title: Reperfusion after stroke sonothrombolysis with microbubbles may predict intracranial bleeding.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Stroke Unit, Department of Neurology, University of Genova, San Martino Hospital, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Dinia
authors.forename: M
authors.initials: M
authors.lastname: Rubiera
authors.forename: M
authors.initials: M
authors.lastname: Ribo
authors.forename: O
authors.initials: O
authors.lastname: Maisterra
authors.forename: G
authors.initials: G
authors.lastname: Ortega
authors.forename: M
authors.initials: M
authors.lastname: del Sette
authors.forename: J
authors.initials: J
authors.lastname: Alvarez-Sabin
authors.forename: C A
authors.initials: CA
authors.lastname: Molina
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002544:Cerebral Infarction / Q000000981:diagnostic imaging / Q000209:etiology; D005260:Female; D006801:Humans; D020300:Intracranial Hemorrhages / Q000000981:diagnostic imaging* / Q000209:etiology*; D008297:Male; D045423:Microbubbles / Q000009:adverse effects*; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D015424:Reperfusion / Q000009:adverse effects; D020521:Stroke / Q000150:complications / Q000628:therapy*; D015912:Thrombolytic Therapy / Q000009:adverse effects*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects; D017585:Ultrasonography, Doppler, Transcranial / Q000009:adverse effects
chemical_list: D010959:Tissue Plasminogen Activator