Effect of Intravenous Alteplase on Ischemic Lesion Water Homeostasis.

Broocks, Gabriel; Kniep, Helge; Kemmling, Andre; Flottmann, Fabian; Nawabi, Jawed; Elsayed, Sarah; Schön, Gerhard; Thomalla, Götz; Fiehler, Jens; Hanning, Uta

BACKGROUND Intravenous (IV) lysis with alteplase is known to increase biomarkers of blood brain barrier breakdown and has therefore been associated with secondary injuries such as hemorrhagic transformation. The impact of alteplase on brain edema formation, however, has not been investigated yet. The purpose was to examine the effects of IV alteplase on ischemic lesion water homeostasis differentiated from final tissue infarct in patients with and without successful endovascular therapy (sET). METHODS 232 middle cerebral artery stroke patients were analyzed. 147 patients received IV alteplase, of which 106 patients received subsequent sET. Out of 85 patients without IV alteplase, 50 received sET. Ischemic brain edema was quantified in admission and follow-up CT using quantitative lesion water uptake (NWU) and its difference was calculated (ΔNWU). The relationship of alteplase on ΔNWU and edema-corrected final infarct volume was analyzed using univariate and multivariate linear regression models. RESULTS The mean ΔNWU was 11.8% (SD,7.9) in patients with alteplase and 11.5% (SD,8.3) in patients without alteplase (p=0.8). Alteplase was not associated with lowered ΔNWU while being associated with reduced edema-corrected tissue infarct volume (-27.4 mL; 95%CI: -49.4 to -5.4 mL; p=0.02), adjusted for ASPECTS and recanalization status. In patients with sET, ΔNWU was 10.5% (95%CI: 6.3-10.5%) for patients with IV alteplase and 8.4% (95%CI: 9.1-12.0) for patients without IV alteplase. CONCLUSION The application of IV alteplase did not significantly alter ischemic lesion water homeostasis, but was associated with reduced edema-corrected tissue infarct volume, which might directly be linked to improved functional outcome.