Abstracts

Women with catamenial epilepsy have increased seizures, often prior to their menstruation. MRS studies (Epperson NC, Arch Gen Psychiatry. 2002) describe lower cortical GABA levels during the luteal phase of the menstrual cycle in healthy women. Since glutamate and GABA play role in seizure generation, we investigated whether the extracellular levels of these neurotransmitters change over the menstrual cycle, and whether gender effects may exist. Microdialysis studies were performed in 52 patients (32 F and 20 M) with CPS who were being evaluated for resective surgery. Menstrual cycle history was obtained in 19 female patients. Microdialysis probes attached to depth electrodes were implanted in the cortex (ctx) and hippocampus (hipp) and the epileptogenisity of the probe site was assessed with intracranial EEG recordings. The interictal basal levels of glutamate and GABA were measured using the zero-flow method and HPLC. Data was analyzed with Wilcoxon test. In the non-epileptic sites, the glutamate levels in the CTX (F 2.4 [plusmn] 0.4 [micro]M, n12 vs. M 2.9 [plusmn] 0.4 [micro]M, n10) and in the HIPP (F 3.0 [plusmn] 0.6 [micro]M, n14 vs. M 2.9 [plusmn] 0.5 [micro]M) were comparable for M and F. However the GABA levels were significantly higher in both the female CTX (F 0.3 [plusmn] 0.1 [micro]M, n12 vs. M 0.1 [plusmn] 0.03 [micro]M, n10, p [lt] 0.03) and HIPP (F 0.4 [plusmn] 0.1 [micro]M, n11 vs. M 0.2 [plusmn] 0.07 [micro]M, t [lt] 0.05). Moreover, while the glutamate levels did not change over the menstrual cycle (follicular phase 3.1 [plusmn] 0.5 [micro]M, n 14 vs. luteal phase 2.4 [plusmn] 0.9 [micro]M, n 5, p [gt] 0.5), the GABA levels were significantly lower during the luteal phase (luteal 0.12 [plusmn] 0.1 [micro]M, n5 vs. follicular 0.5 [plusmn] 0.1 [micro]M, n14, p [lt] 0.02).
Glutamate levels were significantly elevated in the epileptic CTX and HIPP in F and M (CTX F 13.7 [micro]M, n9 vs. M 10.2 [micro]M, n4, p[gt]0.05; HIPP F 12.1 [micro]M, n10 vs. M 11.4 [micro]M, n4, p[gt]0.05). However the GABA levels in the epileptic brain sites were not significantly different in neither gender (p[gt]0.5 for all tests), although there was a general trend for increased GABA levels in the epileptic regions. While basal glutamate levels in the non-epileptic CTX and HIPP are comparable in men and women, the GABA levels are higher in women and fluctuate across their menstrual cycle. GABA levels are much lower during the luteal phase. In both genders, the basal glutamate levels are high in the epileptic CTX and HIPP, while GABA levels do not change significantly. Thus, while the ECF levels of glutamate are tightly regulated, and are not under sex hormone control, the GABA levels are influenced by the menstrual cycle. The decrease in GABA levels during the luteal phase may play role in the catamenial epilepsy. The elevation in the extracellular glutamate (and possibly the marginal increase in the ECF GABA) are a result of the underlying pathology in epilepsy. (Supported by NIH-PO1 NS 39092-01 and BIRCWH 1K12DA14038-01 for I. Cavus)