Authors :
Presenting Author: Meera Karkar, BS – University of Incarnate Word School of Osteopathic Medicine
Charles Szabo, MD – UT Health San Antonio
Amy Werry, PhD – UT Health San Antonio
Olga Gonzalez, ACVP – Texas Biomedical Research Institute
Rationale:
Baboons with genetic generalized epilepsy succumb to sudden unexpected death (SUD), in some cases due to witnessed SUD in epilepsy (SUDEP), in others possibly due to sudden cardiac death (SCD). As cardiac pathology has been reported in epileptic baboons succumbing to SUD, we compared cardiac histopathology baboons with genetic generalized epilepsy (EPIs) to asymptomatic controls (CTLs).
Methods:
Retrospective review of necropsy reports was performed in baboons referred for necropsy at the Texas Biomedical Research Institute, including in 299 electroclinically diagnosed EPI baboons and 112 CTLs. Detailed analysis of cardiac histopathology was conducted in 70 EPI and 80 CTL baboons whose histological slides were available in archived materials. All samples were selected and evaluated by a board-certified veterinary pathologist without knowledge of diagnostic status. Statistical comparisons were performed between the histopathological burden of EPI and CTL baboons, but also for specific histopathologies between males and females as well as between middle-aged and older baboons.
Results:
Forty-six EPIs (73%, 57% female) demonstrated cardiac histopathology compared to 69 CTLs (90%, 84% female) between 10 and 30 years old (see Table 1). While the EPI group was significantly younger, overall cardiac pathology not significantly between the groups when controlled for age. The pathologies included fibrosis, myocarditis, cardiomyopathy, steatosis and arteriosclerosis. When evaluating pathologies more closely linked to SUD, prevalence of endocardial fibrosis and cardiomyopathy were not significantly different between the groups, although these pathologies did demonstrate statistically significant sex differences: both were more common in male >female EPIs and female >male CTLs. Otherwise, the rate of cardiac histopathology for 10-20 (30-60 years in humans) and 21-30 (greater than 60 years in humans) age ranges were similar in both groups. Conclusions:
Cardiac histopathology was not significantly between the EPI and CTL groups, and was similarly distributed among middle-aged and older animals. Sex differences were evident in SUD-specific pathologies in both groups. EPIs were referred for necropsy at a younger age probably due to seizures and epilepsy-related comorbidities. As seizures are not treated in the baboons, this study suggests that environmental factors, including decreased physical activity, tobacco, alcohol or drug use, and less healthy diets, could play a more prominent role in human SUD. This dataset does address whether cardiac pathology appears at an earlier age in EPIs. Nonetheless, this natural nonhuman primate model of genetic generalized epilepsy provides an important resource for better understanding mechanisms of SUD in people with epilepsy. Funding: NIH/NINDS 1R56NS135399-1