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Stroke remains a leading cause of mortality and disability, with ischemic stroke being the most common type. It occurs due to reduced cerebral blood flow, leading to a cascade of events initiated by oxygen and nutrient deprivation, triggering excitotoxicity, oxidative stress, and inflammation and finally culminating in neuronal injury and death. Key molecular players in ischemic stroke include glutamate receptors, acid-sensing ion channels, and purinergic receptors, exacerbating cellular damage through calcium influx, oxidative stress, and mitochondrial dysfunction. Understanding these mechanisms has shaped therapeutic strategies, such as neuroprotective agents and stem cell therapies. Current treatments such as tissue plasminogen activator (tPA) emphasize timely intervention, yet challenges persist in patient-specific variability and accessibility. This review provides an overview of ischemic stroke pathophysiology, emphasizing cellular responses to ischemia and current and future therapeutic approaches including stem cell therapies aimed at mitigating stroke-induced disabilities and improving long-term outcomes. [ABSTRACT FROM AUTHOR]

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]

Stroke is the number one cause of morbidity in the United States and number two cause of death worldwide. There is a critical unmet medical need for more effective treatments of ischemic stroke, and this need is increasing with the shift in demographics to an older population. Recently, several studies have reported the therapeutic potential of stem cell-derived exosomes as new candidates for cell-free treatment in stoke. This review focuses on the use of stem cell-derived exosomes as a potential treatment tool for stroke patients. Therapy using exosomes can have a clear clinical advantage over stem cell transplantation in terms of safety, cost, and convenience, as well as reducing bench-to-bed latency due to fewer regulatory milestones. In this review article, we focus on (1) the therapeutic potential of exosomes in stroke treatment, (2) the optimization process of upstream and downstream production, and (3) preclinical application in a stroke animal model. Finally, we discuss the limitations and challenges faced by exosome therapy in future clinical applications. [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]

This article presents a case study on the use of stem cell therapy for post-stroke patients with Type 2 diabetes. The study involved five patients who received stem cell therapy derived from umbilical cords and cord blood. The therapy, combined with hormonal therapy and lifestyle changes, resulted in reduced glucose levels and improved HbA1c levels in all patients. Patients also reported improvements in mobility, strength, mood, and overall quality of life. While the study suggests that stem cell therapy shows promise in treating these patients, further research with a larger sample size is needed to confirm these findings. [Extracted from the article]

Stroke is the number one cause of morbidity in the United States and number two cause of death worldwide. There is a critical unmet medical need for more effective treatments of ischemic stroke, and this need is increasing with the shift in demographics to an older population. Recently, several studies have reported the therapeutic potential of stem cell-derived exosomes as new candidates for cell-free treatment in stoke. This review focuses on the use of stem cell-derived exosomes as a potential treatment tool for stroke patients. Therapy using exosomes can have a clear clinical advantage over stem cell transplantation in terms of safety, cost, and convenience, as well as reducing bench-to-bed latency due to fewer regulatory milestones. In this review article, we focus on (1) the therapeutic potential of exosomes in stroke treatment, (2) the optimization process of upstream and downstream production, and (3) preclinical application in a stroke animal model. Finally, we discuss the limitations and challenges faced by exosome therapy in future clinical applications.

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]

Objective: Stroke patients with large core infarctions benefit from endovascular intervention, though only approximately 20% are functionally independent at 90 days. We studied prognostic factors for patients presenting with a large computed tomography perfusion (CTP) core., Methods: Retrospective analysis from a health system stroke registry, including consecutive thrombectomy patients treated within 24 hours from August 2020-December 2022 with an anterior circulation large vessel occlusion and CTP core infarct ≥50 milliliters. Logistic regression was used to determine independent predictors of 90-day modified Rankin Scale (mRS) score 4-6. The prognostic ability of previously reported scales was also assessed., Results: In 118 included patients, with mean age 64.3 ± 14.1 years, poor functional outcomes were present in 66 subjects (55.9%). The multivariable regression analysis demonstrated that higher presenting National Institutes of Health Stroke Scale (NIHSS) score (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.02-1.23, p = 0.014), elevated glucose (OR 1.02, 95% CI 1.01-1.03, p = 0.002), absence of treatment with intravenous thrombolysis (OR 4.01, 95% CI 1.35-11.95, p = 0.013), and poor revascularization (OR 4.76, 95% CI 1.24-18.37, p = 0.023) were independently associated with primary outcome. The Charlotte Large artery occlusion Endovascular therapy Outcome Score (CLEOS) predicted 90-day mRS 4-6 (per 25-point increase, OR 1.22, 95% CI 1.10-1.34, p<0.001) and mRS 5-6 (per 25-point increase, OR 1.21, 95% CI 1.10-1.33, p<0.001). Nineteen of 20 (95%) patients with CLEOS ≥ 675 had 90-day mRS scores of 4-6, while 10 of 12 (83.3%) with CLEOS ≥ 725 had 90-day mRS scores of 5-6., Conclusion: We report prognostic factors that can risk stratify thrombectomy patients with large CTP core infarctions., Competing Interests: Dr. Rahul Karamchandani receives research support from Genentech. Dr. Joe Bernard declares stock/stock options from Viz.Ai and personal fees from Stryker, Terumo, and Rapid AI. Dr. Andrew Asimos is a consultant for Rapid AI. All other authors report no disclosures., (Copyright: © 2024 Karamchandani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Stroke is predominantly a condition of older age. So, it seems sensible that specialists working in stroke services should understand the primary clinical syndrome of ageing-frailty. Recent studies have highlighted the prevalence of frailty in stroke and its associated poor outcomes, yet frailty does not feature prominently in stroke research, practice or policy. Frailty-informed stroke care may differ from the interventional management that dominates contemporary practice. However, this is not therapeutic nihilism. A person-centred approach ensures that every care decision is appropriate and based on a shared understanding of the person's goals and likely prognosis. We present a primer on frailty in stroke, describing definition(s), epidemiology and prognostic implications. We discuss the challenges surrounding assessment and management of frailty in stroke units and offer practical guidance suitable for the stroke clinician., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Minor strokes, which account for about 50 % of all ischemic strokes are not necessarily benign and carry a substantial risk of long-term disability. Due to persisting uncertainties regarding optimal recanalization strategies mild strokes may represent a therapeutical challenge for clinicians. The aim of this review is to provide an overview of the current state of knowledge and questions remaining to be answered., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The impact of hospital care quality on patient outcomes in post-stroke aphasia remains unclear. We investigated the impact of nationally-endorsed acute stroke treatments on outcomes post-stroke, by aphasia status., Methods: Patient-level data from the Australian Stroke Clinical Registry (2009-2013) linked to national deaths, hospital emergency presentations and admissions data were used. Aphasia was identified for the index stroke event (ICD-10 diagnosis code R47.0). Impact of receiving an optimal stroke care bundle (stroke unit care, antihypertensive medication at discharge and discharge care plan) and an acute ischemic stroke (AIS) care bundle (stroke unit care, intravenous thrombolysis and aspirin within 48 h of admission) on outcomes were analysed using multivariable regression models with propensity score adjustment., Results: The study included 12,690 patients with a median age of 76, 54 % male, and 26 % with aphasia. Non-receipt of the optimal stroke care bundle was associated with worse survival, compared to optimal care, in people with aphasia (HR: 3.37; 95 % CI 2.10, 5.40; p < 0.05) and without aphasia (HR: 2.10; 95 % CI 1.19, 3.69; p < 0.05). Notably, the dose-response effect on survival was more pronounced in individuals with aphasia. In those who received the AIS care bundle, readmission within 12 months was greater in those without aphasia (vs aphasia, p-value interaction = 0.001), whereas survival was similar (p-value interaction = 0.731)., Conclusions: Survivors of stroke with aphasia who did not receive the optimal stroke care bundle, had worse survival at 12 months post-stroke. Ensuring eligible patients receive the optimal stroke care bundle is crucial for improving their 12-month survival., Competing Interests: Declaration of competing interest D.A.C is the current Data Custodian for the AuSCR. D.A.C reports receiving restricted grants from Boehringer Ingelheim, Ipsen, Medtronic, and Shire outside the work presented today. M.F·K is a member of the AuSCR Management Committee and the Research Advisory Committee of the Stroke Foundation, reports receiving educational grants from Amgen Australia and GSK outside the submitted work. All other authors report no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (Copyright © 2024. Published by Elsevier B.V.)

Background: Data regarding unequal diagnostic and therapeutic access in patients with acute stroke based on ethnicity and race are inconclusive in Europeans. The objectives of our study were to evaluate the effect of race/ethnicity on access to acute stroke care and treatments and outcomes., Methods: In this retrospective cohort study, we enrolled adult patients admitted to the emergency department of a comprehensive stroke center for suspected stroke. Based on race/ethnicity, patients were divided into two main groups: Western European Whites (WEW) and non-Western European Whites (nWEW). We also divided the nWEW group into four subgroups based on the Office of Management and Budget classification of human races and ethnicities (White-Others, Hispanic, Asian, Black). Univariate comparisons and logistic regression analyses were also performed., Results: 9167 patients were enrolled in the study: 582 in the nWEW and 8585 in the WEW group. Patients with ischemic stroke in the nWEW group were significantly younger than those in the other group (p < 0.001). Once adjusted for possible confounders, belonging to the nWEW group was found to be an independent predictor of a lower likelihood of receiving revascularization treatments (p = 0.006), regardless similar onset-to-door times. There were no differences in stroke outcomes and prevalence of stroke mimic diagnosis between the groups., Conclusions: Racial/ethnic disparities in healthcare represent a challenging issue, even in universal healthcare systems, that should be addressed promptly through education campaigns of healthcare personnel and implementation measures, such as integrating readily available interpreter staff for medical emergencies., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: To observe the clinical effect of CHEN Yinglong 's ziwu reinforcing and reducing acupuncture method on post-stroke swallowing dysfunction (PSD) in the pharyngeal phase, and explore its biomechanical mechanism., Methods: A total of 72 patients with PSD in the pharyngeal phase were randomly divided into a ziwu reinforcing and reducing acupuncture group (36 cases, 2 cases dropped out and 1 case was eliminated) and a conventional acupuncture group (36 cases, 1 case dropped out and 1 case was eliminated). The patients in the conventional acupuncture group were treated with conventional acupuncture at Lianquan (CV 23) and bilateral Fengchi (GB 20), Wangu (GB 12), Tongli (HT 5), Zhaohai (KI 6), Hegu (LI 4), Taichong (LR 3). The patients in the ziwu reinforcing and reducing acupuncture group were treated with CHEN Yinglong 's ziwu reinforcing and reducing acupuncture method on the basis of the conventional acupuncture group's acupoints. Both groups were treated with acupuncture for 30 min each time, once a day, and rested for 1 day after 6 days of treatment, and the treatment lasted 4 weeks. Before and after treatment, the standardized swallowing assessment (SSA) score, Rosenbek penetration aspiration scale (PAS) grade, the shortening rate of mandibular-hyoid distance, swallowing quality of life (SWAL-QOL) score were evaluated in the two groups. The removal rate of nasogastric feeding tube was compared in the two groups, and the clinical efficacy and safety of the two groups were compared., Results: After treatment, the SSA scores and PAS grade of the two groups were lower than those before treatment ( P <0.001), and above indexes in the ziwu reinforcing and reducing acupuncture group were lower than those in the conventional acupuncture group ( P <0.01, P <0.05). After treatment, the shortening rates of mandibular-hyoid distance and SWAL-QOL scores in the two groups were higher than those before treatment ( P <0.001), and the shortening rate of mandibular-hyoid distance in the ziwu reinforcing and reducing acupuncture group was higher than that in the conventional acupuncture group ( P <0.001). The removal rate of nasogastric feeding tube in the ziwu reinforcing and reducing acupuncture group was 87.9% (29/33), which was higher than 61.8% (21/34) in the conventional acupuncture group ( P <0.05). The total effective rate of the ziwu reinforcing and reducing acupuncture group was 84.8% (28/33), which was higher than 61.8% (21/34) of the conventional acupuncture group ( P <0.05). Neither group experienced serious adverse reactions., Conclusion: CHEN Yinglong 's ziwu reinforcing and reducing acupuncture method can effectively improve swallowing dysfunction in the pharyngeal phase after stroke, reduce the risk of aspiration, and improve quality of life. Its therapeutic effect may be related to increasing the displacement amplitude of the hyoid bone.

Through collecting the relevant records of "brain" in ancient traditional Chinese medicine literature, the potential structure and function of the "motor system of brain-meridian-muscle region" and "perception system of brain-meridian-cutaneous region" of the human body are analyzed preliminarily. In view of the characteristics of the symptoms of stroke sequela, focusing on the differentiation of disease location and associated with the identification of disease property, the pathogenesis of stroke is determined, "malnutrition of the sea of marrow, dysfunction of meridian muscle region and disharmony of the nutrient and the defensive in the meridian cutaneous region", while, the basic principle of treatment is formulated, "filling up the marrow, replenishing the brain, regulating meridian muscle regions, tonifying qi and facilitating blood circulation in meridians and collaterals". Based on the above, the acupoints selected in treatment and the techniques of acupuncture and moxibustion are clarified. This article presents the references for the clinical practice of acupuncture and moxibustion and provides the individual therapeutic regimen for stroke patients.

Stem cell transplantation offers a promising therapy that can be administered days, weeks, or months after a stroke. We recognize 2 major mitigating factors that remain unresolved in cell therapy for stroke, notably: (1) well-defined donor stem cells and (2) mechanism of action. To this end, we advance the use of ProtheraCytes, a population of non-adherent CD34+ cells derived from human peripheral blood and umbilical cord blood, which have been processed under good manufacturing practice, with testing completed in a phase 2 clinical trial in post-acute myocardial infarction (NCT02669810). We also reveal a novel mechanism whereby ProtheraCytes secrete growth factors and extracellular vesicles (EVs) that are associated with angiogenesis and vasculogenesis. Our recent data revealed that intranasal transplantation of ProtheraCytes at 3 days after experimentally induced stroke in adult rats reduced stroke-induced behavioral deficits and histological damage up to 28 days post-stroke. Moreover, we detected upregulation of human CD63+ EVs in the ischemic brains of stroke animals that were transplanted with ProtheraCytes, which correlated with increased levels of DCX-labeled neurogenesis and VEGFR1-associated angiogenesis and vasculogenesis, as well as reduced Iba1-marked inflammation. Altogether, these findings overcome key laboratory-to-clinic translational hurdles, namely the identification of well-characterized, clinical grade ProtheraCytes and the elucidation of a potential CD63+ EV-mediated regenerative mechanism of action. We envision that additional translational studies will guide the development of clinical trials for intranasal ProtheraCytes allografts in stroke patients, with CD63 serving as a critical biomarker., (© The Author(s) 2024. Published by Oxford University Press.)

