Derivation and validation of a predictive scale to expedite endovascular intervention for acute stroke patients with an intervenable vessel occlusion.

BACKGROUND: Early endovascular intervention team mobilization may reduce reperfusion times and improve clinical outcomes for patients with acute ischemic stroke (AIS) with a possible intervenable vessel occlusion (IVO). In an emergency department or mobile stroke unit, incorporating rapidly available non-contrast CT (NCCT) information with examination findings may improve the accuracy of arterial occlusion prediction scales. For this purpose, we developed a rapid and straightforward IVO predictive instrument-the T3AM2PA1 scale. METHODS: The T3AM2PA1 scale was retrospectively derived from our 'Get with the Guidelines' database. We included all patients with acute stroke alert between January 2017 and August 2018 with a National Institutes of Health Stroke Scale (NIHSS) score between 5 and 25 inclusive. Different pre-intervention variables were collected, including itemized NIHSS and NCCT information. The T3AM2PA1 scale was also compared with other commonly used scales and was validated in a separate sequential retrospective cohort of patients with a full range of NIHSS scores. RESULTS: 574 eligible patients from 2115 acute stroke alerts were identified. The scale was established with five items (CT hyperdense sign, parenchymal hypodensity, lateralizing hemiparesis, gaze deviation, and language disturbance), with a total score of 9. To minimize unnecessary angiography, a cut-off of ≥5 for IVO detection yielded a sensitivity of 52%, a specificity of 90%, and a positive predictive value of 76%. CONCLUSIONS: The T3AM2PA1 scale accurately predicts the presence of clinical IVO in patients with AIS. Adopting the T3AM2PA1 scale could reduce revascularization times, improve treatment outcomes, and potentially reduce disability.

Preliminary experience with diffuse correlation spectroscopy in acute ischemic stroke neurointerventional procedures.

BACKGROUND: Diffuse correlation spectroscopy (DCS) is a non-invasive optical technique that enables continuous blood flow measurements in various organs, including the brain. DCS quantitatively measures blood flow from temporal fluctuations in the intensity of diffusely reflected light caused by the dynamic scattering of light from moving red blood cells within the tissue. METHODS: We performed bilateral cerebral blood flow (CBF) measurements using a custom DCS device in patients undergoing neuroendovascular interventions for acute ischemic stroke. Experimental, clinical, and imaging data were collected in a prospective manner. RESULTS: The device was successfully applied in nine subjects. There were no safety concerns or interference with the standard angiography suite or intensive care unit workflow. Six cases were selected for final analysis and interpretation. DCS measurements with photon count rates greater than 30 KHz had sufficient signal-to-noise to resolve blood flow pulsatility. We found an association between angiographic changes in cerebral reperfusion (partial or complete reperfusion established in stroke thrombectomy cases; temporary flow arrest during carotid artery stenting) and those observed intraprocedurally with CBF measurements via DCS. Limitations of the current technology included sensitivity to the interrogated tissue volume under the probe and the effect of local changes in tissue optical properties on the accuracy of CBF estimates. CONCLUSION: Our initial experience with DCS in neurointerventional procedures showed the feasibility of this non-invasive approach in providing continuous measurement of regional CBF brain tissue properties.

Risk of hemorrhagic transformation with early use of direct oral anticoagulants after acute ischemic stroke: A pooled analysis of prospective studies and randomized trials.

INTRODUCTION: Precise risk of hemorrhagic transformation (HT) in acute ischemic stroke (AIS) remains unknown, leading to delays in anticoagulation initiation for secondary stroke prevention. We sought to assess the rate of HT associated with direct oral anticoagulant (DOAC) initiation within and beyond 48 h post-AIS. METHODS: A pooled analysis of DOAC initiation within 14 days of AIS or transient ischemic attack (TIA) was conducted with six studies (four prospective open label treatment, blinded outcome studies and two randomized trials; NCT02295826 and NCT02283294). The primary endpoint was incident radiographic HT on follow-up imaging (days 7-30). Secondary endpoints included symptomatic HT, new parenchymal hemorrhage, recurrent ischemic events, extracranial hemorrhage, study period mortality, and follow-up modified Rankin Scale score. The results were reported as odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI). RESULTS: We evaluated 509 patients; median infarct volume was 1.5 (0.1-7.8) ml, and median National Institutes of Health Stroke Scale was 2 (0-3). Incident radiographic HT was seen on follow-up scan in 34 (6.8%) patients. DOAC initiation within 48 h from index event was not associated with incident HT (adjusted OR 0.67, [0.30-1.50] P = 0.32). No patients developed symptomatic HT. Conversely, 31 (6.1%) patients developed recurrent ischemic events, 64% of which occurred within 14 days. Initiating a DOAC within 48 h of onset was associated with similar recurrent ischemic event rates compared with those in which treatment was delayed (HR: 0.42, [0.17-1.008] P = 0.052). In contrast to HT, recurrent ischemic events were associated with poor functional outcomes (OR = 6.8, [2.84-16.24], p < 0.001). CONCLUSIONS: In this pooled analysis, initiation of DOAC within 48 h post-stroke was not associated with increased incident risk of HT, and none developed symptomatic HT. The analysis was underpowered to determine the effect of early DOAC use upon recurrent ischemic events.

Association of Stroke Subtype With Hemorrhagic Transformation Mediated by Thrombectomy Pass: Data From the ANGEL-ACT Registry.

BACKGROUND: The role of stroke etiology subtype in patients with acute large vessel occlusion on the occurrence of hemorrhagic transformation (HT) after endovascular treatment is poorly studied, and which factors mediate their relationship remains largely unknown. We utilized nationwide registry data to explore the association of stroke subtype (cardioembolism versus large artery atherosclerosis) with HT and to identify the possible mediators. METHODS: A total of 1015 subjects were selected from the ANGEL-ACT registry (Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke)-a prospective consecutive cohort of acute large vessel occlusion patients undergoing endovascular treatment at 111 hospitals in China between November 2017 and March 2019-and divided into large artery atherosclerosis (n=538) and cardioembolism (n=477) according to the Trial of ORG 10172 in Acute Stroke Treatment criteria. The types of HT included any intracerebral hemorrhage (ICH), parenchymal hematoma, and symptomatic ICH within 24 hours after endovascular treatment. The association between stroke subtype and HT was analyzed using a logistic regression model. Mediation analysis was done to assess how much of the effect of stroke subtype on HT was mediated through the identified mediators. RESULTS: Stroke subtype (cardioembolism versus large artery atherosclerosis) was associated with increased risk of any ICH (29.8% versus 16.5%; odds ratio, 2.03 [95% CI, 1.22-3.36]), parenchymal hematoma (14.3% versus 5.4%; odds ratio, 2.90 [95% CI, 1.38-6.13]), and symptomatic ICH (9.9% versus 4.7%; odds ratio, 2.59 [95% CI, 1.09-6.16]) after adjustment for potential confounders. The more thrombectomy passes in cardioembolism patients had a significant mediation effect on the association of stroke subtype with increased risk of HT (any ICH, 15.9%; parenchymal hematoma, 13.4%; symptomatic ICH, 14.2%, respectively). CONCLUSIONS: Stroke subtype is an independent risk factor for HT within 24 hours following endovascular treatment among acute large vessel occlusion patients. Mediation analyses propose that stroke subtype contributes to HT partly through thrombectomy pass, suggesting a possible pathomechanistic link. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03370939.

No Time to Lose: Cases of Anticoagulant Reversal Before Thrombolysis in Acute Ischemic Stroke Patients.

Direct oral anticoagulant (DOAC) reversal before intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients is well-documented in Europe, specifically for dabigatran: the selective humanized monoclonal antibody fragment idarucizumab, given to neutralize dabigatran prior to IVT, was associated with improved outcomes post-IVT. However, in the United States, this approach is rarely reported and not endorsed by guidelines. Therefore, further reporting on this is needed and neuroradiographic correlation may help validate this concept. At our hospital in Tampa, Florida, two octogenarians with atrial fibrillation, adherent with the DOAC dabigatran, presented with AIS shortly after symptom onset. Both received idarucizumab, then IVT. Clinical outcomes, treatment times, and perfusion-based neuroradiographic parameters were assessed. Patient A had a 41 ml penumbra on computed tomography perfusion (CTP) scan that decreased to 15 ml in final infarct volume on follow-up imaging, resulting in a 26 ml penumbral salvage (63.4%), and National Institutes of Health Stroke Scale (NIHSS) improved from 11 to 9 . Patient B had a 23 ml penumbra on CTP that decreased to 0.5 ml on follow-up imaging, resulting in a 22.5 ml penumbral salvage (97.8%), and NIHSS improved from 9 to 4. Neither developed bleeding complications. Both had delayed door-to-needle times but nevertheless demonstrated clinical neurological improvements. In our limited experience, IVT after immediate DOAC reversal in AIS patients on dabigatran was associated with clinical improvement in NIHSS by 2 to 5 points (with no neuroworsening), and penumbral salvage of ischemic brain tissue on neuroimaging ranging from 63.4% to 97.8%. Further reporting on this may lead to greater IVT use and better outcomes in "DOAC failures", especially for patients without other acute treatment options such as mechanical thrombectomy. Research into other anticoagulant reversal agents pre-IVT in AIS is also warranted.

