PMID- 29331091 OWN - NLM STAT- MEDLINE DCOM- 20190118 LR - 20190917 IS - 1531-8249 (Electronic) IS - 0364-5134 (Print) IS - 0364-5134 (Linking) VI - 83 IP - 2 DP - 2018 Feb TI - Terminal spreading depolarization and electrical silence in death of human cerebral cortex. PG - 295-310 LID - 10.1002/ana.25147 [doi] AB - OBJECTIVE: Restoring the circulation is the primary goal in emergency treatment of cerebral ischemia. However, better understanding of how the brain responds to energy depletion could help predict the time available for resuscitation until irreversible damage and advance development of interventions that prolong this span. Experimentally, injury to central neurons begins only with anoxic depolarization. This potentially reversible, spreading wave typically starts 2 to 5 minutes after the onset of severe ischemia, marking the onset of a toxic intraneuronal change that eventually results in irreversible injury. METHODS: To investigate this in the human brain, we performed recordings with either subdural electrode strips (n = 4) or intraparenchymal electrode arrays (n = 5) in patients with devastating brain injury that resulted in activation of a Do Not Resuscitate-Comfort Care order followed by terminal extubation. RESULTS: Withdrawal of life-sustaining therapies produced a decline in brain tissue partial pressure of oxygen (p(ti) O(2) ) and circulatory arrest. Silencing of spontaneous electrical activity developed simultaneously across regional electrode arrays in 8 patients. This silencing, termed "nonspreading depression," developed during the steep falling phase of p(ti) O(2) (intraparenchymal sensor, n = 6) at 11 (interquartile range [IQR] = 7-14) mmHg. Terminal spreading depolarizations started to propagate between electrodes 3.9 (IQR = 2.6-6.3) minutes after onset of the final drop in perfusion and 13 to 266 seconds after nonspreading depression. In 1 patient, terminal spreading depolarization induced the initial electrocerebral silence in a spreading depression pattern; circulatory arrest developed thereafter. INTERPRETATION: These results provide fundamental insight into the neurobiology of dying and have important implications for survivable cerebral ischemic insults. Ann Neurol 2018;83:295-310. CI - (c) 2018 Authors Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association. FAU - Dreier, Jens P AU - Dreier JP AD - Center for Stroke Research Berlin, Charite-Universitatsmedizin Berlin, Berlin, Germany. AD - Departments of Neurology, Charite-Universitatsmedizin Berlin, Berlin, Germany. AD - Experimental Neurology, Charite-Universitatsmedizin Berlin, Berlin, Germany. AD - Bernstein Center for Computational Neuroscience Berlin, Berlin, Germany. AD - Einstein Center for Neurosciences Berlin, Berlin, Germany. FAU - Major, Sebastian AU - Major S AD - Center for Stroke Research Berlin, Charite-Universitatsmedizin Berlin, Berlin, Germany. AD - Departments of Neurology, Charite-Universitatsmedizin Berlin, Berlin, Germany. AD - Experimental Neurology, Charite-Universitatsmedizin Berlin, Berlin, Germany. FAU - Foreman, Brandon AU - Foreman B AD - UC Gardner Neuroscience Institute. AD - Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, Cincinnati, OH. FAU - Winkler, Maren K L AU - Winkler MKL AD - Center for Stroke Research Berlin, Charite-Universitatsmedizin Berlin, Berlin, Germany. FAU - Kang, Eun-Jeung AU - Kang EJ AD - Center for Stroke Research Berlin, Charite-Universitatsmedizin Berlin, Berlin, Germany. AD - Experimental Neurology, Charite-Universitatsmedizin Berlin, Berlin, Germany. FAU - Milakara, Denny AU - Milakara D AUID- ORCID: 0000-0003-3148-6122 AD - Center for Stroke Research Berlin, Charite-Universitatsmedizin Berlin, Berlin, Germany. FAU - Lemale, Coline L AU - Lemale CL AD - Center for Stroke Research Berlin, Charite-Universitatsmedizin Berlin, Berlin, Germany. AD - Experimental Neurology, Charite-Universitatsmedizin Berlin, Berlin, Germany. AD - Department of Neurosurgery, Charite-Universitatsmedizin Berlin, Berlin, Germany. FAU - DiNapoli, Vince AU - DiNapoli V AD - Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH. AD - Mayfield Clinic, Cincinnati, OH. FAU - Hinzman, Jason M AU - Hinzman JM AD - Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH. FAU - Woitzik, Johannes AU - Woitzik J AD - Center for Stroke Research Berlin, Charite-Universitatsmedizin Berlin, Berlin, Germany. AD - Department of Neurosurgery, Charite-Universitatsmedizin Berlin, Berlin, Germany. FAU - Andaluz, Norberto AU - Andaluz N AD - UC Gardner Neuroscience Institute. AD - Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH. AD - Mayfield Clinic, Cincinnati, OH. FAU - Carlson, Andrew AU - Carlson A AD - Department of Neurosurgery, University of New Mexico, Albuquerque, NM. FAU - Hartings, Jed A AU - Hartings JA AD - UC Gardner Neuroscience Institute. AD - Department of Neurosurgery, University of Cincinnati College of Medicine, Cincinnati, OH. LA - eng GR - P20 GM109089/GM/NIGMS NIH HHS/United States PT - Case Reports PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20180215 PL - United States TA - Ann Neurol JT - Annals of neurology JID - 7707449 SB - IM MH - Adult MH - Aged MH - Brain Death/*physiopathology MH - Brain Ischemia/*physiopathology MH - Cerebral Cortex/blood supply/*physiopathology MH - Cerebrovascular Circulation/physiology MH - Cortical Spreading Depression/*physiology MH - Electrocorticography MH - Female MH - Humans MH - Male MH - Middle Aged PMC - PMC5901399 EDAT- 2018/01/14 06:00 MHDA- 2019/01/19 06:00 PMCR- 2018/04/16 CRDT- 2018/01/14 06:00 PHST- 2017/09/25 00:00 [received] PHST- 2018/01/08 00:00 [revised] PHST- 2018/01/09 00:00 [accepted] PHST- 2018/01/14 06:00 [pubmed] PHST- 2019/01/19 06:00 [medline] PHST- 2018/01/14 06:00 [entrez] PHST- 2018/04/16 00:00 [pmc-release] AID - ANA25147 [pii] AID - 10.1002/ana.25147 [doi] PST - ppublish SO - Ann Neurol. 2018 Feb;83(2):295-310. doi: 10.1002/ana.25147. Epub 2018 Feb 15.