Zyklusabhängige Veränderungen corticaler Exzitabilität bei gesunden Frauen und Patientinnen mit katamenialer Epilepsie: eine TMS Studie

The pathophysiology underlying seizure clustering in female patients with epilepsy in the course of the menstrual cycle is still unclear. Therefore, we investigated cyclical changes of cortical excitability in healthy women and women with catamenial epilepsy using transcranial magnetic stimulation (TMS). Eight healthy women with anovulatory cycles, 12 with ovulatory cycles and six patients with catamenial epilepsy and ovulatory cycles were included in the study. Catamenial epilepsy was defined as doubling of seizure frequency during one or two of the four cycle phases (follicular phase, ovulation, luteal phase and menstruation). On days 8, -14, -7 and 2 of the cycle, resting motor threshold (RMT), cortical silent period (CSP), intracortical inhibition (ICI) and intracortical facilitation (ICF) were investigated. Repeated measures ANOVA with menstrual cycle phase as within-subject factor and group (anovulatory vs. ovulatory cycles; healthy women vs. patients with catamenial epilepsy) as between-subject factor was used for statistical analysis. Significant results were further analysed using non-parametric methods (Friedman-test, Wilcoxon-test and Mann-Whitney U-test). In healthy women there was a significant difference between ovulatory and anovulatory cycles regarding ICI (F=7.4, P=.016), inhibition being reduced in ovulatory cycles on days –14 (Z=-2.3, P=.021), -7 (Z=-2.0, P=.048) and 2 (Z=-2.4, P=.018). Intracortical inhibition varied significantly during anovulatory cycles (c²=8.3, P=.040), due to an increased inhibition on day 2 (Z=-2.2, P=.028 as compared to days 8 and –7). Statistical analysis of the other parameters revealed no significant results (P>.05). Five patients suffered from focal epilepsies (3 right hemispheric, 1 bitemporal and 1 with unknown focus) and one patient had idiopathic generalized epilepsy. All patients experienced perimenstrual seizure clustering and two also showed an increased seizure frequency during the luteal phase. Concerning the CSP, there was a significant effect of the cycle phase in the right hemispheres of the patients (F=7.5, P=.0020), CSP being shorter during menstruation (Z=-2.2, P=.028) an luteal phase (Z=-2.0, P=.043) as compared to the follicular phase. In the left hemispheres of the patients, there was a significant difference of ICI as compared to healthy controls (F=5.3, P=.037), due to increased inhibition in patients on days –14 (Z=-0.56, P=.048) and –7 (Z=-0.21, P=.037). There were no significant differences concerning the other parameters (P>.05). The results obtained from healthy women reveale changes in cortical excitability during anovulatory cycles. Intracortical inhibition, reflecting GABAA-ergic transmission, was increased during menstruation of anovulatory cycles, possibly due to the falling estrogen levels that accompany menstruation in anovulatory cycles. The decreased inhibition in ovulatory as compared to anovulatory cycles on days –14 and –7 may be related to higher estrogen levels during these cycle phases of ovulatory cycles and points to a facilitating effect of estrogens on cortical excitability. In contrast to healthy women, patients with catamenial epilepsy showed a shortened CSP during luteal phase and menstruation, which correlated well with the increased seizure frequency during these cycle phases. The changes in CSP, which reflect GABAB-ergic inhibition, could only be found in the right hemispheres, where the epileptogenic focus was located in most of the patients, and not in the contralateral left hemispheres. This confirms earlier studies which showed changes in GABAB-ergic transmission in hemispheres containing an epileptogenic focus and may present a pathophysiologic correlate for catamenial seizure clustering. In addition, we found an increased inhibition in contralateral hemispheres, also confirming results of earlier studies. Future studies should evaluate a more homogenous patient group as well as patients with anovulatory cycles.