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Trials examining the benefit of thrombectomy in anterior circulation proximal large vessel occlusion stroke have enrolled patients considered to have salvageable brain tissue, who were randomly assigned beyond 6 h and (depending on study protocol) up to 24 h from time last seen well. We aimed to estimate the benefit of thrombectomy overall and in prespecified subgroups through individual patient data meta-analysis. We did a systematic review and individual patient data meta-analysis between Jan 1, 2010, and March 1, 2021, of randomised controlled trials of endovascular stroke therapy. In the Analysis Of Pooled Data From Randomized Studies Of Thrombectomy More Than 6 Hours After Last Known Well (AURORA) collaboration, the primary outcome was disability on the modified Rankin Scale (mRS) at 90 days, analysed by ordinal logistic regression. Key safety outcomes were symptomatic intracerebral haemorrhage and mortality within 90 days. Patient level data from 505 individuals (n=266 intervention, n=239 control; mean age 68·6 years [SD 13·7], 259 [51·3%] women) were included from six trials that met inclusion criteria of 17 screened published randomised trials. Primary outcome analysis showed a benefit of thrombectomy with an unadjusted common odds ratio (OR) of 2·42 (95% CI 1·76–3·33; p<0·0001) and an adjusted common OR (for age, gender, baseline stroke severity, extent of infarction on baseline head CT, and time from onset to random assignment) of 2·54 (1·83–3·54; p<0·0001). Thrombectomy was associated with higher rates of independence in activities of daily living (mRS 0–2) than best medical therapy alone (122 [45·9%] of 266 vs 46 [19·3%] of 238; p<0·0001). No significant difference between intervention and control groups was found when analysing either 90-day mortality (44 [16·5%] of 266 vs 46 [19·3%] of 238) or symptomatic intracerebral haemorrhage (14 [5·3%] of 266 vs eight [3·3%] of 239). No heterogeneity of treatment effect was noted across subgroups defined by age, gender, baseline stroke severity, vessel occlusion site, baseline Alberta Stroke Program Early CT Score, and mode of presentation; treatment effect was stronger in patients randomly assigned within 12–24 h (common OR 5·86 [95% CI 3·14–10·94]) than those randomly assigned within 6–12 h (1·76 [1·18–2·62]; pinteraction=0·0087). These findings strengthen the evidence for benefit of endovascular thrombectomy in patients with evidence of reversible cerebral ischaemia across the 6–24 h time window and are relevant to clinical practice. Our findings suggest that in these patients, thrombectomy should not be withheld on the basis of mode of presentation or of the point in time of presentation within the 6–24 h time window. Stryker Neurovascular.

BackgroundRevascularization after endovascular therapy for acute ischemic stroke is measured by the Thrombolysis In Cerebral Infarction (TICI) scale, yet variability exists in scale definitions. We examined the degree of reperfusion with the expanded TICI (eTICI) scale and association with outcomes in the HERMES collaboration of recent endovascular trials.MethodsThe HERMES Imaging Core, blind to all other data, evaluated angiography after endovascular therapy in HERMES. A battery of TICI scores (mTICI, TICI, TICI2C) was used to define reperfusion of the initial target occlusion defined by non-invasive imaging and conventional angiography.ResultsAngiography of 801 subjects was available, including 797 defined by non-invasive imaging (154 internal carotid artery (ICA), 583 M1, 60 M2) and 748 by conventional angiography (195 ICA, 459 M1, 94 M2). Among 729 subjects in whom the reperfusion grade could be established, using eTICI (3=100%, 2C=90–99%, 2b67=67–89%, 2b50=50–66%) of the conventional angiography target occlusion, there were 63 eTICI 3 (9%), 166 eTICI 2c (23%), 218 eTICI 2b67 (30%), 103 eTICI 2b50 (14%), 100 eTICI 2a (14%), 19 eTICI 1 (3%), and 60 eTICI 0 (8%). Modified Rankin Scale shift analyses from baseline to 90 days showed that increasing TICI grades were linked with better outcomes, with significant distinctions between TICI 0/1 versus 2a (p=0.028), 2a versus 2b50 (p=0.017), and 2b50 versus 2b67 (p=0.014).ConclusionsThe benefit of endovascular therapy in HERMES was strongly associated with increasing degrees of reperfusion defined by eTICI. The eTICI metric identified meaningful distinctions in clinical outcomes and may be used in future studies and routine practice.

