Reperfusion after stroke sonothrombolysis with microbubbles may predict intracranial bleeding

Abstract

Although ultrasound-activated microbubbles (MB) accelerate clot lysis, MB activation has shown to promote blood barrier disruption and bleeding in animal models. We conducted a case-control study aimed to investigate the risk of hemorrhagic transformation (HT) after MB-enhanced sonothrombolysis in acute stroke. We evaluated a total of 296 patients with acute stroke treated with IV tissue plasminogen activator (tPA) <3 hours after stroke onset. One hundred eighty-eight patients received continuous 2-hour TCD monitoring plus 3 doses of 2.5 g of MB after tPA bolus (MB group). These patients were compared with 98 historic stroke patients (control group). The presence and extent of HT on 24-hour CT were blindly assessed. Recanalization rates were higher in the MB compared with the control group at 1, 2, 6, and 12 hours (p < 0.05). MB administration was associated with an increased risk of hemorrhagic infarction (HI)1-HI2 (21% vs 12%, p = 0.026) and a higher degree of clinical improvement at 24 hours (54.9% vs 31.1%, p = 0.004). Parenchymal hematoma (PH)1-PH2 and symptomatic intracranial hemorrhage rates were similar in both groups. Moreover, the extent of bleeding after MB-enhanced sonothrombolysis was correlated with the time to reperfusion. Early (<6 hours) recanalization independently predicted HI in the MB group (odds ratio 6.3, 95% confidence interval 2.3-56) but not in the control group. Delayed (>6 hours) or no recanalization was associated with PH1-PH2 in both the MB group (p = 0.024) and the control group (p = 0.045). This hypothesis-generating study shows that microbubble administration was associated with early recanalization and a high rate of hemorrhagic transformation but does not seem to increase the risk of symptomatic intracranial hemorrhage. However, definitive conclusions cannot be made based on these data.