Trial of Thrombectomy for Stroke with a Large Infarct of Unrestricted Size.

BACKGROUND: The use of thrombectomy in patients with acute stroke and a large infarct of unrestricted size has not been well studied. METHODS: We assigned, in a 1:1 ratio, patients with proximal cerebral vessel occlusion in the anterior circulation and a large infarct (as defined by an Alberta Stroke Program Early Computed Tomographic Score of ≤5; values range from 0 to 10) detected on magnetic resonance imaging or computed tomography within 6.5 hours after symptom onset to undergo endovascular thrombectomy and receive medical care (thrombectomy group) or to receive medical care alone (control group). The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability). The primary safety outcome was death from any cause at 90 days, and an ancillary safety outcome was symptomatic intracerebral hemorrhage. RESULTS: A total of 333 patients were assigned to either the thrombectomy group (166 patients) or the control group (167 patients); 9 were excluded from the analysis because of consent withdrawal or legal reasons. The trial was stopped early because results of similar trials favored thrombectomy. Approximately 35% of the patients received thrombolysis therapy. The median modified Rankin scale score at 90 days was 4 in the thrombectomy group and 6 in the control group (generalized odds ratio, 1.63; 95% confidence interval [CI], 1.29 to 2.06; P<0.001). Death from any cause at 90 days occurred in 36.1% of the patients in the thrombectomy group and in 55.5% of those in the control group (adjusted relative risk, 0.65; 95% CI, 0.50 to 0.84), and the percentage of patients with symptomatic intracerebral hemorrhage was 9.6% and 5.7%, respectively (adjusted relative risk, 1.73; 95% CI, 0.78 to 4.68). Eleven procedure-related complications occurred in the thrombectomy group. CONCLUSIONS: In patients with acute stroke and a large infarct of unrestricted size, thrombectomy plus medical care resulted in better functional outcomes and lower mortality than medical care alone but led to a higher incidence of symptomatic intracerebral hemorrhage. (Funded by Montpellier University Hospital; LASTE ClinicalTrials.gov number, NCT03811769.).

Silent brain infarctions in patients with acute cardioembolic stroke.

INTRODUCTION AND AIM: The advances and the wide use of brain imaging have considerably increased the prevalence of silent brain infarctions (SBI). We aim in this study to determine the prevalence of SBI in patients presenting with acute cardioembolic stroke and the predictive cardiovascular risk factors. METHODS: This retrospective study included 267 patients presenting with acute cardioembolic stroke in the emergency and/or neurology departments of the Hassan II University Hospital Center. Clinical, biological and echocardiographic characteristics were recorded. All patients were screened for SBI by brain imaging. RESULTS: The prevalence of SBI in our series was 46%. A group of 203 non-valvular patients and a group of 64 valvular patients were distinguished. In non-valvular group, the average age was 72.97±10.53years. The prevalence of SBI was 45.3%. Forty-four percent of patients with SBI had atrial fibrillation (AF). In multivariate regression analysis, the history of previous stroke, CHA2DS2-VASc Score≥4, enlarged left atrium (LA), the association of AF with enlarged LA and the lability of International Normalized Ratio in patients initially treated with anticoagulants were significantly associated with the occurrence of SBI (P=0.013, P=0.032, P=0.0001, P=0.01, P=0.03, respectively). Territorial location was significantly the most frequent (P=0.007). In valvular group, the average age was 57.19±14.38years. The prevalence of SBI was 48.4%. In multivariate regression analysis, SBI were significantly associated with moderate or severe mitral stenosis (P=0.02) and with the enlarged LA (P=0.02). In all patients, Modified Rankin Scale at 3 months of discharge from the acute stroke was significantly higher (mRS≥3) in patients with SBI (P=0.04). CONCLUSIONS: SBI requires good management of associated cardiovascular risk factors in a population presenting with initial cardioembolic stroke.

Estimation of prognosis in patients after decompressive craniectomy after malignant hemispheric infarction: multifactorial scoring scale.

BACKGROUND: Patient's age is considered to be one of the most relevant factors in selecting surgical candidates for decompressive hemicraniectomy after malignant hemispheric infarction. However, questions about surgical indication in older patients, patients with consciousness disorder or patients with large infarctions remain unanswered. OBJECTIVE: Our aim was to design a multifactorial scoring scale based on a combination of patient-specific factors in order to optimize the assessment of prognosis in patients after hemicraniectomy malignant strokes. METHODS: In this prospective observational study with a one-year follow-up, we assessed clinical and imaging data of patients who underwent decompressive hemicraniectomy due to malignant brain infarction. Barthel index was used as a single outcome measure to distinguish favorable vs. unfavorable outcomes. Associations between multiple variables and clinical outcome were assessed. Subsequently, a design of a predictive scoring system was proposed. RESULTS: Age of the patient, preoperative level of consciousness, midline shift, and volume of infarction showed a significant association with postoperative Barthel index. According to the identified factors, a multifactorial prognostic scoring system was introduced, aimed to distinguish between favorable and unfavorable outcomes. Using ROC analysis, it has achieved an AUC of 0.74 (95%CI 0.58‒0.89, p=0.01)CONCLUSIONS: Prediction of postoperative outcome should be based on multiple variables. Our scale, based on the clinical and imaging data, can be used during decision-making to estimate potential benefit of decompressive craniectomy in patients after malignant brain infarction (Tab. 5, Fig. 1, Ref. 32). Text in PDF www.elis.sk Keywords: decompressive hemicraniectomy, malignant hemispheric infarction, indication, outcome, prediction.

Acute multiple brain infarctions associated with Streptococcus suis infection: a case report.

Streptococcus suis is one of the most common zoonotic pathogens, in humans and can cause meningitis, endocarditis, arthritis and sepsis. Human cases of Streptococcus suis infection have been reported worldwide, and most of those cases occurred in Asia. Hearing loss is the most common sequela of Streptococcus suis meningitis. Streptococcus suis infection complicated with acute cerebral infarction has rarely been reported. Therefore, to provide a reference for this disease, we reported a case of acute multiple brain infarctions associated with Streptococcus suis infection. In our report, a 69yearold male patient had Streptococcus suis meningitis and sepsis, which were associated with multiple acute cerebral infarctions in the pons and bilateral frontotemporal parietal occipital lobes. After treatment, the patient exhibited cognitive impairment, dyspraxia and irritability. There are limited case reports of cerebral infarction associated with Streptococcus suis infection, and further research is needed to determine the best treatment method.

Impact of serum leptin and adiponectin levels on brain infarcts in patients with mild cognitive impairment and Alzheimer's disease: a longitudinal analysis.

Introduction: The adipokines leptin and adiponectin have been associated with atherosclerosis and the risk of cerebral infarcts. Pre-clinical studies, however, suggest a protective role against ischemic brain damage. In this study we analyzed the relationship between serum leptin and adiponectin levels and the onset or progression of brain infarcts in subjects with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Methods: All data were extracted from the ADNI database. The final population included 566 subjects, with 58 healthy controls, 396 MCI and 112 AD. All patients with available serum leptin and adiponectin levels at baseline were selected. Demographics, neuropsychological test results, CSF biomarkers, regional brain metabolism with FDG-PET data and the number of brain infarcts on longitudinal MRI scans were extracted. Results: Leptin levels were significantly lower in patients with MCI than controls at baseline, while adiponectin levels were not different between the groups. Multivariate logistic regression analysis at baseline for the presence of brain infarcts showed a predictive value for leptin but not for adiponectin. Multivariate longitudinal analysis showed that age was the only significant predictor of brain infarcts development at 15-year follow-up, while serum leptin and adiponectin levels did not play a role in this population. Discussion: The evidence on the pathogenetic or protective role of adipokines on ischemic brain damage is mixed. In this MCI and AD population, serum leptin and adiponectin were not associated with the development of brain infarcts; therefore, these results do not support the use of adipokines as biomarkers of cerebrovascular pathology in this population.

