Abstracts

Rationale: The increased risk of SUDEP is particularly high in patients with drug refractory temporal lobe epilepsy (TLE). In fact, 40% of patients with pharmacoresistant epilepsy (~40% of the TLE population) have one or more abnormalities in cardiac function.  Thus, a number of preictal and postictal ECG measures were assessed in spontaneously seizing animals with chronic epilepsy.  Methods: Chronic video-EEG and ECG were recorded in adult, male rats with pilocarpine-induced epilepsy to assess potential ECG abnormalities associated with chronic epilepsy (n=13 pilocarpine, n=6 control).  Custom-written software incorporating machine-learning algorithms was used to analyze changes in ECG morphology and HRV was analyzed in artifact-free, preictal and postictal ECG recordings. Results: A number of alterations in the morphology of ECG in recordings from chronically epileptic animals. PR intervals were significantly decreased in preictal (p<0.05) and postictal (p<0.05) recordings relative to recordings from control rats.  QT intervals were significantly decreased in postictal recordings compared to ECG recordings from control rats. T-wave duration was significantly longer in preictal and postictal ECG recordings from epileptic rats relative to ECG recordings from control rats. Half-width of the QRS complex was significantly decreased in postictal recordings relative to controls (p<0.0001); and between preictal and postictal phases of the recording (p<0.0001). A composite score utilizing all morphological indices emphasized the increased risk for arrhythmias in postictal recordings (p<0.0001) and relative to control rats (p<0.0001). Postictal ECG recordings of chronically epileptic animals demonstrated differences in measures of HRV relative to control rats including alterations in HR, SDNN, RMSDD, RR interval, and LF/HF (p<0.05).  Seizure frequency was correlated with postictal heart rate, PR interval, QT interval, and QRS complex half-width (Spearman r, p<0.05). Conclusions: These results demonstrate the electrophysiological cardiac abnormalities, including arrhythmias, in a chronic model of acquired temporal lobe epilepsy.  Individually, these ECG abnormalities are risk factors for sudden unexpected/unexplained death in epilepsy (SUDEP); and may be combined as a composite score to be used as a prognostic indicator of risk. Funding: Funded by NIH to HLG (7K22NS083722).