An explanation for sudden death in epilepsy (SUDEP)



This review traces the examination of autonomic, cardiovascular, and respiratory derangements associated with seizure activity in the clinical and preclinical literature generally, and in the author’s animal model specifically, and concludes with the author’s views on the potential mechanisms for sudden death in epilepsy (SUDEP). An animal model that employs kainic acid-induced seizures on a background of urethane anesthesia has permitted unprecedented access to the behavior of autonomic, cardiovascular, and respiratory systems during seizure activity. The result is a detailed description of the major causes of death and how this animal model can be used to develop and test preventative and interventional strategies. A critical translational step was taken when the rat data were shown to directly parallel data from definite SUDEP cases in the clinical literature. The reasons why ventricular fibrillation as a cause of death is so rarely reported and tools for verifying that seizure-associated laryngospasm can induce obstructive apnea as a cause of death are discussed in detail. Many details of the specific kinetics of activation of brainstem neurons serving autonomic and respiratory function remain to be elucidated, but the boundary conditions described in this review provide an excellent framework for more focused studies. A number of studies conducted in animal models of seizure activity and in epilepsy patients have contributed information on the autonomic, cardiovascular, and respiratory consequences of seizure activity spreading through hypothalamus and brainstem to the periphery. The result is detailed information on the systemic impact of seizure spread and the development of an understanding of the essential mechanistic features of sudden unexpected death in epilepsy (SUDEP). This review summarizes translation of data obtained from animal models to biomarkers that are useful in evaluating data from epilepsy patients.


Seizure Laryngospasm Ventricular fibrillation Obstructive apnea 



The author is grateful to his sponsor, Dr. Harumi Hotta of the Tokyo Metropolitan Institute of Gerontology, and for the support of the Japan Society for the Promotion of Science. The research itself was supported with philanthropic contributions, university support, and other sources. This manuscript is an updated review of material that was presented by the author in a number of seminars during the month of March, 2016.


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© The Physiological Society of Japan and Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Physiology and PharmacologyState University of New York Downstate Medical CenterBrooklynUSA
  2. 2.Department of NeurologyState University of New York Downstate Medical CenterBrooklynUSA

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