Therapy For Acute Ischemic Stroke Research Articles

Cerebral Collateral Circulation in the Era of Reperfusion Therapies for Acute Ischemic Stroke.

Clinical outcomes of patients with acute ischemic stroke depend in part on the extent of their collateral circulation. A good collateral circulation has also been associated with greater benefit of intravenous thrombolysis and endovascular treatment. Treatment decisions for these reperfusion therapies are increasingly guided by a combination of clinical and imaging parameters, particularly in later time windows. Computed tomography and magnetic resonance imaging enable a rapid assessment of both the collateral extent and cerebral perfusion. Yet, the role of the collateral circulation in clinical decision-making is currently limited and may be underappreciated due to the use of rather coarse and rater-dependent grading methods. In this review, we discuss determinants of the collateral circulation in patients with acute ischemic stroke, report on commonly used and emerging neuroimaging techniques for assessing the collateral circulation, and discuss the therapeutic and prognostic implications of the collateral circulation in relation to reperfusion therapies for acute ischemic stroke.

The application and perspective of hyperbaric oxygen therapy in acute ischemic stroke: From the bench to a starter?

Stroke has become a significant cause of death and disability globally. Along with the transition of the world's aging population, the incidence of acute ischemic stroke is increasing year by year. Even with effective treatment modalities, patients are not guaranteed to have a good prognosis. The treatment model combining intravenous thrombolysis/endovascular therapy and neuroprotection is gradually being recognized. After the clinical translation of pharmacological neuroprotective agents failed, non-pharmacological physical neuroprotective agents have rekindled hope. We performed a literature review using the National Center for Biotechnology Information (NCBI) PubMed database for studies that focused on the application of hyperbaric oxygen therapy in acute ischemic stroke. In this review, we present the history and mechanisms of hyperbaric oxygen therapy, focusing on the current status, outcomes, current challenges, perspective, safety, and complications of the application of hyperbaric oxygen in animal experiments and human clinical trials. Hyperbaric oxygen therapy, a non-pharmacological treatment, can improve the oxygenation level at the ischemic lesions in increased dissolved oxygen and oxygen diffusion radius to achieve salvage of neurological function, giving a new meaning to acute ischemic stroke.

Timing of symptomatic intracranial hemorrhage after endovascular stroke treatment.

Little is known about the timing of occurrence of symptomatic intracranial hemorrhage (sICH) after endovascular therapy (EVT) for acute ischemic stroke. A better understanding could optimize in-hospital surveillance time points and duration. The aim of this study was to delineate the probability of sICH over time and to identify factors associated with its timing. We retrospectively analyzed data from the Dutch MR CLEAN trial and MR CLEAN Registry. We included adult patients who underwent EVT for an anterior circulation large vessel occlusion within 6.5 h of stroke onset. In patients with sICH (defined as ICH causing an increase of ⩾4 points on the National Institutes of Health Stroke Scale [NIHSS]), univariable and multivariable linear regression analysis was used to identify factors associated with the timing of sICH. This was defined as the time between end of EVT and the time of first CT-scan on which ICH was seen as a proxy. SICH occurred in 205 (6%) of 3391 included patients. Median time from end of EVT procedure to sICH detection on NCCT was 9.0 [IQR 2.9-22.5] hours, with a rapidly decreasing incidence after 24 h. None of the analyzed factors, including baseline NIHSS, intravenous alteplase treatment, and poor reperfusion at the end of the procedure were associated with the timing of sICH. SICHs primarily occur in the first hours after EVT, and less frequently beyond 24 h. Guidelines that recommend to perform frequent neurological assessments for at least 24 h after intravenous alteplase treatment can be applied to ischemic stroke patients treated with EVT.

Pre-Hospital Delay in Acute Ischemic Stroke Care: Current Findings and Future Perspectives in a Tertiary Stroke Center from Romania-A Cross-Sectional Study.

