Thrombectomy for anterior circulation stroke beyond 6 h from time last known well (AURORA): a systematic review and individual patient data meta-analysis.

BACKGROUND: 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. METHODS: 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. FINDINGS: 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). INTERPRETATION: 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. FUNDING: Stryker Neurovascular.

The feasibility of dual-energy CT to predict the probability of symptomatic intracerebral haemorrhage after successful mechanical thrombectomy.

AIM: To study the ability of dual-energy computed tomography (DECT) after successful mechanical thrombectomy (MT) to predict symptomatic intracerebral haemorrhage (sICH) in anterior circulation acute ischaemic stroke (AIS). MATERIALS AND METHODS: From June 2018 to February 2020, 102 AIS patients with DECT performed immediately after successful MT were enrolled prospectively. According to the presence of iodine contrast media extravasation (ICME) on DECT and subsequent sICH development, patients were classified into four groups. The neurological outcome was compared among groups. Imaging parameters, together with clinical factors, were investigated for sICH prediction based on a linear logistic regression model after class-imbalance resolved by Synthetic Minority Sampling Technique (SMOTE) method. RESULTS: Among 102 patients, patients (14.7%, 15/102) with the presence of sICH experienced worse outcomes than others without sICH (p<0.001). No case without ICME was observed with sICH development (0/102). The parameters derived from DECT have excellent performance for sICH prediction after successful MT, which is better than clinical predictive model boosted data (area under the curve [AUC]: DECT 0.87 versus clinical prediction 0.65), cross-validation results (AUC: DECT 0.87 versus clinical prediction 0.65), and original data (AUC: DECT 0.85 versus clinical prediction 0.68). By combining clinical and radiological parameters, the predictive performance for sICH could be further improved with an AUC of 0.90 (95% CI: 0.85-0.96). CONCLUSIONS: Based on DECT parameters acquired immediately after successful MT, the present model was more efficient than the clinical model for accurate prediction of sICH. Rho and ICME volume appeared to be the best parameters for predicting sICH using DECT.

Arteritis and Large Vessel Occlusive Strokes in Children After COVID-19 Infection.

We describe 2 previously healthy children who suffered disabling arterial ischemic strokes because of acute intracranial large vessel occlusion within 3 to 4 weeks of coronavirus disease 2019 (COVID-19) infection. Both children presented from communities with high COVID-19 case rates in the Southwest United States. An 8-year-old American Indian girl experienced severe iron deficiency anemia requiring blood transfusion and presented with bilateral middle cerebral artery (MCA) distribution strokes 3 weeks later. She underwent emergent mechanical thrombectomy of the left MCA with successful clot retrieval but experienced reocclusion of that artery 5 hours after intervention. She also had evidence of cerebral arteritis on catheter angiography and vessel wall imaging, and clot pathology revealed recently formed, unorganized platelet- and fibrin-rich thrombus with sparse clusters of erythrocytes, degenerated histiocytes, few eosinophils, and rare neutrophils. A 16-year old African American boy demonstrated evidence of arteritis on brain magnetic resonance angiography and serological markers of cardiac and renal injury accompanied by positive lupus anticoagulant antibodies. The children described in this report express clinical features inconsistent with focal cerebral arteriopathy, including elevated markers of systemic inflammation in both bilateral MCA strokes in one case and multiple organ system dysfunction in the other case. Neither patient fulfilled criteria for multisystem inflammatory syndrome in children, given absence of fever. These cases illustrate that systemic postinfectious arteritis with cerebrovascular involvement may complicate COVID-19 infection in previously healthy school-aged children, and their presentations may overlap but not fulfill criteria for multisystem inflammatory syndrome in children or focal cerebral arteriopathy.

Fibrin and Platelet-Rich Composition in Retrieved Thrombi Hallmarks Stroke With Active Cancer.

BACKGROUND AND PURPOSE: We aim to investigate whether histopathologic examination of thrombi retrieved from acute ischemic stroke patients undergoing endovascular treatment could distinguish cancer-related stroke from other etiologies. METHODS: Thrombi from patients undergoing endovascular treatment were analyzed. The etiology of stroke was divided into cardioembolism, large artery atherosclerosis, and active cancer groups. All selected thrombi were subjected to hematoxylin and eosin staining. The percentages of fibrin/platelets, red blood cells, and white blood cells within a thrombus were quantified. RESULTS: One-hundred fifty-two patients (active cancer, 19; cardioembolism, 107; large artery atherosclerosis, 26) were included. Thrombi from the active cancer group exhibited a higher fibrin/platelet composition than did those from the cardioembolism and large artery atherosclerosis groups (median, 85.7% versus 43.9% and 42.5%; P<0.001). Fibrin/platelet composition was the only independent factor (odds ratio, 1.05 [95% CI, 1.02-1.08]) in differentiating cancer-related stroke from stroke caused by cardioembolism and large artery atherosclerosis. A fibrin/platelet proportion of ≥65% accurately predicted cancer-related stroke (area under the curve, 0.84; P<0.001). CONCLUSIONS: In thrombi retrieved from patients undergoing endovascular treatment, a high fibrin/platelet composition was a probable indicator of cancer-related stroke.

hUCMSCs Mitigate LPS-Induced Trained Immunity in Ischemic Stroke.

Innate immune memory is a part of the innate immune system that facilitates the elimination of pathogens. However, it may exacerbate neuropathology. In this study, we found that innate immune memory is detrimental in stroke, because it promotes the acute immune response and exacerbates ischemic infarcts. Mesenchymal stem cell therapy has been widely studied for its therapeutic potential in various diseases including stroke, but whether it diminishes innate immune memory has not been studied. Here, our study demonstrates that, after the activation of innate immune memory by lipopolysaccharide, mesenchymal stem cell therapy can diminish innate immune memory though down-regulation of H3 methylation and subsequently protect against stroke. Our results demonstrate that innate immune memory is detrimental in stroke, and we describe a novel potential therapeutic target involving the use of mesenchymal stem cells to treat stroke patients.

