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Preliminary assessments of the feasibility, safety, and effects on neuronal reorganization measured with transcranial magnetic stimulation (TMS) from Constraint-Induced Movement Therapy (CIMT) of the upper extremity were made in eight cases of subacute stroke. Within fourteen days of their stroke, patients were randomly assigned to two weeks of CIMT or traditional therapy. Baseline motor performance and cortical/subcortical representation for movement with TMS were assessed before treatment. Post-treatment assessments were made at the end of treatment and at three months after the stroke. The TMS mapping showed a larger motor representation in the lesioned hemisphere of the CIMT patients as compared to the controls at the three-month follow-up assessment. The enlarged motor representation in the lesioned hemisphere for hand movement correlated with improved motor function of the affected hand, suggesting a link between movement representation size as measured with TMS and functionality. These results suggest that TMS can be safely and effectively used to assess brain function in subacute stroke and further suggest that CIMT may enhance cortical/subcortical motor reorganization and accelerate motor recovery when started within the first two weeks after stroke. [ABSTRACT FROM AUTHOR]

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 T 3 AM 2 PA 1 scale., Methods: The T 3 AM 2 PA 1 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 T 3 AM 2 PA 1 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 T 3 AM 2 PA 1 scale accurately predicts the presence of clinical IVO in patients with AIS. Adopting the T 3 AM 2 PA 1 scale could reduce revascularization times, improve treatment outcomes, and potentially reduce disability., Competing Interests: Competing interests: WSB has received grants from Athersys, BMS, Florida High Tech Corridor, NIH, Reneuron, and VuEssence. His consulting activities include Genentech, VuEssence, with stock options in VuEssence. He has patents planned or pending with USF. His equity positions include holdings in Inur Technologies and Electron Transport Biotech. He also has a financial interest in PRIME Education. MM has received grants from the NIH and has consulted with Balt, Cerenovus, Medtronic, and Rapid Pulse. His testimony work includes Foley Mansfield and Huff Powell Bailey as clients. He has participated as an advisor for Cerenovus and Rapid Pulse. His financial holdings include Bendit Technologies, Borvo Medical, BrainQ, Endostream, Serenity Medical, Synchron, Sim & Cure, QAS AI, Quantanosis AI. ZR has received royalties for his publication on aneurysms and has lectured for Beijing Tiantan Hospital, the Chinese Stroke Association, and the Chinese Institute for Brain Research., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Competing interests: MM: grant: NIH; consultant: Cerenovus, Medtronic; stock options: Bendit Technologies, Borvo Medical, BrainQ, Endostream, Serenity Medical, Synchron, Sim&Cure, QAS.AI, Quantanosis.AI; Assistant Editor for JNIS. WSB: grant: Athersys, BMS, Florida High Tech Corridor, NIH, Reneuron, VuEssence; consultant: Genentech, VuEssence; stock options: VuEssence; other: PRIME Education. ABP: grant: NIH; stock options: SPKL LLC., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: Unsuccessful thrombectomy of acute large vessel occlusions (LVOs) has been associated with unfavourable outcomes. Multiple randomised controlled trials (RCTs) have reported a failure rate of 12%-41% for thrombectomy procedures. Various factors contribute to failed thrombectomy, including technical difficulties in accessing the occlusion, unsuccessful thrombus retrieval, thrombotic reocclusion and pre-existing intracranial atherosclerotic stenosis. Although some studies have explored balloon dilation or permanent stenting as rescue intracranial angioplasty for failed thrombectomy in individual cases, there is currently no evidence from RCTs on this specific topic., Aim: To evaluate the potential superiority of bailout angioplasty over standard treatment in cases of unsuccessful recanalisation (eTICI 0 to 2a) or residual severe stenosis (>70%) after thrombectomy in acute LVO patients within 24 hours of stroke onset., Design: This study is a multicentre, prospective, randomised, controlled clinical trial designed by investigators. It compares bailout angioplasty with standard therapy and follows an open-label treatment approach while maintaining a blinded outcome assessment (PROBE design). Our objective is to allocate 348 patients in a 1:1 ratio to either receive bailout angioplasty as an intervention or standard therapy as a control, following unsuccessful thrombectomy., Outcome: The main measure of interest is the modified Rankin Scale (mRS) Score, which will be assessed in a blinded manner at 90 (±14) days following randomisation. The primary effect size will be determined using ordered logistic regression to calculate the common OR, representing the shift on the six-category mRS Scale at the 90-day mark. Additionally, the safety outcomes will be evaluated, including symptomatic intracranial haemorrhage within 18-36 hours, severe procedure-related complications and mortality within 90 (±14) days, among others., Discussion: The ANGEL-REBOOT study aims to generate substantial evidence regarding the efficacy and safety of bailout intracranial angioplasty as a treatment option for patients with LVO who have experienced unsuccessful thrombectomy., Trial Registration Number: NCT05122286., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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.

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).

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.

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.

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.

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., Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

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., (Copyright © 2019 Rose, Meriwether, Fradley, Renati, Martin, Kasprowicz, Patel, Mokin, Murtagh, Kip, Bozeman, McTigue, Hilker, Kirby, Wick, Tran, Burgin and Labovitz.)

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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.

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., Competing Interests: Disclosures: All authors do not have conflict of interest with any third party related to this work.

