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Respiratory infection can be an immediate precursor to stroke and myocardial infarction. Influenza vaccination is associated with reduced risk of myocardial infarction and hospitalisation for cardiac disease, and influenza vaccination is strongly recommended for patients with heart disease. Evidence on whether the same protective association exists for stroke, and whether this potential effect is consistent across age and risk groups, is conflicting. We aimed to assess the risk of stroke after influenza vaccination in adults.We obtained administrative data from the Alberta Health Care Insurance Plan (which covers all residents of Alberta, Canada) beginning on Sept 30, 2009, or May 15 of the year in which residents were recorded as being 18 years of age. Individuals were censored at the earliest of three events: death, recorded outmigration, or Dec 31, 2018. The outcome of interest was any stroke event, comprising acute ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and transient ischaemic attack. We used Andersen-Gill Cox models to analyse the hazard of any stroke event for individuals with recent (lt;182 days) influenza vaccination compared with those without recent influenza vaccination, with adjustment for age, sex, anticoagulant use, atrial fibrillation, chronic obstructive pulmonary disease, diabetes, hypertension, income quintile, and rural or urban home location. Two-way interaction terms between each individual covariate and vaccination status were used to assess for effect modification by risk factor. The association between vaccination and risk of each type of stroke was also modelled, adjusting for baseline covariates.The study sample consisted of 4 141 209 adults (29 687 899 person-years of observation time) registered under the provincial health-care system between Sept 30, 2009, and Dec 31, 2018. 1 769 565 (42·73%) individuals received at least one vaccination during the study period, and 38 126 stroke events were recorded. Adjusted for demographics and comorbidities, recent influenza vaccination significantly reduced the hazard of stroke (hazard ratio 0·775 [95% CI 0·757-0·793]). This association persisted across all stroke types. We found effect modification by each covariate examined except for home location; however, vaccination was associated with a reduced risk of stroke overall across all ages and risk profiles with the exception of individuals without hypertension.The risk of stroke is reduced among people who have recently been vaccinated against influenza compared with those who have not. This association extended to the entire adult population and was not limited to individuals with a baseline high risk of stroke. Further studies in a variety of settings are needed to evaluate whether influenza vaccination could be used as a public health strategy to prevent stroke.None.

IMPORTANCE: The effectiveness and safety of intravenous alteplase given before or concurrently with endovascular thrombectomy (EVT) is uncertain. Randomized clinical trials suggest there is little difference in outcomes but with only modest precision and insufficient power to analyze uncommon outcomes including symptomatic intracranial hemorrhage (sICH). OBJECTIVE: To determine whether 8 prespecified outcomes are different in patients with acute ischemic stroke treated in routine clinical practice with EVT with alteplase compared with patients treated with EVT alone without alteplase. It was hypothesized that alteplase would be associated with higher risk of sICH. DESIGN, SETTING, AND PARTICIPANTS: This was an observational cohort study conducted from February 1, 2019, to June 30, 2020, that included adult patients with acute ischemic stroke treated with EVT within 6 hours of time last known well, after excluding patients without information on discharge destination and patients with in-hospital stroke. Participants were recruited from Get With The Guidelines–Stroke, a large nationwide registry of patients with acute ischemic stroke from 555 hospitals in the US. EXPOSURES: Intravenous alteplase or no alteplase. MAIN OUTCOMES AND MEASURES: Prespecified outcomes were discharge destination, independent ambulation at discharge, modified Rankin score at discharge, discharge mortality, cerebral reperfusion according to modified Thrombolysis in Cerebral Infarction grade, and sICH. RESULTS: There were 15 832 patients treated with EVT (median [IQR] age, 72.0 [61.0-82.0] years; 7932 women [50.1%]); 10 548 (66.7%) received alteplase and 5284 (33.4%) did not. Patients treated with alteplase were younger, arrived via Emergency Medical Services sooner, were less likely to have certain comorbidities, including atrial fibrillation, hypertension, and diabetes, but had similar National Institutes of Health Stroke Severity (NIHSS) scores. Compared with patients who did not receive alteplase treatment, patients treated with alteplase were less likely to die (11.1% [1173 of 10 548 patients] vs 13.9% [734 of 5284 patients]; adjusted odds ratio [aOR] 0.83; 95% CI, 0.77-0.89; P

Successful reperfusion determines the treatment effect of endovascular thrombectomy. We evaluated stent-retriever characteristics and their relation to reperfusion in the ESCAPE-NA1 trial.Independent re-scoring of reperfusion grade for each attempt was conducted. The following characteristics were evaluated: stent-retriever length and diameter, thrombus position within stent-retriever, bypass effect, deployment in the superior or inferior MCA trunk, use of balloon guide catheter and distal access catheter. Primary outcome was successful reperfusion defined as expanded thrombolysis in cerebral infarction (eTICI) 2b-3 per attempt. The secondary outcome was successful reperfusion eTICI 2b-3 after the first attempt. Separate regression models for each stent-retriever characteristic and an exploratory multivariable modeling to test the impact of all characteristics on successful reperfusion were built.Of 1105 patients in the trial, 809 with the stent-retriever use (1241 attempts) were included in the primary analysis. The stent-retriever was used as the first-line approach in 751 attempts. A successful attempt was associated with thrombus position within the proximal or middle third of the stent (OR 2.06; 95% CI: 1.24-3.40 and OR 1.92; 95% CI: 1.16-3.15 compared to the distal third respectively) and with bypass effect (OR 1.7; 95% CI: 1.07-2.72). Thrombus position within the proximal or middle third (OR 2.80; 95% CI: 1.47-5.35 and OR 2.05; 95% CI: 1.09-3.84, respectively) was associated with first-pass eTICI 2b-3 reperfusion. In the exploratory analysis accounting for all characteristics, bypass effect was the only independent predictor of eTICI 2b-3 reperfusion (OR 1.95; 95% CI: 1.10-3.46).The presence of bypass effect and thrombus positioning within the proximal and middle third of the stent-retriever were strongly associated with successful reperfusion.

Background Intracranial hemorrhage is a known complication after endovascular treatment in patients with acute ischemic stroke due to large vessel occlusion, but the association between radiologic hemorrhage severity and outcome is controversial. Purpose To investigate the prevalence and impact on outcome of intracranial hemorrhage and hemorrhage severity after endovascular stroke treatment. Materials and Methods The Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke (ESCAPE-NA1) trial enrolled participants with acute large vessel occlusion stroke who underwent endovascular treatment from March 1, 2017, to August 12, 2019. Evidence of any intracranial hemorrhage, hemorrhage multiplicity, and radiologic severity, according to the Heidelberg classification (hemorrhagic infarction type 1 [HI1], hemorrhagic infarction type 2 [HI2], parenchymal hematoma type 1 [PH1], and parenchymal hematoma type 2 [PH2]) was assessed at CT or MRI 24 hours after endovascular treatment. Good functional outcome, defined as a modified Rankin score of 0-2 at 90 days, was compared between participants with intracranial hemorrhage and those without intracranial hemorrhage at follow-up imaging and between hemorrhage subtypes. Poisson regression was performed to obtain adjusted effect size estimates for the presence of any intracranial hemorrhage and hemorrhage subtypes at good functional outcome. Results Of 1097 evaluated participants (mean age, 69 years ± 14 [standard deviation]; 551 men), any degree of intracranial hemorrhage was observed in 372 (34%). Good outcomes were less often achieved among participants with hemorrhage than among those without hemorrhage at follow-up imaging (164 of 372 participants [44%] vs 500 of 720 [69%], respectively; P < .01). After adjusting for baseline variables and infarct volume, intracranial hemorrhage was not associated with decreased chances of good outcome (adjusted risk ratio [RR] = 0.91 [95% CI: 0.82, 1.02], P = .10), but there was a graded relationship of radiologic hemorrhage severity and outcomes, whereby PH1 (RR = 0.77 [95% CI: 0.61, 0.97], P = .03) and PH2 (RR = 0.41 [95% CI: 0.21, 0.81], P = .01) were associated with decreased chances of good outcome. Conclusion Any degree of intracranial hemorrhage after endovascular treatment was seen in one-third of participants. A graded association existed between radiologic hemorrhage severity and outcome. Hemorrhagic infarction was not associated with outcome, whereas parenchymal hematoma was strongly associated with poor outcome, independent of infarct volume. © RSNA, 2021 Clinical trial registration no. NCT01778335 Online supplemental material is available for this article.

