{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:20:32Z","timestamp":1792794032937,"version":"4.5.0"},"reference-count":82,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T00:00:00Z","timestamp":1648771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["DR 323\/5-1"],"award-info":[{"award-number":["DR 323\/5-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"name":"German-Israeli Foundation","award":["124\/2008"],"award-info":[{"award-number":["124\/2008"]}]},{"name":"Era-Net Neuron","award":["01EW1212"],"award-info":[{"award-number":["01EW1212"]}]},{"name":"BMBF","award":["01EW2004"],"award-info":[{"award-number":["01EW2004"]}],"id":[{"id":"https:\/\/ror.org\/04pz7b180","id-type":"ROR","asserted-by":"crossref"}]},{"name":"BMBF","award":["168164"],"award-info":[{"award-number":["168164"]}],"id":[{"id":"https:\/\/ror.org\/04pz7b180","id-type":"ROR","asserted-by":"crossref"}]},{"name":"EU 7th Framework Programme for Research","award":["602150"],"award-info":[{"award-number":["602150"]}]},{"name":"EU 7th Framework Programme for Research","award":["SFB Tr3 D10"],"award-info":[{"award-number":["SFB Tr3 D10"]}]},{"name":"EU 7th Framework Programme for Research","award":["323\/6-1"],"award-info":[{"award-number":["323\/6-1"]}]},{"name":"EU 7th Framework Programme for Research","award":["323\/10-1"],"award-info":[{"award-number":["323\/10-1"]}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Bernstein Centre for Computational Neuroscience"},{"DOI":"10.13039\/501100013865","name":"Stiftung Charit\u00e9","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100013865","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001663","name":"Volkswagen Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001663","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100013865","name":"Charit\u00e9 Foundation","doi-asserted-by":"crossref","award":["1704\/1.1"],"award-info":[{"award-number":["1704\/1.1"]}],"id":[{"id":"10.13039\/501100013865","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100013865","name":"Charit\u00e9 Foundation","doi-asserted-by":"crossref","award":["1704\/1.2"],"award-info":[{"award-number":["1704\/1.2"]}],"id":[{"id":"10.13039\/501100013865","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Focal brain damage after aneurysmal subarachnoid haemorrhage predominantly results from intracerebral haemorrhage, and early and delayed cerebral ischaemia. The prospective, observational, multicentre, cohort, diagnostic phase III trial, DISCHARGE-1, primarily investigated whether the peak total spreading depolarization-induced depression duration of a recording day during delayed neuromonitoring (delayed depression duration) indicates delayed ipsilateral infarction.<\/jats:p>\n                  <jats:p>Consecutive patients (n = 205) who required neurosurgery were enrolled in six university hospitals from September 2009 to April 2018. Subdural electrodes for electrocorticography were implanted. Participants were excluded on the basis of exclusion criteria, technical problems in data quality, missing neuroimages or patient withdrawal (n = 25). Evaluators were blinded to other measures.<\/jats:p>\n                  <jats:p>Longitudinal MRI, and CT studies if clinically indicated, revealed that 162\/180 patients developed focal brain damage during the first 2 weeks. During 4.5 years of cumulative recording, 6777 spreading depolarizations occurred in 161\/180 patients and 238 electrographic seizures in 14\/180. Ten patients died early; 90\/170 developed delayed infarction ipsilateral to the electrodes. Primary objective was to investigate whether a 60-min delayed depression duration cut-off in a 24-h window predicts delayed infarction with &amp;gt;0.60 sensitivity and &amp;gt;0.80 specificity, and to estimate a new cut-off. The 60-min cut-off was too short. Sensitivity was sufficient [= 0.76 (95% confidence interval: 0.65\u20130.84), P = 0.0014] but specificity was 0.59 (0.47\u20130.70), i.e. &amp;lt;0.80 (P &amp;lt; 0.0001). Nevertheless, the area under the receiver operating characteristic (AUROC) curve of delayed depression duration was 0.76 (0.69\u20130.83, P &amp;lt; 0.0001) for delayed infarction and 0.88 (0.81\u20130.94, P &amp;lt; 0.0001) for delayed ischaemia (reversible delayed neurological deficit or infarction). In secondary analysis, a new 180-min cut-off indicated delayed infarction with a targeted 0.62 sensitivity and 0.83 specificity. In awake patients, the AUROC curve of delayed depression duration was 0.84 (0.70\u20130.97, P = 0.001) and the prespecified 60-min cut-off showed 0.71 sensitivity and 0.82 specificity for reversible neurological deficits. In multivariate analysis, delayed depression duration (\u03b2 = 0.474, P &amp;lt; 0.001), delayed median Glasgow Coma Score (\u03b2 = \u22120.201, P = 0.005) and peak transcranial Doppler (\u03b2 = 0.169, P = 0.016) explained 35% of variance in delayed infarction. Another key finding was that spreading depolarization-variables were included in every multiple regression model of early, delayed and total brain damage, patient outcome and death, strongly suggesting that they are an independent biomarker of progressive brain injury.<\/jats:p>\n                  <jats:p>While the 60-min cut-off of cumulative depression in a 24-h window indicated reversible delayed neurological deficit, only a 180-min cut-off indicated new infarction with &amp;gt;0.60 sensitivity and &amp;gt;0.80 specificity. Although spontaneous resolution of the neurological deficit is still possible, we recommend initiating rescue treatment at the 60-min rather than the 180-min cut-off if progression of injury to infarction is to be prevented.