Covert Cerebrovascular Changes in People With Heart Disease: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: To determine the prevalence of silent brain infarction (SBI) and cerebral small vessel disease (CSVD) in adults with atrial fibrillation (AF), coronary artery disease, heart failure or cardiomyopathy, heart valve disease, and patent foramen ovale (PFO), with comparisons between those with and without recent stroke and an exploration of associations between heart disease and SBI/CSVD. METHODS: Medline, Embase, and Cochrane Library were systematically searched for hospital-based or community-based studies reporting SBI/CSVD in people with heart disease. Data were extracted from eligible studies. Outcomes were SBI (primary) and individual CSVD subtypes. Summary prevalence (95% confidence intervals [CIs]) were obtained using random-effects meta-analysis. Pooled prevalence ratios (PRs) (95% CI) were calculated to compare those with heart disease with available control participants without heart disease from studies. RESULTS: A total of 221 observational studies were included. In those with AF, the prevalence was 36% (31%-41%) for SBI (70 studies, N = 13,589), 25% (19%-31%) for lacune (26 studies, N = 7,172), 62% (49%-74%) for white matter hyperintensity/hypoattenuation (WMH) (34 studies, N = 7,229), and 27% (24%-30%) for microbleed (44 studies, N = 13,654). Stratification by studies where participants with recent stroke were recruited identified no differences in the prevalence of SBI across subgroups (phomogeneity = 0.495). Results were comparable across participants with different heart diseases except for those with PFO, in whom there was a lower prevalence of SBI [21% (13%-30%), 11 studies, N = 1,053] and CSVD. Meta-regressions after pooling those with any heart disease identified associations of increased (study level) age and hypertensives with more SBIs and WMH (pregression <0.05). There was no evidence of a difference in the prevalence of microbleed between those with and without heart disease (PR [95% CI] 1.1 [0.7-1.7]), but a difference was seen in the prevalence of SBI and WMH (PR [95% CI] 2.3 [1.6-3.1] and 1.7 [1.1-2.6], respectively). DISCUSSION: People with heart disease have a high prevalence of SBI (and CSVD), which is similar in those with vs without recent stroke. More research is required to assess causal links and implications for management. TRIAL REGISTRATION INFORMATION: PROSPERO CRD42022378272 (crd.york.ac.uk/PROSPERO/).

Intensive Blood Pressure Treatment and Subclinical Brain Infarcts: A Secondary Analysis of SPRINT (Systolic Pressure Intervention Trial).

OBJECTIVE: Subclinical brain infarcts (SBI) increase the risk for stroke and dementia, but whether they should be considered equivalent to symptomatic stroke when determining blood pressure targets remains unclear. We tested whether intensive systolic blood pressure (SBP) treatment reduced the risk of new SBI or stroke and determined the association between SBI and cognitive impairment. METHODS: In this secondary analysis of SPRINT (Systolic Pressure Intervention Trial), participants ≥50 years old, with SBP 130-180mmHg and elevated cardiovascular risk but without known clinical stroke, dementia, or diabetes, were randomized to intensive (<120mmHg) or standard (<140mmHg) SBP treatment. Brain magnetic resonance images collected at baseline and follow-up were read for SBI. The occurrence of mild cognitive impairment (MCI) or probable dementia (PD) was evaluated. RESULTS: For 667 participants at baseline, SBI were identified in 75 (11%). At median 3.9 years follow-up, 12 of 457 had new SBI on magnetic resonance imaging (5 intensive, 7 standard), whereas 8 had clinical stroke (4 per group). Baseline SBI (subhazard ratio [sHR] = 3.90; 95% CI 1.49 to 10.24; p = 0.006), but not treatment group, was associated with new SBI or stroke. For participants with baseline SBI, intensive treatment reduced their risk for recurrent SBI or stroke (sHR = 0.050; 95% CI 0.0031 to 0.79; p = 0.033). Baseline SBI also increased risk for MCI or PD during follow-up (sHR = 2.38; 95% CI 1.23 to 4.61; p = 0.010). INTERPRETATION: New cerebral ischemic events were infrequent, but intensive treatment mitigated the increased risk for participants with baseline SBI, indicating primary prevention SBP goals are still appropriate when SBI are present. ANN NEUROL 2024;95:866-875.

Internuclear ophthalmoplegia as a presentation of procedural stroke: a case report.

BACKGROUND: Cardiac catheterization and endovascular procedures are extensively used in modern medicine, and procedural stroke is one of the major complications that the catheterization laboratory team may face in their everyday work. Recognizing the signs and symptoms of procedural stroke is crucial to ensuring appropriate management. We herein report a case of internuclear ophthalmoplegia that caused blurred vision, diplopia, and dizziness on lateral gaze as an unusual presentation of procedural stroke. CASE PRESENTATION: A 60-year-old Thai woman underwent right partial colectomy and was diagnosed with stage IV diffuse large B-cell lymphoma. Pre-chemotherapy echocardiography revealed mild left ventricular systolic dysfunction, and she therefore underwent diagnostic catheterization. Coronary angiography revealed normal coronary arteries, leading to a diagnosis of non-ischemic cardiomyopathy. After the procedure, she immediately developed dizziness and diplopia. During the right lateral gaze, she exhibited impaired adduction of the left eye and horizontal nystagmus of the right eye. A diagnosis of left internuclear ophthalmoplegia was made. Magnetic resonance imaging revealed a tiny area exhibiting characteristics of an acute infarct in the left paramedian midbrain, including the left medial longitudinal fasciculus, which explained the clinical picture. Another region of restricted diffusion indicating an acute infarct was detected in the right inferior cerebellar hemisphere. Magnetic resonance angiography revealed no significant cerebral artery disease. The patient achieved full neurological recovery 6 weeks after symptom onset. CONCLUSION: This report describes an uncommon presentation of procedural stroke that is likely to be misdiagnosed, especially by medical staff unfamiliar with internuclear ophthalmoplegia. Despite the good prognosis of internuclear ophthalmoplegia, appropriate stroke care is crucial in patients with procedural stroke because of the risk of multiple brain infarcts.

