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Abstract Objective Cerebral circulation time (CCT) and collateral score (CS) are associated with functional outcomes in acute ischemic stroke (AIS) patients after endovascular treatment (EVT), and may be related to each other. We aim to determine the relationship between CS and CCT on functional outcomes. Methods We retrospectively enrolled consecutive patients with anterior circulation large vessel occlusion (LVO) AIS who received EVT. CS and CCT were measured based on digital subtraction angiography (DSA). We defined CS 0–2 and 3–4 as poor and good collateral status, respectively, and used change of CCT (cCCT), which was defined as the change of stroke side CCT (sCCT) versus healthy side CCT (hCCT). Mediating analysis was used to evaluate the influence of cCCT on the association between CS and functional outcomes, and ROC curves were further used to explore the predictive ability of the interaction between cCCT and CS for functional outcomes. Results A total of 100 patients were enrolled in the final analysis. A higher cCCT (r = −0.239; p = 0.017) was associated with lower CS, and cCCT mediated the association of CS with functional outcome. Logistic regression analysis found that CS, cCCT and cCCT‐CS interactions were independently associated with functional outcome, and cCCT‐CS interaction has better predictive performance, with a higher area under curve value than CS or cCCT alone (0.79 vs. 0.75 or 0.75). Interpretation To our knowledge, this study provides the first report of the association of collateral status with cCCT, and their interaction effect on functional outcome in AIS‐LVO patients receiving EVT.

Abstract Contrast enhancement (CE) on brain non-contrast computed tomography (NCCT) is common after endovascular thrombectomy (EVT) in patients with acute ischemic stroke (AIS), but its association with clinical outcomes is not well established. The current study aimed to investigate this relationship. We retrospectively reviewed consecutive patients with acute ischemic stroke who had hyperdensity on NCCT immediately after EVT for anterior circulation large vessel occlusion (LVO) from January 2016 to December 2019. We used ASPECTS combined with volume measurement by 3D reconstruction to estimate the extent and location of CE. Multivariable regression analysis was conducted to explore the risk factors associated with clinical outcome. In this study, 113 of 158 (71.52%) anterior circulation AIS-LVO patients had hyperdensity on brain NCCT. After strict inclusion and exclusion criteria, a total of 64 patients were enrolled in the final analysis. In logistic regression analysis, CE-ASPECTS, CE volume, CE at the caudate nucleus, M4 and M6 region were associated with 3-month poor functional outcome after adjusting for confounding factors. The conventional variable model was used for reference, including age, initial NIHSS, the procedure time, stent retriever passes, recanalization status and baseline ASPECTS, with AUC of 0.73. When combined with the above-named variables (conventional variables + CE-ASPECTS + CE volume + CE at caudate nucleus + CE at M4 region + CE at M6 region), the predictive power was significantly improved, with AUC of 0.87 (95% CI 0.78–0.95). The spatial location and volume of CE on NCCT obtained immediately after EVT were independent and strong predictors for poor outcome at 3-months in patients with AIS after excluding definite hemorrhage by 24-h follow up CT.

Background and purposeThe first-pass recanalization of endovascular treatment (EVT) is closely correlated with clinical outcome of patients with large vessel occlusion (LVO) stroke. The aim of the study was to explore whether intra-arterial tenecteplase (TNK) during the first pass of EVT can increase first-pass successful reperfusion and improve the neurological outcome in AIS-LVO patients.Materials and methodsThe BRETIS-TNK trial (ClinicalTrials.gov Identifier: NCT04202458) was a prospective, single-arm, single center study. Twenty-six eligible AIS-LVO patients with large-artery atherosclerosis etiology were consecutively enrolled from December 2019 to November 2021. Intra-arterial TNK (4 mg) after microcatheter navigation through the clot was administered, followed by TNK (0.4 mg/min) given continuously for 20 min after the first retrieval attempt of EVT without confirmation of the reperfusion status by DSA. The 50 control patients comprised of a historical cohort before the BRETIS-TNK trial (from March 2015 to November 2019). Successful reperfusion was defined as modified Thrombolysis In Cerebral Infarction (mTICI) ≥2b.ResultsThe first-pass successful reperfusion rate was higher in the BRETIS-TNK vs. control group (53.8% vs. 36%, p = 0.14), and the difference became statistically significant after propensity score matching (53.8% vs. 23.1%, p = 0.03). There was no difference in symptomatic intracranial hemorrhage between the BRETIS-TNK and control groups (7.7% vs. 10.0%, p = 0.92). There was a trend toward higher proportion of functional independence at 90 days in the BRETIS-TNK comparing with the control group (50% vs. 32%, p = 0.11).ConclusionThis is the first study to report that intra-arterial TNK during the first pass of EVT seems safe and feasible in AIS-LVO patients.

