be attributed to the use of GABAergic antiepileptic drugs, the stability in glutamine across patient groups indicate that extracellular glutamine levels are under tighter metabolic regulation than previously thought. Ann Neurol 2016;80:35–45