Background: Understanding how many patients are eligible for endovascular therapy can help develop more effective stroke systems of care., Objective: To determine the proportion of patients eligible for endovascular therapy., Methods: In this single center retrospective cohort study, we identified patients with acute ischemic stroke from large vessel occlusion (LVO) from January 2014 to December 2015. Selection criteria including LVO location, Alberta stroke program early computed tomography score (ASPECTS) range, hospital arrival time, and the use of intravenous thrombolysis were applied to calculate proportions of patients eligible for endovascular therapy., Results: Of 989 patients with acute ischemic stroke, LVO was identified in 224 (23%) cases. Eighty-four percent of patients admitted within 6 h, 75% of patients admitted within 6 to 12 h, and 77% of patients with M1 and internal carotid artery occlusions admitted within 12 to 24 h had favorable ASPECTS for thrombectomy, defined as ASPECTS ≥ 6. Severity of NIHSS (National Institutes of Health Stroke Scale) was predictive of favorable ASPECTS (odds ratio [OR] 0.20, 95% confidence interval [CI] 0.04-0.74; P = .014 for NIHSS > 10 and OR 0.30, 95% CI 0.12-0.80; P = .014 for NIHSS > 20), whereas time of hospital arrival was not (OR 1.73, 95% CI 0.76-4.03; P = .26). Using all class I, Level of Evidence A American Heart Association guidelines criteria, 4% of patients with acute ischemic stroke were eligible for endovascular therapy. Up to 20% of patients were eligible for endovascular therapy with less restrictive criteria (Class IIb; Level of Evidence C)., Conclusion: Depending on the sets of selection criteria, between 4% (the most restrictive criteria) and 20% (the least restrictive criteria) of patients with LVO are potentially eligible for endovascular therapy.

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., (© 2018 American Heart Association, Inc.)

Background: Favorable imaging profile according to the Alberta Stroke Program Early CT Score (ASPECTS) on non-contrast head CT is a key criterion for the selection of patients with ischemic stroke from large vessel occlusion (LVO) for IA revascularization therapies., Objective: To analyze factors associated with changes in ASPECTS during inter-hospital transfer and to determine how deterioration of ASPECTS affects eligibility for endovascular procedures., Methods: We analyzed factors associated with changes in ASPECTS during inter-hospital transfer and their potential impact on eligibility for IA stroke therapies in patients with anterior circulation ischemic strokes. Clinical and demographic characteristics between patients with favorable (ASPECTS ≥6) and unfavorable (ASPECTS <6) imaging on repeat CT were compared., Results: Stroke evolution towards unfavorable ASPECTS occurred in 13/42 (31%) patients who initially had a favorable imaging profile at outside hospitals. A higher National Institutes of Health Stroke Scale (NIHSS) score was the only significant predictor of ASPECTS decay, whereas other clinical characteristics, such as the use of IV thrombolysis and site of LVO, were similar between the two groups., Conclusions: In our cohort, one out of three patients became ineligible for IA thrombectomy because of unfavorable ASPECTS 'decay' following inter-hospital transfer. Except for NIHSS severity, baseline clinical factors could not identify which patients were at risk for ASPECTS deterioration., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

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., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

In the latest American Heart Association/American College of Cardiology/Heart Rhythm Society atrial fibrillation (AF) guidelines, CHA 2 DS 2 -VASc replaced the CHADS 2 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., (Published by Elsevier Inc.)

Background and Purpose: Sex-specific disparities in stroke care including thrombolytic therapy and early hospital admission are reported. In a large registry of Florida and Puerto Rico hospitals participating in the Get With The Guidelines-Stroke program, we sought to determine sex-specific differences in ischemic stroke performance metrics and overall thrombolytic treatment., Methods: Around 51 317 (49% women) patients were included from 73 sites from 2010 to 2014. Multivariable logistic regression with generalized estimating equations evaluated sex-specific differences in the prespecified Get With The Guidelines-Stroke metrics for defect-free care in ischemic stroke, adjusting for age, race-ethnicity, insurance status, hospital characteristics, individual risk factors, and the presenting stroke severity., Results: As compared with men, women were older (73±15 versus 69±14 years; P<0.0001), more hypertensive (67% versus 63%, P<0.0001), and had more atrial fibrillation (19% versus 16%; P<0.0001). Defect-free care was slightly lower in women than in men (odds ratio, 0.96; 95% confidence interval, 0.93-1.00). Temporal trends in defect-free care improved substantially and similarly for men and women, with a 29% absolute improvement in women (P<0.0001) and 28% in men (P<0.0001), with P value of 0.13 for time-by-sex interaction. Women were less likely to receive thrombolysis (odds ratio, 0.92; 95% confidence interval, 0.86-0.99; P=0.02) and less likely to have a door-to-needle time <1 hour (odds ratio, 0.83; 95% confidence interval, 0.71-0.97; P=0.02) as compared with men., Conclusions: Women received comparable stroke care to men in this registry as measured by prespecified Get With The Guidelines metrics. However, women less likely received thrombolysis and had door-to-needle time <1 hour, an observation that calls for the implementation of interventions to reduce sex disparity in these measures., (© 2016 American Heart Association, Inc.)

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., (© 2016 S. Karger AG, Basel.)

