Effect of Endovascular Thrombectomy for Acute Ischemic Stroke on Cognitive Outcomes: A Secondary Analysis of the ESCAPE Trial.

BACKGROUND AND OBJECTIVES: The effect of endovascular therapy (EVT) for large vessel occlusion stroke on cognitive outcomes is not well understood. We evaluated the effect of EVT on cognitive function in the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial. METHODS: Patient data from the ESCAPE randomized trial were analyzed. Cognitive assessments completed at 90 days after stroke were the Montreal Cognitive Assessment (MoCA), the Sunnybrook Neglect Assessment Procedure (SNAP), the Boston Naming Test (BNT), Trail-making test A (Trails A), and Trail-making test B (Trails B). We used logistic regression to evaluate the association between EVT and favorable cognitive outcome on the 5 separate tests, adjusting for demographic and clinical factors. We used generalized estimating equations and ordinal regression to determine the odds of favorable outcome with EVT on global cognition incorporating the 5 tests. We added final infarct volume (FIV) to the models to assess the relationship of FIV with cognitive outcome. RESULTS: The ESCAPE trial included 315 patients, 165 randomized to EVT and 150 randomized to control. There was higher odds of favorable outcome with EVT for MoCA (adjusted odds ratio [aOR] 2.32, 95% CI 1.30-4.16), SNAP (aOR 3.85, 95% CI 2.00-7.45), BNT (aOR 2.33, 95% CI 1.30-4.17), trails A (aOR 3.50, 95% CI 1.93-6.36), and trails B (aOR 2.56, 95% CI 1.46-4.48). There was higher odds of favorable outcome with EVT on global binary (aOR 2.57, 95% CI 1.67-3.94) and ordinal analyses (aOR 2.83, 95% CI 1.68-4.76) of cognitive function. After adding FIV to the models, both FIV and EVT were significantly associated with cognitive outcome. There was a significant correlation between global cognitive performance and mRS at day 90 (r = -0.78, p < 0.001), with the largest reductions in favorable cognitive outcome from mRS score 4 to 5 and from mRS 2 to 3. DISCUSSION: In this secondary analysis of the ESCAPE trial, EVT was associated with favorable outcome on 5 separate cognitive tests and in global analyses of cognitive benefit. These results provide novel evidence for the effect of EVT on cognition and support the global benefit of treatment with EVT. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with acute ischemic stroke due to intracranial internal carotid artery (ICA) or M1 segment MCA occlusion, including tandem extracranial ICA occlusions, EVT compared with best medical therapy increased odds of favorable cognitive outcome.

Infarcts in a New Territory: Insights From the ESCAPE-NA1 Trial.

BACKGROUND: Infarct in a new territory (INT) is a known complication of endovascular stroke therapy. We assessed the incidence of INT, outcomes after INT, and the impact of concurrent treatments with intravenous thrombolysis and nerinetide. METHODS: Data are from ESCAPE-NA1 trial (Safety and Efficacy of Nerinetide [NA-1] in Subjects Undergoing Endovascular Thrombectomy for Stroke), a multicenter, international randomized study that assessed the efficacy of intravenous nerinetide in subjects with acute ischemic stroke who underwent endovascular thrombectomy within 12 hours from onset. Concurrent treatment and outcomes were collected as part of the trial protocol. INTs were identified on core lab imaging review of follow-up brain imaging and defined by the presence of infarct in a new vascular territory, outside the baseline target occlusion(s) on follow-up brain imaging (computed tomography or magnetic resonance imaging). INTs were classified by maximum diameter (<2, 2-20, and >20 mm), number, and location. The association between INT and clinical outcomes (modified Rankin Scale and death) was assessed using standard descriptive techniques and adjusted estimates of effect were derived from Poisson regression models. RESULTS: Among 1092 patients, 103 had INT (9.3%, median age 69.5 years, 49.5% females). There were no differences in baseline characteristics between those with versus without INT. Most INTs (91/103, 88.3%) were not associated with visible occlusions on angiography and 39 out of 103 (37.8%) were >20 mm in maximal diameter. The most common INT territory was the anterior cerebral artery (27.8%). Almost half of the INTs were multiple (46 subjects, 43.5%, range, 2-12). INT was associated with poorer outcomes as compared to no INT on the primary outcome of modified Rankin Scale score of 0 to 2 at 90 days (adjusted risk ratio, 0.71 [95% CI, 0.57-0.89]). Infarct volume in those with INT was greater by a median of 21 cc compared with those without, and there was a greater risk of death as compared to patients with no INT (adjusted risk ratio, 2.15 [95% CI, 1.48-3.13]). CONCLUSIONS: Infarcts in a new territory are common in individuals undergoing endovascular thrombectomy for acute ischemic stroke and are associated with poorer outcomes. Optimal therapeutic approaches, including technical strategies, to reduce INT represent a new target for incremental quality improvement of endovascular thrombectomy. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02930018.

