Sudden unexpected death in epilepsy: Investigation of autopsy-based studies

Abstract

Epilepsy is a common neurological disorder that is associated with increased morbidity and mortality. Sudden unexpected death in epilepsy (SUDEP) is one of the most common causes for epilepsy-related deaths and its characteristics remain largely unknown, particularly from a forensic autopsy perspective. The present study aimed to investigate the neurological, cardiac, and pulmonary findings for a total of 388 SUDEP decedents, encompassing three cases from our forensic center during 2011–2020 and 385 literature-reported autopsy cases. In the cases mentioned in this study, two of them presented with only mild cardiac abnormalities, such as focal myocarditis and mild coronary atherosclerosis of the left anterior coronary artery. The third one was negative of any pathological findings. After pooling together these SUDEP cases, we found that neurological changes (n = 218 cases, 56.2%) were the most common postmortem findings associated with SUDEP, with cerebral edema/congestion (n = 60 cases, 15.5%) and old traumatic brain injury (n = 58 cases, 14.9%) being the major findings. Interstitial fibrosis, myocyte disarray/hypertrophy, and mild coronary artery atherosclerosis were the most common findings related to primary cardiac pathology, documented in 49 (12.6%), 18 (4.6%), and 15 (3.9%) cases, respectively. Non-specific pulmonary edema was the major finding in the lungs. This is an autopsy-based study that reports the scenario of postmortem findings for SUDEP cases. Our study paves the way for understanding the pathogenesis of SUDEP and the interpretation of death.

Audiogenic epileptic DBA/2 mice strain as a model of genetic reflex seizures and SUDEP

“…SUDEP refers to an unexpected, non-traumatic death in children and adults with epilepsy, where postmortem examination does not reveal any anatomical or toxicological cause of death, including drowning ( 12 , 13 ). Among the most important risk factors for SUDEP are uncontrolled or frequent GTCSs, the duration of epilepsy, prone position at the time of death, young age of first seizure, male sex, neurological comorbidities, polytherapy, ion channel or arrhythmia-related gene mutations, cardiac-respiratory dysfunction, intellectual disability, nocturnal seizures, and non-adherence to ASMs ( 12 , 14 ).…”

“…All the SUDEP cases died at an early age (generally 10–40 years), particularly, patients with intellectual impairment, refractory epilepsy, and poorly controlled epilepsy with a high frequency of GTCS and nocturnal seizures. Studies have suggested a slight male predominance, with the male-to-female ratio being 229:159 ( 13 , 22 ).…”

Hallazgos de autopsias en la muerte súbita en epilepsia. Revisión Bibliográfica y reporte de casos

“…Con los avances en la biología molecular se han identificado genes que codifican para canales iónicos que se coexpresan en el corazón y en el cerebro, lo que podría indicar una susceptibilidad genética común a algunos tipos de arritmias, la epilepsia y SUDEP 17,25,26 23 . Recientemente se valora como fundamental el papel de la apnea central postictial en la SUDEP 20,27 , producida por disfunción autonómica mediada por neurotransmisores en respuesta a la hipoxia que se produce durante la convulsión; la cual se está proponiendo incluso como un biomarcador para SUDEP 27 .…”