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Background Intracranial atherosclerotic stenosis is a leading cause of ischemic stroke and recurrent events due to plaque instability. High‐resolution magnetic resonance imaging identifies plaque enhancement as a key marker of instability. This study evaluated the efficacy of combined high‐intensity statins and proprotein convertase subtilisin/kexin type 9 inhibitors in plaque stabilization. Methods In this prospective, single‐arm study, patients with acute stroke and intracranial atherosclerotic stroke in the M1 segment of the middle cerebral artery or basilar artery were enrolled. After 24 weeks of intensive statin and evolocumab therapy, high‐resolution magnetic resonance imaging assessments of intracranial vessels were conducted at baseline and follow‐up. The primary end point was the change in stenosis degree; secondary end points included changes in plaque enhancement (contrast ratio) and plaque burden. Results Thirty‐six patients (median age, 58 years) participated. After therapy, stenosis decreased from 75.9% (interquartile range, 69.5%–84.8%) to 65.3% (interquartile range, 53.8%–75.0%; P

Few studies have investigated the properties and protein composition of small extracellular vesicles (sEVs) derived from neurons under hypoxic conditions. Presently, the extent of the involvement of these plentiful sEVs in the onset and progression of ischemic stroke remains an unresolved question. Our study systematically identified the characteristics of sEVs derived from neurons under hypoxic conditions (HypEVs) by physical characterization, sEV absorption, proteomics and transcriptomics analysis. The effects of HypEVs on neurites, cell survival, and neuron structure were assessed in vitro and in vivo by neural complexity tests, magnetic resonance imaging (MRI), Golgi staining, and Western blotting of synaptic plasticity-related proteins and apoptotic proteins. Knockdown of Fused in Sarcoma (FUS) small interfering RNA (siRNA) was used to validate FUS-mediated HypEV neuroprotection and mitochondrial mRNA release. Hypoxia promoted the secretion of sEVs, and HypEVs were more easily taken up and utilized by recipient cells. The MRI results illustrated that the cerebral infarction volume was reduced by 45% with the application of HypEVs, in comparison to the non- HypEV treatment group. Mechanistically, the FUS protein is necessary for the uptake and neuroprotection of HypEVs against ischemic stroke as well as carrying a large amount of mitochondrial mRNA in HypEVs. However, FUS knockdown attenuated the neuroprotective rescue capabilities of HypEVs. Our comprehensive dataset clearly illustrates that FUS-mediated HypEVs deliver exceptional neuroprotective effects against ischemic stroke, primarily through the maintenance of neurite integrity and the reduction of mitochondria-associated apoptosis.

Parkinson's disease (PD) is the second most common neurodegenerative disease, and communication between the gut and brain (the gut-brain axis) has been found to be essential in behavior and cognitive function. However, the exact mechanisms underlying microbiota dysbiosis in PD progression have not yet been elucidated. Our study aimed to investigate the correlation between gut microbiota disturbances and feces metabolic disorders in PD. We used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce PD models and observed mice's motor symptoms, dopaminergic (DA) neuron death, and gastrointestinal dysfunction. To identify alterations in microbiota and metabolome, feces were collected from mice and analyzed using 16 S ribosomal RNA sequencing feces metabolomics. Pearson analysis was utilized to investigate correlations between the abundances of gut microbiota components and the levels of gut microbiota metabolites, displaying their interaction networks. Our findings revealed a significant increase in Desulfobacterota in the PD mouse model and 151 differentially expressed fecal metabolites between PD and vehicle mice. Moreover, Pearson correlation analysis suggested that the protective factor N-acetyl-L-leucine (NALL) may be associated with neuroinflammation in the striatum and substantia nigra, which also had a negative relationship with the concentration of Desulfobacterota. Additionally, we found that oral administration of NALL alleviated MPTP-induced Motor Impairments and DA neuronal deficits. All in all, we concluded that the decrease of NALL might lead to a significant increase of Desulfobacterota in the MPTP model mouse and subsequently result in the damage of DA neurons via the gut-brain aix pathway.

Intracranial atherosclerotic ischemic stroke dramatically impacts the quality of life among the elderly. Statins therapy has been proven to be effective in plaque stabilization and alleviation in patients with intracranial atherosclerotic ischemic stroke. According to recent studies, these effects may be directly related to lipid levels rather than specific lipid-lowering drugs. Anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (PCSK-9 inhibitor) are newer effective lipid-lowering drugs increasingly prescribed to patients at high cardiovascular risk to lower LDL cholesterol. Studies have provided evidence that PCSK9 inhibitor combined with statin therapy can lead to a decrease in the plaque volume measured by intravascular ultrasound in coronary heart disease patients. But the efficacy of combination of the two drugs in symptomatic intracranial artery stenosis has been unknown. Here we provide a case which was reported to suggest that a combination of Evolocumab and intensive statin therapy might reverse or alleviate symptomatic intracranial artery stenosis.

