TY  - JOUR
A1  - Lublinsky, Svetlana
A1  - Major, Sebastian
A1  - Kola, Vasilis
A1  - Horst, Viktor
A1  - Santos, Edgar
A1  - Platz, Johannes
A1  - Sakowitz, Oliver
A1  - Scheel, Michael
A1  - Dohmen, Christian
A1  - Graf, Rudolf
A1  - Vatter, Hartmut
A1  - Wolf, Stefan
A1  - Vajkoczy, Peter
A1  - Shelef, Ilan
A1  - Woitzik, Johannes
A1  - Martus, Peter
A1  - Dreier, Jens P.
A1  - Friedman, Alon
T1  - Early blood-brain barrier dysfunction predicts neurological outcome following aneurysmal subarachnoid hemorrhage
T2  - EBioMedicine
N2  - Background: Disease progression and delayed neurological complications are common after aneurysmal subarachnoid hemorrhage (aSAH). We explored the potential of quantitative blood-brain barrier (BBB) imaging to predict disease progression and neurological outcome.
Methods: Data were collected as part of the Co-Operative Studies of Brain Injury Depolarizations (COSBID). We analyzed retrospectively, blinded and semi-automatically magnetic resonance images from 124 aSAH patients scanned at 4 time points (24–48 h, 6–8 days, 12–15 days and 6–12 months) after the initial hemorrhage. Volume of brain with apparent pathology and/or BBB dysfunction (BBBD), subarachnoid space and lateral ventricles were measured. Neurological status on admission was assessed using the World Federation of Neurosurgical Societies and Rosen-Macdonald scores. Outcome at ≥6 months was assessed using the extended Glasgow outcome scale and disease course (progressive or non-progressive based on imaging-detected loss of normal brain tissue in consecutive scans). Logistic regression was used to define biomarkers that best predict outcomes. Receiver operating characteristic analysis was performed to assess accuracy of outcome prediction models.
Findings: In the present cohort, 63% of patients had progressive and 37% non-progressive disease course. Progressive course was associated with worse outcome at ≥6 months (sensitivity of 98% and specificity of 97%). Brain volume with BBBD was significantly larger in patients with progressive course already 24–48 h after admission (2.23 (1.23–3.17) folds, median with 95%CI), and persisted at all time points. The highest probability of a BBB-disrupted voxel to become pathological was found at a distance of ≤1 cm from the brain with apparent pathology (0·284 (0·122–0·594), p < 0·001, median with 95%CI). A multivariate logistic regression model revealed power for BBBD in combination with RMS at 24-48 h in predicting outcome (ROC area under the curve = 0·829, p < 0·001).
Interpretation: We suggest that early identification of BBBD may serve as a key predictive biomarker for neurological outcome in aSAH.
Fund: Dr. Dreier was supported by grants from the Deutsche Forschungsgemeinschaft (DFG) (DFG DR 323/5-1 and DFG DR 323/10–1), the Bundesministerium für Bildung und Forschung (BMBF) Center for Stroke Research Berlin 01 EO 0801 and FP7 no 602150 CENTER-TBI.
Dr. Friedman was supported by grants from Israel Science Foundation and Canada Institute for Health Research (CIHR). Dr. Friedman was supported by grants from European Union's Seventh Framework Program (FP7/2007–2013; grant #602102).
KW  - Aneurysmal subarachnoid hemorrhage
KW  - Blood-brain barrier
KW  - Extended Glasgow outcome scale (eGOS)
KW  - Magnetic resonance imaging (MRI)
KW  - Lesion
KW  - Long term output
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/53563
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-535639
SN  - 2352-3964
N1  - © 2019 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
VL  - 43
SP  - 460
EP  - 472
PB  - Elsevier
CY  - Amsterdam [u. a.]
ER  -