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Background and purpose Methods Results Conclusion The literature lacks large studies on outcomes of cerebrovascular disease (CVD) in patients with muscular dystrophies (MDs). Previous studies primarily focused on ischemic stroke. CVD can add considerable morbidity in patients with MD. We aimed to study the outcomes of CVD in patients with MDs using a national database.Data were abstracted from the 2010–2021 Nationwide Readmission Database. We identified hospitalizations for CVDs including ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and other unspecified CVDs. We used propensity‐score matching to account for selection bias and baseline differences between MD and non‐MD patients in type of CVD, age, biological sex, time of discharge, and comorbidity burden. Outcomes were inpatient mortality, 30‐day and 90‐day readmissions, length of stay, costs and discharge disposition.There were an estimated 6,129,132 CVD hospitalizations, of which 0.03% (weighted N = 2098) were for patients with MD. Ischemic stroke was the most common type, followed by intracerebral hemorrhage. MD was associated with 41% lower odds of a routine discharge, 9% greater costs, and 30% lower odds of 90‐day all‐cause readmissions. Inpatient mortality was higher in the MD cohort, but the difference was not statistically significant. There were no significant differences in other outcomes.The findings of this study provide new insights into the outcomes of CVD in MD patients, highlighting the need for enhanced access to post‐discharge care in such patients. Improved post‐discharge care may help reduce readmissions and avoid longer hospital stays. This study could be valuable for neurologists, rehabilitation physicians, healthcare administrators and economists. [ABSTRACT FROM AUTHOR]

Hydroxysafflor yellow A (HSYA), an active ingredient extracted from Carthami flos, shows potential for treating ischemic stroke. This phase 1 study assessed the safety, tolerability, and pharmacokinetic (PK) properties of HSYA in healthy Chinese volunteers who received intravenous infusions of pure HSYA powder. The study comprised 2 parts. Part A was a randomized, double‐blind, placebo‐controlled dose‐escalation study that evaluated safety and tolerability. This included a single‐dose study with 7 dose levels of HSYA (6.25, 12.5, 25, 50, 75, 100, and 125 mg) in 52 volunteers, and a multidose study (100 and 125 mg) in 16 volunteers. Part B was an open‐label study where 12 volunteers received 75 mg of HSYA once daily for 14 consecutive days to examine PKs. There were no adverse events (AEs) leading to treatment discontinuation by HSYA throughout the treatment period. All reported AEs were mild and did not require special treatment. PK analysis revealed rapid absorption (median Tmax of 1.1 hours) and elimination (median t1/2 4.0 and 4.7 hours) of HSYA. Total body clearance on the 1st and 14th days was 1.7 and 1.6 L/h, respectively. [ABSTRACT FROM AUTHOR]

Key points Stroke is a leading cause of death and disability worldwide. Atrial myopathy, including fibrosis, is associated with an increased risk of ischaemic stroke, but the mechanisms underlying this association are poorly understood. Fibrosis modifies myocardial structure, impairing electrical propagation and tissue biomechanics, and creating stagnant flow regions where clots could form. Fibrosis can be mapped non‐invasively using late gadolinium enhancement magnetic resonance imaging (LGE‐MRI). However, fibrosis maps are not currently incorporated into stroke risk calculations or computational electro‐mechano‐fluidic models. We present multiphysics simulations of left atrial (LA) myocardial motion and haemodynamics using patient‐specific anatomies and fibrotic maps from LGE‐MRI. We modify tissue stiffness and active tension generation in fibrotic regions and investigate how these changes affect LA flow for different fibrotic burdens. We find that fibrotic regions and, to a lesser extent, non‐fibrotic regions experience reduced myocardial strain, resulting in decreased LA emptying fraction consistent with clinical observations. Both fibrotic tissue stiffening and hypocontractility independently reduce LA function, but, together, these two alterations cause more pronounced effects than either one alone. Fibrosis significantly alters flow patterns throughout the atrial chamber, and particularly, the filling and emptying jets of the left atrial appendage (LAA). The effects of fibrosis in LA flow are largely captured by the concomitant changes in LA emptying fraction except inside the LAA, where a multifactorial behaviour is observed. This work illustrates how high‐fidelity, multiphysics models can be used to study thrombogenesis mechanisms in patient‐specific anatomies, shedding light onto the links between atrial fibrosis and ischaemic stroke. Left atrial (LA) fibrosis is associated with arrhythmogenesis and increased risk of ischaemic stroke; its extent and pattern can be quantified on a patient‐specific basis using late gadolinium enhancement magnetic resonance imaging. Current stroke risk prediction tools have limited personalization, and their accuracy could be improved by incorporating patient‐specific information such as fibrotic maps and haemodynamic patterns. We present the first electro‐mechano‐fluidic multiphysics computational simulations of LA flow, including fibrosis and anatomies from medical imaging. Mechanical changes in fibrotic tissue impair global LA motion, decreasing LA and left atrial appendage (LAA) emptying fractions, especially in subjects with higher fibrosis burdens. Fibrotic‐mediated LA motion impairment alters LA and LAA flow near the endocardium and the whole cavity, ultimately leading to more stagnant blood regions in the LAA. [ABSTRACT FROM AUTHOR]

Microglia are critically involved in post‐stroke inflammation affecting neurological outcomes. Lipid droplet (LD) accumulation in microglia results in a dysfunctional and pro‐inflammatory state in the aged brain and worsens the outcome of neuroinflammatory and neurodegenerative diseases. However, the role of LD‐rich microglia (LDRM) under stroke conditions is unknown. Using in vitro and in vivo stroke models, herein accumulation patterns of microglial LD and their corresponding microglial inflammatory signaling cascades are studied. Interactions between temporal and spatial dynamics of lipid profiles and microglial phenotypes in different post‐stroke brain regions are found. Hence, microglia display enhanced levels of LD accumulation and elevated perilipin 2 (PLIN2) expression patterns when exposed to hypoxia or stroke. Such LDRM exhibit high levels of TNF‐α, IL‐6, and IL‐1β as well as a pro‐inflammatory phenotype and differentially expressed lipid metabolism‐related genes. These post‐ischemic alterations result in distinct lipid profiles with spatial and temporal dynamics, especially with regard to cholesteryl ester and triacylglycerol levels, further exacerbating post‐ischemic inflammation. The present study sheds new light on the dynamic changes of brain lipid profiles and aggregation patterns of LD in microglia exposed to ischemia, demonstrating a mutual mechanism between microglial phenotype and function, which contributes to progression of brain injury. [ABSTRACT FROM AUTHOR]

Background and Purpose Methods Results Conclusions Investigating the cost‐effectiveness of future mobile stroke unit (MSU) services with respect to local idiosyncrasies is essential for enabling large‐scale implementation of MSU services. The aim of this study was to assess the cost‐effectiveness for varying urban German settings and modes of operation.Costs of different operating times together with different personnel configurations were simulated. Different possible catchment zones, ischemic stroke incidence, circadian distribution, rates of alternative diagnoses, as well as missed cases were incorporated to model case coverage and patient numbers. Based on internationally reported clinical outcomes of MSUs, a 5‐year Markov model was applied to analyze the cost‐effectiveness for the different program setups.Compared with standard stroke care, MSUs achieved an additional 0.06 quality‐adjusted life years (QALYs) over a 5‐year time horizon. Assuming a catchment zone of 750,000 inhabitants and 8 h/7 day operation resulted in an incremental cost‐effectiveness ratio (ICER) of €37,182 per QALY from a societal perspective and €45,104 per QALY from a healthcare perspective. Lower ICERs were possible when coverage was expanded to 16 h service on 7 days per week and larger populations. Sensitivity analyses revealed that missing ischemic strokes significantly deteriorated economic performance of MSU.Major determinants of cost‐effectiveness should be addressed when setting up novel MSU programs. Catchment zones of more than 500,000–700,000 inhabitants and operating times of at least 12–16 h per day, 7 days per week could enable the most cost‐effective MSU services in the German healthcare system. [ABSTRACT FROM AUTHOR]

Leptomeningeal collaterals (LMCs) are crucial in mitigating the impact of acute ischemic stroke (AIS) by providing alternate blood flow routes when primary arteries are obstructed. This article explores the evolutionary pathophysiology of LMCs, highlighting their critical function in stroke and the genetic and molecular mechanisms governing their development and remodelling. We address the translational challenges of applying animal model findings to human clinical scenarios, emphasizing the need for further research to validate emerging therapies—such as pharmacological agents, gene therapy and mechanical interventions—in clinical settings, aimed at enhancing collateral perfusion. Computational modelling emerges as a promising method for integrating experimental data, which requires precise parameterization and empirical validation. We introduce the ‘Evolucollateral Dynamics’ hypothesis, proposing a novel framework that incorporates evolutionary biology principles into therapeutic strategies, offering new perspectives on enhancing collateral circulation. This hypothesis emphasizes the role of genetic predispositions and environmental influences on collateral circulation, which may impact therapeutic strategies and optimize treatment outcomes. Future research must incorporate human clinical data to create robust treatment protocols, thereby maximizing the therapeutic potential of LMCs and improving outcomes for stroke patients. [ABSTRACT FROM AUTHOR]