Background and objectives: The time interval between stroke onset and hospital arrival is a major barrier for reperfusion therapies in acute ischemic stroke and usually accounts for most of the onset-to-treatment delay. The present study aimed to analyze the pre-hospital delays for patients with acute ischemic stroke admitted to a tertiary stroke center in Romania and to identify the factors associated with a late hospital arrival. Material and methods: The study population consisted of 770 patients hospitalized with the diagnosis of acute ischemic stroke in the University Emergency Hospital Bucharest during a 6-month period, between 1 January and 30 June 2018. Data regarding pre-hospital delays were prospectively collected and analyzed together with the demographic and clinical characteristics of the patients. Results: In total, 31.6% of patients arrived at the hospital within 4.5 h from stroke onset and 4.4% in time intervals between 4.5 and 6 h from the onset, and 28.7% of the patients reached the hospital more than 24 h after onset of symptoms. Transport to hospital by own means was the only factor positively associated with arrival to hospital > 4.5 h from stroke onset and more than doubled the odds of late arrival. Factors negatively associated with hospital arrival > 4.5 h after stroke onset were prior diagnosis of atrial fibrillation, initial National Institute of Health Stroke Scale (NIHSS) score ≥ 16 points, presence of hemianopsia, facial palsy and sensory disturbance. Factors increasing the odds of hospital arrival after 24 h from stroke onset were living alone and living in rural areas. Conclusions: Almost one in three ischemic stroke patients presenting to our center reaches hospital more than 24 h after onset of symptoms. These findings highlight the need for urgent measures to improve not only stroke awareness but also pre-hospital protocols in order to provide timely and appropriate care for our stroke patients.

Estimation of ischemic core in acute ischemic stroke with CT angiography and non-contrast CT: Attenuation changes in ASPECTS regions vs. automated ASPECTS scoring.

PurposeReperfusion therapies for acute ischemic stroke due to large-vessel occlusion (AIS-LVO) are highly time-dependent, and large infarction is related to poor outcomes and risk of symptomatic hemorrhage. It is of significance to investigate and optimize the screening means and selection criteria for reperfusion therapies to identify more appropriate patients with better outcomes. This study aimed to compare the performance of attenuation changes vs. automated Alberta Stroke Program Early CT Score (ASPECTS) and using CT angiography (CTA) source images vs. non-contrast CT (NCCT) in distinguishing the infarction extent of ischemic core volumes ≥ 70 ml within different time windows.MethodsA total of 73 patients with AIS-LVO who received multimodal CT were analyzed. The automated software was used to calculate ASPECTS. Attenuation change was defined as the sum of products of relative Hounsfield unit (rHU) values times weighting factors of all 10 ASPECTS regions. rHU value of each region was the HU of the ischemic side over that of the contralateral. The corresponding weighting factors were the regression coefficients derived from a multivariable linear regression model which was used to correlate regional rHU with ischemic core volumes, because each region in the ASPECTS template is weighted disproportionally in the ASPECTS system. Automated ASPECTS and attenuation changes were both calculated using CTA and NCCT, respectively.ResultsAttenuation changes were correlated with ischemic core volumes within different time windows (Rho ranging from 0.439 to 0.637). In classification of the ischemic core ≥ 70 ml, the performances of attenuation changes were comparable with ASPECTS (area under the curve [AUC] ranging from 0.799 to 0.891), with DeLong’s test (P = 0.079, P = 0.373); using CTA (AUC = 0.842) was not different from NCCT (AUC = 0.838).ConclusionAttenuation changes in ASPECTS regions were correlated with ischemic core volumes. In the classification of infarction volumes, attenuation changes had a high diagnostic ability comparable with automated ASPECTS. Measurement of attenuation changes is not involved in complicated scoring algorithms. This measurement can be used as an available, rapid, reliable, and accurate means to evaluate infarction extent within different time windows. The usefulness of infarction volumes measured by attenuation changes to identify more appropriate patients for reperfusion therapies can be validated in future clinical trials.