Objectives: To report and associate acute cerebral infarctions in 2 young, previously healthy siblings with use of the street drug known as "spice" (a synthetic marijuana product, also known as "K2"), which they independently smoked before experiencing acute embolic-appearing ischemic strokes., Methods: We present history, physical examination, laboratory data, cerebrovascular imaging, echocardiogram, ECG, and hospital course of these patients., Results: We found that in both siblings spice was obtained from the same source. The drug was found to contain the schedule I synthetic cannabinoid JWH-018. Full stroke workup was unrevealing of a stroke etiology; urine drug screen was positive for marijuana., Conclusions: We found that our 2 patients who smoked the street drug spice had a temporal association with symptoms of acute cerebral infarction. This association may be confounded by contaminants in the product consumed (i.e., marijuana or an unidentified toxin) or by an unknown genetic mechanism. The imaging of both patients suggests an embolic etiology, which is consistent with reports of serious adverse cardiac events with spice use, including tachyarrhythmias and myocardial infarctions.

Background: Acute treatment of ischemic stroke patients presenting more than eight-hours after symptom onset remains limited and largely unproven. Partial aortic occlusion using the NeuroFlo catheter can augment cerebral perfusion in animals. We investigated the safety and feasibility of employing this novel catheter to treat ischemic stroke patients eight-hours to 24 h following symptom onset., Methods: A multicenter, single-arm trial enrolled ischemic stroke patients at nine international academic medical centers. Eligibility included age 18-85 years old, National Institutes of Health stroke scale (NIHSS) score between four and 20, within eight-hours to 24 h after symptom onset, and perfusion-diffusion mismatch confirmed by magnetic resonance imaging. The primary outcome was all adverse events occurring from baseline to 30 days posttreatment. Secondary outcomes included stroke severity on neurological indices through 90 days. This study is registered with ClinicalTrials.gov, number NCT00436592., Results: A total of 26 patients were enrolled. Of these, 25 received treatment (one excluded due to aortic morphology); five (20%) died. Favorable neurological outcome at 90 days (modified Rankin score 0-2 vs. 3-6) was associated with lower baseline NIHSS (P  <  0·001) and with longer duration from symptom discovery to treatment. There were no symptomatic intracranial hemorrhages or parenchymal hematomas. Asymptomatic intracranial hemorrhage was visible on computed tomography in 32% and only on microbleed in another 20%., Conclusions: Partial aortic occlusion using the NeuroFlo catheter, a novel collateral therapeutic strategy, appears safe and feasible in stroke patients eight-hours to 24 h after symptom onset., (© 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.)

Background: Increasing age is associated with poor outcome after stroke. The Safety and Efficacy of NeuroFlo Technology in Ischemic Stroke (SENTIS) trial explored the augmentation of collateral circulation to the ischemic penumbra as a novel approach to stroke treatment. The aim of this post hoc analysis was to examine the effect of age on outcomes in the SENTIS trial., Methods: Using data from the randomized controlled SENTIS trial, we explored outcomes of cerebral blood flow augmentation using the NeuroFlo™ device in patients categorized by age strata at 70 and 80 years. We evaluated outcomes of overall serious adverse event (SAE) and intracerebral hemorrhage (ICH) rates, freedom from all-cause and stroke-related mortality, and independent functional outcome as defined by the modified Rankin Scale score (mRS ≤2)., Results: The SENTIS as-treated cohort included 251 patients ≥70 years and 107 patients ≥80 years. Elderly SENTIS patients included a higher percentage of women and Caucasians than the younger group. Patients in the older group more frequently had vascular risk factors including hypertension, previous stroke, transient ischemic attacks and atrial fibrillation. However, baseline risk-factor profile, stroke severity, and time to randomization did not differ between the treated and nontreated elderly patients. The older patients treated with NeuroFlo had significantly higher chances for survival and for obtaining an independent functional state (mRS ≤2) compared with those who were not treated. Rates of SAEs and ICHs did not differ between the treatment groups., Conclusions: NeuroFlo treatment is safe and results in better outcomes for elderly patients. This may be the result of recruitment and support of already existing collateral systems in these patients., (Copyright © 2012 S. Karger AG, Basel.)

Endarterectomy and angioplasty with stenting have emerged as 2 alternative treatments for carotid artery stenosis. This study's objective was to determine the cost-effectiveness of carotid artery stenting (CAS) compared with carotid endarterectomy (CEA) in symptomatic subjects who are suitable for either intervention. A Markov analysis of these 2 revascularization procedures was conducted using direct Medicare costs (2007 US$) and characteristics of a symptomatic 70-year-old cohort over a lifetime. In the base case analysis, CAS produced 8.97 quality-adjusted life-years, compared with 9.64 quality-adjusted life-years for CEA. The incremental cost of stenting was $17,700, and thus CAS was dominated by CEA. Sensitivity analyses show that the long-term probabilities of major stroke or mortality influenced the results. In the base case analysis, CEA for patients with symptomatic stenosis has a greater benefit than CAS, with lower direct costs. With 59% probability, CEA will be the optimal intervention when all of the model assumptions are varied simultaneously., (Copyright (c) 2010 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Damage to the adult, primary visual cortex (V1) causes severe visual impairment that was previously thought to be permanent, yet several visual pathways survive V1 damage, mediating residual, often unconscious functions known as "blindsight." Because some of these pathways normally mediate complex visual motion perception, we asked whether specific training in the blind field could improve not just simple but also complex visual motion discriminations in humans with long-standing V1 damage. Global direction discrimination training was administered to the blind field of five adults with unilateral cortical blindness. Training returned direction integration thresholds to normal at the trained locations. Although retinotopically localized to trained locations, training effects transferred to multiple stimulus and task conditions, improving the detection of luminance increments, contrast sensitivity for drifting gratings, and the extraction of motion signal from noise. Thus, perceptual relearning of complex visual motion processing is possible without an intact V1 but only when specific training is administered in the blind field. These findings indicate a much greater capacity for adult visual plasticity after V1 damage than previously thought. Most likely, basic mechanisms of visual learning must operate quite effectively in extrastriate visual cortex, providing new hope and direction for the development of principled rehabilitation strategies to treat visual deficits resulting from permanent visual cortical damage.