Combined Approach to Eptifibatide and Thrombectomy in Acute Ischemic Stroke Because of Large Vessel Occlusion: A Matched-Control Analysis.

BACKGROUND: In patients undergoing mechanical thrombectomy (MT), adjunctive antithrombotic might improve angiographic reperfusion, reduce the risk of distal emboli and reocclusion but possibly expose patients to a higher intracranial hemorrhage risk. This study evaluated the safety and efficacy of combined MT plus eptifibatide for acute ischemic stroke. METHODS: This was a propensity-matched analysis of data from 2 prospective trials in Chinese populations: the ANGEL-ACT trial (Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischemic Stroke) in 111 hospitals between November 2017 and March 2019, and the EPOCH trial (Eptifibatide in Endovascular Treatment of Acute Ischemic Stroke) in 15 hospitals between April 2019 and March 2020. The primary efficacy outcome was good outcome (modified Rankin Scale score 0-2) at 3 months. Secondary efficacy outcomes included the distribution of 3-month modified Rankin Scale scores and poor outcome (modified Rankin Scale score 5-6) and successful recanalization. The safety outcomes included any intracranial hemorrhage, symptomatic intracranial hemorrhage, and 3-month mortality. Mixed-effects logistic regression models were used to account for within-hospital clustering in adjusted analyses. RESULTS: Eighty-one combination arm EPOCH subjects were matched with 81 ANGEL-ACT noneptifibatide patients. Compared with the no eptifibatide group, the eptifibatide group had significantly higher rates of successful recanalization (91.3% versus 81.5%; P=0.043) and 3-month good outcomes (53.1% versus 33.3%; P=0.016). No significant difference was found in the remaining outcome measures between the 2 groups. All outcome measures of propensity score matching were consistent with mixed-effects logistic regression models in the total population. CONCLUSIONS: This matched-control study demonstrated that MT combined with eptifibatide did not raise major safety concerns and showed a trend of better efficacy outcomes compared with MT alone. Overall, eptifibatide shows potential as a periprocedural adjunctive antithrombotic therapy when combined with MT. Further randomized controlled trials of MT plus eptifibatide should be prioritized. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03844594 (EPOCH), NCT03370939 (ANGEL-ACT).

Direct angiographic intervention for acute ischemic stroke with large vessel occlusion.

Background:Rapid and effective revascularization is the cornerstone of acute ischemic stroke treatment. Endovascular thrombectomy reperfusion has dramatically changed patients' outcomes with large vessel occlusions. Results of randomized controlled trials have shown that the benefit of this treatment is highly time-sensitive. The purpose of this review is to introduce a new approach to acute stroke treatment - direct angiographic intervention for selected patients. Methods & Results:We examined the issues related to the current guideline-based practice, emphasizing whether the benefit of using advanced multimodal imaging is worth the potential resultant disability generated by delayed reperfusion times. The published evidence supporting this novel concept was reviewed, its safety and feasibility discussed, and appropriate predictive tools for patient selection explored.Conclusion:This new approach may provide benefits for appropriately selected patients. Further prospective trials are needed to clarify the risk-versus-benefit of this approach.Abbreviations and Acronyms: AHA: American Heart AssociationAIS: acute ischemic strokeASA: American Stroke AssociationASPECTS: Alberta Stroke Program Early Computed Tomography ScoreCT: computed tomographyCTA: computed tomography angiographyCTP: computed tomography perfusionDMVO: distal, medium vessel occlusionDSA: digital subtraction angiographyED: Emergency DepartmentEVT: endovascular thrombectomyFD: flat detectorIA: intra-arterialIV: intravenousICH: intracerebral hemorrhageMR: magnetic resonanceMRA: magnetic resonance angiographyMSU: mobile stroke unitNIHSS: National Institutes of Health Stroke ScaleNCCT: non-contrast computed tomographyPLVO: proximal, large vessel occlusionPPV: positive predictive valuePWI: magnetic resonance perfusion-weighted imaging.

