Dreier, Jens P., Winkler, Maren K. L., Major, Sebastian ORCID: 0000-0003-0970-1308, Horst, Viktor, Lublinsky, Svetlana, Kola, Vasilis, Lemale, Coline L., Kang, Eun-Jeung, Maslarova, Anna, Salur, Irmak, Lueckl, Janos, Platz, Johannes, Jorks, Devi, Oliveira-Ferreira, Ana, I, Schoknecht, Karl, Reiffurth, Clemens ORCID: 0000-0002-1372-1240, Milakara, Denny ORCID: 0000-0003-3148-6122, Wiesenthal, Dirk, Hecht, Nils, Dengler, Nora F., Liotta, Agustin, Wolf, Stefan, Kowoll, Christina M., Schulte, Andre P., Santos, Edgar ORCID: 0000-0002-8976-5549, Gueresir, Erdem, Unterberg, Andreas W., Sarrafzadeh, Asita, Sakowitz, Oliver W., Vatter, Hartmut, Reiner, Michael, Brinker, Gerrit, Dohmen, Christian, Shelef, Ilan, Bohner, Georg ORCID: 0000-0002-1919-092X, Scheel, Michael ORCID: 0000-0002-3505-2914, Vajkoczy, Peter, Hartings, Jed A., Friedman, Alon, Martus, Peter and Woitzik, Johannes (2022). Spreading depolarizations in ischaemia after subarachnoid haemorrhage, a diagnostic phase III study. Brain, 145 (4). S. 1264 - 1285. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2156

Full text not available from this repository.

Abstract

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. 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. 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 >0.60 sensitivity and >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: 0.65-0.84), P = 0.0014] but specificity was 0.59 (0.47-0.70), i.e. <0.80 (P < 0.0001). Nevertheless, the area under the receiver operating characteristic (AUROC) curve of delayed depression duration was 0.76 (0.69-0.83, P < 0.0001) for delayed infarction and 0.88 (0.81-0.94, P < 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 (0.70-0.97, 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 (beta = 0.474, P < 0.001), delayed median Glasgow Coma Score (beta = -0.201, P = 0.005) and peak transcranial Doppler (beta = 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. 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 >0.60 sensitivity and >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. Focal damage after subarachnoid haemorrhage results from intracerebral haemorrhage and cerebral ischaemia. In a prospective, observational, multicentre, diagnostic phase III trial, DISCHARGE-1, Dreier et al. examine whether monitoring cortical spreading depolarizations can predict delayed infarction-and thus poor outcomes.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Dreier, Jens P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Winkler, Maren K. L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Major, SebastianUNSPECIFIEDorcid.org/0000-0003-0970-1308UNSPECIFIED
Horst, ViktorUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lublinsky, SvetlanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kola, VasilisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lemale, Coline L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kang, Eun-JeungUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maslarova, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salur, IrmakUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lueckl, JanosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Platz, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jorks, DeviUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oliveira-Ferreira, Ana, IUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schoknecht, KarlUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reiffurth, ClemensUNSPECIFIEDorcid.org/0000-0002-1372-1240UNSPECIFIED
Milakara, DennyUNSPECIFIEDorcid.org/0000-0003-3148-6122UNSPECIFIED
Wiesenthal, DirkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hecht, NilsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dengler, Nora F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liotta, AgustinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolf, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kowoll, Christina M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schulte, Andre P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Santos, EdgarUNSPECIFIEDorcid.org/0000-0002-8976-5549UNSPECIFIED
Gueresir, ErdemUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Unterberg, Andreas W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sarrafzadeh, AsitaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sakowitz, Oliver W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vatter, HartmutUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reiner, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brinker, GerritUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dohmen, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shelef, IlanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bohner, GeorgUNSPECIFIEDorcid.org/0000-0002-1919-092XUNSPECIFIED
Scheel, MichaelUNSPECIFIEDorcid.org/0000-0002-3505-2914UNSPECIFIED
Vajkoczy, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hartings, Jed A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Friedman, AlonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martus, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Woitzik, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-697887
DOI: 10.1093/brain/awab457
Journal or Publication Title: Brain
Volume: 145
Number: 4
Page Range: S. 1264 - 1285
Date: 2022
Publisher: OXFORD UNIV PRESS
Place of Publication: OXFORD
ISSN: 1460-2156
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
DELAYED CEREBRAL-ISCHEMIA; BLOOD-BRAIN-BARRIER; IN-VIVO; TRANSCRANIAL DOPPLER; CORTICAL INFARCTS; MIGRAINE AURA; DEPRESSION; VASOSPASM; EDEMA; PROPAGATIONMultiple languages
Clinical Neurology; NeurosciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69788

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item