Context: An increasing number of deaths following severe stroke are due to terminal extubations. Variation in withdrawal-of-care practices suggests the possibility of unnecessary prolongation of suffering or of unwanted deaths., Objectives: To review the available evidence on prognosis in mechanically ventilated stroke patients and to provide an overall framework to optimize decision making for clinicians, patients, and families., Data Sources: Search of MEDLINE from 1980 through March 2005 for English-language articles addressing prognosis in mechanically ventilated stroke patients. From 689 articles identified, we selected 17 for further review. We also identified factors that influence, and decision-making biases that may result, in overuse or underuse of life-sustaining therapies, with a particular emphasis on mechanical ventilation., Evidence Synthesis: Overall mortality among mechanically ventilated stroke patients is high, with a 30-day death rate approximating 58% (range in literature, 46%-75%). Although data are limited, among survivors as many as one third may have no or only slight disability, yet many others have severe disability. One can further refine prognosis according to knowledge of stroke syndromes, early patient characteristics, use of clinical prediction rules, and the need for continuing interventions. Factors influencing preferences for life-sustaining treatments include the severity and pattern of future clinical deficits, the probability of these deficits, and the burdens of treatments. Decision-making biases that may affect withdrawal-of-treatment decisions include erroneous prognostic estimates, inappropriate methods of communicating evidence, misunderstanding patient values and expectations, and failing to appreciate the extent to which patients can physically and psychologically adapt., Conclusions: Although prognosis among mechanically ventilated stroke patients is generally poor, a minority do survive without severe disability. Prognosis can be assessed according to clinical presentation and patient characteristics. There is an urgent need to better understand the marked variation in the care of these patients and to reliably measure and improve the patient-centeredness of such decisions.

Background: Tissue plasminogen activator (TPA) activity may be enhanced with ultrasound, potentially 2 MHz transcranial Doppler (TCD). The authors present Phase I data of the CLOTBUST (Combined Lysis of Thrombus in Brain ischemia using transcranial Ultrasound and Systemic TPA)., Subjects and Methods: Nonrandomized stroke patients with proximal arterial occlusion on a prebolus TCD receiving intravenous 0.9 mg/kg TPA within 3 hours after stroke onset were monitored with portable diagnostic TCD equipment and a standard headframe. Complete recanalization was defined as thrombolysis in brain ischemia (TIBI) flow grades 4-5., Results: 55 patients (mean age 69 +/- 15 years, median baseline NIH Stroke Scale [NIHSS] 18, range 4-29, 90% with 3 9 points) were treated at 125 +/- 36 minutes from symptom onset. TCD monitoring began at 117 +/- 39 minutes. Complete recanalization on TCD within 2 hours after bolus was found in 20 patients (36%). Dramatic recovery (NIHSS score < or = 3) occurred in 20% at 2 hours and in 24% at 24 hours. Overall improvement by > or = 4 NIHSS points was found in 49% at 24 hours. Improvement was associated with recanalization during or shortly after TPA infusion (phi r2 = .5, P = .03); however, in 6/20 patients with complete recanalization (30%), no immediate clinical change was noticed within 2 hours. Overall symptomatic hemorrhage rate was 5.5%., Conclusions: Continuous TCD insonation for up to 2 hours at maximum intensities allowed by current bio-safety guidelines is safe. Dramatic recovery and complete recanalization shortly after TPA bolus are feasible goals for thrombolysis given with TCD monitoring.

Background and Purpose: Cryptogenic stroke is associated with an increased prevalence of patent foramen ovale. The Paradoxical Emboli From Large Veins in Ischemic Stroke (PELVIS) study hypothesized that patients with cryptogenic stroke have an increased prevalence of pelvic deep venous thrombosis (DVT)., Methods: At 5 sites, patients 18 to 60 years of age received an MRI venogram (MRV) of the pelvis within 72 hours of new symptom onset. Clinical data were then determined. Radiologists blinded to clinical data later read the scans., Results: The 95 patients who met entry criteria were scanned. Their mean+/-SD age was 46+/-10 years, and time from stroke onset to pelvic MRV scan was 49+/-16 hours. Compared with those with stroke of determined origin (n=49), patients with cryptogenic stroke (n=46) were significantly younger, had a higher prevalence of patent foramen ovale (61% versus 19%), and had less atherosclerosis risk factors. Cryptogenic patients had more MRV scans with a high probability for pelvic DVT (20%) than patients with stroke of determined origin (4%, P<0.03), with most having an appearance of a chronic DVT., Conclusions: In this study of young stroke patients evaluated early after stroke, patients with cryptogenic stroke showed differences in several clinical features compared with patients with stroke of determined origin, including increased prevalence of pelvic DVT. The results require confirmation but suggest that paradoxical embolus from the pelvic veins may be the cause of stroke in a subset of patients classified as having cryptogenic stroke.

Purpose: The increased prevalence of patent foramen ovale in patients with cryptogenic strokes suggests the occurrence of paradoxical embolism. The identification of deep venous thromboses (DVTs) in this population would strengthen this hypothesis. The purpose of this study was to image the subdiaphragmatic venous system in a cohort of patients with cryptogenic strokes., Materials and Methods: In 37 patients with cryptogenic brain ischemia and interatrial communication, duplex studies of calf, popliteal, and femoral veins, and magnetic resonance imaging venograms of the pelvis veins were performed., Results: In 10 patients, DVTs were diagnosed that were considered to be the cause of cryptogenic brain ischemia on probable (n = 6) or possible (n = 4) bases. In these patients, the median time from stroke to DVT was 3.25 days. In 5 of these 10 patients, DVTs did not involve popliteal and femoral veins, areas thought most important to pulmonary embolism, but instead were isolated to calf or pelvic veins. Although none of these 10 patients had abnormal blood hypercoagulation tests, 8 of the 10 did have clinical conditions suggesting predisposition to developing DVTs, such as concomitant neoplasms or pulmonary embolism., Conclusions: Increased evidence for paradoxical embolism may emerge when diagnostic strategies use multiple imaging methods and evaluate a broad extent of the subdiaphragmatic veins.

Background and Purpose: In animal models, the combination of caffeine and ethanol (caffeinol) provides robust neuroprotection at blood levels that should be easily and safely achieved in humans. This study was designed to determine the safety and tolerability of ascending doses of this combination in stroke patients., Methods: This Food and Drug Administration-approved open-label, single-arm, dose-escalation study had 3 original dose groups: group 1, caffeine 6 mg/kg plus ethanol 0.2 g/kg; groups 2 and 3, incremental increases of caffeine and ethanol by 2 mg/kg and 0.2 g/kg, respectively. Intravenous thrombolysis was encouraged if patients qualified. Drug was started within 6 hours of stroke onset, and blood levels of caffeine and ethanol were drawn at baseline and end of infusion. The target blood caffeine and ethanol ranges were 8 to 10 microg/mL and 30 to 50 mg/dL, respectively. Clinical outcome measurements included the National Institutes of Health Stroke Scale at the end of infusion, at 24 hours, and at discharge. Potential complications from caffeine and ethanol were recorded. Cases were reviewed by an independent stroke neurologist for safety., Results: A total of 23 patients were recruited. Target blood caffeine and ethanol levels were reached in 0 of the 4 patients in the first group. The second dose group (caffeine 8 mg/kg plus ethanol 0.4 g/kg) included 8 patients. The median end-of-infusion caffeine and ethanol levels were within the desired target ranges. Two days after infusion, 1 patient in this group with preexisting cardiac disease and end-of-infusion caffeine and ethanol levels of 10.7 microg/mL and 69 mg/dL developed reversible congestive heart failure and required transfer to an intensive care unit. The original third dose group was canceled given achievement of target blood caffeine and ethanol levels in group 2. However, 3 new dose groups were created in an attempt to minimize the dose of ethanol. Although blood levels were proportional to dose, none of these new dose groups provided optimal blood levels. Congestive heart failure occurred in 1 other patient with previously asymptomatic cardiomyopathy. No other side effects were noted. Concomitant thrombolytic therapy was given in 8 patients, 1 of whom died of intracerebral hemorrhage., Conclusions: Caffeinol alone or combined with intravenous tissue plasminogen activator can be administered safely. Caffeine 8 mg/kg plus ethanol 0.4 g/kg produces target caffeine and ethanol levels of 8 to 10 microg/mL and 30 to 50 mg/dL, respectively. A randomized, placebo-controlled trial is needed to determine the neuroprotective effect of this combination.

We studied whether a computer algorithm or abstractor could diagnose stroke as well as a fellowship-trained stroke neurologist. As part of an ongoing prospective, community-based stroke surveillance project, a diagnostic algorithm was developed, and patients' neurologic signs and symptoms were collected in a computerized database. The abstractors were blinded to the results of this algorithm and were asked to verify whether the patient had a stroke. The separate results of the computer and abstractor were compared with the final diagnosis given by the blinded neurologist. From 1 January through 31 July 2000, 3418 cases were screened. The abstractors yielded sensitivity 91%, specificity 97%, positive predictive value (PPV) 85%, and negative predictive value (NPV) 99%. Three computer algorithms were evaluated. The sensitivities ranged from 83% to 96%, specificity ranged from 88% to 97%, PPV ranged from 54% to 81%, and NPV ranged from 97% to 99%. The use of computer verification or abstractors may obviate the need for physician stroke verification and may greatly improve study efficiency.

Background and Purpose: Power motion mode Doppler (PMD) simultaneously displays flow signal intensity and direction over several centimeters of intracranial space. Insonation protocol for PMD and spectral transcranial Doppler (TCD) with typical PMD flow signatures is described in serial patients with acute stroke symptoms examined via conventional windows with a PMD/TCD unit., Results: Thirty-five patients were studied within 12 hours after stroke onset (age 64 +/- 15 years; 8 received intravenous and 3 intra-arterial thrombolysis). One patient had no temporal window, and 3 patients had suboptimal windows. In 90% of patients, PMD showed more than 1 ipsilateral temporal windows. In 63% of patients (n = 22), PMD simultaneously displayed the entire M1 (65-45 mm) and proximal M2 (45-30 mm) flows, leading to spectral TCD examination of the proximal M2 middle cerebral artery (MCA) in 28 of 35 patients (80%). All patients had sufficient foraminal (depth display = 60-110 mm) and orbital (depth display = 30-80 mm) windows. PMD displayed the entire basilar artery stem (75-100+ mm) in 69% (n = 24) of patients, and the distal basilar flow was detected in all patients by both PMD and TCD. TCD results were normal (12), proximal intracranial stenosis (5), large vessel occlusion (17), and cerebral circulatory arrest (1). Compared to spectral TCD, PMD signatures of similar diagnostic significance were low resistance (vessel identification and recanalization), high resistance (ophthalmic artery identification and distal obstruction), collateral (communicating arteries and leptomeningeal flow), reverberating (circulatory arrest), and branch embolization., Conclusions: PMD is a window-finding tool and a guide for spectral TCD gate placement. PMD facilitates flow detection in the M2 branches and the distal basilar artery. PMD can demonstrate recanalization of the entire MCA main stem and proximal branches, increase the yield of embolus detection and procedure monitoring, and facilitate abnormal flow pattern recognition.

Background and Purpose: Acute-stroke patients receiving standard intravenous tissue plasminogen activator (tPA) have been noted to experience early dramatic recoveries. The prevalence, clinical characteristics, and outcome of patients experiencing dramatic recovery is not well described., Methods: We prospectively studied all patients presenting with acute middle cerebral artery (MCA) stroke syndromes and transcranial Doppler (TCD) evidence of an MCA obstruction. All patients received intravenous tPA per the National Institute of Neurological and Communicative Disorders and Stroke protocol, with serial National Institutes of Health Stroke Scale (NIHSS) scores and continuous TCD monitoring. Dramatic recovery was defined as an improvement of > or =10 NIHSS points or a decrease to an NIHSS score of < or =3 by the end of infusion. Outcome at the end of infusion, at 24 hours, and at long-term follow-up were obtained. The timing and pattern of deficit recovery during dramatic recovery was also studied., Results: Dramatic recovery occurred in 22% of all patients. Compared with patients who did not experience dramatic recovery, those patients who did had significantly lower end-infusion NIHSS (median 2 and range 0 to 16 for dramatic-recovery patients versus median 17 and range 6 to 35 for non-dramatic-recovery patients, P<0.01) and 24-hour NIHSS (median 2 and range 0 to 16 for dramatic-recovery patients versus median 13 and range 2 to 35 for non-dramatic-recovery patients, P<0.01). A long-term modified Rankin Score benefit was noted (median 1 and range 0 to 6 for dramatic-recovery patients versus median 4 and range 0 to 6 for non-dramatic-recovery patients, P<0.01). Baseline clinical characteristics were similar. The only difference was improved TCD-determined flow values at the end of infusion (normal restoration of flow was 58% in dramatic-recovery patients versus 14% in non-dramatic-recovery patients, P<0.01). A characteristic pattern of recovery of deficit was noted., Conclusions: Early dramatic recovery in acute MCA stroke patients treated with intravenous tPA is relatively frequent. The benefit of dramatic recovery is maintained at 24 hours and over the long term. TCD monitoring suggests that dramatic recovery is a result of early restoration of MCA flow during the tPA infusion. The consistent pattern of early clinical recovery may help explain the mechanisms by which thrombolysis improves outcome and could suggest targets for enhancing the therapeutic effect of intravenous tPA.

Background and Purpose: It has been suggested that intravenous tissue plasminogen activator (TPA) would not lyse the large thrombus associated with internal carotid artery (ICA) occlusion and, therefore, would be ineffective in this setting. Vascular imaging, safety, and outcome of TPA therapy for ICA occlusion is not well described. Our goal was to determine the site of occlusion, early recanalization after TPA infusion, and its relationship to outcome., Methods: We reviewed our database of all stroke patients treated with i.v. TPA between July 1997 and July 1999. We identified all cases with carotid occlusion suggested by transcranial Doppler (TCD) and angiography. Occlusion and recanalization were assessed by site including proximal ICA (prICA), terminal ICA (tICA), and middle cerebral artery (MCA). Baseline National Institutes of Health Stroke Scale (NIHSS) scores and follow-up Rankin scores were obtained., Results: We treated 20 patients with carotid occlusion (age 63.9 +/- 10.8 years, 11 males, 9 females). Time to TPA infusion after stroke onset was 128 +/- 66 minutes. Baseline NIHSS scores were 16.4 +/- 5.4. Time to follow-up was 3.5 +/- 4.9 months (2 patients were lost to follow-up). Occlusion sites were prICA 40%, tICA 70%, and concurrent MCA 45%. Multiple sites were involved in 10/20 patients (50%). Among patients with pretreatment and posttreatment vascular imaging studies (n = 18), recanalization in the prICA and tICA was complete in 10%, partial in 16%, and none in 74%. MCA recanalization was complete in 35%, partial in 24%, and none in 41%. At follow-up, Rankin 0-1 was found in 8 patients (44%), Rankin 2-3 in 3 (17%), and Rankin 4-5 in 3 (17%). Mortality was 22% (n = 4) including 1 fatal intracerebral hemorrhage. Improvement was closely related to resumption of MCA flow (P < .01)., Conclusions: Most patients did not recanalize their ICA occlusion after intravenous TPA therapy. However, recanalization of associated proximal MCA clot, found in 45% of our patients, or improved MCA collateral flow was strongly associated with good outcome.

Context: Intravenous tissue-type plasminogen activator (tPA) therapy using the National Institute of Neurological Disorders and Stroke criteria has been given with variable safety to less than 5% of the patients who have ischemic strokes nationwide. Our center is experienced in treating large numbers of stroke patients with intravenous tPA., Objective: To report our total 4-year experience in the treatment of consecutive patients who had an ischemic stroke., Design: Prospective inception cohort registry of all patients seen by our stroke team and an additional retrospective medical record review of all patients treated between January 1, 1996, and June 1, 2000., Setting: A veteran stroke team composed of fellows and stroke-specialty faculty servicing 1 university and 3 community hospitals in a large urban setting., Patients: Consecutive patients with ischemic stroke treated within the first 3 hours of symptom onset., Intervention: According to the National Institute of Neurological Disorders and Stroke protocol, 0.9 mg/kg of intravenous tissue-type plasminogen activator was administered., Main Outcome Measures: Number and proportion treated, patient demographics, time to treatment, hemorrhage rates, and clinical outcome., Results: A total of 269 patients were treated between January 1, 1996, and June 1, 2000. Their mean age was 68 years (age range, 24-93 years); 48% were women. This represented 9% of all patients admitted with symptoms of cerebral ischemia at our most active hospital (over the final 6 months, 13% of all patients with symptoms of cerebral ischemia and 15% of all acute ischemic stroke patients). Before treatment the mean +/- SD National Institutes of Health Stroke Scale (NIHSS) score was 14.4 +/- 6.1 points (median, 14 points; range, 4-33 points). A tPA bolus was given at 137 minutes (range, 30-180 minutes); 28% of the patients were treated within 2 hours. The mean door-to-needle time was 70 minutes (range, 10-129 minutes). The symptomatic intracerebral hemorrhage rate was 5.6% of those patients with a second set of brain scans (4.5% of all patients), with a declining trend from 1996 to 2000. Protocol violations were found in 13% of all patients; the symptomatic intracerebral hemorrhage rate in these patients was 15%. At 24 hours, the NIHSS score was 10 +/- 8 points (median, 8 points; range, 0-36 points). In-hospital mortality was 15% and the patients' discharge NIHSS scores were 7 +/- 7 points (median, 3 points; range, 0-35 points)., Conclusions: Intravenous tPA therapy can be given to up to 15% of the patients with acute ischemic stroke with a low risk of symptomatic intracerebral hemorrhage. Successful experience with intravenous tPA therapy depends on the experience and organization of the treating team and adherence to published guidelines.

Background: No proven neuroprotective treatment exists for ischemic brain injury after cardiac arrest. Mild-to-moderate induced hypothermia (MIH) is effective in animal models., Methods and Results: A safety and feasibility trial was designed to evaluate mild-to-moderate induced hypothermia by use of external cooling blankets after cardiac arrest. Inclusion criteria were return of spontaneous circulation within 60 minutes of advanced cardiac life support, hypothermia initiated within 90 minutes, persistent coma, and lack of acute myocardial infarction or unstable dysrhythmia. Hypothermia to 33 degrees C was maintained for 24 hours followed by passive rewarming. Nine patients were prospectively enrolled. Mean time from advanced cardiac life support to return of spontaneous circulation was 11 minutes (range 3 to 30); advanced cardiac life support to initiation of hypothermia was 78 minutes (range 40 to 109); achieving 33 degrees C took 301 minutes (range 90 to 690). Three patients completely recovered, and 1 had partial neurological recovery. One patient developed unstable cardiac dysrhythmia. No other unexpected complications occurred., Conclusions: Mild-to-moderate induced hypothermia after cardiac arrest is feasible and safe. However, external cooling is slow and imprecise. Efforts to speed the start of cooling and to improve the cooling process are needed.

Background: Intravenous tissue plasminogen activator (TPA) is an approved therapy for acute ischaemic stroke in the United States. We aimed to noninvasively monitor the therapy to determine arterial recanalisation and persisting vascular abnormalities., Methods: We prospectively studied consecutive patients with symptoms of ischaemic stroke who received intravenous TPA and were monitored by 2 MHz transcranial Doppler (TCD) to determine occlusion and recanalisation (TIMI grades equivalent). For outcome assessment we used the National Institutes of Health Stroke Scale (NIHSS) score., Results: Sixty patients were studied (age 71+/-15 years, pre-TPA NIHSS 18+/-6.1, TPA bolus at 141+/-68 min after stroke onset). The internal carotid artery (ICA) was occluded in 25%, middle cerebral artery (MCA) in 80%; combined (ICA+MCA) occlusion was found in 19%; and basilar artery (BA) was occluded in 7%. Also, 2% had normal TCD and 8% of patients had no temporal windows. Complete recanalisation on TCD of all insonated arteries was found in 19 patients (32%) at 44+/-22 min after a TPA bolus. However, 67% of MCA, 25% of BA, and all ICA occlusions did not completely recanalise (TIMI grades 0-2). If flow impairment persisted for more than two hours after a TPA bolus, these patients continued to have significant neurological deficits at 24 hours (15.0+/-8.2 vs 6.3+/-7.3 NIHSS points, p<0.001 in non-parametric statistics). High-grade residual stenoses with microembolic signals were seen on TCD in the MCA and BA (n=3) suggesting continuing clot dissolution. In patients without complete recanalisation (n=36, or 60%), TCD identified lesions potentially amenable to further interventions., Conclusions: Persisting arterial occlusion after intravenous TPA therapy leads to poor short-term outcome. Noninvasive monitoring of TPA therapy with TCD can identify these high-risk patients for combined interventions such as intra-arterial thrombolysis, mechanical clot disruption, stenting or anticoagulation.

Background and Purpose: The authors establish accuracy parameters of a broad diagnostic battery for bedside transcranial Doppler (TCD) to detect flow changes due to internal carotid artery (ICA) stenosis or occlusion., Methods: The authors prospectively studied consecutive patients with stroke or transient ischemic attack referred for TCD. TCD was performed and interpreted at bedside using a standard insonation protocol. A broad diagnostic battery included major criteria: collateral flow signals, abnormal siphon or terminal carotid signals, and delayed systolic flow acceleration in the middle cerebral artery. Minor criteria included a unilateral decrease in pulsatility index (< or = 0.6 or < or = 70% of contralateral side), flow diversion signs, and compensatory velocity increase. Angiography or carotid duplex ultrasound (CDU) was used to grade the degree of carotid stenosis using North American criteria. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of TCD findings were determined., Results: Seven hundred and twenty patients underwent TCD, of whom 517 (256 men and 261 women) had angiography and/or CDU within 8.8 +/- 0.9 days. Age was 63.1 +/- 15.7 years. For a 70% to 99% carotid stenosis or occlusion, TCD had sensitivity of 79.4%, specificity of 86.2%, PPV of 57.0%, NPV of 94.8%, and accuracy of 84.7%. For a 50% to 99% carotid stenosis or occlusion, TCD had sensitivity of 67.5%, specificity of 83.9%, PPV of 54.5%, NPV of 90.0%, and accuracy of 81.6%. TCD detected intracranial carotid lesions with 84.9% accuracy and extracranial carotid lesions with 84.4% accuracy (sensitivity of 88% and 79%, specificity of 85% and 86%, PPV of 24% and 54%, and NPV of 99% and 95%, respectively). The prevalence of the ophthalmic artery flow reversal was 36.4% in patients with > or = 70% stenosis or occlusion. If present, this finding indicated a proximal ICA lesion location in 97% of these patients., Conclusions: In symptomatic patients, bedside TCD can accurately detect flow changes consistent with hemodynamically significant ICA obstruction; however, TCD should not be a substitute for direct carotid evaluation. Because TCD is sensitive and specific for a > or = 70% carotid stenosis or occlusion in both extracranial and intracranial carotid segments, it can be used as a complementary test to refine other imaging findings and detect tandem lesions.

Background: Arterial recanalization precedes clinical improvement or may lead to hemorrhage or reperfusion injury. Speed of clot lysis was not previously measured in human stroke., Methods and Results: Transcranial Doppler (TCD) and the National Institutes of Health Stroke Scale (NIHSS) were used to monitor consecutive patients receiving intravenous tissue plasminogen activator (tPA), before tPA bolus and at 24 hours. Patients with complete or partial recanalization of the middle cerebral or basilar artery on TCD were studied. Recanalization was classified a priori as sudden (abrupt appearance of a normal or stenotic low-resistance signal), stepwise (flow improvement over 1 to 29 minutes), or slow (>/=30 minutes). Recanalization was documented in 43 tPA-treated patients (age 68+/-17 years; NIHSS score 16.8+/-6, median 15 points). tPA bolus was given at a mean of 135+/-61 minutes after symptom onset. Recanalization began at a median of 17 minutes and was completed at 35 minutes after tPA bolus, with mean duration of recanalization of 23+/-16 minutes. Recanalization was sudden in 5, stepwise in 23, and slow in 15 patients. Faster recanalization predicted better short-term improvement (P=0.03). At 24 hours, 80%, 30%, and 13% of patients in these respective recanalization groups had NIHSS scores of 0 to 3. Symptomatic hemorrhage occurred in only 1 patient, who had stepwise recanalization 5.5 hours after stroke onset. Slow or partial recanalization with dampened flow signal was found in 53% of patients with total NIHSS scores >10 points at 24 hours (P=0.01). Complete recanalization (n=25) occurred faster (median 10 minutes) than partial recanalization (n=18; median 30 minutes; P=0.0001)., Conclusions: Rapid arterial recanalization is associated with better short-term improvement, mostly likely because of faster and more complete clot breakup with low resistance of the distal circulatory bed. Slow (>/=30 minutes) flow improvement and dampened flow signal are less favorable prognostic signs. These findings may be evaluated to assist with selection of patients for additional pharmacological or interventional treatment.