title: Intra-arterial administration of microbubbles and continuous 2-MHz ultrasound insonation to enhance intra-arterial thrombolysis.
abstract: BACKGROUND
  Microbubbles (MB) and ultrasound have been shown to enhance thrombolysis. We sought to evaluate safety and efficacy on middle cerebral artery (MCA) recanalization of local MB administration during intra-arterial (IA) thrombolysis and continuous transcranial Doppler (TCD) monitoring.
  
  
  METHODS
  Patients with acute M1-MCA occlusion were treated with intravenous tissue plasminogen activator (iv-tPA) and continuously monitored with TCD. If recanalization was not achieved during first-hour bridging IA-rescue was adopted: MB + tPA direct intraclot microcatheter infusion. TCD flow monitoring allowed continuous insonation at clot location. Recanalization was angiographically assessed (thrombolysis in cerebral infarction [TICI] score) and compared with simultaneous TCD data. IA procedures were stopped at 6 hours. Recanalization was reassessed at 12 hours (TCD). Neurological status was repeatedly assessed (National Institutes of Health Stroke Scale [NIHSS]). At three months, patients were considered independent if mRS <or= 2.
  
  
  RESULTS
  Of the 18 included patients (mean age 72), 16 received standard iv-tPA (.9 mg/kg). Nine patients were recanalized during tPA infusion and 9 patients underwent IA-rescue procedures. Median pre-IA NIHSS score: 20. Median time to IA initiation was 175 +/- 63 minutes. Mean IA doses were tPA = 10 +/- 3 mg and MB = 3 +/- 1 mL. TCD monitoring allowed direct visualization of massive MB arrival during every administration. In-procedure recanalization was observed in 78% (n= 7): complete-TICI3 in 22% (n= 2), partial-TICI2 in 56% (n= 5). Perfect correlation was observed between TICI and TCD scores. At 12 hours complete recanalization increased to 56%, partial to 22%. One patient (11%) experienced symptomatic intracranial hemorrhage accounting for the only death. Median NIHSS evolution was 12 at 24 hours and 10 at discharge. At 3 months 4 patients (44%) were independent.
  
  
  CONCLUSIONS
  The combination of ultrasound and IA MB and tPA may be a strategy to enhance the thrombolytic effect and increase recanalization rates.
authors.affiliation: Unitat Neurovascular, Servei de Neurologia, Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain. marcriboj@hotmail.com
authors.forename: Marc
authors.initials: M
authors.lastname: Ribo
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Molina
authors.forename: Beatriz
authors.initials: B
authors.lastname: Alvarez
authors.forename: Marta
authors.initials: M
authors.lastname: Rubiera
authors.forename: Jose
authors.initials: J
authors.lastname: Alvarez-Sabin
authors.forename: Manel
authors.initials: M
authors.lastname: Matas
mesh_terms: D000368:Aged; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008297:Male; D045423:Microbubbles; D020768:Middle Cerebral Artery / Q000000981:diagnostic imaging; D020521:Stroke / Q000000981:diagnostic imaging / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome; D017585:Ultrasonography, Doppler, Transcranial
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator