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Published Online
on June 12, 2008

Stroke. 2008
Published online before print June 12, 2008, doi: 10.1161/STROKEAHA.107.505420
A more recent version of this article appeared on August 1, 2008
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Submitted on September 25, 2007
Revised on December 12, 2007
Accepted on December 14, 2007

Early Disruption of the Blood–Brain Barrier After Thrombolytic Therapy Predicts Hemorrhage in Patients With Acute Stroke

Andreas Kastrup MD*; Klaus Gröschel MD; Thomas M. Ringer MD; Christoph Redecker MD; Robert Cordesmeyer MD; Otto W. Witte MD; and Christoph Terborg MD

From the Department of Neurology (A.K., K.G., R.C.), University of Göttingen, Göttingen, Germany; and the Department of Neurology (A.K., K.G., T.M.R., C.R., O.W.W., C.T.), University of Jena, Jena, Germany.

* To whom correspondence should be addressed. E-mail: andreas.kastrup{at}medizin.uni-goettingen.de.

Background and Purpose—Leaks of the blood–brain barrier can be detected on postcontrast-enhanced T1-weighted MRIs. Although early disruptions of the blood–brain barrier appear to be an important risk factor for tissue plasminogen activator-related hemorrhages in rodents, little is known about their incidence and consequences in human stroke.

Methods—This is a retrospective analysis of a prospectively collected stroke database over the past 6 years. In 52 patients, multimodal MRI (including diffusion-weighted, perfusion-weighted, and postcontrast-enhanced T1-weighted MRI to detect blood–brain barrier changes) had been performed immediately before systemic thrombolysis and in 48 patients within a median of 30 minutes (interquartile range: 30 to 60 minutes) after recombinant tissue plasminogen activator treatment. The incidence of symptomatic hemorrhage (SICH), defined as any parenchymal hemorrhage leading to deterioration in the patient's clinical condition, was related to several clinical and imaging variables, including early blood–brain barrier changes.

Results—Overall, SICH was detected in 9 (9%) patients and among these, 2 died. Although no blood–brain barrier changes were detectable before thrombolysis, 3 of 48 patients (6.25%) had a parenchymal gadolinium enhancement in the areas of initial infarction after tissue plasminogen activator treatment. All 3 patients developed SICHs at sites corresponding to the areas of enhancement. The presence of a parenchymal enhancement was significantly associated with SICH (P<0.01), whereas other clinical and imaging variables did not predict SICH in this series.

Conclusion—Early parenchymal enhancement after intravenous tissue plasminogen activator is significantly associated with subsequent SICH and could therefore become a useful imaging sign for the rapid initiation of preventive strategies in the future.


Key words: thrombolytic therapy • hemorrhage • magnetic resonance imaging




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A. Kassner, T.P.L. Roberts, B. Moran, F.L. Silver, and D.J. Mikulis
Recombinant Tissue Plasminogen Activator Increases Blood-Brain Barrier Disruption in Acute Ischemic Stroke: An MR Imaging Permeability Study
AJNR Am. J. Neuroradiol., November 1, 2009; 30(10): 1864 - 1869.
[Abstract] [Full Text] [PDF]