Frank L. Silver

Analysis of Workflow and Time to Treatment on Thrombectomy Outcome in the Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE) Randomized, Controlled Trial

Background— The Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE) trial used innovative imaging and aggressive target time metrics to demonstrate the benefit of endovascular treatment in patients with acute ischemic stroke. We analyze the impact of time on clinical outcome and the effect of patient, hospital, and health system characteristics on workflow within the trial. Methods and Results— Relationship between outcome (modified Rankin Scale) and interval times was modeled by using logistic regression. Association between time intervals (stroke onset to arrival in endovascular-capable hospital, to qualifying computed tomography, to groin puncture, and to reperfusion) and patient, hospital, and health system characteristics were modeled by using negative binomial regression. Every 30-minute increase in computed tomography-to-reperfusion time reduced the probability of achieving a functionally independent outcome (90-day modified Rankin Scale 0–2) by 8.3% (P=0.006). Symptom onset-to-imaging time was not associated with outcome (P>0.05). Onset-to-endovascular hospital arrival time was 42% (34 minutes) longer among patients receiving intravenous alteplase at the referring hospital (drip and ship) versus direct transfer (mothership). Computed tomography-to-groin puncture time was 15% (8 minutes) shorter among patients presenting during work hours versus off hours, 41% (24 minutes) shorter in drip-ship patients versus mothership, and 43% (22 minutes) longer when general anesthesia was administered. The use of a balloon guide catheter during endovascular procedures shortened puncture-to-reperfusion time by 21% (8 minutes). Conclusions— Imaging-to-reperfusion time is a significant predictor of outcome in the ESCAPE trial. Inefficiencies in triaging, off-hour presentation, intravenous alteplase administration, use of general anesthesia, and endovascular techniques offer major opportunities for improvement in workflow. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01778335.

tPA use for stroke in the registry of the Canadian Stroke Network

BACKGROUNDnThrombolytic therapy with recombinant tissue plasminogen activator (tPA) has been shown to be cost-effective and safe. Thrombolysis for stroke with tPA is now a standard of care in North America. However, it is only used on a small percentage of patients.nnnMETHODSnThe Registry of the Canadian Stroke Network was a consent-based stroke registry from 21 hospital sites across Canada. Using the thrombolysis data in phase 1 and 2 of the Registry, we sought to describe the use of stroke thrombolysis and its outcomes.nnnRESULTSnA total of 4107 patients were diagnosed with ischemic stroke in phase 1 and 2 of the Registry, of which 8.9% were treated with tPA. In consented tPA patients, the method of tPA administration was 85.8% i.v. only, 9.0% ia only, and 5.2% i.v./i.a. combined. Patients had a median onset-to-treatment time of 167 minutes [IQR 140-188]. One quarter (25.5%) of eligible candidates (time from onset <150 minutes) were treated with tPA. Protocol violations occurred in 27.7% (67/242) of patients with 14.9% (10/67) mortality. Overall, in-hospital mortality was 11.6%. Lower Canadian Neurological Scale score and higher glucose level were predictive of mortality The symptomatic intracerebral hemorrhage (ICH) rate (phase 2 only) was 4.3%. The mean Stroke Impact Scale-16 score at six months was 73.2, approximately equivalent to a modified Rankin scale score of 2.nnnCONCLUSIONSnAt selected hospitals in Canada, thrombolysis use is higher than previously reported rates. Thrombolysis continues to be safe and effective in Canada.

