Stroke Prevention in Atrial Fibrillation: Our Current Failures and Required Research.

Nonvalvular atrial fibrillation is a common rhythm disorder of middle-aged to older adults that can cause ischemic strokes and systemic embolism. Lifelong use of oral anticoagulants reduces the risk of these ischemic events but increases the risk of major and clinically relevant hemorrhages. These medications also require strict compliance for efficacy, and they have nontrivial failure rates in higher-risk patients. Left atrial appendage closure is a nonpharmacological method to prevent ischemic strokes in atrial fibrillation without the need for lifelong anticoagulant use, but this procedure has the potential for complications and residual embolic events. This workshop of the Roundtable of Academia and Industry for Stroke Prevention discussed future research needed to further decrease the ischemic and hemorrhagic risks among patients with atrial fibrillation. A direct thrombin inhibitor, factor Xa inhibitors, and left atrial appendage closure are FDA-approved approaches whereas factor XIa inhibitors are currently being studied in phase 3 randomized controlled trials for stroke prevention. The benefits, risks, and shortcomings of these treatments and future research required in different high-risk patient populations are reviewed in this consensus statement.

Association of Multiple Passes during Mechanical Thrombectomy with Incomplete Reperfusion and Lesion Growth.

INTRODUCTION: Despite complete recanalization by mechanical thrombectomy, abnormal perfusion can be detected on MRI obtained post-endovascular therapy (EVT). The presence of residual perfusion abnormalities post-EVT may be associated with blood-brain barrier breakdown in response to mechanical disruption of the endothelium from multiple-pass thrombectomy. We hypothesize that multiple-pass versus single-pass thrombectomy is associated with a higher rate of residual hypoperfusion and increased lesion growth at 24 h. MATERIALS AND METHODS: For this analysis, we included patients presenting to one of two stroke centers between January 2015 and February 2018 with an acute ischemic stroke within 12 h from symptom onset if they had a large vessel occlusion of the anterior circulation documented on magnetic resonance angiography or CTA, baseline MRI pre-EVT with imaging evidence of hypoperfusion, underwent EVT, and had a post-EVT MRI with qualitatively interpretable perfusion-weighted imaging data at 24 h. MRI Tmax maps using a time delay threshold of >6 s were used to quantitate hypoperfusion volumes. Residual hypoperfusion at 24 h was solely defined as Tmax volume >10 mL with >6 s delay. Complete recanalization was defined as modified treatment in cerebral infarction visualized on angiography at EVT completion. Hyperintense acute reperfusion injury marker was assessed on post-EVT pre-contrast fluid-attenuated inversion recovery at 24 h. Major early neurological improvement was defined as a reduction of the admission National Institutes of Health Stroke Scale by ≥8 points or a score of 0-1 at 24 h. Good functional outcome was defined as 0-2 on the modified Rankin Scale on day 30 or 90. RESULTS: Fifty-five patients were included with median age 67 years, 58% female, 45% Black/African American, 36% White/Caucasian, median admission National Institutes of Health Stroke Scale 19, large vessel occlusion locations: 71% M1, 14.5% iICA, 14.5% M2, 69% treated with intravenous recombinant tissue plasminogen activator. Of these, 58% had multiple-pass thrombectomy, 39% had residual perfusion abnormalities at 24 h, and 64% had severe hyperintense acute reperfusion injury marker at 24 h. After adjusting for complete recanalization, only multiple-pass thrombectomy (odds ratio, 4.3 95% CI, 1.07-17.2; p = 0.04) was an independent predictor of residual hypoperfusion at 24 h. Patients with residual hypoperfusion had larger lesion growth on diffusion-weighted imaging (59 mL vs. 8 mL, p < 0.001), lower rate of major early neurological improvement (24% vs. 70%, p = 0.002) at 24 h, and worse long-term outcome based on the modified Rankin Scale at 30 or 90 days, 5 versus 2 (p < 0.001). CONCLUSIONS: Our findings suggest that incomplete reperfusion on post-EVT MRI is present even in some patients with successful recanalization at the time of EVT and is associated with multiple-pass thrombectomy, lesion growth, and worse outcome. Future studies are needed to investigate whether patients with residual hypoperfusion may benefit from immediate adjunctive therapy to limit lesion growth and improve clinical outcome.

