Abstracts

Rationale: Catamenial epilepsy is the term used to describe women with epilepsy (WWE) who have increased seizure frequency (SzF) during specific phases of their menstrual cycle. One study reported that WWE with a catamenial pattern experienced improvement of their seizure control during pregnancy (Cagnetti et al. Neurology 2014;83(4):339-44). In a prior study, we showed that patients with generalized epilepsy have a lower risk, while focal epilepsy and, in particular, frontal lobe epilepsy have a significantly higher risk of seizure exacerbation during pregnancy.This study aims to: 1) determine the fraction of patients with a catamenial pattern that have seizure worsening during pregnancy; 2) understand the direction and magnitude of influence for the epilepsy type and sex hormones/neurosteroid levels on seizure control during pregnancy. Methods: WWE were enrolled preconception or early in pregnancy. At enrollment, detailed clinical information was obtained, including baseline SzF over the past year and if the participant had noted a catamenial pattern in the past. Participants were prospectively followed throughout pregnancy and the first postpartum year with daily diaries of seizures, AED doses, and adherence. Study visits with blood sampling occurred every 1-3 months. SzF was calculated for each 4-week block during pregnancy and pregnancies were included in the 'seizure worsening' group if any block had a higher SzF than preconception baseline; the rest with same or better SzF comprise the 'seizure stable' group. A subset of participants had plasma assayed from at least two trimesters for concentrations of estradiol (EST), progesterone (PROG) and allopregnanolone (Allo) as previously described by Pennell KD et al. in Steroids 2015; 95:24-31. Results: Among 88 patients with adequate seizure information during pregnancy, there were 14 patients (15.9%) who reported a catamenial pattern: 10 women with focal epilepsy (7 temporal -TLE, 2 frontal - FLE and 1 parietal - PLE) and 4 women with generalized epilepsies (GE). One TLE patient was followed throughout 2 pregnancies, the rest contributed one pregnancy. 7/15 pregnancies (46.6%) had seizure worsening in at least one 4-week pregnancy interval: 2/2 (100%) pregnancies of FLE patients, 4/8 (50%) of TLE patients and 1/4 (25%) of GE patients.Plasma for hormone/neurosteroid levels analyses was available for 9 pregnancies: 5 in the 'seizure worsening' group and 4 in the 'seizure stable' group. When compared to 'seizure stable' group, the 'seizure worsening' group has comparable values for PROG and EST throughout the pregnancy, though Allo levels in the 2nd trimester were higher in the 'seizure worsening' group (t-test, p= 0.055) compared to 'stable seizure' group. There were no differences in Allo levels in the 1st or 3rd trimesters. Conclusions: While the numbers of patients with documented catamenial seizure patterns in our study is limited, the percentage pregnancies displaying seizure worsening is high (46.6%). In this subset of women, focal epilepsy (especially frontal) were associated with a higher risk of seizure worsening than generalized epilepsy. Our limited data suggests more prominent differences in sex hormones/neurosteroid levels in the second trimester, but validation in a larger cohort is necessary. Funding: Supported by an NIH Specialized Center of Research (P50 MH 68036) (ZNS, DJN, PBP), NCRR M01-RR00039, NINDS and NICHD (U01 NS038455) (ZNS, PBP), the BWH Women Brain Initiative and Trustey Award (PEV).