Sonothrombolysis for acute ischemic stroke: a systematic review of randomized controlled trials

Object. Sonothrombolysis has recently been considered an emerging modality for the treatment of stroke. The purpose of the present paper was to review randomized clinical studies concerning the effects of sonothrombolysis associated with tissue plasminogen activator (tPA) on acute ischemic stroke. Methods. Systematic searches for literature published between January 1996 and July 2011 were performed for studies regarding sonothrombolysis combined with tPA for acute ischemic stroke. Only randomized controlled trials were included. Data extraction was based on ultrasound variables, patient characteristics, and outcome variables (rate of intracranial hemorrhages and arterial recanalization). Results. Four trials were included in this study; 2 trials evaluated the effect of transcranial Doppler (TCD) ultrasonography on sonothrombolysis, and 2 addressed transcranial color-coded duplex (TCCD) ultrasonography. The frequency of ultrasound waves varied from 1.8 to 2 MHz. The duration of thrombus exposure to ultrasound energy ranged from 60 to 120 minutes. Sample sizes were small, recanalization was evaluated at different time points (60 and 120 minutes), and inclusion criteria were heterogeneous. Sonothrombolysis combined with tPA did not lead to an increase in symptomatic intracranial hemorrhagic complications. Two studies demonstrated that patients treated with ultrasound combined with tPA had statistically significant higher rates of recanalization than patients treated with tPA alone. Conclusions. Despite the heterogeneity and the limitations of the reviewed studies, there is evidence that sonothrombolysis associated with tPA is a safe procedure and results in an increased rate of recanalization in the setting of acute ischemic stroke when wave frequencies and energy intensities of diagnostic ultrasound systems are used. (http://thejns.org/doi/abs/10.3171/2011.10.FOCUS11251)

Mechanical thrombectomy with solitaire stent retrieval for acute ischemic stroke in a Brazilian population

OBJECTIVE: Large vessel occlusion in acute ischemic stroke is associated with low recanalization rates under intravenous thrombolysis. We evaluated the safety and efficacy of the Solitaire AB stent in treating acute ischemic stroke. METHODS: Patients presenting with acute ischemic stroke were prospectively evaluated. The neurological outcomes were assessed using the National Institutes of Health Stroke Scale and the modified Rankin Scale. Time was recorded from the symptom onset to the recanalization and procedure time. Recanalization was assessed using the thrombolysis in cerebral infarction score. RESULTS: Twenty-one patients were evaluated. The mean patient age was 65, and the National Institutes of Health Stroke Scale scores ranged from 7 to 28 (average 17+/-6.36) at presentation. The vessel occlusions occurred in the middle cerebral artery (61.9%), distal internal carotid artery (14.3%), tandem carotid occlusion (14.3%), and basilar artery (9.5%). Primary thrombectomy, rescue treatment and a bridging approach represented 66.6%, 28.6%, and 4.8% of the performed procedures, respectively. The mean time from symptom onset to recanalization was 356.5+/-107.8 minutes (range, 80-586 minutes). The mean procedure time was 60.4+/-58.8 minutes (range, 14-240 minutes). The overall recanalization rate (thrombolysis in cerebral infarction scores of 3 or 2b) was 90.4%, and the symptomatic intracranial hemorrhage rate was 14.2%. The National Institutes of Health Stroke Scale scores at discharge ranged from 0 to 25 (average 6.9+/-7). At three months, 61.9% of the patients had a modified Rankin Scale score of 0 to 2, with an overall mortality rate of 9.5%. CONCLUSIONS: Intra-arterial thrombectomy with the Solitaire AB device appears to be safe and effective. Large randomized trials are necessary to confirm the benefits of this approach in acute ischemic stroke.