Background The effect of infarct pattern on functional outcome in acute ischemic stroke is incompletely understood. Purpose To investigate the association of qualitative and quantitative infarct variables at 24-hour follow-up noncontrast CT and diffusion-weighted MRI with 90-day clinical outcome. Materials and Methods The Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke, or ESCAPE-NA1, randomized controlled trial enrolled patients with large-vessel-occlusion stroke undergoing mechanical thrombectomy from March 1, 2017, to August 12, 2019. In this post hoc analysis of the trial, qualitative infarct variables (predominantly gray [vs gray and white] matter involvement, corticospinal tract involvement, infarct structure [scattered vs territorial]) and total infarct volume were assessed at 24-hour follow-up noncontrast CT or diffusion-weighted MRI. White and gray matter infarct volumes were assessed in patients by using follow-up diffusion-weighted MRI. Infarct variables were compared between patients with and those without good outcome, defined as a modified Rankin Scale score of 0-2 at 90 days. The association of infarct variables with good outcome was determined with use of multivariable logistic regression. Separate regression models were used to report effect size estimates with adjustment for total infarct volume. Results Qualitative infarct variables were assessed in 1026 patients (mean age ± standard deviation, 69 years ± 13; 522 men) and quantitative infarct variables were assessed in a subgroup of 358 of 1026 patients (mean age, 67 years ± 13; 190 women). Patients with gray and white matter involvement (odds ratio [OR] after multivariable adjustment, 0.19; 95% CI: 0.14, 0.25; P < .001), corticospinal tract involvement (OR after multivariable adjustment, 0.06; 95% CI: 0.04, 0.10; P < .001), and territorial infarcts (OR after multivariable adjustment, 0.22; 95% CI: 0.14, 0.32; P < .001) were less likely to achieve good outcome, independent of total infarct volume. Conclusion Infarct confinement to the gray matter, corticospinal tract sparing, and scattered infarct structure at 24-hour noncontrast CT and diffusion-weighted MRI were highly predictive of good 90-day clinical outcome, independent of total infarct volume. Clinical trial registration no. NCT02930018 © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Mossa-Basha in this issue.

BACKGROUND AND PURPOSE: Infarct volume is an important predictor of clinical outcome in acute stroke. We hypothesized that the association of infarct volume and clinical outcome changes with the magnitude of infarct size. MATERIALS AND METHODS: Data were derived from the Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial, in which patients with acute stroke with large-vessel occlusion were randomized to endovascular treatment plus either nerinetide or a placebo. Infarct volume was manually segmented on 24-hour noncontrast CT or DWI. The relationship between infarct volume and good outcome, defined as mRS 0–2 at 90 days, was plotted. Patients were categorized on the basis of visual grouping at the curve shoulders of the infarct volume/outcome plot. The relationship between infarct volume and adjusted probability of good outcome was fitted with linear or polynomial functions as appropriate in each group. RESULTS: We included 1099 individuals in the study. Median infarct volume at 24 hours was 24.9 mL (interquartile range [IQR] = 6.6–92.2 mL). On the basis of the infarct volume/outcome plot, 4 infarct volume groups were defined (IQR = 0–15 mL, 15.1–70 mL, 70.1–200 mL, >200 mL). Proportions of good outcome in the 4 groups were 359/431 (83.3%), 219/337 (65.0%), 71/201 (35.3%), and 16/130 (12.3%), respectively. In small infarcts (IQR = 0–15 mL), no relationship with outcome was appreciated. In patients with intermediate infarct volume (IQR = 15–200 mL), there was progressive importance of volume as an outcome predictor. In infarcts of > 200 mL, outcomes were overall poor. CONCLUSIONS: The relationship between infarct volume and clinical outcome varies nonlinearly with the magnitude of infarct size. Infarct volume was linearly associated with decreased chances of achieving good outcome in patients with moderate-to-large infarcts, but not in those with small infarcts. In very large infarcts, a near-deterministic association with poor outcome was seen.

Contains fulltext : 235277.pdf (Publisher’s version ) (Closed access) BACKGROUND: Balancing the risks of recurrent ischaemic stroke and intracranial haemorrhage is important for patients treated with antithrombotic therapy after ischaemic stroke or transient ischaemic attack. However, existing predictive models offer insufficient performance, particularly for assessing the risk of intracranial haemorrhage. We aimed to develop new risk scores incorporating clinical variables and cerebral microbleeds, an MRI biomarker of intracranial haemorrhage and ischaemic stroke risk. METHODS: We did a pooled analysis of individual-patient data from the Microbleeds International Collaborative Network (MICON), which includes 38 hospital-based prospective cohort studies from 18 countries. All studies recruited participants with previous ischaemic stroke or transient ischaemic attack, acquired baseline MRI allowing quantification of cerebral microbleeds, and followed-up participants for ischaemic stroke and intracranial haemorrhage. Participants not taking antithrombotic drugs were excluded. We developed Cox regression models to predict the 5-year risks of intracranial haemorrhage and ischaemic stroke, selecting candidate predictors on biological relevance and simplifying models using backward elimination. We derived integer risk scores for clinical use. We assessed model performance in internal validation, adjusted for optimism using bootstrapping. The study is registered on PROSPERO, CRD42016036602. FINDINGS: The included studies recruited participants between Aug 28, 2001, and Feb 4, 2018. 15 766 participants had follow-up for intracranial haemorrhage, and 15 784 for ischaemic stroke. Over a median follow-up of 2 years, 184 intracranial haemorrhages and 1048 ischaemic strokes were reported. The risk models we developed included cerebral microbleed burden and simple clinical variables. Optimism-adjusted c indices were 0·73 (95% CI 0·69-0·77) with a calibration slope of 0·94 (0·81-1·06) for the intracranial haemorrhage model and 0·63 (0·62-0·65) with a calibration slope of 0·97 (0·87-1·07) for the ischaemic stroke model. There was good agreement between predicted and observed risk for both models. INTERPRETATION: The MICON risk scores, incorporating clinical variables and cerebral microbleeds, offer predictive value for the long-term risks of intracranial haemorrhage and ischaemic stroke in patients prescribed antithrombotic therapy for secondary stroke prevention; external validation is warranted. FUNDING: British Heart Foundation and Stroke Association.