MRI-Based Neuroanatomical Predictors of Dysphagia after Acute Ischemic Stroke: A Systematic Review and Meta-Analysis

Background: Considering that the incidence of dysphagia is as high as 55% following acute stroke, we undertook a systematic review of the literature to identify lesion sites that predict its presence after acute ischemic stroke. Methods: We searched 14 databases, 17 journals, 3 conference proceedings and the grey literature using the Cochrane Stroke Group search strategy and terms for MRI and dysphagia. We evaluated study quality using the Cochrane Collaboration’s risk of bias tool and extracted individual-level data. We calculated relative risks in order to model dysphagia according to neuroanatomical lesion sites. Results: Of 964 abstracts, 84 articles met the criteria for full review. Of these 84 articles, 17 met the quality criteria. These 17 articles dealt exclusively with dysphagia after infratentorial stroke and provided MRI correlates of dysphagia for 656 patients. The incidence of dysphagia according to stroke region was 0% in the cerebellum, 6% in the midbrain, 43% in the pons, 40% in the medial medulla and 57% in the lateral medulla. Within these regions, pontine (relative risk 3.7, 95% confidence interval 1.5–7.7), medial medullary (relative risk 6.9, 95% confidence interval 3.4–10.9) and lateral medullary lesions (relative risk 9.6, 95% confidence interval 5.9–12.8) predicted an increased risk of dysphagia. Conclusions: We sought to develop a neuroanatomical model of dysphagia throughout the whole brain. However, the literature that met our quality criteria addressed the MRI correlates of dysphagia exclusively within the infratentorium. Although not surprising, these findings are a first step toward establishing a neuroanatomical model of dysphagia after infratentorial ischemic stroke and provide insight into the assessment of individuals at risk for dysphagia.

Gastrointestinal bleeding after acute ischemic stroke

Objective: Recent studies report that major bleeding is associated with a significant increase in mortality after acute coronary syndrome. Major bleeding has also been reported to be common after ischemic stroke, most often gastrointestinal, but its association with clinical outcome is less certain. We sought to describe the incidence, risk factors, and association with clinical outcomes of gastrointestinal bleeding following acute ischemic stroke. Methods: Consecutive patients with acute ischemic stroke, who were admitted to 11 Ontario hospitals, were identified from the Registry of the Canadian Stroke Network (2003–2006). Stroke severity was measured using the Canadian Neurological Scale. Dependence was measured with the modified Rankin Scale (mRS), and categorized into strokes with no or mild–moderate dependency (mRS 0–3) and those with severe dependence or death (mRS 4–6). Multivariable logistic regression was used to determine the association between gastrointestinal bleeding and clinical outcome (death or severe dependence at hospital discharge and 6-month mortality), independent of comorbidities and in-hospital medical complications. Results: In total, 6,853 patients with acute ischemic stroke were included. One hundred (1.5%) patients experienced gastrointestinal hemorrhage during hospitalization, of which 36 (0.5%) required blood transfusion. On multivariable analyses, previous history of peptic ulcer disease, cancer, and stroke severity were independent predictors of gastrointestinal bleeding. Gastrointestinal hemorrhage was independently associated with death or severe dependence at discharge (OR 3.3; 95% CI 1.9–5.8) and mortality at 6 months (HR 1.5; 95% CI 1.1–2.0). Conclusions: Gastrointestinal hemorrhage is relatively uncommon after acute ischemic stroke but is associated with increased odds of death and severe dependence.

Recommendations for the Management of Intracranial Haemorrhage – Part I: Spontaneous Intracerebral Haemorrhage

This article represents the recommendations for the management of spontaneous intracerebral haemorrhage of the European Stroke Initiative (EUSI). These recommendations are endorsed by the 3 European societies which are represented in the EUSI: the European Stroke Council, the European Neurological Society and the European Federation of Neurological Societies.This article represents the recommendations for the management of spontaneous intracerebral haemorrhage of the European Stroke Initiative (EUSI). These recommendations are endorsed by the 3 European s

Vertebrobasilar Flow Evaluation and Risk of Transient Ischaemic Attack and Stroke study (VERiTAS): Rationale and design