The prevalence of cardiovascular events, stroke, and diabetes worldwide underscores the urgent need for effective and minimally invasive treatments. With nearly 20 million annual casualties attributed to cardiovascular diseases and an estimated 463 million people living with diabetes in 2022. Identifying promising therapeutic candidates is paramount. MicroRNAs, short nucleic acids involved in regulating gene expression, emerge as potential game-changers. Among these, microRNA-24 (miR-24), a hypoxia-sensitive player in endothelial vessels, has protective roles against diverse vascular complications. Following heart infarction and stroke, elevating miR-24 expression proves beneficial by mitigating oxidative stress, inflammation, and apoptosis while enhancing cell survival. It reduces cardiac fibrosis in heart disease, regulates aberrant angiogenesis in cerebral hemorrhagic strokes, and enhances the functionality of cardiomyocytes and brain neurons. In diabetic conditions, augmenting miR-24 expression mitigates complications. Further, being miR-24 also expressed by the skeletal muscle (i.e., myo-miR) in response to exercise, this miRNA may participate in the complex molecular network that systemically spreads the beneficial effects of physical exercise. This review provides a comprehensive vision of the molecular mechanisms underpinning the miR-24 protective effects, offering new insights into its therapeutic potential and proposing a novel avenue for medical intervention., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Introduction: Post stroke elbow spasticity (PSES) affects over a third of individuals following stroke and negatively impacts on functional recovery, comfort and quality of life. Drug therapies have limited efficacy and unwanted side effects, botulinum toxin, although effective, is costly, and conventional electrical stimulation therapies are limited long term by habituation. We aim to investigate the efficacy of Sheffield Adaptive Patterned Electrical Stimulation (SHAPES), that delivers temporally and spatially varying pattern of electrical stimulation, against transcutaneous electrical stimulation (TENS) and standard care at reducing PSES., Methods and Design: Overall, 297 people with PSES will be randomised (1:1:1) to one of 3 arms: Standard care (no electrical stimulation), TENS (conventional patterned electrical stimulation) or SHAPES (adaptive patterned electrical stimulation). Both SHAPES and TENS are delivered using a specially designed electrical stimulation sleeve used for 60 min each day for 6-weeks. Outcome measures are completed at baseline, end of treatment (EOT 6 weeks) and then 6-weeks, 12-weeks and 24-weeks after the end of treatment. Efficacy will be determined based on the proportion of participants experiencing meaningful improvement (18%) in the 7-day Numerical Rating Scale (NRS-S) for PSES, compared between both intervention arms and standard care, and between the two intervention groups. Measures of arm motor function (Action Research Arm Test, MRC scale), and quality of life (SQoL-6D, EQ-5D) will also be measured along with a parallel health economic evaluation., Discussion: The results of the SHAPES trial will inform management of elbow spasticity after stroke. The SHAPES intervention is a low cost, self-administered intervention for the management of spasticity that can be used repeatedly, and if found to be more effective than TENS or control has the potential to be widely implemented in the UK NHS healthcare setting. Furthermore, despite the wide use of TENS in the management of spasticity, this study will provide critically required evidence regarding its efficacy. The trial has been registered with the ISRCTN registry (ISRCTN26060261)., (© 2024. Crown.)

To assess knowledge, attitude, and practice (KAP) of stroke and thrombectomy among medical students in Henan, China. A cross-sectional study was conducted on medical students from 5 universities in Henan, China between June and September, 2022, using a self-administered questionnaire. A total of 1105 medical students [697 (62.1%) females] participated. Their mean KAP scores were 11.1 ± 2.90, 35.37 ± 4.94, and 21.48 ± 5.51 out of 14, 44, and 24, respectively. Structural equation modeling revealed that, age (estimate = 0.351, P = .005) and education (estimate = 0.370, P = .024) positively affected knowledge, while major (estimate = -0.128, P = .017), internship experience in neurosurgery or neurology (estimate = -1.321, P < .001), and family history of stroke (estimate = -0.557, P < .001) negatively influenced knowledge. Knowledge (estimate = 0.649, P < .001) and having seniors over the age of 60 at home (estimate = 1.228, P = .001) had positive effects on attitudes, while internship experience in neurosurgery or neurology (estimate = -0.471, P = .090) and family history of stroke (estimate = -0.596, P = .020) had negative impact on attitudes. Moreover, knowledge (estimate = 0.230, P < .001) and attitudes (estimate = 0.628, P < .001) positively influenced practices, whereas sex (estimate = -1.141, P < .001), internship experience in neurosurgery or neurology (estimate = -0.578, P = .025), and family history of stroke (estimate = -0.523, P = .027) negatively influenced practices. Medical students in Henan, China showed adequate knowledge, positive attitude, and proactive practice toward stroke and thrombectomy. Age, sex, education, major, internship experience in neurosurgery or neurology, family history of stroke, having seniors over the age of 60 at home might have impact on their KAP., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Inadequate physical activity (PA) is increasingly common among stroke patients, we aim to comprehensively analyze the experience of stroke patients delivering physical activity, understand the obstacles and promoting factors of physical activity, and summarize clinical management strategies., Methods: An electronic search of PubMed, Web of Science, Cochrane Library, ProQuest, SinoMed, CNKI, and WanFang Database was conducted for qualitative studies on the experience of PA in stroke patients. The review was appraised using the Joanna Briggs Institute methodology, the subsequent findings were synthesized via the Thomas and Harden approach and the credibility of the research results was evaluated by the CERqual tool., Results: Six thousand five hundred forty-nine findings were yielded through the search, ultimately 11 studies were included through screening, a total of 194 stroke patients participated in the study, and 3 synthesized themes that emerged were identified: barriers to PA, facilitators to PA, and strategies to improve compliance with physical activity in stroke patients. All selected articles were of medium quality and all themes were of medium or high quality., Conclusion: The experience of PA among stroke patients should be given more attention. Healthcare professionals should provide physical activity-related knowledge education, social support, personalized care, improved environments, and create more opportunities for PA. In the future, more tailored interventions should be carried out to develop PA habits and improve compliance., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: National audit programmes are a recognised means of assessing quality of healthcare by collecting and reporting data in relation to evidence-based standards. The Sentinel Stroke National Audit Programme is a prospective audit of processes and outcomes for all stroke patients in England, Wales and Northern Ireland which has historically focused on hospital-based care. Evidence suggests it has been successful in driving quality improvement. What has yet to be explored is the influence of such a national audit programme on community-based healthcare. The aims of this study were to understand how community stakeholders perceive and participate in the audit., Methods: The study used a realist approach, being theory driven and informed by collaborators including stroke clinicians and experts in realist and audit methodology. Contextual determinants and mechanisms were identified from the literature as having the potential to influence quality improvement. These were operationalised into 18 survey items, using a combination of 5-point scales and yes / no responses. Free text options offered the opportunity to expand upon responses. The online survey was distributed using social media, clinical networks and professional bodies. Representation was sought from community stroke stakeholders across England and from roles throughout the audit process including administrative, clinical, management and commissioning., Results: The survey achieved a national sample from a broad range of stakeholders (n=206). Participants reported being engaged in the audit, committing significant resources to participation. National audit feedback was described as being used to support a range of improvement activities, including funding for additional staff and service reorganisation. A number of factors influenced the ability of teams to participate in audit and utilise feedback for quality improvement. These included the online platform, the accuracy of data submitted and leadership support., Conclusions: Findings highlight the work needed in terms of the data captured, organisational audit support and engagement with feedback if the potential of the audit as a tool for quality improvement in community rehabilitation (as highlighted in acute stroke care) is to be realised., (© 2024. The Author(s).)

Background: Mobile stroke units have been shown to deliver faster patient care and improve clinical outcomes. However, costs associated with staffing limit their use to densely populated cities. Using the Melbourne mobile stroke unit, we aim to evaluate the safety, timeliness, and resource efficiency of a telemedicine model, where the neurologist assesses a patient remotely, via telemedicine, compared with an onboard neurologist model. We hypothesize that, without compromising patient safety, the telemedicine model will provide timely care and superior resource efficiency., Methods: Using a prospective, randomized, blinded end-point controlled design, 270 participants consecutively assessed on the Melbourne mobile stroke unit over ≈12 months will be assigned into 2 arms: (1) telemedicine neurologist assessment (intervention) versus (2) onboard assessment (comparator). Enrollment is based on prospectively designated randomized days of neurologist review onboard versus telemedicine. The primary outcome will be the odds that a randomly selected participant in the telemedicine arm will have a better outcome than a randomly selected participant in the onboard arm, measured using a desirability-of-outcome ranking, an outcome measure that includes, in order of importance: (1) safety, (2) scene-to-treatment-decision time metrics, and (3) resource usage. All participants within each arm will be compared with those in the other, resulting in a "win/tie/loss" distribution for telemedicine compared with the onboard model., Conclusions: The study will establish whether use of a telemedicine neurologist delivers superior resource efficiency without compromising patient care. This would enable the broader use of mobile stroke units, particularly relevant to regions with limited access to neurologists, thus improving equity in access to time-critical, lifesaving stroke care., Registration: URL: clinicaltrials.gov; Unique Identifier: NCT05991310.

Background and Aim: The clinical importance and management of vasospasm as a complication during endovascular stroke treatment (EVT) has not been well studied. We sought to investigate current expert opinions in neurointervention and therapeutic strategies of iatrogenic vasospasm during EVT., Methods: We conducted an anonymous international online survey (4 April 2023 to 15 May 2023) addressing treatment standards of neurointerventionalists (NIs) practising EVT. Several illustrative cases of patients with vasospasm during EVT were shown. Two study groups were compared according to the NI's opinion regarding the potential influence of vasospasm on patient outcome after EVT using descriptive analysis., Results: In total, 534 NI from 56 countries responded, of whom 51.5% had performed >200 EVT. Vasospasm was considered a complication potentially influencing the patient's outcome by 52.6% (group 1) whereas 47.4% did not (group 2). Physicians in group 1 more often added vasodilators to their catheter flushes during EVT routinely (43.7% vs 33.9%, p=0.033) and more often treated severe large-vessel vasospasm with vasodilators (75.3% vs 55.9%; p<0.001), as well as extracranial vasospasm (61.4% vs 36.5%, p<0.001) and intracranial medium-vessel vasospasm (27.1% vs 11.2%, p<0.001), compared with group 2. In case of a large-vessel vasospasm and residual and amenable medium-vessel occlusion during EVT, the study groups showed different treatment strategies. Group 2 continued the EVT immediately more often, without initiating therapy to treat the vasospasm first (9.6% vs 21.1%, p<0.001)., Conclusion: There is disagreement among NIs about the clinical relevance of vasospasm during EVT and its management. There was a higher likelihood of use of preventive and active vasodilator treatment in the group that perceived vasospasm as a relevant complication as well as differing interventional strategies for continuing an EVT in the presence of a large-vessel vasospasm., 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.)

Importance: It is unclear how certified stroke center expansion contributes to improved access to stroke treatment and patient outcomes, and whether these outcomes differ by baseline stroke center access., Objective: To examine changes in rates of admission to stroke centers, receipt of thrombolysis and mechanical thrombectomy, and mortality when a community gains a newly certified stroke center within a 30-minute drive., Design, Setting, and Participants: This cohort study compared changes in patient outcomes when a community (defined by area zip code) experienced a stroke center expansion relative to the same community type that did not experience a change in access. Medicare fee-for-service beneficiaries with a primary diagnosis of acute ischemic stroke who were admitted to hospitals between January 1, 2009, and December 31, 2019, were included. The data analysis was performed between October 1, 2023, and September 9, 2024., Exposure: New certification of a stroke center within a 30-minute driving time of a community., Main Outcomes and Measures: The main outcomes were rates of admission to a certified stroke center, receipt of thrombolytics (delivered using drip-and-ship and drip-and-stay methods), mechanical thrombectomy, and 30-day and 1-year mortality estimated using a linear probability model with community fixed effects., Results: Among the 2 853 508 patients studied (mean [SD] age, 79.5 [8.5] years; 56% female), 66% lived in communities that had a stroke center nearby at baseline in 2009, and 34% lived in communities with no baseline access. For patients without baseline access, after stroke center expansion, the likelihood of admission to a stroke center increased by 38.98 percentage points (95% CI, 37.74-40.21 percentage points), and receipt of thrombolytics increased by 0.48 percentage points (95% CI, 0.24-0.73 percentage points). Thirty-day and 1-year mortality decreased by 0.28 percentage points (95% CI, -0.56 to -0.01) and 0.50 percentage points (95% CI, -0.84 to -0.15 percentage points), respectively, after expansion. For patients in communities with baseline stroke center access, expansion was associated with an increase of 9.37 percentage points (95% CI, 8.63-10.10 percentage points) in admission to a stroke center but no significant changes in other outcomes., Conclusions and Relevance: In this cohort study, patients living in communities without baseline stroke center access experienced significant increases in stroke center admission and thrombolysis and a significant decrease in mortality after a stroke center expansion. Improvements were smaller in communities with preexisting stroke center access. These findings suggest that newly certified stroke centers may provide greater benefits to underserved areas and are an important consideration when deciding when and where to expand health care services.

A paediatric stroke is a rare entity that can occur at any age. It may be arterial or venous, ischemic or haemorrhagic, and may occur in the neonatal or paediatric stage of life, as well as in adolescence. Prompt diagnosis means that adequate treatment can be administered and prevents recurrence, minimising the percentage of sequelae. This guide aimed to analyse, prepare and classify the literature currently available in order to determine the best recommendations on the treatment of strokes in paediatric patients. In each section, we attempted to answer the following questions: when should we think in terms of a stroke and thrombosis of the cerebral venous sinuses in a newborn or paediatric patient? What are the recommended complementary studies? Is treatment indicated? What are the recommended treatments? This guide was prepared based on the opinion of experts in the field, in order to determine how the recommendations were assessed according to the 2011 Oxford Levels of Evidence. Finally, the guidelines were reviewed by the scientific committee of the Iberoamerican Academy of Pediatric Neurology for subsequent dissemination.

Background Wearable devices, such as accelerometers, offer novel approaches to measuring post-stroke upper limb activity. Limited studies have explored feasibility of accelerometry. Guided by the Bowen Feasibility Framework, this feasibility study aimed to examine the practicality, acceptability, and limited efficacy of accelerometry in a self-directed upper limb program with stroke survivors using a pre-post study of sequentially eligible inpatients. Method Key metrics were: practicality (60% of participants had 10hours of wear per day for 3 or more days), acceptability (adherence to recommended wear-time), and limited efficacy (correlation between Wolf Motor Function Test (WMFT) and upper limb use from accelerometry data). Results Twelve stroke survivors were recruited over 7 months, mean age 73years (range 39-94years). Eight participants (67%) met the practicality and acceptability criteria. A moderate positive correlation existed between WMFT and upper limb use at admission (r s =0.33, P =0.42) and at discharge (r s =0.42, P =0.34). Conclusion Wearable devices were feasible and acceptable for most stroke survivors, however, one-third found the devices uncomfortable, and this should be factored into sample size calculations of future studies.

Background: Non-invasive brain stimulation (NIBS) has attracted significant attention as it has been proven to be effective in facilitating upper limb motor recovery in patients with stroke. This meta-analysis evaluates the efficacy of dual-site non-invasive brain stimulation (DS-NIBS) in improving upper extremity motor function after stroke., Methods: A PRISMA systematic search was conducted for randomized controlled trials. Two authors independently extracted data, and the quality of included studies was assessed., Results: Ten studies were included in the current review. DS-NIBS demonstrated a significant effect on upper extremity motor function impairment. However, only two studies showed no clear effects of DS-tDCS on upper extremity motor function after stroke. Due to the limited number of studies, the effects of DS-NIBS remain inconclusive., Finding: This review found evidence for the relatively higher efficacy of DS-NIBS on post-stroke upper extremity motor function impairment, compared to the sham and SS-NIBS. Additionally, DS-TMS was found to generate better improvement than DS-tDCS., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Objective: This study aimed to investigate the efficacy of mindfulness meditation on sleep quality and negative emotions in patients with stroke with concurrent coronary heart disease., Methods: This study was a randomised controlled trial. A total of 72 patients with stroke with concurrent coronary heart disease were randomly divided into an observation group and a control group, with 36 patients in each group. The control group received routine treatment plus eszopiclone tablets at a dosage of 3 mg once daily. The observation group received mindfulness meditation in addition to the treatment given to the control group. The Pittsburgh Sleep Quality Index was used to assess sleep status, the Self-Rating Anxiety Scale and Self-Rating Depression Scale were used to assess depression and anxiety, and the Fugl-Meyer Assessment was used to assess motor function. All participants in both groups received a 6-week intervention., Results: Pairwise comparisons revealed that the observation group had better outcomes in sleep quality, sleep onset latency, sleep duration, sleep efficiency, sleep disturbances, daytime function and total scores at both 6 and 12 weeks compared with the control group (p < 0.05). After 12 weeks of intervention, compared with the control group, the total score of sleep quality improved more significantly (9.22 ± 2.35/6.26 ± 2.47). Additionally, different treatment methods had varying effects on anxiety scores, depression scores and motor function scores between the two groups (p < 0.001). Further comparisons showed that the observation group had lower anxiety and depression scores and higher motor function scores at both 6 and 12 weeks compared with the control group (p < 0.05)., Conclusion: Mindfulness meditation can effectively improve sleep quality and reduce negative emotions in patients with stroke with concurrent coronary heart disease, as well as promote the recovery of limb functions., (© 2024 John Wiley & Sons Ltd.)

Background: To investigate the therapeutic benefits of theta burst stimulation on lower-limb motor dysfunction and balance recovery in patients with stroke., Methods: A literature search was performed across CNKI, CBM, WanFang, VIP, PubMed, Embase, Cochrane Library, and Web of Science until November 2023. The Methodological quality of included studies was assessed by using the Cochrane risk-of-bias tool and the PEDro scale, and the meta-analysis was performed by using RevMan 5.3 software. Two independent researchers screened the literature and extracted basic information on participants, interventions, comparisons, outcomes, and studies., Results: Eight studies, including cTBS and iTBS, with 290 participants meeting the inclusion criteria for this systematic review, and 7 studies including only iTBS with 230 participants were included in this meta-analysis. The methodological quality of the studies included ranged from moderate to high. The results showed iTBS had significantly higher scores on the Berg Balance Scale (BBS) than the control group. (MD = 4.57, 95% CI: 1.76 to 7.38, Z = 3.19, P = .001). Subgroup analysis showed CRB-iTBS markedly improved BBS scores (MD = 4.52, 95% CI: 1.78 to 7.27, Z = 3.23, P = .001), whereas LE M1-iTBS did not exhibit a significant enhancement in BBS scores (MD = 6.10, 95% CI: -7.34 to 19.53, Z = 0.89, P = .37); iTBS showed no significant increase in lower-limb motor function (FMA-LE) (MD = 1.80, 95% CI: -1.10 to 4.69, Z = 1.22, P = .22). Subgroup analysis revealed both CRB-iTBS and LE M1-iTBS interventions were not effective in improving FMA-LE (MD = 3.15, 95% CI: -4.70 to 11.00, Z = .79, P = .43; MD = 1.05, 95% CI: -2.20 to 4.30, Z = .63, P = .53); iTBS significantly reduced the MEP latency (P = .004), but did not show a significant improvement in walking performance (10 MWT), mobility (TUG), or activities of daily living [M(BI)] (P > .05)., Conclusion: Based the current study, iTBS can increase patients' balance function. The CRB-iTBS protocol is more effective than the LE M1-iTBS protocol. Additionally, iTBS may be a promising therapy tending to enhance lower-limb motor function, walking performance, mobility, and activities of daily living., Competing Interests: The authors have no any conflict of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aims: Limited understanding of neurobiological mechanisms of repetitive transcranial magnetic stimulation (rTMS) prevents us from choosing optimal therapeutic regimen for patients to improve therapeutic efficiency. Resting-state functional magnetic resonance imaging (rs-fMRI) has been demonstrated to obtain comparable functional readouts across species., Methods: Intermittent and continuous theta burst stimulation were used to stimulate ipsilesional and contralesional hemisphere, respectively, during the subacute phase after stroke. We used a rat middle cerebral artery occlusion stroke model. The amplitude of low-frequency fluctuations and functional connectivity analyses of rs-fMRI were chosen to detect neuron activity and functional connectivity. The expression of neuron activation marker c-Fos and axonal plasticity marker GAP43 was examined by an immunochemistry method to corroborate the results of rs-fMRI., Results: iTBS altered the long-term neuronal activity in bilateral sensorimotor cortex, whereas cTBS influenced immediate neuronal activity of bilateral sensorimotor cortex. In addition, cTBS enhanced interhemispheric and intrahemisheric functional connectivity in contralesional hemisphere, accompanied by axonal and dendritic remodeling in the perilesional cortical areas and contralesional homologous areas after large stroke., Conclusion: rTMS exerted complex effects on brain structural and functional connectivity in addition to affecting cortical excitability. cTBS promoted the compensatory effect of contralesional hemisphere after stroke with large lesions., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background and Purpose: Sonothrombolysis is a potential adjunctive therapy for large vessel occlusion (LVO) stroke. Bedside ultrasound image-guided high-intensity focused ultrasound (HIFU) therapy could deliver higher energy therapeutic ultrasound to the thrombus with higher precision than what was previously accomplished in human trials. The aim is to test the feasibility of diagnostic transcranial contrast-enhanced ultrasound (CEUS) to image the occlusion site and continuously maintain the guidance image on-target for a sufficient exposure time for HIFU to be effective during LVO stroke evaluation and treatment., Methods: This prospective, single center, observational cohort study included adult patients, presenting within 6 hours of stroke symptom onset, with LVO identified on computed tomography angiography (CTA). A hand-held CEUS imaging study was initiated following CTA and lasted up to 30 minutes. The primary outcome is the proportion of patients where a guidance CEUS image of the occlusion was achieved., Results: A CEUS image of the occluded artery was obtained in 32/35 of the included patients. The median total imaging time was 23 minutes (interquartile range 15-30). Patients undergoing thrombectomy had a lower total imaging time (17 vs. 29.5 minutes, p = .002). When imaging was successful, on-target image was maintained for only 58% (standard deviation 23.8%) of total imaging time. No complications related to CEUS were observed., Conclusions: This feasibility study explored the use of diagnostic transcranial CEUS for continuous imaging of occlusion sites in LVO strokes. Challenges in maintaining target image during HIFU were identified, highlighting the need for technical advances for clinical application., (© 2024 The Author(s). Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.)

While the majority of stroke researchers use frequentist statistics to analyze and present their data, Bayesian statistics are becoming more and more prevalent in stroke research. As opposed to frequentist approaches, which are based on the probability that data equal specific values given underlying unknown parameters, Bayesian approaches are based on the probability that parameters equal specific values given observed data and prior beliefs. The Bayesian paradigm allows researchers to update their beliefs with observed data to provide probabilistic interpretations of key parameters, for example, the probability that a treatment is effective. In this review, we outline the basic concepts of Bayesian statistics as they apply to stroke trials, compare them to the frequentist approach using exemplary data from a randomized trial, and explain how a Bayesian analysis is conducted and interpreted., Competing Interests: Dr Ospel is a consultant for Nicolab. Dr Goyal is a consultant for Mentice, Medtronic, MicroVention, and Stryker. Dr Brown reports compensation from MicroVention, Inc, for consultant services and compensation from the Faculty of Arts, University of Calgary, for consultant services. Dr Rinkel reports grants from the Niels Stensen Fellowship. Dr Ganesh reports compensation from Figure 1 for consultant services; grants from the Heart and Stroke Foundation of Canada; compensation from Atheneum for consultant services; grants from the Canadian Cardiovascular Society; compensation from Creative Research Designs for consultant services; grants from Campus Alberta Neuroscience; grants from the Government of Canada; stock options in TheRounds.com; compensation from DeepBench for consultant services; grants from the Alzheimer Society of Canada; grants from Rhodes Scholarships; grants from the Canadian Institutes of Health Research; compensation from the Canadian Association of Neuroscience Nurses for consultant services; grants from Alberta Innovates; stock holdings in Collavidence, Inc; grants from Wellcome Trust; travel support from the American Academy of Neurology; travel support from the American Heart Association; travel support from the University of Calgary; service as an editorial board member for the journal Stroke for American Heart Association; stock options in SnapDx, Inc; grants from MicroVention, Inc; service as a review editor for Stroke for Frontiers in Neurology; compensation from Alexion Pharmaceuticals for other services; grants from Panmure House; compensation from Biogen for other services; compensation from MD Analytics for consultant services; compensation from MyMedicalPanel for consultant services; compensation from CTC Communications Corporation for consultant services; service as an editorial board member for the journals Neurology and Neurology: Clinical Practice for the American Academy of Neurology; grants from the Fondation Brain Canada; and grants from the Sunnybrook Research Institute. Dr Hill reports grants from Boehringer Ingelheim, Medtronic, MicroVention, Inc, the Canadian Institutes of Health Research, NoNO, Inc, and Medtronic; compensation from Merck for end point review committee services; grants from Stryker Corporation; a patent issued for Systems and Methods for Assisting in Decision-Making and Triaging for Acute Stroke Patients licensed to Circle NVI; compensation from Brainsgate Ltd for consultant services; grants from Biogen, Inc, and Medtronic; and employment by the University of Calgary. The other authors report no conflicts.