There are few data on the prevalence and impact of isolated deep grey matter infarction in acute stroke. In this study, we aimed to investigate the prevalence of isolated deep grey matter infarcts and their impact on the outcome. Infarcts on 24-h follow-up imaging (non-contrast head CT or diffusion-weighted MRI) in the ESCAPE-NA1 trial were categorized into predominantly deep grey matter infarcts vs. infarcts involving additional territories (“other infarcts”). Total infarct volume was manually segmented. Baseline characteristics and proportions of good outcome (primary outcome, defined as modified Rankin Score [mRS] 0–2 at 90 days), excellent outcome (mRS 0–1) and mortality were compared between patients with and without predominantly deep grey matter infarcts. Multivariable logistic regression with adjustment for baseline variables and total infarct volume was used to determine a possible association of predominantly deep grey matter infarcts and clinical outcome. Predominantly deep grey matter infarcts were seen in 316/1026 patients (30.8%). Compared to other patients, their ASPECTS was higher, collateral status and reperfusion quality were better and time to treatment was shorter. Good outcome was seen in 239/316 (75.6%) with vs. 374/704 (53.1%) without predominantly deep grey matter infarcts. After adjusting for baseline variables and total infarct volume, predominantly deep grey matter infarcts were independently associated with excellent outcome (adjOR: 1.45 [CI95: 1.04–2.02]), but not with good outcome (adjOR: 1.24 [CI95: 0.86–1.80]) or mortality (adjOR: 0.73 [CI95:0.39–1.35]) Predominantly deep grey matter infarct patterns were seen in 1/3rd of patients and were significantly associated with increased chances of excellent outcome, independent of patient baseline status and infarct size.

Intravenous thrombolysis with alteplase bolus followed by infusion is a global standard of care for patients with acute ischaemic stroke. We aimed to determine whether tenecteplase given as a single bolus might increase reperfusion compared with this standard of care.In this multicentre, open-label, parallel-group, registry-linked, randomised, controlled trial (AcT), patients were enrolled from 22 primary and comprehensive stroke centres across Canada. Patients were eligible for inclusion if they were aged 18 years or older, with a diagnosis of ischaemic stroke causing disabling neurological deficit, presenting within 4·5 h of symptom onset, and eligible for thrombolysis per Canadian guidelines. Eligible patients were randomly assigned (1:1), using a previously validated minimal sufficient balance algorithm to balance allocation by site and a secure real-time web-based server, to either intravenous tenecteplase (0·25 mg/kg to a maximum of 25 mg) or alteplase (0·9 mg/kg to a maximum of 90mg; 0·09 mg/kg as a bolus and then a 60 min infusion of the remaining 0·81 mg/kg). The primary outcome was the proportion of patients who had a modified Rankin Scale (mRS) score of 0-1 at 90-120 days after treatment, assessed via blinded review in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment who did not withdraw consent). Non-inferiority was met if the lower 95% CI of the difference in the proportion of patients who met the primary outcome between the tenecteplase and alteplase groups was more than -5%. Safety was assessed in all patients who received any of either thrombolytic agent and who were reported as treated. The trial is registered with ClinicalTrials.gov, NCT03889249, and is closed to accrual.Between Dec 10, 2019, and Jan 25, 2022, 1600 patients were enrolled and randomly assigned to tenecteplase (n=816) or alteplase (n=784), of whom 1577 were included in the ITT population (n=806 tenecteplase; n=771 alteplase). The median age was 74 years (IQR 63-83), 755 (47·9%) of 1577 patients were female and 822 (52·1%) were male. As of data cutoff (Jan 21, 2022), 296 (36·9%) of 802 patients in the tenecteplase group and 266 (34·8%) of 765 in the alteplase group had an mRS score of 0-1 at 90-120 days (unadjusted risk difference 2·1% [95% CI - 2·6 to 6·9], meeting the prespecified non-inferiority threshold). In safety analyses, 27 (3·4%) of 800 patients in the tenecteplase group and 24 (3·2%) of 763 in the alteplase group had 24 h symptomatic intracerebral haemorrhage and 122 (15·3%) of 796 and 117 (15·4%) of 763 died within 90 days of starting treatment INTERPRETATION: Intravenous tenecteplase (0·25 mg/kg) is a reasonable alternative to alteplase for all patients presenting with acute ischaemic stroke who meet standard criteria for thrombolysis.Canadian Institutes of Health Research, Alberta Strategy for Patient Oriented Research Support Unit.

BackgroundThe DAWN and DEFUSE-3 trials showed the benefit of endovascular treatment (EVT) in acute ischemic stroke patients presenting beyond 6 hours from last known well (LKW) and selected by perfusion imaging criteria. The ESCAPE NA1-trial selected patients based on non-contrast CT (NCCT) Alberta Stroke Program Early CT Score (ASPECTS) and multiphase CT angiography (CTA) collateral status. This study compares baseline characteristics, workflow, and outcomes in the EVT arms of DAWN and DEFUSE-3 with late-window patients from the EVT-only arm of ESCAPE-NA1.MethodsAggregate data on baseline characteristics, workflow, reperfusion quality, final infarct volume, and clinical outcomes (modified Rankin Score [mRS] at 90 days) in subjects enrolled in the DAWN and DEFUSE-3 EVT arms were compared with similar data from the ESCAPE-NA1 control arm (EVT-only arm) presenting beyond 6 hours from LKW using descriptive statistics.ResultsBaseline characteristics among late-window patients in the ESCAPE NA1 trial were similar to those in the DAWN and DEFUSE-3 EVT arms. Median time from LKW-to-puncture in subjects enrolled in the ESCAPE NA1 trial was 9 hrs (IQR: 7.5–11 hours) when compared with DAWN (n=107; 12.8 hours, IQR: 10.6–16.7 hours) and DEFUSE-3 (n=92; 11.5 hours, IQR: 9.2–12.8 hours). Median post-treatment infarct-volume was largest in the ESCAPE NA1-patients (47 mL [IQR: 19–146] vs median 8 mL [IQR: 0–48] in the DAWN group and 35 mL [IQR: 18–82] in DEFUSE-3), while % mRS 0–2 at 90 days were similar across the three trials (ESCAPE NA1: 50/111 [45%], DAWN: 52/107 [49%], DEFUSE-3: 41/92 [45%]).ConclusionPatients enrolled beyond 6 hours from LKW in the ESCAPE-NA1 trial based on NCCT-ASPECTS and mCTA had similar clinical outcomes when compared with patients selected by perfusion imaging in the DAWN and DEFUSE-3 trials.

Background:Acute ischemic stroke may affect women and men differently. We aimed to evaluate sex differences in outcomes of endovascular treatment (EVT) for ischemic stroke due to large vessel occlusion in a population-based study in Alberta, Canada.Methods and Results:Over a 3-year period (April 2015–March 2018), 576 patients fit the inclusion criteria of our study and constituted the EVT group of our analysis. The medical treatment group of the ESCAPE trial had 150 patients. Thus, our total sample size was 726. We captured outcomes in clinical routine using administrative data and a linked database methodology. The primary outcome of our study was home-time. Home-time refers to the number of days that the patient was back at their premorbid living situation without an increase in the level of care within 90 days of the index stroke event. In adjusted analysis, EVT was associated with an increase of 90-day home-time by an average of 6.08 (95% CI −2.74–14.89, p-value 0.177) days in women compared to an average of 11.20 (95% CI 1.94–20.46, p-value 0.018) days in men. Further analysis revealed that the association between EVT and 90-day home-time in women was confounded by age and onset-to-treatment time.Conclusions:We found a nonsignificant nominal reduction of 90-day home-time gain for women compared to men in this province-wide population-based study of EVT for large vessel occlusion, which was only partially explained by confounding.

