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Neutrophil extracellular traps (NETs) are highly associated with inflammatory response and vascular injury after ischemic stroke. As the primary degrader of NETs, DNase 1 is limited by easy deactivation and low efficiency of crossing the blood‐brain barrier (BBB). Here, CD206+ M2‐like macrophages‐derived exosomal (M2exo) system is developed for DNase 1 delivery to achieve enhanced ischemic stroke therapy. The nanoplatform can cross the BBB through transcytosis of exosomes, subsequently clearing NETs by DNase 1 to inhibit inflammatory factors release and prevent vascular injury. Moreover, M2exo induces the polarization of M1 microglia to M2 phenotype, alleviating neuroinflammation via producing anti‐inflammatory cytokines. This nanoplatform exhibits significant efficiency in reducing brain infarct area, improving long‐term neurologic outcomes, and promoting BBB remodeling. The mechanism for the synergistic effect from M2exo and DNase 1 is unveiled at the genetic level through transcriptome analysis. This work provides a paradigm for improving the effectiveness of ischemic stroke therapy. [ABSTRACT FROM AUTHOR]

The endothelial lining of cerebral microvessels is damaged relatively early after cerebral ischemia/reperfusion (I/R) injury and mediates blood-brain barrier (BBB) disruption, neurovascular injury, and long-term neurological deficits. I/R induces BBB leakage within 1 h due to subtle structural alterations in endothelial cells (ECs), including reorganization of the actin cytoskeleton and subcellular redistribution of junctional proteins. Herein, we show that the protein peroxiredoxin-4 (Prx4) is an endogenous protectant against endothelial dysfunction and BBB damage in a murine I/R model. We observed a transient upregulation of Prx4 in brain ECs 6 h after I/R in wild-type (WT) mice, whereas tamoxifen-induced, selective knockout of Prx4 from endothelial cells (eKO) mice dramatically raised vulnerability to I/R. Specifically, eKO mice displayed more BBB damage than WT mice within 1 to 24 h after I/R and worse long-term neurological deficits and focal brain atrophy by 35 d. Conversely, endothelium-targeted transgenic (eTG) mice overexpressing Prx4 were resistant to I/R-induced early BBB damage and had better long-term functional outcomes. As demonstrated in cultures of human brain endothelial cells and in animal models of I/R, Prx4 suppresses actin polymerization and stress fiber formation in brain ECs, at least in part by inhibiting phosphorylation/ activation of myosin light chain. The latter cascade prevents redistribution of junctional proteins and BBB leakage under conditions of Prx4 repletion. Prx4 also tempers microvascular inflammation and infiltration of destructive neutrophils and proinflammatory macrophages into the brain parenchyma after I/R. Thus, the evidence supports an indispensable role for endothelial Prx4 in safeguarding the BBB and promoting functional recovery after I/R brain injury. [ABSTRACT FROM AUTHOR]

Aging compromises the repair and regrowth of brain vasculature and white matter during stroke recovery, but the underlying mechanisms remain elusive. To understand how aging jeopardizes brain tissue repair after stroke, we performed single-cell transcripto mic profiling of young adult and aged mouse brains at acute (3 d) and chronic (14 d) stages after ischemic injury, focusing a priori on the expression of angiogenesis- and oligodendrogenesis-related genes. We identified unique subsets of endothelial cells (ECs) and oligodendrocyte (OL) progenitors in proangiogenesis and pro-oligodendrogenesis phenotypic states 3 d after stroke in young mice. However, this early prorepair transcrip-tomic reprogramming was negligible in aged stroke mice, consistent with the impairment of angiogenesis and oligodendrogenesis observed during the chronic injury stages after ischemia. In the stroke brain, microglia and macrophages (MG/MΦ) may drive angiogenesis and oligodendrogenesis through a paracrine mechanism. However, this reparative cell--cell cross talk between MG/MΦ and ECs or OLs is impeded in aged brains. In support of these findings, permanent depletion of MG/MΦ via antagonism of the colony-stimulating factor 1 receptor resulted in remarkably poor neurological recovery and loss ofpoststroke angiogenesis and oligodendrogenesis. Finally, transplantation of MG/MΦ from young, but not aged, mouse brains into the cerebral cortices of aged stroke mice partially restored angiogenesis and oligodendrogenesis and rejuvenated sensorimotor function and spatial learning and memory. Together, these data reveal fundamental mechanisms underlying the age-related decay in brain repair and highlight MG/MΦ as effective targets for promoting stroke recovery. [ABSTRACT FROM AUTHOR]

Neutrophils are associated with pro‐inflammation and contribute to pathophysiology of ischemic stroke. Prevention of neutrophils from infiltrating into ischemic area can be a potential approach for stroke therapy. In this study, a rod‐shaped polylactic acid polyglycolic acid (PLGA) nanoparticles encapsulated with piceatannol is developed to target and intervene the interaction of neutrophils with inflamed endothelial cells. In contrast to macrophages, neutrophils exhibit enhanced endocytosis of elongated particles. The nanoparticles with aspect ratio (AR) of 5 display higher internalization by neutrophils compared to other nanoparticles. Thus, AR5 nanoparticles are screened out to load with piceatannol (Pic@AR5) for investigating the therapeutic effect against middle cerebral artery occlusion model. It is demonstrated that Pic@AR5 can block the adherence of neutrophils to endothelial cells, inhibiting the infiltration of neutrophils into blood‐brain barrier (BBB). Besides, the inflammatory cytokine of ischemic brain can also be reduced even if a small part of Pic@AR5‐carried neutrophils enter BBB. The nanoparticles release piceatannol within the ischemic region, which inhibit microglial Syk signal and result in alleviation of neuroinflammation. This strategy provides new insights into ischemic stroke therapy. [ABSTRACT FROM AUTHOR]

This paper provides an overview of the usability engineering process and relevant standards informing the development of medical devices, together with adaptations to accommodate situations such as global pandemics where use of traditional face-to-face methods is restricted. To highlight some of those adaptations, a case study of a project developing a novel electronic rehabilitation device is referenced, which commenced in November 2020 amidst the COVID-19 pandemic. The Sheffield Adaptive Patterned Electrical Stimulation (SHAPES) project, led by Sheffield Teaching Hospitals NHS Foundation Trust (STH), aimed to design, manufacture and trial an intervention for use to treat upper arm spasticity after stroke. Presented is an outline and discussion of the challenges experienced in developing the SHAPES health technology intended for at-home use by stroke survivors and in implementing usability engineering approaches. Also highlighted, are the benefits that arose, which can offer easier involvement of vulnerable users and add flexibility in the ways that user feedback is sought. Challenges included: restricted travel; access to usual prototyping facilities; social distancing; infection prevention and control; availability of components; and changing work pressures and demands. Whereas benefits include: less travel; less time commitment; and greater scope for participants with restricted mobility to participate in the process. The paper advocates a more flexible approach to usability engineering and outlines the onward path for development and trialling of the SHAPES technology. [ABSTRACT FROM AUTHOR]

