Gustavo Saposnik

Diagnosis and Management of Cerebral Venous Thrombosis A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

Background— The purpose of this statement is to provide an overview of cerebral venous sinus thrombosis and to provide recommendations for its diagnosis, management, and treatment. The intended audience is physicians and other healthcare providers who are responsible for the diagnosis and management of patients with cerebral venous sinus thrombosis. Methods and Results— Members of the panel were appointed by the American Heart Association Stroke Councils Scientific Statement Oversight Committee and represent different areas of expertise. The panel reviewed the relevant literature with an emphasis on reports published since 1966 and used the American Heart Association levels-of-evidence grading algorithm to rate the evidence and to make recommendations. After approval of the statement by the panel, it underwent peer review and approval by the American Heart Association Science Advisory and Coordinating Committee. Conclusions— Evidence-based recommendations are provided for the diagnosis, management, and prevention of recurrence of cerebral venous thrombosis. Recommendations on the evaluation and management of cerebral venous thrombosis during pregnancy and in the pediatric population are provided. Considerations for the management of clinical complications (seizures, hydrocephalus, intracranial hypertension, and neurological deterioration) are also summarized. An algorithm for diagnosis and management of patients with cerebral venous sinus thrombosis is described.

Effectiveness of virtual reality using Wii gaming technology in stroke rehabilitation: a pilot randomized clinical trial and proof of principle

Background and Purpose— Hemiparesis resulting in functional limitation of an upper extremity is common among stroke survivors. Although existing evidence suggests that increasing intensity of stroke rehabilitation therapy results in better motor recovery, limited evidence is available on the efficacy of virtual reality for stroke rehabilitation. Methods— In this pilot, randomized, single-blinded clinical trial with 2 parallel groups involving stroke patients within 2 months, we compared the feasibility, safety, and efficacy of virtual reality using the Nintendo Wii gaming system (VRWii) versus recreational therapy (playing cards, bingo, or “Jenga”) among those receiving standard rehabilitation to evaluate arm motor improvement. The primary feasibility outcome was the total time receiving the intervention. The primary safety outcome was the proportion of patients experiencing intervention-related adverse events during the study period. Efficacy, a secondary outcome measure, was evaluated with the Wolf Motor Function Test, Box and Block Test, and Stroke Impact Scale at 4 weeks after intervention. Results— Overall, 22 of 110 (20%) of screened patients were randomized. The mean age (range) was 61.3 (41 to 83) years. Two participants dropped out after a training session. The interventions were successfully delivered in 9 of 10 participants in the VRWii and 8 of 10 in the recreational therapy arm. The mean total session time was 388 minutes in the recreational therapy group compared with 364 minutes in the VRWii group (P=0.75). There were no serious adverse events in any group. Relative to the recreational therapy group, participants in the VRWii arm had a significant improvement in mean motor function of 7 seconds (Wolf Motor Function Test, 7.4 seconds; 95% CI, −14.5, −0.2) after adjustment for age, baseline functional status (Wolf Motor Function Test), and stroke severity. Conclusions— VRWii gaming technology represents a safe, feasible, and potentially effective alternative to facilitate rehabilitation therapy and promote motor recovery after stroke.

Guidelines for the Prevention of Stroke in Women A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

Purpose— The aim of this statement is to summarize data on stroke risk factors that are unique to and more common in women than men and to expand on the data provided in prior stroke guidelines and cardiovascular prevention guidelines for women. This guideline focuses on the risk factors unique to women, such as reproductive factors, and those that are more common in women, including migraine with aura, obesity, metabolic syndrome, and atrial fibrillation. Methods— Writing group members were nominated by the committee chair on the basis of their previous work in relevant topic areas and were approved by the American Heart Association (AHA) Stroke Council’s Scientific Statement Oversight Committee and the AHA’s Manuscript Oversight Committee. The panel reviewed relevant articles on adults using computerized searches of the medical literature through May 15, 2013. The evidence is organized within the context of the AHA framework and is classified according to the joint AHA/American College of Cardiology and supplementary AHA Stroke Council methods of classifying the level of certainty and the class and level of evidence. The document underwent extensive AHA internal peer review, Stroke Council Leadership review, and Scientific Statements Oversight Committee review before consideration and approval by the AHA Science Advisory and Coordinating Committee. Results— We provide current evidence, research gaps, and recommendations on risk of stroke related to preeclampsia, oral contraceptives, menopause, and hormone replacement, as well as those risk factors more common in women, such as obesity/metabolic syndrome, atrial fibrillation, and migraine with aura. Conclusions— To more accurately reflect the risk of stroke in women across the lifespan, as well as the clear gaps in current risk scores, we believe a female-specific stroke risk score is warranted.

Virtual Reality in Stroke Rehabilitation A Meta-Analysis and Implications for Clinicians

Background and Purpose— Approximately two thirds of stroke survivors continue to experience motor deficits of the arm resulting in diminished quality of life. Conventional rehabilitation provides modest and sometimes delayed effects. Virtual reality (VR) technology is a novel adjunctive therapy that could be applied in neurorehabilitation. We performed a meta-analysis to determine the added benefit of VR technology on arm motor recovery after stroke. Methods— We searched Medline, EMBASE, and Cochrane literature from 1966 to July 2010 with the terms “stroke,” “virtual reality,” and “upper arm/extremity.” We evaluated the effect of VR on motor function improvement after stroke. Results— From the 35 studies identified, 12 met the inclusion/exclusion criteria totaling 195 participants. Among them, there were 5 randomized clinical trials and 7 observational studies with a pre-/postintervention design. Interventions were delivered within 4 to 6 weeks in 9 of the studies and within 2 to 3 weeks in the remaining 3. Eleven of 12 studies showed a significant benefit toward VR for the selected outcomes. In the pooled analysis of all 5 randomized controlled trials, the effect of VR on motor impairment (Fugl-Meyer) was OR=4.89 (95% CI, 1.31 to 18.3). No significant difference was observed for Box and Block Test or motor function. Among observational studies, there was a 14.7% (95% CI, 8.7%–23.6%) improvement in motor impairment and a 20.1% (95% CI, 11.0%–33.8%) improvement in motor function after VR. Conclusions— VR and video game applications are novel and potentially useful technologies that can be combined with conventional rehabilitation for upper arm improvement after stroke.

Weekends: A Dangerous Time for Having a Stroke?

Background and Purpose— Weekend admissions are associated with higher in-hospital mortality. However, limited information is available concerning the “weekend effect” on stroke mortality. Our aim was to evaluate the impact of weekend admissions on stroke mortality in different settings. Methods— We analyzed all hospital admissions for ischemic stroke from April 2003 to March 2004 through the Hospital Morbidity Database. The Hospital Morbidity Database is a national database that contains patient-level sociodemographic, diagnostic, procedural, and administrative information including all acute care facilities across Canada. The major inclusion criterion was admission to an acute care facility with a principal diagnosis of ischemic stroke. Clinical variables and facility characteristics were included in the analysis. Results— Overall, 26 676 patients were admitted to 606 hospitals for ischemic stroke. Weekend admissions comprised 6629 (24.8%) of all admissions. Seven-day stroke mortality was 7.6%. Weekend admissions were associated with a higher stroke mortality than weekday admissions (8.5% vs 7.4%; odds ratio, 1.17; 95% CI, 1.06 to 1.29). Mortality was similarly affected among patients admitted to rural versus urban hospitals or when the most responsible physician was a general practitioner versus specialist. In the multivariable analysis, weekend admissions were associated with higher early mortality (odds ratio, 1.14; 95% CI, 1.02 to 1.26) after adjusting for age, sex, comorbidities, and medical complications. Conclusions— Stroke patients admitted on weekends had a higher risk-adjusted mortality than did patients admitted on weekdays. Disparities in resources, expertise, and healthcare providers working during weekends may explain the observed differences in weekend mortality.

Scientific Rationale for the Inclusion and Exclusion Criteria for Intravenous Alteplase in Acute Ischemic Stroke A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