Association of covert brain infarct phenotype with stroke recurrence in first-ever manifest ischemic stroke according to etiology.

INTRODUCTION: Covert brain infarcts (CBI) are frequent incidental findings on MRI and associated with future stroke risk in patients without a history of clinically evident cerebrovascular events. However, the prognostic value of CBI in first-ever ischemic stroke patients is unclear and previous studies did not report on different etiological stroke subtypes. We aimed to test CBI phenotypes and their association with stroke recurrence in first-ever ischemic stroke patients according to stroke etiology. PATIENTS AND METHODS: This study is a pooled data analysis of two prospectively collected cohorts of consecutive first-ever ischemic stroke patients admitted to the comprehensive stroke centers of Bern (Switzerland) and Graz (Austria). CBI phenotypes were identified on brain MRI within 72 h after admission. All patients underwent a routine follow-up (median: 12 months) to identify stroke recurrence. RESULTS: Of 1577 consecutive ischemic stroke patients (median age: 71 years), 691 patients showed CBI on brain MRI (44%) and 88 patients had a recurrent ischemic stroke (6%). Baseline CBI were associated with stroke recurrence in multivariable analysis (HR 1.9, 95% CI 1.1-3.3). CBI phenotypes with the highest risk for stroke recurrence were cavitatory CBI in small vessel disease (SVD)-related stroke (HR 7.1, 95% CI 1.6-12.6) and cortical CBI in patients with atrial fibrillation (HR 3.0, 95% CI 1.1-8.1). DISCUSSION AND CONCLUSION: This study reports a ≈ 2-fold increased risk for stroke recurrence in first-ever ischemic stroke patients with CBI. The risk of recurrent stroke was highest in patients with cavitatory CBI in SVD-related stroke and cortical CBI in patients with atrial fibrillation.Subject terms: Covert brain infarcts, stroke.

Deep learning reconstruction for improving the visualization of acute brain infarct on computed tomography.

PURPOSE: This study aimed to investigate the impact of deep learning reconstruction (DLR) on acute infarct depiction compared with hybrid iterative reconstruction (Hybrid IR). METHODS: This retrospective study included 29 (75.8 ± 13.2 years, 20 males) and 26 (64.4 ± 12.4 years, 18 males) patients with and without acute infarction, respectively. Unenhanced head CT images were reconstructed with DLR and Hybrid IR. In qualitative analyses, three readers evaluated the conspicuity of lesions based on five regions and image quality. A radiologist placed regions of interest on the lateral ventricle, putamen, and white matter in quantitative analyses, and the standard deviation of CT attenuation (i.e., quantitative image noise) was recorded. RESULTS: Conspicuity of acute infarct in DLR was superior to that in Hybrid IR, and a statistically significant difference was observed for two readers (p ≤ 0.038). Conspicuity of acute infarct with time from onset to CT imaging at < 24 h in DLR was significantly improved compared with Hybrid IR for all readers (p ≤ 0.020). Image noise in DLR was significantly reduced compared with Hybrid IR with both the qualitative and quantitative analyses (p < 0.001 for all). CONCLUSION: DLR in head CT helped improve acute infarct depiction, especially those with time from onset to CT imaging at < 24 h.

Transcranial Doppler Ultrasonography detection on cerebral infarction and blood vessels to evaluate hypoxic ischemic encephalopathy modeling.