Purpose: Post-stroke cognitive impairment (PSCI) is a common complication of ischemic stroke episodes. Memory impairment is an important component of the poststroke cognitive syndrome. Microglial activation plays a critical role in stroke-induced neuroinflammation. Previous studies have reported that electroacupuncture (EA) provides neuroprotective effects by reducing the expression levels of the Purinergic receptor P2X ligand-gated ion channel 7 (P2X7) and inhibiting neuroinflammation in rat model of ischemic stroke. Further understanding of the role and connections between P2X7R and microglial activation in EA-induced anti-inflammatory can reveal novel targets for post-stroke memory impairment treatment., Methods: A Middle cerebral artery occlusion and reperfusion (MCAO/R) model was established. We used 2'(3')-O-(4-benzoyl) benzoyl ATP (BzATP) as a P2X7R agonist. Following MCAO/R injury, the rats underwent EA therapy at the Baihui (DU20) and Shenting (DU24) acupoints for seven consecutive days. The Barnes maze test was used to evaluate memory function. Following intervention, a T2 weighted images (T2WI) scan was performed to identify changes in cerebral infarction volume in MCAO/R rats. The levels of Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and Interleukin-4 (IL-4), Interleukin-10 (IL-10) in the peri-infarct hippocampal were examined by ELISA. Immunofluorescence was employed to evaluate Iba-1 + / P2X7R + , Iba-1 + / iNOS + and Iba-1 + / Arg-1 + cell populations in the peri-infarct hippocampal DG area. The protein expression of P2X7R, Nuclear factor E2-related factor 2 (Nrf2), Recombinant nlr family, pyrin domain containing protein 3 (NLRP3), Inducible nitric oxide synthase (iNOS) and Arginase-1 (Arg-1) in the peri-infarct hippocampal were investigated using western blot assays. Besides, we also measured the levels of reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA)., Results: We found EA treatment reduced inflammation and oxidative stress, which is consistent with a decrease in P2X7R expression and improved learning and memory functions. In contrast, we found BzATP enhanced inflammation and oxidative stress. Moreover, our results showed EA treatment up-regulated Nrf2, down-regulated NLRP3, and promoted microglia M2 polarization. Finally, EA-mediated positive effects were reversed by intracerebroventricular injection of BzATP, which is consistent with an increase in P2X7R expression., Conclusion: EA ameliorates memory impairment in a rat model of ischemic stroke by reducing inflammation and ROS through the inhibition of P2X7R expression. In turn, this mechanism regulates Nrf2 and NLRP3 expression, suggesting EA is beneficial for ischemic stroke treatment using P2X7R as target., Competing Interests: Declaration of Competing Interest The authors declare the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: To describe healthcare professionals' self-assessed competence in stroke care pathways based on their self-evaluation and identify the factors associated with competence., Design: A cross-sectional, descriptive explorative study design was used., Methods: The data were collected during May and September 2021 through a survey sent to healthcare professionals (N=1200, n=215) working in neurological care. Competence in stroke care pathways was measured using the RN-STROKE, PT-STROKE and OT-STROKE instruments defined by four-factor model. The instruments' validity and reliability were confirmed through exploratory factor analysis and Cronbach's alpha. K-means clustering, one-way ANOVA, Chi Square, Mann Whitney U and Kruskal-Wallis were used to analyze the data. The results were reported as frequencies, percentages, mean and standard deviation. The results were reported according to STROBE guidelines., Results: Four main areas of healthcare professionals' competence in stroke care pathways were identified: (1) counseling and interaction competence (2) competence to use evidence-based information, (3) self-management and development competence, and (4) multiprofessional and collaboration competence. The study then identified three competence profiles of healthcare professionals working in the stroke care pathway. Professionals in Profile A evaluated their competence at the highest level, those in Profile B at the average level, and those in Profile C at the lowest level. Healthcare professionals' occupation and participation in their organisation's expert network were found to be associated with competence profiles., Conclusion: The overall competence of healthcare professionals in the stroke care pathway was rated as good, but competence to use evidence-based information in clinical practice, in particular, should be improved. Organisations should, therefore, increase education and training in this area and provide adequate resources to enable the use of evidence-based information in clinical work., Implications for the Profession And/or Patient Care: The study identifies three profiles relating to healthcare professionals' competence in the stroke care pathway, which can be used to create continuous education and ensure better patient care according to participants' profiles., Reporting Method: The study was reported using the STROBE Statement checklist., Patient or Public Contribution: No patient or public contribution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Delays in hospital presentation limit access to acute stroke treatments. While prior research has focused on patient-level factors, broader ecological and social determinants have not been well studied. We aimed to create a geospatial map of prehospital delay and examine the role of community-level social vulnerability., Methods: We studied patients with ischemic stroke who arrived by emergency medical services in 2015 to 2017 from the American Heart Association Get With The Guidelines-Stroke registry. The primary outcome was time to hospital arrival after stroke (in minutes), beginning at last known well in most cases. Using Geographic Information System mapping, we displayed the geography of delay. We then used Cox proportional hazard models to study the relationship between community-level factors and arrival time (adjusted hazard ratios [aHR] <1.0 indicate delay). The primary exposure was the social vulnerability index (SVI), a metric of social vulnerability for every ZIP Code Tabulation Area ranging from 0.0 to 1.0., Results: Of 750 336 patients, 149 145 met inclusion criteria. The mean age was 73 years, and 51% were female. The median time to hospital arrival was 140 minutes (Q1: 60 minutes, Q3: 458 minutes). The geospatial map revealed that many zones of delay overlapped with socially vulnerable areas (https://harvard-cga.maps.arcgis.com/apps/webappviewer/index.html?id=08f6e885c71b457f83cefc71013bcaa7). Cox models (aHR, 95% CI) confirmed that higher SVI, including quartiles 3 (aHR, 0.96 [95% CI, 0.93-0.98]) and 4 (aHR, 0.93 [95% CI, 0.91-0.95]), was associated with delay. Patients from SVI quartile 4 neighborhoods arrived 15.6 minutes [15-16.2] slower than patients from SVI quartile 1. Specific SVI themes associated with delay were a community's socioeconomic status (aHR, 0.80 [95% CI, 0.74-0.85]) and housing type and transportation (aHR, 0.89 [95% CI, 0.84-0.94])., Conclusions: This map of acute stroke presentation times shows areas with a high incidence of delay. Increased social vulnerability characterizes these areas. Such places should be systematically targeted to improve population-level stroke presentation times., Competing Interests: Disclosures Dr Dhand is Co-Founder and has stock options in ECHAS (Emergency Call for Heart Attack and Stroke). He is also a consultant for Availity and participates in expert witness activities. Dr Bergmark a consultant for Analysis Group and received grant funding from I-Mab Biopharma, and reports grants from Brigham and Women’s Hospital. Dr Fonarow is a consultant for Abbott Pharmaceuticals, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly and Company, Janssen Pharmaceuticals, Medtronic, Merck, Novartis, and Pfizer. Dr Saver is a consultant for Abbott Laboratories, Aeromics, Biogen, Boehringer Ingelheim, BrainQ, BrainGate, CSL Behring, Johnson & Johnson Health Care Systems Inc, Medtronic, MindRhythm, Neuronics Medical, Rapid Medical, Roche, and Stream Medical. He is on the data and safety monitoring board for MIVI Neuroscience. Dr Schwamm is a consultant for Genentech and Medtronic. Dr Sheth is President for Advanced Innovation in Medicine. He has stock options in BrainQ and receives grant support from BARD and Hyperfine. He is a consultant for Astrocyte, Cerevasc, CSL Behring, and Rhaeos. He is on the data and safety monitoring board for Sense. He reports a patent pending for Stroke wearables licensed to Alva Health

Background: Endovascular treatment (EVT) is part of the usual care for proximal vessel occlusion strokes. However, the safety and effectiveness of EVT for distal medium vessel occlusions remain unclear. We sought to compare the clinical outcomes of EVT to medical management (MM) for isolated distal medium vessel occlusions., Methods: This is a retrospective analysis of prospectively collected data from seven comprehensive stroke centers. Patients were included if they had isolated distal medium vessel occlusion strokes due to middle cerebral artery M3/M4, anterior cerebral artery A2/A3, or posterior cerebral artery P1/P2 segments. Patients treated with EVT or MM were compared with multivariable logistic regression and inverse probability of treatment weighting. The primary outcome was the shift in the degree of disability as measured by the modified Rankin Scale (mRS) at 90 days. Secondary outcomes included 90-day good (mRS score, 0-2) and excellent (mRS score, 0-1) outcomes. Safety measures included symptomatic intracranial hemorrhage and 90-day mortality., Results: A total of 321 patients were included in the analysis (EVT, 179; MM, 142; 40.8% treated with intravenous thrombolysis). In the inverse probability of treatment weighting model, there were no significant differences between EVT and MM in terms of the overall degree of disability (mRS ordinal shift; adjusted odds ratio [aOR], 1.25 [95% CI, 0.95-1.64]; P =0.110), rates of good (mRS score, 0-2; aOR, 1.32 [95% CI, 0.97-1.80]; P =0.075) and excellent (aOR, 1.32 [95% CI, 0.94-1.85]; P =0.098) outcomes, or mortality (aOR, 1.20 [95% CI, 0.78-1.85]; P =0.395) at 90 days. The multivariable regression model showed similar findings. Moreover, there was no difference between EVT and MM in rates of symptomatic intracranial hemorrhage in the multivariable regression model (aOR, 0.57 [95% CI, 0.21-1.58]; P =0.277), but the inverse probability of treatment weighting model showed a lower likelihood of symptomatic intracranial hemorrhage (aOR, 0.46 [95% CI, 0.24-0.85]; P =0.013) in the EVT group., Conclusions: This multicenter study failed to demonstrate any significant outcome differences among patients with isolated distal medium vessel occlusions treated with EVT versus MM. These findings reinforce clinical equipoise. Randomized clinical trials are ongoing and will provide more definite evidence., Competing Interests: Disclosures Dr Nogueira reports compensations from Anaconda Biomed for consultant services; from Corindus, Inc‚ for consultant services; from Genentech for consultant services; from Vesalio for consultant services; from Imperative Care for consultant services; from Biogen, Inc‚ for consultant services; from Cerenovus for consultant services; from RapidPulse for consultant services; from Medtronic USA, Inc‚ for consultant services; from Prolong Pharmaceuticals for consultant services; from Perfuze for consultant services; from Ceretrieve for consultant services; from Phenox for consultant services; from Brainomix for consultant services; from Stryker Corporation for consultant services; from NeuroVasc Technologies, Inc‚ for consultant services; and from Viz-AI for consultant services; and reports stock options in Brainomix, Ceretrieve, Viz-AI, Vesalio, Corindus, Inc, and Perfuze. Dr Haussen reports stock options in Viz-AI; compensations from Cerenovus, Stryker, Vesalio Brainomix, Chiesi USA Inc, and Poseydon Medical for consultant services; and compensation from Jacobs institute for data and safety monitoring services. Dr Nguyen received research support from Brainomix, a relation with Idorsia. Dr Ortega-Gutierrez reports consulting fees for advisory roles with Stryker Neurovascular, Medtronic, and Microvention, and receives research support from Medtronic, Carver College of Medicine-University of Iowa, methinks, National Institutes of Health, and Siemens, Stryker, and Microvention. Dr Siegler reports compensations from Ceribell for consultant services and from AstraZeneca for other services. Dr Alaraj reports compensation from Johnson and Johnson for consultant services. Dr Fifi reports compensations from MIVI for data and safety monitoring services and from Stryker Corporation, MicroVention, Inc, Penumbra, Inc, Cerenovus, and Viz-AI for consultant services; and reports stock holdings in Imperative Care. The other authors report no conflicts.