Importance of accounting for loss to follow-up when comparing mortality between immigrants and long-term residents: a population-based retrospective cohort.

OBJECTIVES: To evaluate the association between immigration status and all-cause mortality in different disease cohorts, and the impact of loss to follow-up on the observed associations. DESIGN: Population-based retrospective cohort study using linked administrative health data in Ontario, Canada. SETTING: We followed adults with a first-ever diagnosis of ischaemic stroke, cancer or schizophrenia between 2002 and 2013 from index event to death, loss to follow-up, or end of follow-up in 2018. PRIMARY AND SECONDARY OUTCOME MEASURES: Our outcomes of interest were all-cause mortality and loss to follow-up. For each disease cohort, we calculated adjusted HRs of death in immigrants compared with long-term residents, adjusting for demographic characteristics and comorbidities, with and without censoring for those who were lost to follow-up. We calculated the ratio of two the HRs and the respective CL using bootstrapping methods. RESULTS: Immigrants were more likely to be lost to follow-up than long-term residents in all disease cohorts. Not accounting for this loss to follow-up overestimated the magnitude of the association between immigration status and mortality in those with ischaemic stroke (HR of death before vs after accounting for censoring: 0.78 vs 0.83, ratio=0.95; 95% CL 0.93 to 0.97), cancer (0.74 vs 0.78, ratio=0.96; 0.95 to 0.96), and schizophrenia (0.54 vs 0.56, ratio=0.97; 0.96 to 0.98). CONCLUSIONS: Immigrants to Canada have a survival advantage that varies by the disease studied. The magnitude of this advantage is modestly overestimated by not accounting for the higher loss to follow-up in immigrants.

Incidence of Stroke in Immigrants to Canada: A Province-wide Retrospective Analysis.

OBJECTIVE: To evaluate the association between immigration status and stroke incidence. METHODS: We conducted a retrospective cohort study of 8 million adults (15% immigrants) residing in Ontario, Canada on January 1, 2003, with no history of prior stroke or transient ischemic attack (TIA). Subjects were followed until March 31, 2018 to identify incident stroke or TIA, defined as hospitalization or emergency room visit. We calculated adjusted hazard ratios (HR) of stroke or TIA in immigrants compared to long-term residents using cause-specific hazard models, adjusting for demographics and comorbidities. We evaluated whether the association varied by age, stroke type or country of origin of immigrants. RESULTS: During 109 million person-years follow-up, we observed 235,336 incident stroke or TIA events. Compared to long-term residents, immigrants had a lower rate of stroke or TIA (10.9 vs. 23.4 per 10,000 person-years, HR 0.67; 0.66-0.68). This was true across all age groups and stroke types, with a HR in immigrants vs. long-term residents for ischemic stroke of 0.71 (0.69-0.72), intracerebral hemorrhage 0.89 (0.85-0.93), subarachnoid hemorrhage 0.85 (0.81-0.91), and TIA 0.53 (0.51-0.54). The magnitude of the reduction in stroke risk associated with immigration status was less pronounced in immigrants from the Caribbean (HR 0.95; 0.91-1.00), Latin America (HR 0.85;0.82-0.91) and Africa (HR 0.80; 0.74-0.85) than in those from other world regions. CONCLUSIONS: Immigrants have a lower rate of stroke or TIA than long-term residents with variation by age, stroke type and country of origin. This knowledge may be useful for developing targeted primary stroke prevention strategies.

Immigration Status, Ethnicity, and Long-term Outcomes following Ischemic Stroke.