BackgroundThe effect of head position on stroke is not clear. The current study aimed to observe the effect of head-down tilt on acute ischemic stroke (AIS) patients with large vessel occlusion.MethodsWe observed the influence of head-down tilt position on clinical outcomes, myocardial enzymogram and N-terminal pro b-type Natriuretic Peptide in 4 AIS patients who suffered early neurological deterioration (END). Cerebral perfusion imaging was performed in 3 patients using arterial spin labeling.ResultsIn series of AIS patients with END, head down tilt (-20°) prevented further neurological deterioration and improved clinical outcomes. An increase in cerebral blood flow was observed by arterial spin labeling after head down tilt treatment. No obvious adverse events occurred.ConclusionThe case series suggest that head-down tilt may improve clinical outcome in AIS patients through increasing the cerebral perfusion with no obvious adverse events. The finding needs to be confirmed in future clinical trials.

Background Despite successful recanalization, up to half of patients with acute ischemic stroke caused by large‐vessel occlusion treated with endovascular treatment (EVT) do not recover to functional independence. We aim to evaluate the role of cerebral circulation time (CCT) as outcome predictor after EVT. Methods and Results We retrospectively enrolled consecutive patients with acute ischemic stroke–large‐vessel occlusion undergoing EVT. Three categories of CCT based on digital subtraction angiography were studied: CCT of the stroke side, CCT of the healthy side), and change of CCT of the stroke side versus CCT of the healthy side. Dramatic clinical recovery was defined as a 24‐hour National Institutes of Health Stroke Scale score ≤2 or ≥8 points drop. A modified Rankin Scale score ≤2 at 3 months was considered a favorable outcome. Logistic regression analysis was performed to evaluate the prediction of CCT on prognosis. One hundred patients were enrolled, of which 38 (38.0%) experienced a dramatic clinical recovery and 43 (43.0%) achieved a favorable outcome. Logistic regression analysis found that shorter change of CCT of the stroke side versus CCT of the healthy side and CCT of the stroke side were independent positive prognostic factors for dramatic clinical recovery (odds ratio [OR], 0.189; P=0.033; OR, 0.581; P=0.035) and favorable outcomes (OR, 0.142; P=0.020; OR, 0.581; P=0.046) after adjustment for potential confounders. A model including the change of CCT of the stroke side versus CCT of the healthy side also had significantly higher area under the curve values compared with the baseline model in patients with dramatic clinical recovery (0.780 versus 0.742) or favorable outcome (0.759 versus 0.713). Conclusions To our knowledge, this is the first report that CCT based on digital subtraction angiography data exhibits an independent predictive performance for clinical outcome in patients with acute ischemic stroke–large‐vessel occlusion after EVT. Given that this readily available CCT can provide alternative perfusion information during EVT, a prospective, multicenter trial is warranted.