Background Over one-third of ischaemic strokes occur in the posterior circulation, and a leading cause is atherosclerotic vertebrobasilar disease. Symptomatic vertebrobasilar disease carries a high annual recurrent stroke risk, averaging 10–15% per year. Endovascular angioplasty and stenting are increasingly used but carry risks, and the benefit remains unproven. Determining stroke predictors in this population is critical to identifying high-risk patients for future trials of intervention. Preliminary studies indicate that stroke risk in vertebrobasilar disease is strongly related to haemodynamic compromise, which can be measured noninvasively using quantitative magnetic resonance angiography. Methods/study design The Vertebrobasilar Flow Evaluation and Risk of Transient Ischaemic Attack and Stroke (VERiTAS) study, a prospective multicentre NIH-funded observational study of symptomatic vertebrobasilar stenosis (≥50%) or occlusion, is designed to test the hypothesis that patients demonstrating compromised blood flow as assessed by quantitative magnetic resonance angiography are at higher stroke risk. The study will recruit 80 patients at six sites in North America over 4-years. Upon enrollment, subjects will undergo haemodynamic assessment with blinded quantitative magnetic resonance angiography to assess large vessel flow in the vertebrobasilar territory, and be prospectively designated as compromised or normal flow. Patients will be re-imaged with quantitative magnetic resonance angiography at 6-, 12-, and 24-months, and followed for 12–24-months for the primary end-point of stroke in the vertebrobasilar territory. Conclusion The VERiTAS study is the first prospective study of haemodynamics and stroke risk in the posterior circulation. The results may impact the selection criteria for interventional candidates and also define a low-risk population in whom the risks of invasive interventions would be unnecessary.

Hemodynamic Features of Symptomatic Vertebrobasilar Disease

Background and Purpose— Atherosclerotic vertebrobasilar disease is an important cause of posterior circulation stroke. To examine the role of hemodynamic compromise, a prospective multicenter study, Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS), was conducted. Here, we report clinical features and vessel flow measurements from the study cohort. Methods— Patients with recent vertebrobasilar transient ischemic attack or stroke and ≥50% atherosclerotic stenosis or occlusion in vertebral or basilar arteries (BA) were enrolled. Large-vessel flow in the vertebrobasilar territory was assessed using quantitative MRA. Results— The cohort (n=72; 44% women) had a mean age of 65.6 years; 72% presented with ischemic stroke. Hypertension (93%) and hyperlipidemia (81%) were the most prevalent vascular risk factors. BA flows correlated negatively with percentage stenosis in the affected vessel and positively to the minimal diameter at the stenosis site (P<0.01). A relative threshold effect was evident, with flows dropping most significantly with ≥80% stenosis/occlusion (P<0.05). Tandem disease involving the BA and either/both vertebral arteries had the greatest negative impact on immediate downstream flow in the BA (43 mL/min versus 71 mL/min; P=0.01). Distal flow status assessment, based on an algorithm incorporating collateral flow by examining distal vessels (BA and posterior cerebral arteries), correlated neither with multifocality of disease nor with severity of the maximal stenosis. Conclusions— Flow in stenotic posterior circulation vessels correlates with residual diameter and drops significantly with tandem disease. However, distal flow status, incorporating collateral capacity, is not well predicted by the severity or location of the disease.

Randomized clinical trial of the timing it right stroke family support program: research protocol

BackgroundFamily caregivers provide invaluable support to stroke survivors during their recovery, rehabilitation, and community re-integration. Unfortunately, it is not standard clinical practice to prepare and support caregivers in this role and, as a result, many experience stress and poor health that can compromise stroke survivor recovery and threaten the sustainability of keeping the stroke survivor at home. We developed the Timing it Right Stroke Family Support Program (TIRSFSP) to guide the timing of delivering specific types of education and support to meet caregivers’ evolving needs. The objective of this multi-site randomized controlled trial is to determine if delivering the TIRSFSP across the stroke care continuum improves caregivers’ sense of being supported and emotional well-being.Methods/designOur multi-site single-blinded randomized controlled trial will recruit 300 family caregivers of stroke survivors from urban and rural acute care hospitals. After completing a baseline assessment, participants will be randomly allocated to one of three groups: 1) TIRSFSP guided by a stroke support person (health care professional with stroke care experience), delivered in-person during acute care and by telephone for approximately the first six to 12 months post-stroke, 2) caregiver self-directed TIRSFSP with an initial introduction to the program by a stroke support person, or 3) standard care receiving the educational resource “Let’s Talk about Stroke” prepared by the Heart and Stroke Foundation. Participants will complete three follow-up quantitative assessments 3, 6, and 12-months post-stroke. These include assessments of depression, social support, psychological well-being, stroke knowledge, mastery (sense of control over life), caregiving assistance provided, caregiving impact on everyday life, and indicators of stroke severity and disability. Qualitative methods will also be used to obtain information about caregivers’ experiences with the education and support received and the impact on caregivers’ perception of being supported and emotional well-being.DiscussionThis research will determine if the TIRSFSP benefits family caregivers by improving their perception of being supported and emotional well-being. If proven effective, it could be recommended as a model of stroke family education and support that meets the Canadian Stroke Best Practice Guideline recommendation for providing timely education and support to families through transitions.Trial registrationClinicalTrials.gov: NCT00958607.