Purpose— To critically review and evaluate the science behind individual eligibility criteria (indication/inclusion and contraindications/exclusion criteria) for intravenous recombinant tissue-type plasminogen activator (alteplase) treatment in acute ischemic stroke. This will allow us to better inform stroke providers of quantitative and qualitative risks associated with alteplase administration under selected commonly and uncommonly encountered clinical circumstances and to identify future research priorities concerning these eligibility criteria, which could potentially expand the safe and judicious use of alteplase and improve outcomes after stroke. Methods— Writing group members were nominated by the committee chair on the basis of their previous work in relevant topic areas and were approved by the American Heart Association Stroke Council’s Scientific Statement Oversight Committee and the American Heart Association’s Manuscript Oversight Committee. The writers used systematic literature reviews, references to published clinical and epidemiology studies, morbidity and mortality reports, clinical and public health guidelines, authoritative statements, personal files, and expert opinion to summarize existing evidence and to indicate gaps in current knowledge and, when appropriate, formulated recommendations using standard American Heart Association criteria. All members of the writing group had the opportunity to comment on and approved the final version of this document. The document underwent extensive American Heart Association internal peer review, Stroke Council Leadership review, and Scientific Statements Oversight Committee review before consideration and approval by the American Heart Association Science Advisory and Coordinating Committee. Results— After a review of the current literature, it was clearly evident that the levels of evidence supporting individual exclusion criteria for intravenous alteplase vary widely. Several exclusionary criteria have already undergone extensive scientific study such as the clear benefit of alteplase treatment in elderly stroke patients, those with severe stroke, those with diabetes mellitus and hyperglycemia, and those with minor early ischemic changes evident on computed tomography. Some exclusions such as recent intracranial surgery are likely based on common sense and sound judgment and are unlikely to ever be subjected to a randomized, clinical trial to evaluate safety. Most other contraindications or warnings range somewhere in between. However, the differential impact of each exclusion criterion varies not only with the evidence base behind it but also with the frequency of the exclusion within the stroke population, the probability of coexistence of multiple exclusion factors in a single patient, and the variation in practice among treating clinicians.

Homocysteine-Lowering Therapy and Stroke Risk, Severity, and Disability. Additional Findings From the HOPE 2 Trial

Background and Purpose— Elevated total homocysteine is associated with a higher risk of cerebrovascular disease. It is not known whether lowering homocysteine impacts on stroke risk, both in terms of severity and ischemic vs hemorrhagic stroke subtypes. Our aim was to determine whether vitamin therapy reduces the risk of ischemic and hemorrhagic stroke, as well as stroke-related disability. Methods— We analyzed stroke outcomes among participants of the Heart Outcomes Prevention Evaluation 2 (HOPE 2) trial that randomized 5522 adults with known cardiovascular disease to a daily combination of 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12, or matching placebo, for 5 years. Results— Among 5522 participants, stroke occurred in 258 (4.7%) individuals during a mean of 5 years of follow-up. The geometric mean homocysteine concentration decreased by 2.2 &mgr;mol/L in the vitamin therapy group and increased by 0.80 &mgr;mol/L in the placebo group. The incidence rate of stroke was 0.88 per 100 person-years in the vitamin therapy group and 1.15 per 100 person-years in the placebo group (hazard ratio [HR], 0.75; 95% CI, 0.59–0.97). Vitamin therapy also reduced the risk of nonfatal stroke (HR, 0.72; 95% CI, 0.54–0.95) but did not impact on neurological deficit at 24 hours (P=0.45) or functional dependence at discharge or at 7 days (OR, 0.95; 95% CI, 0.57–1.56). In subgroup analysis, patients aged younger than 69 years, from regions without folic acid food fortification, with higher baseline cholesterol and homocysteine levels, and those not receiving antiplatelet or lipid-lowering drugs at enrollment had a larger treatment benefit. Conclusions— Lowering of homocysteine with folic acid and vitamins B6 and B12 did reduce the risk of overall stroke, but not stroke severity or disability.

IScore A Risk Score to Predict Death Early After Hospitalization for an Acute Ischemic Stroke

