DISCHARGE-1: Depolarisations in ISChaemia after subarachnoid HAemoRrhaGE-1
Zusammenfassung der Projektergebnisse
Focal brain damage after aSAH predominantly results from ICH, ECI and DCI. The prospective, observational, multicentre, cohort, diagnostic phase III trial, DISCHARGE-1, primarily investigated whether the peak total SD-induced depression duration of a recording day during delayed neuromonitoring (delayed PTDDD) indicates delayed ipsilateral infarction. Consecutive patients (n=205) who required neurosurgery were enrolled in six universityhospitals [Campus Benjamin Franklin (n=66) and Campus Virchow Klinikum (n=61), Charité-Universitätsmedizin Berlin; University of Bonn (n=26); Goethe-University Frankfurt (n=23); University of Cologne (n=16); and University Hospital Heidelberg (n=13)] from 09/2009 to 04/2018. Subdural electrodes for ECoG were implanted. Participants were excluded based on 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 two weeks. During 4.5 years of cumulative recording, 6777 SDs 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-minute delayed PTDDD cutoff in a 24-hour window predicts delayed infarction with >0.60 sensitivity and >0.80 specificity, and to estimate a new cutoff. The 60-minutecutoff was too short. Sensitivity was sufficient [=0.76 (95% confidence interval: 0.65-0.84), P=0.0014] but specificity 0.59 (0.47-0.70), i.e. <0.80 (P<0.0001). Nevertheless, the AUROC of delayed PTDDD 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 DND or infarction). In secondary analysis, a new 180-minute-cutoff indicated delayed infarction with a targeted 0.62 sensitivity and 0.83 specificity. In awake patients, AUROC of delayed PTDDD was 0.84 (0.70-0.97, P=0.001) and the prespecified 60-minute-cutoff showed 0.71 sensitivity and 0.82 specificity for reversible neurological deficits. In multivariate analysis, delayed PTDDD (β=0.474, P<0.001), delayed median GCS (β=-0.201, P=0.005), and TCD-determined peak mbfv (β=0.169, P=0.016) explained 35% of variance in delayed infarction. Another key finding was that SD-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. Conclusion: While the 60-minute-cutoff of cumulative depression in a 24-hour window indicated reversible DND, only a 180-minute-cutoff 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-minute- rather than the 180-minute-cutoff if progression of injury to infarction is to be prevented.
Projektbezogene Publikationen (Auswahl)
-
(2022) Spreading depolarisations in ischaemia after subarachnoid haemorrhage, a diagnostic phase III study. Brain 145:1264-1284
Dreier JP, Winkler MKL, Major S, Horst V, Lublinsky S, Kola V, Lemale CL, Kang EJ, Maslarova A, Salur I, Lückl J, Platz J, Jorks D, Oliveira-Ferreira AI, Schoknecht K, Reiffurth C, Milakara D, Wiesenthal D, Hecht N, Dengler NF, Liotta A, Wolf S, Kowoll CM, Schulte AP, Santos E, Güresir E, Unterberg AW, Sarrafzadeh A, Sakowitz OW, Vatter H, Reiner M, Brinker G, Dohmen C, Shelef I, Bohner G, Scheel M, Vajkoczy P, Hartings JA, Friedman A, Martus P, Woitzik J
