Extracellular Glutamate, Glutamine, and GABA in the Hippocampus and Cortex of Refractory Epilepsy Patients

EXTRACELLULAR GLUTAMATE, GLUTAMINE, AND GABA IN THE HIPPOCAMPUS AND CORTEX OF REFRACTORY EPILEPSY PATIENTS. Jonathan C. Romanyshyn and Idil Cavus MD, PhD. Departments of Psychiatry and Neurosurgery, Yale University School of Medicine, New Haven, CT. Antiepileptic drug (AED) resistance affects one third of patients with epilepsy and is associated with significant disability. Brain microdialysis studies on the epileptogenic hippocampus of patients with medication refractory epilepsy have identified elevations in extracellular glutamate, the primary brain excitatory neurotransmitter, both acutely during seizures and chronically during the interictal periods. Whether extracellular glutamate, along with the metabolites glutamine and the inhibitory neurotransmitter GABA (gamma-aminobutyric acid), are elevated in other cortical regions is unknown. In addition, the effect of the administration of AEDs on the extracellular levels of these neurochemicals in patients with medication-refractory epilepsy is also unknown. Microdialysis samples were obtained from probes coupled to the EEG depth electrodes and implanted in the cortex and hippocampus of 81 awake patients with medication-refractory epilepsy undergoing intracranial electroencephalographic (EEG) monitoring. Probes were classified according to location and seizure activity into cortical or hippocampal non-epileptic, epileptogenic, propagated, non-localized or lesion sites. Samples were collected during the interictal period, in all subjects on their full AED dose during the first couple of days of their hospitalization, and then again (in a subset of 38