Tau hyperphosphorylation is a characteristic alteration present in a range of neurological conditions, such as traumatic brain injury (TBI) and neurodegenerative diseases. Treatments targeting high-mobility group box protein 1 (HMGB1) induce neuroprotective effects in these neuropathologic conditions. However, little is known about the interactions between hyperphosphorylated tau and HMGB1 in neuroinflammation. We established a model of TBI with controlled cortical impacts (CCIs) and a tau hyperphosphorylation model by injecting the virus encoding human P301S tau in mice, and immunofluorescence, western blotting analysis, and behavioral tests were performed to clarify the interaction between phosphorylated tau (p-tau) and HMGB1 levels. We demonstrated that p-tau and HMGB1 were elevated in the spatial memory-related brain regions in mice with TBI and tau-overexpression. Animals with tau-overexpression also had significantly increased nucleotide-binding oligomerization domain-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome activation, which manifested as increases in apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), activating caspase-1 and interleukin 1 beta (IL-1β) levels. In addition, NLRP3–/– mice and the HMGB1 inhibitor, glycyrrhizin, were used to explore therapeutic strategies for diseases with p-tau overexpression. Compared with wild-type (WT) mice with tau-overexpression, downregulation of p-tau and HMGB1 was observed in NLRP3–/– mice, indicating that HMGB1 alterations were NLRP3-dependent. Moreover, treatment with glycyrrhizin at a late stage markedly reduced p-tau levels and improved performance in the Y- and T-mazes and the ability of tau-overexpressing mice to build nests, which revealed improvements in spatial memory and advanced hippocampal function. The findings identified that p-tau has a triggering role in the modulation of neuroinflammation and spatial memory in an NLRP3-dependent manner, and suggest that treatment with HMGB1 inhibitors may be a better therapeutic strategy for tauopathies.

Abstract Background The impact of anesthesia strategy on the outcomes of acute ischemic stroke (AIS) patients undergoing endovascular treatment is currently controversy. Thus, we performed this meta-analysis to compare the differences of clinical and angiographic outcomes between general anesthesia (GA) and conscious sedation (CS). Methods A literature search in PubMed, Embase, and Web of Knowledge databases through February 2019 was conducted for related records on GA and CS of AIS undergoing endovascular treatment. The results of the studies were pooled and meta-analyzed with fixed- or random-effect model based on heterogeneity test in total and subgroup analyses. Results Twenty-three studies including 6703 patients were analyzed in this meta-analysis. We found that patients in the GA group have lower odds of favorable functional outcome (mRS scores ≤2) compared with the CS group (odds ratio [OR] = 0.62, 95% confidence interval [CI]: 0.49–0.77), and higher risk of mortality (OR = 1.68, 95% CI: 1.49–1.90), pneumonia (OR = 1.78, 95% CI: 1.40–2.26), symptomatic intracranial hemorrhage (OR = 1.64, 95% CI: 1.13–2.37). However, no significant differences were seen between the groups in the rate of recanalization (OR = 1.07, 95% CI: 0.89–1.28), vessel dissection or perforation (OR = 1.00, 95% CI: 0.98–1.03) and asymptomatic intracranial hemorrhage (OR = 1.19, 95% CI: 0.96–1.47). While in the RCT subgroup analysis, we found patients in the GA group does not show lower rate of favorable functional outcome compared with the CS group (OR = 1.84, 95% CI: 1.17–2.89). And there was no significant difference in the rate of mortality between GA and CS groups during RCT subgroup analysis (OR = 0.74, 95% CI: 0.43–1.27). Conclusions AIS patients performed endovascular treatment under GA compared with CS was associated with worse functional outcome and increased rate of mortality, but differences in worsened outcomes do not exist when one looks into the GA vs. CS RCTs. Moreover, these findings are mainly based on the retrospective studies and additional multi-center randomized controlled trials to definitively address these issues is warranted.

Abstract Traumatic brain injury (TBI) can induce cognitive dysfunction due to the regional accumulation of hyperphosphorylated tau protein (p-tau). However, the factors that cause p-tau to concentrate in specific brain regions remain unclear. Here, we show that AQP4 polarization in the perivascular astrocytic end feet was impaired after TBI, which was most prominent in the ipsilateral brain tissue surrounding the directly impacted region and the contralateral hippocampal CA1 area and was accompanied by increased local p-tau, changes in dendritic spine density and morphology, and upregulation of the adenosine A2A receptor (A2AR). The critical role of the A2AR signaling in these pathological changes was confirmed by alleviation of the impairment of AQP4 polarity and accumulation of p-tau in the contralateral CA1 area in A2AR knockout mice. Given that p-tau can be released to the extracellular space and that the astroglial water transport via AQP4 is involved in tau clearance from the brain interstitium, our results suggest that regional disruption of AQP4 polarity following TBI may reduce the clearance of the toxic interstitial solutes such as p-tau and lead to changes in dendritic spine density and morphology. This may explain why TBI patients are more vulnerable to cognitive dysfunction.