BACKGROUND: This study aimed to observe changes of rats' brain infarction and blood vessels during neonatal hypoxic ischemic encephalopathy (NHIE) modeling by Transcranial Doppler Ultrasonography (TCD) so as to assess the feasibility of TCD in evaluating NHIE modeling. METHODS: Postnatal 7-days (d)-old Sprague Dawley (SD) rats were divided into the Sham group, hypoxic-ischemic (HI) group, and hypoxia (H) group. Rats in the HI group and H group were subjected to hypoxia-1 hour (h), 1.5 h and 2.5 h, respectively. Evaluation on brain lesion was made based on Zea-Longa scores, hematoxylin-eosin (HE) staining and Nissl staining. The brain infarction and blood vessels of rats were monitored and analyzed under TCD. Correlation analysis was applied to reveal the connection between hypoxic duration and infarct size detected by TCD or Nissl staining. RESULTS: In H and HI modeling, longer duration of hypoxia was associated with higher Zea-Longa scores and more severe nerve damage. On the 1 d after modeling, necrosis was found in SD rats' brain indicated by HE and Nissl staining, which was aggravated as hypoxic duration prolonged. Alteration of brain structures and blood vessels of SD rats was displayed in Sham, HI and H rats under TCD. TCD images for coronal section revealed that brain infarct was detected at the cortex and there was marked cerebrovascular back-flow of HI rats regardless of hypoxic duration. On the 7 d after modeling, similar infarct was detected under TCD at the cortex of HI rats in hypoxia-1 h, 1.5 h and 2.5 h groups, whereas the morphological changes were deteriorated with longer hypoxic time. Correlation analysis revealed positive correlation of hypoxic duration with infarct size detected by histological detection and TCD. CONCLUSIONS: TCD dynamically monitored cerebral infarction after NHIE modeling, which will be potentially served as a useful auxiliary method for future animal experimental modeling evaluation in the case of less animal sacrifice.

Spatiotemporal expression patterns of ZBP1 in the brain of mouse experimental stroke model.

Z-DNA binding protein 1 (ZBP1) is a cytosolic nucleic acid sensor, functioning as a critical mediator of inflammation and cell death pathways. Since neuroinflammation could occur in response to damage-associated molecular patterns (DAMPs), ZBP1 might be involved in neuroinflammation after stroke. However, the spatiotemporal expression profile of ZBP1 in the post-stroke brain remains to be elucidated. The aim of this study is to demonstrate the spatiotemporal expression patterns of ZBP1 in the post-stroke brain using a mouse photothrombotic stroke model. Real-time PCR assays showed that ZBP1 is induced on days 3-14 post stroke. ZBP1 immunoreactivity was observed in Iba1-positive microglia/macrophages in peri-infarct regions by immunohistochemistry. ZBP1-positive cells were spread in layers surrounding the infarct core by 7-14 days post stroke. Interestingly, ZBP1 immunoreactivity was also detected in CD206-positive border-associated macrophages (BAMs) in the meninges. Furthermore, ZBP1-expressing cells were positive for antibodies against inflammatory mediators such as Toll-like receptor 4 (TLR4), Toll/IL-1R domain-containing adaptor-inducing IFN-ß (TRIF), and receptor-interacting serine/threonine-protein kinase 1 (RIPK1). Morphological analysis with confocal microscopy showed that the co-localization signals of ZBP1 and its adaptor, TRIF, are increased by glucose oxidase (GOx) treatment, which has been reported to induce mitochondrial DNA (mtDNA) release. These results suggest that ZBP1 is induced in peri-infarct microglia/macrophages and may be involved in DAMPs-mediated neuroinflammation involving mtDNA in the post-infarct brain.

Definition, prediction, prevention and management of patients with severe ischemic stroke and large infarction.

ABSTRACT: Severe ischemic stroke carries a high rate of disability and death. The severity of stroke is often assessed by the degree of neurological deficits or the extent of brain infarct, defined as severe stroke and large infarction, respectively. Critically severe stroke is a life-threatening condition that requires neurocritical care or neurosurgical intervention, which includes stroke with malignant brain edema, a leading cause of death during the acute phase, and stroke with severe complications of other vital systems. Early prediction of high-risk patients with critically severe stroke would inform early prevention and treatment to interrupt the malignant course to fatal status. Selected patients with severe stroke could benefit from intravenous thrombolysis and endovascular treatment in improving functional outcome. There is insufficient evidence to inform dual antiplatelet therapy and the timing of anticoagulation initiation after severe stroke. Decompressive hemicraniectomy (DHC) <48 h improves survival in patients aged <60 years with large hemispheric infarction. Studies are ongoing to provide evidence to inform more precise prediction of malignant brain edema, optimal indications for acute reperfusion therapies and neurosurgery, and the individualized management of complications and secondary prevention. We present an evidence-based review for severe ischemic stroke, with the aims of proposing operational definitions, emphasizing the importance of early prediction and prevention of the evolution to critically severe status, summarizing specialized treatment for severe stroke, and proposing directions for future research.