Early Apixaban Use Following Stroke in Patients With Atrial Fibrillation: Results of the AREST Trial.

BACKGROUND AND PURPOSE: It is unknown when to start anticoagulation after acute ischemic stroke (AIS) from atrial fibrillation (AF). Early anticoagulation may prevent recurrent infarctions but may provoke hemorrhagic transformation as AF strokes are typically larger and hemorrhagic transformation-prone. Later anticoagulation may prevent hemorrhagic transformation but increases risk of secondary stroke in this time frame. Our aim was to compare early anticoagulation with apixaban in AF patients with stroke or transient ischemic attack (TIA) versus warfarin administration at later intervals. METHODS: AREST (Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation) was an open-label, randomized controlled trial comparing the safety of early use of apixaban at day 0 to 3 for TIA, day 3 to 5 for small-sized AIS (<1.5 cm), and day 7 to 9 for medium-sized AIS (≥1.5 cm, excluding full cortical territory), to warfarin, in a 1:1 ratio at 1 week post-TIA, or 2 weeks post-AIS. RESULTS: Although AREST ended prematurely after a national guideline focused update recommended direct oral anticoagulants over warfarin for AF, it revealed that apixaban had statistically similar yet generally numerically lower rates of recurrent strokes/TIA (14.6% versus 19.2%, P=0.78), death (4.9% versus 8.5%, P=0.68), fatal strokes (2.4% versus 8.5%, P=0.37), symptomatic hemorrhages (0% versus 2.1%), and the primary composite outcome of fatal stroke, recurrent ischemic stroke, or TIA (17.1% versus 25.5%, P=0.44). One symptomatic intracerebral hemorrhage occurred on warfarin, none on apixaban. Five asymptomatic hemorrhagic transformation occurred in each arm. CONCLUSIONS: Early initiation of anticoagulation after TIA, small-, or medium-sized AIS from AF does not appear to compromise patient safety. Potential efficacy of early initiation of anticoagulation remains to be determined from larger pivotal trials. Registration: URL: https://www.clinicaltrials.gov/; Unique identifier: NCT02283294.

Current Status of Endovascular Treatment for Acute Large Vessel Occlusion in China: A Real-World Nationwide Registry.

BACKGROUND AND PURPOSE: The benefit of endovascular treatment (EVT) for large vessel occlusion in clinical practice in developing countries like China needs to be confirmed. The aim of the study was to determine whether the benefit of EVT for acute ischemic stroke in randomized trials could be generalized to clinical practice in Chinese population. METHODS: We conducted a prospective registry of EVT at 111 centers in China. Patients with acute ischemic stroke caused by imaging-confirmed intracranial large vessel occlusion and receiving EVT were included. The primary outcome was functional independence at 90 days defined as a modified Rankin Scale score of 0 to 2. Outcomes of specific subgroups in the anterior circulation were reported and logistic regression was performed to predict the primary outcome. RESULTS: Among the 1793 enrolled patients, 1396 (77.9%) had anterior circulation large vessel occlusion (median age, 66 [56-73] years) and 397 (22.1%) had posterior circulation large vessel occlusion (median age, 64 [55-72] years). Functional independence at 90 days was reached in 45% and 44% in anterior and posterior circulation groups, respectively. For anterior circulation population, underlying intracranial atherosclerotic disease was identified in 29% of patients, with higher functional independence at 90 days (52% versus 44%; P=0.0122) than patients without intracranial atherosclerotic disease. In the anterior circulation population, after adjusting for baseline characteristics, procedure details, and early outcomes, the independent predictors for functional independence at 90 days were age <66 years (odds ratio [OR], 1.733 [95% CI, 1.213-2.476]), time from onset to puncture >6 hours (OR, 1.536 [95% CI, 1.065-2.216]), local anesthesia (OR, 2.194 [95% CI, 1.325-3.633]), final modified Thrombolysis in Cerebral Infarction 2b/3 (OR, 2.052 [95% CI, 1.085-3.878]), puncture-to-reperfusion time ≤1.5 hours (OR, 1.628 [95% CI, 1.098-2.413]), and National Institutes of Health Stroke Scale score 24 hours after the procedure <11 (OR, 9.126 [95% CI, 6.222-13.385]). CONCLUSIONS: Despite distinct characteristics in the Chinese population, favorable outcome of EVT can be achieved in clinical practice in China. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03370939.

Untreated Stroke as Collateral Damage of COVID-19: "Time Is Brain" Versus "Stay at Home".

For decades, neurologists have been advocating that anyone with acute focal deficits report immediately to the closest hospital's emergency room. Major advancements in the hyperacute diagnosis and treatment of stroke have justified our call-to-action slogan of "Time is Brain"-faster therapy leads to superior outcomes. However, this mantra has been recently usurped by the catchphrase "Stay at Home" during the coronavirus disease 2019 (COVID-19) pandemic. Fewer patients are presenting to hospitals with acute stroke; our census is down. Presumably the etiology of this phenomenon is either strict "social distancing" that some people may misperceive to exclude even emergent situations, or fears of contracting the virus while hospitalized. In this Short Report, we describe the year-over-year drop in stroke volume (ischemic and hemorrhagic both) coinciding with a paradoxical rise in acute reperfusion therapies at our university hospital. These data imply that stroke patients with mild/moderate symptoms are most likely staying home, and not receiving urgent therapies, and correspondingly, only the most severely disabled stroke patients are ultimately seeking and receiving help. We must remind our patients and the general public that our services are essential and available, as stroke still remains a medical emergency, and carries a likely higher overall mortality risk than COVID-19. As neurologists, we also must be vigilant for the atypical presentations and varied etiologies of stroke associated with COVID-19 as well.

Protocol for AREST: Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation-A Randomized Controlled Trial of Early Anticoagulation After Acute Ischemic Stroke in Atrial Fibrillation.

Background: Optimal timing to initiate anticoagulation after acute ischemic stroke (AIS) from atrial fibrillation (AF) is currently unknown. Compared to other stroke etiologies, AF typically provokes larger infarct volumes and greater concern of hemorrhagic transformation, so seminal randomized trials waited weeks to months to begin anticoagulation after initial stroke. Subsequent data are limited and non-randomized. Guidelines suggest anticoagulation initiation windows between 3 and 14 days post-stroke, with Class IIa recommendations, and level of evidence B in the USA and C in Europe. Aims: This open-label, parallel-group, multi-center, randomized controlled trial AREST (Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation) is designed to evaluate the safety and efficacy of early anticoagulation, based on stroke size, secondary prevention of ischemic stroke, and risks of subsequent hemorrhagic transformation. Methods: Subjects are randomly assigned in a 1:1 ratio to receive early apixaban at day 0-3 for transient ischemic attack (TIA), 3-5 for small-sized AIS (<1.5 cm), and 7-9 for medium-sized AIS (1.5 cm or greater but less than a full cortical territory), or warfarin at 1 week post-TIA or 2 weeks post-stroke. Large AISs are excluded. Study Outcomes: Primary: recurrent ischemic stroke, TIA, and fatal stroke; secondary: intracranial hemorrhage (ICH); hemorrhagic transformation (HT) of ischemic stroke; cerebral microbleeds (CMBs); neurologic disability [e.g., modified Rankin Scores (mRS), National Institutes of Health Stroke Scale (NIHSS), Stroke Specific Quality of Life scale (SS-QOL)]; and cardiac biomarkers [e.g., AF burden, transthoracic echo (TTE)/transesophageal echo (TEE) abnormalities]. Sample Size Estimates: Enrollment goal was 120 for 80% power (two-sided type I error rate of 0.05) to detect an absolute risk reduction of 16.5% postulated to occur with apixaban in the primary composite outcome of fatal stroke/recurrent ischemic stroke/TIA within 180 days. Enrollment was suspended at 91 subjects in 2019 after a focused guideline update recommended direct oral anticoagulants (DOACs) over warfarin in AF, excepting valvular disease (Class I, level of evidence A). Discussion: AREST will offer randomized controlled trial data about timeliness and safety of anticoagulation in AIS patients with AF. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02283294.

Disparities and Temporal Trends in the Use of Anticoagulation in Patients With Ischemic Stroke and Atrial Fibrillation.

Background and Purpose- Ischemic stroke (IS) secondary to atrial fibrillation (AF) is largely preventable with the use of anticoagulation. We sought to identify race-ethnicity and sex disparities with the use of direct oral anticoagulants (DOACs), aspirin, and warfarin in IS patients with AF and to identify temporal trends in the utilization of these medications. Methods- The FLiPER-AF Stroke Study (Florida Puerto Rico Atrial Fibrillation) included 24 040 IS cases enrolled in the Florida-Puerto Rico Collaboration to Reduce Stroke Registry from 2010 to 2016. Multivariable logistic regression models were performed to evaluate the effect of race-ethnicity and sex on utilization of DOACs, aspirin, and warfarin for stroke prevention in AF after adjustment for sociodemographic, hospital, and clinical factors. Results- Among 24 040 IS cases, 54% were women and 10% black, 12% FL-Hispanics, 4% PR-Hispanic, and 74% whites. From 2010 to 2016, DOAC use increased from 0% to 36%, warfarin use decreased from 51% to 17%, and aspirin use remained relatively stable (42%-40%). After adjustment, blacks had higher odds of warfarin (odds ratio, 1.22; 95% CI, 1.07-1.40) prescription at discharge compared with whites. Men had higher rates of aspirin (42.1% versus 38.8%), warfarin (33.6% versus 28.9%), and DOAC (21.3% versus 19.3%) use compared with women. After adjustment, women had lower odds of being discharged on aspirin (odds ratio, 0.92; 95% CI, 0.86-0.98) or warfarin (odds ratio, 0.91; 95% CI, 0.84-0.99). There was no sex difference in use of DOACs. Conclusions- Our study confirmed the increasing use of DOACs, downtrending use of warfarin, whereas aspirin use remained similar over the years. There are sex and race-ethnicity disparities in anticoagulation use in IS patients with AF. It is critical to understand underlying drivers of these disparities to develop better practice strategies for stroke prevention in patients with AF. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT03627806.

Indications for Mechanical Thrombectomy-Too Wide or Too Narrow?

The indications for mechanical thrombectomy (MT) have expanded since the American Heart Association/American Stroke Association reported its first guidelines for MT in 2013. Multiple subsequent randomized clinical trials of MT have proved its efficacy, including the DAWN (DWI [diffusion weighted imaging] or CTP [computed tomography perfusion] Assessment with Clinical Mismatch in the Triage of Wake-up and Late Presenting Strokes Undergoing Neurointervention with Trevo) and DEFUSE-3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke-3) trials. The current guidelines from the American Heart Association/American Stroke Association provide class I support for the use of MT for the following indications: 1) internal carotid artery (ICA)/M1 middle cerebral artery (MCA) occlusion, symptom onset <6 hours, National Institutes of Health Stroke Scale score of ≥6, Alberta Stroke Program Early Computed Tomography Score of ≥6; and 2) large vessel occlusions in the anterior circulation, symptom onset 6-16 hours, and meeting the DAWN or DEFUSE-3 eligibility criteria. Class IIa evidence is also available for the use of MT for large vessel occlusions in the anterior circulation, symptom onset 16-24 hours, and meeting other DAWN eligibility criteria. In clinical practice, these class I and IIa indications for MT have been well followed. However, many other potential indications are available, including 1) M2 or M3 MCA occlusion, symptom onset <6 hours; 2) Alberta Stroke Program Early Computed Tomography Score <6, ICA or M1 MCA occlusion, symptom onset <6 hours; 3) National Institutes of Health Stroke Scale score <6, ICA or M1 occlusion, symptom onset <6 hours; 4) tandem occlusions; and 5) posterior circulation occlusion <6 hours. The present review analyzed the available data to provide support for further prospective clinical trials regarding these potential indications.

Disparities and Temporal Trends in Stroke Care Outcomes in Patients with Atrial Fibrillation: The FLiPER-AF Stroke Study.

BACKGROUND AND PURPOSE: Atrial Fibrillation (AF) is the most common cardiac cause of ischemic stroke. However, the relation between AF and stroke care outcomes in diverse populations is understudied. We aimed to evaluate sex and race-ethnic disparities associated with AF in hospital stroke outcomes utilizing data from the FLorida PuErto Rico Atrial Fibrillation (FLiPER-AF) Stroke Study. METHODS: The study included 104,308 ischemic stroke cases with available information on AF status enrolled in a state-wide stroke registry from 2010 to 2016. Multivariable logistic regression models were performed to evaluate the association between AF and stroke outcomes and the modification effects on the associations by sex and by race-ethnicity, adjusted for socio-demographic status, vascular risk factors and stroke severity. RESULTS: AF was present in 23% of ischemic stroke cases. AF was associated with worse disability at discharge (OR=1.11, 95% CI, 1.04-1.18), less discharge to home (OR=0.89, 0.85-0.92), and longer length of hospital stay (LOS>6 days, OR=1.53, 1.46-1.60). Interaction analyses showed that the association between AF and less discharge to home was stronger in women than men (p for interaction <0.001), as well as in FL-whites than in FL-blacks, FL-Hispanics or PR-Hispanics (p for interaction=0.002). The association between AF and prolonged LOS was more prominent in PR-Hispanics than in FL-blacks, FL-Hispanics, or FL-whites (p for interaction <0.001). From 2010 to 2016, the effects of AF on hospital length of stay attenuated (p for interaction<0.001). CONCLUSIONS: AF was associated with poor disability at discharge, less discharge to home, and prolonged hospital length of stay for acute stroke care. The effect of AF on length of stay attenuated over time. Sex and race-ethnic disparities were observed in the effect of AF on being less discharge to home and prolonged hospital stay. Further research is needed to identify and modify the biologic and systems of care contributors to these disparities.

Predictors of Thrombolysis Administration in Mild Stroke: Florida-Puerto Rico Collaboration to Reduce Stroke Disparities.

BACKGROUND AND PURPOSE: Mild stroke is the most common cause for thrombolysis exclusion in patients acutely presenting to the hospital. Thrombolysis administration in this subgroup is highly variable among different clinicians and institutions. We aim to study the predictors of thrombolysis in patients with mild ischemic stroke in the FL-PR CReSD registry (Florida-Puerto Rico Collaboration to Reduce Stroke Disparities). METHODS: Among 73 712 prospectively enrolled patients with a final diagnosis of ischemic stroke or TIA from January 2010 to April 2015, we identified 7746 cases with persistent neurological symptoms and National Institutes of Health Stroke Scale ≤5 who arrived within 4 hours of symptom onset. Multilevel logistic regression analysis with generalized estimating equations was used to identify independent predictors of thrombolytic administration in the subgroup of patients without contraindications to thrombolysis. RESULTS: We included 6826 cases (final diagnosis mild stroke, 74.6% and TIA, 25.4%). Median age was 72 (interquartile range, 21); 52.7% men, 70.3% white, 12.9% black, 16.8% Hispanic; and median National Institutes of Health Stroke Scale, 2 (interquartile range, 3). Patients who received thrombolysis (n=1281, 18.7%) were younger (68 versus 72 years), had less vascular risk factors (hypertension, diabetes mellitus, and dyslipidemia), had lower risk of prior vascular disease (myocardial infarction, peripheral vascular disease, and previous stroke), and had a higher presenting median National Institutes of Health Stroke Scale (4 versus 2). In the multilevel multivariable model, early hospital arrival (arrive by 0-2 hours versus ≥3.5 hours; odds ratio [OR], 8.16; 95% confidence interval [CI], 4.76-13.98), higher National Institutes of Health Stroke Scale (OR, 1.87; 95% CI, 1.77-1.98), aphasia at presentation (OR, 1.35; 95% CI, 1.12-1.62), faster door-to-computed tomography time (OR, 1.81; 95% CI, 1.53-2.15), and presenting to an academic hospital (OR, 2.02; 95% CI, 1.39-2.95) were independent predictors of thrombolysis administration. CONCLUSIONS: Mild acutely presenting stroke patients are more likely to receive thrombolysis if they are young, white, or Hispanic and arrive early to the hospital with more severe neurological presentation. Identification of predictors of thrombolysis is important in design of future studies to assess the use of thrombolysis for mild stroke.

Racial-Ethnic Disparities in Acute Stroke Care in the Florida-Puerto Rico Collaboration to Reduce Stroke Disparities Study.