Effect of an individualized versus standard blood pressure management during mechanical thrombectomy for anterior ischemic stroke: the DETERMINE randomized controlled trial

BackgroundHypotension and blood pressure (BP) variability during endovascular therapy (EVT) for acute ischemic stroke (AIS) due to an anterior large vessel occlusion (LVO) is associated with worse outcomes. However, the optimal BP threshold during EVT is still unknown given the lack of randomized controlled evidence. We designed the DETERMINE trial to assess whether an individualized BP management during EVT could achieve better functional outcomes compared to a standard BP management.MethodsThe DETERMINE trial is a multicenter, prospective, randomized, controlled, open-label, blinded endpoint clinical trial (PROBE design). AIS patients with a proximal anterior LVO are randomly assigned, in a 1:1 ratio, to an experimental arm in which mean arterial pressure (MAP) is maintained within 10% of the first MAP measured before EVT, or a control arm in which systolic BP (SBP) is maintained within 140–180 mm Hg until reperfusion is achieved or artery closure in case of EVT failure. The primary outcome is the rate of favorable functional outcomes, defined by a modified Rankin Scale (mRS) between 0 and 2 at 90 days. Secondary outcomes include excellent outcome and ordinal analysis of the mRS at 90 days, early neurological improvement at 24 h (National Institutes of Health Stroke Scale), final infarct volume, symptomatic intracranial hemorrhage rates, and all-cause mortality at 90 days. Overall, 432 patients will be included.DiscussionDETERMINE will assess the clinical relevance of an individualized BP management before reperfusion compared to the one size fits all approach currently recommended by international guidelines.Trial registrationClinicalTrials.gov, NCT04352296. Registered on 20th April 2020.

Three Days Delayed Recanalization Improved Neurological Function in pMCAO Rats by Increasing M2 Microglia-Possible Involvement of the IL-4R/STAT6/PPARγ Pathway.

Current approved therapies for acute ischemic stroke have a restricted therapeutic time window. Delayed recanalization, which has been utilized clinically in patients who have missed the time window for administration, may be a promising alternative for stroke patients. However, the underlying molecular mechanisms remain undiscovered. Herein, we hypothesized that delayed recanalization would increase M2 microglial polarization through the IL-4R (interleukin-4 receptor)/STAT6 (signal transducer and activators of transcription 6)/PPARγ (peroxisome proliferator-activated receptor γ) pathway, subsequently promoting stroke recovery in rats. The permanent middle cerebral artery occlusion (pMCAO) model was induced via intravascular filament insertion. Recanalization was induced by withdrawing the filament at 3days after MCAO (rMCAO). Interleukin (IL)-4 was administered intranasally at 3days after pMCAO. AS1517499, a specific STAT6 inhibitor, was administered intranasally at 3days after MCAO induction. Immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA), western blot analysis, volumetric measurements of brain infarct, and neurological behavior tests were conducted. Delayed recanalization at 3days after MCAO increased the polarization of M2 microglia, decreased inflammation, and improved neurological behavior. IL-4 treatment administered on the 3rd day after pMCAO increased M2 microglial polarization, improved neurological behavior, and reduced infarction volume of pMCAO rats. The inhibition of STAT6 decreased the level of p-STAT6 and PPARγ in rats treated with delayed recanalization. Delayed recanalization improved neurological function by increasing microglial M2 polarization, possibly involved with the IL-4R/STAT6/PPARγ pathway after MCAO in rats.

M1, M2: Time to Bid Adieu!

M1, M2: Time to Bid Adieu!

Reperfusion therapy in acute ischaemic stroke due to cervical and cerebral artery dissection: Results from a Spanish multicentre study

IntroductionIschaemic stroke (IS) due to cervical and cerebral artery dissection (CAD) is a rare entity, and few data are available on the use of such reperfusion therapies as intravenous fibrinolysis and mechanical thrombectomy in these patients. We analysed the use of these treatments in patients with IS due to CAD and compared them against patients receiving reperfusion treatment for IS of other aetiologies. MethodsWe conducted an observational, retrospective, multicentre study of patients with IS due to CAD recorded in the National Stroke Registry of the Spanish Society of Neurology during the period 2011−2019. Comparative analyses were performed between: a) patients with CAD treated and not treated with reperfusion therapies and b) patients treated with reperfusion for IS due to CAD and patients treated with reperfusion for IS due to other causes. Epidemiological data, stroke variables, and outcomes at discharge and at 3 months were included in the analysis. ResultsThe study included 21,037 patients with IS: 223 (1%) had IS due to CAD, of whom 68 (30%) received reperfusion treatment. Reperfusion treatments were used less frequently in cases of vertebral artery dissection and more frequently in patients with carotid artery occlusion. Compared to patients with IS due to other causes, patients with CAD were younger, more frequently underwent mechanical thrombectomy, and less frequently received intravenous fibrinolysis. Rates of haemorrhagic complications, mortality, and independence at 3 months were similar in both groups. ConclusionsReperfusion therapy is frequently used in patients with IS due to CAD. The outcomes of these patients demonstrate the efficacy and safety of reperfusion treatments, and are comparable to the outcomes of patients with IS due to other aetiologies.

Reperfusion therapy in acute ischemic stroke

Background: Until mid-2010, intravenous thrombolysis remains the only reperfusion therapy for acute ischemic stroke. In 2015, the five pivotal endovascular recanalization therapy (ERT) trials demonstrated that ERT improved the prognosis of acute ischemic stroke with large artery occlusion within 6 hours after onset. Currently, ERT has been established as a crucial acute ischemic stroke treatment option. The prognosis of acute ischemic stroke is known to be time-dependent. Several studies addressed that ERT expands the time window for reperfusion therapy; thereby, improving prognosis.Current Concepts: Recent randomized clinical trials revealed that ERT improved the outcome in patients even within the late time window of up to 24 hours of stroke onset. The trials enrolled participants who had target mismatch, defined as either clinical-core or perfusion-core mismatch, which prompted an update of the national guidelines in several countries. To select the patients with stroke who were eligible for ERT, advanced imaging tools could be recommended.Discussion and Conclusion: According to the updated ERT guidelines, stroke centers were recommended to establish an appropriate imaging protocol and strategy for patients with acute ischemic stroke who were within the late time window. Additionally, if ERT is further practiced nationally, more manpower and infrastructure for patients with stroke should be supported at the stroke center.

Development of a carotid artery thrombolysis stroke model in mice

AbstractRecanalization with restored cerebral perfusion is the primary goal of thrombolytic therapy in acute ischemic stroke. The identification of adjunctive therapies that can be safely used to enhance thrombolysis in stroke remains an elusive goal. We report here the development of a mouse in situ carotid artery thrombolysis (iCAT) stroke model involving graded cerebral ischemia to induce unihemispheric infarction after thrombotic occlusion of the common carotid artery (CCA). Electrolytic-induced thrombotic occlusion of the left CCA enabled real-time assessment of recanalization and rethrombosis events after thrombolysis with recombinant tissue-type plasminogen activator (rtPA). Concurrent transient stenosis of the right CCA induced unihemispheric hypoperfusion and infarction in the left middle cerebral artery territory. Real-time assessment of thrombolysis revealed recanalization rates <30% in rtPA-treated animals with high rates of rethrombosis. Addition of the direct thrombin inhibitor argatroban increased recanalization rates to 50% and reduced rethrombosis. Paradoxically, this was associated with increased cerebral ischemia and stroke-related mortality (25%-42%). Serial analysis of carotid and cerebral blood flow showed that coadministration of argatroban with rtPA resulted in a marked increase in carotid artery embolization, leading to distal obstruction of the middle cerebral artery. Real-time imaging of carotid thrombi revealed that adjunctive anticoagulation destabilized platelet-rich thrombi at the vessel wall, leading to dislodgement of large platelet emboli. These studies confirm the benefits of anticoagulants in enhancing thrombolysis and large artery recanalization; however, at high levels of anticoagulation (∼3-fold prolongation of activated partial thromboplastin time), this effect is offset by increased incidence of carotid artery embolization and distal middle cerebral artery occlusion. The iCAT stroke model should provide important new insight into the effects of adjunctive antithrombotic agents on real-time thrombus dynamics during thrombolysis and their correlation with stroke outcomes.