Neuroprotective Action of Tacrolimus before and after Onset of Neonatal Hypoxic-Ischaemic Brain Injury in Rats.

(1) Background: Neonatal brain injury can lead to permanent neurodevelopmental impairments. Notably, suppressing inflammatory pathways may reduce damage. To determine the role of neuroinflammation in the progression of neonatal brain injury, we investigated the effect of treating neonatal rat pups with the immunosuppressant tacrolimus at two time points: before and after hypoxic-ischaemic (HI)-induced injury. (2) Methods: To induce HI injury, postnatal day (PND) 10 rat pups underwent single carotid artery ligation followed by hypoxia (8% oxygen, 90 min). Pups received daily tacrolimus (or a vehicle) starting either 3 days before HI on PND 7 (pre-HI), or 12 h after HI (post-HI). Four doses were tested: 0.025, 0.05, 0.1 or 0.25 mg/kg/day. Pups were euthanised at PND 17 or PND 50. (3) Results: All tacrolimus doses administered pre-HI significantly reduced brain infarct size and neuronal loss, increased the number of resting microglia and reduced cellular apoptosis (p < 0.05 compared to control). In contrast, only the highest dose of tacrolimus administered post-HI (0.25 mg/kg/day) reduced brain infarct size (p < 0.05). All doses of tacrolimus reduced pup weight compared to the controls. (4) Conclusions: Tacrolimus administration 3 days pre-HI was neuroprotective, likely mediated through neuroinflammatory and cell death pathways. Tacrolimus post-HI may have limited capacity to reduce brain injury, with higher doses increasing rat pup mortality. This work highlights the benefits of targeting neuroinflammation during the acute injurious period. More specific targeting of neuroinflammation, e.g., via T-cells, warrants further investigation.

Rationale and design of a randomized clinical trial evaluating the efficacy of mechanical neuroprotection in reducing the risk of silent brain infarcts associated with percutaneous left atrial appendage closure: study protocol for a LAAC-SBI trial.

BACKGROUND: Left atrial appendage closure (LAAC) procedures prevent cardioembolic stroke in patients with atrial fibrillation who have contraindications to oral anticoagulant medications. However, these procedures carry certain risks of peri-procedural complications. One such complication is silent brain infarcts (SBI), which can lead to cognitive impairment and mood disturbances. The implementation of mechanical neuroprotection systems during LAAC procedures may reduce the risk of SBI and associated cognitive and mood disorders. METHODS: The LAAC-SBI trial is a prospective, multicenter, randomized, and double-blind interventional study. The study aims to enroll a total of 240 patients, with 120 patients allocated to each group. The study group will evaluate the use of the Sentinel CPS during LAAC, while the control group will undergo LAAC procedures without the Sentinel CPS. The primary endpoint of the study is the number of new SBIs or stroke foci detected by diffusion-weighted magnetic resonance imaging (DW MRI). Secondary endpoints include deterioration of cognitive function, development of dementia syndrome, and occurrence of depressive disorders. These endpoints will be assessed using questionnaire tools such as the Montreal Cognitive Assessment (MoCA), Trail Making Test (TMT), Controlled Oral Word Association Test (COWAT), and Hospital Anxiety and Depression Scale (HADS). The observational period for patients in the study is 2 years. DISCUSSION: If the study demonstrates a favorable outcome with reduced incidence of SBI and improved cognitive and mood outcomes in patients receiving cerebral protection devices during LAAC, it will have significant implications for clinical management standards. This would support the use of neuroprotection devices not only for LAAC but also in procedures such as atrial fibrillation ablation or transcatheter mitral valve interventions, where the risk of embolic events and subsequent brain injury may also be present. TRIAL REGISTRATION: ClinicalTrials.gov NCT05369195. Registration on 11.05.2022.

Knockout of Rnf213 Ameliorates Cerebral Ischemic-reperfusion Injury by Inhibiting Neuronal Apoptosis Through the Akt/GSK-3ß/ß-catenin/Bcl-2 Pathway.

