Abstracts

Rationale: Sudden unexplained death in epilepsy (SUDEP) accounts for ~15% of deaths of people with epilepsy. Sudden death is >20x more common than in the general population. By definition causes are not clear, but both cardiac and respiratory malfunctions have been implicated. We used the intrahippocampal Tetanus Neuro-Toxin (TeNT) chronic model of temporal lobe epilepsy to investigate the effects of repeated brief epileptic seizures on the electrocardiogram (ECG) of freely moving rats. Methods: We recorded ECoG and ECG using electrodes and Telemetry Research devices implanted under isofluorane general anaesthesia in 8 adult male Wistar rats. Two weeks later we performed intrahippocampal injection of 2.5ng tetanus neurotoxin (TeNT) in 1 µl PBS (toxin omitted in controls). Animals were housed with naïve companion rats and video-recorded for seizure classification. Results: Electrographic seizures (lasting 30-133s) developed after ~4 days with an average number per animal in the range of 7-18 per day. Every epileptic rat experienced dramatic changes in heart activity associated with seizures. In 76 analyzed seizures an initial transient ictal bradycardia (lasting 38±2s) occurred in 89% (lasting 38±2s with heart rate falling to as low as 70 beats per minute). This was followed by late-ictal or postictal tachycardia in 93% of seizures, reaching 448±4 bpm, that persisted for 864±87s postictally. Arrhythmias occurred in 71% of seizures, with: missed beats (59%), ventricular premature depolarisations (22%) and ventricular fibrillation (17%) seen both in isolation and in concert. Typically the P-wave transiently disappeared during seizures to be replaced with signs of atrial fibrillation. Conclusions: These preliminary data indicate that repeated brief epileptic seizures result in several cardiac pathophysiologies. Most seizures were associated with arrhythmias and with postictal tachycardia. More capable devices able to monitor a greater number of critical cardio-respiratory, cerebral and vagal and other autonomic variables are necessary to understand the underlying mechanisms and to develop potential therapies. Such devices are under joint development and evaluation with the Purdue team and will be presented.