Background: Dl-3-n-Butylphthalide (NBP) has the potential to improve clinical outcomes in acute ischemic stroke patients by improving collateral circulation. We aimed to evaluate the efficacy and safety of NBP in patients with non-disabling minor ischemic stroke and transient ischemic attack (TIA).Methods: The BRIDGE (the observation study on clinical effectiveness of NBP on patients with non-disabling ischemic cerebrovascular disease) is a prospective registry to monitor the efficacy and safety of NBP therapy in acute non-disabling ischemic stroke or high-risk TIA. Non-disabling minor ischemic stroke patients within 48 h were enrolled across 51 stroke centers in China. We divided patients into NBP compliance or non-compliance groups according to their adherence to NBP. The primary outcome was the favorable functional outcome at 90 days, defined as a modified Rankin scale (mRS)

With the aging population, stroke has gradually become the leading cause of death and disability among adults. It is necessary to verify whether multi-delay pseudo-continuous arterial spin labeling (pCASL) MRI can be used as a standard neuroimaging protocol in the patients with ischemic stroke. We aimed to investigate the clinical utility of multi-delay pCASL for evaluating cerebral perfusion in ischemic stroke disease. Twenty-one ischemic stroke patients [18 men and 3 women; median age, 62 years (age range, 37–84 years)] were enrolled in this study. All patients underwent examinations, including the multi-delay pCASL protocol (using 6 PLDs between 1,000 and 3,500 ms) and computed tomography perfusion (CTP). The cerebral blood flow (CBF) and arterial transit time (ATT) maps were obtained by the multi-delay pCASL protocol, while CBF and mean transit time (MTT) maps were derived by CTP measurements. Based on the voxel level analysis, Pearson correlation coefficients were used to estimate the associations between the two modalities in the gray matter, white matter, and whole brain of each subject. Moderate to high positive associations between ASL-CBF and CTP-CBF were acquired by voxel-level-wise analysis in the gray matter, white matter, and whole brain of the enrolled patients (all P < 0.005), and the average Pearson correlation coefficients were 0.647, 0.585, and 0.646, respectively. Highly significant positive correlations between ASL-ATT and CTP-MTT were obtained by voxel-level-wise associations in the gray matter, white matter, and whole brain (all P < 0.005), and the average Pearson correlation coefficients were 0.787, 0.707, and 0.799, respectively. In addition, significant associations between ASL and CT perfusion were obtained in the gray, white matter and whole brain, according to the subgroup analyses of patient’s age and disease stage. There is a correlation between perfusion parameters from multi-delay pCASL and CT perfusion imaging in patients with ischemic stroke. Multi-delay pCASL is radiation-free and non-invasive, and could be an alternative method to CT scans for assessing perfusion in ischemic stroke disease.

Prior studies have shown that patients with minor ischemic stroke have substantial disability rates at hospital discharge. We sought to determine whether blood pressure variability (BPV) estimated by average real variability (ARV) is one of the predictors of poor outcome at 90 days. Four hundred fifty-one consecutive patients with ischemic stroke treated within 7 days after onset were enrolled prospectively. Baseline magnetic resonance imaging (MRI) was performed on all subjects. Blood pressure was measured for all recruited patients every 2 hours in the first 24 hours after admission, followed by measurements collected every 4 hours from day 2 to day 7 after admission. ARV was used to estimate BPV. A total of 192 patients with minor ischemic stroke were enrolled, and 11 of them (5.7%) had poor outcomes. Univariate regression analysis showed that early neurological deterioration (X2 = 21.44, P = 0.000), severe symptomatic large artery stenosis or occlusion (X2 = 9.260, P = 0.000), large artery atherosclerotic stroke (X2 = 7.14, P = 0.002), total cholesterol (TC), and D2-7 SBP-ARV (t = 5.449, P = 0.001) of the poor outcome group were significantly higher than those of the good outcome group. Multivariate logistic regression analysis showed that early neurological deterioration (OR 4.369, 95% CI 3.54, 15.65; P = 0.001), severe symptomatic large artery stenosis or occlusion (OR 5.56, 95% CI 3.56, 13.65; P = 0.000), large artery atherosclerotic stroke (OR 3.56, 95% CI 1.45, 7.48; P = 0.004), and D2-7 SBP-ARV (OR 3.96, 95% CI 1.90, 20.18, P = 0.008) were significantly related to poor outcomes. In conclusion, approximately 5.7% of minor ischemic stroke patients had poor outcomes. D2-7 SBP-ARV, early neurologic deterioration, severe symptomatic artery stenosis or occlusion, and large atherosclerotic stroke were the independent risk factors of poor short-term outcomes.

