Ken Uchino

Site of Arterial Occlusion Identified by Transcranial Doppler Predicts the Response to Intravenous Thrombolysis for Stroke

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) (ORadj: 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 (ORadj: 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.

Dabigatran Association With Higher Risk of Acute Coronary Events: Meta-analysis of Noninferiority Randomized Controlled Trials

BACKGROUND The original RE-LY (Randomized Evaluation of Long-term Anticoagulant Therapy) trial suggested a small increased risk of myocardial infarction (MI) with the use of dabigatran etexilate vs warfarin in patients with atrial fibrillation. We systematically evaluated the risk of MI or acute coronary syndrome (ACS) with the use of dabigatran. METHODS We searched PubMed, Scopus, and the Web of Science for randomized controlled trials of dabigatran that reported on MI or ACS as secondary outcomes. The fixed-effects Mantel-Haenszel (M-H) test was used to evaluate the effect of dabigatran on MI or ACS. We expressed the associations as odds ratios (ORs) and their 95% CIs. RESULTS Seven trials were selected (N = 30,514), including 2 studies of stroke prophylaxis in atrial fibrillation, 1 in acute venous thromboembolism, 1 in ACS, and 3 of short-term prophylaxis of deep venous thrombosis. Control arms included warfarin, enoxaparin, or placebo administration. Dabigatran was significantly associated with a higher risk of MI or ACS than that seen with agents used in the control group (dabigatran, 237 of 20,000 [1.19%] vs control, 83 of 10,514 [0.79%]; OR(M-H), 1.33; 95% CI, 1.03-1.71; P = .03). The risk of MI or ACS was similar when using revised RE-LY trial results (OR(M-H), 1.27; 95% CI, 1.00-1.61; P = .05) or after exclusion of short-term trials (OR(M-H), 1.33; 95% CI, 1.03-1.72; P = .03). Risks were not heterogeneous for all analyses (I(2) = 0%; P ≥ .30) and were consistent using different methods and measures of association. CONCLUSIONS Dabigatran is associated with an increased risk of MI or ACS in a broad spectrum of patients when tested against different controls. Clinicians should consider the potential of these serious harmful cardiovascular effects with use of dabigatran.

Moyamoya disease in Washington State and California

The authors identified 298 diagnoses of moyamoya in California and Washington from hospital discharge databases during the period 1987 to 1998. The incidence was 0.086/100,000 persons. The ethnicity-specific incidence rate ratios compared to whites were 4.6 (95% CI: 3.4 to 6.3) for Asian Americans, 2.2 (95% CI: 1.3 to 2.4) for African Americans, and 0.5 (95% CI: 0.3 to 0.8) for Hispanics. The incidence of moyamoya in Washington and California was lower than reported in Japan, but the rate among U.S. Asians is similar.

Emergent Stenting of Extracranial Internal Carotid Artery Occlusion in Acute Stroke Has a High Revascularization Rate

Background and Purpose— Acute ischemic stroke attributable to extracranial internal carotid artery (ICA) occlusion is frequently associated with severe disability or death. In selected cases, revascularization with carotid artery stenting has been reported, but the safety, recanalization rate, and clinical outcomes in consecutive case series are not known. Methods— We retrospectively reviewed all of the cases of ICA occlusions that underwent cerebral angiography with the intent to revascularize over a 38-month period. Two groups were identified: (1) patients who presented with an acute clinical presentation within 6 hours of symptom onset (n=15); and (2) patients who presented subacutely with neurologic fluctuations because of the ICA occlusion (n=10). Results— Twenty-five patients with a mean age of 62±11 years and median National Institutes of Health Stroke Scale (NIHSS) of 14 were identified. Twenty-three of the 25 patients (92%) were successfully revascularized with carotid artery stenting. Patients in group 1 were younger and more likely to have a tandem occlusion and higher baseline NIHSS when compared with group 2. Patients in group 2 were more likely to show early clinical improvement defined as a reduction of their NIHSS by ≥4 points and a modified Rankin Score of ≤2 at 30-day follow-up. Two clinically insignificant adverse events were noted: 1 asymptomatic hemorrhage and 1 nonflow-limiting dissection. Conclusions— Endovascular treatment of acute ICA occlusion appears to have a high-recanalization rate and be relatively safe in our cohort of patients with acute ICA occlusion. Future prospective studies are necessary to determine which patients are most likely to benefit from this form of therapy.

