Background and Purpose— We sought to evaluate the effects of administration of microbubbles (MBs) on the beginning, speed, and degree of middle cerebral artery (MCA) recanalization during systemic thrombolysis and continuous 2-MHz pulsed-wave transcranial Doppler (TCD) monitoring. Methods— We evaluated 111 patients with acute stroke attributable to MCA occlusion treated with intravenous tissue plasminogen activator (tPA). Thirty-eight patients were treated with tPA plus continuous 2-hour TCD monitoring plus 3 doses of 2.5 g (400 mg/mL) of galactose-based MBs given at 2, 20, and 40 minutes after tPA bolus (MB group). These patients were compared with 73 patients who were allocated to receive tPA plus continuous 2-hour TCD ultrasound (US) monitoring (tPA/US group) or tPA plus placebo monitoring (tPA group), most of whom were enrolled in a previous study of US-enhanced thrombolysis. The beginning, degree, and time to maximum completeness of recanalization during the first 2 hours of tPA bolus were recorded. Results— Median prebolus National Institutes of Health Stroke Scale (NIHSS) score was 18. Eighty patients (72%) had a proximal and 31 (28%) a distal MCA occlusion on TCD. Thirty-seven patients (33%) received tPA/US, 38 (34%) received tPA/US/MB, and 36 (32%) were treated with tPA alone. Stroke severity, time to treatment, location of MCA occlusion, and presence of carotid artery disease were similar among groups. Two-hour recanalization was seen in 14 (39%), 25 (68%), and 27 patients (71%) in the tPA, tPA/US, and tPA/US/MB groups, respectively ( P =0.004). Two-hour complete recanalization rate was significantly ( P =0.038) higher in the tPA/US/MB group (54.5%) compared with tPA/US (40.8%) and tPA (23.9%) groups. The time to beginning of recanalization after tPA bolus was 26±18 minutes in the tPA/US group and 19±12 minutes in the tPA/US/MB group ( P =0.12). Four patients (3.6%) experienced symptomatic intracranial hemorrhage: 2 (5.5%), 1 (2.7%), and 1 patient (2.6%) who received tPA only, tPA/US, and tPA/US/MB, respectively, experienced symptomatic intracranial hemorrhage. At 24 hours, 31%, 41%, and 55% of tPA, tPA/US, and tPA/US/MB improved >4 points in the NIHSS score. Conclusions— Administration of MBs induces further acceleration of US-enhanced thrombolysis in acute stroke, leading to a more complete recanalization and to a trend toward better short- and long-term outcome.

After a transient ischemic attack (TIA) or minor stroke, the long-term risk of stroke and other vascular events is not well known. In this follow-up to a report on 1-year outcomes from a registry of TIA clinics in 21 countries that enrolled 4789 patients with a TIA or minor ischemic stroke from 2009 through 2011, we examined the 5-year risk of stroke and vascular events.

Background and Purpose— We aimed to determine clinical and hemodynamic predictors of early reocclusion (RO) in stroke patients treated with intravenous tissue plasminogen activator (tPA). Methods— We studied 142 consecutive stroke patients with a documented middle cerebral artery (MCA) occlusion treated with intravenous tPA. All patients underwent carotid ultrasound and transcranial Doppler (TCD) examination before tPA bolus. National Institutes of Health Stroke Scale (NIHSS) scores were performed at baseline and serially for <24 hours. TCD monitoring of MCA recanalization (RE) and RO was performed during the first 2 hours after tPA bolus and repeated when clinical deterioration occurred 16 points ( P =0.009), higher leukocytes count ( P =0.042), beginning of RE 16 at baseline (odds ratio [OR], 7.1; 95% CI, 1.3 to 32) and severe ipsilateral carotid disease (OR, 13.3; 95% CI, 3.2 to 54) remained as independent predictors of RO. Conclusions— Stroke severity and ipsilateral severe carotid artery disease independently predict RO after tPA-induced MCA RE.

Background and Purpose— The risk of recurrent stroke is highest within the first few weeks after a transient ischemic attack (TIA), and it is likely to be related to the underlying pathology. We sought to study the early risk of recurrent stroke by etiologic subtype. Methods— We prospectively studied 388 TIA patients. The cause of TIA was classified according to the Trial of ORG 10172 criteria: large-artery atherosclerosis (LAA, n=90), cardioembolism (n=87), small-vessel disease (n=68), undetermined (n=127), and other determined cause (n=16). Patients were followed up at 3 months. Risk factors and clinical symptoms for each subtype were recorded. Results— The duration of symptoms and clinical symptoms varied significantly among the different subtypes. LAA was associated with recurrent short episodes of weakness, whereas speech impairment and cortical symptoms were associated with cardioembolism ( P <0.05). The association of vascular risk factors was highest in LAA ( P <0.05). New strokes were recorded in 35 (9%) patients. Recurrent stroke risk varied among subtypes ( P <0.001): LAA, 20.0%; cardioembolism, 11.5%; undetermined, 4.7%; small-vessel disease, 1.5%; and other cause, 0%. Cox proportional-hazards multivariate analyses did not identify any independent predictor of further cerebral ischemic events for LAA, cardioembolism, undetermined, or small-vessel disease. Conclusions— The risk of early recurrent stroke is highest in patients with LAA. This supports the need for urgent carotid and transcranial imaging for identifying those patients at highest risk. Some risk factors and clinical symptoms are related to some etiologic subtypes, but stronger predictors of stroke recurrence are needed to identify those patients with highest risk for each TIA subtype.

Background and Purpose— Recently, a new definition of transient ischemic attack (TIA) has been proposed based on the duration of symptoms and diffusion-weighted imaging (DWI) findings. We investigate the value of temporal and neuroimaging data on the prognoses of TIA patients. Methods— Clinical data, symptom duration, DWI, and ultrasonographic findings were collected in 83 consecutive classical TIA patients attended in the emergency department. Stroke recurrence, myocardial infarction, or any vascular event was recorded at follow-up (mean of 389 days). Results— A total of 27 (32.5%) patients revealed focal abnormalities on DWI, whereas 37(44.6%) had symptoms lasting >1 hour. Large-artery disease was detected in 37 (44.6%) patients. Twenty (24.1%) patients experienced an endpoint: 2 (2.4%) myocardial infarctions, 16 (19.3%) cerebral ischemic events, and 2 cases (2.4%) of peripheral arterial disease. Cox proportional hazards multivariate analyses identified the association of symptoms >1 hour with DWI abnormalities as independent predictors of further cerebral ischemic events or any vascular event (hazard ratio [HR], 5.02; CI, 1.37 to 18.30; P =0.015; and HR, 3.77; CI, 1.09 to 13.00; P =0.029). Large-artery occlusive disease also remained an independent predictor of both endpoints (HR, 4.22; CI, 1.17 to 15.22; P =0.028; and HR, 3.60; CI, 1.14 to 11.39; P =0.0293). Conclusions— TIA patients with DWI abnormalities associated with duration of symptoms >1 hour and those with large-artery occlusive disease have a higher risk of further vascular events. Routine use of DWI and Doppler ultrasonographic examinations will be useful for identifying TIA patients at high risk to plan aggressive prevention therapies.