Incidence, predictors, and outcomes of malignant cerebral edema in acute basilar artery occlusion after endovascular treatment: a secondary analysis of the ATTENTION trial.

OBJECTIVE: Malignant cerebral edema (MCE) is a life-threatening complication of ischemic stroke. Few studies have evaluated MCE in patients with acute basilar artery occlusion (BAO) receiving endovascular treatment (EVT). Therefore, the authors investigated the incidence, predictors, and functional outcomes of MCE in BAO patients undergoing EVT. METHODS: This was a post hoc analysis of the Endovascular Treatment for Acute Basilar Artery Occlusion (ATTENTION) trial, a prospective, randomized, multicenter clinical trial that compared endovascular treatment with conventional care of patients with BAO at 36 centers in China. Brain edema was retrospectively assessed using the Jauss score for all available follow-up scans, and patients with a Jauss score ≥ 4 were classified as having MCE. Clinical functional independence was defined as a modified Rankin Scale (mRS) score of 0-2, and a good outcome was defined as an mRS score of 0-3 at the 90-day follow-up. Univariate and multivariate analyses were used to explore the predictors of MCE and the impact of MCE on prognosis. RESULTS: A total of 189 patients were analyzed, and 13.2% of patients developed MCE. Multivariate analysis showed that the baseline Glasgow Coma Scale (GCS) score (OR 0.722, 95% CI 0.548-0.950; p = 0.020) and the number of procedures (OR 1.594, 95% CI 1.051-2.419; p = 0.028) were significantly associated with MCE. After adjusting for confounding factors, the presence of MCE was significantly associated with a lower rate of functional independence (OR 0.115, 95% CI 0.023-0.563; p = 0.008), a lower rate of good outcome (OR 0.092, 95% CI 0.023-0.360; p = 0.001), and a higher rate of mortality (OR 5.373, 95% CI 2.055-14.052; p = 0.001) at the 90-day follow-up. CONCLUSIONS: MCE is not uncommon in BAO patients undergoing EVT and is associated with poor outcomes. Baseline GCS score and the number of procedures were predictors of MCE. In clinical practice, it is crucial that physicians identifying MCE after EVT in patients with BAO and identification of MCE will help in the selection of an appropriate pharmacological treatment strategy and close monitoring.

Elabela ameliorates neuronal pyroptosis and mitochondrial fission via APJ/ZBP1 signaling in ischemic stroke.

Pyroptosis signifies a significant form of programmed neuronal demise subsequent to ischemic stroke. In our prior investigations, we demonstrated that the Elabela (ELA)-Apelin receptor (APJ) axis alleviated neuronal death by improving collateral circulation and mitigating ferroptosis in a murine model of middle cerebral artery occlusion (MCAO). However, the connection between ELA and neuronal pyroptosis remains further elucidation. Here, we observed an upregulation of ELA and APJ expression in both murine brain specimens and cultured HT-22 hippocampal neurons exposed to experimental ischemic stroke. ELA administration markedly diminished the infarct size in comparison to controls. ELA treatment ameliorated neurological deficits and anxiety-like symptoms in mice with stroke, concurrently inhibiting pyroptosis and mitochondria fission in neurons. Conversely, ELA knockdown yielded the opposite effects. Utilizing RNA-sequencing analysis, we identified a candidate for pyroptosis priming, Z-DNA-binding protein 1 (ZBP1), which was suppressed in ELA-treated HT-22 neurons during oxygen-glucose deprivation/reperfusion (OGD/R). Subsequent co-immunoprecipitation analyses demonstrated the binding between APJ and ZBP1. Specifically, APJ suppressed ZBP1 to inhibit NLRP3 inflammasome activation and dynamin-related protein 1-mediated mitochondrial fission in neurons. In summary, our findings suggest that ELA functions as a stroke-induced signal limiting neuronal pyroptosis and mitochondrial fission via APJ/ZBP1 signaling, thereby underscoring ELA as a potential therapeutic target for ischemic stroke treatment.

Effects of admission hyperglycemia and intravenous thrombolysis allocation in acute basilar artery occlusion after endovascular treatment: Analysis of the ATTENTION registry.