This study investigates the effect of agmatine on reducing mortality, neurobehavioral alterations, infarct size, and expression of pro‐inflammatory cytokines in mice subjected to bilateral carotid thrombosis. Under pentobarbital anesthesia, the left common carotid artery was exposed to 6% FeCl3. Thirty‐two days later, the same procedure was performed on the right common carotid artery. Subsequently, Agmatine (100 mg/kg) was administered 15 min after the second procedure, and in another experimental group, the dose of Agmatine was repeated at 72 h. Administration of agmatine extended survival in ischemic animals up to 72 h for the single‐dose group and up to 96 h for the repeated‐dose group, without significant increases in neurological deficits or infarct area size. This neurobehavioral effect was also observed in sham animals treated with agmatine. In ischemic animals, agmatine administration improved digging behavior and reduced recovery times, consistently shorter in those animals treated with repeated doses. RT‐PCR analyses revealed a positive regulation of the cytokine IL‐1β in agmatine‐treated animals, which has been associated with recovery stages. The results suggest that the observed effect may be attributed to the multiple interactions of agmatine with ischemic cascade events, highlighting its anti‐inflammatory role. [ABSTRACT FROM AUTHOR]

Background and Purpose: Intraarterial thrombolysis as an adjunct to mechanical thrombectomy is increasingly being considered to enhance reperfusion in acute ischemic stroke patients. Intraarterial thrombolysis may increase the risk of post‐thrombectomy intracerebral hemorrhage (ICH) in certain patient subgroups. Methods: We analyzed acute ischemic stroke patients treated with mechanical thrombectomy in a multicenter registry. The occurrence of any (asymptomatic and symptomatic) post‐thrombectomy ICH was ascertained using standard definition requiring serial neurological examinations and computed tomographic scans acquired within 48 hours of the thrombectomy. We determined the risk of ICH in subgroups defined by clinical characteristics and the use of intravenous (IV) thrombolysis. Results: A total of 146 (7.5%) patients received intraarterial thrombolysis among 1953 acute ischemic stroke patients who underwent mechanical thrombectomy. The proportion of patients who developed any ICH was 26 (17.8%) and 510 (28.2%) among patients who were and were not treated with intraarterial thrombolysis, respectively (p =.006). The proportion of patients who developed symptomatic ICH was 4 (2.7%) and 30 (1.7%) among patients who were and were not treated with intraarterial thrombolysis, respectively (p =.34). Among patients who received IV thrombolysis (n = 1042), the proportion of patients who developed any ICH was 9 (16.7%) and 294 (30.7%) among patients who were and were not treated with intraarterial thrombolysis, respectively (p =.028). The risk was not different in strata defined by age, gender, location of occlusion, preprocedure National Institutes of Health Stroke Scale score, time interval between symptom onset and thrombectomy, Alberta Stroke Program Early CT Score, systolic blood pressure, and serum glucose concentrations. Conclusions: In patients undergoing mechanical thrombectomy, the risk of any ICH and symptomatic ICH was not increased with intraarterial thrombolysis, including in those who had already received IV thrombolytics. [ABSTRACT FROM AUTHOR]

Background and Purpose: Ischemic strokes due to isolated posterior cerebral artery (PCA) occlusions represent 5% of all strokes but have significant impacts on patients' quality of life, primarily due to visual deficits and thalamic involvement. Current guidelines for acute PCA occlusion management are sparse, and the prognostic value of perfusion imaging parameters remains underexplored. Methods: We conducted a retrospective analysis of 32 patients with isolated PCA occlusions treated at Johns Hopkins Medical Institutions between January 2017 and March 2023. Patients underwent pretreatment perfusion imaging, with perfusion parameters analyzed using RAPID software. The primary outcome was short‐term clinical outcome as measured by the National Institutes of Health Stroke Scale (NIHSS) at discharge. Results: The median age of the cohort was 70 years, with 34% female and 66% male. Significant correlations were found between NIHSS at discharge and various perfusion parameters, including time‐to‐maximum (Tmax) >6 seconds (ρ =.55, p =.004), Tmax >8 seconds (ρ =.59, p =.002), Tmax >10 seconds (ρ =.6, p =.001), mismatch volume (ρ =.51, p =.008), and cerebral blood volume (CBV) < 34% (ρ =.59, p =.002). Conclusions: Tmax and CBV volumes significantly correlated with discharge NIHSS with marginal superiority of Tmax >10 seconds and CBV <42% volumes. These findings suggest that CT and MR perfusion imaging can play a crucial role in the acute management of PCA strokes, though larger, standardized studies are needed to validate these results and refine imaging thresholds specific to posterior circulation infarcts. [ABSTRACT FROM AUTHOR]

A 35‐year‐old woman with antiphospholipid syndrome, with 29‐week pregnancy, developed left hemiparesis. Diffusion‐weighted imaging showed a low Alberta Stroke Program Early Computed Tomography (ASPECT) score. The right internal carotid artery occlusion was recanalized by mechanical thrombectomy (MT) and a pathologically white thrombus was confirmed. Clot analysis‐guided anti‐coagulant/platelet therapy was continued, and the patient delivered at 38 weeks and was discharged with a modified Rankin Scale score of 1. We conclude that MT should be considered, even in pregnancy with antiphospholipid syndrome and low ASPECT scores. [ABSTRACT FROM AUTHOR]

Background: Strokes in young individuals often stem from unusual causes. Posterior circulation ischemic stroke caused by vertebral artery insufficiency due to atlantoaxial instability or dislocation is rare. We present a case of posterior circulation ischemic stroke due to an unstable os odontoideum and review the current literature. The clinical features and imaging manifestations are described to promote awareness of etiology, early diagnosis, and assessment. Case Presentation: A 24‐year‐old male presented with recurrent right‐sided limb numbness and weakness and cerebellar ataxia due to posterior circulation ischemic stroke. The work‐up revealed thrombosis reformation in the tortuous left vertebral artery. It is noteworthy that the patient developed compression and chronic damage of the vertebral artery secondary to atlantoaxial instability and lateral dislocation due to an os odontoideum. He underwent antiplatelet and anticoagulant therapy, cervical traction, and posterior atlantoaxial screw fixation and fusion with iliac crest autograft. The postoperative course was uneventful. At 6‐month follow‐up, the patient had a solid fusion mass and rigid stability of the atlantoaxial joint without neurologic deficits or ischemic sequelae. Conclusions: For unexplained posterior circulation ischemic stroke, it is important to consider unstable os odontoideum as a potential etiology, especially in pediatric and young adult male patients. Atlantoaxial instability and dislocation with os odontoideum, especially when occurring laterally, may cause insufficiency of the vertebral artery and subsequent posterior circulation ischemic strokes. The significance of lateral atlantoaxial dislocation in the genesis of vertebral artery injury and the necessity for specific positional imaging are emphasized. [ABSTRACT FROM AUTHOR]

Introduction: Understanding the spatiotemporal location of the spontaneous termination of ventricular tachycardia (VT) may provide new insights for ablation. To test the hypothesis that spontaneous VT termination most frequently occurs at the VT exit due to source‐sink mismatch and to characterize electrophysiological properties of the sites termination during VT and with extra‐stimulus technique. Methods: Retrospective analysis of intraoperative mapping studies of nine patients with ischemic cardiopathy or repaired tetralogy of Fallot. Simultaneous endocardial and epicardial mapping was performed in both ventricles using a custom mapping array during VT. Electrogram (EGM) characteristics before and at the moment of termination were analyzed including: cycle length oscillations, EGM heterogeneity and a variation in the systolic/diastolic path. The decrements to extra stimulus were analysed for termination sites and other diastolic sites. Results: Nine VTs in seven patients demonstrated spontaneous VT termination. Seven VTs (77.8%) spontaneously terminated in the final third of the systolic interval, one (11.1%) in early diastole and one (11.1%) in mid diastole. Cycle length oscillations (prolongation, shortening, and no change) were seen in equal frequency. Four VTs (44.4%) showed alternans in the local EGM at the site of termination and this was more prevalent than alternans at other sites in the diastolic pathway (p <.001). Only one‐third of VTs showed a change in activation pattern before termination. There was no difference based on etiology. During substrate characterization with extra‐stimulus pacing, sites of spontaneous termination showed greater decrement than other sites of the VT circuit during pacing (43.5 ± 14.5 ms vs. 31.2 ± 31.2 ms; p =.003). Conclusion: The entrance zone rather than the exit is the commonest site for the spontaneous termination of VT in the human heart. These sites tend to demonstrate EGM alternans during VT and greater decrement during extrastimulus pacing. These findings may help guide future studies into improving the success of VT ablation. [ABSTRACT FROM AUTHOR]

Insertion of a nasogastric tube (NGT) is generally considered safe; however, it is not without risk, and in cases of misplacement, complications and even death may occur. In this article, we reported a case of NGT misplacement in a 75‐year‐old male, which resulted in aspiration pneumonia. We also reviewed published cases of NGT misplacement. Clinicians should pay enough attention to the confirmation of the proper placement of an NGT. A systematic approach for NGT insertion and confirmation is required to prevent misplacement. [ABSTRACT FROM AUTHOR]

Direct oral anticoagulants are the primary stroke prevention option in patients with atrial fibrillation. Anticoagulant use before stroke, however, might inhibit clinician comfort with thrombolysis if a stroke does occur. Resuming anticoagulants after ischemic stroke is also problematic for fear of hemorrhage. We describe extensive literature showing that thrombolysis is safe after stroke with direct anticoagulant use. Early reinstitution of direct anticoagulant treatment is associated with lower risk of embolic recurrence and lower hemorrhage risk. The use of direct anticoagulants before, during, and after thrombolysis appears to be safe and is likely to promote improved outcomes after ischemic stroke. ANN NEUROL 2024;96:871–886 [ABSTRACT FROM AUTHOR]

Ischaemic stroke is a common condition that can lead to cerebral ischaemia–reperfusion injury. Phillygenin (PHI), a natural bioactive compound derived from Forsythia suspensa, has been shown to play a crucial role in regulating inflammation across various diseases. However, its specific regulatory effects in ischaemic stroke progression remain unclear. In this study, we established a middle cerebral artery occlusion (MCAO) rat model. Treatment with PHI (50 or 100 mg/kg) significantly reduced cerebral infarction in MCAO rats. PHI treatment also mitigated the increased inflammatory response observed in these rats. Additionally, PHI suppressed microglial activation by reducing iNOS expression, a marker of M1‐type polarization of microglia, and attenuated increased brain tissue apoptosis in MCAO rats. Furthermore, PHI's anti‐inflammatory effects in MCAO rats were abrogated upon co‐administration with GW9662, a peroxisome proliferator‐activated receptor γ (PPARγ) inhibitor. In summary, PHI attenuated microglial activation and apoptosis in cerebral ischaemia–reperfusion injury through PPARγ activation, suggesting its potential as a therapeutic agent for mitigating cerebral ischaemia–reperfusion injury. [ABSTRACT FROM AUTHOR]

Background and purpose: Training and education is essential for best practice medicine and is especially important in a rapidly evolving field such as neurology. Due to improved imaging techniques and laboratory testing, there is a better understanding of the pathophysiology of diseases. As a result more treatments have become available. The most important developments in neurology over the last two decades and their effect on training and education are described. In addition, how future training should be aware of the challenges ahead of us is described. Methods: This is a narrative review describing developments and challenges based on personal experience and the literature. Results: Due to major developments in radiological and immunological testing, major changes have been seen in different subspecialties of neurology, including but not limited to, the treatment of ischaemic stroke, the development of new entities in the field of demyelinating diseases and auto‐immune encephalitis, and diffuse glioma. These developments challenge the education and training in neurology with, ahead of us, technological developments, an aging population, and potentially more superspecialization. Conclusion: Although there are differences in the training curricula between European countries, the developments and future challenges within the field of neurology are very similar. In the development of future curricula it is important to face these developments and challenges and to adapt to them. [ABSTRACT FROM AUTHOR]

Objective: Ischemic stroke is a significant cause of disability and death worldwide. Randomized clinical trials (RCTs) are important in changing guidelines and treatment strategies. This study aimed to analyze the progress of RCTs in ischemic stroke and to guide future research directions. Methods: Ischemic stroke‐related RCT articles were identified in six high‐impact medical journals using the Web of Science Core Collection database. Google Scholar was used to check whether relevant articles were included in the guidelines. The characteristics of these articles were analyzed and future research hotspots were predicted. Results: 389 relevant articles were included in the analysis. The number of articles increased rapidly from 1972 to 2022, from 5 (1.3%; 1972–1982) to 208 (53.5%; 2013–2022) articles. 338 (86.9%) articles were included in relevant guidelines. According to corresponding author location, Europe was the source of the highest number of publications (183; 47.0%), followed by the Americas (152; 39.1%) and the Western Pacific (54; 13.9%). The number of publications steadily increased over time in the USA, England, Canada, Australia, Germany, and France, and surged in China and Spain, especially in the last 5 years. In recent years, endovascular therapy has accounted for the majority of ischemic stroke‐related RCT articles. Conclusions: Numerous RCTs related to ischemic stroke have been conducted in recent decades, and both the number of articles and their contribution to guideline updates are increasing. Also, a shift in research topics was observed. However, great regional imbalances in this research exist, calling for more research to be conducted in specific regions to promote the generalizability of trial conclusions. [ABSTRACT FROM AUTHOR]

Xinglou Chengqi decoction (XLCQD) is a Chinese formula that offers benefits in ischemic stroke. However, the underlying mechanism of the effects of XLCQD‐mediated anti‐ischemic stroke effects remains obscure. This study investigates the ferroptosis mechanism of XLCQD against cerebral ischemia/reperfusion (I/R) injury using rat models of middle cerebral artery occlusion/reperfusion (MCAO/R). Ferroptosis differs from traditional cell death pathways and is linked to oxidative stress‐induced lipid peroxidation and glutathione (GSH) depletion, which is essential to the development of ischemic stroke. In this study, it is shown that XLCQD improves brain infarction, neurological dysfunction, and histopathological changes caused by MCAO/R exposure, and improving I/R‐induced oxidative damage through inhibition of ferroptosis via (Solute Carrier Family 7 Member 11) SLC7A11/ (glutathione peroxidase 4) GPX4 pathway. Interestingly, it is found that XLCQD‐mediated protection in I/R is reversed by the silence of SLC7A11. XLCQD intervention significantly promotes GSH content and suppresses Reactive Oxygen Species(ROS), iron accumulation, as well as Malondialdehyde (MDA) generation, are markedly abrogated when SLC7A11 is knockdown by SLC7A11‐shRNA transfection, indicating that SLC7A11 is the main target of XLCQD to further trigger intracellular events. In conclusion, XLCQD attenuates in vivo cerebral I/R injury by reducing ferroptosis via the SLC7A11/GPX4 pathway. [ABSTRACT FROM AUTHOR]

Aims: To investigate the risk factors for neurogenic lower urinary tract dysfunction (NLUTD) in patients with acute ischemic stroke (AIS), and develop an internally validated predictive nomogram. The study aims to offer insights for preventing AIS‐NLUTD. Methods: We conducted a retrospective study on AIS patients in a Shenzhen Hospital from June 2021 to February 2023, categorizing them into non‐NLUTD and NLUTD groups. The bivariate analysis identified factors for AIS‐NLUTD (p < 0.05), integrated into a least absolute shrinkage and selection operator (LASSO) regression model. Significant variables from LASSO were used in a multivariate logistic regression for the predictive model, resulting in a nomogram. Nomogram performance and clinical utility were evaluated through receiver operating characteristic curves, calibration curves, decision curve analysis (DCA), and clinical impact curve (CIC). Internal validation used 1000 bootstrap resamplings. Results: A total of 373 participants were included in this study, with an NLUTD incidence rate of 17.7% (66/373). NIHSS score (OR = 1.254), pneumonia (OR = 6.631), GLU (OR = 1.240), HGB (OR = 0.970), and hCRP (OR = 1.021) were used to construct a predictive model for NLUTD in AIS patients. The model exhibited good performance (AUC = 0.899, calibration curve p = 0.953). Internal validation of the model demonstrated strong discrimination and calibration abilities (AUC = 0.898). Results from DCA and CIC curves indicated that the prediction model had high clinical utility. Conclusions: We developed a predictive model for AIS‐NLUTD and created a nomogram with strong predictive capabilities, assisting healthcare professionals in evaluating NLUTD risk among AIS patients and facilitating early intervention. [ABSTRACT FROM AUTHOR]

Purpose: Differentiating ischemic brain damage is critical for decision making in acute stroke treatment for better outcomes. We examined the sensitivity of amide proton transfer (APT) MRI, a pH‐weighted imaging technique, to achieve this differentiation. Methods: In a rat stroke model, the ischemic core, oligemia, and the infarct‐growth region (IGR) were identified by tracking the progression of the lesions. APT MRI signals were measured alongside ADC, T1, and T2 maps to evaluate their sensitivity in distinguishing ischemic tissues. Additionally, stroke under hyperglycemic conditions was studied. Results: The APT signal in the IGR decreased by about 10% shortly after stroke onset, and further decreased to 35% at 5 h, indicating a progression from mild to severe acidosis as the lesion evolved into infarction. Although ADC, T1, and T2 contrasts can only detect significant differences between the IGR and oligemia for a portion of the stroke duration, APT contrast consistently differentiates between them at all time points. However, the contrast to variation ratio at 1 h is only about 20% of the contrast to variation ratio between the core and normal tissues, indicating limited sensitivity. In the ischemic core, the APT signal decreases to about 45% and 33% of normal tissue level at 1 h for the normoglycemic and hyperglycemic groups, respectively, confirming more severe acidosis under hyperglycemia. Conclusion: The sensitivity of APT MRI is high in detecting severe acidosis of the ischemic core but is much lower in detecting mild acidosis, which may affect the accuracy of differentiation between the IGR and oligemia. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Interpretation Whereas highly cost‐effective and cost‐saving for patients with small infarcts, whether endovascular thrombectomy (EVT) remains cost‐effective in patients with extensive ischemic injury is uncertain.We conducted a model‐based cost‐effectiveness analysis from the United States, Australian, and Spanish societal perspectives, using a 7‐state Markov model, with each state defined by the modified Rankin Scale (mRS) score. Initial probabilities at 3 months were derived from the SELECT2 trial. All other model inputs, including transition probabilities, health care and non‐health care costs, and utility weights, were sourced from published literature and government websites. Our analysis included extensive sensitivity and subgroup analyses.EVT in patients with large ischemic stroke improved health outcomes and was associated with lower costs from a societal viewpoint. EVT was cost‐effective with a mean between‐group difference of 1.24 quality‐adjusted life years (QALYs), and a cost‐saving of $23,409 in the United States, $10,691 in Australia, and $30,036 in Spain, in addition to uncosted benefits in productivity for patients and carers. Subgroup analyses were directionally consistent with the overall population, notably with preserved cost‐effectiveness in older patients (≥ 70 years) and those with more severe strokes (National Institutes of Health Stroke Scale [NIHSS] ≥ 20). Sensitivity analyses were largely consistent with the base‐case results.EVT demonstrated cost‐effectiveness in patients with large core across different settings in the United States, Australia, and Spain, including older patients and those with more severe strokes. These results further support adaptation of systems of care to accommodate the expansion of thrombectomy eligibility to patients with large cores and maximize EVT benefits. ANN NEUROL 2024 [ABSTRACT FROM AUTHOR]