Association of diabetes mellitus and admission glucose levels with outcome after endovascular therapy in acute ischaemic stroke in anterior circulation.

Background and purposeWe aimed to assess the association of diabetes mellitus (DM) and admission hyperglycaemia (AH), respectively, and outcome in patients with acute ischaemic stroke with large vessel occlusion in the anterior circulation treated with endovascular therapy (EVT) in daily clinical practice.MethodsConsecutive EVT patients admitted to our stroke centre between February 2015 and April 2020 were included in this observational cohort study. Patients with versus without DM and with versus without AH (glucose ≥ 7.8 mmol/L) were compared.ResultsWe included 1020 patients (48.9% women, median age = 73.1 years); 282 (27.6%) had DM, and 226 (22.2%) had AH. Patients with versus without DM less often showed successful reperfusion (odds ratio [OR]adjusted = 0.61, p = 0.023) and worse 3‐month functional outcome (modified Rankin Scale [mRS] = 0–2: 31.3% vs. 48%, ORadjusted = 0.59, p = 0.004; death: 38.9% vs. 24.1%, ORadjusted = 1.75, p = 0.002; mRS shift: p adjusted < 0.0001; if moderate/good collaterals and mismatch, mRS = 0–2: ORadjusted = 0.52, p = 0.005; death: ORadjusted = 1.95, p = 0.005). If analysis was additionally adjusted for AH, only mRS shift was still significantly worse in patients with DM (p adjusted = 0.012). Patients with versus without AH showed similar successful reperfusion rates and worse 3‐month functional outcome (mRS = 0–2: 28.3% vs. 50.4%, ORadjusted = 0.52, p < 0.0001; death: 40.4% vs. 22.4%, ORadjusted = 1.80, p = 0.001; mRS shift: p adjusted < 0.0001; if moderate/good collaterals and mismatch, mRS = 0–2: ORadjusted = 0.38, p < 0.0001; death: ORadjusted = 2.39, p < 0.0001). If analysis was additionally adjusted for DM, 3‐month functional outcome remained significantly worse in patients with AH (mRS = 0–2: ORadjusted = 0.58, p = 0.004; death: ORadjusted = 1.57, p = 0.014; mRS shift: p adjusted = 0.004). DM independently predicted recurrent/progressive in‐hospital ischaemic stroke (OR = 1.71, p = 0.043) together with admission National Institutes of Health Stroke Scale score (OR = 0.95, p = 0.005), and AH independently predicted in‐hospital symptomatic intracranial haemorrhage (OR = 2.21, p = 0.001). The association of admission continuous glucose levels and most outcome variables was (inversely) J‐shaped.ConclusionsHyperglycaemia more than DM was associated with worse 3‐month outcome in the patients studied, more likely so in the case of moderate/good collaterals and mismatch in admission imaging.

Prediction of Hemorrhage Transformation after Revascularization Therapy in Acute Ischemic Stroke Based on IVIM

Prediction of Hemorrhage Transformation after Revascularization Therapy in Acute Ischemic Stroke Based on IVIM

Annexin V-Modified Platelet-Biomimetic Nanomedicine for Targeted Therapy of Acute Ischemic Stroke.

Thromboembolic stroke is typically characterized by the activation of platelets, resulting in thrombus in the cerebral vascular system, leading to high morbidity and mortality globally. Intravenous thrombolysis by tissue plasminogen activator (tPA) administration within 4.5 h from the onset of symptoms is providing a standard therapeutic strategy for ischemic stroke, but this reagent simultaneously shows potential serious adverse effects, e.g., hemorrhagic transformation. Herein, a novel delivery platform based on Annexin V and platelet membrane is developed for tPA (APLT-PA) to enhance targeting efficiency, therapeutic effects, and reduce the risk of intracerebral hemorrhage in acute ischemic stroke. After preparation by extrusion of platelet membrane and subsequent insertion of Annexin V to liposomes, APLT-PA exhibits a high targeting efficiency to activated platelet in vitro and thrombosis site in vivo, due to the binding to phosphatidylserine (PS) and activated platelet membrane proteins. One dose of APLT-PA leads to obvious thrombolysis and significant improvement of neurological function within 7 days in mice with photochemically induced acute ischemic stroke. This study provides a novel, safe platelet-biomimetic nanomedicine for precise thrombolytic treatment of acute ischemic stroke, and offers new theories for the design and exploitation of cell-mimetic nanomedicine for diverse biomedical applications.

