title: Brain biomarkers for identifying excited delirium as a cause of sudden death.
abstract: Excited delirium (ED) syndrome is a serious medical condition associated with acute onset of agitated violent behavior that often culminates in a sudden unexplained death. While the contribution of restraint, struggle and the use of conductive energy devices (CED) to the cause and manner of death raise controversy, a CNS dysfunction of dopamine signaling may underlie the delirium and fatal autonomic dysfunction. We conducted a mortality review for a case series of ninety excited delirium deaths and present results on the association of a 2-protein biomarker signature. We conducted quantitative analyses of the dopamine transporter and heat shock protein 70 validated for specificity and degree of interindividual variation. Incident circumstances, force measures, autopsy and toxicology results were determined for all subjects. A majority of the victims in this case series tested positive for cocaine in blood and brain, although four had no licit or illicit drugs or alcohol measured at autopsy. Mean core body temperature where recorded was 40.7 degrees C. The expression of the heat shock protein HSPA1B transcript was elevated 1.8-4-fold in postmortem brain. The elevation of Hsp70 in autopsy brain specimens confirms that hyperthermia is an associated symptom and often a harbinger of death in these cases. Dopamine transporter levels were below the range of values measured in age-matched controls, providing pathologic evidence for increased risk of chaotic dopamine signaling in excited delirium. When combined with descriptions of the decedents' behavior prior to death, a 2-protein biomarker signature can serve as a reliable forensic tool for identifying the excited delirium syndrome at autopsy.
authors.affiliation: Department Neurology, Miller School of Medicine, University of Miami, 1501 NW 9th Avenue, Miami, FL 33136, USA. dmash@med.miami.edu
authors.forename: Deborah C
authors.initials: DC
authors.lastname: Mash
authors.forename: Linda
authors.initials: L
authors.lastname: Duque
authors.forename: John
authors.initials: J
authors.lastname: Pablo
authors.forename: Yujing
authors.initials: Y
authors.lastname: Qin
authors.forename: Nikhil
authors.initials: N
authors.lastname: Adi
authors.forename: W Lee
authors.initials: WL
authors.lastname: Hearn
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Hyma
authors.forename: Steven B
authors.initials: SB
authors.lastname: Karch
authors.forename: Henrik
authors.initials: H
authors.lastname: Druid
authors.forename: Charles V
authors.initials: CV
authors.lastname: Wetli
mesh_terms: D000328:Adult; D000662:Amphetamines / Q000032:analysis; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D016022:Case-Control Studies; D003042:Cocaine / Q000031:analogs & derivatives / Q000032:analysis; D003645:Death, Sudden / Q000209:etiology*; D003693:Delirium / Q000175:diagnosis* / Q000378:metabolism / Q000523:psychology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000032:analysis; D005260:Female; D053803:Forensic Genetics; D049429:Forensic Pathology; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D014158:Transcription, Genetic; D014754:Violence / Q000523:psychology
chemical_list: D000662:Amphetamines; D015415:Biomarkers; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; D018840:HSP70 Heat-Shock Proteins; C525621:HSPA1B protein, human; C005618:benzoylecgonine; D003042:Cocaine