Previous studies by us and others have shown that RING finger protein 213 (RNF213) is associated with cerebrovascular disease and systemic vasculopathy. Indeed, Rnf213 mRNA expression is increased in cerebral ischemia reperfusion injury (CIRI). The purpose of the present study was to investigate the role of Rnf213 in CIRI. Using the middle cerebral artery occlusion (MCAO) model, we confirmed that the expression of RNF213 protein was significantly upregulated in neurons in the ischemic penumbra. Rnf213 knockout mice were successfully generated using CRISPR/Cas9 technology. According to TTC staining and Bederson neurological scale, removal of Rnf213 decreased brain infarct volume and improved neurological deficit score, although the restoration of cerebral blood flow after MCAO was similar in WT and Rnf213-/- mice. In addition, the levels of p-Akt, p-GSK-3ß, ß-catenin and Bcl-2 were significantly increased 24 h after MCAO in the ischemic penumbra of the Rnf213-/- mice compared to WT mice, indicating that Rnf213 removal may ameliorate neuronal apoptosis by regulating the Akt/GSK-3ß/ß-catenin/Bcl-2 signaling pathway. Taken together, our study reveals that Rnf213 regulates neuronal apoptosis in CIRI, therefore impacting on brain infarct volume in brain ischemia.

PFT-α protects the blood-brain barrier through the Wnt/ß-catenin pathway after acute ischemic stroke.

The dysfunction of blood-brain barrier (BBB) plays a pivotal role in brain injury and subsequent neurological deficits of ischemic stroke. The current study aimed to examine the potential correlation between p53 inhibition and the neuroprotective effect of on the BBB. Rat middle cerebral artery occlusion and reperfusion model (MCAO/R) and oxygen-glucose deprivation/re-oxygenation model (OGD/R) were employed to simulate cerebral ischemia-reperfusion (CI/R) injury occurrence in vivo and in vitro. mNSS and TTC staining were applied to evaluate neurological deficits and brain infarct volumes. Evans blue (EB) staining was carried out to examine the permeability of BBB. RT-qPCR and Western blot to examine the mRNA and protein levels. Cell viabilities were detected by CCK-8. Flow cytometry and ELISA assay were employed to examine apoptosis and neuroinflammation levels. TEER value and sodium fluorescein were carried out to explore the permeability of HBMEC cells. PFT-α inhibited P53 and promoted the expression of ß-catenin and cyclin D1, which were reversed by DKK1. PFT-α inhibited neurological deficits, brain infarct volume, neuroinflammation, apoptosis, and BBB integrity than the MCAO/R rats; however, this inhibition was reversed by DKK1. PFT-α promoted OGD/R-induced cell viability in NSCs, and suppressed inflammation and apoptosis, but DKK1 weakened the effect of PFT-α. PFT-α increased OGD/R-induced TEER values in cerebrovascular endothelial cells, inhibited sodium fluorescein permeability, and increased the mRNA levels of tight junction protein, but they were all attenuated by DKK1. PFT-α protects the BBB after acute ischemic stroke via the Wnt/ß-catenin pathway, which in turn improves neurological function.

Blood Pressure Management After Endovascular Therapy for Acute Ischemic Stroke: The BEST-II Randomized Clinical Trial.