ObjectiveTo undertake an effectiveness and safety analysis of EVT in patients with LVO and NIH Stroke Scale (NIHSS) score ≤6 using datasets of multicenter and multinational nature.MethodsWe pooled patients with anterior circulation occlusion from 3 prospective international cohorts. Patients were eligible if presentation occurred within 12 hours from last known well and baseline NIHSS ≤6. Primary outcome was modified Rankin Scale (mRS) score 0–1 at 90 days. Secondary outcomes included neurologic deterioration at 24 hours (change in NIHSS of ≥2 points), mRS 0–2 at 90 days, and 90-day all-cause mortality. We used propensity score matching to adjust for nonrandomized treatment allocation.ResultsAmong 236 patients who fit inclusion criteria, 139 received EVT and 97 received medical management. Compared to medical management, the EVT group was younger (65 vs 72 years; p < 0.001), had more proximal occlusions (p < 0.001), and less frequently received concurrent IV thrombolysis (57.7% vs 71.2%; p = 0.04). After propensity score matching, clinical outcomes between the 2 groups were not significantly different. EVT patients had an 8.6% (95% confidence interval [CI] −8.8% to 26.1%) higher rate of excellent 90-day outcome, despite a 22.3% (95% CI, 3.0%–41.6%) higher risk of neurologic deterioration at 24 hours.ConclusionsEVT for LVO in patients with low NIHSS score was associated with increased risk of neurologic deterioration at 24 hours. However, both EVT and medical management resulted in similar proportions of excellent clinical outcomes at 90 days.Classification of evidenceThis study provides Class III evidence that for patients with acute anterior circulation ischemic strokes and LVO with NIHSS < 6, EVT and medical management result in similar outcomes at 90 days.

Recombinant tissue plasminogen activator improves outcomes in acute ischemic stroke. Alteplase may result in thrombus migration (TM) distally to a critical arterial supply that can worsen perfusion to eloquent brain tissue. Alteplase-related stroke recanalization and clot migration in vertebral artery (VA) occlusion whereby the clot migrates to the basilar artery (BA) may be harmful. We identified seven subjects with isolated symptomatic vertebral occlusion. Two cases suffered early neurologic deterioration due to TM from VA to BA following alteplase. Precautionary transfer to thrombectomy centers may be warranted in alteplase-treated symptomatic VA occlusions in case of migration to basilar occlusion.

We thank Drs. Khunte and Malhotra for their comments on our study.1 As we have stated in the Discussion section of our article, onset-to-treatment times were not available for our analysis, but we agree that their hypothesis could certainly be true. We are not sure where they saw the increased hemorrhage rate reported in our article because data about intracranial hemorrhages were unverifiable in the Safe Implementation of Treatments in Stroke–Thrombectomy (SITS-TBY) registry and could not be evaluated for our study.1 Furthermore, the MR CLEAN Registry group published a paper recently, which “found no evidence of an association of prior antiplatelet therapy with the risk of symptomatic intracranial hemorrhage after endovascular treatment, nor on functional outcome, reperfusion, or mortality.”2

Silent brain infarction (SBI) may be associated with cognitive decline in the general population. We systematically reviewed prior literature on: (1) SBI and cognition cross-sectionally; (2) baseline SBI and future cognitive decline and risk for cognitive disorders including dementia, and (3) incident SBI and the emergence of cognitive decline or cognitive disorders. The MEDLINE and EMBASE databases were searched for relevant studies. Data were independently extracted by two reviewers. Quality was assessed using the Newcastle Ottawa Scale. Data were pooled using a random effects model when more than two comparable estimates were found. Thirty relevant studies were identified: 17 had a cross-sectional design, 10 evaluated the association of baseline SBI with future cognitive decline, and 5 evaluated the association of incident SBI with cognitive decline. Most cross-sectional studies reported lower cognitive performance in persons with SBI. The pooled risk for incident dementia in persons with SBI was 1.48 (95% CI 1.12–1.97), but there was significant heterogeneity (p = 0.009); removing one outlier eliminated the heterogeneity (p = 0.53), giving a lower but still significant estimate (hazard ratio 1.27, 95% CI 1.06–1.51). The pooled risk for incident MCI was not increased in persons with SBI (hazard ratio 0.83, 95% CI 0.40 to 1.72), but there was significant heterogeneity (p

Background and Purpose The modified Rankin Scale (mRS) is the most widely used primary outcome measure in acute stroke trials. However, substantial interobserver variability impairs outcome assessment as well as reduces power of clinical trials. Guided by the International Classification of Functioning, Disability and Health, we developed a comprehensive, hierarchical assessment tool (miFUNCTION) to address the shortcomings of the modified Rankin Scale and deliver a more thorough understanding of disability following stroke. Methods The initial construct validity of miFUNCTION was established in a pilot study of patients at an outpatient stroke prevention clinic that had been diagnosed with stroke within 60 days. To further assess criterion validity, miFUNCTION was compared against the modified Rankin Scale and other outcome measures within the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial. Logistic regression analysis with miFUNCTION as an outcome was used to demonstrate the beneficial effect of endovascular treatment. Results The pilot study showed moderate inter-observer agreement (k = 0.585, p Conclusions miFUNCTION is strongly associated with the degree of disability following stroke both in an outpatient setting and a clinical trial. Further work remains to assess sensitivity to change and to improve the inter-observer reliability of the scale.

BackgroundThe optimal treatment and prognosis for stroke patients with tandem cervical carotid occlusion are unclear. We analyzed outcomes and treatment strategies of tandem occlusion patients in the ESCAPE-NA1 trial.MethodsESCAPE-NA1 was a multicenter international randomized trial of nerinetide versus placebo in 1105 patients with acute ischemic stroke who underwent endovascular treatment. We defined tandem occlusions as complete occlusion of the cervical internal carotid artery (ICA) on catheter angiography, in addition to a proximal ipsilateral intracranial large vessel occlusion. Baseline characteristics and outcome parameters were compared between patients with tandem occlusions versus those without, and between patients with tandem occlusion who underwent ICA stenting versus those who did not. The influence of tandem occlusions on functional outcome was analyzed using multivariable regression modeling.ResultsAmong 115/1105 patients (10.4%) with tandem occlusions, 62 (53.9%) received stenting for the cervical ICA occlusion. Of these, 46 (74.2%) were stented after and 16 (25.8%) before the intracranial thrombectomy. A modified Rankin Score (mRS) of 0–2 at 90 days was achieved in 82/115 patients (71.3%) with tandem occlusions compared with 579/981 (59.5%) patients without tandem occlusions. Tandem occlusion did not impact functional outcome in the adjusted analysis (OR 1.5, 95% CI 0.95 to 2.4). Among the subgroup of patients with tandem occlusion, cervical carotid stenting was not associated with different outcomes compared with no stenting (mRS 0–2: 75.8% vs 66.0%, adjusted OR 2.0, 95% CI 0.8 to 5.1).ConclusionsTandem cervical carotid occlusion in patients with acute large vessel stroke did not lower the odds of good functional outcome in our study. Functional outcomes were similar irrespective of the management of the cervical ICA occlusion (stenting vs not stenting).

Purpose: In this post-hoc analysis of the ESCAPE-NA1 trial, we investigated the prevalence of deep grey matter infarcts and their influence on clinical outcome. Methods: Infarcts on 24 hour follow up imaging (non contrast head CT or diffusion-weighted MRI) were categorized as predominantly deep grey matter infarcts (caudate and/or lentiform nucleus infarcts with sparing of the superficial grey matter and white matter) vs. other infarcts. Total infarct volume was manually segmented in all patients. When MRI follow-up was available, deep grey matter and grey matter infarct volumes were segmented separately. Multivariable logistic regression with adjustment for key minimization variables and by infarct volume was used to assess the association of predominantly deep grey matter infarcts and good outcome. Results: Of the 1026 included patients, 316 (30.8%) had predominantly deep grey matter infarcts. Cumulative proportions of good outcome for overall, grey matter, deep grey matter, and superficial grey matter infarct volumes are shown in the figure. Good outcomes were more frequently achieved in patients with predominantly deep grey matter infarcts (239/316 [75.6%] vs. 374/704 [53.1%]). Deep infarcts were tightly correlated with infarct volume (Pearson rho -0.35) and in multivariable analysis deep grey matter infarcts were predictive of outcome overall; when examined in volume percentiles, there was no effect of deep infarct location. Conclusion: Predominantly deep grey matter infarcts are associated with good outcomes. Deep grey matter infarct location favorable prognosis is associated with small overall infarct size.