Background and Purpose Methods Results Conclusions Decompressive hemicraniectomy (DH) improves survival and functional outcome in large middle cerebral artery (MCA) infarcts. However, long‐term cognitive outcomes after DH remain underexplored. In a cohort of patients with large right‐hemisphere MCA infarction undergoing DH, we assessed the rates of long‐term cognitive impairment over 3‐year follow‐up.We prospectively evaluated consecutive patients included in the Lille Decompressive Surgery Database (May 2005–April 2022) undergoing DH according to existing guidelines for large hemisphere MCA infarction. We included patients with right‐sided stroke and screened with the Mini‐Mental State Examination (MMSE) in at least one of the prespecified follow‐ups (3‐month, 1‐year, 3‐year). Cognitive impairment was defined as an MMSE score < 24. We included only right‐hemisphere strokes to avoid testing biases related to severe aphasia. We compared clinical and neuroimaging data in patients with and without cognitive impairment.Three hundred four patients underwent DH during the study period. Among 3‐month survivors, 95 had a right‐hemisphere stroke and underwent at least one cognitive screening (median age = 51 years, 56.8% men). Forty‐four patients (46.3%) exhibited cognitive impairment at least once during the 3‐year follow‐up. Baseline characteristics did not significantly differ between patients with and without cognitive impairment. Regarding long‐term temporal trends, cognitive impairment was observed in 23 of 76 (30.3%), 25 of 80 (31.3%), and 19 of 66 (28.8%) patients at 3‐month, 1‐year, and 3‐year follow‐up, respectively, and it was associated with higher rates of functional disability (all p < 0.05).The persistently high rates of cognitive impairment after DH highlight the importance of cognitive monitoring to improve the long‐term management of survivors. [ABSTRACT FROM AUTHOR]

Background and purpose Methods Results Conclusions This study aimed to investigate the association between iron content in grey matter (GM) nuclei and functional outcome in acute ischaemic stroke (AIS) patients utilizing quantitative susceptibility mapping.Forty AIS patients and 40 age‐, sex‐ and education‐matched healthy controls underwent quantitative susceptibility mapping to assess susceptibility values, which are positively correlated with iron content, in the caudate nucleus, putamen, globus pallidus, thalamus, red nucleus and substantia nigra. The nuclei on the contralateral side were measured in AIS patients to minimize confounding due to oedema or haemorrhage. Functional outcome was determined by the modified Rankin Scale (mRS) score at 3 months after stroke. Poor outcome was defined as mRS >2, whilst a good outcome was defined as ≤2.Susceptibility values were significantly higher in most contralateral GM nuclei in AIS patients than in the corresponding left or right nuclei in healthy controls. AIS patients with poor outcome showed significantly lower susceptibility value than those with good outcome in the contralateral caudate nucleus, but no significant differences were observed in other GM nuclei. Binary logistic regression analysis revealed a significant association between the susceptibility value of the contralateral caudate nucleus and poor outcome after adjustment for confounders (adjusted odds ratio 0.692, 95% confidence interval 0.486–0.986, p = 0.042). Receiver operating characteristic curve analysis showed an acceptable ability of the susceptibility value of the contralateral caudate nucleus to predict poor outcome (area under the curve 0.740, p = 0.013).Lower iron content in the contralateral caudate nucleus was associated with poor functional outcome in AIS patients. [ABSTRACT FROM AUTHOR]

T lymphocytes play a vital role in the immune‐inflammatory response following a stroke. However, the specific mechanisms behind the contrasting functions of T cells in the brain and peripheral tissues after a stroke remain unclear and require further investigation. T‐cell receptors (TCRs) are essential in controlling how T lymphocytes develop and become active. This study aims to gain a deeper understanding of the biological function of T lymphocytes by analyzing the TCR repertoire in patients who have experienced an acute ischemic stroke (AIS). High‐throughput TCR sequencing was conducted on peripheral blood samples from 25 AIS patients and 10 healthy controls. We compared the percentage of T cells and the characteristics of the TCR repertoire, specifically focusing on the recombination of V(D)J gene fragments and the diversity of the complementarity determining region 3 (CDR3) of the Vβ gene. Additionally, this study analyzed the potential biological significance of the skewed TCR repertoire in AIS patients. In patients with AIS, the proportion of circulating lymphocytes (LY%) decreased while the systemic immune‐inflammatory index (SII) increased compared to healthy controls. The average number of TCR read pairs decreased, corresponding with the presence of lymphopenia. However, the recombination of V(D)J gene fragments, the number of CDR3 clonotypes, and the diversity of CDR3 was elevated in the peripheral blood of AIS patients. Furthermore, the increased number of CDR3 amino acid or nucleotide clonotypes was negatively correlated with neurologic deficits but positively correlated with AIS patients' systemic immune condition and functional outcomes. Our findings suggest that both immunosuppression and enhanced antigen‐specific T‐cell response may exist in the periphery of the AIS patients. Further investigation into the mechanisms underlying these opposing changes may lead to the discovery of novel targets to reverse immunosuppression or mitigate the detrimental effects of T cells in the lesioned brain of AIS patients. [ABSTRACT FROM AUTHOR]

Background and Purpose Methods Results Conclusions The influence of intracranial arteriosclerosis (ICAR) on acute ischaemic stroke (AIS) prognosis is unclear. This study explored its impact, focusing on ICAR subtypes categorized by intracranial carotid artery calcification (ICAC) patterns: intimal or atherosclerotic versus internal elastic lamina calcification or non‐atherosclerotic. The aim was to determine their effect on AIS prognosis in patients undergoing endovascular treatment (EVT).This prospective cohort study included consecutive AIS patients with anterior circulation large vessel occlusion undergoing EVT. ICAC, the hallmark of ICAR, was assessed using non‐contrast computed tomography to quantify volume and establish the predominant ICAR subtype. The primary outcome was long‐term functional outcome, measured by the 90‐day modified Rankin Scale score. Secondary outcomes included first‐pass effect, revascularization degree, symptomatic intracranial haemorrhage and 24‐h infarct volume. Multivariate‐adjusted linear and logistic regression models were used to assess the association of ICAC volume and subtype with these outcomes.From January 2021 to February 2022, 181 patients were included, of whom 172 (95%) had ICAC. Internal elastic lamina calcification was the predominant subtype in 103 (57%), intimal in 52 (29%) and mixed in 17 (9%). The intimal or atherosclerotic ICAC pattern was linked to poorer functional outcomes (adjusted odds ratio 2.12, 95% confidence interval [CI] 1.10–4.09), decreased first‐pass effect probability (adjusted odds ratio 0.42, 95% CI 0.21–0.84) and higher infarct volume (adjusted β value 22.11, 95% CI 0.55–43.67).A predominant intimal ICAC subtype, linked to underlying atherosclerosis, correlated with larger infarct volume and poorer 90‐day functional outcomes in EVT‐treated AIS patients. Intracranial atherosclerosis appears to be a relevant factor hampering clinical benefits post‐EVT. [ABSTRACT FROM AUTHOR]

Introduction Aims Materials and Methods Results Conclusion Cerebral ptosis is defined as the drooping of eyelids due to lesions in the cerebral hemispheres. Cerebral ptosis is due to either unilateral or bilateral hemispheric damage without brainstem involvement. Ischemic strokes are the most common etiology leading to hemispheric damage.To assess the prevalence of cerebral ptosis in ischemic strokes and to correlate the presence of cerebral ptosis with the outcome of the patients. To also assess the demographic profile of these patients.This is a retrospective study from June 2022 to August 2024. All patients diagnosed as acute stroke presenting with cerebral ptosis within day 3 of stroke were included. Patients with a reduced level of consciousness, brainstem involvement, and those with signs of impending herniation were excluded. The modified Rankin scale (mRS) on the day of admission and the day of discharge were compared.There were 26 patients with cerebral ptosis among 649 patients admitted with anterior circulation stroke (prevalence 4.01%). 84.6% (n = 12) had right hemisphere involvement and 15.4% (n = 4) had left side involvement. 88.5% (n− = 23) had middle cerebral artery territory involvement and 7.7% (n = 2) had internal carotid artery territory involvement. The mean mRS on admission was 4.42 and 4.81 on discharge (paired t‐test 0.015). mRS 6 (death) was observed in four patients.Cerebral ptosis is a supranuclear disorder with the most common etiology being vascular insult to the cerebral hemisphere. It is an ominous and rare clinical sign. Identification of this entity is important, and it is not to be confused with a reduced level of consciousness. [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]

Objective Methods Results Interpretation The association between gait speed and adverse outcomes after stroke has not been fully illustrated. This study aimed to explore the association of gait speed on long‐term outcomes in minor stroke or transient ischemic attack (TIA).We performed a longitudinal study with acute minor stroke or TIA based on a subgroup of the Third China National Stroke Registry data. The gait speed was evaluated using a 10‐meter walking test at discharge and 3 months after the stroke onset. The primary outcomes were poor functional outcomes at 1 year, defined by a modified Rankin Score (mRS) of 2–6. Additional outcomes included all‐cause death, ambulate dependency (mRS score 4–6), cognitive impairment (Montreal Cognitive Assessment <26), stroke recurrence, and composite vascular events.The study sample included a total of 1542 stroke patients with a median age of 60 (53–68). At 1‐year follow‐up, 140 (9.20%) patients experienced poor functional outcomes. Faster gait speed at discharge was associated with lower incidence of poor functional outcome (OR = 0.89; 95% CI, 0.84–0.94), cognitive impairment (OR = 0.93; 95% CI, 0.89–0.96), ischemic stroke recurrence (HR = 0.92; 95% CI, 0.87–0.98), and composite vascular events (HR =0.94; 95% CI, 0.89–0.99) at 1 year. Faster gait speed at 3 months was associated with lower incidence of poor functional outcome (OR = 0.90; 95% CI, 0.85–0.95), ambulate dependency (OR = 0.86; 95% CI, 0.77–0.97), and cognitive impairment (OR = 0.92; 95% CI, 0.88–0.95) at 1 year.Our findings indicated that slow gait speed after minor stroke or TIA may be an independent predictor for long‐term poor outcomes. Gait speed may be considered as a vital sign during follow‐up in post‐stroke patients. [ABSTRACT FROM AUTHOR]

Background Methods Results Interpretation The study aimed to compare outcomes of mechanical thrombectomy (MT) in pediatric patients with acute ischemic stroke (AIS) caused by focal cerebral arteriopathy (FCA) versus cardioembolism (CE).Data from the Save ChildS and KidClot cohorts were merged. Children with AIS because of FCA or CE that underwent MT were included. The study used the Childhood Arterial Ischemic Stroke Standardized Classification and Diagnostic Evaluation (CASCADE) for stroke cause assessment. Descriptive statistics and multivariable regression models were used to analyze final modified thrombolysis in cerebral infarction (mTICI) scores, periprocedural complications, and functional outcomes assessed by the modified Rankin scale (mRS) at 6 to 12 months.The analysis included 60 children with 14 FCA and 46 CE cases. CE etiology was associated with better revascularization (good to excellent thrombolysis in cerebral infarction scores) and shift toward better outcomes (common adjusted odds ratio of mRs for CE vs FCA: 0.27, 95% CI: [0.06–0.97], p = 0.039), with no difference in favorable outcome rates. FCA was associated with significantly lower rates of excellent revascularization (21% vs 65%, p < 0.001). No difference in complications' rates was observed between the groups (7.2% in FCA vs 5.5%, p = 0.69).We found that pediatric AIS because of CE etiology has more favorable procedural outcomes compared to FCA following MT. This translated to mixed functional outcomes that may be more favorable in the CE group. These findings highlight the need for further research to refine treatment protocols for pediatric stroke, particularly in understanding and managing FCA in children. ANN NEUROL 2024 [ABSTRACT FROM AUTHOR]

Objective Methods Results Interpretation We evaluated the effect of CHA2DS2‐VASc score and prior use of oral anticoagulants (OACs) on endovascular treatment (EVT) in patients with acute ischemic stroke and atrial fibrillation (AF).Patients with AF who received EVT in 353 centers in Japan (2018–2020) were included. The outcomes were symptomatic intracerebral hemorrhage (sICH), in‐hospital mortality, functional independence, and successful and complete reperfusion. The effects of CHA2DS2‐VASc score, its components, and prior use of OACs were assessed via a multiple logistic regression model.Of the 6984 patients, 780 (11.2%) used warfarin and 1168 (16.7%) used direct oral anticoagulants (DOACs) before EVT. Based on the CHA2DS2‐VASc score, 6046 (86.6%) presented a high risk (≥2 for males and ≥3 for females) while 938 (13.4%) had intermediate to low risks. Higher CHA2DS2‐VASc scores were associated with increased sICH, in‐hospital mortality, and decreased functional independence, regardless of prior OACs. For patients with a high‐risk category, prior DOACs increased the odds of successful and complete reperfusion (adjusted odds ratio [95% confidence interval (CI)], 1.27 [1.00–1.61] and 1.30 [1.10–1.53]). For those with integrated intermediate to low risks, neither prior warfarin nor DOAC affected the outcomes. Regardless of total CHA2DS2‐VASc scores, patients with congestive heart failure or left ventricular dysfunction, hypertension, age >75 years, or female benefited similarly from prior DOAC use.Prior DOAC use for patients with high‐ and selected intermediate‐risk CHA2DS2‐VASc scores increased prevalence of successful and complete reperfusion. These findings may provide supplemental evidence to introduce preventive DOAC for patients with AF. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Methods Results Conclusions The aim of this study is to determine whether there are any changes in hemorheological parameters, including whole blood viscosity (WBV), plasma viscosity, erythrocyte aggregation, and erythrocyte deformability, in acute ischemic stroke patients, and to establish their relationship with stroke etiology. The study also aims to observe the changes in these parameters, if any, over time and after treatment, and to assess the correlation between risk factors for ischemic stroke and neuroimaging findings.This was a prospective observational study including 70 patients diagnosed with acute ischemic stroke within the first 3 days of the onset of symptoms and 96 healthy controls. Stroke patients were categorized based on TOAST criteria, and hemorheological parameters were measured at admission and on the fifth day post‐treatment. Erythrocyte aggregation and deformability were measured using a laser ektacytometer, and viscosity assessment was conducted with a rotational viscometer.Stroke patients exhibited significant differences from the control group in aggregation amplitude, aggregation index, and aggregation half‐time (p = 0.001, p = 0.013, p = 0.009, respectively) and showed elevated maximum value of elongation index (p = 0.000). No significant differences in WBV and plasma viscosity were observed between the groups. Post‐treatment, the small vessel occlusion subgroup demonstrated a notable reduction in WBV. Additionally, homocysteine levels showed a positive correlation with scattered white matter lesions in basal ganglia and infratentorial regions (p = 0.002, p = 0.039, respectively).Increased predisposition to erythrocyte aggregation may contribute to the occurrence of acute ischemic stroke. Moreover, gaining the ability of erythrocytes to deform and increase blood flow may serve as a compensatory mechanism in the chronic vascular disease process. The risk factors for ischemic stroke may exhibit connections to specific areas within the brain. [ABSTRACT FROM AUTHOR]

Aims: Dopamine transporter (DAT) can regulate DA homeostasis and has been implicated in many nervous system diseases. Whether DAT is involved in the protection against ischemic stroke is unclear. Methods: In vivo microdialysis measurements of DA were recorded in the ischemic penumbral area of mice with middle cerebral artery occlusion (MCAO). DAT coding gene, Slc6a3 mutation, and DAT overexpression animals were performed MCAO. Madopar (compound formulation of levodopa) and nomifensine (DA reuptake inhibitor) were administered in MCAO animals. Brain slices were prepared in Slc6a3 mutation or wild‐type (WT) animals with MCAO to record miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs). The effects of DA and its dopamine‐1 receptor (D1R) antagonists (SCH‐23390) on mEPSCs, mIPSCs, and neurons protection were recorded. Results: MCAO caused a prominent increase in DA. Slc6a3 mutation significantly attenuated the ischemic injury, whereas DAT overexpression aggravated this injury. Both nomifensine and madopar protected against brain injury. Slc6a3 mutation and DA restored the disturbance of mEPSCs and mIPSC, and protected against neuron death, which was abolished by SCH‐23390. Conclusion: DAT inhibition might be explored as a strategy for ischemic stroke prevention. DA and D1R involve in the restoration of synaptic dysfunction and neuron protection. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to explore the relationship between atrial fibrillation (AF), cerebral small vessel disease (CSVD), and ischemic stroke. Methods: Data were extracted from China's Third National Stroke Registry (CNSR‐III), which registered 15,166 patients in China. A total of 12,180 ischemic stroke patients were included excluding those diagnosed with TIA or without MRI. Logistic regression was to explore the relationship between AF, CSVD, and poor functional outcomes at 12‐month follow‐up. Cox regression is to explore AF, CSVD, and stroke recurrence as well as all‐cause mortality at 12‐month follow‐up. Results: The average age was 62.40 ± 11.22 years old, and 8362 (68.65%) were men at baseline. Patients with AF had an increased risk of stroke recurrence and all‐cause mortality at 12‐month follow‐up. Those with AF and CSVD imaging such as lacunes, white matter hyperintensity (WMH), and the presence of cerebral microbleeds (CMBs) had an increased risk of poor prognosis. And those with both AF and CSVD burden had an increased risk of worse prognosis at 12‐month follow‐up. Conclusion: Among Chinese patients with acute ischemic stroke, those with AF were associated with a higher risk of 12‐month mortality and stroke recurrence. When AF was combined with some CSVD imaging features such as lacunes, WMH, presence of CMBs or burdens, the 12‐month poor prognosis worsened. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate the relationship between systemic immune‐inflammation index (SII) and short‐term mortality in acute ischemic stroke (AIS) with internal carotid artery (ICA) severe stenosis and stroke associated pneumonia (SAP) patients. Methods: Information on general demographic, laboratory data, CT angiography, magnetic resonance angiography, or digital subtraction angiography were obtained. The predictive power was evaluated by assessing the area under the receiver operating characteristic (ROC) curve. The logistic regression was performed to assess the association of SII and short‐term mortality in severe stenosis ICA‐AIS and SAP patients. Result: Among 342 patients with severe stenosis ICA‐AIS and SAP, death occurred in 66 patients during 120 days follow‐up. Multivariate regression analyses indicated that increased SII predicts higher mortality in 120 days follow‐up, and the risk of short‐term mortality in SII > 666.31 × 109/L group is increased 4.671‐fold. Patients with SII > 666.31 × 109/L had higher proportion of male, hypertension, smoking, higher admission NIHSS score, higher systolic blood pressure, and higher proportion of 120 days mortality. Higher SII predicted a worse 120 days mortality was worked out by Kaplan–Meier methods. Conclusion: An elevated SII was remarkably associated with 120 days mortality in severe stenosis ICA‐AIS and SAP patients. [ABSTRACT FROM AUTHOR]