Improving the Predictive Accuracy of Recanalization on Stroke Outcome in Patients Treated With Tissue Plasminogen Activator

Background and Purpose— Although early recanalization is a powerful predictor of stroke outcome after thrombolysis, some stroke patients remain disabled despite tissue plasminogen activator (tPA)–induced recanalization. Therefore, we sought to investigate whether the predictive accuracy of early recanalization on stroke outcome is improved when combined with clinical and radiological information. Methods— We evaluated 177 patients with nonlacunar strokes in the middle cerebral artery (MCA) treated with intravenous tPA who were followed up during 3 months. Transcranial Doppler monitoring of recanalization was conducted during the first hours after tPA administration. The relative contribution of clinical, transcranial Doppler, and radiological information on stroke outcome was evaluated. We used logistic regression to derive a predictive model for good outcome (modified Rankin Scale score ≤2) after thrombolysis. Results— Median National Institutes of Health Stroke Scale (NIHSS) score before tPA was 16. At 3 months, 87 patients (49.2%) became functionally independent (modified Rankin Scale score ≤2). In a logistic regression model, degree of recanalization within 300 minutes (P <0.001), proximal MCA occlusion (P <0.001), baseline NIHSS score (P =0.0013), systolic blood pressure (P =0.0116), and early ischemic changes on CT (P =0.0253) independently predicted outcome at 3 months. A 5-item score was developed on the basis of the factors significantly associated with stroke outcome in the logistic regression (total score range, 0 to 7). The likelihood of good outcome at 3 months was 0.82 (95% CI, 0.72 to 0.92) in patients who scored 0 to 2, 0.51 (95% CI, 0.36 to 0.66) in those who scored 3 to 4, and 0.15 (95% CI, 0.05 to 0.25) in those who scored 5 to 7 points. Conclusions— The combination of clinical, radiological, and hemodynamic information predicts with a high accuracy long-term stroke outcome during or shortly after intravenous tPA administration.

Safety, Feasibility, and Short-Term Follow-Up of Drug-Eluting Stent Placement in the Intracranial and Extracranial Circulation

Background and Purpose— The use of bare metal stents to treat symptomatic intracranial stenosis may be associated with significant restenosis rates. The advent of drug-eluting stents (DESs) in the coronary circulation has resulted in a reduction of restenosis rates. We report our technical success rate and short-term restenosis rates after stenting with DESs in the intracranial and extracranial circulation. Methods— This study was a retrospective review of the period between April 1, 2004, and April 15, 2006, of 59 patients with 62 symptomatic intracranial or extracranial atherosclerotic lesions at 2 medical centers (University of Pittsburgh and Borgess Medical Center). Results— The mean age of our cohort was 61±12 years. The location of the 62 lesions was as follows: extracranial vertebral artery 31 (50%), intracranial vertebral artery or basilar artery 18 (29%), extracranial internal carotid artery (ICA) near the petrous bone 5 (8%), and intracranial ICA 8 (13%). There were 2 (3%) periprocedural complications: 1 non—flow-limiting dissection and 1 disabling stroke. Fifty vessels were available for follow-up angiography or computed tomography angiography at a median time of 4.0±2 months. A total of 2 of 36 extracranial stents (7%) and 1 of 26 intracranial stents (5%) were found to have restenosis ≥50% at follow-up. Conclusions— This report demonstrates that DES delivery in the intracranial and extracranial circulation is technically feasible. A small percentage of patients developed short-term in-stent restenosis. Longer-term follow-up is required in the setting of a prospective study to determine the late restenosis rates for DESs in comparison with bare metal stents.

Clinical Deterioration After Intravenous Recombinant Tissue Plasminogen Activator Treatment A Multicenter Transcranial Doppler Study

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.

