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.

Background and Purpose-Although tandem internal carotid artery/middle cerebral artery (MCA; TIM) occlusion has been associated with low recanalization rate after IV tissue plasminogen activator (tPA), its independent contribution on stroke outcome remains unknown. Moreover, whether the relative resistance to thrombolysis in tandem lesions varies depending on the location of MCA clot remains uncertain. Methods-Two hundred and twenty-one consecutive stroke patients with an acute MCA occlusion treated with IV tPA were studied. Emergent carotid artery ultrasound and transcranial Doppler (TCD) examinations were performed in all patients before treatment. Recanalization was assessed on TCD at 2 hours of tPA bolus. National Institutes of Health Stroke Scale (NIHSS) scores were obtained at baseline and after 24 hours. Modifed Rankin Scale score was used to assess outcome at 3 months. Results-Median prebolus NIHSS score was 16 points. On TCD, 156 (71.6%) patients had a proximal and 65 (29.4%) a distal MCA occlusion. TIM occlusion was identified in 44 (19.9%) patients. Eighteen (41.9%) patients with and 123 (69.5%) without TIM lesions achieved an MCA recanalization (Pϭ0.01). In a logistic regression model, hyperglycemia Ͼ140 mg/dL (odds ratio [OR] 3.3, 95% CI, 1.6 to 6.8) and the presence of TIM occlusion (OR 2.8, 95% CI, 1.1 to 6.9) emerged as independent predictors of absence of recanalization. However, the independent contribution of TIM lesions on poor response to thrombolysis varied depending on the location of MCA occlusion. TIM occlusion independently predicted resistance to thrombolysis in patients with proximal (OR 4.63, 95% CI, 1.79 to 11.96), but not in those with distal MCA occlusion. Patients with TIM occlusion had worse short-(PϽ0.0001) and long-term (PϽ0.0001) clinical outcome. Conclusions-TIM occlusion independently predicts poor outcome after IV thrombolysis. However, its impact varies depending on the location of MCA clot. Therefore, emergent carotid ultrasound plus TCD examinations may improve the selection of patients for more aggressive reperfusion strategies.

Background and Purpose-Hyperglycemia (HG) has a deleterious effect in stroke patients by accelerating ischemic brain damage; moreover, its antifibrinolytic effect may also influence reperfusion. We aimed to study the effect of acute/chronic HG on tissue-type plasminogen activator (tPA)-induced recanalization. Methods-We studied 139 consecutive stroke patients with documented intracranial artery occlusion treated with intravenous tissue-type plasminogen activator (tPA). Admission glucose levels were recorded (in mg/dL). The existence of previous chronic HG was determined by plasma levels of glycosylated hemoglobin (HbA1c, %) and fructosamine (in mol/L). Transcranial Doppler monitoring assessed complete recanalization 2 hours after tPA bolus. National Institutes of Health Stroke Scale (NIHSS) scores were obtained at baseline and 48 hours. Results-On admission, the median NIHSS score was 18 and mean glucose value was140Ϯ63 mg/dL. At 2 hours, 32% of patients (nϭ44)

Summary Background Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. Methods We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. Findings Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1·34 years [IQR 0·19–2·44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1·35 (95% CI 1·20–1·50) for the composite outcome of intracranial haemorrhage and ischaemic stroke; 2·45 (1·82–3·29) for intracranial haemorrhage and 1·23 (1·08–1·40) for ischaemic stroke. The aHR increased with increasing cerebral microbleed burden for intracranial haemorrhage but this effect was less marked for ischaemic stroke (for five or more cerebral microbleeds, aHR 4·55 [95% CI 3·08–6·72] for intracranial haemorrhage vs 1·47 [1·19–1·80] for ischaemic stroke; for ten or more cerebral microbleeds, aHR 5·52 [3·36–9·05] vs 1·43 [1·07–1·91]; and for ≥20 cerebral microbleeds, aHR 8·61 [4·69–15·81] vs 1·86 [1·23–2·82]). However, irrespective of cerebral microbleed anatomical distribution or burden, the rate of ischaemic stroke exceeded that of intracranial haemorrhage (for ten or more cerebral microbleeds, 64 ischaemic strokes [95% CI 48–84] per 1000 patient-years vs 27 intracranial haemorrhages [17–41] per 10...

Background and Purpose-Intravenous thrombolysis in stroke achieves arterial recanalization in Ϸ50% of cases.Determining temporal profile of recanalization may address patient selection and potential benefits of further rescue reperfusion techniques. Methods-We studied 179 consecutive intravenous tissue plasminogen activator (t-PA)-treated patients with intracranial artery occlusion. Continuous transcranial Doppler assessed recanalization (none-partial-complete) at 60 minutes (early), 120 minutes (delayed) after t-PA bolus, and 6 hours (late) from symptom onset. Outcomes were determined: National Institutes of Health Stroke Scale (NIHSS; 48-hour NIHSS) and 3-month modified Rankin Scale (mRS). Results-On admission, 68% of patients presented proximal middle cerebral artery occlusion, median NIHSS 17.Early recanalization was complete for 30 patients (17%), partial for 50 (28%), and none for 99 (55%). Delayed recanalization was complete for 56 patients (31%), partial for 39 (22%), and none for 84 (47% T hrombolytic therapy with intravenous tissue plasminogen activator (t-PA) for acute ischemic stroke has shown to be effective by increasing and anticipating recanalization of the occluded brain vessels. 1,2 In the last years, different studies using multiple methods to assess cerebral flow described recanalization rates ranging from 30% to 60% in the first 6 to 24 hours after t-PA treatment. [2][3][4][5][6] However, the timing and temporal profile of recanalization in the very first hours after t-PA bolus remain uncertain. Continuous transcranial Doppler (TCD) monitoring at the bedside seems to be the best diagnostic tool to assess real-time recanalization. 7,8 The CLOTBUST study recently reported a 38% rate of complete recanalization at 2 hours after t-PA bolus in patients who received continuous ultrasound. 3 Nevertheless, detailed description of the temporal profile of partial versus complete recanalization during this time remains unknown. One hour after thrombolytic treatment initiation, information about the likelihood of complete recanalization during the following hours may help physicians identify those patients in whom intravenous t-PA will fail to induce early recanalization, making them eligible for rescue reperfusion therapies. We aim to study the probability and temporal profile of recana- Patients and MethodsFrom February 2002 to June 2005, all patients with an acute (Ͻ6 hours from symptom onset) stroke admitted to the emergency department of a university hospital were prospectively studied. A total of 928 patients were evaluated and underwent urgent extracranial and TCD ultrasound examination. Patients with an inadequate temporal bone window were excluded. A total of 179 patients had a TCD-documented intracranial occlusion and fulfilled established criteria for t-PA treatment (0.9 mg/kg). 1 None of these patients received rescue recanalization therapies. Clinical ProtocolA detailed history of vascular risk factors was obtained from each patient. To identify potential mechanism of cerebral infarction, ...