Search

Background and Purpose— Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods— We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results— Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients ( P =0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4–3.7; P P =0.005) and hemorrhagic (odds ratio, 2.4; 95% CI, 1.2–4.9; P =0.01) end points separately. Conclusions— Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients.

Background: Outcomes after subarachnoid hemorrhage (SAH) have been rarely examined in large cohorts. Methods: This is an extension of the International Stroke Outcomes Study (INSTRUCT) pooling 13 ‘ideal’ stroke incidence studies (n=657 with SAH from 1993-2017, median age 56 years; 46% men). The primary outcomes were mortality and functional outcome (mRS score 3-5). Harmonized study factors included age, sex, behaviors (current smoking, alcohol intake), comorbidities (history of hypertension, ischemic heart disease, atrial fibrillation), stroke severity (e.g. NIHSS score) and year of stroke. In the pooled dataset, we estimated predictors of mortality using Poisson regression, to estimate incidence rate ratio (IRR) at 1 month (11 studies), 1 year (12 studies) and 5 years (7 studies). Generalized equation estimates in the log-binomial family were used to calculate risk ratios (RRs) for predictors of poor functional outcome at 1 month (5 studies) and 1 year (8 studies). Results: Mortality was 33% at 1 month, 43% at 1 year, and 47% at 5 years (Fig 1). Poor functional outcome was 25% at 1 month and 15% at 1 year (Fig 1). In multivariable analysis, age and stroke severity were associated with mortality at all time points, together with current smoking at 1 and 5 years, and history of hypertension at 5 years (Fig 2). Poor functional outcome was predicted by age (RR 1.03; 95% CI 1.01-1.04) at 1 month and by age (RR 1.04; 95% CI 1.00-1.08) and stroke severity (RR 1.94; 95% CI 1.02-2.87) at 1 year. Conclusion: Risk factors that predict SAH incidence including hypertension and smoking make outcomes worse. Better management of older patients and those with severe strokes could improve outcomes after SAH.

Introduction: As women suffer worse functional outcomes of stroke than men, they may also face more challenges with community reintegration but data are scarce. We examined sex differences in participation after stroke and which factors might account for these disparities. Methods: INSTRUCT is an individual participant data pooling study of incident strokes obtained from 13 population-based cohorts worldwide. Two of the cohorts (Melbourne ’96-‘99 and Auckland ’02-‘03) included assessment of participation at 5 years after stroke using the London Handicap Scale (LHS). The LHS is used to assess the individual’s perspective of their involvement in life situations including orientation (person’s awareness of surroundings), physical independence, mobility, occupation, social interaction and economic self-efficiency. The total score ranges from 0 (worst disadvantage) to 100 (no disadvantage). Linear regression was used to compare LHS total scores and sub-domains for women compared to men. Study-specific multivariable models incorporated adjustment for socio-demographics, stroke-related factors, pre-stroke health and post-stroke factors were combined using random-effects meta-analysis. Results: At 5 years after stroke, there were data on participation for 351/592 (59%) of survivors in Melbourne and 266/881 (30%) of survivors in Auckland. Women suffered greater participation restriction than men (total LHS, pooled mean difference, MD -5.55 [95% CI -8.47, -2.63]). The magnitude of the difference attenuated after adjusting for covariates (pooled MD -2.48 [-4.99, 0.03]). Significant confounders in study-specific models included age, stroke severity, pre-stroke dependency and pre-stroke dementia for Melbourne; and age, stroke severity and pre-stroke dependency for Auckland. In sub-dimensions, women had greater restriction than men in mobility, physical independence and occupation. Additionally, women in Melbourne experienced poorer social integration and orientation than men. Conclusion: Greater restriction in participation after stroke among women than men was mostly attributable to their advanced age and greater pre-stroke dependency. Interventions targeting participation could reduce the impact of stroke in women.

Background and Purposes— This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. Methods— The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00–1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08–2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P =0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30–1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632–0.763; P =0.0001) for ischemic outcome events and 0.585 (0.493–0.678; P =0.10) for major bleedings. Results— The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529–0.763; P =0.009) for ischemic outcome events and 0.407 (0.275–0.540; P =0.14) for hemorrhagic outcome events. Conclusions— In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings.

Background and Purpose —Prognosis of ischemic stroke in young adults is reported as favorable, and transient ischemic attack (TIA) is commonly considered a benign event. We investigated long-term outcome and prognostic predictors of cerebral ischemia in patients under 45 years of age. Methods —Three hundred thirty-three patients aged 15 to 44 years who suffered from a first-ever TIA or ischemic stroke were prospectively followed up with annual clinical evaluation or complete phone interview. End points were the composite outcome event of stroke, myocardial infarction, and vascular or nonvascular death and death from all causes. The probability of event-free survival was estimated by the Kaplan-Meier method. Univariate and multivariate estimates of hazard ratios were calculated according to the Cox proportional hazards analysis. Results —An average follow-up of 96 months was available in 330 patients (99.1%). Survival was worse in patients with stroke at entry (86.5%) than in those with TIA (97.1%). Mortality in both groups was significantly higher than in the general population (standardized mortality ratio [SMR] 14.5, P P =0.002). The average annual mortality rate was higher during the first (3.94%, 95% CI 1.84 to 6.04) than in the subsequent years. The average annual incidence rate of new stroke was higher in patients with stroke than in those with TIA at entry, and it declined from 1.56% (95% CI 0.21 to 2.91) during the first year to 0.06% (95% CI 0.04 to 0.08) at the end of the follow-up. Myocardial infarction occurred later, after the first year, with similar rates in patients with stroke and TIA at entry. The average annual rates of new stroke (2.36%), myocardial infarction (1.68%), and death (3.05%) were higher in patients with the mixed atherothrombotic and cardioembolic etiology than in the remaining patients. Male gender, age >35 years, stroke at entry, and cardiac diseases were independent predictors of the composite outcome event at the Cox regression analysis, whereas only stroke at entry and cardiac diseases predicted death from all causes. Conclusions —Stroke and TIA in young adults have severe prognostic implications, because the mortality risk was highly increased with respect to the general population. Preventive measures are strongly recommended in the presence of any unfavorable prognostic profile.

Background and Purpose— Several studies have assessed the possible increased risk of hemorrhagic stroke in migraineurs, drawing differing conclusions. No meta-analysis on the topic has been published to date. Methods— Multiple electronic databases (MEDLINE, EMBASE, Science Citation Index, and the Cochrane Library) were systematically searched up to March 2013 for studies dealing with migraine and hemorrhagic stroke. We selected case–control and cohort studies with a clear definition of the diagnostic criteria for migraine and hemorrhagic stroke, using an adjusted model or a matching procedure that could control for potential confounders, and reporting effect estimates with 95% confidence intervals (CIs) or enough data to allow calculation of those numbers. Adjusted odds ratios and hazard ratios were used to estimate effect size. Results— Of 11 264 records, we identified 8 studies (4 case–control and 4 cohort studies) involving a total of 1600 hemorrhagic strokes, which were included in the meta-analysis. The overall pooled adjusted effect estimate of hemorrhagic stroke in subjects with any migraine versus control subjects was 1.48 (95% CI, 1.16–1.88; P =0.002), with moderate statistical heterogeneity (I 2 =54.7%; P value for Q test=0.031). The risk of hemorrhagic stroke in subjects with migraine with aura (1.62; 95% CI, 0.87–3.03; P =0.129) was not significant. Compared with control subjects, the risk of hemorrhagic stroke was greater in females with any migraine (1.55; 95% CI, 1.16–2.07; P =0.003) and in female migraineurs aged less than 45 years (1.57; 95% CI, 1.10–2.24; P =0.012). Conclusions— Available studies suggest that subjects with migraine have an increased risk of hemorrhagic stroke. Further studies are needed to address the hemorrhagic stroke risk according to migraine type, age, sex, and hemorrhagic stroke type.