Sickle Cell Trait and Risk of Ischemic Stroke in Young Adults.

BACKGROUND AND PURPOSE: Approximately 8% of Blacks have sickle cell trait (SCT), and there are conflicting reports from recent cohort studies on the association of SCT with ischemic stroke (IS). Most prior studies focused on older populations, with few data available in young adults. METHODS: A population-based case-control study of early-onset IS was conducted in the Baltimore-Washington region between 1992 and 2007. From this study, 342 Black IS cases, ages 15 to 49, and 333 controls without IS were used to examine the association between SCT and IS. Each participant's SCT status was established by genotyping and imputation. For analysis, χ2 tests and logistic regression models were performed with adjustment for potential confounding variables. RESULTS: Participants with SCT (n=55) did not differ from those without SCT (n=620) in prevalence of hypertension, previous myocardial infarction, diabetes mellitus, and current smoking status. Stroke cases had increased prevalence in these risk factors compared with controls. We did not find an association between SCT and early-onset IS in our overall population (odds ratio=0.9 [95% CI, 0.5-1.7]) or stratified by sex in males (odds ratio=1.26 [95% CI, 0.56-2.80]) and females (odds ratio=0.67 [95% CI, 0.28-1.69]). CONCLUSIONS: Our data did not find evidence of increased risk of early-onset stroke with SCT.

Smoking and Risk of Ischemic Stroke in Young Men.

BACKGROUND AND PURPOSE: There is a strong dose-response relationship between smoking and risk of ischemic stroke in young women, but there are few data examining this association in young men. We examined the dose-response relationship between the quantity of cigarettes smoked and the odds of developing an ischemic stroke in men under age 50 years. METHODS: The Stroke Prevention in Young Men Study is a population-based case-control study of risk factors for ischemic stroke in men ages 15 to 49 years. The χ2 test was used to test categorical comparisons. Logistic regression models were used to calculate the odds ratio for ischemic stroke occurrence comparing current and former smokers to never smokers. In the first model, we adjusted solely for age. In the second model, we adjusted for potential confounding factors, including age, race, education, hypertension, myocardial infarction, angina, diabetes mellitus, and body mass index. RESULTS: The study population consisted of 615 cases and 530 controls. The odds ratio for the current smoking group compared with never smokers was 1.88. Furthermore, when the current smoking group was stratified by number of cigarettes smoked, there was a dose-response relationship for the odds ratio, ranging from 1.46 for those smoking <11 cigarettes per day to 5.66 for those smoking 40+ cigarettes per day. CONCLUSIONS: We found a strong dose-response relationship between the number of cigarettes smoked daily and ischemic stroke among young men. Although complete smoking cessation is the goal, even smoking fewer cigarettes may reduce the risk of ischemic stroke in young men.

Time to recanalisation in patients with cerebral venous thrombosis under anticoagulation therapy.

BACKGROUND AND PURPOSE: Few studies have investigated the rates of recanalisation after cerebral venous thrombosis (CVT). Our objective was to investigate the recanalisation rate and to identify predictors of recanalisation in patients with CVT. METHODS: We included 102 patients with confirmed first-ever, non-septic CVT. All patients received anticoagulation for 12 months or until complete recanalisation. To assess recanalisation, patients underwent MR venography every 3 months until partial or complete recanalisation or for 12 months after diagnosis. We conducted two parallel analyses of complete recanalisation versus partial and no recanalisation versus any recanalisation. As a secondary objective we explored the influence of recanalisation on outcome and recurrent events. We calculated the probability of recanalisation using Kaplan-Meier analysis and conducted multivariate analysis using a Cox model. RESULTS: The mean age of patients was 33.5±11 years (80 (78.4%) women). Survival analysis indicated that 50% of the patients had any recanalisation (grades I, II and III) by 64 days and complete recanalisation (grade III) by 169 days. Adjusted Cox proportional model revealed that age <50 years (HR=11.5 95% CI=1.58 to 84.46, p=0.01) and isolated superior sagittal sinus thrombosis (HR=0.39, 95% CI=0.14 to 1.04, p=0.05) predict complete recanalisation, while age <50 years (HR=4.79; 95% CI=1.69 to 13.5, p=0.003) predicts any recanalisation. Patients with complete recanalisation had a greater chance of good functional outcome (HR=5.17; 95% CI=2.8 to 9.53, p<0.001). CONCLUSIONS: We found that recanalisation occurs over time, until month 11. Complete recanalisation may influence functional outcome.

