title: Site of arterial occlusion identified by transcranial Doppler predicts the response to intravenous thrombolysis for stroke.
abstract: OBJECTIVE
  The objective of this study was to examine clinical outcomes and recanalization rates in a multicenter cohort of stroke patients receiving intravenous tissue plasminogen activator by site of occlusion localized with bedside transcranial Doppler. Angiographic studies with intraarterial thrombolysis suggest more proximal occlusions carry greater thrombus burden and benefit less from local therapy.
  
  
  METHODS
  Using validated transcranial Doppler criteria for specific arterial occlusion (Thrombolysis in Brain Ischemia flow grades), we compared the rate of dramatic recovery (National Institutes of Health Stroke Scale score < or =2 at 24 hours) and favorable outcomes at 3 months (modified Rankin Scale < or =1) for each occlusion site. We determined the likelihood of recanalization at various occlusion sites and its predictors. Then, stepwise logistic regression was used to determine predictors of complete recanalization.
  
  
  RESULTS
  Three hundred thirty-five patients had a mean age 69+/-13 years and 48.5% were women (median baseline National Institutes of Health Stroke Scale score 16 [range, 3 to 32], mean time to transcranial Doppler 140+/-84 minutes, and mean time to intravenous tissue plasminogen activator 145+/-68 minutes). Distal middle cerebral artery occlusion had an OR of 2 for complete recanalization (50 of 113 [44.2%], 95% CI: 1.1 to 3.1, P=0.005), proximal middle cerebral artery 0.7 (49 of 163 [30%], 95% CI: 0.4 to 1.1, P=0.13), terminal internal carotid artery 0.1 (one of 17 [5.9%], 95% CI: 0.015 to 0.8, P=0.015), tandem cervical internal carotid artery/middle cerebral artery 0.7 (6 of 22 [27%], 95% CI: 0.3 to 1.9, P=0.5), and basilar artery 0.96 (3 of 10 [30%], 95% CI: 0.2 to 4, P=0.9). Prerecombinant tissue plasminogen activator National Institutes of Health Stroke Scale score, systolic blood pressure, glucose, and Thrombolysis in Brain Ischemia flow grade at the occlusion site were the negative independent predictors for complete recanalization in the final model. There were no associations among time to treatment, stroke mechanisms, or recanalization rate. Patients with no flow (Thrombolysis in Brain Ischemia 0) at the occlusion site had less probability of complete recanalization than patients with dampened flow (Thrombolysis in Brain Ischemia 3) (OR(adj): 0.256, 95% CI: 0.11 to 0.595, P=0.002). Continuous transcranial Doppler monitoring (exposure to ultrasound) was a positive predictor for complete recanalization (OR(adj): 3.02, 95% CI: 1.396 to 6.514, P=0.005). National Institutes of Health Stroke Scale score < or =2 at 24 hours was achieved in 66 of 305 patients (22%): distal middle cerebral artery 33% (35 of 107), tandem cervical internal carotid artery/middle cerebral artery 24% (5 of 21), proximal middle cerebral artery 16% (24 of 155), basilar artery 25% (2 of 8), and none of the patients with terminal internal carotid artery had dramatic recovery (0%, n=14; P=0.003). Modified Rankin Scale score < or =1 was achieved in 90 of 260 patients (35%): distal middle cerebral artery 52% (50 of 96), proximal middle cerebral artery 25% (33 of 131), tandem cervical internal carotid artery/middle cerebral artery 21% (3 of 14), terminal internal carotid artery 18% (2 of 11), and basilar artery 25% (2 of 8) (P<0.001). Patients with distal middle cerebral artery occlusion were twice as likely to have a good long-term outcome as patients with proximal middle cerebral artery (OR: 2.1, 95% CI: 1.1 to 4, P=0.025).
  
  
  CONCLUSIONS
  Clinical response to thrombolysis is influenced by the site of occlusion. Patients with no detectable residual flow signals as well as those with terminal internal carotid artery occlusions are least likely to respond early or long term.
authors.affiliation: Department of Medicine (Neurology), University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Maher
authors.initials: M
authors.lastname: Saqqur
authors.forename: Ken
authors.initials: K
authors.lastname: Uchino
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Demchuk
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Molina
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Garami
authors.forename: Sergio
authors.initials: S
authors.lastname: Calleja
authors.forename: Naveed
authors.initials: N
authors.lastname: Akhtar
authors.forename: Finton O
authors.initials: FO
authors.lastname: Orouk
authors.forename: Abdul
authors.initials: A
authors.lastname: Salam
authors.forename: Ashfaq
authors.initials: A
authors.lastname: Shuaib
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Alexandrov
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001157:Arterial Occlusive Diseases / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D020521:Stroke / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D015912:Thrombolytic Therapy / Q000379:methods*; D017585:Ultrasonography, Doppler, Transcranial / Q000379:methods*