There are few data on the prevalence and impact of isolated deep grey matter infarction in acute stroke. In this study, we aimed to investigate the prevalence of isolated deep grey matter infarcts and their impact on the outcome.Infarcts on 24-h follow-up imaging (non-contrast head CT or diffusion-weighted MRI) in the ESCAPE-NA1 trial were categorized into predominantly deep grey matter infarcts vs. infarcts involving additional territories ("other infarcts"). Total infarct volume was manually segmented. Baseline characteristics and proportions of good outcome (primary outcome, defined as modified Rankin Score [mRS] 0-2 at 90 days), excellent outcome (mRS 0-1) and mortality were compared between patients with and without predominantly deep grey matter infarcts. Multivariable logistic regression with adjustment for baseline variables and total infarct volume was used to determine a possible association of predominantly deep grey matter infarcts and clinical outcome.Predominantly deep grey matter infarcts were seen in 316/1026 patients (30.8%). Compared to other patients, their ASPECTS was higher, collateral status and reperfusion quality were better and time to treatment was shorter. Good outcome was seen in 239/316 (75.6%) with vs. 374/704 (53.1%) without predominantly deep grey matter infarcts. After adjusting for baseline variables and total infarct volume, predominantly deep grey matter infarcts were independently associated with excellent outcome (

Background and Purpose— The mobile stroke unit (MSU) brings imaging and thrombolysis to patients in the field. The MSU has the potential to decrease time from onset to thrombolysis; however, this depends on the location of the patient, the MSU, and the hospital. The MSU will only be able to treat a small subset of patients it is dispatched to. Using conditional probability modeling, we evaluate in which scenarios the MSU exhibits clear benefit over the direct-to-mothership method. Methods— Previously published conditional probability models for drip-and-ship versus mothership transport were modified to reflect MSU workflow. It was assumed that the MSU was dispatched from the endovascular therapy center. Eight scenarios were generated, varying treatment efficiency on the MSU and at the endovascular therapy center and the threshold for dispatching the MSU (low threshold: low treatment rate but few missed patients; high threshold: higher treatment rate, potential for missed treatment opportunities). Results— The relative difference in outcomes between the MSU and mothership was small. Geographic areas where the MSU is superior to mothership increase in size as treatment time on the MSU decreases. When a high-threshold dispatch system is used, the area where the MSU is superior decreases, but the relative difference in predicted outcomes between the MSU and mothership increases. The largest relative difference favoring the MSU was found in areas where the patient would forgo access to alteplase, based upon a 4.5-hour treatment threshold, using mothership transport. Conclusions— There are few scenarios where MSU transport predicts substantially superior outcomes to the mothership method when the MSU is dispatched from the endovascular therapy center. Outcomes using the MSU are maximized when dispatch criteria that maximize patients eligible for thrombolysis treatment are used and treatment times on the MSU are short relative to those of the endovascular therapy center.

Background: A heterogeneous patient population receives endovascular treatment (EVT) for acute ischemic stroke due to proximal large vessel occlusion every day. We aimed to conduct a population-based study of EVT in the province of Alberta, Canada, to understand the effectiveness in a complete population and how the magnitude of effect differs from the artificial world of clinical trials. Methods and Results: Within a three year period (April 2015 - March 2018), 576 patients fit the inclusion criteria of our study and constituted the EVT group of our analysis. The medical treatment group of the ESCAPE trial had 150 patients. Thus our total sample size was 726. We captured outcomes in clinical routine using administrative data and a linked database methodology. Primary outcome of our study was home-time. Home-time refers to the number of days that the patient was back at pre-morbid living situation without increase in level of care within 90 days of index stroke event. Median age of patients was 70 years (interquartile range (IQR) 59 - 81) and 47.8% were female. Median National Institutes of Health Stroke Scale (NIHSS) score was 17 (IQR 13 - 20). EVT was associated with an increased 90-day home-time by an average of 8.5 days compared to medical treatment alone using Cragg hurdle regression (p = 0.009). Age and higher NIHSS score were associated with decreased 90-day home-time (both p = 0.001). Multivariable logistic regression showed no association between EVT and mortality at 90 days (odds ratio 0.76, 95% confidence interval 0.47 - 1.24). Conclusions: EVT for acute ischemic stroke due to proximal large vessel occlusion was effective in our province-wide population-based study and results in increased 90-day home-time by ~8.5 days. Home-time is a novel and patient-centered outcome that reflects health circumstances that are easy to understand and meaningful to patients and their caregivers.

Objective: To derive a plasma biomarker protein panel from a list of 141 candidate proteins which can differentiate transient ischaemic attack (TIA)/minor stroke from non-cerebrovascular (mimic) conditions in emergency department (ED) settings. Design: Prospective clinical study (#NCT03050099) with up to three timed blood draws no more than 36 h following symptom onset. Plasma samples analysed by multiple reaction monitoring-mass spectrometry (MRM-MS). Participants: Totally 545 participants suspected of TIA enrolled in the EDs of two urban medical centres. Outcomes: 90-day, neurologist-adjudicated diagnosis of TIA informed by clinical and radiological investigations. Results: The final protein panel consists of 16 proteins whose patterns show differential abundance between TIA and mimic patients. Nine of the proteins were significant univariate predictors of TIA [odds ratio (95% confidence interval)]: L-selectin [0.726 (0.596–0.883)]; Insulin-like growth factor-binding protein 3 [0.727 (0.594–0.889)]; Coagulation factor X [0.740 (0.603–0.908)]; Serum paraoxonase/lactonase 3 [0.763 (0.630–0.924)]; Thrombospondin-1 [1.313 (1.081–1.595)]; Hyaluronan-binding protein 2 [0.776 (0.637–0.945)]; Heparin cofactor 2 [0.775 (0.634–0.947)]; Apolipoprotein B-100 [1.249 (1.037–1.503)]; and von Willebrand factor [1.256 (1.034–1.527)]. The scientific plausibility of the panel proteins is discussed. Conclusions: Our panel has the potential to assist ED physicians in distinguishing TIA from mimic patients.

Summary Even though stroke presents as a variety of clinical syndromes, neuroimaging is the most important biomarker to help differentiate between stroke subtypes and assess treatment eligibility. Therapeutic advances have led to intravenous thrombolysis with tissue-type plasminogen activator and endovascular treatment for proximal vessel occlusion in the anterior cerebral circulation being standard care for acute ischaemic stroke. Providing access to this care has implications for existing systems of care for stroke and their organisation and has reintroduced the possibility of adjuvant and neuroprotective treatment strategies in acute ischaemic stroke. The use of neuroimaging for patient selection and speed of diagnosis and delivery of treatment are the dominant themes of modern ischaemic stroke care.