The Get With The Guidelines-Stroke program which, began 20 years ago, is one of the largest and most important nationally representative disease registries in the United States. Its importance to the stroke community can be gauged by its sustained growth and widespread dissemination of findings that demonstrate sustained increases in both the quality of care and patient outcomes over time. The objectives of this narrative review are to provide a brief history of Get With The Guidelines-Stroke, summarize its major successes and impact, and highlight lessons learned. Looking to the next 20 years, we discuss potential challenges and opportunities for the program., Competing Interests: Disclosures Dr Fonarow reports consulting for Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Janssen/Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer. Dr Messe reports consulting for Terumo and EmStop, a provisional patent for a stroke monitor, which has been licensed to Neuralert Technologies, and equity in Neuralert Technologies. Dr Sheth reports grant support from National Institutes of Health, American Heart Association, and Hyperfine; consulting from Astrocyte, CSL Behring, Rhaeos, Cerevasc, Bexorg Sense and Philips Data and Safety Monitoring Board; and patent with Alva. The other authors report no conflicts.

Introduction: As a marker of chronic cerebral small vessel disease, leukoaraiosis (LA) was reported to impact the recruitment of collaterals in acute ischemic stroke (AIS). We intended to explore the impact of LA on the infarct growth rate (IGR) and clinical outcome by impaired collateral development in AIS patients with large vessel occlusion (LVO) who underwent endovascular thrombectomy (EVT)., Patients and Methods: Two hundred thirty-six AIS patients who underwent EVT were retrospectively reviewed. The severity of LA was graded using the Fazekas scale with non-contrast CT. IGR was calculated by the acute core volume on CT perfusion divided by the time from stroke onset to imaging. The collateral status after LVO was assessed using the ASITN/SIR collateral scale. The clinical outcomes after EVT were evaluated using a modified Rankin Scale ( mRS ). The Alberta stroke program early CT score ( ASPECTS ), the National Institutes of Health Stroke Scale (NIHSS) score at admission, and the modified treatment in cerebral infarction ( mTICI ) score after EVT were also included. Correlations between those factors were analyzed., Results: Patients with severe LA had significantly larger core volume on CTP ( p  = 0.022) and lower collateral grade ( p  < 0.001). Faster IGR was significantly associated with higher LA severity (adjusted odds ratio [aOR]: 1.53; 95% CI: 1.02-2.33; p  = 0.046), higher NIHSS (aOR: 1.04; 95% CI: 1.00-1.09; p  = 0.032) and impaired collaterals (aOR: 2.26; 95% CI: 1.27-4.03; p  = 0.005). In mediation analysis, collaterals explained 33% of the effect of LA on fast IGR. There was correlation between the severity of LA and mRS ( p  = 0.007)., Discussion and Conclusion: The increasing severity of LA is associated with impaired collateral status and fast infarct growth. These findings suggest that LA may become a predictive imaging biomarker for the likelihood of progression of tissue injury and clinical outcome after EVT in acute large vessel occlusion stroke., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: Disclosures The author reports compensation from Penumbra, Inc, for data and safety monitoring services; compensation from Medtronic for consultant services; and service as a member of the Board of Directors for the American Heart Association.

Background: Inpatient telestroke programs have emerged as a solution to provide timely stroke care in underserved areas, but their successful implementation and factors influencing their effectiveness remain underexplored. This study aimed to qualitatively evaluate the perspectives of inpatient clinicians located at spoke hospitals participating in a newly established inpatient telestroke program to identify implementation barriers and facilitators., Methods: This was a formative evaluation relying on semistructured qualitative interviews with 16 inpatient providers (physicians and nurse practitioners) at 5 spoke sites of a hub-and-spoke inpatient telestroke program. The Integrated-Promoting Action on Research Implementation in Health Services framework guided data analysis, focusing on the innovation, recipients, context, and facilitation aspects of implementation. Interviews were transcribed and coded using thematic analysis., Results: Fifteen themes were identified in the data and mapped to the Integrated-Promoting Action on Research Implementation in Health Services framework. Themes related to the innovation (the telestroke program) included easy access to stroke specialists, the benefits of limiting patient transfers, concerns about duplicating tests, and challenges of timing inpatient telestroke visits and notes to align with discharge workflow. Themes pertaining to recipients (care team members and patients) were communication gaps between teams, concern about the supervision of inpatient telestroke advanced practice providers and challenges with nurse empowerment. With regard to the context (hospital and system factors), providers highlighted familiarity with telehealth technologies as a facilitator to implementing inpatient telestroke, yet highlighted resource limitations in smaller facilities. Facilitation (program implementation) was recognized as crucial for education, standardization, and buy-in., Conclusions: Understanding barriers and facilitators to implementation is crucial to determining where programmatic changes may need to be made to ensure the success and sustainment of inpatient telestroke services., Competing Interests: Disclosures Dr Melton is a fiduciary officer for the American College of Medical Informatics, the American Medical Informatics Association, and the President and Chair of the Board of Directors at Fairview Health Services. She is the Chief Analytics and Care Innovation Officer at the University of Minnesota, and she is a consultant at Washington University School of Medicine in St. Louis. She has grants with the Agency for Healthcare Research and Quality, the Food and Drug Administration, the National Institutes of Health, and the US Department of Defense. The other authors report no conflicts.

Background: The treatments based on motor control and motor learning principles have gained popularity in the last 20 years, as well as non-invasive brain stimulations that enhance neuroplastic changes after stroke. However, the effect of intermittent theta burst stimulation (iTBS) in addition to evidence-based, intensive neurorehabilitation approaches such as modified constraint-induced movement therapy (mCIMT) is yet to be investigated., Aim: We aim to establish a protocol for a randomized controlled study investigating the efficiency of mCIMT primed with iTBS after stroke., Methods: In this randomized controlled, single-blind study, patients with stroke (N = 17) will be divided into 3 groups: (a) mCIMT + real iTBS, (b) mCIMT + sham iTBS, and (c) mCIMT alone. 600-pulse iTBS will be delivered to the primary motor cortex on the ipsilesional hemisphere, and then, patients will receive mCIMT for 1 h/session, 3 sessions/week for 5 weeks. Upper extremity recovery will be assessed with Fugl-Meyer Test-Upper Extremity and Wolf Motor Function Test. Electrophysiological assessments, such as Motor-Evoked Potentials, Resting Motor Threshold, Short-Intracortical Inhibition, and Intracortical Facilitation, will also be included., Conclusions: In this study, a protocol of an ongoing intervention study investigating the effectiveness of iTBS on ipsilesional M1 prior to the mCIMT in patients with stroke is proposed. This will be the first study to research priming mCIMT with iTBS and it may have the potential to reveal the true effect of the iTBS when it is added to the high-quality neurorehabilitation approaches., Trial Registration: Trial registration number: NCT05308667., (© 2024. The Author(s) under exclusive licence to Belgian Neurological Society.)

