Abstracts

Rationale: In women with catamenial epilepsy, seizures worsen at certain times of each menstrual cycle. Reports concerning the prevalence of this syndrome vary. It is possible that catamenial patterns are underestimated because the EEG exhibits patterns more than convulsive behaviors. We tested this hypothesis using EEG recording of intact epileptic female rats. We chose an animal model of temporal lobe epilepsy (TLE), because patients with foci in the temporal lobe appear to be more susceptible to catamenial patterns (Herzog, 1999; Quigg et al., 2009). Methods: Adult male and female Sprague-Dawley rats (2-3 months old) were treated with pilocarpine or kainic acid to elicit status epilepticus (SE), and after 1 hr they were treated with pentobarbital (10-20 mg/kg, i.p.). The selective estrogen-response modulator raloxifene (1-2 mg/kg, s.c.) was injected before pilocarpine. To record EEG, rats were implanted with 2 twisted bipolar electrodes in the dorsal hippocampus bilaterally and 4 epidural screws over the frontal and occipital cortices bilaterally. After 1-2 weeks, rats were recorded daily between 9:00 and 12:00 a.m. to collect up to 30 min of EEG during spontaneous periods of exploration, immobility, and sleep. Wideband signals (1-6000 Hz) were amplified 350x and transmitted by a digital telemetry device (Bio-Signal Group). The signal was amplified 2x, and sampled at 2 kHz/channel. The EEG was quantified using Insight (Persyst), custom-written macros in Igor (Wavemetrics), and Matlab (Mathworks). The regularity of the the estrous cycle was evaluated daily by vaginal cytology. Results: Generalized interictal spiking (IIS), which occurred primarily during immobility and sleep, waxed and waned with the stage of the estrous cycle, with the most robust increase on estrous morning (n=4). All animals that became acyclic (n=10) or were ovariectomized (n=4) lost the cyclic increase in IIS frequency. In males, IIS frequency did not exhibit a cyclic pattern (n=2). Spontaneous stage 3-5 seizures were not exhibited when animals were evaluated with continuous video monitoring for 2 weeks (n=4), suggesting that intermittent convulsive seizures did not influence IIS frequency. However, the EEG often displayed 1-10s periods of continuous epileptiform activity accompanied by freezing behavior, suggesting non-convulsive seizures. In addition, stage 5 (convulsive) seizures were often triggered by handling when it involved restraint. Notably, these EEG findings appeared to be similar in rats treated with either pilocarpine or kainic acid. Conclusions: SE in the intact female rat can lead to a cyclic increase in IIS frequency. The pattern that is exhibited appears to simulate the perimenstrual pattern of seizure exacerbation in catamenial epilepsy. Cyclic changes in IIS frequency were not detected in animals without regular estrous cycles, ovariectomized females, or males. The data suggest that catamenial epilepsy may be underestimated if convulsions are the only analysis of seizures.