Background and Purpose— White matter lesions (WML) are associated with cognitive decline, increased stroke risk, and disability in old age. We hypothesized that superimposed acute cerebrovascular occlusion on chronic preexisting injury (leukoaraiosis) leads to worse outcome after minor cerebrovascular event, both using quantitative (volumetric) and qualitative (Fazekas scale) assessment, as well as relative total brain volume. Methods— WML volume assessment was performed in 425 patients with high-risk transient ischemic attack (TIA; motor/speech deficits >5 minutes) or minor strokes from the CATCH study (CT and MRI in the Triage of TIA and Minor Cerebrovascular Events to Identify High Risk Patients). Complete baseline characteristics and outcome assessment were available in 412 patients. Primary outcome was disability at 90 days, defined as modified Rankin Scale score of >1. Secondary outcomes were stroke progression, TIA recurrence, and stroke recurrence. Analysis was performed using descriptive statistics and regression models including interaction terms. Results— Median age was 69 years, 39.8% were female. Sixty-two patients (15%) had unfavorable outcome with disability at 90 days (modified Rankin Scale score >1). Higher Fazekas scores were strongly correlated with higher WML volume ( r =0.79). Both higher Fazekas score and higher WMH volume were associated with disability at 90 days in univariate regression (odds ratio 1.22; 95% confidence interval, 1.04–1.43 and odds ratio, 1.25 per milliliter increase; 95% confidence interval, 1.02–1.54, respectively) but not with stroke progression, TIA recurrence, or stroke recurrence. In multivariable-adjusted analyses, additive interaction terms were associated with unfavorable outcome (adjusted odds ratio 3.99, 95% confidence interval, 1.87–8.49). Conclusions— Our data suggest that quantitative and qualitative WML assessments are highly correlated and comparable in TIA/minor stroke patients. WML burden is associated with short-term outcome of patients with good prestroke function in the presence of intracranial stenosis/occlusion.

Background and Purpose— Acute minor neurological deficits are a common complaint in the emergency department and differentiation of transient ischemic attack/minor stroke from a stroke mimic is difficult. We sought to assess the ability of white matter hyperintensity (WMH) volume to aid the diagnosis in such patients. Methods— This is a post hoc analysis of the previously published SpecTRA study (Spectrometry in TIA Rapid Assessment) of adult patients that presented to the emergency department with acute minor neurological deficits between December 2013 and March 2017. WMH volumes were measured if fluid-attenuated inversion recovery imaging was available. Outcomes of interest were final diagnosis, symptoms at presentation, and 90-day stroke recurrence. Results— WMH volume was available for 1485 patients. Median age was 70 years (interquartile range, 59–80), and 46.7% were female. Mean WMH volume was higher in transient ischemic attack/minor strokes compared with stroke mimics (1.71 ln mL [95% CI, 1.63–1.79 ln mL] versus 1.15 ln mL [95% CI, 1.02–1.27 ln mL], P P =0.035). Conclusions— The combination of diffusion-weighted imaging positivity and high WMH volume was associated with lower odds of focal symptoms at presentation in patients seen with minor neurological deficits in the emergency department. This suggests that WMH volume might be an important consideration and the absence of focal symptoms at presentation should not discourage clinicians from further investigating patients with suspected cerebral ischemia.

Contains fulltext : 208975.pdf (Publisher’s version ) (Open Access) 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 [1.23-1.82]). 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 1000 patient-years; and for >/=20 cerebral microbleeds, 73 ischaemic strokes [46-108] per 1000 patient-years vs 39 intracranial haemorrhages [21-67] per 1000 patient-years). INTERPRETATION: In patients with recent ischaemic stroke or transient ischaemic attack, cerebral microbleeds are associated with a greater relative hazard (aHR) for subsequent intracranial haemorrhage than for ischaemic stroke, but the absolute risk of ischaemic stroke is higher than that of intracranial haemorrhage, regardless of cerebral microbleed presence, antomical distribution, or burden. FUNDING: British Heart Foundation and UK Stroke Association.

ObjectiveTo assess cerebrovascular reactivity in response to a visual task in participants with cerebral amyloid angiopathy (CAA), Alzheimer disease (AD), and mild cognitive impairment (MCI) using fMRI.MethodsThis prospective cohort study included 40 patients with CAA, 22 with AD, 27 with MCI, and 25 healthy controls. Each participant underwent a visual fMRI task using a contrast-reversing checkerboard stimulus. Visual evoked potentials (VEPs) were used to compare visual cortex neuronal activity in 83 participants. General linear models using least-squares means, adjusted for multiple comparisons with the Tukey test, were used to estimate mean blood oxygen level–dependent (BOLD) signal change during the task and VEP differences between groups.ResultsAfter adjustment for age and hypertension, estimated mean BOLD response amplitude was as follows: CAA 1.88% (95% confidence interval [CI] 1.60%–2.15%), AD 2.26% (1.91%–2.61%), MCI 2.15% (1.84%–2.46%), and control 2.65% (2.29%–3.00%). Only patients with CAA differed from controls (p = 0.01). In the subset with VEPs, group was not associated with prolonged latencies or lower amplitudes. Lower BOLD amplitude response was associated with higher white matter hyperintensity (WMH) volumes in CAA (for each 0.1% lower BOLD response amplitude, the WMH volume was 9.2% higher, 95% CI 6.0%–12.4%) but not other groups (p = 0.002 for interaction) when controlling for age and hypertension.ConclusionsMean visual BOLD response amplitude was lowest in participants with CAA compared to controls, without differences in VEP latencies and amplitudes. This suggests that the impaired visual BOLD response is due to reduced vascular reactivity in CAA. In contrast to participants with CAA, the visual BOLD response amplitude did not differ between those with AD or MCI and controls.

Background and Purpose: The modified Rankin Scale (mRS) is the most widely used primary outcome measure in acute stroke trials. However, substantial inter-observer variability impairs outcome assessment and reduces power of clinical trials. Guided by the International Classification of Functioning, Disability and Health (ICF), we developed a comprehensive, hierarchical assessment tool (miFUNCTION) to address the shortcomings of the mRS and deliver a more thorough understanding of disability following stroke (figure 1). Methods: The construct validity of miFUNCTION was initially established in a pilot study of patients at an outpatient stroke prevention clinic that had been diagnosed with stroke within 60 days. To further assess criterion validity, miFUNCTION was compared against the mRS and other outcome measures within the ESCAPE trial. Logistic regression analysis with miFUNCTION as an outcome was used to demonstrate the benefit of endovascular treatment. Results: The pilot study showed moderate inter-observer agreement (k=0.585, p Conclusions: miFUNCTION is strongly associated with the degree of disability following stroke both in an outpatient setting and clinical trial. Further work remains to assess sensitivity to change and to improve the inter-observer reliability of the scale.

Background Five randomized controlled trials recently demonstrated efficacy of endovascular treatment in acute ischemic stroke. Telestroke networks can improve stroke care in rural areas but their role in patients undergoing endovascular treatment is unknown. Aim We compared clinical outcomes of endovascular treatment between anterior circulation stroke patients transferred after teleconsultation and those directly admitted to a tertiary stroke center. Methods Data derived from consecutive patients with intracranial large vessel occlusion who underwent endovascular treatment from January 2010 to December 2014 at our tertiary stroke center. We compared baseline characteristics, onset-to-treatment times, symptomatic intracranial hemorrhage, in-hospital mortality, reperfusion (modified Treatment in Cerebral Infarction 2b/3), and favorable functional outcome (modified Rankin scale ≤ 2) at discharge between patients transferred from spoke hospitals and those directly admitted. Results We studied 151 patients who underwent emergent endovascular treatment for anterior circulation stroke: median age 70 years (interquartile range, 62–75); 55% men; median National Institutes of Health Stroke Scale score 15 (12–20). Of these, 48 (31.8%) patients were transferred after teleconsultation and 103 (68.2%) were primarily admitted to our emergency department. Transferred patients were younger (p = 0.020), received more frequently intravenous tissue plasminogen activator (p = 0.008), had prolonged time from stroke onset to endovascular treatment initiation (p Conclusions Telestroke networks may enable delivery of endovascular treatment to selected ischemic stroke patients transferred from remote hospitals that is equitable to patients admitted directly to tertiary hospitals.