Predictors of Very Poor Outcome after Mechanical Thrombectomy for Acute Basilar Artery Occlusion.

Prognosis for patients with acute basilar artery occlusion (BAO) remains poor. Successful revascularization is a main predictor of favorable clinical outcomes after mechanical thrombectomy for BAO. However, even if mechanical thrombectomy is successful, some patients have a poor clinical outcome, including vegetative state and mortality. This study investigated the factors that are predictive of extremely poor clinical outcomes despite successful revascularization after mechanical thrombectomy for BAO. We evaluated 35 consecutive patients who presented with acute ischemic stroke due to BAO and who were successfully treated with mechanical thrombectomy. A very poor outcome was defined as a modified Rankin Scale (mRS) score of 5 or 6 at 3 months after treatment. The associations between the clinical, imaging, procedural factors, and poor outcome were evaluated. Using univariate analyses, there were significant differences in the preoperative National Institute of Health Stroke Scale (NIHSS) score (22.0 ± 9.0 vs. 30.5 ± 4.3, p <0.001), and infarct volume in brain stem (0.11 ± 0.19 cc vs. 2.55 ± 1.56 cc, p <0.001) between the control and very poor outcome groups. In receiver operating characteristic (ROC) curve analysis, the area under ROC curve of infarct volume in brain stem was 0.891 to predict very poor outcome. Preoperative infarct volume in brain stem is strong predictor for very poor outcome. The infarct volume in brain stem is useful for deciding treatment indications.

Predictors of Favorable Outcome after Endovascular Thrombectomy in MRI: Selected Patients with Acute Basilar Artery Occlusion.

BACKGROUND AND PURPOSE: Clinical outcomes after endovascular treatment for acute basilar artery occlusions need further investigation. Our aim was to analyze predictors of a 90-day good functional outcome defined as mRS 0-2 after endovascular treatment in MR imaging-selected patients with acute basilar artery occlusions. MATERIALS AND METHODS: We analyzed consecutive MR imaging-selected patients with acute basilar artery occlusions endovascularly treated within the first 24 hours after symptom onset. Successful and complete reperfusion was defined as modified TICI scores 2b-3 and 3, respectively. Outcome at 90 days was analyzed in univariate and multivariate analysis regarding baseline patient treatment characteristics and periprocedural outcomes. RESULTS: One hundred ten patients were included. In 10 patients, endovascular treatment was aborted for failed proximal/distal access. Overall, successful reperfusion was achieved in 81.8% of cases (n = 90; 95% CI, 73.3%-88.6%). At 90 days, favorable outcome was 31.8%, with a mortality rate of 40.9%; the prevalence of symptomatic intracranial hemorrhage within 24 hours was 2.7%. The median time from symptom onset to groin puncture was 410 minutes (interquartile range, 280-540 minutes). In multivariable analysis, complete reperfusion (OR = 6.59; 95% CI, 2.17-20.03), lower pretreatment NIHSS (OR = 0.77; 95% CI, 0.64-0.94), the presence of posterior communicating artery collateral flow (OR = 2.87; 95% CI, 1.05-7.84), the absence of atrial fibrillation (OR = 0.18; 95% CI, 0.03-0.99), and intravenous thrombolysis administration (OR = 2.75; 95% CI, 1.04-7.04) were associated with 90-day favorable outcome. CONCLUSIONS: In our series of MR imaging-selected patients with acute basilar artery occlusions, complete reperfusion was the strongest predictor of a good outcome. Lower pretreatment NIHSS, the presence of posterior communicating artery collateral flow, the absence of atrial fibrillation, and intravenous thrombolysis administration were associated with favorable outcome.

Long-Term Outcomes of Acute Endovascular Thrombectomy: Tokyo/tama-Registry of Acute Endovascular Thrombectomy (TREAT).

OBJECTIVE: Mechanical thrombectomy (MT) is the recommended treatment for patients with acute ischemic stroke due to large cerebral vessel occlusion (LVO). However, few studies have investigated long-term outcomes after MT. The aim of this study was to investigate functional outcomes at long-term follow-up (1 year after MT) in patients undergoing MT for anterior circulation LVO in real-world clinical practice. METHODS: This was a retrospective and prospective observational study using data from TREAT (Tokyo/tama-Registry of Acute Endovascular Thrombectomy), a multicenter registry of MT for acute LVO in the Tokyo metropolitan area. All subjects emergently transferred and treated with MT from January 2015 to December 2018 were selected. Patients' baseline characteristics and stroke-related parameters were evaluated. The primary outcome was the modified Rankin Scale (mRS) score 1 year after MT. The secondary outcomes were risk factors for long-term good outcomes (mRS score 0-2); transfer system (stroke bypass vs. secondary transfer) was also evaluated as a potential factor associated with good long-term outcomes. RESULTS: A total of 162 cases (mean age 73.0 years, age range 30-97 years; 59.9% male) whose mRS scores at 1 year were obtained were analyzed. The median admission National Institutes of Health Stroke Scale (NIHSS) score was 17. Overall, 42.6% of the patients achieved functional independence at 1-year follow-up. Lower initial NIHSS score and mRS score 0-2 at 90 days were the independent predictors for good long-term outcomes. Stroke bypass was associated with a higher initial NIHSS score and mRS score 0 at 1 year. CONCLUSIONS: A significant number of patients experience a good long-term outcome after MT.