Background Our recent pilot study suggests intra-arterial tenecteplase (TNK) during the first pass of endovascular treatment (EVT) seems safe, may increase first-pass reperfusion and good outcome in acute ischaemic stroke (AIS) patients with large-vessel occlusion (LVO).Aims To determine the efficacy and safety of intra-arterial TNK administration during EVT in AIS-LVO patients presenting up to 24 hours from symptom onset.Sample size estimates A maximum of 380 patients are required to test the superiority hypothesis with 80% power according to a two-side 0.05 level of significance, stratified by age, gender, baseline systolic blood pressure, prestroke modified Rankin Scale (mRS), baseline National Institute of Health stroke scale, baseline ASPECTS, time from onset to groin puncture, intravenous thrombolysis before EVT, stroke territory and stroke aetiology.Design Intra-arterial TNK during thrombectomy for acute stroke (BRETIS-TNK II) study is a prospective, randomised, adaptive enrichment, open-label, blinded end point, multicentre study. Eligible AIS-LVO patients are randomly assigned into the experimental group and control group with a ratio of 1:1. The experimental group will be treated with intra-arterial infusion of TNK during EVT. The control group will be treated with standard EVT.Outcome The primary end point is a favourable outcome, defined as an mRS score of 0–2 at 90 days. The primary safety end point is symptomatic intracranial haemorrhage within 48 hours, which is defined as an increase in the National Institutes of Health Stroke Scale score of ≥4 points as a result of the intracranial haemorrhage.Conclusions The results of BRETIS-TNK II will provide evidence for the efficacy and safety of intra-arterial TNK administration during EVT in AIS patients with LVO.

Background The aim of the study was to establish a reliable scoring tool to identify the probability of symptomatic intracranial hemorrhage (sICH) in anterior circulation stroke patients with contrast enhancement (CE) on brain non-contrast CT (NCCT) after endovascular thrombectomy (EVT). Methods We retrospectively reviewed consecutive patients with acute ischemic stroke (AIS) who had CE on NCCT immediately after EVT for anterior circulation large vessel occlusion (LVO). We used the Alberta stroke program early CT score (ASPECTS) scoring system to estimate the extent and location of CE. Multivariable logistic regression was performed to derive an sICH predictive score. The discrimination and calibration of this score were assessed using the area under the receiver operator characteristic curve, calibration curve, and decision curve analysis. results In this study, 194 of 322 (60.25%) anterior circulation AIS-LVO patients had CE on NCCT. After excluding 85 patients, 109 patients were enrolled in the final analysis. In multivariate regression analysis, age ≥70 years (adjusted OR (aOR) 9.23, 95% CI 2.43 to 34.97, P < 0.05), atrial fibrillation (AF) (aOR 4.17, 95% CI 1.33 to 13.12, P < 0.05), serum glucose ≥11.1 mmol/L (aOR 9.39, 95% CI 2.74 to 32.14, P < 0.05), CE-ASPECTS < 5 (aOR 3.95, 95% CI 1.30 to 12.04 P < 0.05), and CE at the internal capsule (aOR 3.45, 95% CI 1.03 to 11.59, P < 0.05) and M1 region (aOR 3.65, 95% CI 1.13 to 11.80, P < 0.05) were associated with sICH. These variables were incorporated as the CE-age-glucose-AF (CAGA) score. The CAGA score demonstrated good discrimination and calibration in this cohort, as well as the fivefold cross validation. Conclusion The CAGA score reliably predicted sICH in patients with CE on NCCT after EVT treatment. [ABSTRACT FROM AUTHOR]