Immediate changes in stroke lesion volumes post thrombolysis predict clinical outcome.

BACKGROUND AND PURPOSE: We hypothesize that reversal in diffusion-weighted imaging (DWI) volume at 24 hours predicts favorable clinical outcome only if accompanied by immediate reperfusion. Our aim was to quantify the immediate DWI and mean transit time changes at 2 and 24 hours after intravenous tissue-type plasminogen activator to evaluate the effect of reperfusion and DWI change on outcome. METHODS: Patients were selected from the Lesion Evolution in Stroke and Ischemia On Neuroimaging Project if they had an acute MRI with evaluable DWI and perfusion-weighted imaging, were treated with standard intravenous tissue-type plasminogen activator, had post-thrombolysis MRI with evaluable DWI and perfusion-weighted imaging at 2 and 24 hours and had follow-up fluid attenuated inversion recovery MRI at discharge through 90 days. A reader measured the DWI, mean transit time, and fluid attenuated inversion recovery volumes using a validated technique. A vascular neurologist scored the National Institutes of Health Stroke Scale at admit, 2, and 24 hours and the modified Rankin Scale at discharge, 5, 30, and 90 days. Favorable clinical outcome was defined as modified Rankin Scale of 0 or 1. RESULTS: Seventy-one patients met the study criteria with mean (±SD) age of 71.6 (±16.4) years, 58% women, median admit National Institutes of Health Stroke Scale 9 (interquartile range, 4-18), median onset to triage 45 minutes (30-65), and median first MRI to intravenous tissue-type plasminogen activator 47 minutes (39-59). In binary multiple logistic regression analysis, younger age (odds ratio, 1.165; P=0.014; 95% confidence interval [CI], 1.031-1.316), lower admit National Institutes of Health Stroke Scale (odds ratio, 1.221; P=0.012; 95% confidence interval, 1.045-1.427), decrease in mean transit time volume at 2 hours (odds ratio, 1.021; P=0.031; 95% confidence interval, 1.002-1.040), and decrease in DWI volume at 24 hours (odds ratio, 1.173; P=0.027; 95% confidence interval, 1.018-1.351) were significant predictors of favorable clinical outcome. CONCLUSIONS: Reversal of the DWI volume at 24 hours because of immediate reperfusion in patients post thrombolysis is predictive of favorable clinical outcome.

Assessing reperfusion with whole-brain arterial spin labeling: a noninvasive alternative to gadolinium.

BACKGROUND AND PURPOSE: Arterial spin labeling (ASL) is a perfusion imaging technique that does not require gadolinium. The study aimed to assess the reliability of ASL for evaluating reperfusion in acute ischemic stroke in comparison with dynamic susceptibility contrast (DSC) imaging. METHODS: The study included 24 patients with acute ischemic stroke on admission and 24-hour follow-up ASL and DSC scans. Two readers rated images for interpretability and evidence of reperfusion. Cohen unweighted κ was used to assess (1) inter-rater reliability between readers for determining interpretability and the presence of reperfusion, (2) agreement between ASL and DSC for determining reperfusion for individual raters, and (3) agreement between ASL and DSC for determining reperfusion after consensus. RESULTS: Inter-rater reliability for both ASL and DSC was moderate to good (κ of 0.67 versus 0.55, respectively). Reader 1 rated 16 patients as having interpretable ASL and DSC when compared with 15 patients for reader 2. The κ between ASL and DSC for determining reperfusion was 0.50 for reader 1 and 0.595 for reader 2. After consensus, 18 ASL and 17 DSC image sets were rated interpretable for reperfusion and 13 had both interpretable ASL and DSC scans, yielding a κ for assessment of reperfusion of 0.8. CONCLUSIONS: Inter-rater reliability of ASL and DSC was moderate to good. Agreement between ASL and DSC for determining reperfusion was moderate for each individual rater and increased substantially after consensus. ASL is a noninvasive and practical alternative to DSC for reperfusion assessments in patients with confirmed acute ischemic stroke.

Negative diffusion-weighted imaging after intravenous tissue-type plasminogen activator is rare and unlikely to indicate averted infarction.

BACKGROUND AND PURPOSE: Some patients treated with intravenous (IV) tissue-type plasminogen activator (tPA) have negative diffusion-weighted imaging (DWI) on follow-up imaging. Without a visible infarct, there may be uncertainty as to whether the patient was having a stroke that was averted by tPA or whether the symptoms had not been cerebrovascular in origin. We evaluated patients presenting with suspected acute stroke with a positive DWI lesion before IV tPA to determine the probability of finding a negative DWI up to 48 hours after treatment. METHODS: We included patients from the Lesion Evolution in Stroke and Ischemia On Neuroimaging (LESION) project who had acute MRI screening with a positive DWI lesion before IV tPA treatment and had follow-up MRI up to 48 hours later. Experienced readers interpreted all acute and follow-up MRIs looking for ischemic lesions on DWI. RESULTS: There were 231 patients who met study inclusion criteria, of which 225 patients (97.4%) had a persistent positive DWI corresponding to the acute stroke lesion on all follow-up imaging. Four patients (1.7%) had transient DWI lesion reversal with positive DWI on subsequent follow-up imaging. There were only 2 cases (0.9%) of complete DWI lesion reversal on all follow-up imaging. CONCLUSIONS: Averted infarction after IV tPA is rare, occurring in 0.9% of patients with pretreatment positive DWI evidence of acute ischemia. For IV tPA-treated patients who have a negative DWI on follow-up imaging, a cause other than acute stroke should be explored.

Predictors of acute stroke mimics in 8187 patients referred to a stroke service.

BACKGROUND: Some patients seen by a stroke team do not have cerebrovascular disease but a condition that mimics stroke. The purpose of this study was to determine the rate and predictors of stroke mimics in a large sample. METHODS: This is an analysis of data from consecutive patients seen by the National Institutes of Health Stroke Program over 10 years. Data were collected prospectively as a quality improvement initiative. Patients with a cerebrovascular event or a stroke mimic were compared with the Student t or Pearson chi-square test as appropriate, and logistic regression was done to identify independent predictors. RESULTS: The analysis included 8187 patients: 30% had a stroke mimic. Patients with a stroke mimic were younger, and the proportion of patients with a stroke mimic was higher among women, patients without any risk factors, those seen as a code stroke or who arrived to the emergency department via personal vehicle, and those who had the onset of symptoms while inpatients. The proportion of patients with a stroke mimic was marginally higher among African-Americans than Caucasians. Factors associated with the greatest odds of having a stroke mimic in the logistic regression were lack of a history of hypertension, atrial fibrillation or hyperlipidemia. CONCLUSIONS: One third of the patients seen by a stroke team over 10 years had a stroke mimic. Factors associated with a stroke mimic may be ascertained by an emergency physician before calling the stroke team.

Variability in the use of intravenous thrombolysis for mild stroke: experience across the SPOTRIAS network.

BACKGROUND: Current guidelines do not define the lower severity threshold for thrombolysis. In this study, we describe the variability of treatment of mild stroke patients across a network of academic stroke centers. METHODS: Stroke centers within the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) prospectively collect data on patients treated with intravenous recombinant tissue plasminogen activator (IV rt-PA), including demographics, pretreatment National Institutes of Health Stroke Scale (NIHSS) scores, and in-hospital mortality. We examined the variability in proportion of total tissue plasminogen activator-treated patients in the NIHSS categories (0-3, 4-5, or ≥ 6) and associated outcomes. RESULTS: A total of 2514 patients with reported NIHSS scores were treated with IV rt-PA between January 1, 2005 and December 31, 2009. The proportion of patients with mild stroke (NIHSS scores of 0-3) who were treated with IV rt-PA varied substantially across the centers (2.7-18.0%; P < .001). There were 5 deaths in the 256 treated with an NIHSS score of 0-3 (2.0%). The proportion of treated patients across the network with an NIHSS score of 0 to 3 increased from 4.8% in 2005 to 10.7% in 2009 (P = .001). CONCLUSIONS: There is substantial variability in the proportion of treated patients who have mild stroke across the SPOTRIAS centers, reflecting a paucity of data on how to best treat patients with mild stroke. Randomized trial data for this group of patients are needed to clarify the use of rt-PA in patients with the mildest strokes.

Pseudocontinuous arterial spin labeling quantifies relative cerebral blood flow in acute stroke.

BACKGROUND AND PURPOSE: The aim of this study was to test whether arterial spin labeling (ASL) can detect significant differences in relative cerebral blood flow (rCBF) in the core, mismatch, and reverse-mismatch regions, and whether rCBF values measured by ASL in those areas differ from values obtained using dynamic susceptibility contrast (DSC) MRI. METHODS: Acute stroke patients were imaged with diffusion-weighted imaging (DWI) and perfusion-weighted imaging (ASL and DSC) MRI. An expert reader segmented the ischemic lesion on DWI and the DSC time-to-peak (TTP) maps. Three regions were defined: core (DWI+, TTP+), mismatch (DWI-, TTP+), and reverse-mismatch (DWI+, TTP-). For both ASL and DSC, rCBF maps were created with commercially available software, and the ratio was calculated as the mean signal intensity measured on the side of the lesion to that of the homologous region in the contralateral hemisphere. Values obtained from core, mismatch, and reverse-mismatch were used for paired comparison. RESULTS: Twenty-eight patients were included in the study. The mean age was 65.6 (16.9) years, with a median baseline National Institutes of Health Stroke Scale score of 10 (interquartile range, 4-17). Median time from last known normal to MRI was 5.7 hours (interquartile range, 2.9-22.6). Mean rCBF ratios were significantly higher in the mismatch 0.53 (0.23) versus the core 0.39 (0.33) and reverse-mismatch 0.68 (0.49) versus the core 0.38 (0.35). Differences in rCBF measured with DSC and ASL were not significant. CONCLUSIONS: ASL allows for the measurement of rCBF in the core and mismatch regions. Values in the mismatch were significantly higher than in the core, suggesting there is potential salvageable tissue.

Tissue factor pathway inhibitor, activated protein C resistance, and risk of ischemic stroke due to postmenopausal hormone therapy.

BACKGROUND AND PURPOSE: To test whether changes in plasma tissue factor pathway inhibitor (TFPI) levels or activated protein C resistance (normalized activated protein C resistance ratio [nAPCsr]) modify the increased risk of ischemic stroke due to postmenopausal hormone therapy. METHODS: Nested case-control study of 455 cases of ischemic stroke and 565 matched control subjects in the Women's Health Initiative trials of postmenopausal hormone therapy. RESULTS: Baseline free TFPI was associated with ischemic stroke risk (OR per SD increase, 1.17; 95% CI, 1.01-1.37; P=0.039), but baseline nAPCsr was not (OR per SD increase, 0.89; 95% CI, 0.75-1.05; P=0.15). Baseline TFPI levels and nAPCsr did not modify the effect of postmenopausal hormone therapy on ischemic stroke. Treatment-induced mean changes of -28% in free TFPI and +65% in nAPCsr did not change the risk of ischemic stroke (interaction P=0.452 and 0.971, respectively). In subgroup analyses, baseline nAPCsr was inversely associated with lacunar strokes (OR per SD increase, 0.74; 95% CI, 0.57-0.96; P=0.025) and baseline free TFPI interacted with treatment to increase large vessel atherosclerotic strokes (P=0.008). CONCLUSIONS: Procoagulant changes in TFPI or nAPCsr do not modify the increased ischemic stroke risk due to postmenopausal hormone therapy. Clinical Trial Registration- URL: www.clinicaltrials.gov. Unique identifier: NCT 00000611.

Impact of acute ischemic stroke treatment in patients >80 years of age: the specialized program of translational research in acute stroke (SPOTRIAS) consortium experience.

BACKGROUND AND PURPOSE: Few studies have addressed outcomes among patients ≥80 years treated with acute stroke therapy. In this study, we outline in-hospital outcomes in (1) patients ≥80 years compared with their younger counterparts; and (2) those over >80 years receiving intra-arterial therapy (IAT) compared with those treated with intravenous recombinant tissue-type plasminogen activator (IV rtPA). METHODS: Stroke centers within the Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) prospectively collected data on all patients treated with IV rtPA or IAT from January 1, 2005, to December 31, 2010. IAT was defined as receiving any endovascular therapy; IAT was further divided into bridging therapy when the patient received both IAT and IV rtPA and endovascular therapy alone. In-hospital mortality was compared in (1) all patients aged ≥80 years versus younger counterparts; and (2) IAT, bridging therapy, and endovascular therapy alone versus IV rtPA only among those age ≥80 years using multivariable logistic regression. An age-stratified analysis was also performed. RESULTS: A total of 3768 patients were included in the study; 3378 were treated with IV rtPA alone and 808 with IAT (383 with endovascular therapy alone and 425 with bridging therapy). Patients ≥80 years (n=1182) had a higher risk of in-hospital mortality compared with younger counterparts regardless of treatment modality (OR, 2.13; 95% CI, 1.60-2.84). When limited to those aged ≥80 years, IAT (OR, 0.95; 95% CI, 0.60-1.49), bridging therapy (OR, 0.82; 95% CI, 0.47-1.45), or endovascular therapy alone (OR, 1.15; 95% CI, 0.64-2.08) versus IV rtPA were not associated with increased in-hospital mortality. CONCLUSIONS: IAT does not appear to increase the risk of in-hospital mortality among those aged >80 years compared with IV thrombolysis alone.

Whole-brain arterial spin labeling perfusion MRI in patients with acute stroke.

BACKGROUND AND PURPOSE: Perfusion MRI can be used to identify patients with acute ischemic stroke who may benefit from reperfusion therapies. The risk of nephrogenic systemic fibrosis, however, limits the use of contrast agents. Our objective was to evaluate the ability of arterial spin labeling (ASL), an alternative noninvasive perfusion technique, to detect perfusion deficits compared with dynamic susceptibility contrast (DSC) perfusion imaging. METHODS: Consecutive patients referred for emergency assessment of suspected acute stroke within a 7-month period were imaged with both ASL and DSC perfusion MRI. Images were interpreted in a random order by 2 experts blinded to clinical information for image quality, presence of perfusion deficits, and diffusion-perfusion mismatches. RESULTS: One hundred fifty-six patients were scanned with a median time of 5.6 hours (range, 3.0-17.7 hours) from last seen normal. Stroke diagnosis was clinically confirmed in 78 patients. ASL and DSC imaging were available in 64 of these patients. A perfusion deficit was detected with DSC in 39 of these patients; ASL detected 32 of these index perfusion deficits, missing 7 lesions. The median volume of the perfusion deficits as determined with DSC was smaller in patients who were evaluated as normal with ASL than in those with a deficit (median [interquartile range], 56 [10-116] versus 114 [41-225] mL; P=0.01). CONCLUSIONS: ASL can depict large perfusion deficits and perfusion-diffusion mismatches in correspondence with DSC. Our findings show that a fast 2½-minute ASL perfusion scan may be adequate for screening patients with acute stroke with contraindications to gadolinium-based contrast agents.

Comprehensive stroke centers and the 'weekend effect': the SPOTRIAS experience.

BACKGROUND AND PURPOSE: Previous studies have found mortality among ischemic stroke patients to be higher on weekends. We sought to evaluate whether weekend admission was associated with worse outcomes in a large comprehensive stroke center (CSC) cohort. METHODS: Consecutive ischemic stroke patients presenting within 6 h of symptom onset were identified using the 8 CSC SPOTRIAS (Specialized Programs of Translational Research in Acute Stroke) database. Patients who received intra-arterial therapy or who were enrolled in a nonobservational clinical trial were excluded. All patients meeting the inclusion criteria were then divided into two groups: weekday admissions or weekend admissions. Weekend admission was defined as Friday 17:01 to Monday 08:59. The remainder were classified as weekday admissions. Multivariate logistic regression was used, adjusting for age, stroke severity on admission [according to the National Institutes of Health Stroke Scale (NIHSS)] and admission glucose, in order to compare the outcomes of the weekend versus the weekday groups. RESULTS: Eight thousand five hundred and eighty-one subjects from the combined SPOTRIAS database were screened from 2002 to 2009; 2,090 (24.4%) of these met the inclusion criteria. There was no significant difference in tissue plasminogen activator treatment rates between the weekday and weekend groups (58.5 vs. 60.4%, p = 0.397). Weekend admission was not a significant independent predictor of inhospital mortality (8.4 vs. 9.9%, p = 0.056), length of stay (4 vs. 5 days, p = 0.442), favorable discharge disposition (38.0 vs. 42.2%, p = 0.122), favorable functional outcome at discharge (41.6 vs. 43.4%, p = 0.805), favorable 90-day functional outcome (54.2 vs. 46.9%, p = 0.301), or 90-day mortality (18.2 vs. 19.8%, p = 0.680) when adjusting for age, NIHSS and admission glucose. CONCLUSIONS: In this large cohort of ischemic stroke patients treated at CSCs, we did not observe the 'weekend effect.' This may be due to access to stroke specialists 24 h a day on 365 days a year, nurses with stroke experience and the organized system for delivering care that is available at CSCs. These results suggest that EMS protocol should be reexamined regarding the preferential delivery of weekend stroke victims to hospitals that provide all levels of reperfusion therapy. This further highlights the importance of organized stroke care.

