Background and Purpose— 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 ≤2 at 24 hours) and favorable outcomes at 3 months (modified Rankin Scale ≤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 ≤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 ≤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.

Background and Purpose— Patients may experience clinical deterioration (CD) after treatment with intravenous recombinant tissue plasminogen activator (rt-PA). We evaluated the ability of flow findings on transcranial Doppler to predict CD and outcomes on modified Rankin Scale. Methods— Patients with acute stroke received intravenous rt-PA within 3 hours of symptom onset at four academic centers. CD was defined as an increase in the National Institutes of Health Stroke Scale (NIHSS) score by 4 points or more within 24 hours. Poor long-term outcome was defined by modified Rankin Scale ≥2 at 3 months. Transcranial Doppler findings were interpreted using the Thrombolysis in Brain Ischemia flow grading system as persistent arterial occlusion, reocclusion, or complete recanalization. Multiple regression analysis was used to identify transcranial Doppler flow as a predictor for CD after controlling for age, sex, baseline NIHSS, hypertension, and glucose. Results— A total of 374 patients received intravenous rt-PA at 142±60 minutes (median pretreatment NIHSS score 16 points). At the end of intravenous rt-PA infusion, transcranial Doppler showed persistent arterial occlusion in 219 patients (59%), arterial reocclusion in 54 patients (14%), and complete recanalization in 101 patients (27%). CD occurred in 44 patients: 36 had persistent arterial occlusion or reocclusion (82%), 13 symptomatic intracerebral hemorrhage (29%), and both persistent occlusion/reocclusion and symptomatic intracerebral hemorrhage in 10 patients (23%). After adjustment, patient risk for CD with persistent occlusion was OR 1.7 (95% CI: 0.7 to 4) and with arterial reocclusion 4.9 (95% CI: 1.7 to 13) ( P =0.002). Patient risk for poor long-term outcomes with persistent occlusion, partial recanalization, or reocclusion was OR 5.2 (95% CI: 2.7 to 9, P =0.001). Conclusions— Inability to achieve or sustain vessel patency at the end of rt-PA infusion correlates with the likelihood of clinical deterioration and poor long-term outcome. Early arterial reocclusion on transcranial Doppler is highly predictive of CD and poor outcome.

Background and Purpose— We routinely perform an urgent bedside neurovascular ultrasound examination (NVUE) with carotid/vertebral duplex and transcranial Doppler (TCD) in patients with acute cerebral ischemia. We aimed to determine the yield and accuracy of NVUE to identify lesions amenable for interventional treatment (LAITs). Methods— NVUE was performed with portable carotid duplex and TCD using standardized fast-track (<15 minutes) insonation protocols. Digital subtraction angiography (DSA) was the gold standard for identifying LAIT. These lesions were defined as proximal intra- or extracranial occlusions, near-occlusions, ≥50% stenoses or thrombus in the symptomatic artery. Results— One hundred and fifty patients (70 women, mean age 66±15 years) underwent NVUE at median 128 minutes after symptom onset. Fifty-four patients (36%) received intravenous or intra-arterial thrombolysis (median National Institutes of Health Stroke Scale (NIHSS) score 14, range 4 to 29; 81% had NIHSS ≥10 points). NVUE demonstrated LAITs in 98% of patients eligible for thrombolysis, 76% of acute stroke patients ineligible for thrombolysis (n=63), and 42% in patients with transient ischemic attack (n=33), P <0.001. Urgent DSA was performed in 30 patients on average 230 minutes after NVUE. Compared with DSA, NVUE predicted LAIT presence with 100% sensitivity and 100% specificity, although individual accuracy parameters for TCD and carotid duplex specific to occlusion location ranged 75% to 96% because of the presence of tandem lesions and 10% rate of no temporal windows. Conclusions— Bedside neurovascular ultrasound examination, combining carotid/vertebral duplex with TCD yields a substantial proportion of LAITs in excellent agreement with urgent DSA.

Background: Symptomatic intracerebral hemorrhage (sICH) is the most unfavorable complication after IV thrombolytic treatment. We aimed to determine the relationship between early recanalization and the risk of sICH. Methods: Patients with acute stroke received IV tissue plasminogen activator (rt-PA) within 3 hours of symptom onset with transcranial Doppler (TCD) monitoring at four academic centers. sICH was defined as parenchymal hemorrhage on CT in relation to neurologic worsening (NIH Stroke Scale [NIHSS] ≥4) within 72 hours after treatment. Poor outcome was defined as modified Rankin Scale 3-6 at 3 months. Early recanalization was graded with Thrombolysis in Brain Ischemia (TIBI) system. Multiple logistic regression analyses were used to identify predictors of sICH. Results: A total of 349 patients received rt-PA at median 134 ± 32 minutes (mean age 69 ± 13 years, 186 men [53%]). Median pretreatment NIHSS score was 16 points (interquartile range: 12-20). Median time to TCD was 130 ± 40 minutes. At the end of rt-PA infusion, 135 patients (38%) had no recanalization, 101 (29%) partial, and 113 (32%) complete recanalization. sICH occurred in 26 patients (7.4%). Of the 135 patients without early recanalization, 18 (13%) had sICH, as compared to 4 (4%) of the 109 subjects with partial recanalization and 4 (3.5%) of 113 with complete recanalization, p = 0.005. After adjustment for age, sex, baseline NIHSS score, glucose, blood pressure, and time to treatment, patients with persistent occlusion had sixfold higher risk of sICH (OR = 6, 95% CI 1.5-21.3, p = 0.01). Conclusion: The risk of tPA-related symptomatic intracerebral hemorrhage (sICH) is low after early and complete restoration of blood flow. Arterial occlusion persistent beyond tissue plasminogen activator infusion emerges as an independent predictor of higher risk of sICH in patients treated with systemic thrombolysis.