Background: Interhospital transfer is an important but resource-intensive pattern of care. The use for stroke patients is highly dependent upon health system structure. We examined the impact of hospital transfers for stroke care in Canada. Methods: We analyzed hospital administrative data within the Canadian Institute for Health Information (CIHI) Database for the 3 fiscal years 2011/12, 2012/13 and 2013/14. Patients with clinical stroke syndrome (ischemic or hemorrhagic) were identified using International Classification of Diseases. Stroke centers were defined by Heart & Stroke Foundation of Canada stroke report. Results: During the 3-year period,397 patients in Canada (excluding Quebec) were admitted to hospital for clinical stroke syndrome. Median age was 75 (interquartile range [IQR] 64–84) years; 50.6 % were male. Less than 5% (n=4030) of patients were transferred. Patients transferred to stroke centers were younger (pConclusion: Younger patients were transferred more frequently to stroke centers; older patients were more likely treated in community hospitals. Sole stroke center care was associated with high discharge rate to home; transfer to a stroke center was associated with high discharge rate to rehabilitation and lower mortality rates.

Background and Purpose— Transient focal neurological episodes occur in cerebral amyloid angiopathy (CAA) and can mimic transient ischemic attack (TIA). Risk factors and outcomes of minor ischemic stroke or TIA might differ in patients with and without cerebral microbleeds (CMBs), including CAA-consistent lobar CMB. Methods— Baseline magnetic resonance imaging (MRI) was analyzed for CMBs and cortical superficial siderosis in 416 patients in the prospective computed tomography and MRI in the CATCH study (Triage of TIA and Minor Cerebrovascular Events to Identify High Risk Patients). Clinical symptoms, baseline characteristics, recurrence, and 90-day modified Rankin Scale were prospectively collected. MRI white-matter hyperintensity was measured using the Fazekas scale. Results— CMBs were detected in 65 (15.6%) and cortical superficial siderosis in 11 patients (2.6%). Lobar CMBs were present in 49 (11.8%). In multivariable logistic regression adjusted for risk factors and age, subcortical Fazekas score was associated with lobar CMB (odds ratio, 2.07; 95% confidence interval, 1.23–3.48; P =0.006). Forty-two patients (10.1%) had lobar-only CMBs with or without cortical superficial siderosis consistent with modified Boston criteria for possible/probable CAA. The possible/probable CAA pattern was not predictive of recurrent TIA (odds ratio, 0.42; 95% confidence interval, 0.05–3.31; P =0.41), stroke (odds ratio, 1.24; 95% confidence interval, 0.26–5.99; P =0.79), or 90-day modified Rankin Scale score ≥2 (odds ratio, 1.38; 95% confidence interval, 0.62–3.07; P =0.42). Conclusions— CMBs in TIA and minor stroke are moderately common but do not predict recurrence or 90-day outcome. CAA-related transient focal neurological episodes and TIA have overlapping clinical symptoms, suggesting that MRI may be needed for differentiation.

Despite declining age-standardized stroke incidence in high-income countries, stroke incidence is rising in low- and middle-income countries.1 Globally, the absolute burden of stroke was high in 2010 with 16.9 million first-ever strokes, 5.9 million stroke-related deaths, and 102 million disability-adjusted life-years lost.1 These numbers are projected to increase. Surveillance provides an understanding of stroke frequency, burden, distribution, and determinants. These data are essential for monitoring trends over time, guiding judicious resource allocation, and for the design, implementation, and evaluation of interventions aimed at stroke prevention, treatment, and rehabilitation.2 Collecting data specifically for research purposes can be costly and time-consuming, limiting the sample size, period of follow-up, and geographical distribution of subjects. Surveillance requires continuous data collection in large geographic areas over years; therefore, attention has been paid to secondary use data. Health services utilization data, or administrative health data, provide a wealth of information for health services researchers and for stroke surveillance. However, the information collected and ascertainment methods are heterogeneous between countries and even between jurisdictions within a country, making the data vulnerable to selection and measurement bias. Comparing international data is also challenging.3 In this review, we discuss the strengths and weaknesses of administrative health data for stroke surveillance. Administrative health data are routinely generated through interactions with healthcare systems. They are collected for payment, monitoring, planning, priority setting, and evaluation of health services provision. Sources include, but are not limited to, hospitalizations, emergency department and ambulatory care visits, and physician billings. Unlike prospective clinical research data collection, administrative health data are accumulated in a distributed manner over a prolonged period of time. As a result, these data capture a large number of individuals and a wide range of demographic information, including race/ethnicities, geographical areas (eg, rural versus urban), and institutions (eg, community versus …

The purpose of this article is to review advances in stroke treatment in the hyperacute period. With recent evolutions of technology in the fields of imaging, thrombectomy devices, and emergency room workflow management, as well as improvement in statistical methods and study design, there have been ground breaking changes in the treatment of acute ischemic stroke. We describe how stroke presents as a clinical syndrome and how imaging as the most important biomarker will help differentiate between stroke subtypes and treatment eligibility. The evolution of hyperacute treatment has led to the current standard of care: intravenous thrombolysis with tissue-type plasminogen activator and endovascular treatment for proximal vessel occlusion in the anterior cerebral circulation. All patients with acute ischemic stroke are in need of hyperacute secondary prevention because the risk of recurrence is highest closest to the index event. The dominant themes of modern stroke care are the use of neurovascular imaging and speed of diagnosis and treatment.

BackgroundDementia prevalence is rising, and it will double in the next 20 years. This study sought to understand the prevalence of dementia in hospitalized patients with ischemic stroke, and its impact on outcomes.MethodsUsing the Canadian Institute of Health Information’s (CIHI) Discharge Abstract Database (DAD), all acute ischemic stroke admissions from April 2003 to March 2015 in Canada (excluding Quebec) were analyzed. Concurrent dementia at the time of admission was assessed based on hospital diagnostic codes. Characteristics and in-hospital outcomes were compared in patients with and without dementia using χ2 and negative binomial, as well as Poisson regression analysis.ResultsDuring the observed period, 313,138 people were admitted to a hospital in Canada for an ischemic stroke. Of those, 21,788 (7.0%) had a concurrent diagnosis of dementia. People with dementia had older median age (84 vs. 76 years; pppppInterpretationApproximately 1 in 13 hospitalized ischemic stroke patients has coded dementia. Patients with ischemic stroke and concurrent dementia have higher mortality, face significantly more dependence after stroke and utilize greater healthcare resources than stroke patients without dementia. Causative conclusions are limited by the administrative data source. Early care planning and coordination could potentially optimize outcomes.

Introduction: The Mobile Stroke Unit (MSU) has brought stroke imaging and alteplase administration to the field, possibly shortening onset to needle time in some situations. However, for patients needing endovascular therapy (EVT) onset to groin puncture times may be lengthened due to additional travel time. For patients with suspected large vessel occlusion (LVO) using the Los Angeles Motor Scale (LAMS) we compare the probability of good outcome for patients taken direct to Comprehensive Stroke Centre (CSC) (mothership) and patients utilizing the MSU. Methods: Using conditional probability models for patients with suspected LVO (LAMS ≥4) the probability of good outcome for the mothership and MSU scenarios were generated. Good outcome was defined using a sliding dichotomy, where for LVO patients it was defined as mRS 0-2 as 90 days, and for non-LVO patients it was defined as mRS 0-1. Data from the HERMES collaboration was used for EVT patients, data from the Emberson meta-analysis (extrapolated to the HERMES population for LVO) was used for alteplase treated patients. Probability of good outcome for intracranial hemorrhage and stroke mimics was considered time invariant. Results: The results are visualized in a small metropolitan area with one CSC and one MSU which is housed at the CSC. In the area immediately surrounding the CSC both the MSU and mothership methods predict equivalent outcomes, however moving further away from the CSC mothership predicts better outcomes due to the additional travel time for the MSU. If the MSU does not lead to time savings when the patient arrives at the CSC this mothership area is expanded. Conclusions: From a patient outcomes perspective in a system where a single MSU is housed at a single CSC there are no area where the MSU shows benefit over the mothership approach. In the area where both models predict equivalent outcomes the individual environment and cost-effectiveness must be taken into context when deciding the best transport strategy.

