ArticleFrontiers in neurology
Beyond the seizure: unveiling the mechanism of death in SUDEP through integrated scene and autopsy analysis.
Article in Frontiers in neurology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 authors.
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Abstract
Objective: Sudden unexpected death in epilepsy (SUDEP) remains a major cause of mortality in epilepsy, yet its underlying mechanisms are incompletely understood. This study aimed to investigate respiratory- and cardiac-driven death mechanisms in SUDEP by integrating scene investigation findings, toxicology, and forensic autopsy data using composite indices. Methods: We retrospectively analyzed 128 definite SUDEP cases autopsied between 2019 and 2024. Scene characteristics (body position, witness presence), toxicological results, organ weights, and histopathological findings were reviewed. Respiratory-related mechanisms were assessed using the Airway Protective Failure Index (APFI_ext), Pulmonary Edema (PE) and Bleeding Index (PEBI), and Lung-to-Brain Ratio (LBR). Cardiac-related mechanisms were evaluated using the Coronary-Arrhythmic Burden Score (CABS) and Cardiac Vulnerability Index (CVI+). Penalized logistic regression models and receiver operating characteristic (ROC) analyses were applied to assess discriminative performance. Results: The median age was 33 years, and 59.4% of cases were male. Most deaths occurred unwitnessed, and 71.9% of individuals were found in the prone position. Upper airway findings were frequent among prone cases, including tracheal froth (85.1%), vomit (14.9%), and laryngeal edema (10.4%). PE was observed in 94.5% of cases. APFI_ext demonstrated strong discrimination for prone position (ROC-AUC ≈ 0.92), whereas lung-weight-based indices alone showed limited discriminatory value. Higher body mass index was associated with prone position ( Discussion: These findings support a predominantly respiratory-driven mechanism in SUDEP, characterized by postictal airway compromise and pulmonary stress, while highlighting a secondary cardiac vulnerability that may contribute in older individuals. Integrating scene investigation with autopsy-based composite indices provides a practical framework for phenotypic classification of SUDEP and may inform targeted prevention strategies focused on respiratory monitoring and positional risk reduction.
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