This study was to investigate the admission hyperglycemia and modified effect of intravenous thrombolysis (IVT) on clinical outcomes in acute basilar artery occlusion (BAO) patients receiving endovascular treatment (EVT). We prospectively recruited acute BAO patients from 48 stroke centers across 22 Chinese provinces in the ATTENTION registry from 2017 to 2021. Hyperglycemia on admission was defined as glucose ≥7.8 â€‹mmol/L. We performed multivariable logistic regression analysis to evaluate the correlation of hyperglycemia on admission with the primary outcome defined as a modified Rankin scale (mRS) score of <4 â€‹at 90 days, and the secondary outcomes defined as successful recanalization, mRS 0-1 and 0-2 â€‹at 90 days. Safety outcomes were symptomatic intracranial hemorrhage (sICH) and mortality within 90 days. There were 1195 patients with acute BAO treated with EVT of whom 519 had hyperglycemia on admission. Hyperglycemia on admission was inversely associated with favorable neurological outcomes (mRS 0-3: adjusted odd ratio [aOR] 0.69, 95 â€‹% confidence intervals [CI] 0.54-0.89, P â€‹= â€‹0.004; mRS 0-1: aOR 0.67, 95 â€‹% CI 0.50-0.90, P â€‹= â€‹0.008; mRS 0-2: aOR 0.73, 95 â€‹% CI 0.56-0.95; P â€‹= â€‹0.02). Hyperglycemia on admission was not correlated to sICH nor successful recanalization. In the subgroup of BAO patients treated with direct EVT, those with hyperglycemia on admission had a higher mortality rate, and overall worse clinical outcomes at 90 days than patients without hyperglycemia. A significant interaction was observed between IVT and hyperglycemia on admission (Pinteraction â€‹= â€‹0.017). In patients with acute BAO treated with EVT, hyperglycemia on admission was associated with worse functional outcomes at 90 days but was not correlated with sICH nor successful recanalization. The effect of admission hyperglycemia appears to be modified by IVT allocation. Unique identifier: ChiCTR2000041117.

Predictors of good outcomes and mortality after thrombectomy for basilar artery occlusion within 12 hours of onset.

BACKGROUND: Patients with acute basilar artery occlusion (ABAO) who undergo combined standard medical treatment (SMT) and endovascular thrombectomy (EVT) may still have unsatisfactory outcomes. This study was conducted to identify the factors that may impact their outcomes. METHODS: We retrospectively reviewed the data of all patients with ABAO combined with SMT and EVT in the endovascular treatment for acute basilar artery occlusion (ATTENTION) trial. A good outcome is defined as a modified Rankin Scale (mRS) score of 0-3, a poor outcome as mRS score of 4-6, and mortality as death at 90-day follow-up. The study analyzed various factors influencing the patients' good outcomes and mortality. RESULTS: The study included 221 patients (148 men and 73 women). Among these patients, 45.7% achieved an mRS score of 0-3, while the overall mortality rate was 37.1% (82/221). A good outcome was significantly associated with younger age (adjusted OR 0.96; 95% CI 0.93 to 0.99; P=0.019), a baseline posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS) of 8-10 (adjusted OR 2.34; 95% CI 1.07 to 5.12; P=0.034), and post-procedure pc-ASPECTS of 8-10 (adjusted OR 1.40; 95% CI 1.07 to 1.84; P=0.013). Additionally, time from puncture to reperfusion (adjusted OR 2.02; 95% CI 1.2 to 3.41; P=0.008) and intracranial hemorrhage (adjusted OR 3.59; 95% CI 1.09 to 11.8; P=0.035) were associated with 90-day mortality. CONCLUSIONS: Younger age, baseline pc-ASPECTS of 8-10, and higher post-procedure pc-ASPECTS could effectively predict good outcomes for patients with ABAO undergoing EVT. Additionally, a prolonged time from puncture to reperfusion and intracranial hemorrhage can independently predict mortality. TRIAL REGISTRATION NUMBER: NCT04751708.

The Role of Hyperdense Basilar Artery Sign in Predicting Outcome of Acute Basilar Artery Occlusion within Twelve Hours of Onset.