Background: Stroke is a second leading cause of death globally, with an estimated one in four adults suffering a stroke in their lifetime. We aimed to describe the clinical characteristics, quality of care, and outcomes in adults with stroke in urban Northwestern Tanzania., Methods: We analyzed de-identified data from a prospective stroke registry from Bugando Medical Centre in Mwanza, the second largest city in Tanzania, between March 2020 and October 2022. This registry included all adults ⩾18 years admitted to our hospital who met the World Health Organization clinical definition of stroke. Information collected included demographics, risk factors, stroke severity using the National Institutes of Health Stroke Scale, brain imaging, indicators for quality of care, discharge modified Rankin Scale, and in-hospital mortality. We examined independent factors associated with mortality using logistic regression., Results: The cohort included 566 adults, of which 52% (294) were female with a mean age of 65 ± 15 years. The majority had a first-ever stroke 88% (498). Premorbid hypertension was present in 86% (488) but only 41% (200) were taking antihypertensive medications before hospital admission; 6% (32) had HIV infection. Ischemic strokes accounted for 66% (371) but only 6% (22) arriving within 4.5 h of symptom onset. In-hospital mortality was 29% (127). Independent factors associated with mortality were severe stroke (adjusted odds ratio (aOR) = 1.81, 95% confidence interval (CI) = 1.47-2.24, p < 0.001), moderate to severe stroke (aOR = 1.49, 95% CI = 1.22-1.84, p < 0.001), moderate stroke (aOR = 1.80, 95% CI = 1.52-2.14, p < 0.001), leukocytosis (aOR = 1.19, 95% CI = 1.03-1.38, p = 0.022), lack of health insurance coverage (aOR = 1.15, 95% CI = 1.02-1.29, p = 0.025), and not receiving any form of venous thromboembolism prophylaxis (aOR = 1.18, 95% CI = 1.02-1.37, p = 0.027)., Conclusion: We report a stroke cohort with poor in-hospital outcomes in urban Northwestern Tanzania. Early diagnosis and treatment of hypertension could prevent stroke in this region. More work is needed to raise awareness about stroke symptoms and to ensure that people with stroke receive guidelines-directed therapy., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Health care teams along the stroke recovery continuum have a responsibility to support care transitions and return to the community. Ideally, individualized care will consider patient and family preferences, best available evidence, and health care professional input. Person-centered care can improve patient-practitioner interactions through shared decision-making in which health professionals and institutions are sensitive to those for whom they provide care. However, it is unclear how the concepts of person-centered care have been described in reports of stroke transitional care interventions., Methods: A secondary analysis of a systematic review and meta-analysis was undertaken. We retrieved all included articles (n=17) and evaluated the extent to which each intervention explicitly addressed 7 domains of person-centered care: alignment of care with patients' values, preferences, and needs; coordination of care; information and education; physical comfort; emotional support; family and friend involvement; and smooth transition and continuity of care., Results: Most of the articles included some aspects of person-centeredness; we found that certain domains were not addressed in the descriptions of transitional care interventions, and no articles mentioned all 7 domains of person-centered care. We identified 3 implications for practice and research: (1) delineating person-centered care components when reporting interventions, (2) elucidating social and cultural factors relevant to the study sample and intervention, and (3) clearly describing the role of family and nonmedical support in the intervention., Conclusions: There is still room for greater consistency in the reporting of person-centeredness in stroke transitions of care interventions, despite a long-standing definition and conceptualization of person-centered care in academic and clinically focused literature.

Introduction: Reperfusion therapies represent promising treatments for patients with Central Retinal Artery Occlusion (CRAO), but access is limited due to low incidence and lack of protocols. We aimed to describe the benefit of implementing a Retinal Stroke-Code protocol regarding access to reperfusion, visual acuity and aetiological assessment., Patients and Methods: Prospective cohort study performed at a Comprehensive Stroke Centre. Criteria for activation were sudden monocular, painless vision loss within 6 h from onset. Eligible patients received IAT when immediately available and IVT otherwise. All patients were followed by ophthalmologists to assess best-corrected visual acuity (BCVA) and visual complications, and by neurologists for aetiological workup. Visual amelioration was defined as improvement of at least one Early Treatment Diabetic Retinopathy Study (ETDRS) letter from baseline to 1 week., Results: Of 49 patients with CRAO, 15 (30.6%) received reperfusion therapies (12 IVT, 3 IAT). Presentation beyond 6 h was the main contraindication. Patients receiving reperfusion therapies had better rates of visual improvement (33.3% vs 5.9%, p  = 0.022). There were no complications related to reperfusion therapies. Rates of neovascular glaucoma were non-significantly lower in patients receiving reperfusion therapies (13.3% vs 20.6%, p  = 0.701). Similar rates of atherosclerotic, cardioembolic and undetermined aetiologies were observed, leading to 10 new diagnosed atrial fibrillation and five carotid revascularizations., Conclusion: A comprehensive acute management of CRAO is feasible despite low incidence. In our study, reperfusion therapies were safe and associated with higher rates of visual recovery. A similar etiological workup than ischemic stroke led to of high proportion of underlying aetiologies., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Shoalhaven District Memorial Hospital is a rural (MM3) secondary hospital which is over an hour travel time from the nearest tertiary centre. The objective of the present study was to pilot the implementation of the BEFAST (Balance, Eyes, Face, Arms, Speech and Time) stroke screening tool at the ED, and determine whether its usage improved timely stroke detection., Methods: During initial implementation and training (October-December 2019), triage nurses consulted with senior medical officers before activating stroke calls. Data were collected for the subsequent 24 months (January 2020-2022), and retrospective records for confirmed strokes during a 24-month period prior to BEFAST implementation (October 2017-2019) were also collected. The main outcome measures were triage category, CT scan result time, discharge destination, length of stay (LOS) and Modified Rankin Score (MRS)., Results: After BEFAST implementation, patients (n = 268) were three times more likely to be triaged at category 1 or 2, and door-to-CT scan time was reduced by 20.7 min on average. More patients were discharged to their usual residence and more quickly (LOS 7.9 vs 11.1 days). MRS 90 days after stroke was less, and patients were nearly twice as likely to experience an improvement in neurological symptoms., Conclusions: Patient outcomes were improved after implementation of the BEFAST stroke triage tool. More stroke patients were identified upon presentation to the ED, and in a timely fashion. For those with a stroke diagnosis, time-critical interventions can take place earlier, allowing patients to return home sooner, and with less disability., (© 2024 Australasian College for Emergency Medicine.)

Background: Comprehensive stroke centers (CSC) offer state-of-the-art stroke care in metropolitan centers. However, in rural areas, sufficient stroke expertise is much scarcer. Recently, telemedical stroke networks have offered instant consultation by stroke experts, enabling immediate administration of intravenous thrombolysis (IVT) on-site and decision on thrombectomy. While these immediate decisions are made during the consult, the impact of the network structures on stroke care in spoke hospitals is still not well described., Aims: This study was performed to determine if on-site performance in rural hospitals and patient outcome improve over time through participation and regular medical staff training within a telemedical stroke network., Methods: In this retrospective study, we analyzed data from stroke patients treated in four regional hospitals within the telemedical Neurovascular Network of Southwest Bavaria (NEVAS) between 2014 and 2019. We only included those patients that were treated in the regional hospitals until discharge at home or to neurorehabilitation. Functional outcome (modified Rankin scale) at discharge, mortality rate and periprocedural intracranial hemorrhage served as primary outcome parameters. Door-to-imaging and door-to-needle times were secondary outcome parameters., Results: In 2014-2019, 5,379 patients were treated for acute stroke with 477 receiving IVT. Most baseline characteristics were comparable over time. For all stroke patients, door-to-imaging times increased over the years, but significantly improved for potential IVT candidates and those finally treated with IVT. The percentage of patients with door-to-needle time <30 min increased from 10% to 25%. Clinical outcome at discharge improved for all stroke patients treated in the regional hospitals. Particularly for patients treated with IVT, good clinical outcome (modified Rankin scale 0-2) at discharge increased from 2014 to 2019 by 19% and mortality rates dropped from 13% to 5%., Conclusions: 24-h/7-day telemedical support and regular on-site medical staff training within a structured telemedicine stroke network such as NEVAS significantly improve on-site stroke care in rural areas, leading to a considerable benefit in clinical outcome., Data Access Statement: The data that support the findings of this study are available upon reasonable request and in compliance with the local and international ethical guidelines., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Despite global progress in stroke care, challenges persist, especially in Low- and Middle-Income countries (LMIC). The Middle East and North Africa Stroke and Interventional Neurotherapies Organization (MENA-SINO) Stroke Program Accreditation Initiative aims to improve stroke care regionally., Material & Method: A 2022 survey assessed stroke unit readiness in the Middle East and North Africa (MENA) + region, revealing significant regional disparities in stroke care between high-income and low-income countries. Additionally, it demonstrated interest in the accreditation procedure and suggested that regional stroke program accreditation will improve stroke care for the involved centers., Conclusion: An accreditation program that is specifically tailored to the regional needs in the MENA + countries might be the solution. In this brief review, we will discuss potential challenges faced by such a program and we will put forward a well-defined 5-step accreditation process, beginning with a letter of intent, through processing the request and appointment of reviewers, the actual audit, the certification decisions, and culminating in granting a MIENA-SINO tier-specific certificate with recertification every 5 years., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Background: In-hospital stroke refers to a stroke arising in a patient during hospital admission for another condition. Between 2 and 17% of all inpatient strokes are in-hospital strokes., Aim: To compare the outcomes and performance on quality-of-care stroke measures of in-hospital stroke cases with community-onset strokes., Methods: Data collected for the Irish Annual Audit of Stroke from an Irish university teaching hospital was analysed for a 2-year period from 1 st January 2020 to 31 st December 2021. A retrospective cohort study was conducted to compare baseline characteristics, outcomes, and performance on standardised quality-of-care measures between the cohorts., Results: The rate of IHS was 15.6%. Median age was 73 years and 72 years for in-hospital and community-onset strokes respectively. Amongst in-hospital strokes, COVID-19 co-diagnosis (9.1% versus 1.3%; p = .0004), admission to intensive care (52.3% versus 5.3%; p < .0001), discharge to long term care (6.8% versus 2.3%; p = .04), mortality (12.5% versus 7.6%; p = .13), and modified Rankin score of two or more at discharge (58.0% versus 38.1%; p = .001), were more likely compared to community-onset strokes. Thrombolysis rates were lower (7.3% versus 12.0%; p = .22) and thrombectomy rates higher (9.8% versus 6.6;% p = .32), albeit non-significantly. Median time to thrombolysis was slower amongst in-hospital strokes (105 min versus 66 min; p = .03) and they were less likely to be admitted to the stroke unit (43.2% versus 78.5%; p < .0001)., Conclusions: When compared with community-onset stroke, in-hospital stroke represents a distinct stroke subgroup with poorer outcomes and delays to thrombolysis emphasising the need for standardised approaches to evaluation and management., (© 2023. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Objective: The objective of the study was to determine the effect of task-oriented training on the dexterous movements of hands in Hemiplegic post-stroke patients. Methods: This study has been registered on site ClinicalTrial.gov with clinical trial number NCT05201196. The study was Randomized controlled trial, 18 patients were recruited that meet the inclusion criteria, randomly allocated to task-oriented training Group A ( n  = 9) and Conventional Therapy Group B ( n  = 9). Both exercise trainings were applied for 45 min/session, 5 times/week for 6 weeks. Fugl-Meyer Assessment Scale Motor, sensory and coordination portion, Wolf Motor Function Scale and Barthel Index were used as outcome measures, assessed patients at Baseline, after 3 weeks and 6 weeks after training. Data were analyzed by SPSS version 23. Results: The results suggested the mean Age was 60.78 ± 9.08 and 61.33 ± 6.78 for Group A and Group B, respectively. Average BMI was 23.66 ± 2.66 for Task-oriented group and 21.36 ± 2.46 for Conventional group. Fugl-Meyer scale shows significant P-value 0.03 post treatment compare to pre-treatment which was .283, Wolf Motor Function test and Barthel Index also showed significant P -values as 0.023 and 0.007, respectively, indicating that Task-oriented training shows more significant improvements than conventional group. Conclusion: Task-based training produced statistically significant as well as clinically meaningful enhancement in the dexterous hand movements of acute and subacute stroke patients than conventional therapy and ultimately improves the functional independence in their daily activities such as feeding, bathing and hygiene.

Competing Interests: Disclosures None.

Objectives: We evaluated the on-scene time of emergency medical services (EMS) for cases where discrimination between acute stroke and epileptic seizures at the initial examination was difficult and identified factors linked to delays in such scenarios., Materials and Methods: A retrospective review of cases with suspected seizure using the EMS database of fire departments across six Japanese cities between 2016 and 2021 was conducted. Patient classification was based on transport codes. We defined cases with stroke-suspected seizure as those in whom epileptic seizure was difficult to differentiate from stroke and evaluated their EMS on-scene time compared to those with epileptic seizures., Results: Among 30,439 cases with any seizures, 292 cases of stroke-suspected seizure and 8,737 cases of epileptic seizure were included. EMS on-scene time in cases of stroke-suspected seizure was shorter than in those with epileptic seizure after propensity score matching (15.1±7.2 min vs. 17.0±9.0 min; p = 0.007). Factors associated with delays included transport during nighttime (odds ratio [OR], 1.73, 95 % confidence interval [CI] 1.02-2.93, p = 0.041) and transport during the 2020-2021 pandemic (OR, 1.77, 95 % CI 1.08-2.90, p = 0.022)., Conclusion: This study highlighted the difference between the characteristics in EMS for stroke and epileptic seizure by evaluating the response to cases with stroke-suspected seizure. Facilitating prompt and smooth transfers of such cases to an appropriate medical facility after admission could optimize the operation of specialized medical resources., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cerebrovascular disease is a common and potentially life-threatening illness if not triaged and/or treated appropriately. The diagnosis is made based on a combination of clinical history and neuroimaging studies. The majority of strokes can be prevented, and this process often begins in the primary care office through the careful assessment of vascular risk factors. Appropriate workup aims to pinpoint a pathogenic mechanism and guide therapy. Stroke treatment has rapidly advanced over the past several years, resulting in improved outcomes., Competing Interests: Disclosure Dr P. Banyas and Dr A. Jadhav have no relevant disclosures. Drs P. Banyas and A. Jadhav contributed equally to this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: With the rising global burden of stroke-related morbidity, and increased focus on patient-centered healthcare, patient reported outcome measures (PROMs) are increasingly used to inform healthcare decision-making. Some stroke patients with cognitive or motor impairments are unable to respond to PROMs, so proxies may respond on their behalf; the reliability of which remains unclear. The aim of the study is to update a 2010 systematic review to investigate the inter-rater reliability of proxy respondents answering PROMs for stroke patients., Materials and Methods: Studies on the reliability of proxy respondents in stroke were searched within CINAHL, Embase, PsycInfo, and WoS databases (01/07/22, 08/07/22). Fifteen studies were included for review. ICC and k-statistic were extracted for PROMs scales and categorized as poor (0.80). Bias was assessed using the CCAT., Results: Five studies reported PROMs with inter-rater reliability scores ranging from 0.80. Two studies reported activities of daily living (ADLs) scores ranging from 0.41 to 0.80 and 8 studies reported quality of life (QoL) measures with scores ranging from 0.80. Subcategories of these scales included physical (ICC/k-statistic 0.41- >0.8), cognitive (ICC/k-statistic 0.40-0.80), communication (ICC/k-statistic <0.4-0.80,) and psychological (ICC/k-statistic <0.40-0.60) measures., Conclusions: Proxy respondents are reliable sources for PROM reports on physical domains in ADLs, PROMs and QoL scales. Proxy reports for measures of communication and psychological domains had greater variability in reliability scores, ranging from poor to substantial; hence, caution should be applied when interpreting proxy reports for these domains., Competing Interests: Declaration of competing interest The authors have declared no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

Acidic postconditioning by transient CO 2 inhalation applied within minutes after reperfusion has neuroprotective effects in the acute phase of stroke. However, the effects of delayed chronic acidic postconditioning (DCAPC) initiated during the subacute phase of stroke or other acute brain injuries are unknown. Mice received daily DCAPC by inhaling 5%/10%/20% CO 2 for various durations (three cycles of 10- or 20-min CO 2 inhalation/10-min break) at days 3-7, 7-21, or 3-21 after photothrombotic stroke. Grid-walk, cylinder, and gait tests were used to assess motor function. DCAPC with all CO 2 concentrations significantly promoted motor functional recovery, even when DCAPC was delayed for 3-7 days. DCAPC enhanced the puncta density of GAP-43 (a marker of axon growth and regeneration) and synaptophysin (a marker of synaptogenesis) and reduced the amoeboid microglia number, glial scar thickness and mRNA expression of CD16 and CD32 (markers of proinflammatory M1 microglia) compared with those of the stroke group. Cerebral blood flow (CBF) increased in response to DCAPC. Furthermore, the mRNA expression of TDAG8 (a proton-activated G-protein-coupled receptor) was increased during the subacute phase of stroke, while DCAPC effects were blocked by systemic knockout of TDAG8, except for those on CBF. DCAPC reproduced the benefits by re-expressing TDAG8 in the peri-infarct cortex of TDAG8-/- mice infected with HBAAV2/9-CMV-TDAG8-3flag-ZsGreen. Taken together, we first showed that DCAPC promoted functional recovery and brain tissue repair after stroke with a wide therapeutic time window of at least 7 days after stroke. Brain-derived TDAG8 is a direct target of DCAPC that induces neuroreparative effects., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Objectives: The field of vascular neurology has undergone significant advances over the last decade, and care has become more complex. However, vascular neurology training programs remain underdeveloped in many countries, despite stroke impact on health care. There are efforts towards building a nationally regulated curricula in some countries. Still, comprehensive planning and implementation of these programs may be needed on a global scale, especially in countries where stroke treatment is not fully implemented. We aim to comprehensively analyze vascular neurology trainees' profiles in Brazil to describe training program contents from trainees and program directors' perspectives., Methods: We performed an observational, cross-sectional, web-based survey study to describe trainee and program-specific characteristics at vascular neurology fellowship training programs in Brazil. The study was conducted from June to September 2023 using a secure web-based survey sent to active fellows and program directors from all known vascular neurology fellowship programs in the country. All respondents were required to provide informed consent., Results: We obtained a 100 % response rate of a total of 12 programs distributed in 7 federal states. Notably, 57 % of the 28 surveyed fellows were women, 60 % were aged 25-30, and 70 % self-identified as White. All fellows had prior neurology training, and 60 % engaged in the program just following residency. Exposure to various training experiences was favorable, except for simulation-based learning and telestroke training. Program directors perceived exposure to be sufficient for most components but similarly found deficiencies in telestroke and simulation-based learning. Scientific productivity was low, with about two-thirds of fellows having no publications or abstracts. Most fellows (92.6 %) reported performing non-fellowship medical activities to supplement their incomes., Discussion: In conclusion, the number of vascular neurology training programs and trainees in Brazil is currently insufficient and exhibits an uneven geographic distribution. Despite this, the clinical training provided is extensive, and there is generally some funding available for fellows. These insights highlight the need for strategic improvements in Brazil's stroke education and could inform similar developments in other nations., Competing Interests: Declaration of competing interest The authors report no disclosures relevant to the study., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Upper limb impairments are common consequences of stroke. Noninvasive brain stimulation (NIBS) and virtual reality (VR) play crucial roles in improving upper limb function poststroke. This review aims to evaluate the effects of combined NIBS and VR interventions on upper limb function post-stroke and to provide recommendations for future studies in the rehabilitation field. PubMed, MEDLINE, PEDro, SCOPUS, REHABDATA, EMBASE, and Web of Science were searched from inception to November 2023. Randomized controlled trials (RCTs) encompassed patients with a confirmed stroke diagnosis, administrated combined NIBS and VR compared with passive (i.e., rest) or active (conventional therapy), and included at least one outcome assessing upper limb function (i.e., strength, spasticity, function) were selected. The quality of the included studies was assessed using the Cochrane Collaboration tool. Seven studies met the eligibility criteria. In total, 303 stroke survivors (Mean age: 61.74 years) were included in this review. According to the Cochrane Collaboration tool, five studies were classified as "high quality," while two were categorized as "moderate quality". There are mixed findings for the effects of combined NIBS and VR on upper limb function in stroke survivors. The evidence for the effects of combined transcranial direct current stimulation and VR on upper limb function post-stroke is promising. However, the evidence regarding the effects of combined repetitive transcranial magnetic stimulation and VR on upper limb function is limited. Further randomized controlled trials with long-term follow-up are strongly warranted., (© 2024. Fondazione Società Italiana di Neurologia.)

Reduced left ventricular ejection fraction ≤40%, a known risk factor for adverse cardiac outcomes and recurrent acute ischemic stroke, may be detected during an acute ischemic stroke hospitalization. A multidisciplinary care paradigm informed by neurology and cardiology expertise may facilitate the timely implementation of an array of proven heart failure-specific therapies and procedures in a nuanced manner to optimize brain and cardiac health., Competing Interests: Disclosures Dr Merkler has received fees for medicolegal consulting. Dr Freeman has received salary support from the American College of Cardiology National Cardiovascular Data Registry and the National Heart, Lung, and Blood Institute; has received consulting/Advisory Board fees (modest) from Boston Scientific, Medtronic, Janssen Pharmaceuticals, and Biosense Webster; and has equity interest in PaceMate. Dr Krumholz is the editor-in-chief of the Journal of the American College of Cardiology; works under contract with the Centers for Medicare and Medicaid Services to support quality measurement programs, was a recipient of a research grant from Johnson & Johnson, through Yale University, to support clinical trial data sharing; was a recipient of a research agreement, through Yale University, from the Shenzhen Center for Health Information for work to advance intelligent disease prevention and health promotion; collaborates with the National Center for Cardiovascular Diseases in Beijing; receives payment from the Arnold & Porter Law Firm for work related to the Sanofi clopidogrel litigation, from the Martin Baughman Law Firm for work related to the Cook Celect inferior vena cava filter litigation, and from the Siegfried and Jensen Law Firm for work related to Vioxx litigation; chairs a Cardiac Scientific Advisory Board for UnitedHealth; was a member of the IBM Watson Health Life Sciences Board; is a member of the Advisory Board for Element Science, the Advisory Board for Facebook, and the Physician Advisory Board for Aetna; and is the co-founder of Hugo Health, a personal health information platform, and cofounder of Refactor Health, a healthcare AI-augmented data management company. Dr Ahmad has received consulting fees from Sanofi, Amgen, and Cytokinetics and has received research funding from Boehringer Ingelheim, AstraZeneca, Cytokinetics, and Relypsa. Dr Sharma is a co-inventor of US Provisional Patent Application No. 63/505,006, Methods of Training an Algorithm To Predict Ischemic Stroke Etiology; reports funding from the National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS; K23NS121634). The other authors report no conflicts.