Organised stroke care has become a keystone in delivering efficient and effective treatment to patients with stroke with improved outcomes. Delivering timely acute reperfusion therapy to those with acute ischaemic strokes is key to good recovery. Emergency stroke unit (ESU) is a novel organised stroke care system developed in China. It centralises all necessary procedures for the diagnosis and treatment of acute stroke into one unit that can perform clinical assessment, imaging examination and acute treatments. In ESU, artificial intelligence algorithms are used to aid in reading brain images and making clinical decisions. Therefore, ESU can significantly enhance the efficiency of emergent stroke care. In this guideline, we aim to clarify the concept, construction standards and personnel requirements of an ESU, standardise ESU-based acute stroke triage and treatment workflow, establish metrics of quality control, facilitate the construction and promotion of ESU and continue the improvement of the quality of stroke care.

Aim Stroke is characterised by high morbidity, mortality and disability, which seriously affects the health and safety of the people. Stroke has become a serious public health problem in China. Organisational stroke management can significantly reduce the mortality and disability rates of patients with stroke. We provide this evidence-based guideline to present current and comprehensive recommendations for organisational stroke management.Methods A formal literature search of MEDLINE (1 January 1997 through 30 September 2019) was performed. Data were synthesised with the use of evidence tables. Writing group members met by teleconference to discuss data-derived recommendations. The Chinese Stroke Association’s Levels of Evidence grading algorithm was used to grade each recommendation.Results Evidence-based guidelines are presented for the organisational management of patients presenting with stroke. The focus of the guideline was subdivided into prehospital first aid system of stroke, rapid diagnosis and treatment of emergency in stroke centre, organisational management of stroke unit and stroke clinic, construction of regional collaborative network among stroke centres and evaluation and continuous improvement of stroke medical quality.Conclusions The guidelines offer an organisational stroke management model for patients with stroke which might help dramatically.

Objective The impact of thrombus migration (TM) prior to endovascular thrombectomy (EVT) on clinical outcomes and revascularisation rates remains unknown. We aimed to examine whether preinterventional TM modifies the treatment effects of direct EVT versus bridging EVT in acute large vessel occlusion patients.Methods All patients undergoing catheter angiography in the Direct Intra-arterial thrombectomy in order to Revascularise acute ischaemic stroke patients with large vessel occlusion Efficiently in Chinese Tertiary hospitals: A Multicentre randomised clinical Trial were included. TM was determined by radiologists unaware of the study by analysing discrepancies between computed tomographic angiography at baseline and first-run digital subtraction angiography before EVT. The primary outcome was the score on the modified Rankin scale (mRS) assessed at 90 days.Results Of 627 included patients, the TM rate was 11.3% (71/627). In the multivariable logistic regression model, baseline National Institutes of Health Stroke Scale score (adjusted OR 0.956, 95% CI 0.916 to 0.999; p=0.043) and intravenous thrombolysis (adjusted OR 2.614, 95% CI 1.514 to 4.514; p

BACKGROUND Tenecteplase is an effective thrombolytic agent for eligible patients with stroke who are treated within 4.5 hours after the onset of stroke. However, data regarding the effectiveness of tenecteplase beyond 4.5 hours are limited. METHODS In a trial conducted in China, we randomly assigned patients with large-vessel occlusion of the middle cerebral artery or internal carotid artery who had salvageable brain tissue as identified on perfusion imaging and who did not have access to endovascular thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or standard medical treatment 4.5 to 24 hours after the time that the patient was last known to be well (including after stroke on awakening and unwitnessed stroke). The primary outcome was the absence of disability, which was defined as a score of 0 or 1 on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability), at day 90. The key safety outcomes were symptomatic intracranial hemorrhage and death. RESULTS A total of 516 patients were enrolled; 264 were randomly assigned to receive tenecteplase and 252 to receive standard medical treatment. Less than 2% of the patients (4 in the tenecteplase group and 5 in the standard-treatment group) underwent rescue endovascular thrombectomy. Treatment with tenecteplase resulted in a higher percentage of patients with a modified Rankin scale score of 0 or 1 at 90 days than standard medical treatment (33.0% vs. 24.2%; relative rate, 1.37; 95% confidence interval, 1.04 to 1.81; P=0.03). Mortality at 90 days was 13.3% with tenecteplase and 13.1% with standard medical treatment, and the incidence of symptomatic intracranial hemorrhage within 36 hours after treatment was 3.0% and 0.8%, respectively. CONCLUSIONS In this trial involving Chinese patients with ischemic stroke due to large-vessel occlusion, most of whom did not undergo endovascular thrombectomy, treatment with tenecteplase administered 4.5 to 24 hours after stroke onset resulted in less disability and similar survival as compared with standard medical treatment, and the incidence of symptomatic intracranial hemorrhage appeared to be higher. [ABSTRACT FROM AUTHOR]