Profiling the neurovascular unit unveils detrimental effects of osteopontin on the blood–brain barrier in acute ischemic stroke

Blood–brain barrier (BBB) dysfunction, characterized by degradation of BBB junctional proteins and increased permeability, is a crucial pathophysiological feature of acute ischemic stroke. Dysregulation of multiple neurovascular unit (NVU) cell types is involved in BBB breakdown in ischemic stroke that may be further aggravated by reperfusion therapy. Therefore, therapeutic co-targeting of dysregulated NVU cell types in acute ischemic stroke constitutes a promising strategy to preserve BBB function and improve clinical outcome. However, methods for simultaneous isolation of multiple NVU cell types from the same diseased central nervous system (CNS) tissue, crucial for the identification of therapeutic targets in dysregulated NVU cells, are lacking. Here, we present the EPAM-ia method, that facilitates simultaneous isolation and analysis of the major NVU cell types (endothelial cells, pericytes, astrocytes and microglia) for the identification of therapeutic targets in dysregulated NVU cells to improve the BBB function. Applying this method, we obtained a high yield of pure NVU cells from murine ischemic brain tissue, and generated a valuable NVU transcriptome database (https://bioinformatics.mpi-bn.mpg.de/SGD_Stroke). Dissection of the NVU transcriptome revealed Spp1, encoding for osteopontin, to be highly upregulated in all NVU cells 24 h after ischemic stroke. Upregulation of osteopontin was confirmed in stroke patients by immunostaining, which was comparable with that in mice. Therapeutic targeting by subcutaneous injection of an anti-osteopontin antibody post-ischemic stroke in mice resulted in neutralization of osteopontin expression in the NVU cell types investigated. Apart from attenuated glial activation, osteopontin neutralization was associated with BBB preservation along with decreased brain edema and reduced risk for hemorrhagic transformation, resulting in improved neurological outcome and survival. This was supported by BBB-impairing effects of osteopontin in vitro. The clinical significance of these findings is that anti-osteopontin antibody therapy might augment current approved reperfusion therapies in acute ischemic stroke by minimizing deleterious effects of ischemia-induced BBB disruption.

Rural-urban differences in functional outcomes after acute stroke therapy within the stroke belt

IntroductionThe Southeastern United States (US) has the highest stroke mortality rate in the country. A high proportion of its population lives in rural areas. Rural patients with stroke have worse outcomes than their urban counterparts. We compared 90-day modified Rankin Score (mRS) between patients living in urban versus rural areas who received endovascular intervention for acute stroke. MethodsWe performed a retrospective analysis of patients who received acute stroke therapy at a comprehensive stroke center in the Southeastern US from 2014 to 2018. Individuals were classified as rural or urban dwellers based on 2010 Rural-Urban Commuting Area Codes. Stepwise logistic regression models were performed using clinical and demographic characteristics to compare good (mRS 0–1) vs poor (mRS 2–6) functional outcomes between urban and rural patients. Results232 patients were included (185 urban and 47 rural). Urban and rural groups had similar composition of age, gender, and proportion of African-Americans. Mean baseline NIH stroke scale was higher in rural patients (17.0 vs 14.8 respectively, p-value=0.03.). Our model for poor functional outcome at 90-days revealed only older age as a significant risk factor (OR 0.97, 95% CI 0.95–0.99). ConclusionsOur study found that for patients receiving acute therapy for ischemic stroke, there were no significant differences in functional outcome between urban versus rural patients. Only older age predicted poor functional outcome at 90 days. Our study demonstrates that patients from rural areas may not have worse mortality rates or poor outcomes and can recover similarly to those from urban areas.