BACKGROUND: The correlation between hyperdense basilar artery sign (HDBAS) and outcome after acute basilar artery occlusion (ABAO) is debated. Our objective was to determine the usefulness of HDBAS in predicting the outcomes of patients with ABAO after endovascular treatment (EVT), intravenous thrombolysis (IVT), and best medical treatment (BMT). METHODS: The study participants were selected from the ATTENTION trial. The primary outcome of the study was a 90-day modified Rankin Scale (mRS) score, and the secondary outcome was the recanalization rate, any intracranial hemorrhage, and 90-day mortality. RESULTS: The study comprised 276 participants, with cohorts for EVT (n = 188), IVT (n = 82), and BMT (n = 88). In the EVT cohort, HDBAS was not associated with 90-day mRS score (adjusted odds ratio [OR], 0.87; 95% confidence interval [CI], 0.51-1.48; P = 0.6029), the recanalization after 24 hours of onset (adjusted OR, 0.76; 95% CI, 0.30-3.61; P = 0.9422), and 90-day mortality (adjusted OR, 0.77; 95% CI, 0.41-1.46; P = 0.4238). In the IVT cohort, HDBAS was not associated with a 90-day mRS score (adjusted OR, 0.69; 95% CI, 0.31-1.56; P = 0.3742), the recanalization after 24 hours of onset (adjusted OR, 2.24; 95% CI, 0.47-10.78; P = 0.3132), and 90-day mortality (adjusted OR, 0.64; 95% CI, 0.26-1.57; P = 0.3264). Similarly, in the BMT cohort, HDBAS was not associated with 90-day mRS score (adjusted OR, 1.11; 95% CI, 0.47-2.63; P = 0.8152), the recanalization after 24 hours of onset (adjusted OR, 1.27; 95% CI, 0.40-4.02; P = 0.6874), and 90-day mortality (adjusted OR, 1.17; 95% CI, 0.46-2.96; P = 0.748). CONCLUSIONS: HDBAS may not be a reliable predictor of outcomes for patients with ABAO, regardless of whether they received EVT, IVT, or BMT.

Intra-arterial tenecteplase following endovascular therapy in patients with acute posterior circulation arterial occlusion: study protocol and rationale.

BACKGROUND: Recently, a randomized controlled trial showed a beneficial effect of intra-arterial thrombolysis following successful endovascular thrombectomy (EVT) in patients with acute ischemic stroke due to large vessel occlusion in the anterior circulation. Due to differences in response to thrombolytics in occlusion of the posterior circulation, the purpose of ATTENTION IA is to explore the adjunct benefit of intra-arterial thrombolysis after successful recanalization in patients presenting with large and medium vessel occlusion of the posterior circulation. METHODS: ATTENTION-IA is an investigator-initiated, multicenter, prospective, randomized clinical trial with open-label treatment and blinded endpoint assessment (PROBE). After achieving successful recanalization (expanded Thrombolysis In Cerebral Infarction (eTICI) 2b-3) of an occlusion of the vertebral, basilar, or posterior cerebral artery, patients will be randomized 1:1 to receive intra-arterial tenecteplase or standard of care. The primary effect parameter is a modified Rankin Score of 0-1 at day 90. RESULTS: The trial recently completed enrollment, and data collection/verification is ongoing. The final results will be made available on completion of enrollment and follow-up. CONCLUSIONS: ATTENTION-IA will provide definitive evidence for the efficacy and safety of adjunct intra-arterial tenecteplase after successful EVT in patients with an acute posterior circulation arterial occlusion stroke presenting within 24 hours of symptom onset. TRIAL REGISTRATION: ClinicalTrials.gov NCT05684172.

TMAO Promotes NLRP3 Inflammasome Activation of Microglia Aggravating Neurological Injury in Ischemic Stroke Through FTO/IGF2BP2.

Objective: Stroke is a kind of cerebrovascular disease with high mortality. TMAO has been shown to aggravate stroke outcomes, but its mechanism remains unclear. Materials and Methods: Mice were fed with 0.12% TMAO for 16 weeks. Then, mice were made into MCAO/R models. Neurological score, infarct volume, neuronal damage and markers associated with inflammation were assessed. Since microglia played a crucial role in ischemic stroke, microglia of MCAO/R mice were isolated for high-throughput sequencing to identify the most differentially expressed gene following TMAO treatment. Afterward, the downstream pathways of TMAO were investigated using primary microglia. Results: TMAO promoted the release of inflammatory cytokines in the brain of MCAO/R mice and promoted the activation of OGD/R microglial inflammasome, thereby exacerbating ischemic stroke outcomes. FTO/IGF2BP2 inhibited NLRP3 inflammasome activation in OGD/R microglia by downregulating the m6A level of NLRP3. TMAO can inhibit the expression of FTO and IGF2BP2, thus promoting the activation of NLRP3 inflammasome in OGD/R microglia. In conclusion, these results demonstrated that TMAO promotes NLRP3 inflammasome activation of microglia aggravating neurological injury in ischemic stroke through FTO/IGF2BP2. Conclusion: Our results demonstrated that TMAO promotes NLRP3 inflammasome activation of microglia aggravating neurological injury in ischemic stroke through FTO/IGF2BP2. These findings explained the molecular mechanism of TMAO aggravating ischemic stroke in detail and provided molecular mechanism for clinical treatment.

Basilar artery occlusion location and clinical outcome: data from the ATTENTION multicenter registry.