Gender differences in carotid imaging and revascularization following stroke

Background: Carotid endarterectomy is performed less often in women than in men, but it is unknown whether this reflects differences in screening rates, disease prevalence, or other factors. Methods: This was a cohort study of consecutive patients with acute stroke or TIA admitted to 11 Ontario stroke centers participating in the Registry of the Canadian Stroke Network between July 1, 2003, and September 30, 2007. We compared rates of carotid imaging, the severity of carotid stenosis, and rates of carotid endarterectomy or angioplasty within 6 months of the index event in women vs men. Results: We studied 6,389 patients (48% women) with ischemic stroke or TIA. Women were less likely than men to undergo carotid imaging (81% vs 86%, p < 0.0001); however, when the analysis was limited to patients without apparent contraindications to surgery, 92% received carotid imaging, with no difference between women and men. Women were less likely than men to have severe carotid stenosis (7.4% vs 11.5%, p < 0.0001). Women were half as likely as men to undergo carotid revascularization within 6 months of the index event (odds ratio 0.51, 95% confidence interval 0.37 to 0.70), but this gender difference was no longer significant in the subgroup with severe carotid stenosis (odds ratio 0.75, 95% confidence interval 0.49 to 1.15). Conclusions: Although women with ischemic stroke or TIA are less likely than men to undergo carotid screening and revascularization, this difference is largely explained by potential contraindications to surgery and by sex differences in the severity of carotid disease.

Intracerebral Hemorrhage: Outcomes and Eligibility for Factor VIIa Treatment in a National Stroke Registry

Background: Intracerebral hemorrhage (ICH) is a devastating form of stroke for which the lack of treatment options, high mortality rate, and the tendency to severely disable result in high social and economic burden. Methods: We analyzed data in the Registry of the Canadian Stroke Network (RCSN). We sought to: (1) provide a descriptive analysis of ICH; (2) determine the proportion of ICH patients that might have been eligible for treatment with recombinant activated factor VII (rFVIIa) using criteria from a recent phase II trial; (3) compare 6-month outcomes of ICH patients with those of ischemic stroke patients, matched for gender, age, and stroke severity. Results: In the RCSN, 11% of all strokes were nontraumatic ICH. The median Canadian Neurological Scale score was 7. A minority (33%) of patients arrived to the emergency department in less than 3 h from onset. In this cohort, in-hospital mortality was 15%. At 6 months, a further 9% of patients had died and 58% had a slight to no disability (Stroke Impact Scale-16 score ≧75). Approximately 20% of ICH patients would have been eligible for rFVIIa treatment. Compared to ischemic stroke, ICH showed a trend towards increased mortality at discharge (OR: 1.96, CI: 0.99–3.87). At 6-month follow-up, ICH showed increased mortality (OR: 2.27, CI: 1.29–3.97), yet functional outcomes were not significantly different. Conclusion: ICH patients had a higher case-fatality rate when compared to acute ischemic stroke, but survivors had similar functional outcomes. In Canada, about one fifth of ICH patients might potentially benefit from rFVIIa if it is approved, with the major exclusion factor being time.