<\/jats:p>","DOI":"10.1093\/brain\/awab457","type":"journal-article","created":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T15:20:36Z","timestamp":1639495236000},"page":"1264-1284","source":"Crossref","is-referenced-by-count":102,"title":["Spreading depolarizations in ischaemia after subarachnoid haemorrhage, a diagnostic phase III study"],"prefix":"10.1093","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7459-2828","authenticated-orcid":false,"given":"Jens P.","family":"Dreier","sequence":"first","affiliation":[{"name":"Centre for Stroke Research Berlin, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"},{"name":"Department of Experimental Neurology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"},{"name":"Department of Neurology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"},{"name":"Bernstein Centre for Computational Neuroscience Berlin, Berlin, Germany"},{"name":"Einstein Centre for Neurosciences Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maren K. L.","family":"Winkler","sequence":"additional","affiliation":[{"name":"Centre for Stroke Research Berlin, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"},{"name":"Robert Koch-Institute, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0970-1308","authenticated-orcid":false,"given":"Sebastian","family":"Major","sequence":"additional","affiliation":[{"name":"Centre for Stroke Research Berlin, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"},{"name":"Department of Experimental Neurology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"},{"name":"Department of Neurology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor","family":"Horst","sequence":"additional","affiliation":[{"name":"Centre for Stroke Research Berlin, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Lublinsky","sequence":"additional","affiliation":[{"name":"Department of Brain & Cognitive Sciences, Zlotowski Centre for Neuroscience, Faculty of Health Sciences, Ben-Gurion University of the Negev, Soroka University Medical Centre, Beer-Sheva, Israel"},{"name":"Department of Physiology & Cell Biology, Zlotowski Centre for Neuroscience, Faculty of Health Sciences, Ben-Gurion University of the Negev, Soroka University Medical Centre, Beer-Sheva, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasilis","family":"Kola","sequence":"additional","affiliation":[{"name":"Centre for Stroke Research Berlin, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coline L.","family":"Lemale","sequence":"additional","affiliation":[{"name":"Centre for Stroke Research Berlin, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"},{"name":"Department of Experimental Neurology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate 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Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Platz","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Herz-Neuro-Zentrum Bodensee, Kreuzlingen, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devi","family":"Jorks","sequence":"additional","affiliation":[{"name":"Centre for Stroke Research Berlin, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"},{"name":"Bernstein Centre for Computational Neuroscience Berlin, Berlin, Germany"},{"name":"Clienia Schl\u00f6ssli AG, Privatklinik f\u00fcr Psychiatrie und Psychotherapie, Oetwil am See, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana I.","family":"Oliveira-Ferreira","sequence":"additional","affiliation":[{"name":"Centre for Stroke Research Berlin, Charit\u00e9 \u2013 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens","family":"Reiffurth","sequence":"additional","affiliation":[{"name":"Centre for Stroke Research Berlin, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"},{"name":"Department of Experimental Neurology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3148-6122","authenticated-orcid":false,"given":"Denny","family":"Milakara","sequence":"additional","affiliation":[{"name":"Centre for Stroke Research Berlin, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu 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Germany"},{"name":"Department of Neurosurgery, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora F.","family":"Dengler","sequence":"additional","affiliation":[{"name":"Centre for Stroke Research Berlin, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"},{"name":"Department of Neurosurgery, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agustin","family":"Liotta","sequence":"additional","affiliation":[{"name":"Centre for Stroke Research 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and Berlin Institute of Health, Berlin, Germany"},{"name":"Department of Neurosurgery, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina M.","family":"Kowoll","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 P.","family":"Schulte","sequence":"additional","affiliation":[{"name":"Department of Spinal Surgery, Krankenhaus der Augustinerinnen, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Heidelberg University Hospital, Ruprecht-Karls-University 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Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Bohner","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Scheel","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Vajkoczy","sequence":"additional","affiliation":[{"name":"Centre for Stroke Research Berlin, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t 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