Hippocampal microdialysis during spontaneous intraoperative epileptiform activity.

ABSTRACT

BACKGROUND: The actual mechanisms underlying human hippocampal epileptogenicity, a process ultimately mediated by neurochemical events, remains to be fully elucidated. We submit early insight data regarding microdialysis (MD) recovery of the neuroactive amino acids glutamate, aspartate and gamma-aminobutyric acid (GABA) from the intraoperative and intact, spontaneously epileptiform human hippocampus. METHOD: Generally anaesthetised temporal lobe epilepsy (TLE) patients (N=7) undergoing therapeutic and anatomically standardised resective surgery were also subjected to ipsilateral anterior hippocampal MD with concomitant hippocampal electrocorticography (ECoG). Recovered 10-min dialysate samples were quantified for glutamate, aspartate and GABA using high-performance liquid chromatography; corresponding ECoG data was assessed for epileptiform activity (EA); mesial resection tissue was postoperatively examined and graded for hippocampal sclerosis. FINDINGS: Mean 'Sample 3' dialysate absolute recovery of glutamate, aspartate and GABA from hippocampi with minimal EA (N=5) was ( micro M+/-SEM) 6.406+/-2.143, 0.600+/-0.215, and 0.357+/-0.093, respectively. In contrast, 'Sample 3' dialysate absolute glutamate, aspartate and GABA levels ( micro M) from the hippocampi of two patients with vigorous EA were 101.099 and 211.861, 21.860 and 14.482, and 4.241 and 4.817, respectively. Mesial resection tissue in all cases demonstrated hippocampal sclerosis, though the histopathological degree of sclerosis varied between patients. INTERPRETATION: These preliminary intraoperative findings suggest that dialysate glutamate, aspartate, and GABA levels from the sclerotic anterior hippocampus likely reflects the functional status of the sampled tissue - i.e., lower levels of these neuroactive amino acids are to be expected during quiescent or minimal EA versus considerably higher levels corresponding to vigorous EA.