BACKGROUND: Acute basilar artery occlusion is a disabling and life-threatening condition. The purpose of this study was to evaluate the impact of occluded vessel location on the prognostic outcomes of patients who underwent endovascular treatment for acute basilar artery occlusion. METHODS: Patient data for this study were obtained from the ATTENTION registry. Baseline data of the patients were described and compared across different occlusion locations. Univariable and multivariable regression analyses were performed to assess the effect of occluded vessel location on associated prognostic outcomes. RESULTS: A total of 1672 patients were included in the analysis, with 583 having distal occlusion, 540 having middle occlusion, and 549 having proximal occlusion. Unlike distal occlusion, both proximal and middle occlusions were significantly and negatively associated with favorable clinical outcomes (for modified Rankin Scale score 0-3: adjusted odds ratio (aOR) 0.634, 95% confidence interval (95% CI) 0.493 to 0.816, P<0.001 in middle occlusion, and aOR 0.620, 95% CI 0.479 to 0.802, P<0.001 in proximal occlusion). Mortality was higher in patients with proximal and middle occlusions (aOR 1.461, 95% CI 1.123 to 1.902, P=0.005 in middle occlusion, and aOR 1.648, 95% CI 1.265 to 2.147, P<0.001 in proximal occlusion). The occluded vessel location was not associated with symptomatic intracranial hemorrhage. CONCLUSIONS: Proximal and middle basilar artery occlusions were predominantly associated with poor clinical outcomes and increased risk of death following endovascular treatment.

Anesthetic Management and Outcomes of Endovascular Treatment of Basilar Artery Occlusion: Results From the ATTENTION Registry.

BACKGROUND AND PURPOSE: To examine the clinical and safety outcomes after endovascular treatment (EVT) for acute basilar artery occlusion (BAO) with different anesthetic modalities. METHODS: This was a retrospective analysis using data from the Endovascular Treatment for Acute Basilar Artery Occlusion (ATTENTION) registry. Patients were divided into two groups defined by anesthetic modality performed during EVT: general anesthesia (GA) or non-general anesthesia (non-GA). The association between anesthetic management and clinical outcomes was evaluated in a propensity score matched (PSM) cohort and an inverse probability of treatment weighting (IPTW) cohort to adjust for imbalances between the two groups. RESULTS: Our analytic sample included 1,672 patients from 48 centers. The anesthetic modality was GA in 769 (46.0%) and non-GA in 903 (54.0%) patients. In our primary analysis with the PSM-based cohort, non-GA was comparable to GA concerning the primary outcome (adjusted common odds ratio [acOR], 1.01; 95% confidence interval [CI], 0.82 to 1.25; P=0.91). Mortality at 90 days was 38.4% in the GA group and 35.8% in the non-GA group (adjusted risk ratio, 0.95; 95% CI, 0.83 to 1.08; P=0.44). In our secondary analysis with the IPTW-based cohort, the anesthetic modality was significantly associated with the distribution of modified Rankin Scale at 90 days (acOR: 1.45 [95% CI: 1.20 to 1.75]). CONCLUSION: In this nationally-representative observational study, acute ischemic stroke patients due to BAO undergoing EVT without GA had similar clinical and safety outcomes compared with patients treated with GA. These findings provide the basis for large-scale randomized controlled trials to test whether anesthetic management provides meaningful clinical effects for patients undergoing EVT.

Effect of routine inflammatory markers on clinical outcomes in acute basilar artery occlusion after endovascular thrombectomy: Results from ATTENTION registry.

BACKGROUND: To investigate the relationship between clinical routine inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), white blood cell count (WBC), neutrophils, lymphocytes, and platelets with clinical outcomes in acute basilar artery occlusion (BAO) patients receiving endovascular treatment (EVT). METHODS: We recruited 2134 acute BAO patients from 48 stroke centers across 22 Chinese provinces in the ATTENTION registry from 2017 to 2021. Blood samples were drawn at admission. An unfavorable functional outcome was defined using a modified Rankin Scale (mRS) of 4-6 at 90 days. Safety outcomes included mortality within 90 days and symptomatic intracerebral hemorrhage within 3 days. RESULTS: A total of 1044 patients were included in the final study. After adjusting for confounding factors, the upper quartiles of WBC and NLR were related to 90-day unfavorable functional outcome (mRS = 4-6) compared with those in the lowest quartile (WBC: quartile 4, odds ratio (OR) = 1.85, 95% confidence interval (CI) = 1.22-2.80; NLR: quartile 4, OR = 2.02, 95% CI = 1.34-3.06). The higher quartiles of WBC and NLR were also related to the increased risk of mortality at 90 days. Restricted cubic spline regression analysis showed an incremental trend between NLR and 90-day unfavorable functional outcome (Pnonlinearity = 0.055). In subgroup analysis, a significant interaction was found between NLR and bridging therapy for predicting unfavorable functional outcome (P = 0.006). CONCLUSION: Higher WBC and NLR on admission are significantly related to unfavorable functional outcome and mortality at 90 days in acute BAO patients receiving EVT. Significant interaction was found between increased NLR and bridging therapy on these outcome measures.

