title: From unwitnessed fatality to witnessed rescue: Pharmacologic intervention in sudden unexpected death in epilepsy.
abstract: The mechanisms of sudden unexpected death in epilepsy (SUDEP) have been difficult to define, as most cases occur unwitnessed, and physiologic recordings have been obtained in only a handful of cases. However, recent data obtained from human cases and experimental studies in animal models have brought us closer to identifying potential mechanisms. Theories of SUDEP should be able to explain how a seizure starting in the forebrain can sometimes lead to changes in brainstem cardiorespiratory control mechanisms. Herein we focus on three major themes of work on the causes of SUDEP. First, evidence is reviewed identifying postictal hypoventilation as a major contributor to the cause of death. Second, data are discussed that brainstem serotonin and adenosine pathways may be involved, as well as how they may contribute. Finally, parallels are drawn between SIDS and SUDEP, and we highlight similarities pointing to the possibility of shared pathophysiology involving combined failure of respiratory and cardiovascular control mechanisms. Knowledge about the causes of SUDEP may lead to potential pharmacologic approaches for prevention. We end by describing how translation of this work may result in future applications to clinical care.
authors.affiliation: Departments of Neurology and Molecular Physiology & Biophysics, University of Iowa & Veteran's Affairs Medical Center, Iowa City, Iowa, U.S.A.
authors.forename: George B
authors.initials: GB
authors.lastname: Richerson
authors.affiliation: Robert Stone Dow Neurobiology Laboratories, Legacy Research Institute Portland, Portland, Oregon, U.S.A.
authors.forename: Detlev
authors.initials: D
authors.lastname: Boison
authors.affiliation: Departments of Pharmacology and Neurology and Division of Neurosurgery, Southern Illinois University School of Medicine, Springfield, Illinois, U.S.A.
authors.forename: Carl L
authors.initials: CL
authors.lastname: Faingold
authors.affiliation: Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Philippe
authors.initials: P
authors.lastname: Ryvlin
mesh_terms: D000241:Adenosine / Q000378:metabolism; D001049:Apnea / Q000209:etiology; D001933:Brain Stem / Q000378:metabolism; D003645:Death, Sudden / Q000517:prevention & control*; D004827:Epilepsy / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007040:Hypoventilation / Q000209:etiology; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D058915:Purinergic P1 Receptor Antagonists / Q000627:therapeutic use*; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*
chemical_list: D000241:Adenosine; D009292:Narcotic Antagonists; D058915:Purinergic P1 Receptor Antagonists; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Adenosine; Apnea; Bradycardia; Hypoventilation; SUDEP; Serotonin