OBJECTIVE: To assess the association between immigration status and ethnicity and the outcomes of mortality and vascular event recurrence following ischemic stroke in Ontario, Canada. METHODS: We conducted a retrospective cohort study using linked administrative and clinical registry-based data from 2002 to 2018 and compared hazards of all-cause mortality and vascular event recurrence in immigrants and long-term residents using inverse probability of treatment weighting accounting for age, sex, income and comorbidities. We stratified analyses by age (≤ 75 and > 75 years) and used interaction terms to evaluate if the association between immigration status and outcomes varied with age or ethnicity. RESULTS: We followed 31,918 adult patients, of whom 2740 (8.6%) were immigrants, for a median follow-up of 5 years. Immigrants had a lower mortality than long-term residents (46.1% vs. 64.5%) which was attenuated after adjustment (hazard ratio 0.94; 95% confidence interval 0.88-1.00), but persisted in those aged under 75 years (HR 0.82; 0.74-0.91). Compared to their respective ethnic long-term resident counterparts, the adjusted hazard of death was higher in South Asian immigrants, similar in Chinese immigrants, and lower in other immigrants (P value for interaction = 0.003). The adjusted hazard of vascular event recurrence (HR 1.01; 0.92-1.11) was similar in immigrants and long-term residents, and this observation persisted across all age and ethnic groups. CONCLUSIONS: Long-term mortality following ischemic stroke is lower in immigrants and long-term residents, but is similar after adjustment of baseline characteristics, and it is modified by age at the time of stroke and by ethnicity.

Stroke Incidence by Sex Across the Lifespan.

BACKGROUND AND PURPOSE: We evaluated the influence of age on the association between sex and the incidence of stroke or transient ischemic attack (TIA) using a population-based cohort from Ontario, Canada. METHODS: We followed a cohort of adults (≥18 years) without prior stroke from January 1, 2003 (cohort start date) to March 31, 2018, to identify incident events. We calculated hazard ratios (HRs), in women compared to men, of incident stroke or TIA, adjusted for demographics and comorbidities, overall and stratified by stroke type. We calculated piecewise adjusted HRs for each decade of age to evaluate the effect of age on sex differences in stroke incidence. RESULTS: We followed 9.2 million adults for a median of 15 years and observed 280,197 incident stroke or TIA events. Compared with men, women had an overall lower adjusted hazard of stroke or TIA (HR, 0.82 [95% CI, 0.82-0.83]), with similar findings across all stroke types except for subarachnoid hemorrhage (HR, 1.29 [95% CI, 1.24-1.33]). We found a U-shaped association between age and sex differences in the incidence of stroke or TIA: compared with men, the hazard of stroke was higher in women among those aged ≤30 years (HR, 1.26 [95% CI, 1.10-1.45]), lower among those between ages 40 and 80 years (eg, age 50-59, HR, 0.69 [95% CI, 0.68-0.70]), and similar among those aged ≥80 years (HR, 0.99 [95% CI, 0.98-1.01]). CONCLUSIONS: Overall, women have a lower hazard of stroke than men, but this association varies by age and across stroke types. Recognition of age-sex variations in stroke incidence can help guide prevention efforts to reduce stroke incidence in both men and women.

Decreased Stroke Presentation Rates at a Comprehensive Stroke Center during COVID-19.

We reviewed stroke care delivery during the COVID-19 pandemic at our stroke center and provincial telestroke system. We counted referrals to our prevention clinic, code strokes, thrombolysis, endovascular thrombectomies, and activations of a provincial telestroke system from February to April of 2017-2020. In April 2020, there was 28% reduction in prevention clinic referrals, 32% reduction in code strokes, and 26% reduction in telestroke activations compared to prior years. Thrombolysis and endovascular thrombectomy rates remained constant. Fewer patients received stroke services across the spectrum from prevention, acute care to telestroke care in Ontario, Canada, during the COVID-19 pandemic.

Early Recanalization With Alteplase in Stroke Because of Large Vessel Occlusion in the ESCAPE Trial.

BACKGROUND AND PURPOSE: Quantitating the effect of intravenous alteplase on the technical outcome of early recanalization of large vessel occlusions aids understanding. We report the prevalence of early recanalization in patients with stroke because of large vessel occlusion treated with and without intravenous alteplase and endovascular thrombectomy, and its association with clinical outcome. METHODS: Patients with acute ischemic stroke with large vessel occlusion from the ESCAPE trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times Trial) were included in this post hoc analysis. Outcomes of interest were the prevalence of early recanalization (1) and good outcome (2), defined as modified Rankin Scale score of 0 to 2 at 90 days. RESULTS: Among 147 patients who did not receive endovascular thrombectomy, early recanalization occurred in 4/30 (13.3%) patients without and 48/117 (41.0%) patients with intravenous alteplase (adjusted risk ratios, 3.2 [95% CI, 1.2-8.1]). Good outcome was achieved by 34/116 (29.3%) of patients who received intravenous alteplase versus 10/29 (34.5%) who did not receive alteplase (adjusted risk ratios, 1.0 [95% CI, 0.6-1.5) and by 20/52 (38.5%) patients with versus 24/93 (25.8%) without early recanalization (adjusted risk ratios, 1.9 [95% CI, 1.2-2.9]). CONCLUSIONS: Early recanalization was confirmed as a strong predictor of good outcome in patients who did not undergo endovascular thrombectomy and was improved with intravenous alteplase, yet a majority of patients (59.0%) did not achieve early reperfusion. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01778335.