Multimodal Reperfusion Therapy for Acute Ischemic Stroke: Factors Predicting Vessel Recanalization

Background and Purpose— Endovascular therapies using mechanical and pharmacological modalities for large vessel occlusions in acute stroke are rapidly evolving. Our aim was to determine whether one modality is associated with higher recanalization rates. Methods— We retrospectively reviewed 168 consecutive patients treated with intra-arterial (IA) therapy for acute ischemic stroke between May 1999 and November 15, 2005. Demographic, clinical, radiographic, angiographic, and procedural notes were reviewed. Recanalization was defined as achieving thrombolysis in myocardial infarction 2 or 3 flow after intervention. A logistic regression model was constructed to determine independent predictors of successful recanalization. Results— A total of 168 patients were reviewed with a mean age of 64±13 years and mean National Institutes of Health Stroke Scale score of 17±4. Recanalization was achieved in 106 (63%) patients. Independent predictors of recanalization include: the combination of IA thrombolytics and glycoprotein IIb/IIIa inhibitors (odds ratio [OR], 2.9 [95% CI, 1.04 to 6.7]; P<0.048), intracranial stent placement with angioplasty (OR, 4.8 [95% CI, 1.8 to 10.0]; P<0.001), or extracranial stent placement with angioplasty (OR, 4.2 [95% CI, 1.4 to 9.8]; P<0.014). Lesions at the terminus of the internal carotid artery were recalcitrant to revascularization (OR, 0.34 [95% CI, 0.16 to 0.73]; P value 0.006). Conclusions— Intracranial or extracranial stenting or combination therapy with IA thrombolytics and glycoprotein IIb/IIIa inhibitors in the setting of multimodal therapy is associated with successful recanalization in patients treated with multimodal endovascular reperfusion therapy for acute ischemic stroke.

Symptomatic intracerebral hemorrhage and recanalization after IV rt-PA A multicenter study

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.

Mechanical Approaches Combined With Intra-Arterial Pharmacological Therapy Are Associated With Higher Recanalization Rates Than Either Intervention Alone in Revascularization of Acute Carotid Terminus Occlusion

Background and Purpose— Acute stroke attributable to internal carotid artery terminus occlusion carries a poor prognosis. Vessel recanalization is crucial to improve clinical outcome. Historically, pharmacological thrombolysis alone has low recanalization rates. We sought to determine whether adjunctive mechanical approaches achieve better vessel recanalization and functional outcome. Methods— We retrospectively reviewed 75 consecutive endovascular cases of acute internal carotid artery terminus occlusions treated at our center between 1998 and 2008. Mechanical approaches (MERCI retrieval/angioplasty/stent) with and without adjunctive intra-arterial pharmacological therapy (urokinase or tissue plasminogen activator) was compared to intra-arterial lytics alone. Univariate and multivariate analyses were performed to determine predictors of recanalization (thrombolysis in myocardial infarction grades 2 to 3) and favorable functional outcome (modified Rankin score ≤2) at 3 months. Results— Lowest recanalization rates were observed with intra-arterial lytics alone (3/17, 17.6%). MERCI embolectomy combined with intra-arterial lytics was associated with the highest recanalization rates (18/21, 85.7%; P<0.0001). MERCI embolectomy alone achieved 46.2% recanalization rates (6/13; P=0.23). Angioplasty or stenting and intra-arterial lytics achieved 25% (2/8; P=0.65) and 40% (4/10; P=0.085) recanalization, respectively. In multivariate analysis, combination of MERCI embolectomy with intra-arterial lytics (OR, 16.2; CI, 4.6–77.6), or any mechanical technique with intra-arterial lytics (OR, 6.7; CI, 2.5–19.5) independently predicted thrombolysis in myocardial infarction 2 to 3 recanalization. Clinically significant parenchymal hemorrhage rates were 7.5% with combination (3/38) and 12.5% with pharmacological therapies (2/16; P=0.46). Using stepwise logistic regression, age (OR, 0.95; CI, 0.90–0.995), baseline NIHSS (OR, 0.82; CI, 0.70–0.96), and thrombolysis in myocardial infarction 2 to 3 recanalization (OR, 4.0; CI, 1.1–14.4) were associated with favorable functional outcome. Conclusions— Combined mechanical and intra-arterial pharmacological therapy is associated with higher recanalization rates than either intervention alone in acute internal carotid artery terminus occlusion revascularization.