Influences of different referral modes on clinical outcomes after endovascular therapy for acute ischemic stroke

Background and purposeAs endovascular thrombectomy (EVT) is time-dependent, it is crucial to refer patients promptly. Current referral modes include Mothership (MS), Drip and Ship (DS) and Drive the Doctor (DD). The purpose of this study was to investigate the influences of different referral modes on the clinical outcomes of patients with acute ischemic stroke after EVT. MethodsA total of 349 patients from 15 hospitals between April 2017 and March 2020 were enrolled. The primary outcomes include poor outcome (modified Rankin Scale score of 3 to 6), symptomatic intracranial hemorrhage transformation (sICH), mortality and cost. Regression analysis was used to assess the association of referral modes with poor outcome, sICH, mortality and cost in acute ischemic stroke patients.ResultsAmong the 349 patients, 83 were in DD group (23.78%), 85 in MS group (24.36%) and 181 in DS group (51.86%). There were statistically significant differences in intravenous thrombolysis, onset-to-door time, onset-to-puncture time, puncture-to-recanalization time, door-to-puncture time, door-to-recanalization time, and cost among the DD, MS, and DS groups (59.04% vs 35.29% vs 33.15%, P<0.001; 90 vs 166 vs 170 minutes, P<0.001; 230 vs 270 vs 270 minutes, P<0.001; 82 vs 54 vs 51 minutes, P<0.001; 110 vs 85 vs 96 minutes, P=0.004; 210 vs 146 vs 150 minutes, P<0.001; 64258 vs 80041 vs 70750 Chinese Yuan, P=0.018). In terms of sICH, mortality and poor outcome, there was no significant difference among the DD, MS, and DS groups (22.89% vs 18.82% vs 19.34%, P=0.758; 24.10% vs 24.71% vs 29.83%, P=0.521; 64.47% vs 64.71% vs 68.51%, P=0.827). The results of multiple regression analysis indicated that there was no independent correlation between different referral modes regarding sICH (ORMS: 0.50, 95%CI: 0.18, 1.38, P=0.1830; ORDS: 0.47, 95%CI: 0.19, 1.16, P=0.1000), mortality (ORMS: 0.56, 95%CI: 0.19, 1.67, P=0.2993; ORDS: 0.65, 95%CI: 0.25, 1.69, P=0.3744) and poor outcome (ORMS: 0.61, 95%CI: 0.25, 1.47, P=0.2705; ORDS: 0.53, 95%CI: 0.24, 1.18, P=0.1223). However, there was a correlation between MS group and cost (β=30449.73, 95%CI: 11022.18, 49877.29; P=0.0023). The multiple regression analysis on patients finally admitted in comprehensive stroke center (MS+DS) versus patients finally admitted in primary stroke center (DD) showed that DD mode was independently associated with lower costs (β=-19438.86, 95%CI: -35977.79, -2899.94; P=0.0219).ConclusionThere was no independent correlation between three referral modes and sICH, mortality, poor outcome correspondingly. Different referral modes can be implemented in clinical practice according to the situations encountered. Compared to MS and DS modes, DD mode is more economical.

Safety and efficacy of endovascular thrombectomy in acute ischemic stroke treated with anticoagulants: a systematic review and meta-analysis

BackgroundEndovascular thrombectomy (EVT) is an effective therapy in acute ischemic stroke (AIS) with large vessel occlusion, especially for those who are unsuitable for intravenous thrombolysis. However, the safety and efficacy of EVT in AIS patients who receiving oral anticoagulants (OACs) is unclear, especially for the risk of symptomatic intracranial hemorrhage (sICH). MethodsDatabase of PubMed, Embase, and Cochrane Library were searched from Jan 1, 2000, through the final search date of Jun 2, 2021. Eligible studies for enrollment required outcomes reported for events of sICH, mortality, functional status, and successful reperfusion. Meta-analysis was conducted to compare the outcomes difference after EVT between AIS patients with or without OACs use. The primary safety outcome was sICH after EVT, and the primary efficacy outcome was functional status at 3 months. ResultsOne thousand nine hundred forty studies were screened for eligibility and 15 of them were included in the meta-analysis. Compared the OACs group to control arm, vitamin K antagonists (VKAs) was associated with higher risk of sICH (OR 1.49, 95% CI 1.10–2.02) and mortality (OR 1.67, 95% CI 1.35–2.06). Poor functional outcomes were noted both in the VKAs and direct oral anticoagulants (DOACs) groups (OR 0.62, 95% CI 0.54–0.71 and OR 0.61, 95% CI 0.53–0.71, respectively). No differences in successful reperfusion were observed.ConclusionsComparing with DOACs, VKAs use was associated with a higher risk of sICH and mortality after EVT. Patients who did not receive OACs exhibited more favorable outcomes. The successful reperfusion did not differ between groups. However, results for mortality and functional outcomes have to be interpreted with caution since they are based on non-randomized data and unadjusted proportions.

