Sude DANIŞMAN, Caner BEŞKOÇ, Emrah YÜCESAN, Nihan Hande AKÇAKAYA
Turkish Journal of Neurology - 2026;32(1):1-10
Sudden unexpected death in epilepsy (SUDEP) is one of the most devastating complications of epilepsy, posing a significant challenge for clinicians, geneticists, and forensic specialists. It is defined as a sudden, unexpected, nontraumatic, and nondrowning death in individuals with epilepsy, with no identifiable toxicological or anatomical cause found during postmortem examination. It accounts for a significant portion of epilepsy-related mortality. The heterogeneous nature of SUDEP complicates accurate diagnosis, classification, and epidemiological assessment, particularly in cases lacking comprehensive death scene investigation or autopsy. Emerging evidence suggests that SUDEP is a multifactorial phenomenon involving complex interactions between seizure-induced respiratory dysfunction, autonomic instability, and cardiac arrhythmogenesis. Findings from monitored cases indicate that terminal apnea often precedes cardiac arrest, underscoring the central role of postictal respiratory failure. However, conventional autopsy often fails to reveal specific structural abnormalities, making SUDEP a diagnosis of exclusion in forensic practice. The integration of molecular autopsy has significantly advanced the understanding of SUDEP by identifying pathogenic variants in genes associated with cardiac channelopathies and epilepsy syndromes. Next-generation sequencing technologies have enabled comprehensive genetic screening in autopsy-negative cases, linking neuronal excitability and cardiac electrophysiology. These findings highlight the shared molecular mechanisms underlying epilepsy and sudden cardiac death and offer opportunities for family-based risk assessment and preventive interventions. A multidisciplinary approach that combines clinical evaluation, standardized forensic investigation, and genomic analysis is essential to improve diagnostic accuracy and risk stratification. Continued research integrating genetic, physiological, and epidemiological data is crucial to advancing precision medicine strategies and reducing the global burden of SUDEP.