Ticagrelor Versus Clopidogrel in Patients With Acute Coronary Syndromes and a History of Stroke or Transient Ischemic Attack

Background-Patients with acute coronary syndromes and history of stroke or transient ischemic attack (TIA) have an increased rate of recurrent cardiac events and intracranial hemorrhages. Methods and Results-We evaluated treatment effects of ticagrelor versus clopidogrel in patients with acute coronary syndrome with and without a history of prior stroke or TIA in the PLATelet inhibition and patient Outcomes (PLATO) trial. Of the 18 624 randomized patients, 1152 (6.2%) had a history of stroke or TIA. Such patients had higher rates of myocardial infarction (11.5% versus 6.0%), death (10.5% versus 4.9%), stroke (3.4% versus 1.2%), and intracranial bleeding (0.8% versus 0.2%) than patients without prior stroke or TIA. Among patients with a history of stroke or TIA, the reduction of the primary composite outcome and total mortality at 1 year with ticagrelor versus clopidogrel was consistent with the overall trial results: 19.0% versus 20.8% (hazard ratio, 0.87; 95% confidence interval, 0.66-1.13; interaction P=0.84) and 7.9% versus 13.0% (hazard ratio, 0.62; 95% confidence interval, 0.42-0.91). The overall PLATO-defined bleeding rates were similar: 14.6% versus 14.9% (hazard ratio, 0.99; 95% confidence interval, 0.71-1.37), and intracranial bleeding occurred infrequently (4 versus 4 cases, respectively). Conclusions-Patients with acute coronary syndrome with a prior history of ischemic stroke or TIA had higher rates of clinical outcomes than patients without prior stroke or TIA. However, the efficacy and bleeding results of ticagrelor in these high-risk patients were consistent with the overall trial population, with a favorable clinical net benefit and associated impact on mortality.

Predictors of early mortality after acute ischaemic stroke.

BACKGROUND The study set out to identify clinical, laboratory and radiological predictors of early mortality after an acute ischaemic stroke (AIS) and to analyse medical and neurological complications that caused death. METHODS A total of 479 consecutive patients (mean age 63+/-14 years) with AIS underwent stroke examination and treatment. Examination included clinical evaluation, laboratory tests, and brain CT and/or MRI. Follow-up data at 30 days were available for 467 patients (93%) who were included in the present analysis. RESULTS The median National Institute of Health Stroke Study (NIHSS) score on admission was 6. A total of 62 patients (13%) died within 30 days. The cause of death was the initial event in 43 (69%), pneumonia in 12 (19%), intracerebral haemorrhage in 9 (15%), recurrent stroke in 6 (10%), myocardial infarction in 2 (3%), and cancer in 1 (2%) of the patients. In univariate comparisons, advanced age (p<0.001), hypertension (p=0.013), coronary disease (p=0.001), NIHSS score (p<0.001), undetermined stroke etiology (p=0.031), relevant co-morbidities (p=0.008), hyperglycemia (p<0.001), atrial fibrillation (p<0.001), early CT signs of ischemia (p<0.001), dense artery sign (p<0.001), proximal vessel occlusion (p<0.001), and thrombolysis (p=0.008) were associated with early mortality. In multivariate analysis, advanced age (HR=1.12; 95% CI 1.05-1.19; p<0.001) and high NIHSS score on admission (HR=1.15, 95% CI 1.05-1.25; p=0.002) were independent predictors of early mortality. CONCLUSIONS We report 13% mortality at 30 days after AIS. More than two thirds of the deaths are related to the initial stroke. Advanced age and high NIHSS score are the only independent predictors of early mortality in this series.

Coagulation factor XIII activation peptide and subunit levels in patients with acute ischaemic stroke: a pilot study

We have recently shown that FXIII activation peptide (AP-FXIII) can be measured in plasma. The objective of this pilot study was to investigate for the first time if AP-FXIII can be detected in plasma from patients with acute ischaemic stroke.

Impact of Retrievable Stents on Acute Ischemic Stroke Treatment

Retrievable stents combine the high recanalization rate of stents and the capability of removing the thrombus offered by mechanical thrombectomy devices. We hypothesized that retrievable stents shorten time to recanalization in the multimodal approach for endovascular stroke treatment.

Acute ischemic stroke in children versus young adults

The aim of this study was to compare children and young adults with acute ischemic stroke (AIS) in 2 large registries.

Intracranial Hemorrhage, Outcome, and Mortality After Intra-Arterial Therapy for Acute Ischemic Stroke in Patients Under Oral Anticoagulants

Use of intravenous tissue-type plasminogen activator (IV tPA) for acute ischemic stroke is restricted to patients with an international normalized ratio (INR) less than 1.7. However, a recent study showed increased risk of symptomatic intracranial hemorrhage after IV tPA use in patients with oral anticoagulants (OAC) even with an INR less than 1.7. The present study assessed the risk of symptomatic intracranial hemorrhage, clinical outcome, and mortality after intra-arterial therapy (IAT) in patients with and without previous use of OAC.

