title: Elevated basal glutamate and unchanged glutamine and GABA in refractory epilepsy: Microdialysis study of 79 patients at the yale epilepsy surgery program.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Psychiatry, Yale School of Medicine, New Haven, CT.|Department of Neurosurgery, Yale School of Medicine, New Haven, CT.
authors.forename: Idil
authors.initials: I
authors.lastname: Çavuş
authors.affiliation: Department of Neurosurgery, Yale School of Medicine, New Haven, CT.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Romanyshyn
authors.affiliation: Department of Neurosurgery, Yale School of Medicine, New Haven, CT.
authors.forename: Jeremy T
authors.initials: JT
authors.lastname: Kennard
authors.affiliation: Department of Neurology, Yale School of Medicine, New Haven, CT.
authors.forename: Pue
authors.initials: P
authors.lastname: Farooque
authors.affiliation: Department of Neurosurgery, Yale School of Medicine, New Haven, CT.
authors.forename: Anne
authors.initials: A
authors.lastname: Williamson
authors.affiliation: Department of Neurosurgery, Yale School of Medicine, New Haven, CT.|Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT.
authors.forename: Tore
authors.initials: T
authors.lastname: Eid
authors.affiliation: Department of Neurology, Yale School of Medicine, New Haven, CT.
authors.forename: Susan S
authors.initials: SS
authors.lastname: Spencer
authors.affiliation: Department of Neurology, Yale School of Medicine, New Haven, CT.
authors.forename: Robert
authors.initials: R
authors.lastname: Duckrow
authors.affiliation: Yale Center for Clinical Investigation Biostatistics Unit.
authors.forename: James
authors.initials: J
authors.lastname: Dziura
authors.affiliation: Department of Neurosurgery, Yale School of Medicine, New Haven, CT.
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Spencer
mesh_terms: D000293:Adolescent; D000328:Adult; D002540:Cerebral Cortex / Q000378:metabolism*; D002648:Child; D000069279:Drug Resistant Epilepsy / Q000378:metabolism*; D004567:Electrodes, Implanted; D004569:Electroencephalography; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D017551:Microdialysis; D008875:Middle Aged; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D005973:Glutamine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid