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More than 25 years have passed since the US Food and Drug Administration approved IV recombinant tissue plasminogen activator (alteplase) for the treatment of acute ischemic stroke. This landmark decision brought a previously untreatable disease into a new therapeutic landscape, providing inspiration for clinicians and hope to patients. Since that time, the use of alteplase in the clinical setting has become standard of care, continually improving with quality measures such as door-to-needle times and other metrics of specialized stroke unit care. The past decade has seen more widespread use of alteplase in the prehospital setting with mobile stroke units and telestroke and beyond initial time windows via the use of CT perfusion or MRI. Simultaneously, the position of alteplase is being challenged by new lytics and by the concept of its bypass altogether in the era of endovascular therapy. We provide an overview of alteplase, including its earliest trials and how they have shaped the current therapeutic landscape of ischemic stroke treatment, and touch on new frontiers for thrombolytic therapy. We highlight the critical role of thrombolytic therapy in the past, present, and future of ischemic stroke care.

Despite years of basic research and pioneering clinical work, ischemic stroke remains a major public health concern. Prior STAIR (Stroke Treatment Academic Industry Roundtable) conferences identified both failures of clinical trial design and failures in preclinical assessment in developing putative ischemic stroke treatments. At STAIR XI, participants in workshop no. 1 Top Priorities for Neuroprotection sought to redefine the neuroprotection paradigm and given the paucity of evidence underlying preclinical assessment, offer consensus-based recommendations. STAIR proposes the term brain cytoprotection or cerebroprotection to replace the term neuroprotection when the intention of an investigation is to demonstrate that a new, candidate treatment benefits the entire brain. Although “time is still brain,” tissue imaging techniques have been developed to identify patients with both predicted core injury and penumbral, salvageable brain tissue, regardless of time after stroke symptom onset. STAIR XI workshop participants called this imaging approach a tissue window to select patients for recanalization. Elements of the neurovascular unit show differential vulnerability evolving over differing time scales in different brain regions. STAIR proposes the term target window to suggest therapies that target the different elements of the neurovascular unit at different times. Based on contemporary principles of rigor and transparency, the workshop updated, revised, and enhanced the STAIR preclinical recommendations for developing new treatments in 2 phases: an exploratory qualification phase and a definitive validation phase. For new, putative treatments, investigators should carefully characterize the mechanism of action, the pharmacokinetics/pharmacodynamics, demonstrate target engagement, and confirm penetration through the blood-brain barrier. Before clinical trials, testing of candidate molecules in stroke models could proceed in a comprehensive manner using animals of both sexes and to include significant variables such as age and comorbid conditions. Comprehensive preclinical assessment might include multicenter, collaborative testing, for example, network trials. In the absence of a proven cerebroprotective agent to use as a gold standard, however, it remains speculative whether such comprehensive preclinical assessment can effectively predict clinical outcome.

Background and Purpose: In patients with acute large vessel occlusion, the natural history of penumbral tissue based on perfusion time-to-maximum (T max ) delay is not well established in relation to late-window endovascular thrombectomy. In this study, we sought to evaluate penumbra consumption rates for T max delays in patients with large vessel occlusion evaluated between 6 and 16 hours from last known normal. Methods: This is a post hoc analysis of the DEFUSE 3 trial (The Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke), which included patients with an acute ischemic stroke due to anterior circulation occlusion within 6 to 16 hours of last known normal. The primary outcome is percentage penumbra consumption, defined as (24-hour magnetic resonance imaging infarct volume–baseline core infarct volume)/(T max 6 or 10 s volume–baseline core volume). We stratified the cohort into 4 categories based on treatment modality and Thrombolysis in Cerebral Infarction (TICI score; untreated, TICI 0-2a, TICI 2b, and TICI3) and calculated penumbral consumption rates in each category. Results: We included 141 patients, among whom 68 were untreated. In the untreated versus TICI 3 patients, a median (interquartile range) of 53.7% (21.2%–87.7%) versus 5.3% (1.1%–14.6%) of penumbral tissue was consumed based on T max >6 s ( P max >10 s, we saw a difference of 165.4% (interquartile range, 56.1%–479.8%) versus 25.7% (interquartile range, 3.2%–72.1%; P max >6 s ( P =0.52) or T max >10 s ( P =0.92). Conclusions: Among extended window endovascular thrombectomy patients, T max >10-s mismatch volume may comprise large volumes of salvageable tissue, whereas nearly half the T max >6-s mismatch volume may remain viable in untreated patients at 24 hours.

Background and Purpose: The National Institutes of Health Stroke Scale (NIHSS) measured at an early time point is an appealing surrogate marker for long-term functional outcome of stroke patients treated with endovascular therapy. However, definitions and analytical methods for an early NIHSS-based outcome measure that optimize power and precision in clinical studies are not well-established. Methods: In this post-hoc analysis of our prospective observational study that enrolled endovascular therapy-treated patients at 12 comprehensive stroke centers across the US, we compared the ability of 24-hour NIHSS, ΔNIHSS (baseline minus 24-hour NIHSS), and percentage change (NIHSS×100/baseline NIHSS), analyzed as continuous and dichotomous measures, to predict 90-day modified Rankin Scale (mRS) using logistic regression (adjusted for age, baseline NIHSS, glucose, hypertension, Alberta Stroke Program Early CT Score, time to recanalization, recanalization status, and intravenous thrombolysis) and Spearman ρ. Results: Of 485 patients in the BEST (Blood Pressure After Endovascular Stroke Therapy) cohort, 446 (92%) with 90-day follow-up data were included. An absolute 24-hour NIHSS, adjusted for baseline in multivariable modeling, had the highest predictive power of all definitions evaluated (aR 2 0.368 and adjusted odds ratio 0.79 [0.75–0.84], P 2 0.444 and adjusted odds ratio 0.84 [0.8–0.86] for ordinal mRS). For predicting mRS score of 0–2 with a cut point, the second most efficient approach, the optimal threshold for 24-hour NIHSS score was ≤7 (sensitivity 80.1%, specificity 80.4%; adjusted odds ratio 12.5 [7.14–20], P P Conclusions: Twenty-four–hour NIHSS, adjusted for baseline, was the strongest predictor of both dichotomous and ordinal 90-day mRS outcomes for endovascular therapy-treated patients. A dichotomous 24-hour NIHSS score of ≤7 was the second-best predictor. Although ΔNIHSS, continuous and dichotomized at ≥4, predicted 90-day outcomes, absolute 24-hour NIHSS definitions performed better.

Background and Purpose: Although most strokes present with mild symptoms, these have been poorly represented in clinical trials. The objective of this study is to describe multidimensional outcomes, identify predictors of worse outcomes, and explore the effect of thrombolysis in this population. Methods: This prospective observational study included patients with ischemic stroke or transient ischemic attack, a baseline National Institutes of Health Stroke Scale (NIHSS) score 0 to 5, presenting within 4.5 hours from symptom onset. The primary outcome was a 90-day modified Rankin Scale score of 0 to 1; secondary outcomes included good outcomes in the Barthel Index, Stroke Impact Scale-16, and European Quality of Life. Multivariable models were created to determine predictors of outcomes and the effect of alteplase. Results: A total of 1765 participants were included from 100 Get With The Guidelines-Stroke participating hospitals (age, 65±14; 42% women; final diagnosis of ischemic stroke, 90%; transient ischemic attack, 10%; 57% received alteplase). At 90 days, 37% were disabled and 25% not independent. Worse outcomes were noted for older individuals, women, non-Hispanic Blacks and Hispanics, Medicaid recipients, smokers, those with diabetes, atrial fibrillation, prior stroke, higher baseline NIHSS, visual field defects, and extremity weakness. Similar outcomes were noted for the alteplase-treated and untreated groups. Alteplase-treated patients were younger (64±13 versus 67±1.4) with higher NIHSS (2.9±1.4 versus 1.7±1.4). After adjusting for age, sex, race/ethnicity, and baseline NIHSS, we did not identify an effect of alteplase on the primary outcome but did find an association with Stroke Impact Scale-16 in the restricted sample of baseline NIHSS score 3–5. Few symptomatic intracerebral hemorrhages were recorded ( Conclusions: A large proportion of stroke patients presenting with low NIHSS have a disabled outcome. Baseline predictors of worse outcomes are described. An effect of alteplase on outcomes was not identified in the overall cohort, but a suggestion of efficacy was noted in the NIHSS 3–5 subgroup. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02072681.

BackgroundIntracerebral hemorrhage (ICH) occurs in ~20%–30% of stroke patients undergoing endovascular therapy (EVT). However, there is conflicting evidence regarding the effect of asymptomatic ICH (aICH) on post-EVT outcomes. We sought to evaluate the effect of aICH on immediate and 90-day post-EVT neurological outcomes.MethodsIn this post-hoc analysis of the multicenter, prospective Blood Pressure after Endovascular Therapy (BEST) study we identified subjects with ICH following EVT. This population was divided into no ICH, aICH, and symptomatic ICH (sICH). Associations with 90-day modified Rankin Scale (mRS) dichotomized by functional independence (0–2 vs 3–6) and early neurological recovery (ENR) were determined using univariate/multivariate logistic regression models.ResultsOf 485 patients enrolled in BEST, 446 had 90-day follow-up data available. 92 (20.6%) developed aICH, and 18 (4%) developed sICH. Compared with those without ICH, aICH was not associated with worse 90-day outcome or lower ENR (OR 0.84 [0.53–1.35], P=0.55, aOR 0.84 [0.48–1.44], P=0.53 for 90-day mRS 0–2; OR 0.77 [0.48–1.23], P=0.34, aOR 0.72 [0.43–1.22] for ENR). aICH was not associated with 90-day outcome or ENR in patients with mTICI ≥2 b (OR 0.78 [0.48–1.26], P=0.33 for 90-day mRS 0–2; OR 0.89 [0.69–1.12], P=0.15 for ENR). A higher proportion of patients with aICH had mTICI ≥2 b than those without ICH (97%vs 87%, P=0.01).ConclusionsaICH was not associated with worse outcomes in patients with large-vessel stroke treated with EVT. aICH was more frequent in patients with successful recanalization. Further validation of our findings in large cohort studies of EVT-treated patients is warranted.

Background and Purpose: The Alberta Stroke Program Early Computed Tomography (CT) Score (ASPECTS) and CT perfusion (CTP) are commonly used to predict the ischemic core in acute ischemic strokes. CT angiography source images (CTA-SI) can also provide additional information to identify the extent of ischemia. Our objective was to investigate the correlation of noncontrast CT (NCCT) ASPECTS and CTA-SI ASPECTS with CTP core volumes. Methods: We utilized a single institutional, retrospective registry of consecutive patients with acute ischemic stroke with large vessel occlusion between May 2016 and May 2018. We graded ASPECTS both on baseline NCCT and CTA-SI and measured CTP core using automated RAPID software (cerebral blood flow Results: A total of 52 patients fit the inclusion criteria of large vessel occlusion in 6 to 24 hours and baseline imaging work up of NCCT, CTA, and CTP. The median age was 63 (interquartile range=53.5–75) and 38.46% were female. The median NCCT ASPECTS was 7 (interquartile range=6–9), CTA-SI ASPECTS was 5 (interquartile range=4–7), and CTP core was 14.5 mL (interquartile range=0–46 mL). There was a moderate correlation between NCCT ASPECTS and CTP core (r s =−0.55, P s =−0.50, P =0.0002). The optimal NCCT ASPECTS cutoff score to detect CTP core ≤70 mL was ≥6 (sensitivity, 0.84; specificity, 0.57; positive predictive value, 0.93; negative predictive value, 0.36) and the optimal CTA-SI ASPECTS was ≥5 (sensitivity, 0.76; specificity, 0.71; positive predictive value, 0.94; negative predictive value, 0.31). Conclusions: There was a moderate correlation between NCCT and CTA-SI ASPECTS in predicting CTP defined ischemic core in delayed time windows. Further studies are needed to determine if NCCT and CTA imaging could be used for image-based patient selection when CTP imaging is not available.

Background and Purpose: Accumulating evidence from randomized controlled clinical trials suggests that tenecteplase may represent an effective treatment alternative to alteplase for acute ischemic stroke. In the present systematic review and meta-analysis, we sought to compare the efficacy and safety outcomes of intravenous tenecteplase to intravenous alteplase administration for acute ischemic stroke patients with large vessel occlusions (LVOs). Methods: We searched MEDLINE (Medical Literature Analysis and Retrieval System Online) and Scopus for published randomized controlled clinical trials providing outcomes of acute ischemic stroke with confirmed LVO receiving intravenous thrombolysis with either tenecteplase at different doses or alteplase at a standard dose of 0.9 mg/kg. The primary outcome was the odds of modified Rankin Scale score of 0 to 2 at 3 months. Results: We included 4 randomized controlled clinical trials including a total of 433 patients. Patients with confirmed LVO receiving tenecteplase had higher odds of modified Rankin Scale scores of 0 to 2 (odds ratio, 2.06 [95% CI, 1.15–3.69]), successful recanalization (odds ratio, 3.05 [95% CI, 1.73–5.40]), and functional improvement defined as 1-point decrease across all modified Rankin Scale grades (common odds ratio, 1.84 [95% CI, 1.18–2.87]) at 3 months compared with patients with confirmed LVO receiving alteplase. There was little or no heterogeneity between the results provided from included studies regarding the aforementioned outcomes (I 2 ≤20%). No difference in the outcomes of early neurological improvement, symptomatic intracranial hemorrhage, any intracranial hemorrhage, and the rates of modified Rankin Scale score 0 to 1 or all-cause mortality at 3 months was detected between patients with LVO receiving intravenous thrombolysis with either tenecteplase or alteplase. Conclusions: Acute ischemic stroke patients with LVO receiving intravenous thrombolysis with tenecteplase have significantly better recanalization and clinical outcomes compared with patients receiving intravenous alteplase.

Background Intravenous recombinant tissue plasminogen activator is the only proven effective medication for the treatment of acute ischemic stroke. Two approaches that may augment recombinant tissue plasminogen activator thrombolysis and prevent arterial reocclusion are direct thrombin inhibition with argatroban and inhibition of the glycoprotein 2b/3a receptor with eptifibatide. Aim The multi-arm optimization of stroke thrombolysis trial aims to determine the safety and efficacy of intravenous therapy with argatroban or eptifibatide as compared with placebo in acute ischemic stroke patients treated with intravenous recombinant tissue plasminogen activator within 3 h of symptom onset. Sample size estimate A maximum of 1200 randomized subjects to test the superiority of argatroban or eptifibatide to placebo in improving 90-day modified Rankin scores. Methods and design Multiarm optimization of stroke thrombolysis is a multicenter, multiarm, adaptive, single blind, randomized controlled phase 3 clinical trial conducted within the National Institutes of Health StrokeNet clinical trial network. Patients treated with 0.9 mg/kg intravenous recombinant tissue plasminogen activator within 3 h of stroke symptom onset are randomized to receive intravenous argatroban (100 µg/kg bolus followed by 3 µg/kg/min for 12 h), intravenous eptifibatide (135 µg/kg bolus followed by 0.75 µg/kg/min infusion for 2 h) or IV placebo. Patients may receive endovascular thrombectomy per usual care. Study outcomes The primary efficacy outcome is improved modified Rankin score assessed at 90 days post-randomization. Discussion Multiarm optimization of stroke thrombolysis is an innovative and collaborative project that is the culmination of many years of dedicated efforts to improve outcomes for stroke patients.

SUMMARY: Small vessel disease, a disorder of cerebral microvessels, is an expanding epidemic and a common cause of stroke and dementia. Despite being almost ubiquitous in brain imaging, the clinicoradiologic association of small vessel disease is weak, and the underlying pathogenesis is poorly understood. The STandards for ReportIng Vascular changes on nEuroimaging (STRIVE) criteria have standardized the nomenclature. These include white matter hyperintensities of presumed vascular origin, recent small subcortical infarcts, lacunes of presumed vascular origin, prominent perivascular spaces, cerebral microbleeds, superficial siderosis, cortical microinfarcts, and brain atrophy. Recently, the rigid categories among cognitive impairment, vascular dementia, stroke, and small vessel disease have become outdated, with a greater emphasis on brain health. Conventional and advanced small vessel disease imaging markers allow a comprehensive assessment of global brain heath. In this review, we discuss the pathophysiology of small vessel disease neuroimaging nomenclature by means of the STRIVE criteria, clinical implications, the role of advanced imaging, and future directions.

Background and Purpose— The first of the 2 NINDS (National Institute of Neurological Disorders and Stroke) Study trials did not show a significant increase in early neurological improvement, defined as National Institutes of Health Stroke Scale (NIHSS) improvement by ≥4, with alteplase treatment. We hypothesized that early neurological improvement defined as a percentage change in NIHSS (percent change NIHSS) at 24 hours is superior to other definitions in predicting 3-month functional outcomes and using this definition there would be treatment benefit of alteplase over placebo at 24 hours. Methods— We analyzed the NINDS rt-PA Stroke Study (Parts 1 and 2) trial data. Percent change NIHSS was defined as ([admission NIHSS score−24-hour NIHSS score]×100/admission NIHSS score] and delta NIHSS as (admission NIHSS score−24-hour NIHSS score). We compared early neurological improvement using these definitions between alteplase versus placebo patients. We also used receiver operating characteristic curve to determine the predictive association of early neurological improvement with excellent 3-month functional outcomes (Barthel Index score of 95–100 and modified Rankin Scale score of 0–1), good 3-month functional outcome (modified Rankin Scale score of 0–2), and 3-month infarct volume. Results— There was a significantly greater improvement in the 24-hour median percent change NIHSS among patients treated with alteplase compared with the placebo group (28% versus 15%; P =0.045) but not median delta NIHSS (3 versus 2; P =0.471). Receiver operating characteristic curve comparison showed that percent change NIHSS (ROC percent ) was better than delta NIHSS (ROC delta ) and admission NIHSS (ROC admission ) with regards to excellent 3-month Barthel Index (ROC percent , 0.83; ROC delta , 0.76; ROC admission , 0.75), excellent 3-month modified Rankin Scale (ROC percent , 0.83; ROC delta , 0.74; ROC admission , 0.78), and good 3-month modified Rankin Scale (ROC percent , 0.83; ROC delta , 0.76; ROC admission , 0.78). Conclusions— In the NINDS rt-PA trial, alteplase was associated with a significant percent change improvement in NIHSS at 24 hours. Percent change in NIHSS may be a better surrogate marker of thrombolytic activity and 3-month outcomes.

BACKGROUND AND PURPOSE: The increased severity of white matter disease is associated with worse outcomes and an increased rate of intracerebral hemorrhage in patients with ischemic stroke undergoing thrombolytic treatment. However, whether white matter disease is associated with outcomes in patients undergoing endovascular treatment remains unclear. MATERIALS AND METHODS: In this prespecified exploratory analysis of our prospective multi-institutional study that enrolled consecutive adult patients with anterior circulation ischemic stroke undergoing endovascular treatment from November 2017 to September 2018, we compared the following outcomes between patients with none-to-minimal (van Swieten score, 0–2) and moderate-to-severe (van Swieten score, 3–4) white matter disease using logistic regression: 90-day mRS 3–6, death, intracerebral hemorrhage, successful recanalization, and early neurologic recovery. RESULTS: Of the 485 patients enrolled in the Blood Pressure after Endovascular Stroke Therapy (BEST) study, 389 had white matter disease graded (50% women; median age, 68 years; range, 58–79 years). A van Swieten score of 3–4 (n = 74/389, 19%) was associated with a higher rate of 90-day mRS of 3–6 (45% versus 18%; adjusted OR, 2.73; 95% CI, 1.34–5.93; P = .008). Although the death rate was higher in patients with van Swieten scores of 3–4 (26% versus 15%), the adjusted likelihood was not significantly different (adjusted OR, 1.14; 95% CI, 0.56–2.26; P = .710). Ordered regression revealed a shift toward worse mRS scores with increasing van Swieten scores (adjusted common OR, 3.04; 95% CI, 1.93–4.84; P

Limited data exist evaluating the effect of blood pressure (BP) on clinical outcomes among patients with acute ischemic stroke with large vessel occlusion treated with mechanical thrombectomy (MT). We sought to evaluate the association of BP levels on clinical outcomes among patients with acute ischemic stroke with large vessel occlusion treated with MT. Studies were identified that reported the association of systolic BP (SBP) or diastolic BP levels before, during, or after MT on the outcomes of patients with acute ischemic stroke treated with MT. Unadjusted and adjusted analyses of studies reporting odds ratios (OR adj ) per 10 mm Hg BP increment were performed. Our analysis included 25 studies comprising 6474 patients. Higher pre-MT mean SBP ( P =0.008) and post-MT maximum SBP ( P =0.009) levels were observed in patients who died within 3 months. Patients with 3-month functional independence were noted to have lower pre-MT ( P P adj , 1.19 [95% CI,1.00–1.43]; I 2 =78%, P value for Cochran Q test: 0.001) and symptomatic intracranial hemorrhage (OR adj , 1.65 [95% CI, 1.11–2.44]; I 2 =0%, P value for Cochran Q test: 0.80), respectively. Increasing pre- and post-MT mean SBP levels were associated with lower odds of 3-month functional independence (OR adj , 0.86 [95% CI, 0.77–0.96]; I 2 =18%, P value for Cochran Q test: 0.30) and (OR adj , 0.80 [95% CI, 0.72–0.89]; I 2 =0%, P value for Cochran Q test: 0.51), respectively. In conclusion, elevated BP levels before and after MT are associated with adverse outcomes among patients with acute ischemic stroke with large vessel occlusion.

Ocean waves are an abundant source of energy. This energy of the ocean can be converted into useful electrical energy using electrical generators. Linear generators have received tremendous attention in energy harvesting technology due to its unique ability to convert the energy without any intermediate converter. The principal objective of this study is to present the various types of linear electrical generators which have been investigated so far for direct drive ocean wave energy conversion and describe the working principle of each type with the difference. In this study, after a brief description of the basic electrical generator, various types of generators, including the linear and flat generators available in the literature are reviewed and discussed based on the design configuration of different types of magnet arrangements. Linear generators have been compared in terms of core type, flux path, the location of PMs, etc. The research gaps have been identified and future research directions have been suggested.

Background and Purpose: Clinical fluctuations in ischemic stroke symptoms are common, but fluctuations before hospital arrival have not been previously characterized. Methods: A standardized qualitative assessment of fluctuations before hospital arrival was obtained in an observational study that enrolled patients with mild ischemic stroke symptoms (National Institutes of Health Stroke Scale [NIHSS] score of 0–5) present on arrival to hospital within 4.5 hours of onset, in a subset of 100 hospitals participating in the Get With The Guidelines–Stroke quality improvement program. The number of fluctuations, direction, and the overall improvement or worsening was recorded based on reports from the patient, family, or paramedics. Baseline NIHSS on arrival and at 72 hours (or discharge if before) and final diagnosis and stroke subtype were collected. Outcomes at 90 days included the modified Rankin Scale, Barthel Index, Stroke Impact Scale 16, and European Quality of Life. Prehospital fluctuations were examined in relation to hospital NIHSS change (admission to 72 hours or discharge) and 90-day outcomes. Results: Among 1588 participants, prehospital fluctuations, consisting of improvement, worsening, or both were observed in 35.5%: 25.1% improved once, 5.3% worsened once, and 5.1% had more than 1 fluctuation. Those who improved were less likely and those who worsened were more likely to receive alteplase. Those who improved before hospital arrival had lower change in the hospital NIHSS than those who did not fluctuate. Better adjusted 90-day outcomes were noted in those with prehospital improvement compared to those without any fluctuations. Conclusions: Fluctuations in neurological symptoms and signs are common in the prehospital setting. Prehospital improvement was associated with better 90-day outcomes, controlling for admission NIHSS and alteplase treatment. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT 02072681.

Background: It is unclear what factors clinicians consider when deciding about endovascular thrombectomy (EVT) in acute ischemic stroke patients with a pre-existing disability. We aimed to explore international practice patterns and preferences for EVT in patients with a pre-stroke disability, defined as a modified Rankin score (mRS) ≥ 2.Methods: Electronic survey link was sent to principal investigators of five major EVT trials and members of a professional interventional neurology society.Results: Of the 81 survey-responding clinicians, 57% were neuro-interventionalists and 33% were non-interventional stroke clinicians. Overall, 64.2% would never or almost never consider EVT for a patient with pre-stroke mRS of 4-5, and 49.3% would always or almost always offer EVT for a patient with pre-stroke mRS 2-3. Perceived benefit of EVT (89%) and severity of baseline disability (83.5%) were identified as the most important clinician-level and patient-level factors that influence EVT decisions in these patients.Conclusion: In this survey of 80 respondents, we found that EVT practice for patients with pre-stroke disability across the world is heterogenous and depends upon patient characteristics. Individual clinician opinions substantially alter EVT decisions in pre-stroke disabled patients.

Background and Purpose: Mild ischemic stroke patients enrolled in randomized controlled trials of thrombolysis may have a different symptom severity distribution than those treated in routine clinical practice. Methods: We compared the distribution of the National Institutes of Health Stroke Scale (NIHSS) scores, neurological symptoms/severity among patients enrolled in the PRISMS (Potential of r-tPA for Ischemic Strokes With Mild Symptoms) randomized controlled trial to those with NIHSS score ≤5 enrolled in the prospective MaRISS (Mild and Rapidly Improving Stroke Study) registry using global P values from χ 2 analyses. Results: Among 1736 participants in MaRISS, 972 (56%) were treated with alteplase and 764 (44%) were not. These participants were compared with 313 patients randomized in PRISMS. The median NIHSS scores were 3 (2–4) in MaRISS alteplase-treated, 1 (1–3) in MaRISS non–alteplase-treated, and 2 (1–3) in PRISMS. The percentage with an NIHSS score of 0 to 2 was 36.3%, 73.3%, and 65.2% in the 3 groups, respectively ( P P Conclusions: Patients randomized in PRISMS had comparable deficit and syndromic severity to patients not treated with alteplase in the MaRISS registry and lesser severity than patients treated with alteplase in MaRISS. The PRISMS trial cohort is representative of mild patients who do not receive alteplase in current broad clinical practice.

The first European Stroke Organization (ESO) standard operating procedure (SOP) published in 2015 aimed at the implementation the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to provide evidence-based guidelines for stroke management. This second ESO-SOP is aiming at further increase of the practicability of ESO guidelines and its technical implications. Authors comprised of the members of the ESO guideline Board and ESO Executive Committee. The final document was agreed on by several internal reviews. The second SOP comprises of the following aspects: rational for the SOP, the introduction of expert consensus statements, types of guideline documents, structures involved and detailed description of the guideline preparation process, handling of financial and intellectual conflicts of interest (CoI), involvement of ESO members in the guideline process, review process, authorship and publication policy, updating of guidelines, cooperation with other societies, and dealing with falsified data. This second SOP supersedes the first SOP published in 2015.

Introduction Intracerebral hemorrhage is the deadliest form of stroke. Hematoma expansion, growth of the hematoma between the baseline computed tomography scan and a follow-up computed tomography scan at 24 ± 6 h, predicts long-term disability or death. Recombinant factor VIIa (rFVIIa) has reduced hematoma expansion in previous clinical trials with a variable effect on clinical outcomes, with the greatest impact on hematoma expansion and potential benefit when administered within 2 h of symptom onset. Methods Factor VIIa for Hemorrhagic Stroke Treatment at Earliest Possible Time (FASTEST, NCT03496883) is a randomized controlled trial that will enroll 860 patients at ∼100 emergency departments and mobile stroke units in five countries. Patients are eligible for enrollment if they have acute intracerebral hemorrhage within 2 h of symptom onset confirmed by computed tomography, a hematoma volume of 2 to 60 mL, no or small volumes of intraventricular hemorrhage, do not take anticoagulant medications or concurrent heparin/heparinoids (antiplatelet medications are permissible), and are not deeply comatose. Enrolled patients will receive rFVIIa 80 µg/kg or placebo intravenously over 2 min. The primary outcome measure is the distribution of the ordinal modified Rankin Scale at 180 days. FASTEST is monitored by a Data Safety Monitoring Board. Safety endpoints include thrombotic events (e.g. myocardial infarction). Human subjects research is monitored by an external Institutional Review Board in participating countries. Discussion In the US, FASTEST will be first NIH StrokeNet Trial with an Exception from Informed Consent which allows enrollment of non-communicative patients without an immediately identifiable proxy.

The modified Rankin Scale (mRS), a 7-level, clinician-reported, measure of global disability, is the most widely employed outcome scale in acute stroke trials. The scale’s original development preceded the advent of modern clinimetrics, but substantial subsequent work has been performed to enable the mRS to meet robust contemporary scale standards. Prior research and consensus recommendations have focused on modernizing 2 aspects of the mRS: operationalized assignment of scale scores and statistical analysis of scale distributions. Another important characteristic of the mRS still requiring elaboration and specification to contemporary clinimetric standards is the Naming of scale outcomes. Recent clinical trials have used a bewildering variety, often mutually contradictory, of rubrics to describe scale states. Understanding of the meaning of mRS outcomes by clinicians, patients, and other clinical trial stakeholders would be greatly enhanced by use of a harmonized, uniform set of labels for the distinctive mRS outcomes that would be used consistently across trials. This statement advances such recommended rubrics, developed by the Stroke Therapy Academic Industry Roundtable collaboration using an iterative, mixed-methods process. Specific guidance is provided for health state terms (eg, Symptomatic but Nondisabled for mRS score 1; requires constant care for mRS score 5) and valence terms (eg, excellent for mRS score 1; very poor for mRS score 5) to employ for 23 distinct numeric mRS outcomes, including: all individual 7 mRS levels; all 12 positive and negative dichotomized mRS ranges, positive and negative sliding dichotomies; and utility-weighted analysis of the mRS.

BACKGROUND AND PURPOSE In patients with symptomatic vertebrobasilar intracranial atherosclerotic disease (ICAD), impaired distal flow predicts recurrent stroke, but limited data exist on the association between perfusion status and recurrent stroke in anterior circulation ICAD. METHODS This is a retrospective study of patients hospitalized for symptomatic ICAD with 50-99% stenosis of the intracranial carotid or middle cerebral artery. The primary outcome is recurrent symptomatic ischemic stroke in the territory of the artery with ≥50% stenosis within 90 days. The primary predictor is distal hypoperfusion on magnetic resonance (MR) or computed tomography (CT) perfusion, defined as a ≥15 mL volume of territory of the symptomatic artery with Tmax >6 seconds. RESULTS Fifty patients met inclusion criteria, including 15 (30%) with recurrent stroke and 15 (30%) with distal hypoperfusion. Distal hypoperfusion was present in 10 of 15 (66.7%) with recurrent stroke versus 5 of 35 (14.3%) without recurrent stroke (P

Recent positive trials have thrust acute cerebral perfusion imaging into the routine evaluation of acute ischemic stroke. Updated guidelines state that in patients with anterior circulation large vessel occlusions presenting beyond 6 hours from time last known well, advanced imaging selection including perfusion-based selection is necessary. Centers that receive patients with acute stroke must now have the capability to perform and interpret CT or magnetic resonance perfusion imaging or provide rapid transfer to centers with the capability of selecting patients for a highly impactful endovascular therapy, particularly in delayed time windows. Many stroke centers are quickly incorporating the use of automated perfusion processing software to interpret perfusion raw data. As CT perfusion (CTP) is being assimilated in real-world clinical practice, it is essential to understand the basics of perfusion acquisition, quantification, and interpretation. It is equally important to recognize the common technical and clinical diagnostic challenges of automated CTP including ischemic core and penumbral misclassifications that could result in underestimation or overestimation of the core and penumbra volumes. This review highlights the pitfalls of automated CTP along with practical pearls to address the common challenges. This is particularly tailored to aid the acute stroke clinician who must interpret automated perfusion studies in an emergency setting to make time-dependent treatment decisions for patients with acute ischemic stroke.

Treatment of acute ischemic stroke (AIS) has evolved significantly in the past few years. Endovascular treatment (EVT) is now proved to be efficacious up to 24 hours from onset in properly selected patients. The recently updated 2018 American Heart Association-American Stroke Association guidelines reflect the important role of imaging in triage and patient selection for EVT of AIS. Pretreatment imaging in patients with acute stroke should (a) allow assessment for intracranial hemorrhage and demonstrate (b) the extent of early ischemic changes, (c) the presence of large arterial occlusion, and (d) in some cases potential salvageable tissue before the decision to proceed with EVT. The authors review how multimodality imaging can be used for EVT selection in the context of the recent guidelines. They highlight the importance of having streamlined imaging workflows that are integrated with clinical decision making to maximize treatment efficiency. Knowledge of the various imaging criteria including perfusion imaging used for EVT selection is highlighted. The authors discuss variable imaging paradigms used for selection of patients in the early and late windows (who present before vs after 6 hours from onset of symptoms), as reflected in the latest guidelines and in relation to their level of evidence. Finally, they focus on challenges in the subgroups of patients who were excluded from recent EVT trials and with limited evidence to prove the efficacy of EVT, such as patients with low NIHSS (National Institutes of Health Stroke Scale) score, distal occlusion, or large ischemic core. ©RSNA, 2019 See discussion on this article by Leslie-Mazwi.

Rationale Although mild and rapidly improving stroke symptoms are the most common first stroke presentation, this group has been understudied in acute stroke trials. Observational and retrospective studies suggest residual disability in one third of patients. Aims To elucidate long-term outcomes of patients with mild and rapidly improving stroke, evaluate the predictors of outcome, and examine the association with alteplase treatment. Sample size The initial estimate of 2650 participants to detect a 9% difference in non-disabled 90-day outcomes between alteplase-treated and untreated participants was revised to 2000 after a pre-planned re-estimation based on actual treatment rates. Methods and design Prospective observational study of patients with mild ischemic stroke (NIHSS ≤ 5) or rapidly improving stroke symptoms evaluated within 4.5 h from onset. Outcomes The primary outcome is the proportion of patients with modified Rankin Scale (mRS) ≥ 2 at 90 days; the primary safety outcome is symptomatic hemorrhagic transformation within 36 h among those treated with alteplase. Secondary outcomes include the 90-day Barthel Index, Stroke Impact Scale 16, European Quality of Life scale, mRS at 30 days, and 30- and 90-day mortality. Discussion MaRISS will define outcomes and their predictors and clarify the effects of alteplase in patients with mild and rapidly improving stroke symptoms, providing clinicians with important information to manage this population.

Objective The substantial clinical improvement in acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT), combined with the poor response of proximal intracranial occlusions to intravenous thrombolysis (IVT), led to questions regarding the utility of bridging therapy (BT; IVT followed by MT) compared to direct mechanical thrombectomy (dMT) for AIS patients with large vessel occlusion (LVO). Methods We aimed to investigate the comparative safety and efficacy of BT and dMT in AIS patients. We included all observational studies and post hoc analyses from randomized controlled clinical trials that provided data on the outcomes of AIS patients with LVO stratified by IVT treatment status prior to MT. Results We identified 38 eligible observational studies (11,798 LVO patients, mean age = 68 years, 56% treated with BT). In unadjusted analyses, BT was associated with a higher likelihood of 3-month functional independence (odds ratio [OR] = 1.52, 95% confidence interval [CI] = 1.32-1.76), 3-month functional improvement (common OR [cOR] for 1-point decrease in modified Rankin Scale score = 1.52, 95% CI = 1.18-1.97), early neurological improvement (OR = 1.21, 95% CI = 1.83-1.76), successful recanalization (OR = 1.22, 95% CI = 1.02-1.46), and successful recanalization with ≤2 device passes (OR = 2.28, 95% CI = 1.43-3.64) compared to dMT. BT was also related to a lower likelihood of 3-month mortality (OR = 0.64, 95% CI = 0.57-0.73). In the adjusted analyses, BT was independently associated with a higher likelihood of 3-month functional independence (adjusted OR = 1.55, 95% CI = 1.26-1.91) and lower odds of 3-month mortality (adjusted OR = 0.80, 95% CI = 0.66-0.97) compared to dMT. The two groups did not differ in functional improvement (adjusted cOR = 1.24, 95% CI = 0.89-1.74) or symptomatic intracranial hemorrhage (adjusted OR = 0.87, 95% CI = 0.61-1.25). Interpretation BT appears to be associated with improved functional independence without evidence for safety concerns, compared to dMT, for AIS patients with LVO. ANN NEUROL 2019;86:395-406.

Background and purpose Studies have shown an association between infarct patterns and recurrent stroke in patients with symptomatic intracranial stenosis (sICAS) but there are limited data on associations with perfusion imaging mismatch profile. We aim to determine the association between infarct pattern, optimal mismatch profile definition, and recurrent cerebrovascular events (RCVE) in patients with anterior circulation sICAS. Methods This is a retrospective study of consecutive patients with acutely sICAS admitted to a comprehensive stroke center over 18 month's period. Patients with sICAS underwent magnetic resonance perfusion (MRP) imaging within 24 hours from admission. Infarct patterns (internal BZ [IBZ], cortical BZ [CBZ], and core/perforator [C/P]) and RCVE within 90 days, were independently adjudicated by two reviewers. We compared mismatch profiles and recurrent event rates across infarct patterns. Results Twenty-five patients met inclusion criteria; 28% had IBZ infarcts and overall RCVE rate was 32.0%. When compared to patients without IBZ infarcts, those with IBZ infarcts were more likely to have a target mismatch profile using Tmax > 6 seconds (60% vs. 6.7%, P = .007) and RCVE (62.5% vs. 11.8%, P = .01). There were no associations between CBZ and C/P infarcts and target mismatch profiles and RCVE. Conclusion IBZ infarcts may be a surrogate marker of distal perfusion status and RCVE risk. Larger multicenter, prospective, core-lab blindly adjudicated studies are needed to confirm our findings.

Background Mechanical thrombectomy (MT) has become the cornerstone of acute ischaemic stroke management in patients with large vessel occlusion (LVO). The aim of this guideline document is to assist physicians in their clinical decisions with regard to MT. Methods These Guidelines were developed based on the standard operating procedure of the European Stroke Organisation and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. An interdisciplinary working group identified 15 relevant questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote evidence based recommendations. Expert opinion was provided if not enough evidence was available to provide recommendations based on the GRADE approach. Results We found high quality evidence to recommend MT plus best medical management (BMM, including intravenous thrombolysis whenever indicated) to improve functional outcome in patients with LVO-related acute ischaemic stroke within 6 hours after symptom onset. We found moderate quality of evidence to recommend MT plus BMM in the 6-24h time window in patients meeting the eligibility criteria of published randomized trials. These guidelines further detail aspects of prehospital management, patient selection based on clinical and imaging characteristics, and treatment modalities. Conclusions MT is the standard of care in patients with LVO-related acute stroke. Appropriate patient selection and timely reperfusion are crucial. Further randomized trials are needed to inform clinical decision making with regard to the mothership and drip-and-ship approaches, anesthaesia modalities during MT, and to determine whether MT is beneficial in patients with low stroke severity or large infarct volume.

BackgroundMechanical thrombectomy (MT) has become the cornerstone of acute ischemic stroke management in patients with large vessel occlusion (LVO).ObjectiveTo assist physicians in their clinical decisions with regard toMT.MethodsThese guidelines were developed based on the standard operating procedure of the European Stroke Organisation and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. An interdisciplinary working group identified 15 relevant questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote evidence-based recommendations. Expert opinion was provided if not enough evidence was available to provide recommendations based on the GRADE approach.ResultsWe found high-quality evidence to recommend MT plus best medical management (BMM, including intravenous thrombolysis whenever indicated) to improve functional outcome in patients with LVO-related acute ischemic stroke within 6 hours after symptom onset. We found moderate quality of evidence to recommend MT plus BMM in the 6–24h time window in patients meeting the eligibility criteria of published randomized trials. These guidelinesdetails aspects of prehospital management, patient selection based on clinical and imaging characteristics, and treatment modalities.ConclusionsMT is the standard of care in patients with LVO-related acute stroke. Appropriate patient selection and timely reperfusion are crucial. Further randomized trials are needed to inform clinical decision-making with regard tothe mothership and drip-and-ship approaches, anesthaesia modalities during MT, and to determine whether MT is beneficial in patients with low stroke severity or large infarct volume.

Background and ObjectivesTo explore the association between blood pressure (BP) levels after endovascular thrombectomy (EVT) and the clinical outcomes of patients with acute ischemic stroke (AIS) patients with large vessel occlusion (LVO).MethodsA study was eligible if it enrolled patients with AIS >18 years of age with an LVO treated with either successful or unsuccessful EVT and provided either individual or mean 24-hour systolic BP values after the end of the EVT procedure. Individual patient data from all studies were analyzed with a generalized linear mixed-effects model.ResultsA total of 5,874 patients (mean age 69 ± 14 years; 50% women; median NIH Stroke Scale score on admission 16) from 7 published studies were included. Increasing mean systolic BP levels per 10 mm Hg during the first 24 hours after the end of the EVT were associated with a lower odds of functional improvement (unadjusted common odds ratio [OR] 0.82, 95% confidence interval [CI] 0.80–0.85; adjusted common OR 0.88, 95% CI 0.84–0.93) and modified Rankin Scale score ≤2 (unadjusted OR 0.82, 95% CI 0.79–0.85; adjusted OR 0.87, 95% CI 0.82–0.93) and a higher odds of all-cause mortality (unadjusted OR 1.18, 95% CI 1.13–1.24; adjusted OR 1.15, 95% CI 1.06–1.23) at 3 months. Higher 24-hour mean systolic BP levels were also associated with an increased likelihood of early neurologic deterioration (unadjusted OR 1.14, 95% CI 1.07–1.21; adjusted OR 1.14, 95% CI 1.03–1.24) and a higher odds of symptomatic intracranial hemorrhage (unadjusted OR 1.20, 95% CI 1.09–1.29; adjusted OR 1.20, 95% CI 1.03–1.38) after EVT.DiscussionIncreased mean systolic BP levels in the first 24 hours after EVT are independently associated with a higher odds of symptomatic intracranial hemorrhage, early neurologic deterioration, 3-month mortality, and worse 3-month functional outcomes.

Background: The University of Cincinnati Stroke Team provides acute stroke care to the southwest Ohio, northern Kentucky, and southeast Indiana catchment area of ~2 million people and 30 healthcare facilities. We previously published a significant decline in stroke activations and reperfusion treatment (IV thrombolysis and EVT) rates following state announcements of COVID-19 mitigation measures. Here, we update these trends after state reopening guidelines. Methods: We compared Stroke Team activations and reperfusion treatments logged in a prospectively collected database, comparing the same period in 2020 versus 2019. Kentucky and Ohio announced school and restaurant closures on March 12 and 13, respectively, followed by Indiana. A stepwise reopening of our tristate area started on May 1, 2020. We also compared trends in activations and treatment rates before (Weeks 1-10), during (Weeks 11-17), and after (Weeks 18-26) the lifting of COVID-19 mitigation efforts using the Poisson test, and graphically with segmented regression analysis. Results: Compared to 2019, stroke team activations declined by 12% in 2020 (95% CI 7 - 16%; p Conclusion: The initial decline in stroke team activations during COVID-19 mitigation efforts was followed by an increase in activations after reopening. Hospital capacity and 911 services remained fully intact, suggesting that the reduction in activations were related to reduced presentation by patients for emergent stroke care.

Objective: We aim to investigate infarct patterns and 90-day recurrence in patients with symptomatic intracranial atherosclerotic disease. Background: Large artery atherosclerosis subtype carries a high risk of early recurrent stroke despite medical management. Predictors of recurrence remain poorly understood. We hypothesized that border-zone infarcts are associated with a higher risk of recurrence. Design/Methods: We included consecutive patients admitted to NYU Langone Health (Manhattan and Brooklyn campuses) over 32-months with a diagnosis of acute ischemic stroke secondary to symptomatic intracranial or tandem atherosclerosis. Patients with purely extracranial stenosis were excluded. The primary predictor was infarct pattern (border-zone vs. non-border-zone infarction), defined in accordance to previous studies. We used univariate and multivariable cox-regression models to determine associations between infarct pattern and recurrent cerebrovascular events (RCVE) at 90-days. Results: Ninety-nine patients met the inclusion criteria; 95 were intracranial and 4 were tandem lesions. The mean age was 70 years, 58.6% were men, 15.1% Black and 16.1% Asian. The median symptom onset to arrival time was 1 day, nearly 74.7% of patients were treated with dual antiplatelet therapy and 99% were treated with high intensity statin. Within 90 days of follow up, 19.2% (19/99) had RCVE. In univariate analyses, the only factor associated with RCVE was border-zone infarct pattern when compared to non-border-zone infarct pattern (30.2% vs. 10.7%, p=0.02). In cox regression models, after adjusting for age and sex, border-zone infarct pattern was associated with increased risk of RCVE (adjusted HR 3.21 95% CI 1.21-8.51, p=0.019). Sensitivity analyses excluding patients with tandem lesions (n = 4) did not meaningfully change our findings (adjusted HR 3.04 95% CI 1.11-8.31, p=0.031). Conclusions: In real world post-SAMMPRIS medically treated patients with ICAD, infarct pattern was predictive of 90-day RCVE. Border-zone infarcts are likely a surrogate marker of impaired distal blood flow, highlighting the importance of targeting stroke mechanisms and developing alternative treatment strategies for this high-risk cohort.

Background: Hypertension is an important risk factor in the development of acute ischemic stroke (AIS). African American (AA) race is strongly associated with both hypertension and uncontrolled hypertension despite treatment, yet little is known about racial differences in presenting blood pressure (BP) in AIS. This study sought to describe differences in presenting BP and acute antihypertensive treatment between AA and white AIS patients who received and did not receive alteplase within a population. Methods: Using the Greater Cincinnati/Northern Kentucky Stroke Study (GCNKSS) database for years 2005, 2010 and 2015, we selected patients with a diagnosis of AIS using ICD-9/10 codes in adults ≥ 18 yrs of age presenting to a local ED within 4.5 hrs of symptom onset. Candidates were stratified by race and alteplase use. Socio-demographics, stroke risk factors, stroke severity, BP on arrival, and acute BP treatment were compared using chi-square, t-tests or Wilcoxon rank sum test, as appropriate. Results (Table 1): Of 1838 AIS patients included in the analysis, 392 (21%) received IV alteplase. AA patients were younger in both groups who received and did not receive alteplase. On presentation, AA stroke patients had higher diastolic BP. AA patients were more likely to receive 2 or more BP lowering medications compared to white patients in the alteplase treated group and the untreated group. Conclusion: AA patients presenting within 4.5 hours of AIS symptom onset are more likely to have elevated diastolic BP and to receive multiple BP lowering medications compared to white patients. These findings were significant regardless of alteplase treatment. To our knowledge, we report the first population-based distribution of BP, and medical treatment of BP, upon presentation to an ED in AIS. Further study is needed to determine if these racial differences in elevated BP and refractoriness of BP and/or aggressive treatment contribute to outcome differences.

Introduction: Patients without prior functional deficits who suffer mild stroke (NIHSS Methods: Hospitalized strokes from the Greater Cincinnati Northern Kentucky Stroke Study were used. Included patients had an initial NIHSS Results: Of 1268 ischemic strokes, 353 (28%) were functionally dependent at discharge. Increased baseline NIHSS was associated with worse outcome on the mRS. Leg, LOC questions, and sensation NIHSS subscores were the best predictors of outcome. Multivariable analysis identified age, race, hypertension, chronic kidney disease, heart failure, and post-stroke dysphagia as independently associated with discharge mRS ≥3. Discussion: Our results agree with and complement the results of prior studies. They are not limited by inclusion/exclusion criteria or referral bias. Rather, our major limitation is the retrospective estimation of NIHSS and mRS based on physician descriptive documentation rather than direct score assessment. Our results may allow for modeling to better predict outcome which in turn can inform clinical decision making and trial design.

Introduction: A main goal for hospital admission following acute ischemic stroke (AIS) is to establish the mechanism of stroke (MoS) allowing for patient specific secondary prevention of stroke interventions. We previously reported on diagnostic testing trends and MoS determination from 1993 through 2010. We updated this analysis with 2015 data to better understand the effects of trends in diagnostic testing on MoS determination. Methods: Patients with AIS aged > 20 years from all study time periods (Table) of the population based GCNKSS were included. Charts were abstracted in a systematic way for tests performed during the hospital stay. Only first-ever ischemic stroke cases, evaluated in an emergency department were used for this analysis. Stroke experts reviewed these events and adjudicated the mechanism of stroke according to modified TOAST criteria. We looked at and compared trends for testing and MoS. Results: Our analysis included 7226 patients. Basic patient demographics, MoS categories and tests across study periods are detailed in the Table. There were significant increases in EKG (7%), TTE (35%), TEE (7%), HCT (4%), brain MRI (65%), MRA (30%) and CTA (28%). Across study periods, cardioembolic (4.1%), small vessel disease (3%), large artery disease (0.9%) and other (1.5%) MoS increased while unknown MoS decreased (-9.5%). Discussion: From 1993/1994 to 2015 there has been a significant increase of in-hospital testing in AIS and decreases in undetermined MoS. Cardioembolic and small vessel disease MoS categories increased the most. Despite a significant increase in vessel imaging, large artery disease and “other determined” MoS categories are largely unchanged. Further research is required to elucidate the occult MoS underlying the undetermined category. Based on our analysis it appears unlikely to be significantly associated with our current definition of stroke associated with large artery disease defined as ≥ 50% ipsilateral stenosis.

Introduction: The availability of rapid tissue and vessel imaging for TIA has increased, but the utilization rates of these and other diagnostic and management strategies for TIA over time are unknown. Objective: To investigate trends in TIA diagnostic and management strategies over time in the Greater Cincinnati Northern Kentucky Stroke Study (GCNKSS). Methods: The GCNKSS is a population-based study of 1.3 million people living in a 5-county area of southern Ohio and Northern Kentucky. For this study, all physician-adjudicated, first-ever cases of TIA (defined clinically as sudden onset of focal symptoms lasting < 24 hours) presenting to an emergency department over five study periods (1993/4, 1999, 2005, 2010, 2015) were included. Use of AHA-recommended aspects of TIA management as well as disposition of TIA patients (admission to hospital or discharge from ED) and length of stay were compared across study periods. Rates of acute infarct on MRI were also reported. Trends were examined using the Cochran-Armitage test for trend. Results: In total, over all study periods, there were 2251 first-ever TIAs. Overall, 14% (n=311) occurred in Black individuals, and 57% (n=1275) occurred in women. Utilization of diagnostic modalities [non-contrast CT brain, vascular imaging (CTA, MRA, or carotid dopplers), tissue imaging (MRI), and echocardiogram] increased significantly over time (all p Conclusions: The management of TIA has changed significantly over time. Utilization of tissue and vessel imaging as well as echocardiogram during the hospital stay has increased; in 2015, the vast majority of patients with TIA in this population-based study received each of these testing modalities and were admitted to a hospital for TIA work-up. Further work is needed to understand the best practices for work-up of suspected TIA.

Background: Functional outcomes are improved when AIS patients receive faster treatment. The first medical contact for many AIS patients is with emergency medical services (EMS) providers. We hypothesize that AIS treatment is faster when EMS providers suspect stroke. Methods: We performed a retrospective analysis of the Greater Cincinnati/Northern Kentucky Stroke Study, a comprehensive study of stroke patients in a large geographical area with 1.3 million inhabitants whose demographics are representative of the United States. We compared AIS patients age ≥18 years transported by EMS in 2015 with an EMS impression of “stroke” or “weakness/numbness” to those with other EMS impressions. Primary outcome was thrombolysis rate, and secondary outcomes were times from EMS scene arrival to ED arrival, CT, and treatment and times from ED arrival to CT and treatment. Chi-square and Mann-Whitney U-tests were used to compare treatment rates and times, respectively. Logistic regression (for rates) and median regression (for times) adjusted for NIHSS, GCS, age, sex, race, and prior stroke history. Results: Among 2,486 confirmed AIS patients from 1/1/2015-12/31/2015, 868 were transported by EMS, including 595 (69%) with EMS suspected stroke. Compared to EMS non-suspected strokes, patients with EMS suspected stroke patients were more likely to receive thrombolysis (18% vs 8%; OR 2.67, 95% CI 1.63-4.47) and had faster prehospital transport (30 vs 32 min, p=0.02), ED arrival to CT (27 vs 46 min, p Conclusions: In a large population-based study, EMS stroke identification is associated with a higher rate of and faster thrombolysis. Efforts to increase accuracy of EMS stroke identification is likely to have significant clinical impact by shortening treatment times.

Background: Although most strokes present with mild symptoms, these have been poorly represented in clinical trials. The objective is to describe multidimensional outcomes, identify predictors of worse outcomes and explore the effect of thrombolysis in this population. Methods: This prospective observational study included patients with ischemic stroke or TIA presenting with stroke symptoms and a baseline NIHSS 0-5 within 4.5 hours from symptom onset. The primary outcome was a 90-day modified Rankin Scale (mRS) 0-1; secondary outcomes included good outcomes in the Barthel Index, Stroke Impact Scale-16 (SIS-16) and European Quality of Life. Multivariable models were created to determine predictors of outcomes and the effect of alteplase. Results: A total of 1765 participants were included from 100 Get With The Guidelines (GWTG)-Stroke participating hospitals (age 65 + 14, 42% women, final diagnosis ischemic stroke 90%, TIA 10%, 57% received alteplase). At 90 days, 37% were disabled and 25% not independent. Worse outcomes were noted for older individuals, women, non-Hispanic Blacks and Hispanics, Medicaid, smokers, those with diabetes, atrial fibrillation, prior stroke, higher baseline NIHSS, visual field defects, arm and leg weakness. Similar outcomes were noted for the alteplase-treated and the untreated groups. Alteplase treated patients were younger (64 + 13 vs. 67 + 1.4) with a higher NIHSS (2.9 + 1.4 vs. 1.7 + 1.4). After adjusting for age, sex, race-ethnicity, and baseline NIHSS, we did not identify an effect of alteplase on the primary outcome but did find an effect on SIS-16 in the restricted sample of baseline NIHSS 3-5. Very few symptomatic hemorrhages were recorded (3/999). Conclusions: A large proportion of stroke patients presenting with a low NIHSS have a disabled outcome. Baseline predictors of worse outcomes are described. An effect of alteplase on outcomes was not identified in the overall cohort but an indication of efficacy was noted in the NIHSS 3-5 subgroup.

Background: Data from the Greater Cincinnati Northern Kentucky Stroke Study (GCNKSS) have demonstrated stable or increasing stroke incidence rates in young adults with differences by sex and race, suggesting the need for targeted approaches to stroke prevention in the young. We aimed to describe trends over time in prevalence of stroke risk factors among adults ages 20-54 with stroke by sex and race. Methods: Cases of incident stroke (IS, ICH, SAH) occurring in those 20-54 years old and living in a 5-county area of southern Ohio/northern Kentucky were ascertained during 5 study periods (1993-1994, 1999, 2005, 2010, 2015). All physician-adjudicated inpatient events and a sampling of outpatient events were included, excluding nursing home events. Data on risk factors (hypertension, diabetes, obesity (BMI≥30), and high cholesterol) diagnosed prior to stroke were abstracted from medical records, and prevalence of each risk factor was reported over time in race/sex groups. Trends over time were examined using the Cochran-Armitage test. Results: Over the 5 study periods, 1204 incident strokes were included; 49% were women, 33% were black, and mean age was 46 (SD 7) years. Premorbid hypertension increased over time in Black women (48% in 1993/4 to 76% in 2015, p=0.005) but not in any other race/sex group (all p>0.05). Premorbid high cholesterol increased significantly in all race/sex groups (Figure, all p Conclusions: Among patients aged 20-54 with incident stroke in a large population-based study, the change in the prevalence of hypertension and high cholesterol differed by sex and race, while obesity and diabetes were stable over time in all race/sex groups. Future research is needed to address risk factor control at a population level and to understand the role of undiagnosed pre-stroke risk factors in the young.

Introduction: In patients with acute large vessel occlusion, the definition of penumbral tissue based on T max delay perfusion imaging is not well established in relation to late-window endovascular thrombectomy (EVT). In this study, we sought to evaluate penumbra consumption rates for T max delays in patients treated between 6 and 16 hours from last known normal. Methods: This is a secondary analysis of the DEFUSE-3 trial, which included patients with an acute ischemic stroke due to anterior circulation occlusion within 6-16 hours of last known normal. The primary outcome is percentage penumbra consumption defined as (24 hour infarct volume-core infarct volume)/(Tmax volume-baseline core volume). We stratified the cohort into 4 categories (untreated, TICI 0-2a, TICI 2b, and TICI3) and calculated penumbral consumption rates. Results: We included 143 patients, of which 66 were untreated, 16 had TICI 0-2a, 46 had TICI 2b, and 15 had TICI 3. In untreated patients, a median (IQR) of 48% (21% - 85%) of penumbral tissue was consumed based on Tmax6 as opposed to 160.6% (51% - 455.2%) of penumbral tissue based on Tmax10. On the contrary, in patients achieving TICI 3 reperfusion, a median (IQR) of 5.3% (1.1% - 14.6%) of penumbral tissue was consumed based on Tmax6 and 25.7% (3.2% - 72.1%) of penumbral tissue based on Tmax10. Conclusion: Contrary to prior studies, we show that at least 75% of penumbral tissue with Tmax > 10 sec delay can be salvaged with successful reperfusion and new generation devices. In untreated patients, since infarct expansion can occur beyond 24 hours, future studies with delayed brain imaging are needed to determine the optimal T max delay threshold that defines penumbral tissue in patients with proximal anterior circulation large vessel occlusion.

Background and ObjectivesTo determine the impact of endovascular therapy for large vessel occlusion stroke in patients with vs those without premorbid disability.MethodsWe performed a post hoc analysis of the TREVO Stent-Retriever Acute Stroke (TRACK) Registry, which collected data on 634 consecutive patients with stroke treated with the Trevo device as first-line endovascular thrombectomy (EVT) at 23 centers in the United States. We included patients with internal carotid or middle cerebral (M1/M2 segment) artery occlusions, and the study exposure was patient- or caregiver-reported premorbid modified Rank Scale (mRS) score ≥2 (premorbid disability [PD]) vs premorbid mRS score of 0 to 1 (no PD [NPD]). The primary outcome was no accumulated disability, defined as no increase in 90-day mRS score from the patient's premorbid mRS score.ResultsOf the 634 patients in TRACK, 407 patients were included in our cohort, of whom 53 (13.0%) had PD. The primary outcome of no accumulated disability was achieved in 37.7% (20 of 53) of patients with PD and 16.7% (59 of 354) of patients with NPD (p < 0.001), while death occurred in 39.6% (21 of 53) and 14.1% (50 of 354) (p < 0.001), respectively. The adjusted odds ratio of no accumulated disability for patients with PD was 5.2 (95% confidence interval [CI] 2.4–11.4, p < 0.001) compared to patients with NPD. However, the adjusted odds ratio for death in patients with PD was 2.90 (95% CI 1.38–6.09, p = 0.005).DiscussionIn this study of patients with anterior circulation acute ischemic stroke treated with EVT, we found that PD was associated with a higher probability of not accumulating further disability compared to patients with NPD but also with higher probability of death.Classification of EvidenceThis study provides Class II evidence that in anterior circulation acute ischemic stroke treated with EVT, patients with PD compared to those without disability were more likely not to accumulate more disability but were more likely to die.

Domain-specific endpoints are assessments that correspond to the output of individual neural systems and are useful for capturing treatment effects on specific behaviors. By contrast, global endpoints combine several attributes into a single score and are useful for capturing broad treatment effects in a summary way. While global endpoints have become the de facto mechanism required to define benefit in stroke trials, they also have important limitations, some of which might be addressed by simultaneously measuring domain-specific endpoints. Substantial opportunity remains to identify quantifiable patient benefit that would otherwise not be captured by global endpoints. Potential advantages of incorporating domain-specific endpoints in acute stroke trials are discussed, such as increased granularity of measurement, improved understanding of how therapies affect the brain between acute treatment and day 90, and optimized therapeutic translation. Potential disadvantages are also considered, including time and cost of administering domain-specific endpoints, as well as statistical implications. Domain-specific endpoints and global endpoints are not mutually exclusive, and both capture clinical benefits to patients. Incorporating a broader set of outcome assessments in stroke trials, including both global and domain-specific endpoints, is warranted.

Background and Purpose: Large-scale observational studies of acute ischemic stroke (AIS) promise to reveal mechanisms underlying cerebral ischemia. However, meaningful quantitative phenotypes attainable in large patient populations are needed. We characterize a dynamic metric of AIS instability, defined by change in National Institutes of Health Stroke Scale score (NIHSS) from baseline to 24 hours baseline to 24 hours (NIHSS baseline – NIHSS 24hours = ΔNIHSS 6-24h ), to examine its relevance to AIS mechanisms and long-term outcomes. Methods: Patients with NIHSS prospectively recorded within 6 hours after onset and then 24 hours later were enrolled in the GENISIS study (Genetics of Early Neurological Instability After Ischemic Stroke). Stepwise linear regression determined variables that independently influenced ΔNIHSS 6 –24h . In a subcohort of tPA (alteplase)-treated patients with large vessel occlusion, the influence of early sustained recanalization and hemorrhagic transformation on ΔNIHSS 6–24h was examined. Finally, the association of ΔNIHSS 6 –24h with 90-day favorable outcomes (modified Rankin Scale score 0–2) was assessed. Independent analysis was performed using data from the 2 NINDS-tPA stroke trials (National Institute of Neurological Disorders and Stroke rt-PA). Results: For 2555 patients with AIS, median baseline NIHSS was 9 (interquartile range, 4–16), and median ΔNIHSS 6 –24h was 2 (interquartile range, 0–5). In a multivariable model, baseline NIHSS, tPA-treatment, age, glucose, site, and systolic blood pressure independently predicted ΔNIHSS 6 –24h (R 2 =0.15). In the large vessel occlusion subcohort, early sustained recanalization and hemorrhagic transformation increased the explained variance (R 2 =0.27), but much of the variance remained unexplained. ΔNIHSS 6 –24h had a significant and independent association with 90-day favorable outcome. For the subjects in the 2 NINDS-tPA trials, ΔNIHSS 3 –24h was similarly associated with 90-day outcomes. Conclusions: The dynamic phenotype, ΔNIHSS 6–24h , captures both explained and unexplained mechanisms involved in AIS and is significantly and independently associated with long-term outcomes. Thus, ΔNIHSS 6 –24h promises to be an easily obtainable and meaningful quantitative phenotype for large-scale genomic studies of AIS.

Supplemental Digital Content is available in the text., Background and Purpose: Anecdotal evidence suggests that the coronavirus disease 2019 (COVID-19) pandemic mitigation efforts may inadvertently discourage patients from seeking treatment for stroke with resultant increased morbidity and mortality. Analysis of regional data, while hospital capacities for acute stroke care remained fully available, offers an opportunity to assess this. We report regional Stroke Team acute activations and reperfusion treatments during COVID-19 mitigation activities. Methods: Using case log data prospectively collected by a Stroke Team exclusively serving ≈2 million inhabitants and 30 healthcare facilities, we retrospectively reviewed volumes of consultations and reperfusion treatments for acute ischemic stroke. We compared volumes before and after announcements of COVID-19 mitigation measures and the prior calendar year. Results: Compared with the 10 weeks prior, stroke consultations declined by 39% (95% CI, 32%–46%) in the 5 weeks after announcement of statewide school and restaurant closures in Ohio, Kentucky, and Indiana. Results compared with the prior year and time trend analyses were consistent. Reperfusion treatments also appeared to decline by 31% (95% CI, 3%–51%), and specifically thrombolysis by 33% (95% CI, 4%–55%), but this finding had less precision. Conclusions: Upon the announcement of measures to mitigate COVID-19, regional acute stroke consultations declined significantly. Reperfusion treatment rates, particularly thrombolysis, also appeared to decline qualitatively, and this finding requires further study. Urgent public education is necessary to mitigate a possible crisis of avoiding essential emergency care due to COVID-19.

Background and Purpose— We aimed to compare functional and procedural outcomes of patients with acute ischemic stroke with none-to-minimal (modified Rankin Scale [mRS] score, 0–1) and moderate (mRS score, 2–3) prestroke disability treated with mechanical thrombectomy. Methods— Consecutive adult patients undergoing mechanical thrombectomy for an anterior circulation stroke were prospectively identified at 2 comprehensive stroke centers from 2012 to 2018. Procedural and 90-day functional outcomes were compared among patients with prestroke mRS scores 0 to 1 and 2 to 3 using χ 2 , logistic, and linear regression tests. Primary outcome and significant differences in secondary outcomes were adjusted for prespecified covariates. Results— Of 919 patients treated with mechanical thrombectomy, 761 were included and 259 (34%) patients had moderate prestroke disability. Ninety-day mRS score 0 to 1 or no worsening of prestroke mRS was observed in 36.7% and 26.7% of patients with no-to-minimal and moderate prestroke disability, respectively (odds ratio, 0.63 [0.45–0.88], P =0.008; adjusted odds ratio, 0.90 [0.60–1.35], P =0.6). No increase in the disability at 90 days was observed in 22.4% and 26.7%, respectively. Rate of symptomatic intracerebral hemorrhage (7.3% versus 6.2%, P =0.65), successful recanalization (86.7% versus 83.8%, P =0.33), and median length of hospital stay (5 versus 5 days, P =0.06) were not significantly different. Death by 90 days was higher in patients with moderate prestroke disability (14.3% versus 40.3%; odds ratio, 4.06 [2.82–5.86], P P Conclusions— One-third of patients undergoing mechanical thrombectomy had a moderate prestroke disability. There was insufficient evidence that functional and procedural outcomes were different between patients with no-to-minimal and moderate prestroke disability. Patients with prestroke disability were more likely to die by 90 days.

Frequency and outcomes of mechanical thrombectomy (MT) in clinical practice for patients with severe pre-stroke disability are largely unknown. In this case series, we aim to describe the disability make-up and outcomes of 33 patients with severe pre-stroke disability undergoing MT. Patients with a permanent, severe, pre-stroke disability (modified Rankin Score, mRS, 4-5) were identified from a prospectively-maintained database of consecutive, MT-treated, anterior circulation acute ischemic stroke patients at two comprehensive stroke centers in the United States. We present details on the cause of disability and socio-demographic status as well as procedural and functional outcomes. This study, despite the lack of inferential testing due to limited sample size, provides insight into demographics and outcomes of MT-treated patients with severe pre-stroke disability. Rate of return to functional baseline as well as rates of procedural success and complications were comparable to that reported in the literature for patients without any pre-existing disability.

Background and Purpose— Sex differences in stroke incidence over time were previously reported from the GCNKSS (Greater Cincinnati/Northern Kentucky Stroke Study). We aimed to determine whether these differences continued through 2015 and whether they were driven by particular age groups. Methods— Within the GCNKSS population of 1.3 million, incident (first ever) strokes among residents ≥20 years of age were ascertained at all local hospitals during 5 periods: July 1993 to June 1994 and calendar years 1999, 2005, 2010, and 2015. Out-of-hospital cases were sampled. Sex-specific incidence rates per 100 000 were adjusted for age and race and standardized to the 2010 US Census. Trends over time by sex were compared (overall and age stratified). Sex-specific case fatality rates were also reported. Bonferroni corrections were applied for multiple comparisons. Results— Over the 5 study periods, there were 9733 incident strokes (56.3% women). For women, there were 229 (95% CI, 215–242) per 100 000 incident strokes in 1993/1994 and 174 (95% CI, 163–185) in 2015 ( P P Conclusions— Overall stroke incidence decreased from the early 1990s to 2015 for both sexes. Future studies should continue close surveillance of sex differences in the 20- to 44-year and ≥85-year age groups, and future stroke prevention strategies should target strokes in the young- and middle-age groups, as well as intracerebral hemorrhage.

Humans are not able to detect all kinds of visible objects' movement. The human eyes can detect large motions like passing of vehicles, trains, waves of water, etc. and their ears are capable of catching smaller and faster movement of sound. So the human can notice the motion that are large and that can change the average shape or location of objects. The motion that does not change the average shape or location of the object is unnoticed or unseen by the naked human eye. These small and minute motions of the visible object are known as vibration. The unnoticed movement of the visible object are silent but carry an enormous amount of information and that is unknown by humans. The objects surface vibrates when a wave of sound hits an object or when it is under the influence of some unknown forces or wind. The information from these vibrating objects surface can be gathered with the use of many traditional vibration sensors. With the technological advancements in the field of computer vision and graphics shows how a camera can serve as a tool for extracting and analyzing the vibrations from the visible objects surface. This information from the vibrating visible objects surface can be very useful in many applications ranging from audio recovery to structural health monitoring and non-destructive testing of the civil structures. This review paper focuses on the use of the camera as a vibration sensor for extracting the information from vibrating objects surface and explains how this extracted information can be useful in numerous applications such as Extraction of the sound from video, recovery of speech, CCTV surveillance, structural health monitoring of the various objects, non-destructive testing, approximating the material properties of the various fabrics, predicting the properties of the various rods or objects under the influence of unknown forces and many more.