Association of reperfusion with brain edema in patients with acute ischemic stroke: A secondary analysis of the MR CLEAN Trial

W. Taylor Kimberly*, Bruna Garbugio Dutra, Anna M.M. Boers, Heitor C.B.R. Alves, Olvert A. Berkhemer, Lucie A. van den Berg, Kevin N. Sheth, Yvo B.W.E.M. Roos, Aad van der Lugt, Ludo F.M. Beenen, Diederik W.J. Dippel, Wim H. van Zwam, Robert J. van Oostenbrugge, Hester F. Lingsma, Henk A. Marquering, Charles B.L.M. Majoie, Peter J. Koudstaal, Lucie A. van den Berg, Paul H.J. Nederkoorn, Debbie BeumerJulie Staals, Jelis Boiten, Marieke J.H. Wermer, L. Jaap Kappelle, Ewoud J. Van Dijk, Wouter J. Schonewille, Jeannette Hofmeijer, Jacques A. van Oostayen, Patrick C. Vroomen, Paul L.M. de Kort, Koos Keizer, Sebastiaan F. de Bruijn, J. S.Peter Van Den Berg, Tobien H.C.M.L. Schreuder, Leo A.M. Aerden, H. Zwenneke Flach, Marieke C. Visser, Heleen M. den Hertog, Patrick A. Brouwer, Bart J. Emmer, Marieke E.S. Sprengers, René van den Berg, Geert J. Lycklama à Nijeholt, Marianne A.A. van Walderveen, Rob H. Lo, Joost de Vries, Jan Albert Vos, Omid Eshghi, Alexander V. Tielbeek, Lukas C. van Dijk, Boudewijn A.A.M. van Hasselt, Roel J.J. Heijboer, René J. Dallinga, Joseph C.J. Bot, Dick G Gerrits, Puck SS Fransen, Henk A. Marquering, Ewout W. Steyerberg, Albert J. Yoo, Sjoerd F.M. Jenniskens, Renske M. van den Berg-Vos, Giorgos B. Karas, Martin Brown, Thomas Liebig, Theo Stijnen, Tommy Andersson, Heinrich Mattle, Nils Wahlgren, Esther van der Heijden, Naziha Ghannouti, Nadine Fleitour, Imke Hooijenga, Corina Puppels, Wilma Pellikaan, Annet Geerling, Annemieke Lindl-Velema, Gina van Vemde, Ans de Ridder, Paut Greebe, José de Bont-Stikkelbroeck, Joke de Meris, Kirsten Janssen, Willy Struijk, Silvan Licher, Nikki Boodt, Adriaan Ros, Esmee Venema, Ilse Slokkers, Raymie Jayce Ganpat, Maxim Mulder, Nawid Saiedie, Alis Heshmatollah, Stefanie Schipperen, Stefan Vinken, Tiemen van Boxtel, Jeroen Koets

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

106 Citations (Scopus)


IMPORTANCE: It is uncertain whether therapeutic reperfusion with endovascular treatment yields more or less brain edema.

OBJECTIVE: To elucidate the association between reperfusion and brain edema. The secondary objectives were to evaluate whether brain edema could partially be responsible for worse outcomes in patients with later reperfusion or lower Alberta Stroke Program Early Computed Tomography Score.

DESIGN, SETTING, AND PARTICIPANTS: This was a post hoc analysis of the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN), which was a prospective, randomized, multicenter clinical trial of endovascular treatment compared with conventional care of patients with acute anterior circulation ischemic stroke. Of 502 patients enrolled from December 2010 to June 2014, 2 patients declined to participate. Additionally, exclusion criteria were absence of follow-up imaging or presence of parenchymal hematoma, resulting in 462 patients included in this study. Brain edema was assessed retrospectively, from December 10, 2016, to July 24, 2017, by measuring midline shift (MLS) in all available follow-up scans. Observers were blinded to clinical data.

MAIN OUTCOMESAND MEASURES: Midline shift was assessed as present or absent and as a continuous variable. Reperfusion status was assessed by the modified thrombolysis in cerebral infarction score in the endovascular treatment arm. The modified arterial occlusive lesion score was used to evaluate the recanalization status in both arms. The modified Rankin scale score at 90 days was used for functional outcome. RESULTS Of 462 patients, the mean (SD) age was65 (11) years, and 41.8% (n = 193) were women. Successful reperfusion and recanalization were associated with a reduced likelihood of having MLS (adjusted common odds ratio, 0.25; 95% CI, 0.12-0.53; P < .001 and adjusted common odds ratio, 0.34; 95% CI, 0.21-0.55; P < .001, respectively). Midline shift was partially responsible for worse modified Rankin scale scores in patients without reperfusion or recanalization (MLS changed the logistic regression coefficients by 30.3% and 12.6%, respectively). In patients with delayed reperfusion or lower Alberta Stroke Program Early Computed Tomography Score, MLS mediated part of the worse modified Rankin scale scores, corresponding to a change in the regression coefficient of 33.3% and 64.2%, respectively.

CONCLUSIONS AND RELEVANCE: Successful reperfusion was associated with reduced MLS. This study identifies an additional benefit of reperfusion in relation to edema, as well as rescuing ischemic brain tissue at risk for infarction.

Original languageEnglish
Pages (from-to)453-461
Number of pages9
JournalJAMA Neurology
Issue number4
Publication statusPublished - 1 Apr 2018
Externally publishedYes


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