title: Ultrasound-enhanced thrombolysis for acute ischemic stroke: phase I. Findings of the CLOTBUST trial.
abstract: BACKGROUND
  Tissue plasminogen activator (TPA) activity may be enhanced with ultrasound, potentially 2 MHz transcranial Doppler (TCD). The authors present Phase I data of the CLOTBUST (Combined Lysis of Thrombus in Brain ischemia using transcranial Ultrasound and Systemic TPA).
  
  
  METHODS
  Nonrandomized stroke patients with proximal arterial occlusion on a prebolus TCD receiving intravenous 0.9 mg/kg TPA within 3 hours after stroke onset were monitored with portable diagnostic TCD equipment and a standard headframe. Complete recanalization was defined as thrombolysis in brain ischemia (TIBI) flow grades 4-5.
  
  
  RESULTS
  55 patients (mean age 69 +/- 15 years, median baseline NIH Stroke Scale [NIHSS] 18, range 4-29, 90% with 3 9 points) were treated at 125 +/- 36 minutes from symptom onset. TCD monitoring began at 117 +/- 39 minutes. Complete recanalization on TCD within 2 hours after bolus was found in 20 patients (36%). Dramatic recovery (NIHSS score < or = 3) occurred in 20% at 2 hours and in 24% at 24 hours. Overall improvement by > or = 4 NIHSS points was found in 49% at 24 hours. Improvement was associated with recanalization during or shortly after TPA infusion (phi r2 = .5, P = .03); however, in 6/20 patients with complete recanalization (30%), no immediate clinical change was noticed within 2 hours. Overall symptomatic hemorrhage rate was 5.5%.
  
  
  CONCLUSIONS
  Continuous TCD insonation for up to 2 hours at maximum intensities allowed by current bio-safety guidelines is safe. Dramatic recovery and complete recanalization shortly after TPA bolus are feasible goals for thrombolysis given with TCD monitoring.
authors.affiliation: Center for Noninvasive Brain Perfusion Studies, Stroke Treatment Team, University of Texas-Houston Medical School, Houston, TX, USA. avalexandrov@att.net
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Alexandrov
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Demchuk
authors.forename: W Scott
authors.initials: WS
authors.lastname: Burgin
authors.forename: David J
authors.initials: DJ
authors.lastname: Robinson
authors.forename: James C
authors.initials: JC
authors.lastname: Grotta
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D002536:Cerebral Arteries / Q000000981:diagnostic imaging / Q000187:drug effects; D002544:Cerebral Infarction / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D003131:Combined Modality Therapy; D004867:Equipment Design; D005260:Female; D006801:Humans; D020766:Intracranial Embolism / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009460:Neurologic Examination; D010865:Pilot Projects; D019095:Point-of-Care Systems; D012107:Research Design; D013673:Technology Assessment, Biomedical; D015912:Thrombolytic Therapy / Q000295:instrumentation*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*; D016896:Treatment Outcome; D014464:Ultrasonic Therapy / Q000295:instrumentation*; D017585:Ultrasonography, Doppler, Transcranial / Q000295:instrumentation*
chemical_list: D010959:Tissue Plasminogen Activator