Abstracts

Rationale: In addition to its seizure-suppressing properties, levetiracetam (LEV) has been shown to possess potential antiepileptogenic effects in various animal models. In this study we used a well-characterized model of cortical dysplasia (CD) to explore the role of postnatal administration of LEV prior to a second hit - which leads to the expression of seizures in these animals. Methods: Twenty-six male Sprague Dawley rats were divided into two groups of eight (in utero LEV-, postnatal LEV-; in utero LEV-, postnatal LEV+) and two groups of six & four (in utero LEV+, postnatal LEV-; in utero LEV+, postnatal LEV+). From E12-16 the pregnant mothers either received 54mg/kg s.c. LEV q8 or 54mg/kg s.c. LO60 (inactive LEV entantiomer) q8. All rats were irradiated with 145cGY in utero on day E17. After birth and from PND42 to 48, they were given either 54mg/kg s.c. LEV q8 or 54mg/kg s.c. LO60 q8. On PND55 all were implanted with epidural electrodes over the frontal and parietal regions bilaterally. On PND60 all rats were given a convulsive dose (50mg/kg s.c.) of pentylenetetrazol (PTZ; second hit) & their behavior & EEG was monitored for a subsequent eight hours. Results: Rats who received LEV displayed in greater numbers less severe seizures in comparison to control rats; control: 5 rats Stage 6 & 3 rats Stage 2; postnatal LEV only: 3 rats Stage 6 & 5 rats Stage 2; in utero LEV only: 3 rats Stage 4 & 3 rats Stage 2; in utero & postnatal LEV: 3 rats Stage 4 & 3 rats Stage 2 (Pinel & Rovner). Latency to first EEG change was longer in the groups, who received in utero LEV in comparison to controls (474s ± 269s vs. 166s ± 71s; p< 0.05). Likewise latency to the first absence-like episode (based on Video-EEG and behavioral observation) was prolonged (584s ± 163s vs. 268s ± 97s; p< 0.01). Conclusions: Pre-treatment with LEV appears to impede the expression of acute seizures induced by a second hit in CD rats, particularly when LEV is administered in utero. These findings suggest a disease modifying effect of LEV in this animal model. Further experiments with larger numbers are ongoing in an effort to confirm these results.