Delayed diagnosis of acute ischemic stroke in children - a registry-based study in Switzerland

QUESTIONS UNDER STUDY/PRINCIPLES: After arterial ischemic stroke (AIS) an early diagnosis helps preserve treatment options that are no longer available later. Paediatric AIS is difficult to diagnose and often the time to diagnosis exceeds the time window of 6 hours defined for thrombolysis in adults. We investigated the delay from the onset of symptoms to AIS diagnosis in children and potential contributing factors.

Intra-Arterial Thrombolysis for Acute Ischemic Stroke in Octogenarians

It is unclear whether octogenarians benefit from intra-arterial thrombolysis (IAT) for the treatment of acute ischemic stroke (AIS). The aim of the present study was to compare baseline characteristics, clinical outcome and complications of patients aged ≥80 with those of patients aged <80 years.

[Mechanical Thrombectomy for Acute Ischemic Stroke.]

The therapy of acute ischemic stroke aims at fast recanalization of the occluded brain vessel. In contrast to intravenous thrombolysis (IVT), endovascular approaches yield higher recanalization rates especially in large vessel occlusions. Mechanical thrombectomy with the Merci Retriever received FDA approval in 2004 as an adjunct to IVT or in the case of failed recanalization after IVT. The time window for treatment is 8 h from stroke onset. However, the recanalization rate was 55 %, still leaving space for further improvement. In addition to the Merci Retriever, the Penumbra System received FDA approval in 2008. The newest endovascular approach comprising retrievable intracranial stents results in an increased recanalization rate exceeding 90 % and has markedly reduced the time to recanalization. On the other hand, the complication rate has not increased yet. These promising results suggest a combined therapy for acute ischemic stroke. In a first step IVT can be started independently of the size of the treating hospital and in a next step the patient is transferred to a neuroradiological center. If vessel occlusion persists, additional endovascular recanalization is performed (bridging concept). Patients who don't qualify for IVT are candidates for mechanical thrombectomy up to 8 h after stroke onset.

Sleep-disordered breathing in acute ischemic stroke and transient ischemic attack: effects on short- and long-term outcome and efficacy of treatment with continuous positive airways pressure - rationale and design of the SAS CARE study

Sleep-disordered breathing represents a risk factor for cardiovascular morbidity and mortality and negatively affects short-term and long-term outcome after an ischemic stroke or transient ischemic attack. The effect of continuous positive airways pressure in patients with sleep-disordered breathing and acute cerebrovascular event is poorly known. The SAS CARE 1 study assesses the effects of sleep-disordered breathing on clinical evolution, vascular functions, and markers within the first three-months after an acute cerebrovascular event. The SAS CARE 2 assesses the effect of continuous positive airways pressure on clinical evolution, cardiovascular events, and mortality as well as vascular functions and markers at 12 and 24 months after acute cerebrovascular event.

Future trials of endovascular mechanical recanalisation therapy in acute ischemic stroke patients - A position paper endorsed by ESMINT and ESNR : Part II: methodology of future trials

Based on current data and experience, the joint working group of the European Society of Minimally Invasive Neurological Therapy (ESMINT) and the European Society of Neuroradiology (ESNR) make suggestions on trial design and conduct aimed to investigate therapeutic effects of mechanical thrombectomy (MT). We anticipate that this roadmap will facilitate the setting up and conduct of successful trials in close collaboration with our neighbouring disciplines.

Future trials of endovascular mechanical recanalisation therapy in acute ischemic stroke patients: a position paper endorsed by ESMINT and ESNR : Part I: Current situation and major research questions

A new era of stroke treatment may have begun with mechanical thrombectomy (MT) by fully deployed closed-cell self-expanding stents (stent-triever). Multiple case series and the first randomised controlled trials (RCTs) have now been published. More studies are under way involving large numbers of patients, which in turn has resulted in less strict "pragmatic" study protocols. Problems with current trials include a lack of standardisation in the conduct of the recanalisation procedure, the definition of primary endpoints such as the grade of arterial recanalisation and tissue reperfusion, and the post-surgical care provided. In Part 1 of this two part series, we outline the current situation and the major research questions.