Introduction: Ischemic stroke with large vessel occlusion (LVO) cannot be definitively diagnosed without imaging. The Mobile Stroke Unit (MSU) has brought this capability (along with alteplase administration) to the field. In areas with widespread urban sprawl, having MSUs stationed in the community may improve patient outcomes. However, this is also dependent on how accurately dispatch can assess suspected stroke with LVO over the phone. We compare the probability of good outcome for patients taken direct to Comprehensive Stroke Centre (CSC) (mothership) vs utilizing a MSU at varying levels of dispatcher accuracy in identifying ischemic stroke with suspected LVO. Methods: Conditional probability models for patients with suspected LVO for mothership and MSU scenarios were generated. The positive predictive value (PPV) of dispatcher screening was varied from 25% to 75%. A sliding dichotomy was used to define good outcome, mRS 0-2 at 90 days was used for LVO patients and mRS 0-1 was used for non-LVO patients. Data from the HERMES collaboration was used for EVT patients, data from the Emberson meta-analysis (extrapolated to the HERMES population for LVO) was used for alteplase treated patients. Probability of good outcome for intracranial hemorrhage and stroke mimics was considered time invariant. Results: The results are visualized using temporal-spatial diagrams with one CSC and four MSUs stationed around the CSC with each MSU covering one quarter of the city. If dispatcher accuracy is poor the area where MSU predicts the best outcome is large as more non-LVO strokes, which benefit from fast alteplase, will be picked up. However, as dispatcher accuracy in identifying LVO increases the mothership areas also increase as the MSU would impose delays in these patients receiving EVT. Conclusions: The ability to accurately dispatch the MSU to patients with suspected LVO impacts transport decision making. This should be considered when designing a stroke system containing a MSU.

Introduction: The Mobile Stroke Unit (MSU) has brought stroke imaging and alteplase administration to the field, shortening onset to needle time in some situations. In areas with widespread urban sprawl, having MSUs stationed in the community may improve patient outcomes. For patients with suspected large vessel occlusion (LVO) using the Los Angeles Motor Scale (LAMS) we compare the probability of good outcome for patients taken direct to Comprehensive Stroke Centre (CSC) (mothership) vs. utilizing multiple MSUs. Methods: Using conditional probability models for patients with suspected stroke with LVO (LAMS ≥4) the probability of good outcome for the mothership and MSU scenarios were generated. A sliding dichotomy was used to define good outcome, mRS 0-2 at 90 days was used for LVO patients and mRS 0-1 was used for non-LVO patients. Data from the HERMES collaboration was used for EVT patients, data from the Emberson meta-analysis (extrapolated to the HERMES population for LVO) was used for alteplase treated patients. Probability of good outcome for intracranial hemorrhage and stroke mimics was considered time invariant. Results: The results are visualized using temporal-spatial diagrams with one CSC and four MSUs stationed at various distances from the CSC with each MSU covering one quarter of the city. The addition of four MSUs in a small geographic area (60 min radius from CSC) does not predict improved patient outcomes. However, as the size of the geographic area increases the relevance of the MSU becomes apparent in the areas closest to the MSU. Conclusions: From a patient outcomes perspective multiple MSUs may be necessary to have the possibility of superior patient outcomes than the mothership transport method if they are situated far away from the CSC. This in addition to the individual environment and cost-effectiveness should be taken into context when deciding the best place to house future MSUs.

Although major advances for the treatment of acute ischemic stroke have recently been made through clinical trials, there is still much work to be done and as is common, more and new questions have arisen that will influence how future trials are designed. This chapter will give an overview on the implications of the human ischemia-reperfusion model, discuss advanced neuroimaging as the now established biomarker for stroke and trial eligibility, and review why stroke systems of care have to be considered for future trials.

Stroke is a leading cause of adult disability and the fourth leading cause of death in Canada. Most strokes are ischemic and functional outcome is highly time-dependent, making fast diagnosis and treatment initiation crucial. This poses a challenge in vast geographical areas where stroke neurology expertise is only available in urban centres. In this article we review the rationale for telestroke networks and their current implementation in Canada. Telestroke networks enable stroke-specific procedures to be performed by less experienced physicians under the guidance of stroke neurology experts. We also present evidence that the safety and effectiveness of intravenous alteplase in community hospitals in a telestroke network seems to be comparable with that achieved in dedicated stroke centres. It is thus a viable option to guarantee an aging population access to stroke care across large geographic regions with faster treatment and access to more advanced treatment options by means of transfer to a comprehensive centre if necessary. Although telestroke networks have an upfront implementation cost, they can lead to reduced direct and indirect costs for the health care system by reducing days spent in the hospital as well as disability with the need for long-term care. Telestroke networks can also be used for identification and enrollment of patients into emergency stroke trials and thus provide a more representative sample of the population and increase recruitment. Standardization of regional telestroke networks could lead to collaborations with larger data acquisitions for research purposes and quality control in the future.

Cognitive function is an important component of aging and predicts quality of life, functional independence, and risk of institutionalization. Advances in our understanding of the role of cardiovascular risks have shown them to be closely associated with cognitive impairment and dementia. Because many cardiovascular risks are modifiable, it may be possible to maintain brain health and to prevent dementia in later life. The purpose of this American Heart Association (AHA)/American Stroke Association presidential advisory is to provide an initial definition of optimal brain health in adults and guidance on how to maintain brain health. We identify metrics to define optimal brain health in adults based on inclusion of factors that could be measured, monitored, and modified. From these practical considerations, we identified 7 metrics to define optimal brain health in adults that originated from AHA’s Life’s Simple 7: 4 ideal health behaviors (nonsmoking, physical activity at goal levels, healthy diet consistent with current guideline levels, and body mass index 2 ) and 3 ideal health factors (untreated blood pressure

See related article, p 2632 Preclinical stroke research faces a substantial transition. Past classical rodent stroke models and study designs revealed numerous potential targets for novel stroke therapies; yet, subsequent clinical stroke trials failed to confirm promising preclinical findings. Pharmacological and mechanical recanalization therapies, representing the only strategies that have substantially improved acute ischemic stroke outcomes, were largely developed omitting conventional preclinical methods.1–3 In this issue of Stroke , a National Institute of Neurological Disorders and Stroke consensus group comprising leading academic, industry, and Food and Drug Administration (FDA) experts working at the forefront of stroke research has recently published guidelines for improved translational studies.4 Distinguishing between explorative (basic) versus confirmative (translational) studies has been suggested. Exploratory research uses simpler rodent models but a broad spectrum of basic science methods to gain comprehensive information on a putative treatment target. Subsequent confirmative research adopts study designs similar to those used in clinical stroke trials and puts more emphasis on predictive stroke models and study end points using larger and adequate sample sizes for necessary statistical power.5 The group’s recommendations reflect latest developments and concepts in the field, aiming to ultimately enhance the predictive value of …