The intra-arterial selective cooling infusion system: Amathematical temperature analysis and in vitro experiments for acute ischemic stroke therapy.

IntroductionThe neuroprotection of acute ischemic stroke patients can be achieved by intra‐arterial selective cooling infusion using cold saline, which can decrease brain temperature without influencing the body core temperature. This approach can lead to high burdens on the heart and decreased hematocrit in the scenario of loading a high amount of liquid for longtime usage. Therefore, autologous blood is utilized as perfusate to circumvent those side effects.MethodsIn this study, a prototype instrument with an autologous blood cooling system was developed and further evaluated by a mathematical model for brain temperature estimation.ResultsHypothermia could be achieved due to the adequate cooling capacity of the prototype system, which could provide the lowest cooling temperature into the blood vessel of 10.5°C at 25 rpm (209.7 ± 0.8 ml/min). And, the core body temperature did not alter significantly (−0.7 ~ −0.2°C) after 1‐h perfusion. The cooling rate and temperature distributions of the brain were analyzed, which showed a 2°C decrease within the initial 5 min infusion by 44 ml/min and 13.7°C perfusate.ConclusionThis prototype instrument system could safely cool simulated blood in vitro and reperfuse it to the target cerebral blood vessel. This technique could promote the clinical application of an autologous blood perfusion system for stroke therapy.

Urgent computed tomography angiography in paediatric stroke.

To improve delivery of acute therapies for acute ischaemic stroke (AIS). We identified factors influencing the speed of diagnosis and delivery of acute therapies in a prospective cohort of 21 children with suspected AIS (eight with AIS, 13 stroke mimics) and explored them in a retrospective cohort with confirmed AIS. Approximately half of the prospective and total AIS cohorts presented with acute, sustained hemiparesis, and were diagnosed relatively quickly. AIS was suspected and diagnosed more slowly in the half presenting with symptoms other than sustained hemiparesis. Thirty-one out of 51 patients with AIS (19 females, 32 males, mean age 8 years 6 months, SD 5 years 4 months) had arterial abnormalities identified by computed tomography angiography (CTA) or magnetic resonance angiography (MRA): 11 with large vessel occlusion, six with dissection, five with moyamoya disease, nine with other arteriopathies. Among these patients, those initially imaged with CTA were diagnosed more quickly than those with initial magnetic resonance imaging/angiography, which facilitated thrombectomy and thrombolytic therapy. Twenty out of 51 had AIS without arterial abnormalities on CTA or MRA: eight with lenticulostriate vasculopathy and 12 with other small-vessel AIS. Among these patients, 80% were ineligible for thrombolysis for reasons beyond delay to diagnosis, and all showed good outcomes with supportive treatments alone. Clinical features at presentation influence rapidity with which childhood AIS is suspected and diagnosed. Readily available CTA can direct thrombectomy in patients with large vessel occlusion and thrombolysis in most, but not all, eligible patients. Children with acute ischaemic stroke (AIS) commonly present with symptoms other than sustained hemiparesis. Stroke is more slowly recognized in these patients, which limits potential therapies. Computed tomography angiography (CTA) accurately identifies AIS with large vessel occlusion, enabling timely endovascular thrombectomy. CTA is sufficient to direct thrombolytic therapy in most eligible children. Most childhood AIS without arterial abnormalities identified by CTA had good outcomes.