Background: It is a well-established fact that post-stroke depression (PSD) is a prevalent condition that affects a significant proportion of individuals who have suffered a stroke. Hence, our research endeavors to explore the safety, efficacy and the potential molecular mechanism of transcutaneous auricular vagus nerve stimulation (ta-VNS) for the treatment of depression in PSD patients by conducting a double-blind, sham-controlled, randomized trial., Methods: Patients who had experienced strokes and exhibited depressive symptoms, with a Hamilton Depression Scale (HAMD-17) score of ≥8 and met the DSM-IV criteria, were diagnosed with PSD. A volunteer sample of participants (N = 80) were randomly divided into either the ta-VNS group (which received ta-VNS in addition to conventional treatment) or the control group (which received conventional treatment only), in a 1:1 ratio. The effectiveness of the interventions was evaluated using the 17-item Hamilton Rating Scale for Depression (HAMD-17), Zung Self-Rating Depression Scale (SDS), and Barthel Index (BI) scores. Furthermore, Plasma BDNF, CREB1, and 5-HT levels were measured before and after treatment., Results: The concomitant application of ta-VNS demonstrated a remarkable reduction in HAMD-17 and SDS scores, leading to noteworthy enhancements in patients' daily functioning, as evidenced by improved activities of daily living, at all assessed time points, in contrast to the control group (p < 0.0001). Notably, the ta-VNS group exhibited superior effects in modulating the measured neurotrophic biomarkers when compared to the control group (p < 0.05)., Conclusions: The synergistic approach of combining ta-VNS with conventional treatment has demonstrated remarkable efficacy and tolerability in managing depression following a stroke., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: This study investigates prehospital delays in recurrent Acute Ischemic Stroke (AIS) patients, aiming to identify key factors contributing to these delays to inform effective interventions., Methods: A retrospective cohort analysis of 1419 AIS patients in Shenzhen from December 2021 to August 2023 was performed. The study applied the Extreme Gradient Boosting (XGBoost) algorithm and SHapley Additive exPlanations (SHAP) for identifying determinants of delay., Results: Living with others and lack of stroke knowledge emerged as significant risk factors for delayed hospital presentation in recurrent AIS patients. Key features impacting delay times included residential status, awareness of stroke symptoms, presence of conscious disturbance, diabetes mellitus awareness, physical weakness, mode of hospital presentation, type of stroke, and presence of coronary artery disease., Conclusion: Prehospital delays are similarly prevalent among both recurrent and first-time AIS patients, highlighting a pronounced knowledge gap in the former group. This discovery underscores the urgent need for enhanced stroke education and management., Practice Implication: The similarity in prehospital delay patterns between recurrent and first-time AIS patients emphasizes the necessity for public health initiatives and tailored educational programs. These strategies aim to improve stroke response times and outcomes for all patients., Competing Interests: Declaration of Competing Interest All the authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Despite being widely applied in clinical practice, the wake-promoting effect of acupuncture in poststroke coma patients remains controversial., Objective: This study aimed to evaluate the efficacy of acupuncture for the treatment of poststroke coma., Methods: Randomized controlled trials (RCTs) of acupuncture for treating poststroke coma were identified in PubMed, Cochrane Library, EMBASE, CNKI, WanFang and VIP up to 25 November 2023. The main outcomes were Glasgow Coma Scale (GCS) score, National Institute of Health Stroke Scale (NIHSS) score, awakening ratio and clinically effective ratio. Stata 17 and Review Manager 5.4 software were used for mate analysis., Results: A total of 34 RCTs involving 2757 patients were included. GCS (WMD = 1.78; 95% CI: 1.35 to 2.21) and NIHSS score (WMD = -2.84; 95% CI: -3.84 to -1.84) were significantly increased in acupuncture group compared with control group. Acupuncture combined with routine treatment may be better than routine treatment in improving the awakening ratio (RR= 1.65; 95% CI: 1.24 to 2.91) and the clinically effective ratio (RR= 1.20; 95% CI: 1.13 to 1.27). Some methodological flaws were identified in the included studies, including non-implementation of blinding, inappropriate disease assessment and heterogeneous interventions., Conclusions: The existing evidence suggests that acupuncture combined with conventional treatment may be an effective treatment for poststroke coma patients. In the meantime, more high-quality RCTs are needed to demonstrate these findings due to methodological weaknesses like randomization, blinding, heterogeneous interventions and long-term follow-up., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Stroke is a leading cause of death globally, yet End-of-Life (EOL) symptoms and their management in these patients are not well understood., Purpose: This integrative review aims to critique and synthesize research on EOL symptoms and symptom management in adult patients with stroke in the last 2 years of life in all settings., Methods: The Whittemore and Knafl integrative review methodology guided this review. PubMed, CINAHL, Scopus, Web of Science, and Google Scholar were used for the literature search. Included studies were published in English and quantitatively examined symptoms and symptom management. Quality appraisal was guided by the Effective Public Health Practice Project (EPHPP) assessment tool., Results: Seven studies, all rated weak, were included in this review. A total of 2175 adult patients from six countries were represented. Results are classified into three main themes: EOL symptom experience, symptom assessment, and symptom management. Commonly reported EOL symptoms among adults with stroke include both stroke-specific (dysphagia, dysarthria) and non-specific symptoms (pain, dyspnea, constipation, and psychological distress). However, communication difficulties and the infrequent use of standardized tools for symptom assessment limit what is known about the EOL symptom experience. Although the relief of pain is generally well-documented, dyspnea and anxiety are much more poorly controlled., Conclusions: There is a need for better assessment and management of EOL symptoms in patients with stroke. Established palliative and EOL care guidelines need to be incorporated into clinical practice to ensure access to high-quality care., Competing Interests: Declaration of Conflicting InterestsThe author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Stroke poses challenges to the physiological, psychosocial and spiritual well-being of affected individuals. As the impacts of stroke might not be reversible, a shift in focus to providing care is desirable. Visual art interventions using visual and symbolic art can help participants to express their feelings, give them a sense of choice and the feeling that they are retaining a sense of control, promote insights, restructure their sense of cognition and instil hope. There have been few studies on visual art interventions involving older people with stroke and none in residential care homes (RCHs). Theoretical support and rigorous research designs on the subject are lacking. Thus, this study seeks to address this research gap by examining the feasibility of a visual art intervention for older people in RCHs and exploring the impacts on their holistic well-being., Methods: This was a single-blinded, two-arm, randomised controlled feasibility study grounded on Watson's Caring Theory. The Holistic Well-Being Scale and Caring Factor Survey were used in the study, with three assessment time-points: before the intervention (T1), at the mid-point of the intervention (T2) and immediately after the intervention (T3)., Results: Sixty-one older people with stroke were recruited from 14 RCHs and randomised into the intervention and control groups. The recruitment rate was 44.53%, and the retention rate for the intervention group was 93.55%. Implementing the programme was affordable (at approximately US$126/head), the duration was acceptable (721 min) and the feedback from participants and staff of the RCHs was positive., Conclusions: The visual art intervention programme proved to be clinically feasible. This study adds new insights to the development of visual art interventions and to the caring sciences. The efficacy of the programme on holistic well-being has yet to be confirmed., (© 2024 The Authors. Scandinavian Journal of Caring Sciences published by John Wiley & Sons Ltd on behalf of Nordic College of Caring Science.)

Purpose: Stroke treatments are time-sensitive, and thus early and correct recognition of stroke by Emergency Medical Services is essential for outcomes. This is particularly important with the adaption of mobile stroke units. In this systematic review, we therefore aimed to provide a comprehensive overview of Emergency Medical Services dispatcher recognition of stroke., Methods: The review was registered on PROSPERO and the PRISMA guidelines were applied. We searched PubMed, Embase, and Cochrane Review Library. Screening and data extraction were performed by two observers. Risk of bias was assessed using the QUADAS-2 instrument., Findings: Of 1200 papers screened, 24 fulfilled the inclusion criteria. Data on sensitivity was reported in 22 papers and varied from 17.9% to 83.0%. Positive predictive values were reported in 12 papers and ranged from 24.0% to 87.7%. Seven papers reported specificity, which ranged from 20.0% to 99.1%. Six papers reported negative predictive value, ranging from 28.0% to 99.4%. In general, the risk of bias was low., Discussion: Stroke recognition by dispatchers varied greatly, but overall many patients with stroke are not recognised, despite the initiatives taken to improve stroke literacy. The available data are of high quality, however Asian, African, and South American populations are underrepresented., Conclusion: While the data are heterogenous, this review can serve as a reference for future research in emergency medical dispatcher stroke recognition and initiatives to improve prehospital stroke recognition., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: HC is Chair of Action Plan for Stroke in Europe Implementation, Co-chair Scientific Stroke Panel, EAN and Senior Guest Editor: AHA Stroke. She has received grants from the Velux foundation, Tværsfonden, Helsefonden, the Hartmann Brothers Foundation, The Lundbeck Foundation, and the Novo Nordic Foundation. HC also co-authored the paper by Viereck et al. included in this review. HC has received honoraria from Bayer and BMS and receives royalties from Gyldendal publishing. CK has received grants from the Novo Nordic Foundation, Lundbeck Foundation and Trygfonden and is Vicechair (since 2023 Chair) of the Danish Resuscitation Council (unpaid) and the Vicechair of Danish Stroke Society (unpaid). JW, BHH, MVS, HCC and SNB have no conflicting interest to declare.

Objective: The aims of the present study were to determine how renal disease is associated with the time to receive hyperacute stroke care., Methods: The present study involved a 5-year cohort of all patients admitted to stroke units in South Australia., Results: In those with pre-existing renal disease there were no significant differences in the time taken to receive a scan, thrombolysis or endovascular thrombectomy., Conclusions: The present study shows that in protocolised settings there were no significant delays in hyperacute stroke management for patients with renal disease., (© 2024 The Authors. Emergency Medicine Australasia published by John Wiley & Sons Australia, Ltd on behalf of Australasian College for Emergency Medicine.)

