Advanced imaging improves prediction of hemorrhage after stroke thrombolysis
Article first published online: 26 FEB 2013
Copyright © 2012 American Neurological Association
Annals of Neurology
Volume 73, Issue 4, pages 510–519, April 2013
How to Cite
Campbell, B. C. V., Christensen, S., Parsons, M. W., Churilov, L., Desmond, P. M., Barber, P. A., Butcher, K. S., Levi, C. R., De Silva, D. A., Lansberg, M. G., Mlynash, M., Olivot, J.-M., Straka, M., Bammer, R., Albers, G. W., Donnan, G. A. and Davis, S. M. (2013), Advanced imaging improves prediction of hemorrhage after stroke thrombolysis. Ann Neurol., 73: 510–519. doi: 10.1002/ana.23837
- Issue published online: 21 MAY 2013
- Article first published online: 26 FEB 2013
- Accepted manuscript online: 13 DEC 2012 07:32AM EST
- Manuscript Accepted: 30 NOV 2012
- Manuscript Revised: 30 OCT 2012
- Manuscript Received: 1 MAY 2012
- NIH . Grant Number: RO1 NS39325
- principal investigator [PI], G.W.A. . Grant Number: K24 NS044848
- PI, G.W.A. . Grant Number: K23 NS051372
- NIH . Grant Number: R01 EB002711
Very low cerebral blood volume (VLCBV), diffusion, and hypoperfusion lesion volumes have been proposed as predictors of hemorrhagic transformation following stroke thrombolysis. We aimed to compare these parameters, validate VLCBV in an independent cohort using DEFUSE study data, and investigate the interaction of VLCBV with regional reperfusion.
The EPITHET and DEFUSE studies obtained diffusion and perfusion magnetic resonance imaging (MRI) in patients 3 to 6 hours from onset of ischemic stroke. EPITHET randomized patients to tissue plasminogen activator (tPA) or placebo, and all DEFUSE patients received tPA. VLCBV was defined as cerebral blood volume<2.5th percentile of brain contralateral to the infarct. Parenchymal hematoma (PH) was defined using European Cooperative Acute Stroke Study criteria. Reperfusion was assessed using subacute perfusion MRI coregistered to baseline imaging.
In DEFUSE, 69 patients were analyzed, including 9 who developed PH. The >2 ml VLCBV threshold defined in EPITHET predicted PH with 100% sensitivity, 72% specificity, 35% positive predictive value, and 100% negative predictive value. Pooling EPITHET and DEFUSE (163 patients, including 23 with PH), regression models using VLCBV (p<0.001) and tPA (p=0.02) predicted PH independent of clinical factors better than models using diffusion or time to maximum>8 seconds lesion volumes. Excluding VLCBV in regions without reperfusion improved specificity from 61 to 78% in the pooled analysis.
VLCBV predicts PH after stroke thrombolysis and appears to be a more powerful predictor than baseline diffusion or hypoperfusion lesion volumes. Reperfusion of regions of VLCBV is strongly associated with post-thrombolysis PH. VLCBV may be clinically useful to identify patients at significant risk of hemorrhage following reperfusion. ANN NEUROL 2013;73:510–519