Endovascular treatment of acute basilar artery occlusion in patients with and without atrial fibrillation: results from the ATTENTION registry.

Background: Previous studies have shown a potential beneficial effect of endovascular therapy (EVT) in patients with acute basilar artery occlusion (BAO). It was unclear that whether atrial fibrillation (AF) can affect the clinical outcomes for BAO patients treated with EVT. Objectives: To investigate the association between AF and clinical outcomes, and whether AF can modify the efficacy and safety of EVT in patients with BAO. Design: We conducted a multicenter, nationwide, retrospective analysis to investigate how the presence of AF affects treatment allocation for BAO patients. Methods: The endovascular treatment for acute basilar artery occlusion (ATTENTION) registry was a multicenter, prospective study in China that included acute BAO patients who underwent EVT or received best medical management (BMM) between 2017 and 2021. The outcomes include the distribution of 3-month modified Rankin scale (mRS) score, functional independence (defined as mRS 0-3), symptomatic intracerebral hemorrhage, and mortality. Results: 2134 patients were included in the study, of which 619 had AF and 1515 did not have AF. The median age was 65 (interquartile range [IQR]: 56-73) years, and 689 (32.3%) patients were female. Multivariate regression analysis indicated no significant association existed between AF and the distribution of mRS (adjusted common odds ratio, 1.05 [95% CI: 0.88, 1.25]; p = 0.564) at 90 days. Similarly, AF was not found to have a significant association with and other measured outcomes, or with the effects of EVT in AF subgroups for at 90 days as measured by ordinal mRS (p for heterogeneity = 0.247). Finally, no significant differences were found for symptomatic intracerebral hemorrhage and mortality within 90 days between the EVT and BMM groups across AF subgroups. Conclusions: Our results illustrated that the effect of EVT did not differ statistically in acute ischemic stroke patients with and without AF. Moreover, no significant association between AF and functional or safety outcomes could be detected at 90 days.

Intraarterial thrombolytics as an adjunct to mechanical thrombectomy in patients with basilar artery occlusion.

BACKGROUND AND PURPOSE: There are limited data regarding safety and effectiveness of concurrent intraarterial thrombolytics as adjunct to mechanical thrombectomy in acute ischemic stroke patients with basilar artery occlusion. METHODS: We analyzed data from a prospective multicenter registry to assess the independent effect of intraarterial thrombolysis on (1) favorable outcome (modified Rankin Scale 0-3) at 90 days; (2) symptomatic intracranial hemorrhage (sICH) within 72 hours; and (3) death within 90 days post-enrollment after adjustment for potential confounders. RESULTS: There was no difference in the adjusted odds of achieving favorable outcome at 90 days (odds ratio [OR] = 1.1, 95% confidence interval [CI]: 0.73-1.68) in patients who received intraarterial thrombolysis (n = 126) compared with those who did not receive intraarterial thrombolysis (n = 1546) despite significantly higher use in patients with postprocedure modified Thrombolysis in Cerebral Infarction (mTICI) grade <3. There were no differences in adjusted odds of sICH within 72 hours (OR = 0.8, 95% CI: 0.31-2.08) or death within 90 days (OR = 0.91, 95% CI: 0.60-1.37). In subgroup analyses, intraarterial thrombolysis was associated with (nonsignificantly) higher odds of achieving a favorable outcome at 90 days among patients aged between 65 and 80 years, those with National Institutes of Health Stroke Scale score <10, and those with postprocedure mTICI grade 2b. CONCLUSIONS: Our analysis supported the safety of intraarterial thrombolysis as adjunct to mechanical thrombectomy in acute ischemic stroke patients with basilar artery occlusion. Identification of patient subgroups in whom intraarterial thrombolytics appeared to be more beneficial may assist in future clinical trial designs.

Elabela-APJ axis attenuates cerebral ischemia/reperfusion injury by inhibiting neuronal ferroptosis.