BACKGROUND: Racial-ethnic disparities in acute stroke care can contribute to inequality in stroke outcomes. We examined race-ethnic disparities in acute stroke performance metrics in a voluntary stroke registry among Florida and Puerto Rico Get With the Guidelines-Stroke hospitals. METHODS AND RESULTS: Seventy-five sites in the Florida Puerto Rico Stroke Registry (66 Florida and 9 Puerto Rico) recorded 58 864 ischemic stroke cases (2010-2014). Logistic regression models examined racial-ethnic differences in acute stroke performance measures and defect-free care (intravenous tissue plasminogen activator treatment, in-hospital antithrombotic therapy, deep vein thrombosis prophylaxis, discharge antithrombotic therapy, appropriate anticoagulation therapy, statin use, smoking cessation counseling) and temporal trends. Among ischemic stroke cases, 63% were non-Hispanic white (NHW), 18% were non-Hispanic black (NHB), 14% were Hispanic living in Florida, and 6% were Hispanic living in Puerto Rico. NHW patients were the oldest, followed by Hispanics, and NHBs. Defect-free care was greatest among NHBs (81%), followed by NHWs (79%) and Florida Hispanics (79%), then Puerto Rico Hispanics (57%) (P<0.0001). Puerto Rico Hispanics were less likely than Florida whites to meet any stroke care performance metric other than anticoagulation. Defect-free care improved for all groups during 2010-2014, but the disparity in Puerto Rico persisted (2010: NHWs=63%, NHBs=65%, Florida Hispanics=59%, Puerto Rico Hispanics=31%; 2014: NHWs=93%, NHBs=94%, Florida Hispanics=94%, Puerto Rico Hispanics=63%). CONCLUSIONS: Racial-ethnic/geographic disparities were observed for acute stroke care performance metrics. Adoption of a quality improvement program improved stroke care from 2010 to 2014 in Puerto Rico and all Florida racial-ethnic groups. However, stroke care quality delivered in Puerto Rico is lower than in Florida. Sustained support of evidence-based acute stroke quality improvement programs is required to improve stroke care and minimize racial-ethnic disparities, particularly in resource-strained Puerto Rico.

Gender-Specific Differences for Risk of Disability and Death in Atrial Fibrillation-Related Stroke.

In the latest American Heart Association/American College of Cardiology/Heart Rhythm Society atrial fibrillation (AF) guidelines, CHA2DS2-VASc replaced the CHADS2 stroke risk assessment to determine prophylactic anticoagulation, reflecting female gender's association with stroke incidence in AF. However, little investigation has been pursued of potential risk factors associated with worsened stroke severity. In this study, we examined patients with AF with ischemic stroke patient characteristics associated with increased stroke severity. Using the Get With The Guidelines-Stroke database, we retrospectively identified 221 consecutive patients with AF diagnosed with acute ischemic stroke and performed in depth chart review, evaluating demographics, labs, and co-morbidities. We analyzed the modified Rankin Scale (mRS) at discharge as a surrogate for stroke severity, defining severe stroke as fatal (mRS of 6) or disabling (mRS 4 to 5), requiring max assistance with ambulation or activities of daily living. Female gender, advanced age, and decreased body surface area were associated with disabling or fatal stroke (68.3% of patients with mRS 4 to 6 vs 50% with mRS 0 to 3, 78.4 vs 71.1 year, and 1.83 vs 1.92, respectively). Using a backward elimination approach revealed a logistic regression model with statistically significant odds ratios (ORs) for female gender (OR 1.99) and age (OR 1.04), and borderline significant for a history of coronary artery disease (OR 1.89). In conclusion, female gender is associated in the AF population with a twofold risk of severe disabling or fatal ischemic stroke, a finding that persists after controlling for potential confounders. This finding highlights the potential benefit from appropriate anticoagulation use for stroke prophylaxis in the AF population.

Constitutional Chromoanagenesis of Distal 13q in a Young Adult with Recurrent Strokes.

Constitutional chromoanagenesis events, which include chromoanasynthesis and chromothripsis and result in highly complex rearrangements, have been reported for only a few individuals. While rare, these phenomena have likely been underestimated in a constitutional setting as technologies that can accurately detect such complexity are relatively new to the mature field of clinical cytogenetics. G-banding is not likely to accurately identify chromoanasynthesis or chromothripsis, since the banding patterns of chromosomes are likely to be misidentified or oversimplified due to a much lower resolution. We describe a patient who was initially referred for cytogenetic testing as a child for speech delay. As a young adult, he was referred again for recurrent strokes. Chromosome analysis was performed, and the rearrangement resembled a simple duplication of 13q32q34. However, SNP microarray analysis showed a complex pattern of copy number gains and a loss consistent with chromoanasynthesis involving distal 13q (13q32.1q34). This report emphasizes the value of performing microarray analysis for individuals with abnormal or complex chromosome rearrangements.