Natural History of Hemodynamics in Vertebrobasilar Disease: Temporal Changes in the VERiTAS Study Cohort.

BACKGROUND AND PURPOSE: The role of regional hypoperfusion as a contributor to stroke risk in atherosclerotic vertebrobasilar disease has recently been confirmed by the observational VERiTAS (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke) Study. We examined the stability of hemodynamic status over time and its relationship to stroke risk in patients from this prospective cohort. METHODS: VERiTAS enrolled patients with recently symptomatic ≥50% atherosclerotic stenosis/occlusion of vertebral and/or basilar arteries. Large vessel flow in the vertebrobasilar territory was assessed using quantitative magnetic resonance angiography, and patients were designated as low or normal flow based on distal territory regional flow, incorporating collateral capacity. Patients underwent standard medical management and follow-up for primary outcome event of vertebrobasilar territory stroke. Quantitative magnetic resonance angiography imaging was repeated at 6, 12, and 24 months. Flow status over time was examined relative to baseline and relative to subsequent stroke risk using a cause-specific proportional hazard model, with flow status treated as a time-varying covariate. Mean blood pressure was examined to assess for association with changes in flow status. RESULTS: Over 19±8 months of follow-up, 132 follow-up quantitative magnetic resonance angiography studies were performed in 58 of the 72 enrolled patients. Of the 13 patients with serial imaging who had low flow at baseline, 7 (54%) had improvement to normal flow at the last follow-up. Of the 45 patients who had normal flow at baseline, 3 (7%) converted to low flow at the last follow-up. The mean blood pressure did not differ in patients with or without changes in flow status. The time-varying flow status remained a strong predictor of subsequent stroke (hazard ratio, 10.3 [95% CI, 2.2-48.7]). CONCLUSIONS: There is potential both for improvement and worsening of hemodynamics in patients with atherosclerotic vertebrobasilar disease. Flow status, both at baseline and over time, is a risk factor for subsequent stroke, thus serving as an important prognostic marker. Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT00590980.

Association Between Immigration Status and Acute Stroke Care: A Retrospective Study.

Background and Purpose- Immigrants to high-income countries have a lower incidence of stroke compared with long-term residents; however, little is known about the care and outcomes of stroke in immigrants. Methods- We used linked clinical and administrative data to conduct a retrospective cohort study of adults seen in the emergency department or hospitalized with ischemic stroke or transient ischemic attack between July 1, 2003, and April 1, 2013, and included in the provincial stroke registry. We ascertained immigration status using immigration records and compared processes of stroke care delivery between immigrants (defined as those immigrating after 1985) and long-term residents. In the subgroup with ischemic stroke, we calculated inverse probability treatment weight (IPTW)-adjusted risk ratios for disability on discharge (modified Rankin Scale score of 3 to 5), accounting for demographic characteristics and comorbid conditions to compare outcomes between immigrants and long-term residents. Results- We included 34 987 patients with ischemic stroke or transient ischemic attack, of whom 2649 (7.6%) were immigrants. Immigrants were younger than long-term residents at the time of stroke/transient ischemic attack (median age 67 years versus 76 years; P<0.001). In the subgroup with ischemic stroke, there were no differences in stroke care delivery, except that a higher proportion of immigrants received thrombolysis than long-term residents (21.2% versus 15.5%; P<0.001). Immigrants with ischemic stroke had a higher adjusted risk of being disabled on discharge (adjusted risk ratio, 1.18; 95% CI, 1.13-1.22) compared to long-term residents. Conclusions- Stroke care is similar in Canadian immigrants and long-term residents. Future research is needed to confirm the observed association between immigration status and disability after stroke and to identify factors underlying the association.

Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): a multicentre, double-blind, randomised controlled trial.

BACKGROUND: Nerinetide, an eicosapeptide that interferes with post-synaptic density protein 95, is a neuroprotectant that is effective in preclinical stroke models of ischaemia-reperfusion. In this trial, we assessed the efficacy and safety of nerinetide in human ischaemia-reperfusion that occurs with rapid endovascular thrombectomy in patients who had an acute ischaemic stroke. METHODS: For this multicentre, double-blind, randomised, placebo-controlled study done in 48 acute care hospitals in eight countries, we enrolled patients with acute ischaemic stroke due to large vessel occlusion within a 12 h treatment window. Eligible patients were aged 18 years or older with a disabling ischaemic stroke at the time of randomisation, had been functioning independently in the community before the stroke, had an Alberta Stroke Program Early CT Score (ASPECTS) greater than 4, and vascular imaging showing moderate-to-good collateral filling, as determined by multiphase CT angiography. Patients were randomly assigned (1:1) to receive intravenous nerinetide in a single dose of 2·6 mg/kg, up to a maximum dose of 270 mg, on the basis of estimated or actual weight (if known) or saline placebo by use of a real-time, dynamic, internet-based, stratified randomised minimisation procedure. Patients were stratified by intravenous alteplase treatment and declared endovascular device choice. All trial personnel and patients were masked to sequence and treatment allocation. All patients underwent endovascular thrombectomy and received alteplase in usual care when indicated. The primary outcome was a favourable functional outcome 90 days after randomisation, defined as a modified Rankin Scale (mRS) score of 0-2. Secondary outcomes were measures of neurological disability, functional independence in activities of daily living, excellent functional outcome (mRS 0-1), and mortality. The analysis was done in the intention-to-treat population and adjusted for age, sex, baseline National Institutes of Health Stroke Scale score, ASPECTS, occlusion location, site, alteplase use, and declared first device. The safety population included all patients who received any amount of study drug. This trial is registered with ClinicalTrials.gov, NCT02930018. FINDINGS: Between March 1, 2017, and Aug 12, 2019, 1105 patients were randomly assigned to receive nerinetide (n=549) or placebo (n=556). 337 (61·4%) of 549 patients with nerinetide and 329 (59·2%) of 556 with placebo achieved an mRS score of 0-2 at 90 days (adjusted risk ratio 1·04, 95% CI 0·96-1·14; p=0·35). Secondary outcomes were similar between groups. We observed evidence of treatment effect modification resulting in inhibition of treatment effect in patients receiving alteplase. Serious adverse events occurred equally between groups. INTERPRETATION: Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo. FUNDING: Canadian Institutes for Health Research, Alberta Innovates, and NoNO.

Geographic Access to Stroke Care Services in Rural Communities in Ontario, Canada.

BACKGROUND: Optimal stroke care requires access to resources such as neuroimaging, acute revascularization, rehabilitation, and stroke prevention services, which may not be available in rural areas. We aimed to determine geographic access to stroke care for residents of rural communities in the province of Ontario, Canada. METHODS: We used the Ontario Road Network File database linked with the 2016 Ontario Acute Stroke Care Resource Inventory to estimate the proportion of people in rural communities, defined as those with a population size <10,000, who were within 30, 60, and 240 minutes of travel time by car from stroke care services, including brain imaging, thrombolysis treatment centers, stroke units, stroke prevention clinics, inpatient rehabilitation facilities, and endovascular treatment centers. RESULTS: Of the 1,496,262 people residing in rural communities, the majority resided within 60 minutes of driving time to a center with computed tomography (85%), thrombolysis (81%), a stroke unit (68%), a stroke prevention clinic (74%), or inpatient rehabilitation (77.0%), but a much lower proportion (32%) were within 60 minutes of driving time to a center capable of providing endovascular thrombectomy (EVT). CONCLUSIONS: Most rural Ontario residents have appropriate geographic access to stroke services, with the exception of EVT. This information may be useful for jurisdictions seeking to optimize the regional organization of stroke care services.

A Feasibility Study Involving Recruitment and Screening for Aphasia in Acute Stroke: Emerging Viability of the English Adaptation of the Language Screening Test (LASTen).