Objectives: This study aims to demonstrate the capacity of natural language processing and topic modeling to manage and interpret the vast quantities of scholarly publications in the landscape of stroke research. These tools can expedite the literature review process, reveal hidden themes, and track rising research areas., Materials and Methods: Our study involved reviewing and analyzing articles published in five prestigious stroke journals, namely Stroke, International Journal of Stroke, European Stroke Journal, Translational Stroke Research, and Journal of Stroke and Cerebrovascular Diseases. The team extracted document titles, abstracts, publication years, and citation counts from the Scopus database. BERTopic was chosen as the topic modeling technique. Using linear regression models, current stroke research trends were identified. Python 3.1 was used to analyze and visualize data., Results: Out of the 35,779 documents collected, 26,732 were classified into 30 categories and used for analysis. "Animal Models," "Rehabilitation," and "Reperfusion Therapy" were identified as the three most prevalent topics. Linear regression models identified "Emboli," "Medullary and Cerebellar Infarcts," and "Glucose Metabolism" as trending topics, whereas "Cerebral Venous Thrombosis," "Statins," and "Intracerebral Hemorrhage" demonstrated a weaker trend., Conclusions: The methodology can assist researchers, funders, and publishers by documenting the evolution and specialization of topics. The findings illustrate the significance of animal models, the expansion of rehabilitation research, and the centrality of reperfusion therapy. Limitations include a five-journal cap and a reliance on high-quality metadata., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Stroke is a common cause of mortality in the United States. However, the economic burden of stroke on the healthcare system is not well known. In this study, we aim to calculate the annual cumulative and per-patient cost of stroke., Methods: We conducted a retrospective analysis of Nationwide Emergency Department Sample (NEDS). We calculate annual trends in cost for stroke patients from 2006 to 2019. A multivariate linear regression with patient characteristics (e.g. age, sex, Charlson Comorbidity Index) as covariates was used to identify factors for higher costs., Results: In this study time-period, 2,998,237 stroke patients presented to the ED and 2,481,171 (83 %) were admitted. From 2006 to 2019, the cumulative ED cost increased by a factor of 7.0 from 0.49 ± 0.03 to 3.91 ± 0.16 billion dollars (p < 0.001). The cumulative inpatient (IP) cost increased by a factor of 2.7 from 14.42 ± 0.78 to 37.06 ± 2.26 billion dollars (p < 0.001. Per-patient ED charges increased by a factor of 3.0 from 1950 ± 64 to 7818 ± 260 dollars (p < 0.001). Per-patient IP charges increased by 89 % from 40.22 +/- 1.12 to 76.06 ± 3.18 thousand dollars (p < 0.001)., Conclusion: Strokes place an increasing financial burden on the US healthcare system. Certain patient demographics including age, male gender, more comorbidities, and insurance type were significantly associated with increased cost of care., Competing Interests: Declaration of competing interest None of the authors have any conflicting interest., (Copyright © 2024. Published by Elsevier Inc.)

Objective: To examine the relationship between stroke care infrastructure and stroke quality-of-care outcomes at 29 spoke hospitals participating in the Medical University of South Carolina (MUSC) hub-and-spoke telestroke network., Materials and Methods: Encounter-level data from MUSC's telestroke patient registry were filtered to include encounters during 2015-2022 for patients aged 18 and above with a clinical diagnosis of acute ischemic stroke, and who received intravenous tissue plasminogen activator. Unadjusted and adjusted generalized estimating equations assessed associations between time-related stroke quality-of-care metrics captured during the encounter and the existence of the two components of stroke care infrastructure-stroke coordinators and stroke center certifications-across all hospitals and within hospital subgroups defined by size and rurality., Results: Telestroke encounters at spoke hospitals with stroke coordinators and stroke center certifications were associated with shorter door-to-needle (DTN) times (60.9 min for hospitals with both components and 57.3 min for hospitals with one, vs. 81.2 min for hospitals with neither component, p <.001). Similar patterns were observed for the percentage of encounters with DTN time of ≤60 min (63.8% and 68.9% vs. 32.0%, p <.001) and ≤45 min (34.0% and 38.4% vs. 8.42%, p <.001). Associations were similar for other metrics (e.g., door-to-registration time), and were stronger for smaller (vs. larger) hospitals and rural (vs. urban) hospitals., Conclusions: Stroke coordinators or stroke center certifications may be important for stroke quality of care, especially at spoke hospitals with limited resources or in rural areas., Competing Interests: Declaration of competing interest We declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: Inadequate trunk function is the underlying cause of many problems such as impaired balance and mobility. Although there have been trunk-based physiotherapy approaches in recent years, almost all of these approaches focus on motor problems. This study aims to investigate the effects of sensory training combined with trunk-centered Bobath exercises on trunk control and proprioception, balance, gait, and the activity of daily living (ADL)., Materials and Methods: This study is a randomized controlled trial included with twenty-seven stroke patients. Participants were separated into two groups, Group 1; 'sensory training combined with trunk-centered Bobath exercises' and Group 2; 'trunk-centered Bobath exercises'. Trunk-centered Bobath exercises were used for motor training. Sensory training included transcutaneous electric nerve stimulation and a set of exercises that provide tactile and proprioceptive stimulation. Trunk Impairment Scale, Trunk Reposition Error, Berg Balance Scale, 2-minute walk test, and Barthel Index were used to assess trunk control, trunk proprioception, balance, gait, and ADL respectively., Results: Intra-group analysis results showed that trunk control, trunk proprioception, balance, gait, and ADL improved in both groups after treatment ( p  < 0.05). The changes in the Trunk Reposition Error values of the participants in Group 1 before and after treatment was found to be significantly higher than Group 2 ( p  < 0.05)., Conclusions: The findings indicated that the application of trunk-centered motor training is effective in improving trunk proprioception and trunk control, balance, gait, and ADL in stroke patients. Also, sensory training combined with trunk-centered motor training was found more effective in improving trunk proprioception than solely motor training.

Introduction: IVT use declined globally in 2020 due to the Corona Virus Disease 2019 (COVID-19) pandemic, but it increased in South China. This study was conducted to evaluate the association of establishing Stroke Prevention Centers (SPCs) at primary hospitals with IVT increase in South China., Materials and Methods: We conducted a longitudinal observational study across 336 hospitals in 114 areas in South China during 2020-2022. Data regarding certified stroke centers, IVT volumes, and IVT rates were collected. Correlations between IVT rates and the number or density of stroke centers were accessed. IVT use was compared among areas with different levels of stroke centers or on different certification process., Results: During 2020-2022, there were 83, 125, and 152 stroke centers, with 26, 65, and 92 SPCs, respectively. IVT therapies were 12,795, 17,266, and 20,411, representing a 29.8% increase/year (all p  < 0.001). IVT rates increased from 7.2% in 2020 to 8.8% and 10.4% in 2021 and 2022, demonstrating a 22.2% increase/year (all p  < 0.001). IVT rates correlated with the number and density of SPCs (all p  < 0.05). IVT rates were higher in areas equipped with SPCs than in those without stroke centers (all p  < 0.05). IVT rates consistently increased during the SPC certification process from 1 year before through the certification and subsequent maintenance (both p  < 0.05)., Discussion and Conclusion: Well-organised SPCs and IVT therapy demonstrated substantial increase during the 3-year period. Certification of SPCs at primary hospitals is associated with improved IVT therapy in South China even with city lockdown during COVID-19 pandemic., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Acute ischemic stroke is a critical health condition that requires timely intervention. Following admission, clinicians typically use perfusion imaging to facilitate treatment decision-making. While deep learning models leveraging perfusion data have demonstrated the ability to predict post-treatment tissue infarction for individual patients, predictions are often represented as binary or probabilistic masks that are not straightforward to interpret or easy to obtain. Moreover, these models typically rely on large amounts of subjectively segmented data and non-standard perfusion analysis techniques. To address these challenges, we propose a novel deep learning approach that directly predicts follow-up computed tomography images from full spatio-temporal 4D perfusion scans through a temporal compression. The results show that this method leads to realistic follow-up image predictions containing the infarcted tissue outcomes. The proposed compression method achieves comparable prediction results to using perfusion maps as inputs but without the need for perfusion analysis or arterial input function selection. Additionally, separate models trained on 45 patients treated with thrombolysis and 102 treated with thrombectomy showed that each model correctly captured the different patient-specific treatment effects as shown by image difference maps. The findings of this work clearly highlight the potential of our method to provide interpretable stroke treatment decision support without requiring manual annotations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)