Background— A predictive model of stroke mortality may be useful for clinicians to improve communication with and care of hospitalized patients. Our aim was to identify predictors of mortality and to develop and validate a risk score model using information available at hospital presentation. Methods and Results— This retrospective study included 12 262 community-based patients presenting with an acute ischemic stroke at multiple hospitals in Ontario, Canada, between 2003 and 2008 who had been identified from the Registry of the Canadian Stroke Network (8223 patients in the derivation cohort, 4039 in the internal validation cohort) and the Ontario Stroke Audit (3720 for the external validation cohort). The mortality rates for the derivation and internal validation cohorts were 12.2% and 12.6%, respectively, at 30 days and 22.5% and 22.9% at 1 year. Multivariable predictors of 30-day and 1-year mortality included older age, male sex, severe stroke, nonlacunar stroke subtype, glucose ≥7.5 mmol/L (135 mg/dL), history of atrial fibrillation, coronary artery disease, congestive heart failure, cancer, dementia, kidney disease on dialysis, and dependency before the stroke. A risk score index stratified the risk of death and identified low- and high- risk individuals. The c statistic was 0.850 for 30-day mortality and 0.823 for 1-year mortality for the derivation cohort, 0.851 for the 30-day model and 0.840 for the 1-year mortality model in the internal validation set, and 0.790 for the 30-day model and 0.782 for the 1-year model in the external validation set. Conclusion— Among patients with ischemic stroke, factors identifiable within hours of hospital presentation predicted mortality risk at 30 days and 1 year. The predictive score may assist clinicians in estimating stroke mortality risk and policymakers in providing a quantitative tool to compare facilities.

Risk factors, inpatient care, and outcomes of pneumonia after ischemic stroke

Objectives: Pneumonia is the most common medical complication after stroke. Although several risk factors have been reported, the role of common comorbidities in the development of pneumonia is not well established. Moreover, there is discrepancy in the literature regarding the impact of pneumonia on stroke outcomes. Methods: This is a multicenter retrospective cohort study including consecutive patients with ischemic stroke admitted to Regional Stroke Centers participating in the Registry of Canadian Stroke Network in July 2003–March 2007. Pneumonia was defined as a complication that occurred within the first 30 days of the stroke and was confirmed radiographically. The main outcome measure was adjusted 30-day mortality. Secondary outcomes were adjusted 7- and 365-day mortality, institutionalization, length of stay, and modified Rankin score on discharge. We also assessed the impact of organized stroke care on pneumonia development and mortality. Results: Overall, 8,251 patients were included in the study. Stroke-associated pneumonia was observed in 587 patients (7.1*). Pneumonia increased 30-day (odds ratio [OR] 2.2 [95% confidence interval (CI) 1.8–2.7]) and 1-year mortality (OR 3.0 [95% CI 2.5–3.7]), but not 7-day mortality. Pneumonia was associated with poor functional outcome. Higher access to organized inpatient care resulted in a reduction of 30-day mortality (OR 0.50 [95% CI 0.41–0.61]). Older age, male sex, stroke severity, dysphagia, chronic obstructive pulmonary disease, coronary artery disease, nonlacunar ischemic stroke, and preadmission dependency were independent predictors of pneumonia. Conclusions: Development of pneumonia after stroke was associated with mortality at 30 days and 1 year, longer length of stay, and dependency at discharge. Patients who received more inpatient stroke services had reduced mortality after pneumonia.

Stroke in South America. A Systematic Review of Incidence, Prevalence, and Stroke Subtypes

BACKGROUND AND PURPOSE Stroke is a leading cause of mortality and disability in South America because of an increase in life expectancy and changes in the lifestyle of the population. Because epidemiological and clinical characteristics of stroke vary according to regional factors, we need to know the peculiarities of stroke on this continent. METHODS We performed a systematic review of articles on stroke in South America, with emphasis on those providing information on the incidence and prevalence of stroke (community-based studies) and the pattern of stroke subtypes (hospital-based studies). RESULTS Seven papers provided information on stroke epidemiology; 11 gave data on the pattern of stroke subtypes. Community-based studies showed crude stroke prevalence rates ranging from 1.74 to 6.51 per 1000 and annual incidence rates from 0.35 to 1.83 per 1000. Hospital-based stroke registries consistently reported a high frequency of intracranial hemorrhages, which accounted for 26% to 46% of all strokes. Among patients with cerebral infarctions, intracranial atherosclerotic lesions and small-vessel disease have been common pathogenic mechanisms underlying the stroke. In most studies, hypertensive arteriolopathy was the most common cause of both infarctions and hemorrhages. CONCLUSIONS Stroke has been poorly studied in South America. Available data suggest that the prevalence and incidence of stroke are lower than in developing countries. The pattern of stroke subtypes seems to be different from that reported in other regions of the world, with a higher frequency of cerebral hemorrhages, small-vessel disease, and intracranial atherosclerotic lesions. Such differences may be related to genetic, environmental, or sociocultural factors and to differences in the control of stroke risk factors.