Impaired Brain Metabolic Networks: Changes in Extracellular Glutamate, Glutamine, GABA in Drug-Resistant Epilepsy Patients
Abstract number :
1.508
Submission category :
2. Translational Research / 2A. Human Studies
Year :
2023
Submission ID :
1312
Source :
www.aesnet.org
Presentation date :
12/2/2023 12:00:00 AM
Published date :
Authors :
Presenting Author: Idil Cavus, MD, PhD – Neurosurgery Dept, Yale University
Dennis Spencer, MD – Harvey and Kate Cushing Professor Emeritus, Director Epilepsy Surgery, Neurosurgery, Yale University; Sharona Ben-Haim, MD – Director, Epilepsy Surgery, Neurosurgery, University of California, San Diego, CA; Tore Eid, MD, PhD – Laboratory Medicine – Yale University; Robert Duckrow, MD – Neurology – Yale University; Jonathan Romanyshyn, MD – Surgeon, Department of Surgery, USCF - Fresno, CA; Ralitza Gueorguieva, PhD – Biostatistics – Yale University
Rationale: Using microdialysis probes coupled to depth EEG-electrodes implanted in drug-resistant epilepsy patients, we reported that the interictal extracellular glutamate (GLU) levels in epileptogenic sites are significantly elevated compared to non-epileptic sites, while GABA and glutamine (GLN) were unchanged (1). Given the recent understanding of epileptic networks (2), we examined the interictal GLU, GLN, and GABA levels in seizure propagation areas. GABA/GLU and GLN/GLU ratios were used as indices of inhibitory control and GLN-GLU cycling, respectively. To examine the effect of anti-seizure medications (ASMs), interictal levels were measured when patients were on their regular dose of ASMs and following ASM taper to induce their habitual seizures.
Methods: A total of 92 drug-resistant epilepsy patients undergoing investigation to localize their ictal focus were implanted with 116 custom combined microdialysis probes/depth electrodes and cortical surface electrodes in brain areas suspected of ictogenesis. Audio-visual, intracranial EEG, clinical, and imaging data were used to determine the epileptogenic (n=30; epi), propagated (n=44, prop) and non-epileptic sites (n=42, non-epi). Interictal period was defined as minimum of 6 hours before or after any seizures. Microdialysis and HPLC methods were described in (1). For statistical analysis, data were log-transformed, separate mixed models were fitted to assess differences by classification (epi, non-epi and prop) and ASM effect (on/off medication), with fixed effects for classification, location (cortex, hippocampus) and seizure type (MTE, neocortical). Random subject effect was used to account for correlations of probes within an individual.
Results: While on ASM, interictal GLU levels were significantly elevated in epi and in prop cortical and hippocampal regions (p<
Translational Research