Importance: The effects of moderate systolic blood pressure (SBP) lowering after successful recanalization with endovascular therapy for acute ischemic stroke are uncertain. Objective: To determine the futility of lower SBP targets after endovascular therapy (<140 mm Hg or 160 mm Hg) compared with a higher target (≤180 mm Hg). Design, Setting, and Participants: Randomized, open-label, blinded end point, phase 2, futility clinical trial that enrolled 120 patients with acute ischemic stroke who had undergone successful endovascular therapy at 3 US comprehensive stroke centers from January 2020 to March 2022 (final follow-up, June 2022). Intervention: After undergoing endovascular therapy, participants were randomized to 1 of 3 SBP targets: 40 to less than 140 mm Hg, 40 to less than 160 mm Hg, and 40 to 180 mm Hg or less (guideline recommended) group, initiated within 60 minutes of recanalization and maintained for 24 hours. Main Outcomes and Measures: Prespecified multiple primary outcomes for the primary futility analysis were follow-up infarct volume measured at 36 (±12) hours and utility-weighted modified Rankin Scale (mRS) score (range, 0 [worst] to 1 [best]) at 90 (±14) days. Linear regression models were used to test the harm-futility boundaries of a 10-mL increase (slope of 0.5) in the follow-up infarct volume or a 0.10 decrease (slope of -0.005) in the utility-weighted mRS score with each 20-mm Hg SBP target reduction after endovascular therapy (1-sided α = .05). Additional prespecified futility criterion was a less than 25% predicted probability of success for a future 2-group, superiority trial comparing SBP targets of the low- and mid-thresholds with the high-threshold (maximum sample size, 1500 with respect to the utility-weighted mRS score outcome). Results: Among 120 patients randomized (mean [SD] age, 69.6 [14.5] years; 69 females [58%]), 113 (94.2%) completed the trial. The mean follow-up infarct volume was 32.4 mL (95% CI, 18.0 to 46.7 mL) for the less than 140-mm Hg group, 50.7 mL (95% CI, 33.7 to 67.7 mL), for the less than 160-mm Hg group, and 46.4 mL (95% CI, 24.5 to 68.2 mL) for the 180-mm Hg or less group. The mean utility-weighted mRS score was 0.51 (95% CI, 0.38 to 0.63) for the less than 140-mm Hg group, 0.47 (95% CI, 0.35 to 0.60) for the less than 160-mm Hg group, and 0.58 (95% CI, 0.46 to 0.71) for the high-target group. The slope of the follow-up infarct volume for each mm Hg decrease in the SBP target, adjusted for the baseline Alberta Stroke Program Early CT score, was -0.29 (95% CI, -0.81 to ∞; futility P = .99). The slope of the utility-weighted mRS score for each mm Hg decrease in the SBP target after endovascular therapy, adjusted for baseline utility-weighted mRS score, was -0.0019 (95% CI, -∞ to 0.0017; futility P = .93). Comparing the high-target SBP group with the lower-target groups, the predicted probability of success for a future trial was 25% for the less than 140-mm Hg group and 14% for the 160-mm Hg group. Conclusions and Relevance: Among patients with acute ischemic stroke, lower SBP targets less than either 140 mm Hg or 160 mm Hg after successful endovascular therapy did not meet prespecified criteria for futility compared with an SBP target of 180 mm Hg or less. However, the findings suggested a low probability of benefit from lower SBP targets after endovascular therapy if tested in a future larger trial. Trial Registration: ClinicalTrials.gov Identifier: NCT04116112.

[Effects of simultaneous use of Cerebrolysin and alteplase on hemorrhagic transformation of brain infarction and functional outcome in stroke patients: CEREHETIS, a randomized, multicenter pilot trial]. / Effekty sovmestnogo primeneniya Tserebrolizina i alteplazy na gemorragicheskuyu transformatsiyu infarkta mozga i funktsional'nyi iskhod u bol'nykh ishemicheskim insul'tom: pilotnoe randomizirovannoe mnogotsentrovoe klinicheskoe issledovanie CEREHETIS.

OBJECTIVE: The study aimed to assess effects of the simultaneous use of Cerebrolysin and intravenous thrombolysis (Alteplase) on hemorrhagic transformation (HT) and functional outcome as well as to analyze the treatment safety in acute stroke patients. MATERIAL AND METHODS: It was a prospective, randomized, open-label, multicenter, parallel-group, active-controlled pilot study (Trial Registration Number: ISRCTN87656744, https://doi.org/10.1186/ISRCTN87656744, Trial registration date: 16/02/2021). The intervention group (n=126) was treated with Cerebrolysin infusion (30 mL) started simultaneously with Alteplase (0.9 mg/kg) via a separate IV line. The Cerebrolysin treatment continued for 14 consecutive days with the baseline therapy along. The control group (n=215) received only Alteplase and the baseline therapy. The primary endpoints were the rate of any and symptomatic hemorrhagic transformation (HT) from admission to day 14. Secondary endpoints were treatment safety and functional outcome measured with the National Institutes of Health stroke scale (NIHSS) in 24 h and on day 14, and with the modified Rankin scale (mRS) on day 90. RESULTS: Treatment with Cerebrolysin resulted in a significant reduction of the symptomatic HT rate with an odds ratio of 0.248 (95% CI: 0.072-0.851; p=0.019). No serious adverse events related to Cerebrolysin were observed. On day 14, the intervention group showed a significant reduction in the NIHSS score (p=0.045). However, no difference in the mRS score was observed on day 90, but there was a trend towards its improvement. CONCLUSION: The combination of Cerebrolysin and Alteplase was safe and significantly reduced the rate of symptomatic HT and improved early neurological deficit. However, no difference in functional outcome was found on day 90, but there was a trend towards favorable functional outcome.