Ferroptosis is a form of non-apoptotic cell death caused by iron-dependent peroxidation of lipids. It contributes to ischemic stroke-induced neuronal damage. Elabela (ELA), a novel endogenous ligand for Apelin receptor (APJ), regulates oxidative stress and exerts a protective role in cardiovascular disease. However, the effect of ELA-APJ axis on cellular ferroptosis in cerebral ischemia/reperfusion (I/R) remains elusive. The present study showed that ELA and APJ were expressed on neurons and increased after cerebral I/R injury. The I/R insult triggered typical molecular and morphological features of neuronal ferroptosis, including iron and MDA accumulation, mitochondrial shrink and membrane rupture, upregulation of positive ferroptosis regulators and downregulation of negative regulators. ELA-32 treatment reduced brain infarction and ameliorated neurobehavioral deficits and cognitive dysfunction. Moreover, ELA-32 administration alleviated neuronal ferroptosis, accompanied by reduced iron deposition, decreased mitochondrial damage, relived lipid peroxidation and glutathione reduction. Such effects of ELA-32 were abolished by AAV-APJ-RNAi or nuclear factor erythroid 2-related factor 2 (NRF2) inhibitor ML385. Mechanistically, ELA was shown to bind to APJ and activate NRF2/ARE anti-oxidative signaling pathway via Gα13. Together, these findings suggested that ELA-APJ axis mitigates neuronal ferroptosis after ischemic stroke and that the ELA-32 peptide may be a putative therapeutic avenue for ischemic stroke.

Trial of Endovascular Treatment of Acute Basilar-Artery Occlusion.

BACKGROUND: Data from trials investigating the effects and risks of endovascular thrombectomy for the treatment of stroke due to basilar-artery occlusion are limited. METHODS: We conducted a multicenter, prospective, randomized, controlled trial of endovascular thrombectomy for basilar-artery occlusion at 36 centers in China. Patients were assigned, in a 2:1 ratio, within 12 hours after the estimated time of basilar-artery occlusion to receive endovascular thrombectomy or best medical care (control). The primary outcome was good functional status, defined as a score of 0 to 3 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]), at 90 days. Secondary outcomes included a modified Rankin scale score of 0 to 2, distribution across the modified Rankin scale score categories, and quality of life. Safety outcomes included symptomatic intracranial hemorrhage at 24 to 72 hours, 90-day mortality, and procedural complications. RESULTS: Of the 507 patients who underwent screening, 340 were in the intention-to-treat population, with 226 assigned to the thrombectomy group and 114 to the control group. Intravenous thrombolysis was used in 31% of the patients in the thrombectomy group and in 34% of those in the control group. Good functional status at 90 days occurred in 104 patients (46%) in the thrombectomy group and in 26 (23%) in the control group (adjusted rate ratio, 2.06; 95% confidence interval [CI], 1.46 to 2.91, P<0.001). Symptomatic intracranial hemorrhage occurred in 12 patients (5%) in the thrombectomy group and in none in the control group. Results for the secondary clinical and imaging outcomes were generally in the same direction as those for the primary outcome. Mortality at 90 days was 37% in the thrombectomy group and 55% in the control group (adjusted risk ratio, 0.66; 95% CI, 0.52 to 0.82). Procedural complications occurred in 14% of the patients in the thrombectomy group, including one death due to arterial perforation. CONCLUSIONS: In a trial involving Chinese patients with basilar-artery occlusion, approximately one third of whom received intravenous thrombolysis, endovascular thrombectomy within 12 hours after stroke onset led to better functional outcomes at 90 days than best medical care but was associated with procedural complications and intracerebral hemorrhage. (Funded by the Program for Innovative Research Team of the First Affiliated Hospital of USTC and others; ATTENTION ClinicalTrials.gov number, NCT04751708.).

Endovascular Treatment Versus Best Medical Management in Acute Basilar Artery Occlusion Strokes: Results From the ATTENTION Multicenter Registry.

BACKGROUND: The authors compare the effectiveness and safety of endovascular treatment (EVT) versus best medical management (BMM) in strokes attributable to acute basilar artery occlusion (BAO). METHODS: The present analysis was based on the ongoing, prospective, multicenter ATTENTION (Endovascular Treatment for Acute Basilar Artery Occlusion) trial registry in China. Our analytic sample comprised 2134 patients recruited at 48 sites between 2017 and 2021 and included 462 patients who received BMM and 1672 patients who received EVT. We performed an inversed probability of treatment weighting analysis. Qualifying patients had to present within 24 hours of estimated BAO. The primary clinical outcome was favorable functional outcome (modified Rankin Scale score, 0-3) at 90 days. We also performed a sensitivity analysis with the propensity score matching-based and the instrumental variable-based analysis. RESULTS: In our primary analysis using the inversed probability of treatment weighting-based analysis, there was a significantly higher rate of favorable outcome at 90 days among EVT patients compared with BMM-treated patients (adjusted relative risk, 1.42 [95% CI, 1.19-1.65]; absolute risk difference, 11.8% [95% CI, 6.9-16.7]). The mortality was significantly lower (adjusted relative risk, 0.78 [95% CI, 0.69-0.88]; absolute risk difference, -10.3% [95% CI, -15.8 to -4.9]) in patients undergoing EVT. Results were generally consistent across the secondary end points. Similar associations were seen in the propensity score matching-based and instrumental variable-based analysis. CONCLUSIONS: In this real-world study, EVT was associated with significantly better functional outcomes and survival at 90 days. Well-designed randomized studies comparing EVT with BMM in the acute BAO are needed. REGISTRATION: URL: www.chictr.org.cn; Unique identifier: ChiCTR2000041117.