Background: The association among coronary heart disease, ischemic stroke, and hydrocephalus remains ambiguous. Objectives: There is a need for a Mendelian randomization study to evaluate the underlying causality between coronary heart disease, ischemic stroke, and hydrocephalus. Methods: The data source utilized genome‐wide association studies, employing a threshold of p < 5 × 10−8 to identify single nucleotide polymorphisms strongly linked to ischemic stroke and coronary heart disease as instrumental variables (IVs). Five methods—inverse variance weighted (IVW), Mendelian randomization (MR) Egger, Weighted Median, Weighted mode, and Simple mode—utilized the selected IVs to estimate the causality between ischemic stroke, coronary heart disease, and hydrocephalus. Results: The IVW demonstrated that ischemic stroke and coronary heart disease serve as risk factors for hydrocephalus (odds ratio [OR] = 1.650, 95% CI: 1.066–2.554, p = 0.025; OR = 1.307, 95% CI: 1.023–1.668, p = 0.032). Both the MR‐Egger intercept test and Cochran's Q test affirmed the relative reliability of the IVW analysis results. However, no evidence of a reverse causation was observed between hydrocephalus and coronary heart disease or ischemic stroke. Conclusions: Coronary heart disease and Ischemic stroke may increase the risk of hydrocephalus. [ABSTRACT FROM AUTHOR]

Background: Hypoperfusion Intensity Ratio (HIR) is associated with collaterals and outcome in acute ischemic stroke (AIS). We investigated whether a combined assessment of HIR and collaterals could provide an added value. Methods: Retrospective single‐center study, including AIS patients with large vessel occlusion and endovascular treatment 0–24 h from onset. Predictors of FIV and outcome (90 days modified Rankin Scale 0–1) were investigated with linear and logistic regression respectively. Subjects were stratified in three groups: poor collaterals (grade 0–3) with poor HIR (≥.4), good collaterals (grade 4–5) with poor HIR/poor collaterals with good HIR (<.4) and good collaterals with good HIR. Results: We included 337 patients (median age 77, 53.1% males), of whom 100 (29.7%) had excellent outcome. One hundred and forty five patients with favourable collateral and HIR profiles had smaller infarct (median poor collaterals with poor HIR 41 mL, good collaterals with poor HIR/poor collaterals with good HIR 21 mL and good collaterals with good HIR 11 mL, p <.001) and higher rates of excellent outcome (poor collaterals with poor HIR 15.7%, good collaterals with poor HIR/poor collaterals with good HIR 26.2% and good collaterals with good HIR 39.3% p =.001). Logistic regression showed that patients with favourable collateral and HIR profiles had the highest odds of good outcome (OR: 3.83, 95% CI 1.62–9.08, p =.002). Conclusion: Collaterals and HIR are independent predictors of final infarct lesion and outcome in stroke patients and their integration provides an added value. These findings might inform clinical practice and future trials. [ABSTRACT FROM AUTHOR]

Poststroke fatigue (PSF) is a common, underestimated sequel of stroke that affects the quality of life of patients. In this study, the authors investigate the prevalence of PSF in three equal groups: control, ischemic, and hemorrhagic stroke patients. Some of the multidimensional factors that predict PSF are examined, and the implications for improvement of stroke management are highlighted. [ABSTRACT FROM AUTHOR]

Background: Stroke after durable left ventricular assist device (d‐LVAD) implantation portends high mortality. The incidence of ischemic and hemorrhagic stroke and the impact on stroke outcomes of temporary mechanical circulatory support (tMCS) management among patients requiring bridge to d‐LVAD with micro‐axial flow‐pump (mAFP, Abiomed) is unsettled. Methods: Consecutive patients, who underwent d‐LVAD implantation after being bridged with mAFP at 19 institutions, were retrospectively included. The incidence of early ischemic and hemorrhagic stroke after d‐LVAD implantation (<60 days) and association of pre‐d‐LVAD characteristics and peri‐procedural management with a specific focus on tMCS strategies were studied. Results: Among 341 patients, who underwent d‐LVAD implantation after mAFP implantation (male gender 83.6%, age 58 [48–65] years, mAFP 5.0/5.5 72.4%), the early ischemic stroke incidence was 10.8% and early hemorrhagic stroke 2.9%. The tMCS characteristics (type of mAFP device and access, support duration, upgrade from intra‐aortic balloon pump, ECMELLA, ECMELLA at d‐LVAD implantation, hemolysis, and bleeding) were not associated with ischemic stroke after d‐LVAD implant. Conversely, the device model (mAFP 2.5/CP vs. mAFP 5.0/5.5: HR 5.6, 95%CI 1.4–22.7, p = 0.015), hemolysis on mAFP support (HR 10.5, 95% CI 1.3–85.3, p = 0.028) and ECMELLA at d‐LVAD implantation (HR 5.0, 95% CI 1.4–18.7, p = 0.016) were associated with increased risk of hemorrhagic stroke after d‐LVAD implantation. Both early ischemic (HR 2.7, 95% CI 1.9–4.5, p < 0.001) and hemorrhagic (HR 3.43, 95% CI 1.49–7.88, p = 0.004) stroke were associated with increased 1‐year mortality. Conclusions: Among patients undergoing d‐LVAD implantation following mAFP support, tMCS characteristics do not impact ischemic stroke occurrence, while several factors are associated with hemorrhagic stroke suggesting a proactive treatment target to reduce this complication. [ABSTRACT FROM AUTHOR]

Background: Frailty is associated with adverse cardiovascular outcomes independent of age and comorbidities, yet the independent influence of frailty progression on cardiovascular outcomes remains uncertain. Methods: To determine whether frailty progression is associated with adverse cardiovascular outcomes, independent of baseline frailty and age, we evaluated all Medicare Fee‐for‐Service beneficiaries ≥65 years at cohort inception with continuous enrollment from 2003 to 2015. Linear mixed effects models, adjusted for baseline frailty and age, were used to estimate change in a validated claims‐based frailty index (CFI) over a 5‐year period. Survival analysis was used to examine frailty progression and risk of adverse health outcomes. Results: There were 8.9 million unique patients identified, mean age 77.3 ± 7.2 years, 58.7% female, 10.9% non‐White race. In total, 60% had frailty progression and 40% frailty regression over median follow‐up of 2.4 years. Compared to those with frailty regression, when adjusting for age and baseline CFI, those with frailty progression had a significantly greater risk of incident major adverse cardiovascular and cerebrovascular events (MACCE) (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.31–1.31), all‐cause mortality (HR 1.34, 95% CI 1.34–1.34), acute myocardial infarction (HR 1.08, 95% CI 1.07–1.09), heart failure exacerbation (HR 1.30, 95% CI 1.29–1.30), ischemic stroke (HR 1.14, 95% CI 1.14–1.15). There was also a graded increase in risk of each outcome with more rapid progression, as well as significantly fewer days alive at home (DAH) with more rapid progression compared to the slowest progression group (270.4 ± 112.3 vs. 308.6 ± 93.0 days, rate ratio 0.88, 95% CI 0.87–0.88, p < 0.001). Conclusions: In this large, nationwide sample of older Medicare beneficiaries, frailty progression, independent of age and baseline frailty, was associated with fewer DAH and a graded risk of MACCE, all‐cause mortality, myocardial infarction, heart failure, and ischemic stroke compared to those with frailty regression. [ABSTRACT FROM AUTHOR]