See related article, p 1770. Community-based registries are considered the best source of information on stroke incidence, risk factors, characteristics, and outcome. They can be used for developing adequate strategies for stroke care and prevention. Criteria to perform an ideal stroke incidence study had been defined and refined in the past 2 decades and include standards for definitions, methods, and data presentation.1–4 Complying with those criteria makes the obtained results reliable and the studies comparable to one another. However, community-based registries are challenging and are extremely time, labor, and resource demanding.5,6 Cross-sectional, cohort, and case-control studies, not at the community level, are routinely performed to obtain reliable data on several aspects concerning stroke characteristics and care. They can be as challenging as community-based registries, particularly when high numbers of subjects need to be included to ensure statistical power. Furthermore, those same studies do not reflect disparities across a nation because they are usually performed in geographic regions that more likely involve centers with active teams promoting better stroke care. ### Administrative Coding Data: Advantages and Pitfalls Alternatively, administrative coding data (also called claims data or billing) have been introduced as a tool for stroke research because they are associated with less resource wasting. Nearly all Western countries currently collect hospital discharge data in some form. They are anonymous, plentiful, inexpensive, and widely available in electronic format.7 In addition, they are quickly retrievable, thereby offering a remarkable advantage in terms of cost and affordability. Furthermore, because stroke is prominently a hospital-managed condition, administrative data might be suitable for monitoring its epidemiology. The advantage is greater when multiple years of data are needed for the analysis, such as when monitoring time trends or assessing the impact of different treatment strategies by using observations before and after the change. Administrative files typically …

The Early Stroke Trial is a randomized, placebo-controlled, double-masked, multicenter study to assess the safety and efficacy of monosialoganglioside in patients who have suffered an ischemic stroke of the cerebral hemispheres. Only patients who could be evaluated and treated within 5 hours after the onset of stroke were considered; within each center, subjects were stratified by age, sex, and clinical severity. Patients were randomly allocated to receive a specified sequence of intravenous and intramuscular doses of either monosialoganglioside or identical-appearing placebo for 21 days. Patients were followed up for 4 months after randomization. Neurological status was measured primarily by using the Canadian Neurological Scale. After assessing the effect of treatment on survival, the principal measure of efficacy will be the change in neurological status between baseline and the 4-month follow-up among survivors. Sixteen clinical centers, 15 in Europe and one in North America, entered a total of 792 eligible patients during a 36-month recruitment period (from May 1987 to April 1990). In our series there were more men than women, and the relative frequency of patients increased with advancing age. The most frequently associated cardiovascular conditions were hypertension, atrial fibrillation, and peripheral vascular disease. Approximately 46% of the patients were admitted to a hospital within 1 hour and 81%, within 2 hours after the onset of stroke. About 22% first received the study treatment within 3 hours and 57%, within 4 hours. This study demonstrates the feasibility of large-scale trials with the onset of treatment within 5 hours after an ischemic stroke.

Background and Purpose— The purpose of this study was to evaluate the incidence and prognosis of intracerebral hemorrhage. Methods— We analyzed data referring to our prospective population-based registry, including patients with a first-ever stroke followed up to 10 years. Results— In a 5-year period, we included 549 patients (247 men and 302 women; mean age±SD, 73.6±12.5 years) with an intracerebral hemorrhage. The crude annual incidence rate was 36.9 per 100000 (95% CI, 33.8 to 40.0), 32.9 per 100000 when standardized to the 2006 European population, and 15.9 per 100000 when standardized to the world population. The case-fatality rate was 34.6% (95% CI, 30.6 to 38.6) at 7 days; it increased to 50.3% (95% CI, 46.1 to 54.5) at 30 days and to 59.0% (95% CI, 54.9 to 63.1) at 1 year. Diabetes mellitus and posterior fossa hemorrhage were associated with an increased risk of 7- and 30-day mortality, whereas older age was associated with an increased risk of 30-day mortality only. At the Kaplan-Meier analysis, the 10-year survival rate was 24.1% (95% CI, 20.1 to 28.1). Conclusions— Intracerebral hemorrhage is characterized by a severe prognosis, mostly in the short term. Because of the high proportion of fatal events that occurs early after the stroke, it is mandatory to identify and apply specific therapeutic strategies for patients with intracerebral hemorrhage.

Background and Purpose— Atrial fibrillation (AF) is a major risk factor for ischemic stroke and its prevalence increases steeply with age. Population-based data on its influence on stroke outcome are scarce. Methods— We evaluated the prevalence of AF and its influence on prognosis in patients with a first-ever ischemic stroke from a population-based registry. Results— The presence of AF at stroke onset and during the acute phase was confirmed by a standard electrocardiogram in 869 (24.6%) of 3530 patients with ischemic stroke. With respect to patients without the arrhythmia, those with AF were more frequently women, aged 80 years and older, with coronary heart disease and peripheral arterial disease. The presence of AF was associated with high 30-day (32.5%; 95% CI, 29.3 to 35.6) and 1-year case-fatality rates (49.5%; 95% CI, 46.2 to 52.8), with a higher stroke recurrence rate within the first year of follow-up (6.6% versus 4.4%; P =0.046) and with the worst survival after an average follow-up of 45.2 months ( P Conclusions— We found a high prevalence of AF in patients with a first-ever ischemic stroke, especially among elderly women. The overall contribution of AF to stroke mortality was relevant, suggesting that together with new strategies to prevent the development of the arrhythmia more appropriate treatments are needed, mostly in elderly women.

