Abstracts

Rationale: Sudden Unexpected Death in Epilepsy (SUDEP) is a common cause of premature mortality for individuals with epilepsy. In the MORTality in Epilepsy Monitoring Unit Study (MORTEMUS), 9 patients who had video electroencephalography (EEG) and electrocardiography (ECG) monitoring at the time of death showed that terminal apnea preceded terminal asystole. This led to a ‘unified’ hypothesis of SUDEP, implicating respiratory dysfunction as the main cause of death. However, cardiac dysfunction including bradycardia and transient asystole preceded terminal apnoea in 5 patients, suggesting that the underlying mechanism is more complex. Furthermore, post-terminal apnea ECG revealed changes in heart rhythm and PQRST waveform in some patients. In these patients, we propose that the post-terminal apnea ECG could be pulseless electrical activity (PEA), characterised by a detectable electrical heart activity but lack of patient response and pulse due to low cardiac contractility and output. In this study, we investigated the occurrence of PEA following terminal seizure using mouse models.

Methods: We have developed a unique SUDEP mouse model, a cross between a LQTS mouse (Kcnh2^+/-) and a developmental and epileptic encephalopathy mouse (Hcn1^M294L/+). We performed electrocardiogram (ECG) and electrocorticography (ECoG) recordings in the double mutant Kcnh2^+/-/Hcn1^M294L/+ mice to measure cardiac and brain function respectively and capture spontaneous death. ECG-ECoG before and after terminal seizure were also recorded following proconvulsant pentylenetetrazole (PTZ) injection in wildtype (WT) mice. Paired t-test was used for comparison between baseline and post-terminal seizure ECG and ECoG parameters. Statistical significance was set at P< 0.05.