The effectiveness of various stroke treatments depends on the anatomical variability of the cerebral vasculature, particularly the collateral blood vessel network. Collaterals at the level of the Circle of Willis and distal collaterals, such as the leptomeningeal arteries, serve as alternative avenues of flow when the primary pathway is obstructed during an ischemic stroke. Stroke treatment typically involves catheterization of the primary pathway, and the potential risk of further flow reduction to the affected brain area during this treatment has not been previously investigated. To address this clinical question, we derived the lumped parameters for catheterized blood vessels and implemented a corresponding distributed compartment (0D) model. This 0D model was validated against an experimental model and benchmark test cases solved using a 1D model. Additionally, we compared various off‐center catheter trajectories modeled using a 3D solver to this 0D model. The differences between them were minimal, validating the simplifying assumption of the central catheter placement in the 0D model. The 0D model was then used to simulate blood flows in realistic cerebral arterial networks with different collateralization characteristics. Ischemic strokes were modeled by occlusion of the M1 segment of the middle cerebral artery in these networks. Catheters of different diameters were inserted up to the obstructed segment and flow alterations in the network were calculated. Results showed up to 45% maximum blood flow reduction in the affected brain region. These findings suggest that catheterization during stroke treatment may have a further detrimental effect for some patients with poor collateralization. [ABSTRACT FROM AUTHOR]

Background and Purpose Experimental Approach Key Results Conclusion and Implications Transient receptor potential vanilloid 2 (TRPV2) is a Ca2+‐permeable non‐selective cation channel. Despite the significant roles of TRPV2 in immunological response, cancer progression and cardiac development, pharmacological probes of TRPV2 remain to be identified. We aimed to discover TRPV2 inhibitors and to elucidate their molecular mechanism of action.Fluorescence‐based Ca2+ assay in HEK‐293 cells expressing murine TRPV2 was used to identify plumbagin as a novel TRPV2 inhibitor. Patch‐clamp, in silico docking and site‐directed mutagenesis were applied to investigate the molecular mechanisms critical for plumbagin interaction. ELISA and qPCR were used to assess nitric oxide release and mRNA levels of inflammatory mediators, respectively. si‐RNA interference was used to knock down TRPV2 expression, which was validated by western blotting. Neurological and histological analyses were used to examine brain injury of mice following middle cerebral artery occlusion/reperfusion (MCAO/R).Plumbagin is a potent TRPV2 negative allosteric modulator with an IC50 value of 0.85 μM, exhibiting >14‐fold selectivity over TRPV1, TRPV3 and TRPV4. Plumbagin suppresses TRPV2 activity by decreasing the channel open probability without affecting the unitary conductance. Moreover, plumbagin binds to an extracellular pocket formed by the pore helix and flexible loop between transmembrane helices S5 and S6 of TRPV2. Plumbagin effectively suppresses LPS‐induced inflammation of BV‐2 microglia and ameliorates brain injury of MCAO/R mice.Plumbagin is a novel pharmacological probe to study TRPV2 pathophysiology. TRPV2 is a novel molecular target for the treatment of neuroinflammation and ischemic stroke. [ABSTRACT FROM AUTHOR]

Ischemic stroke is a significant global health issue, ranking fifth among all causes of death and a leading cause of serious long‐term disability. Ischemic stroke leads to severe outcomes, including permanent brain damage and neuronal dysfunction. Therefore, decreasing and preventing neuronal injuries caused by stroke has been the focus of therapeutic research. In recent years, many studies have shown that fluctuations in hormonal levels influence the prognosis of ischemic stroke. Thus, it is relevant to understand the role of hormones in the pathophysiological mechanisms of ischemic stroke for preventing and treating this health issue. Here, we investigate the contribution of the prolactin/vasoinhibin axis, an endocrine system regulating blood vessel growth, immune processes, and neuronal survival, to the pathophysiology of ischemic stroke. Male mice with brain overexpression of prolactin or vasoinhibin by adeno‐associated virus (AAV) intracerebroventricular injection or lacking the prolactin receptor (Prlr−/−) were exposed to transient middle cerebral artery occlusion (tMCAO) for 45 min followed by 48 h of reperfusion. Overexpression of vasoinhibin or the absence of the prolactin receptor led to an increased lesion volume and decreased survival rates in mice following tMCAO, whereas overexpression of prolactin had no effect. In addition, astrocytic distribution in the penumbra was altered, glial fibrillary acidic protein and S100b mRNA expressions were reduced, and interleukin‐6 mRNA expression increased in the ischemic hemisphere of mice overexpressing vasoinhibin. Of note, prolactin receptor‐null mice (Prlr−/−) showed a marked increase in serum vasoinhibin levels. Furthermore, vasoinhibin decreased astrocyte numbers in mixed hippocampal neuron–glia cultures. These observations suggest that increased vasoinhibin levels may hinder astrocytes' protective reactivity. Overall, this study suggests the involvement of the prolactin/vasoinhibin axis in the pathophysiology of ischemic stroke‐induced brain injury and provides insights into the impact of its dysregulation on astrocyte reactivity and lesion size. Understanding these mechanisms could help develop therapeutic interventions in ischemic stroke and other related neurological disorders. [ABSTRACT FROM AUTHOR]

Objective: To examine the combined impact of migraine and gestational diabetes mellitus (GDM) on the risks of premature (persons aged ≤60 years) major adverse cardiovascular and cerebrovascular events (MACCE) based on a composite endpoint of fatal and non‐fatal myocardial infarction (MI) and stroke. Background: Migraine and GDM are risk factors for cardiovascular disease. It is unknown how the combination of migraine and GDM may affect cardiovascular disease risk. Methods: In a Danish population‐based cohort longitudinal study, we established four cohorts among women with at least one pregnancy during 1996–2018: women with migraine, women with GDM, women with both migraine and GDM, and women free of migraine and free of GDM. Risks of premature MACCE and component endpoints were assessed for each cohort. Results: We included 1,307,456 women free of migraine and free of GDM, 56,811 women with migraine, 24,700 women with GDM, and 1484 women with migraine and GDM. The 20‐year absolute risk of MACCE was 1.3% (MI: 0.4%, ischemic stroke: 0.6%, hemorrhagic stroke: 0.3%) among women free of migraine and free of GDM, 2.3% (MI: 0.8%, ischemic stroke: 1.2%, hemorrhagic stroke: 0.5%) among women with migraine, 2.2% (MI: 1.0%, ischemic stroke: 1.0%, hemorrhagic stroke: 0.4%) among women with GDM, and 3.7% (MI: 1.7%, ischemic stroke: 1.7%, hemorrhagic stroke: 0.3%) among women with both migraine and GDM. The 20‐year adjusted hazard ratio of premature MACCE was 1.65 (95% confidence interval [CI] 1.49–1.82) for women with migraine; 1.64 (95% CI 1.37–1.96) for women with GDM; and 2.35 (95% CI 1.03–5.36) for women with both GDM and migraine when compared with women free of migraine and free of GDM. Conclusions: Migraine and GDM were each independently associated with an increased risk of MACCE. Risk of premature MACCE was greatest among women with both migraine and GDM, although this risk estimate was imprecise. Plain Language Summary: Migraine and gestational diabetes are both risk factors for cardiovascular disease, but it is unknown how the combination of migraine and gestational diabetes affects cardiovascular disease risk. In this study, we found an increased risk of cardiovascular disease among women with migraine only and among women with gestational diabetes only. The risk of cardiovascular disease was greatest among women with both migraine and gestational diabetes. [ABSTRACT FROM AUTHOR]

Background and purpose: Parent artery atherosclerosis is an important aetiology of recent subcortical ischaemic stroke (RSIS). However, comparisons of RSIS with different degrees of parent artery atherosclerosis are lacking. Methods: Prospectively collected data from our multicentre cohort (all were tertiary centres) of the Stroke Imaging Package Study between 2015 and 2017 were retrospectively reviewed. The patients with RSIS defined as a single clinically relevant diffusion‐weighted imaging positive lesion in the territory of lenticulostriate arteries were categorized into three subgroups: (1) normal middle cerebral artery (MCA) on magnetic resonance angiography and high‐resolution magnetic resonance imaging (HR‐MRI); (2) low‐grade MCA atherosclerosis (normal or <50% stenosis on magnetic resonance angiography and with MCA plaques on HR‐MRI); (3) steno‐occlusive MCA atherosclerosis (stenosis ≥50% or occlusion). The primary outcome was 90‐day functional dependence (modified Rankin Scale score >2). The clinical and imaging findings were compared between subgroups. Results: A total of 239 patients (median age 60.0 [52.0–67.0] years, 72% male) were enrolled, including 140 with normal MCA, 64 with low‐grade MCA atherosclerosis and 35 with steno‐occlusive MCA atherosclerosis. Patients with steno‐occlusive MCA atherosclerosis had the largest infarct volume. Low‐grade MCA atherosclerosis was independently associated with cerebral microbleeding, more severe perivascular spaces in basal ganglia and higher total cerebral small vessel disease burden. Low‐grade MCA atherosclerosis was an independent determinant of 90‐day functional dependence (odds ratio 3.897; 95% confidence interval 1.309–11.604). Conclusions: Our study suggested RSIS with varying severity of parent artery atherosclerosis exhibits distinctive clinical and neuroimaging characteristics, with low‐grade MCA atherosclerosis associating with higher cerebral small vessel disease burden and worse prognosis. [ABSTRACT FROM AUTHOR]

Background and purpose: The aim of this study is to investigate the efficacy and safety of preoperative versus intraoperative tirofiban in patients with large vessel occlusion (LVO) due to large artery atherosclerosis (LAA). Methods: This is a retrospective multicenter cohort study based on the RESCUE‐RE (Registration Study for Critical Care of Acute Ischemic Stroke After Recanalization) trial enrolling patients with anterior circulation LVO classified as LAA within 24 h of onset. Patients were divided into three groups: preoperative tirofiban (PT), intraoperative tirofiban (IT), and no tirofiban (NT). Propensity score matching (PSM) was used to balance baseline characteristics. The efficacy outcomes included 90‐day functional independence (modified Rankin Scale score = 0–2) and early partial recanalization (EPR; defined as a modified Thrombolysis in Cerebral Infarction score = 1–2a). The safety outcomes included symptomatic intracranial hemorrhage (sICH). Results: A total of 104 matched triplets were obtained through PSM. Compared with NT, PT increased 90‐day functional independence (60.8% vs. 42.3%, p = 0.008) and EPR (42.7% vs. 18.3%, p < 0.001) rate, with a tendency to increase the asymptomatic intracranial hemorrhage (aICH) proportion (28.8% vs. 18.3%, p = 0.072). Compared with IT, PT had a higher 90‐day functional independence (60.8% vs. 45.2%, p = 0.025) and EPR (42.7% vs. 20.2%, p = 0.001) rate, with no significant difference in sICH (14.4% vs. 7.7%, p = 0.122) and aICH (28.8% vs. 21.2%, p = 0.200). Compared with NT, IT had a lower 90‐day mortality rate (9.6% vs. 24.0%, p = 0.005). Conclusions: Tirofiban shows good adjuvant therapy potential in acute ischemic stroke–LVO due to LAA patients. PT is associated with higher rates of EPR and better therapeutic efficacy. In addition, EPR may be a potential way to improve prognosis. [ABSTRACT FROM AUTHOR]

Aim: This nationwide cohort study evaluated the impact of sodium–glucose co‐transporter‐2 inhibitors (SGLT2i) on patients with type 2 diabetes mellitus (T2DM) after ischaemic stroke (IS), aiming to compare clinical outcomes between SGLT2i‐treated patients and those not receiving SGLT2i. Materials and Methods: Utilizing Taiwan's National Health Insurance Research Database, we identified 707 patients with T2DM treated with SGLT2i and 27 514 patients not treated with SGLT2i after an IS, respectively, from 1 May 2016 to 31 December 2019. Propensity score matching was applied to balance baseline characteristics. The follow‐up period extended from the index date (3 months after the index acute IS) until the independent occurrence of the study outcomes, 6 months after discontinuation of the index drug, or the end of the study period (31 December 2020), whichever came first. Results: After propensity score matching, compared with the non‐SGLT2i group (n = 2813), the SGLT2i group (n = 707) exhibited significantly lower recurrent IS rates (3.605% per year vs. 5.897% per year; hazard ratio: 0.55; 95% confidence interval: 0.34–0.88; p = 0.0131) and a significant reduction in all‐cause mortality (5.396% per year vs. 7.489% per year; hazard ratio: 0.58; 95% confidence interval: 0.39–0.85; p = 0.0058). No significant differences were observed in the rates of acute myocardial infarction, cardiovascular death, heart failure hospitalization, or lower limb amputation. Conclusions: Our findings indicate significantly lower risks of recurrent IS and all‐cause mortality among patients with T2DM receiving SGLT2i treatment. Further studies are required to validate these results and investigate the underlying mechanisms behind the observed effects. [ABSTRACT FROM AUTHOR]

Background: Despite advances in imaging techniques and treatment modalities, tools to predict recovery after stroke remain limited. Objective: To determine if transcranial Doppler (TCD) mean flow velocities were predictive of functional recovery following ischemic stroke. Methods: Data were collected from patients with stroke admitted to an academic tertiary care facility in the southeastern region of the United States between 2012 and 2019 who had a middle cerebral artery distribution ischemic stroke, TCD, and were discharged to our inpatient rehabilitation facility. Mean flow velocities were categorized as low (<40 cm/s), normal (40–80 cm/s), or high (>80 cm/s). Functional Independence Measure (FIM) scores were collected on admission to and discharge from inpatient rehabilitation. Multiple linear regression models were used to assess the differences in mean FIM score changes by categories of mean flow velocities. Results: We enrolled 57 patients, mean age 60 years, 73.7% male. Compared to the normal velocity group, those with abnormally low velocities had a significantly smaller change in their FIM score (adjusted β = −8.42; p =.01). Compared to the normal velocity group, those with abnormally high velocities experienced a greater change in FIM score, but this association was not statistically significant (beta = 1.12; p =.77). Conclusions: In this limited population, we found that low mean flow velocity as measured by TCD ultrasonography after a middle cerebral artery stroke is associated with poorer functional recovery following inpatient rehabilitation. Our results suggest that the value of TCD ultrasonography as a tool to predict motor recovery after stroke warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: The triglyceride–glucose (TyG) index has demonstrated correlations with adverse clinical outcomes in patients with ischaemic stroke, coronary heart disease and cardiac failure. However, its association with overall mortality in individuals concurrently experiencing heart failure (HF) and chronic kidney disease (CKD) remains inadequately explored. Methods: Utilizing the Medical Information Mart for Intensive Care IV (Version 2.2) repository, subjects underwent quartile stratification based on the TyG index. The primary endpoint was all‐cause mortality during hospitalization. Cox proportional hazard models were employed to examine the correlation between TyG and all‐cause mortality in HF patients with CKD. Evaluation involved Kaplan–Meier (KM) analysis and restricted cubic splines (RCSs) to compare mortality rates during hospitalization and 1 year after admission across cohorts with varying TyG index levels. Results: A cohort of 1537 HF and CKD patients participated. Cox regression analysis revealed elevated TyG levels as an independent risk factor for both in‐hospital and 1 year mortality. RCS analysis indicated a rising, non‐linear association between TyG levels and all‐cause mortality (P value for non‐linear <0.001). KM survival curves demonstrated a statistically significant reduction in survival rates within the high TyG index group compared with the low one (log‐rank P < 0.001). Conclusions: The TyG index exhibited substantial independent prognostic value for elevated in‐hospital and 1 year all‐cause mortality among the cohort with HF and CKD. These findings suggest that assessing the TyG index could play a crucial role in developing novel therapeutic strategies to improve outcomes for this high‐risk demographic. [ABSTRACT FROM AUTHOR]

Introduction: Ginkgo Folium tablet (GFT) is a patented traditional Chinese medicine prepared from Ginkgo biloba leaves extract (GBE). However, the current quality indicators for GFT or GBE as designated by the Chinese Pharmacopoeia are insufficient in preventing counterfeit events. Objective: This study aimed to putatively identify compounds in GFT and to further develop a quality marker (Q‐marker) system for GFT. Methods: A novel strategy utilizing database‐aided ultrahigh‐performance liquid chromatography‐quadrupole‐orbitrap mass spectrometry was employed to analyze the lyophilized aqueous powder of GFT. Subsequently, the identified compounds underwent quantum chemical calculations, network pharmacology, and molecular simulations through in silico approaches to evaluate the Q‐marker principles of traceability, specificity, and efficiency‐relevance. Results: The results revealed the putative identification of a total of 66 compounds, including 36 flavonoids, 7 phenolic acids and derivatives, 5 terpene lactones, 4 fatty acids and derivatives, 3 alkaloids, 1 amino acid, and 10 other compounds. Particularly, 16 compounds were unexpectedly observed, and seven compounds met the Q‐marker principles. Conclusion: This study recommends the seven compounds, namely, (−)‐gallocatechin, matrine, (−)‐epicatechin, ginkgolide C, ginkgolide A, ginkgolide B, and curdione, as the anti‐counterfeiting pharmacopoeia Q‐markers for GFT. The reconstruction of the Q‐marker system for GFT not only enhances the understanding of the compounds in GFT and other GBE‐based preparations but also provides valuable recommendations for the Pharmacopoeia Commission. A total of seven compounds, namely, (−)‐gallocatechin, matrine, (−)‐epicatechin, ginkgolide C, ginkgolide A, ginkgolide B, and curdione, have been recommended as the anti‐counterfeiting pharmacopoeia quality markers for Ginkgo Folium tablet. [ABSTRACT FROM AUTHOR]

Ischemic stroke (IS) is a leading cause of morbidity and mortality globally and triggers a series of reactions leading to primary and secondary brain injuries and permanent neurological deficits. Microglia in the central nervous system play dual roles in neuroprotection and responding to ischemic brain damage. Here, an IS model is employed to determine the involvement of microglia in phagocytosis at excitatory synapses. Additionally, the effects of pharmacological depletion of microglia are investigated on improving neurobehavioral outcomes and mitigating brain injury. RNA sequencing of microglia reveals an increase in phagocytosis‐associated pathway activity and gene expression, and C‐type lectin domain family 7 member A (Clec7a) is identified as a key regulator of this process. Manipulating microglial Clec7a expression can potentially regulate microglial phagocytosis of synapses, thereby preventing synaptic loss and improving neurobehavioral outcomes after IS. It is further demonstrat that microglial Clec7a interacts with neuronal myeloid differentiation protein 2 (MD2), a key molecule mediating poststroke neurological injury, and propose the novel hypothesis that MD2 is a ligand for microglial Clec7a. These findings suggest that microglial Clec7a plays a critical role in mediating synaptic phagocytosis in a mouse model of IS, suggesting that Clec7a may be a therapeutic target for IS. [ABSTRACT FROM AUTHOR]