Evidence generated from randomized clinical trials (RCTs) plays an indispensable role in advancing clinical stroke care. Although the number of stroke-related RCTs published every year has grown exponentially over the past 25 years, the execution and completion of RCTs, particularly those conducted in a hyperacute setting, have grown more complicated and challenging over the years. In addition to the practical challenges associated with conducting a clinical trial, like obtaining human subjects approval, identifying clinical sites, training trial personnel, and enrolling the target number of patients within the available funding and timeline, the complexity of contemporary RCT designs and analyses has become much more exacting. It is no longer sufficient to have a decent understanding of the 2-arm, placebo-controlled RCT, combined with a rudimentary grasp of the P value; things are now much more complicated. Innovations in trial design and analysis, including adaptive, Bayesian, platform, and noninferiority designs, have occurred to address the problems of poor trial efficiency. However, these advances require the end user to have a much greater level of understanding regarding the rationale, conduct, analysis, and interpretation of each design. While these newer designs seek greater efficiency, there are inevitably tradeoffs that need to be understood. In this month's edition of Stroke , we introduce a new series designed to help fill in these knowledge gaps. Over the next few months, 4 papers will be published that address major design innovations (adaptive, Bayesian, platform, and noninferiority) with the aim of illustrating how these approaches can make trials more efficient (where efficiency is defined as getting to the right answer, sooner, with a potentially lower sample size). In addition to introducing this series, this current article also reviews traditional hypothesis testing and the common misinterpretations of the P value; fortunately, new philosophical schools of inference are beginning to vanquish the overreliance on the P value. We are excited about the opportunity to educate the Stroke readership about these new trial designs and the profound implications that they bring., Competing Interests: None.

Designing a clinical trial to evaluate the efficacy of an intervention is often complicated by uncertainty over aspects of the study population, potential treatment effects, most relevant outcomes, dropouts, and other factors. However, once participants begin to be enrolled and partial trial data become available, this level of uncertainty is reduced. Adaptive clinical trials are designed to take advantage of the accumulating data during the conduct of a trial to make changes according to prespecified decision rules to increase the likelihood of success or statistical efficiency. Common adaptive rules address early stopping for benefit or futility, sample size reestimation, adding or dropping treatment arms or altering randomization ratios, and changing the eligibility criteria to focus on responder patient subgroups. Adaptive clinical trials are gaining popularity for clinical stroke research. We provide an overview of the methods, practical considerations, challenges and limitations, and potential future role of adaptive clinical trials in advancing knowledge and practice in stroke., Competing Interests: Drs Crawford, Lorenzi, and Lewis report employment by Berry Consultants LLC. Dr Saville was previously employed by Berry Consultants LLC and is now the owner of Adaptix Trials LLC. Drs Crawford, Lorenzi, Saville, and Lewis and other staff of Berry Consultants LLC were involved in the design and operation of several of the clinical trials referenced in this review. Dr Lewis also reports funding from the National Institutes of Health; compensation from the National Academies of Sciences, Engineering, and Medicine for other services; and employment of the American Medical Association. Dr Anderson reports research grants from the National Health and Medical Research Council of Australia, the Medical Research Council and Medical Research Foundation of the United Kingdom, and Takeda and Penumbra. He has received consulting fees for being an Advisor to AstraZeneca Australia.

Background: The Get With The Guidelines-Stroke program is a quality improvement initiative designed to enhance adherence to evidence-based stroke care. Since its inception in 2003, over 2800 hospitals in the United States have participated in the program., Methods: We examined patient characteristics, adherence to performance measures, and in-hospital outcomes in patients hospitalized for acute ischemic stroke, subarachnoid hemorrhage, intracerebral hemorrhage, and transient ischemic attack in The Get With The Guidelines-Stroke hospitals from 2003 through 2022. We quantified temporal changes in performance measure adherence and clinical outcomes over time. Performance measure denominators consisted of patients who were eligible, excluding those with contraindications., Results: Over the 20 years of the program, a total of 7837 849 stroke cases (median age 71 years, 51.0% female; 69.2% ischemic strokes, 3.9% SAHs, 11.5% ICHs, and 15.3% TIAs) were entered into the registry. Except for antithrombotics at discharge, in which the baseline performance was >92%, there was sustained improvement in all performance metrics regardless of type of cerebrovascular event ( P <0.01 for all). In patients with acute ischemic stroke, large improvements were observed for anticoagulation for atrial fibrillation (55.7% in 2003 to 97.2% in 2022), smoking cessation counseling (44.7%-97.8%), dysphagia screening (53.8%-83.5%), thrombolytic treatment for patients arriving by 3.5 hours, treat by 4.5 hours (15.2%-92.9%), door-to-needle time within 60 minutes (19.0%-75.3%), and endovascular door-to-puncture time within 90 minutes (54.7%-62.8%). Similar improvements were also observed for measures relevant to patients with subarachnoid hemorrhage, intracerebral hemorrhage, and transient ischemic attack. Multivariable analysis showed that there was a sustained increase in odds of receiving each performance measure over time, independent of patient and hospital characteristics for each type of cerebrovascular event. After risk adjustment, there were temporal trends that patients were less likely to be discharged to a skilled nursing facility, and, for ischemic stroke only, more likely to be discharged directly home., Conclusions: During the first 20 years, Get With The Guidelines-Stroke participation was associated with sustained improvement in evidence-based care and outcomes for patients with stroke and transient ischemic attack in the United States., Competing Interests: Dr Xian reports research funding from the American Heart Association and the National Institute on Aging (R01AG062770 and R01AG066672);grants from Daiichi Sankyo Company; grants from Genentech; travel support from Boehringer Ingelheim; and grants from Janssen Pharmaceuticals Inc. Dr Smith reports service as an editor for the Stroke journal. Dr Saver reports consulting fees for advising on rigorous and safe clinical trial design and conduct from Abbott, Acticor, Aeromics, Amgen, Argenica, Astrocyte, Bayer, Biogen, Boehringer Ingelheim, BrainsGate, BrainQ, CSL Behring, Filterlex, Genentech, Johnson&Johnson, MindRhythm, Medtronic, NeuroMerit, Neuronics, Novo Nordisk, Occlutech, Phenox, Phillips, QuantalX, Rapid Medical, Roche, and Stream Biomedical; compensation from MIVI Neuroscience for data and safety monitoring services; and stock options in Rapid Medical, Neuronics Medical, and MindRhythm. Dr Sheth reports grant support from National Institutes of Health, American Heart Association, and Hyperfine; consulting from Astrocyte, Rhaeos, Cerevasc, Bexorg, Sense and Philips Data and Safety Monitoring Board; and patent with Alva; and compensation from Certus for consultant services; stock options in BrainQ. Dr Messé reports personal compensation from Novo Nordisk for work on the Clinical Event Committee for ONWARDS and Zeus Trials; Terumo for work on the Subject Selection Committee for the RelayBranch Trial; WL Gore for work on the Data Safety Monitoring Committee for the GORE CARDIOFORM Septal Occluder Post Marketing Trial; and Conformal Medical for work on the Clinical Event Committee for work on the Conformal left atrial appendage closure trial. He also reports equity in Neuralert Technologies. Dr Schwamm reports consulting for Genentech (member of TIMELESS steering committee NCT03785678), LifeImage, Penumbra (DSMB MIND NCT03342664), Medtronic (co-PI Stroke AF NCT02700945, advise on stroke prevention), grant funding from NINDS (PI, U24NS107243; Co-I, R01NS111952) and PCORI (R-1609-35995), and serves as member board of directors for the American Heart Association. Dr Fonarow reports consulting for Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Eli Lilly, Johnson & Johnson, Medtronic, Merck, Novartis, and Pfizer. The other authors report no conflicts.

Objectives: To evaluate the efficacy and safety of acupuncture combined with five-element music (FEM) as an therapeutic strategy for the physical and mental state of Post-stroke depression patients., Design and Setting: Multicenter, randomized clinical trial conducted at 3 hospitals in China and enrolling 237 patients with PSD between June 2019 and April 2021. Participants mild/moderate PSD (17-item GRID Hamilton Depression Scale (HAMD) score 7-24) were randomly assigned (1:1) to acupuncture combined with FEM (AFEM) group or cognitive behavioral therapy (CBT) group., Main Outcome Measures: The primary outcome was change and differences between the groups in HAMD-17 from baseline to week 12. Secondary outcomes included Fugl-Meyer Assessment Scale score and Stroke-Specific Quality of Life Scale (SS-QOL) score., Results: The 237 patients in this intention-to-treat analysis were randomized into either the AFEM group (n=119) or the cognitive behavioral therapy (CBT) group (n=118). Of these 237 participants, 225 (94.9 %) completed all outcome measurements at week 12. The AFEM and CBT groups both showed significant improvement in HAMD-17 from baseline to week 12. Patients in the AFEM group had significantly lower HAMD-17 scores of -3.56 at week 8 (95 % CI,-4.59 to -2.53; p <.001) and -3.50 at week 12 (95 % CI,-4.53 to -2.46; p<.001) than patients in the CBT group. The SS-QOL score improved significantly at week 12. The Fugl-Meyer score was significantly lower in the AFEM group than in the CBT group at week 4, but this difference was not statistically significant upon follow-up at weeks 8 and 12. The incidence of treatment-related adverse events was 2.1 % in the AFEM group, with no serious adverse events reported., Conclusions: The results suggest that acupuncture and five-element music significantly improve the depressive symptoms in this cohort of Chinese PSD patients, and the toxicities were similar with CBP group., Registration: This study registered with the ClinicalTrials.gov Identifier: ChiCTR1900023741., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Strokes involving sensory pathways can result in contralesional pain syndromes often refractory to pharmacologic interventions. Scrambler therapy (ST) is a noninvasive electroanalgesia device used to treat pain caused by peripheral neuropathy; however, data are scarce regarding its use in conditions secondary to central nervous system pathology. We evaluate the efficacy of ST to treat poststroke pain., Methods: Twenty patients with a history of prior stroke resulting in contralesional pain were randomized to receive ST or Sham as an adjunct to their stable medication regimen. Participants underwent 5 consecutive daily 40-min sessions. The study was blinded to patient and assessor. Pain scores (0-10) were recorded at baseline, pre- and postsession, and 4 weeks after final treatment. Student's t-tests compared differences in the mean change in pain score between groups immediately post-treatment #5, and at 4-weeks. The chi-squared analysis compared the proportion of patients in each group with >50% pain reduction., Results: Participants randomized to ST had a mean change in pain score of -3.73 (SD 2.85) postintervention and -2.57 (SD 2.07) at 4 weeks, while the Sham group had a mean change in score of -0.94 (SD 1.36) and -0.25 (SD 0.84) (p between groups = 0.012, 0.004, respectively). Significantly more participants treated with ST reported a >50% reduction in pain immediately postintervention compared to Sham (70% vs. 10%, p = 0.006), but not at follow-up (30% vs. 10%, p = ns)., Interpretation: ST may effectively decrease poststroke pain compared to Sham. Larger studies are needed to evaluate confounders such as stroke location, time from stroke, and concomitant treatment with medications., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Introduction: Audits are an integral part of effective modern healthcare. The collection of data for audits can be resource intensive. Large language models (LLM) may be able to assist. This pilot study aimed to assess the feasibility of using a LLM to extract stroke audit data from free-text medical documentation., Method: Discharge summaries from a one-month retrospective cohort of stroke admissions at a tertiary hospital were collected. A locally-deployed LLM, LLaMA3, was then used to extract a variety of routine stroke audit data from free-text discharge summaries. These data were compared to the previously collected human audit data in the statewide registry. Manual case note review was undertaken in cases of discordance., Results: Overall, there was a total of 144 data points that were extracted (9 data points for each of the 16 patients). The LLM was correct in 135/144 (93.8%) of individual datapoints. This performance included binary categorical, multiple-option categorical, datetime, and free-text extraction fields., Conclusions: LLM may be able to assist with the efficient collection of stroke audit data. Such approaches may be pursued in other specialties. Future studies should seek to examine the most effective way to deploy such approaches in conjunction with human auditors and researchers., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose of Review: Sickle cell anemia (SCA) is an autosomal recessive inherited hemoglobinopathy that results in a high risk of stroke. SCA primarily affects an underserved minority population of children who are frequently not receiving effective, multi-disciplinary, preventative care. This article reviews primary and secondary stroke prevention and treatment for children with SCA for the general adult and pediatric neurologist, who may play an important role in providing critical neurologic evaluation and care to these children., Recent Findings: Primary stroke prevention is efficacious at reducing ischemic stroke risk, but it is not consistently implemented into clinical practice in the United States, resulting in these children remaining at high risk. Acute symptomatic stroke management requires neurology involvement and emergent transfusion to limit ischemia. Furthermore, while chronic transfusion therapy is a proven secondary preventative modality for those with prior symptomatic or silent cerebral infarcts, it carries significant burden. Newer therapies (e.g., stem cell therapies and voxelotor) deserve further study as they may hold promise in reducing stroke risk and treatment burden. Effective primary and secondary stroke prevention and treatment remain a challenge. Informing and engaging neurology providers to recognize and provide critical neurologic evaluation and treatment has potential to close care gaps., (© 2024. The Author(s).)

Background: Although assessment of frailty is increasingly being included in routine practice, its effects on hospital outcomes is not well studied. In this study, we used a national database to estimate the effects of frailty on hospital outcomes among stroke patients., Methods: This study was a retrospective analysis of data from Nationwide Inpatient Sample (NIS) database collected during the years 2016 to 2019. Adult patients 45 years and older with a primary diagnosis of stroke were included for the analysis. Primary outcome was frequency of frailty among stroke patients. Secondary outcomes were in-hospital mortality, prolonged length of stay, mechanical ventilation, and acute renal failure. Frailty levels were assessed by using the Hospital Frailty Risk Score (HFRS)., Results: Among 2,031,085 stroke hospitalizations, 362,140 (17.8 %) were non-frail, 1,333,000 (65.6 %) were pre-frail, and 335,945 (16.6 %) were frail. Regression analysis showed that the odds of mortality were significantly higher among frail (aOR, 2.82, 95 % CI: 2.63-3.04) and pre-frail (aOR, 1.62, 95 % CI: 1.53-1.73) patients, compared to non-frail patients. Similarly, the odds of mechanical ventilation were significantly higher among frail (aOR, 9.72, 95 % CI: 8.84-10.69) and pre-frail (aOR, 3.41, 95 % CI: 3.12-3.73) patients. The odds of acute renal failure were significantly higher among frail (aOR, 6.96, 95 % CI: 6.62-7.33) and pre-frail (aOR, 2.94, 95 % CI: 2.80-3.08) patients., Conclusion: Collaborative efforts by neurologists, neurosurgeons, and physiatrists towards identifying frailty and incorporating it in risk estimation measures could help improve management strategies, resource utilization, and optimization of patient outcomes among frail stroke patients., 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: Despite multiple calls for more inclusive studies, most clinical trial eligibility criteria remain too restrictive. Thrombectomy trials have been no exception., Methods: We review the landmark trials that have shown the benefits of thrombectomy, their eligibility criteria, and consequences on clinical practice. We discuss the rationale behind various reasons for exclusions. We also examine the logical problem involved in using eligibility criteria as indications for treatment., Results: Most thrombectomy trials have been too restrictive. This has been shown by a plethora of follow-up studies that have refuted most of the previously recommended trial eligibility restrictions. Meanwhile, the effect of clinical recommendations based on restrictive eligibility criteria is that treatment has been denied to the majority of patients who could have benefitted. Trial eligibility criteria cannot be used to make clinical decisions or recommendations unless, like any other medical diagnosis, they have been shown capable of reliably differentiating patients into those that will, and those that will not benefit from treatment. This goal can only be achieved with all-inclusive pragmatic trials., Conclusion: Restrictive eligibility criteria render clinical trials incapable of guiding medical decisions or recommendations., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objectives: Hospital readmissions are associated with poor health outcomes including illness severity and medical complications. The objective of this study was to identify characteristics associated with 30-day post-stroke readmission in an academic urban hospital network., Materials and Methods: We collected data on patients admitted with stroke from 2017 through 2022 who were readmitted within 30 days of discharge and compared them to a subset of non-readmitted stroke patients. Chart review was used to collect demographics, characteristics of the stroke, co-morbid conditions, in-hospital complications, and post-discharge care. Univariate analyses followed by regression analysis were used to assess characteristics associated with post-stroke readmission., Results: We identified 4743 patients with stroke (18 % hemorrhagic, mean age 70.1 (standard deviation (SD) 17.2), 47.3 % female) discharged from the stroke services, of whom 282 (5.9 %) patients were readmitted within 30 days of index hospitalization. Univariate analyses identified 18 significantly different features between admitted and readmitted patients. Regression analysis revealed characteristics associated with readmission included private insurance (odds ratio (OR) 0.4, confidence interval (CI) 0.3-0.6, p < 0.001), comorbid peripheral vascular disease (PVD) (OR 2.7, CI 1.3-5.5, p = 0.009), malignancy (OR 1.6, CI 1.0-2.6, p = 0.04), seizure (OR 3.4, CI 1.4-8.2, p = 0.007), thrombolytic administration (OR 0.4, CI 0.2-0.7, p = 0.003), undergoing thrombectomy (OR 5.4, CI 2.9-10.1, p < 0.001), and higher discharge modified Rankin Scale score (OR 1.2, CI 1.0-1.3, p = 0.047)., Conclusions: Our data demonstrate that thrombectomy, high discharge Rankin score, comorbid malignancy, seizure or PVD, and lack of thrombolytic administration or private insurance predict readmission., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Objective: The Berg Balance Scale (BBS), Performance-Oriented Mobility Assessment (POMA), and Dynamic Gait Index (DGI) are crucial standard tools used to evaluate functional balance. However, their minimal important difference (MID) threshold is yet to be established. The objective of this research was to explore the MID for BBS, POMA, and DGI in people suffering from chronic stroke., Methods: A total of 130 chronic stroke patients were assessed using BBS, POMA and DGI before and after undergoing interventions. The treatment procedures included a series of task-oriented exercises focusing on motor re-learning. In anchor-based approach, the Clinical Global Impression of Improvement scale served as the anchor. The Receiver Operating Characteristic (ROC) curve was employed to identify the best MID cut-off point for BBS, POMA, and DGI. In the distribution-based approach, one-third standard deviation (SD), half SD, one standard error of measurement (SEM), and the total score of BBS, POMA and DGI were used to determine the MID., Results: The MID from the ROC curve was greater than 2 points for BBS, greater than 1 point for POMA and DGI. For the distribution-based approach, the MIDs corresponding to one-third of the SD, half of the SD, and one SEM for BBS were 1.92, 3.20, and 0.90; for POMA were 1.47, 2.45, and 1.96; for DGI were 1.48, 2.47, and 1.16 points, respectively., Conclusion: BBS, POMA and DGI are suitable instruments for assessing functional balance in individuals with chronic stroke, with demonstrable MID. Additionally, the results indicated that DGI has higher sensitivity and specificity than the other examined scales for distinguishing between groups without change and those with minimal balance improvement after receiving interventions., Competing Interests: Declaration of competing interest No conflict of interest was reported by the author(s)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Low-frequency whole body vibration (WBV; 40 Hz) therapy after stroke reduces ischemic brain damage, motor, and cognitive deficits in middle-aged rats of both sexes. However, the underlying mechanisms responsible for WBV induced ischemic protections remain elusive. In the current study, we hypothesize that post-stroke WBV initiates transcriptional reprogramming in the cortex of middle-aged female rats which is responsible for the observed reduced stroke consequences. Middle-aged female Sprague-Dawley rats that remained in constant diestrus (reproductively senescent) were randomized to either sham or transient middle cerebral artery occlusion (tMCAO; 90 min) surgery. A day after induction of tMCAO, animals received either WBV or no-WBV treatment for 15 min twice a day for five days for a week. Post-treatment, cortical tissue was analyzed for gene expression using RNA sequencing (RNAseq) and gene enrichment analysis via Enrichr. The RNAseq data analysis revealed significant changes in gene expression due to WBV therapy and the differentially expressed genes are involved in variety of biological processes like neurogenesis, angiogenesis, excitotoxicity, and cell death. Specifically, observed significant up-regulation of 116 and down-regulation of 258 genes after WBV in tMCAO exposed rats as compared to the no-WBV group. The observed transcriptional reprogramming will identify the possible mechanism(s) responsible for post-stroke WBV conferred ischemic protection and future studies will be needed to confirm the role of the genes identified in the current study., Competing Interests: Declaration of competing interest Ami P. Raval serves as a Techinal Editor, American Heart Association Stroke, and a Section Editor for Experimental Neurology., (Published by Elsevier Ltd.)

Background: In-hospital falls are frequent post-stroke medical complications and will remain of concern because it may not be possible to prevent all of them. We aimed to i) compare admission clinical and sociodemographic characteristics between fallers and non-fallers ii) determine falls characteristics iii) compare length of stay (LOS), discharge functional independence, ambulation and destination between fallers and non-fallers., Methods: A matched case-control study, comparing individuals (n = 302) who fell during inpatient post-acute rehabilitation, matched (on time to admission, age and motor Functional Independence Measure (mFIM)) to individuals (n = 302) who didn´t fall, admitted within 3 months post-injury to a center between 2008 and 2023. Ambulation was assessed using the Functional Ambulation Category (FAC)., Results: Mean age at admission was 50±8 years. No baseline differences were seen between groups in the proportion of patients with aphasia, diabetes, dyslipidemia, hypertension, neglect, atrial fibrillation, dysphagia, dominant side affected, medication for depression, FAC assessment, body mass index and educational level. A first-fall in the first week was experienced by 22.2 % and in the first three weeks by 54.3 %. Most falls occurred at the patients' room (75.1 %) mostly due to distractions (55.3 %) and transferring without help (32.4 %) with 18 % occurring in the bathroom, fallers were alone in 68.6 % of the cases. Fallers had an 8-day longer mean LOS compared to non-fallers, yet there were no differences in discharge mFIM or FAC scores. While non-fallers had a higher proportion of poor mFIM outcomes (28.5 % vs. 17.9 %) and no ambulation (20.7 % vs. 12.4 %), fallers showed greater mFIM gains (26 vs. 22 points). Discharge destinations were similar across both groups., Conclusions: Despite no baseline differences, fallers experienced longer stays with comparable independence and ambulation scores at discharge. Most falls occurred in patients' rooms during unsupervised activities. Preventive recommendations have been provided to address these risks and enhance patient safety., Competing Interests: Declaration of competing interest The authors declare that 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 Elsevier Inc. All rights reserved.)

Aim(s): To explore the meaning of healthcare self-management support for post-discharged stroke patients., Method: Rodgers' evolutionary approach was used to identify antecedents, attributes, related terms, surrogate terms and consequences., Data Source: Literature from 2012 to 2022 was searched from MEDLINE, CINAHL, PsycINFO and Google Scholar., Results: Three antecedents preceded healthcare self-management support for post-discharged stroke patients: loss of inpatient support, preparedness for self-management and presence of self-management support. Healthcare self-management support for post-discharged stroke patients was defined by eight attributes: pre-discharge assessment and planning; provision of continuous education and training; collaborative goal-setting; reinforcement and documentation of vital information; coordination of post-discharge care; provision of rehabilitation support and promoting community reintegration; provision of counselling support; and using clear communication, patient empowerment and promoting self-efficacy. The identified consequences of the concept were as follows: improved patient outcomes; improved life quality; decreased healthcare cost; decreased re-admission rate and inpatient care burden; and decreased complication rate., Conclusion: Healthcare self-management support for post-discharged stroke patients is an emerging concept that can help to significantly improve stroke patients' health outcomes and life quality. However, its applicability is uncertain considering the workload, time and resources available to healthcare professionals. There is a need for future studies to focus on the feasibility and applicability of this concept in clinical practice and to identify any challenges healthcare providers may have in supporting stroke patients after discharge., Impact: This concept analysis brings clarity to the concept of healthcare self-management support of post-discharged stroke patients and distinguishes it from other self-management supports. It provides an opportunity for further studies and a pathway for generalized healthcare self-management support for stroke patients after discharge to improve health outcomes and quality of life., No Patient or Public Contribution: No patients, service users, caregivers or members of the public were involved in conducting this concept analysis., (© 2024 The Authors. Journal of Advanced Nursing published by John Wiley & Sons Ltd.)