OBJECTIVES: We describe recruitment feasibility for language screening in acute stroke using the English adaptation the Language Screening Test (LASTen), originally developed in French. We also elucidate preliminary measurement properties of LASTen in patients with and without aphasia. DESIGN: Prospective eligibility tracking, recruitment, and screening for aphasia using the 2 parallel forms, LASTen-A and LASTen-B. SETTING: The Neurovascular Unit and the Transient Ischemic Attack and Minor Stroke Unit of a tertiary care hospital. PARTICIPANTS: Stroke patients (N=12) with hyperacute to subacute stroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Numbers of eligible patients and recruitment viability, individual performance indicators for both LASTen versions (15 points each) in 12 patients grouped by aphasia status, and reliability of the 2 parallel forms. RESULTS: There were 25 eligible stroke patients over 1 month. All 12 recruited patients consented to testing. The patients ranged in age from 29 to 85 years, and 5 were women. Three patients had intracerebral hemorrhage, and 6 had aphasia (mild to severe). The median LASTen scores in patients with and without aphasia were 10 (interquartile range, 8) and 15 (interquartile range, 0), respectively. Five patients had discrepant scores across versions involving a 1-point difference. One patient with aphasia had a 5-point difference, demonstrating improvement on the second version. The Pearson correlation coefficient was 0.95 for parallel form reliability. CONCLUSIONS: Our study confirmed that LASTen appears to function as designed. There was score heterogeneity for patients with aphasia and desired ceiling effects for those without aphasia, alongside excellent parallel form reliability. The findings provide the impetus for a large-scale diagnostic accuracy trial in acute stroke patients.

Automated CT Perfusion Imaging Versus Non-contrast CT for Ischemic Core Assessment in Large Vessel Occlusion.

PURPOSE: There is increasing use of automated computed tomography perfusion (CTP) to aid thrombectomy decision in emergent large vessel occlusion. It is important to understand the performance of these software packages in predicting ischemic core and tissue-at-risk in the real-world setting. The aim of this study was to evaluate whether ischemic core on non-contrast CT (NCCT) and automated CTP correspond and predict infarct extent after thrombectomy for ischemic stroke. METHODS: Consecutive patients with acute anterior circulation large vessel occlusion undergoing successful thrombectomy (TICI 2b/3) were studied. All patients had baseline CT, CTP with RAPID post-processing software (RAPID-CTP), and post-thrombectomy 24 h CT. Ischemic cores were assessed by two blinded raters independently using the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) on each modality. The interrater agreement for ASPECTS, and correlation between baseline CT-ASPECTS, RAPID-CTP-ASPECTS, and 24h CT-ASPECTS were calculated. RESULTS: A total of 86 patients with a mean age of 70.3 years (SD 16.5) were studied. The median baseline CT-ASPECTS was 9.5 (interquartile range, IQR 8-10), median RAPID-CTP-ASPECTS was 9 (IQR 8-10), and mean RAPID-CTP-ischemic core volume was 14.4 ml (SD 27.9 ml). The mean mismatch volume (difference of Tmax > 6s and cerebral blood flow (CBF) < 30%) was 128.6 ml (SD 126.0 ml). There was substantial correlation between baseline and 24h CT-ASPECTS (rs: 0.62; p < 0.001), but poor correlation between RAPID-CTP-ASPECTS and RAPID-CTP ischemic core volume with 24h NCCT-ASPECTS (rs: 0.21; p = 0.06 and -0.16; p = 0.15 respectively). The positive predictive value of any established infarct for baseline CT-ASPECTS was 81%, while that of RAPID-CTP-ASPECTS was 64%. CONCLUSION: In this series of successfully revascularized patients, ischemic core as estimated by RAPID-CTP-ASPECTS did not correlate with the baseline CT and tended to depict a larger infarct core than the infarct extent as assessed by 24h CT-ASPECTS.

Infarct Patterns in Patients with Atherosclerotic Vertebrobasilar Disease in Relation to Hemodynamics.

INTRODUCTION: Distal territory blood flow is independently associated with subsequent strokes in symptomatic vertebrobasilar atherosclerotic disease. We aimed to assess infarct patterns in relation to hemodynamic status in the prospective Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS) study. METHODS: Distal territory blood flow was measured using quantitative magnetic resonance angiography (MRA) in 72 patients with symptomatic atherosclerotic vertebrobasilar disease, and then dichotomized into normal (n = 54) and low (n = 18) flow. Patients were followed longitudinally on standard medical management. Two observers blinded to flow status independently reviewed the imaging performed at the time of subsequent strokes, in order to adjudicate the likely mechanism based on infarct patterns. The frequency of stroke mechanisms was qualitatively compared based on flow status. RESULTS: During a median follow-up period of 23 months, 10/72 patients had a subsequent stroke; 5 of these had low distal flow. Infarct patterns were adjudicated to be consistent with hemodynamic (n = 2), embolic (n = 4), and junctional plaque/perforator (n = 4) infarcts. Hemodynamic infarcts were seen in 40% (2/5) low-flow patients, in comparison to 0% (0/5) normal-flow patients. CONCLUSION: In contrast to normal-flow patients, those with low distal flow seem to be uniquely susceptible to hemodynamic infarctions, although other patterns of infarction can also be seen in these hemodynamically impaired patients.