Registry-based randomized controlled trials are defined as pragmatic trials that use registries as a platform for case records, data collection, randomization, and follow-up. Recently, the application of registry-based randomized controlled trials has attracted increasing attention in health research to address comparative effectiveness research questions in real-world settings, mainly due to their low cost, enhanced generalizability of findings, rapid consecutive enrollment, and the potential completeness of follow-up for the reference population, when compared with conventional randomized effectiveness trials. However several challenges of registry-based randomized controlled trials have to be taken into consideration, including registry data quality, ethical issues, and methodological challenges. In this article, we summarize the advantages, challenges, and areas for future research related to registry-based randomized controlled trials.

The purpose of this study was to investigate whether low cerebral blood flow (CBF) is associated with subsequent development of white matter hyperintensities (WMH). Patients were included from a longitudinal magnetic resonance (MR) imaging study of minor stroke/transient ischemic attack patients. Images were co-registered and new WMH at 18 months were identified by comparing follow-up imaging with baseline fluid-attenuated inversion recovery (FLAIR). Regions-of-interest (ROIs) were placed on FLAIR images in one of three categories: (1) WMH seen at both baseline and follow-up imaging, (2) new WMH seen only on follow-up imaging, and (3) regions of normal-appearing white matter at both time points. Registered CBF maps at baseline were used to measure CBF in the ROIs. A multivariable model was developed using mixed-effects logistic regression to determine the effect of baseline CBF on the development on new WMH. Forty patients were included. Mean age was 61 ± 11 years, 30% were female. Low baseline CBF, female sex, and presence of diabetes were independently associated with the presence of new WMH on follow-up imaging. The odds of having new WMH on follow-up imaging reduces by 0.61 (95% confidence interval = 0.57 to 0.65) for each 1 mL/100 g per minute increase in baseline CBF. We conclude that regions of white matter with low CBF develop new WMH on follow-up imaging.

Background Corticosteroids are frequently used in practice to treat patients with neurological disorders. However, its effect for stroke and traumatic brain injury (TBI) remains controversial. This study aimed to systematically review and evaluate efficacy and safety of corticosteroids for the treatment of stroke and TBI. Methods We searched Ovid-Medline and Ovid-Embase databases for randomised controlled trials (RCTs) and cohort studies evaluating the efficacy and safety of corticosteroids in patients with ischaemic stroke, intracerebral haemorrhage (ICH), subarachnoid haemorrhage (SAH) or TBI. The treatment intervention was corticosteroid, and the control was placebo or routine care. Outcome measures were death, functional outcomes and adverse events. We calculated odds ratio (OR) and 95% confidence interval (CI) for the effect size, pooled the results using random-effects modelling, and assessed heterogeneity by I 2 statistic. Results We identified 47 studies (41 RCTs and 6 cohort studies). Nine studies enrolled patients with ischaemic stroke ( n  = 2806), 6 studies for ICH ( n  = 1229), 1 study recruited both ischaemic stroke ( n  = 13) and ICH ( n  = 27), 10 studies for SAH ( n  = 1318) and 21 studies for TBI ( n  = 12,414). Dexamethasone was the most used corticosteroid (28 studies). Corticosteroids reduced risk of death at 3 months after ischaemic stroke ( n  = 1791; 31% vs. 26%, OR 0.77, 95% CI 0.62–0.95; df  = 1, I 2  = 0%) and after ICH (1 study; n  = 850; 44% vs. 27%, OR 0.48, 95% CI 0.35–0.64), had no effect on death at 1 month after SAH (1 study; n  = 140; 22% vs. 32%, OR 1.73, 95% CI 0.81–3.68), and increased risk of death at 6 months after TBI ( n  = 10,755; 23% vs. 27%, OR 1.20, 95% CI 1.10–1.32; df  = 6, I 2  = 0%). The pooled analyses found no significant effect of corticosteroids on functional outcome after ischaemic stroke, ICH, SAH or TBI, respectively. Conclusion Corticosteroids reduced the risk of death and in selected patients with stroke, such as those with large artery occlusion after thrombectomy, but increased the risk of death after TBI, had no effect on functional outcomes. Further trials are needed to identify individual stroke patients who may benefit from corticosteroids. Systematic review registration International Prospective Register of Systematic Reviews (CRD42023474473).