Visual perfusion-diffusion mismatch is equivalent to quantitative mismatch.

BACKGROUND AND PURPOSE: The concept of stroke MRI mismatch based on qualitative evaluation of diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) has been applied in clinical practice for several years. The benefit of MRI in providing pathological evidence of ischemia before thrombolytic treatment has been demonstrated. The purpose of this study is to determine the reliability of the qualitative method and compare it with quantitative mismatch measurement in thrombolytic-treated patients. METHODS: Patients (n=70) were selected from the Lesion Evolution of Stroke and Ischemic On Neuroimaging (LESION) database if they: (1) were treated with intravenous recombinant tissue plasminogen activator; (2) had a pretreatment MRI with evaluable DWI and PWI; and (3) had acute ischemic lesion volume >10 mL on DWI as determined by core imaging laboratory measurements. Quantitative mismatch was defined as a difference of >50 mL between abnormal mean transit time and DWI volumes. Sample characteristics and postdischarge modified Rankin Scale for the positive mismatch patients were compared between the subgroups identified by qualitative versus quantitative methods. RESULTS: Patient characteristics and thrombolytic outcomes (sex, age, National Institutes of Health Stroke Scale, mismatch volume, and modified Rankin Scale) did not differ for mismatch patients identified by qualitative versus quantitative methods. Qualitative mismatch selection among neurologists had a high sensitivity (0.82), specificity (0.80), accuracy (0.81), and positive predictive value (0.88) compared with quantitative measurements. CONCLUSIONS: We observed that qualitative evaluation of mismatch identified the same thrombolytic-treated patients compared with retrospective quantitative mismatch measurements.

Carotid endarterectomy benefits patients with CKD and symptomatic high-grade stenosis.

Endarterectomy is generally recommended for symptomatic high-grade (70 to 99%) stenosis of the internal carotid artery, but whether this procedure is beneficial among patients with chronic kidney disease (CKD) is unknown. In this re-analysis of data from the North American Symptomatic Carotid Endarterectomy Trial, we included patients with symptomatic stenosis and either stage 3 CKD (n = 524) or preserved kidney function (n = 966; estimated GFR > or = 60). For medically treated patients with high-grade stenosis, risk for ipsilateral stroke at 2 yr was significantly higher in patients with CKD than in those with preserved renal function (31.6 versus 19.3%; P = 0.042); carotid endarterectomy significantly reduced this risk by 82 and 51%, respectively. To prevent one ipsilateral stroke, the number needed to treat by endarterectomy was four for patients with CKD and 10 for patients with preserved renal function. Compared with patients with preserved renal function, those with CKD had similar rates of perioperative stroke and death but higher rates of cardiac events. In conclusion, patients with stage 3 CKD and symptomatic high-grade carotid stenosis gain a large benefit in stroke risk reduction after endarterectomy.

TRANSCENDS: A Career Development Program for Underrepresented in Medicine Scholars in Academic Neurology.

BACKGROUND: The Training in Research for Academic Neurologists to Sustain Careers and Enhance the Numbers of Diverse Scholars (TRANSCENDS) program is a career advancement opportunity for individuals underrepresented in biomedical research, funded by the National Institute and Neurological Disorders and Stroke; and American Academy of Neurology (AAN). OBJECTIVE: To report on qualitative and quantitative outcomes in TRANSCENDS. DESIGN: Early career individuals (neurology fellows and junior faculty) from groups underrepresented in medicine were competitively selected from a national pool of applicants (2016-2019). TRANSCENDS activities comprised an online Clinical Research degree program, monthly webinars, AAN meeting activities, and mentoring. Participants were surveyed during and after completion of TRANSCENDS to evaluate program components. OUTCOMES: Of 23 accepted scholars (comprising four successive cohorts), 56% were women; 61% Hispanic/Latinx, 30% Black/African American, 30% assistant professors. To date, 48% have graduated the TRANSCENDS program and participants have published 180 peer-reviewed articles. Mentees' feedback noted that professional skills development (i.e., manuscript and grant writing), networking opportunities, and mentoring were the most beneficial elements of the program. Stated opportunities for improvement included: incorporating a mentor-the-mentor workshop, providing more transitional support for mentees in the next stage of their careers, and requiring mentees to provide quarterly reports. CONCLUSIONS: TRANSCENDS is a feasible program for supporting underrepresented in medicine neurologists towards careers in research and faculty academic appointments attained thus far have been sustained. While longer term outcomes and process enhancements are warranted, programs like this may help increase the numbers of diverse academic neurologists, and further drive neurological innovation.

Optimizing stroke clinical trial design: estimating the proportion of eligible patients.

BACKGROUND AND PURPOSE: Clinical trial planning and site selection require an accurate estimate of the number of eligible patients at each site. In this study, we developed a tool to calculate the proportion of patients who would meet a specific trial's age, baseline severity, and time to treatment inclusion criteria. METHODS: From a sample of 1322 consecutive patients with acute ischemic cerebrovascular syndromes, we developed regression curves relating the proportion of patients within each range of the 3 variables. We used half the patients to develop the model and the other half to validate it by comparing predicted vs actual proportions who met the criteria for 4 current stroke trials. RESULTS: The predicted proportion of patients meeting inclusion criteria ranged from 6% to 28% among the different trials. The proportion of trial-eligible patients predicted from the first half of the data were within 0.4% to 1.4% of the actual proportion of eligible patients. This proportion increased logarithmically with National Institutes of Health Stroke Scale score and time from onset; lowering the baseline limits of the National Institutes of Health Stroke Scale score and extending the treatment window would have the greatest impact on the proportion of patients eligible for a stroke trial. CONCLUSIONS: This model helps estimate the proportion of stroke patients eligible for a study based on different upper and lower limits for age, stroke severity, and time to treatment, and it may be a useful tool in clinical trial planning.

Reversible diffusion-weighted imaging lesions in acute ischemic stroke: A systematic review.

OBJECTIVES: To systematically review the literature for reversible diffusion-weighted imaging (DWIR) lesions and to describe its prevalence, predictors, and clinical significance. METHODS: Studies were included if the first DWI MRI was performed within 24 hours of stroke onset and follow-up DWI or fluid-attenuated inversion recovery (FLAIR)/T2 was performed within 7 or 90 days, respectively, to measure DWIR. We abstracted clinical, imaging, and outcomes data. RESULTS: Twenty-three studies met the study criteria. The prevalence of DWIR was 26.5% in DWI-based studies and 6% in FLAIR/T2-based studies. DWIR was associated with recanalization or reperfusion of the ischemic tissue with or without the use of tissue plasminogen activator (t-PA) or endovascular therapy, earlier treatment with t-PA, shorter time to endovascular therapy after MRI, and absent or less severe perfusion deficit within the DWI lesion. DWIR was associated with early neurologic improvement in 5 of 6 studies (defined as improvement in the NIH Stroke Scale (NIHSS) score by 4 or 8 points from baseline or NIHSS score 0 to 2 at 24 hours after treatment or at discharge or median NIHSS score at 7 days) and long-term outcome in 6 of 7 studies (defined as NIHSS score ≤1, improvement in the NIHSS score ≥8 points, or modified Rankin Scale score up to ≤2 at 30 or 90 days) likely due to reperfusion. CONCLUSIONS: DWIR is seen in up to a quarter of patients with acute ischemic stroke, and it is associated with good clinical outcome following reperfusion. Our findings highlight the pitfalls of DWI to define ischemic core in the early hours of stroke.