Background and Purpose Changes in stroke incidence are likely to occur as a consequence of aging of the population, but evidence for this hypothesis is lacking. Methods A prospective community-based registry of first-ever strokes (1994 to 1998) classified according to the International Classification of Diseases, 9th Revision (ICD-9) was established in the L’Aquila district, central Italy, with a total population of 297 838 (1991 census). Patients were identified by active monitoring of multiple sources, including general practitioners. Results In 1994, 819 patients (398 men and 421 women; mean±SD age, 74.8±11.3 years) suffered from a first-ever stroke. Eighty-nine percent of the patients had neuroimaging studies of the brain and were reclassified with the recent Application of the International Classification of Diseases to Neurology (ICD-10 NA). The occurrence of subarachnoid hemorrhage, intracerebral hemorrhage, cerebral infarction, and ill-defined events was 2.9%, 14.9%, 80.2%, and 2.0%, respectively. Crude annual incidence of first-ever stroke was 2.75/1000 (95% confidence interval [CI], 2.57 to 2.94) and 24.23/1000 (95% CI, 21.65 to 27.10) in patients older than 80 years. Incidence rates were higher in men and steeply increased with age. The standardized rate was 2.37/1000 for the Italian and 2.28/1000 for the European population. The 30-day case-fatality rate was 25.6% (95% CI, 22.8% to 28.7%). The occurrence of death, disability, and full recovery at 1 year was 36.9%, 38.9%, and 24.2%, respectively. No differences were found in stroke incidence and case-fatality according to income and urban or rural residences. Conclusions In our population-based study, we found a high stroke incidence notably in the older age subgroups, suggesting that rather than declining, stroke is only being postponed until later in life.

The etiology of stroke in the young is different from that in older patients and remains unknown in almost one third of the cases. To gain further insight into both pathogenic and etiologic determinants, we prospectively studied a large number of consecutive young adults with focal cerebral ischemia. Three hundred thirty-three patients aged 15-44 years with transient ischemic attack or ischemic stroke within the 8 weeks before hospital admission were recruited and investigated by using a standardized protocol of clinical evaluation, blood tests, electrocardiography, echocardiography, chest roentgenography, and brain computed tomography. Presumed etiology was diagnosed by prospectively applied criteria. Women predominated (61%) among patients under 35 years of age, mainly due to the frequency of cerebral ischemia related to oral contraceptive use, while men outnumbered women (60%) among patients over that age because of a higher prevalence of atherothrombotic disease. Potential cerebral embolism of cardiac origin was the presumed cause of stroke in 23.7%, but conventional sources of emboli were found only in 7.5% of cases. There was a low prevalence of atrial fibrillation among young patients with cerebral ischemia. Mitral valve prolapse was found in 8.4%, as expected, predominantly (71.4%) among the younger patients. The prevalence of stroke over transient ischemic attack was proportional to the likelihood of cardiac embolism. Acute alcohol intoxication was considered a precipitating factor in only three patients. The percentages of cerebral ischemia attributed to arterial dissection (0.3%), oral contraceptive use in women (8.1%), migraine (1.2%), and other associated medical diseases (1.5%) were lower than reported in recent clinical series. Two different groups of pathogenic determinants predominate in younger women and in older men, supporting public health measures aimed at strict medical control of the recognized cerebrovascular risk factors.

The circulating white blood cells of patients with brain infarction were labelled in vitro with Indium-111 tropolonate; the cells were reinjected to study the inflammatory process by gamma camera imaging. Eight patients with acute cerebral ischemic infarct were studied during the first two weeks after the onset of neurological symptoms. In seven cases a well defined area of increased radioactivity was revealed in the infarcted hemisphere indicating active migration and tracking of labelled leukocytes in cerebral infarct. This method allows monitoring of the cellular inflammatory response in human cerebral infarcts and adds another imaging technique.