title: Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke.
abstract: BACKGROUND
  Transcranial Doppler ultrasonography that is aimed at residual obstructive intracranial blood flow may help expose thrombi to tissue plasminogen activator (t-PA). Our objective was to determine whether ultrasonography can safely enhance the thrombolytic activity of t-PA.
  
  
  METHODS
  We treated all patients who had acute ischemic stroke due to occlusion of the middle cerebral artery with intravenous t-PA within three hours after the onset of symptoms. The patients were randomly assigned to receive continuous 2-MHz transcranial Doppler ultrasonography (the target group) or placebo (the control group). The primary combined end point was complete recanalization as assessed by transcranial Doppler ultrasonography or dramatic clinical recovery. Secondary end points included recovery at 24 hours, a favorable outcome at three months, and death at three months.
  
  
  RESULTS
  A total of 126 patients were randomly assigned to receive continuous ultrasonography (63 patients) or placebo (63 patients). Symptomatic intracerebral hemorrhage occurred in three patients in the target group and in three in the control group. Complete recanalization or dramatic clinical recovery within two hours after the administration of a t-PA bolus occurred in 31 patients in the target group (49 percent), as compared with 19 patients in the control group (30 percent; P=0.03). Twenty-four hours after treatment of the patients eligible for follow-up, 24 in the target group (44 percent) and 21 in the control group (40 percent) had dramatic clinical recovery (P=0.7). At three months, 22 of 53 patients in the target group who were eligible for follow-up analysis (42 percent) and 14 of 49 in the control group (29 percent) had favorable outcomes (as indicated by a score of 0 to 1 on the modified Rankin scale) (P=0.20).
  
  
  CONCLUSIONS
  In patients with acute ischemic stroke, continuous transcranial Doppler augments t-PA-induced arterial recanalization, with a nonsignificant trend toward an increased rate of recovery from stroke, as compared with placebo.
authors.affiliation: Stroke Treatment Team, University of Texas-Houston Medical School, Houston 77030, USA. avalexandrov@att.net
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Alexandrov
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Molina
authors.forename: James C
authors.initials: JC
authors.lastname: Grotta
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Garami
authors.forename: Shiela R
authors.initials: SR
authors.lastname: Ford
authors.forename: Jose
authors.initials: J
authors.lastname: Alvarez-Sabin
authors.forename: Joan
authors.initials: J
authors.lastname: Montaner
authors.forename: Maher
authors.initials: M
authors.lastname: Saqqur
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Demchuk
authors.forename: Lemuel A
authors.initials: LA
authors.lastname: Moyé
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hill
authors.forename: Anne W
authors.initials: AW
authors.lastname: Wojner
mesh_terms: D000208:Acute Disease; D000368:Aged; D002545:Brain Ischemia / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000628:therapy*; D003131:Combined Modality Therapy; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000628:therapy*; D007275:Injections, Intravenous; D015912:Thrombolytic Therapy / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome; D014464:Ultrasonic Therapy; D017585:Ultrasonography, Doppler, Transcranial
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator