Abstracts

The damage to the anterior mesial temporal structures in mesial temporal lobe epilepsy (mTLE) is thought to be more extensive. Our group has previously reported that anterior hippocampus is more bioenergetically impaired compared to the posterior hippocampus (Firlik et al. 2001, Epilepsia 42 Suppl.7:67) and that the epileptogenic hippocampus is marked by increased extracellular Glutamate (Glu) (Cavus et al. 2002, Epilepsia 43 Suppl.7:247). Therefore, using microdialysis we measured the levels of several neurometabolytes in the anterior (pes) and posterior (body) of the epileptogenic hippocampus in neurosurgical patients with mTLE.
Microdialysis studies were performed in 7 patients with mTLE who were being evaluated for temporal lobectomy. Microdialysis probes attached to depth electrodes were implanted in the ipsilateral pes and body of the hippocampus. The interictal basal levels of glutamate (Glu), glutamine (Gln), GABA, glucose (Glc) and lactate (Lac) were measured using the zero-flow method 5-60 hrs prior to any seizure activity and HPLC. Data was log-transformed and analyzed using paired t-tests and and correlation (z score) statistics.
In 5 patients the epileptogenic focus was localized to the hippocampal pes, and in 2 patients to both the pes and the body. The Glu levels were significantly elevated in the pes in all patients (10.4 11.6 vs 4.8 [plusmn] 5.6 microM, p [lt] 0.003). Although Gln levels were similar in the pes and the body (730.4 [plusmn] 539.3 vs 873.8 [plusmn] 765.8 microM), the Gln/Glu ratio was significantly decreased in the pes (108.9 [plusmn] 67.6 vs 283.5 [plusmn] 213.9, p [lt] 0.002). The lower Gln/Glu ratio indicates impairment in the glutamate-glutamine cycling in the pes. There were no significant differences between the pes and the body for all other measurements (GABA 782.6 [plusmn] 870.3 vs 461.5 nM; Glc 2.3 [plusmn] 1.93 mMvs 2.3 1.7; Lac 6.0 [plusmn] 1.4 vs 5.7 [plusmn] 4.0 mM; p[gt]0,05). However for all neurometabolytes except Lac, there were highly significant correlations between their levels in the pes and the body (p [lt] 0.02): 70-90% of the variability in the body was explained by the variability in the pes.
The extracellular Glu levels were more elevated and the glutamate-glutamine cycling was more impaired in the pes vs. the body of the epileptogenic hippocampus. The relative elevation of Glu in the pes may be a consequence of impaired Glu reuptake or reverse transporter release due to impaired energy supply. This is consistent with the increased impairment in the bioenergetic status in the anterior vs posterior hippocampus reported previously from our group.
[Supported by: NIH-PO1 NS 39092-01 and BIRCWH 1K12DA14038-01 for I. Cavus]