Acute ischemic stroke is a leading cause of mortality and disability worldwide. Neuroinflammation following ischemia‐reperfusion plays a critical role in the disease's pathogenesis. Neutrophil aggregation and clearance within the brain parenchyma influence neuroinflammatory damage during ischemic stroke. Microglia‐mediated phagocytosis plays a pivotal role in mitigating neuroinflammation and promoting brain parenchyma recovery. However, the mechanisms underlying the cross‐talk between neutrophils and microglia remain poorly understood. Here, this study demonstrates that neutrophils can trigger microglial functional change to inhibit microglial phagocytosis and promote pyroptosis, which is regulated by neutrophil‐derived myeloid‐related protein 14. Additionally, interleukin‐1β released by pyroptotic microglia further upregulates myeloid‐related protein 14 expression and facilitates neutrophil mobilization from the bone marrow, establishing a self‐sustaining inflammatory loop. Therefore, neutrophils accumulate in the brain parenchyma and further exacerbate microglial neuroinflammation in the ischemic brain. These findings reveal a previously unknown interaction between neutrophils and microglia after acute ischemic stroke and suggest that targeting myeloid‐related protein 14 may provide a novel therapeutic strategy for ischemic stroke therapy. These study underscores the pivotal role of neutrophil‐derived myeloid‐related protein 14 (MRP14) in the pathophysiology of acute ischemic stroke (AIS). MRP14 not only disrupts mitochondrial function, thereby inhibiting microglial phagocytosis of neutrophils, but also activates microglial pyroptosis, exacerbating neuroinflammation following AIS. Targeting MRP14 could offer a promising therapeutic strategy to mitigate neuroinflammation and improve outcomes for patients with AIS.

We hypothesized that the association between BP and endovascular treatment (EVT) outcomes would differ by baseline perfusion and recanalization status. We identified 388 ICA or M1 occlusion patients who underwent EVT ≤ 24 h from onset with successful recanalization (TICI ≥ 2b). BP was measured at 5-min intervals from arrival and during the procedure. Systolic BPs (SBP) were summarized as dropmax (the maximal decrease over two consecutive measurements), incmax (the maximal increase), mean, coefficient of variation (cv), and standard deviation. Adequate baseline perfusion was defined as hypoperfusion intensity ratio (HIR) ≤ 0.5; infarct proportion as the volume ratio of final infarcts within the T max  > 6 s region. In the adequate perfusion group, infarct proportion was closely associated with SBP dropmax (β ± SE ( P -value); 1.22 ± 0.48, (< 0.01)), SBP incmax (1.12 ± 0.33, (< 0.01)), SBP cv (0.61 ± 0.15 (< 0.01)), SBP sd (0.66 ± 0.08 (< 0.01)), and SBP mean (0.71 ± 0.37 (0.053) before recanalization. The associations remained significant only in SBP dropmax , SBP incmax , and SBP mean after recanalization. SBP incmax , SBP cv and SBP sd showed significant associations with modified Rankin Scale score at 3 months in the pre-recanalization period. In the poor perfusion group, none of the SBP indices was associated with any stroke outcomes regardless of recanalization status. BP may show differential associations with stroke outcomes by the recanalization and baseline perfusion status.

Recombinant tissue plasminogen activator improves outcomes in acute ischemic stroke. Alteplase may result in thrombus migration (TM) distally to a critical arterial supply that can worsen perfusion to eloquent brain tissue. Alteplase-related stroke recanalization and clot migration in vertebral artery (VA) occlusion whereby the clot migrates to the basilar artery (BA) may be harmful. We identified seven subjects with isolated symptomatic vertebral occlusion. Two cases suffered early neurologic deterioration due to TM from VA to BA following alteplase. Precautionary transfer to thrombectomy centers may be warranted in alteplase-treated symptomatic VA occlusions in case of migration to basilar occlusion.

Blood-brain barrier (BBB) permeability has been proposed as a predictor of hemorrhagic transformation (HT) after tissue plasminogen activator (tPA) administration; however, the reliability of perfusion computed tomography (PCT) permeability imaging for predicting HT is uncertain. We aimed to determine the performance of high-permeability region size on PCT (HPrs-PCT) in predicting HT after intravenous tPA administration in patients with acute stroke. We performed a multimodal CT protocol (non-contrast CT, PCT, CT angiography) to prospectively study patients with middle cerebral artery occlusion treated with tPA within 4.5 hours of symptom onset. HT was graded at 24 hours using the European-Australasian Acute Stroke Study II criteria. ROC curves selected optimal volume threshold, and multivariate logistic regression analysis identified predictors of HT. The study included 156 patients (50% male, median age 75.5 years). Thirty-seven (23,7%) developed HT [12 (7,7%), parenchymal hematoma type 2 (PH-2)]. At admission, patients with HT had lower platelet values, higher NIHSS scores, increased ischemic lesion volumes, larger HPrs-PCT, and poorer collateral status. The negative predictive value of HPrs-PCT at a threshold of 7mL/100g/min was 0.84 for HT and 0.93 for PH-2. The multiple regression analysis selected HPrs-PCT at 7mL/100g/min combined with platelets and baseline NIHSS score as the best model for predicting HT (AUC 0.77). HPrs-PCT at 7mL/100g/min was the only independent predictor of PH-2 (OR 1, AUC 0.68, p = 0.045). HPrs-PCT can help predict HT after tPA, and is particularly useful in identifying patients at low risk of developing HT.