Rural-Urban Differences in Stroke Risk Factors, Incidence, and Mortality in People With and Without Prior Stroke.

Background Rural residence is associated with stroke incidence and mortality, but little is known about potential rural/urban differences in ambulatory stroke care. Methods and Results We used the CANHEART (Cardiovascular Health in Ambulatory Care Research Team) cohort, created from linked administrative databases from the province of Ontario, Canada, and divided into primary (N=6 207 032) and secondary (N=75 823) prevention cohorts based on the absence or presence of prior stroke. We defined rural communities as those with a population size of ≤10 000 and within each of the primary and secondary prevention cohorts, compared cardiovascular risk factors and care between rural and urban areas. We then calculated sex-/age-standardized rates of stroke incidence and mortality per 1000 person-years between January 1, 2008 and December 31, 2012 and used cause-specific hazard models to compare outcomes in rural versus urban areas adjusting for age, sex, income, ethnicity, smoking, physical activity and comorbid conditions, and accounting for the competing risk of death in the model for the occurrence of stroke incidence. In the primary prevention cohort, rural residents were less likely than urban ones to be screened for diabetes mellitus (70.9% versus 81.3%) and hyperlipidemia (66.2% versus 78.4%) and less likely to achieve diabetes mellitus control (hemoglobin A1c ≤7% in 51.3% versus 54.3%; P<0.001 for all comparisons). In the secondary prevention cohort, the prevalence and treatment of risk factors were similar in rural and urban residents. After adjustment for sociodemographic and comorbid conditions, rural residence was associated with higher rates of stroke and all-cause mortality in both the primary prevention (adjusted hazard ratio [aHR] for stroke, 1.06; 95% CI, 1.04-1.09; aHR for mortality, 1.09; 95% CI, 1.08-1.10) and the secondary prevention cohort (aHR for stroke, 1.11; 95% CI, 1.02-1.19; aHR for mortality, 1.07; 95% CI, 1.03-1.11). Conclusions In this population-based study of over 6 million people with universal access to physician and hospital services, risk factors were more prevalent but less likely to be controlled in rural than in urban residents without prior stroke, whereas in those with prior stroke, risk factor prevalence and treatment were similar. Rural residence was associated with the rate of stroke and death even after adjustment for risk factors. Future efforts should focus not only on control of known vascular risk factors but also on addressing other determinants of health in rural communities.

Postpartum Period Is a Risk Factor for Cerebral Venous Thrombosis.

Background and Purpose- Pregnancy and the postpartum period are generally considered to be risk factors for cerebral venous thrombosis (CVT), but no controlled studies have quantified the risk. Methods- Case-control study using data of consecutive adult patients with CVT from 5 academic hospitals and controls from the Dutch MEGA study (Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis). Men, women over the age of 50, women using oral contraceptives or with a recent abortion or miscarriage were excluded. We adjusted for age and history of cancer, and stratified for pregnancy versus postpartum, and 0 to 6 versus 7 to 12 weeks postpartum. Results- In total 163/813 cases and 1230/6296 controls were included. Cases were younger (median 38 versus 41 years) and more often had a history of cancer (14% versus 4%) than controls. In total 41/163 (25%) cases and 82/1230 (7%) controls were pregnant or postpartum (adjusted odds ratio, 3.8; 95% CI, 2.4-6.0). The association was fully attributable to an increased risk of CVT during the postpartum period (adjusted odds ratio, 10.6; 95% CI, 5.6-20.0). We found no association between pregnancy and CVT (adjusted odds ratio, 1.2; 95% CI, 0.6-2.3). The risk was highest during the first 6 weeks postpartum (adjusted odds ratio, 18.7; 95% CI, 8.3-41.9). Conclusions- Women who have recently delivered are at increased risk of developing CVT, while there does not seem to be an increased risk of CVT during pregnancy.

