Abstracts

Rationale: The interictal microdialysate basal glutamate levels are elevated in the epileptogenic hippocampus and cortex in patients with intractable epilepsy (Cavus et al., Annals of Neurology, 2005). Here we studied the effect of AEDs on brain glutamate, glutamine, and GABA in these patients. Methods: Patients with complex partial seizures undergoing intracranial EEG monitoring for seizure localization were implanted with microdialysis probes coupled to depth electrodes in suspected seizure onset sites. Basal interictal collections were obtained at a 0.2 μL/min flow rate at least 4 hours before or after any seizures: 1) on therapeutic medication dose 2-3 d post-implantation and 2) at maximum drug taper. Probes were classified as hippocampal or cortical and were further subdivided into seizure onset, seizure propagation, and uninvolved by the EEG data. There were 93 probes in 37 patients; 39 probes in non-localizing patients or within lesion regions were excluded. Of the 53 cortical probes, there were 3 onset, 25 propagation, and 9 uninvolved. Of the 23 hippocampal probes, there were 3 onset, 9 propagation, and 4 uninvolved. The microdialysate was evaluated for glutamate, glutamine, and GABA by HPLC and the data was analyzed by mixed-models ANOVA. Results: Following the withdrawal of AEDs, glutamate significantly increased in both the hippocampal (12.8 to 18.5 μM) and cortical (17.2 to 59.6 μM) onset region (p>0.05), while declining in the cortical propagated (41.5 to 32.9 μM) and remaining relatively unchanged in the hippocampal propagated (29.3 to 30.9 μM), cortical uninvolved (3.2 to 4.1 μM), and hippocampal uninvolved (4.5 to 2.6 μM). Glutamine declined significantly (p<0.03) in the cortical onset (678 to 430 μM) and also declined in cortical propagated (750 to 651 μM), cortical uninvolved (799 to 594 μM), and hippocampal propagated (532 to 468 μM) while increasing significantly in the hippocampal onset (441 to 744 μM, p<0.05). GABA significantly declined in cortical onset (2333 to 485 nM, p<0.05) and remained relatively unchanged in cortical propagated (1565 to 1503 nM), cortical uninvolved 256 to 152 nM), hippocampal propagated (624 to 504 nM), and hippocampal uninvolved (151 to 95 nM), while markedly increasing in hippocampal onset (461 to 1581 nM, p<0.05). Conclusions: These data indicate that AED taper has complex and differential effects on brain glutamate, glutamine and GABA in the hippocampus vs. cortex, and in the uninvolved vs. propagated vs. seizure onset regions. The increase in basal glutamate in the seizure onset regions may be related to the increased epileptogenicity of these regions. The glutamate-glutamine metabolism may be differentially affected in the cortex vs. hippocampus. The paradoxical increase in GABA in the hippocampal onset is of interest.