Initial symptoms of vertebrobasilar artery occlusions and the outcomes after endovascular treatment.

BACKGROUND: Acute vertebrobasilar artery occlusion (VBAO) is a devastating disease in stroke patients. This study was aimed to identify the initial symptoms of patients with acute VBAO receiving endovascular treatment and determine its associations with clinical outcomes. METHODS: Patients with VBAO receiving endovascular treatment at 21 stroke centres in China were recruited for this derivation cohort A data-driven approach of latent class analysis was applied to identify distinct symptom typologies of VBAO patients. Multivariable binary and ordinary logistic regressions were used to evaluate the associations between symptom subtypes and clinical outcomes. RESULTS: A total of 548 patients were analysed in this study. Four distinct subgroups were defined: the vestibular symptom group (32.8%), anterior circulation mimic group (26.5%), non-specific symptom group (14.8%) and severe VBAO symptom group (25.9%). Compared with severe VBAO symptoms, non-specific symptoms were independently associated with higher rates of favourable outcome and functional independence at the 3 months [odds ratio (OR) 2.46, 95% confidence interval (CI) 1.15-5.28; OR 3.46, 95% CI 1.54-7.79]and 1 year follow-up (OR 2.25, 95% CI 1.05-4.82; OR 2.69, 95% CI 1.22-5.92), and better functional improvement (shift in mRS score) at the 3 months (OR 2.05, 95% CI 1.15-3.67). CONCLUSION: We identified four distinctive subtypes based on the initial symptoms of VBAO patients. Severe VBAO symptoms were associated with poor outcomes while non-specific and vestibular symptoms were indicators of a favourable outcome.

The Value of Contrast-Enhanced Ultrasound in the Evaluation of Carotid Web.

Objectives: The purpose of this study was to investigate whether contrast-enhanced ultrasound (CEUS) is more advantageous than conventional ultrasound in the diagnosis of carotid web (CaW) and to compare the clinical characteristics of patients in different age groups. Methods: Seventeen patients admitted to the hospital from October 2019 to December 2021 were included in our study. Patients were initially diagnosed with CaW using digital subtraction angiography (DSA), and conventional ultrasound and CEUS were completed. Baseline patient data were analyzed and compared between the <60 years old CaW group and the ≥60 years old CaW group to explore the differences between the two groups. Then, comparing the accuracy of conventional ultrasound and CEUS. Results: A total of 17 CaW patients participated in this study, including 4 female patients (23.5%) and 13 male patients (76.5%), with an average age of 59.41 (±10.86) years. There were 9 patients (52.9%) with left CaW and 8 patients (47.1%) with right CaW. Acute ischemic stroke (AIS) occurred in 14 patients (82.4%). Thrombosis occurred in five of 17 patients (29.4%). There was a significant statistical difference about the thrombosis between the <60 years old CaW group and the ≥60 years old CaW group [<60 years group: 0 (0%), ≥60 years group: 5 (62.5%), P = 0.005]. Seven patients (41.2%) received medical management, nine patients (52.9%) had carotid artery stenting (CAS), and one patient (5.9%) had carotid endarterectomy (CEA). None of the patients had recurrent stroke during the follow-up period. The diagnostic rate of CaW and thrombus by CEUS was higher than that by conventional ultrasound, and there was a significant statistical difference in the diagnosis of thrombus between CEUS and conventional ultrasound (χ2 = 4.286, P = 0.038). Conclusions: CEUS may have a higher diagnostic accuracy for CaW with thrombosis, and it has a higher clinical application prospect.

Thyroid Function Affects the Risk of Post-stroke Depression in Patients With Acute Lacunar Stroke.