Hypoperfusion Symptoms Poorly Predict Hemodynamic Compromise and Stroke Risk in Vertebrobasilar Disease.

Background and Purpose- Cerebral hypoperfusion symptoms (defined as symptoms related to change in position, effort or exertion, or recent change in antihypertensive medication) have been used in stroke studies as a surrogate for detecting hemodynamic compromise. However, the validity of these symptoms in identifying flow compromise in patients has not been well established. We examined whether hypoperfusion symptoms correlated with quantitative measurements of flow compromise in the prospective, observational VERiTAS study (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke). Methods- VERiTAS enrolled patients with recent vertebrobasilar transient ischemic attack or stroke and ≥50% atherosclerotic stenosis or occlusion in vertebral or basilar arteries. Hemodynamic status using vertebrobasilar large vessel flow was measured using quantitative magnetic resonance angiography, and patients were designated as low, borderline, or normal flow based on distal territory regional flow, incorporating collateral capacity. The presence of qualifying event hypoperfusion symptoms was assessed relative to the quantitatively determined flow status (normal versus borderline/low) and also examined as a predictor of subsequent stroke risk. Results- Of the 72 enrolled subjects, 66 had data on hypoperfusion symptoms available. On initial quantitative magnetic resonance angiography designation, 43 subjects were designated as normal flow versus 23 subjects designated as low flow (n=16) or borderline flow (n=7). Of these, 5 (11.6%) normal flow and 3 (13.0%) low/borderline flow subjects reported at least one qualifying event hypoperfusion symptom ( P=0.99, Fisher exact test). Hypoperfusion symptoms had a positive predictive value of 37.5% and negative predictive value of 65.5% for low/borderline flow status. Compared with flow status, which strongly predicted subsequent stroke risk, hypoperfusion symptoms were not associated with stroke outcome ( P=0.87, log-rank test). Conclusions- These results suggest that hypoperfusion symptoms alone correlate poorly with actual hemodynamic compromise as assessed by quantitative magnetic resonance angiography and subsequent stroke risk in vertebrobasilar disease, and are not a reliable surrogate for flow measurement. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT00590980.

Importance of Collateralization in Patients With Large Artery Intracranial Occlusive Disease: Long-Term Longitudinal Assessment of Cerebral Hemodynamic Function.

Patients with large artery intracranial occlusive disease (LAICOD) are at risk for both acute ischemia and chronic hypoperfusion. Collateral circulation plays an important role in prognosis, and imaging plays an essential role in diagnosis, treatment planning, and prognosis of patients with LAICOD. In addition to standard structural imaging, assessment of cerebral hemodynamic function is important to determine the adequacy of collateral supply. Among the currently available methods of assessment of cerebral hemodynamic function, measurement of cerebrovascular reactivity (CVR) using blood oxygen level-dependent (BOLD) MRI and precisely controlled CO2 has shown to be a safe, reliable, reproducible, and clinically useful method for long-term assessment of patients. Here, we report a case of long-term follow-up in a 28-year-old Caucasian female presented to the neurology clinic with a history of TIAs and LAICOD of the right middle cerebral artery (MCA). Initial structural MRI showed a right MCA stenosis and a small right coronal radiate lacunar infarct. Her CVR study showed a large area of impaired CVR with a paradoxical decrease in BOLD signal with hypercapnia involving the right MCA territory indicating intracerebral steal. The patient was managed medically with anticoagulant and antiplatelet therapy and was followed-up for over 9 years with both structural and functional imaging. Cortical thickness (CT) measures were longitudinally assessed from a region of interest that was applied to subsequent time points in the cortical region exhibiting steal physiology and in the same region of the contralateral healthy hemisphere. In the long-term follow-up, the patient exhibited improvement in her CVR as demonstrated by the development of collaterals with negligible changes to CT. Management of patients with LAICOD remains challenging since no revascularization strategies have shown efficacy except in patients with moyamoya disease. Management is well defined for acute ischemia where the presence and the adequacy of the collateralization dictate the need for intervention. Long-term assessment in neurovascular uncoupling (i.e., chronic ischemia) may reveal improvements in CVR as the durability of compensatory collaterals improve, even in cases with no intervention. Thus, assessment of cerebrovascular hemodynamics using CVR measurements coupled with time-of-flight MR angiography can be useful in the clinical management of patients with LAICOD.