Abstracts

Rationale: SUDEP is rare in children despite childhood onset epilepsy being a strong risk factor. Cardiac mechanisms for SUDEP have mostly focused on abnormalities in electrocardiography. An alternative and largely unexplored factor is damage to the myocardium provoked by seizures, supported by early evidence that linked myocyte injury with SUDEP from autopsy data. Our hypothesis is that repeated acute insult to the cardiac muscle in childhood, due to seizure-related outcomes, may lead to cumulative chronic myocardial ischemia and/or fibrosis which increases the risk of subsequent SUDEP or electrical abnormalities that lead to SUDEP. Short and long term myocardial interstitial changes and impairment can be evaluated using speckle tracking echocardiography and measurement of strain (myocardial tissue deformation). Methods: Children with refractory convulsive seizures were identified from the pediatric epilepsy population at the Childrens National Health System (CNHS) in Washington, DC. Speckle tracking echocardiography and a one minute ECG were performed in the outpatient CNHS cardiology unit. The echocardiogram involves routine ultrasound images with post-processing for strain analysis. One age and gender matched normal control was selected for each case from retrospective CNHS patients in whom the echo was already performed for clinical purposes with non-significant findings. Strain measurements were obtained from the echocardiograms in two dimensions, longitudinal and circumferential, by a single reader. Longitudinal and circumferential rates (i.e, the deformation by time) were also calculated. Lower negative values of strain and strain rate indicate greater impairment. Two-tailed T-tests were used to examine the differences between cases and controls. Results: Data from 8 children (3 males, 5 females) have been analyzed to date and enrollment is ongoing. The average age of cases is 12.3 years (range 6-20) and of controls 11.1 years (range 6-19). The epilepsy diagnosis of the cases includes 5 with Dravet syndrome, 1 with SCN2A epileptic encephalopathy, and 2 with refractory epilepsy. The average duration of epilepsy is 9.7 years (range 5-19). All 8 cases had normal ECGs. Despite this small sample size, circumferential strain was significantly lower in the cases than the controls (-22.63 vs -26.85, p=.01). Longitudinal strain was also lower in the cases than the controls (-23.03 vs -24.12) but did not reach significance. Longitudinal and circumferential strain rate were both similar in the cases and controls (-1.4 vs -1.3 and -1.5 vs -1.40). Conclusions: We have identified a potential biomarker for subclinical myocardial dysfunction that can be identified in childhood. Successful identification of children and young adults with impaired strain on echocardiography, a relatively easy and non-invasive test, provides the opportunity to monitor them over time for myocardial impairment and to implement a targeted treatment, which may prevent or reduce the risk of SUDEP or myocardial injury later in life. Funding: This research is supported by a grant from the Children's National Board of Visitors