Objective: This study aimed to investigate whether thyroid function profiles are associated with post-stroke depression (PSD) and evaluate the mediation effect of cerebral small vessel disease (cSVD) on the association of thyroid function profiles and PSD in patients with acute ischemic lacunar stroke. Methods: In this study, 372 patients with confirmed acute ischemic lacunar stroke within 3 days of onset were consecutively recruited. Serum levels of thyroid hormones and thyroid antibodies were detected on admission. Lacunar infarcts, white matter lesions, cerebral microbleeds, and enlarged perivascular spaces were rated using validated scales. The severity of depression was scored with the 24-item Hamilton Depression Scale in the hospital after a week of stroke onset. Multivariate regression was utilized to analyze the association of thyroid function profiles and PSD. Mediation analysis was employed to evaluate the effect of cSVD on the association of thyroid function profiles and PSD. Results: A total of 87 (23.4%) participants were diagnosed with depression after stroke. Serum thyroid-stimulating hormone (TSH) levels were significantly higher in patients with PSD than in those without PSD, while free triiodothyronine (FT3) and free thyroxine (FT4) were not significantly different between the two groups. After adjusting for potential confounders, serum TSH levels were positively associated with the risk of PSD (OR = 1.228; 95% CI: 1.053-1.431, p = 0.009). A similar association was also found between the total cSVD burden score and PSD (OR = 2.137; 95% CI: 1.634-2.793, p < 0.001). Further mediation analysis indicated that 26.37% of the association between TSH and PSD was mediated by cSVD. Conclusions: Serum TSH levels on admission can probably predict depression after acute ischemic lacunar stroke.

Endovascular treatment for acute basilar artery occlusion: A multicenter randomized controlled trial (ATTENTION).

BACKGROUND AND HYPOTHESIS: Recently, two multicenter randomized controlled trials (RCT) failed to show a significantly beneficial effect of endovascular treatment (EVT) in patients with acute basilar artery occlusion (BAO). However, both trials suffered from equipoise issues which may have hindered the validity of the trial results. Therefore, additional RCT studies are needed to explore the potential benefit of EVT in patients presenting with BAO. STUDY DESIGN: ATTENTION is an investigator-initiated, multicenter, prospective, randomized, controlled clinical trial with open-label treatment and blinded outcome assessment (PROBE) of EVT versus best medical management (BMM). The primary effect parameter is a modified Rankin Score of 0-3 at day 90. DISCUSSION: ATTENTION will provide evidence for the efficacy and safety of EVT in stroke patients within 12 h after BAO. TRIAL REGISTRATION: ClinicalTrials.gov NCT04751708.

Markers of Epstein-Barr virus and Human Herpesvirus-6 infection and multiple sclerosis clinical progression.

BACKGROUND: Infections with Epstein-Barr virus (EBV) and human herpesvirus-6 (HHV-6) have been implicated in multiple sclerosis (MS) onset but little work has studied their relationships in early disease. OBJECTIVE: Evaluate associations between markers of EBV and HHV-6 infection/reactivation and MS conversion, relapse and EDSS/MSSS amongst 205 CIS participants with EBV/HHV-6 data followed over 5 years. METHOD: Baseline serological and viral load measures of EBV and HHV-6 exposure/reactivation were measured and infectious mononucleosis (IM) history recorded. Conversion to MS and relapses were assessed annually, and EDSS/MSSS measured at 5-year review. Determinants of MS conversion and relapse assessed by Cox regression, and disability progression by linear regression. RESULTS: IM history showed a strong positive trend with higher relapse risk (aHR=1.45,95%CI=0.97-2.16) but was not associated with MS conversion (aHR=0.92,95%CI=0.57-1.48). Anti-HHV-6 IgG titre>40 also showed strong positive trends with higher relapse (aHR=1.61,95%CI=0.99-2.63) and MS conversion risks (aHR=1.48,95%CI=0.89-2.46). Anti-HHV-6 IgG titre≥640 was significantly associated with higher MSSS (0.15(95%CI=0.00,0.30) and also showed a strong positive trend with higher EDSS 0.10(95%CI=-0.02,0.21). HHV-6 DNA detection showed strong positive trends with 83%(95%CI=-6-357) and 77%(95%CI=-4-328) higher MS conversion and relapse risk. Anti-EBV-EA-D IgG titre was associated with a lower annualised disability progression by EDSS (ptrend=0.037) and also showed strong positive trend with higher MSSS (ptrend=0.053). No associations were seen for other serological or viral load markers. CONCLUSION: Overall, our data provides evidence that higher HHV-6 IgG was associated with increased risk of MS conversion and relapse but of borderline significance, and greater annualised disability progression, while that for EBV was more limited.