Identifying novel risk genes in intracranial aneurysm by integrating human proteomes and genetics.

Genome-wide association studies (GWAS) have become increasingly popular for detecting numerous loci associated with intracranial aneurysm (IA), but how these loci function remains unclear. In this study, we employed an integrative analytical pipeline to efficiently transform genetic associations and identify novel genes for IA. Using multidimensional high-throughput data, we integrated proteome-wide association studies (PWAS), transcriptome-wide association studies (TWAS), Mendelian randomization (MR) and Bayesian co-localization analyses to prioritize genes that can increase IA risk by altering their expression and protein abundances in the brain and blood. Moreover, single-cell RNA sequencing (scRNA-seq) of the circle of Willis was performed to enrich filtered genes in cells, and gene set enrichment analysis (GSEA) was conducted for each gene using bulk RNA-seq data for IA. No significant genes with cis-regulated plasma protein levels were proven to be associated with IA. The protein abundances of five genes in the brain were found to be associated with IA. According to cellular enrichment analysis, these five genes were expressed mainly in the endothelium, fibroblasts and vascular smooth muscle cells. Only three genes, CNNM2, GPRIN3 and UFL1, passed MR and Bayesian co-localization analyses. While UFL1 was not validated in confirmation PWAS as it was not profiled, it was validated in TWAS. GSEA suggested these three genes are associated with the cell cycle. In addition, the protein abundance of CNNM2 was found to be associated with IA rupture (based on PWAS, MR and co-localization analyses). Our findings indicated that CNNM2, GPRIN3 and UFL1 (CNNM2 correlated with IA rupture) are potential IA risk genes that may provide a broad hint for future research on possible mechanisms and therapeutic targets for IA.

Clinical, Imaging Characteristics and Outcome of Intracerebral Hemorrhage Caused by Structural Vascular Lesions.

BACKGROUND: The objective of this study was to investigate the clinical, imaging, and outcome characteristics of intracerebral hemorrhage (ICH) caused by structural vascular lesions. METHODS: We retrospectively analyzed data from a prospective observational cohort study of patients with spontaneous ICH admitted to the First Affiliated Hospital of Chongqing Medical University between May 2016 and April 2021. Good outcome was defined as modified Rankin Scale score of 0-3 at 3 months. The clinical and imaging characteristics were compared between primary ICH and ICH caused by structural vascular lesions. Multivariable logistic regression analysis was performed to test the associations of etiology with clinical outcome. RESULTS: All patients enrolled in this study were Asian. Compared with patients with primary ICH, those with structural vascular lesions were younger (48 vs. 62 years, P < 0.001), had a lower incidence of hypertension (26.4% vs. 81.7%, P < 0.001) and diabetes (7.4% vs. 16.2%, P = 0.003), and had mostly lobar hemorrhages (49.1% vs. 22.8%). ICH from structural vascular lesions had smaller baseline hematoma volume (8.4 ml vs. 13.8 ml, P = 0.010), had lower mortality rate at 30 days and 3 months (5.8% vs. 12.0%, P = 0.020; 6.7% vs. 14.8%, P = 0.007), and are associated with better functional outcome at 3 months (88% vs.70.3%, P < 0.001). CONCLUSIONS: Compared with primary ICH, ICH due to vascular lesions has smaller hematoma volume and less severe neurological deficit at presentation and better functional outcomes.

Optimal intraventricular hemorrhage volume cutoff for predicting poor outcome in patients with intracerebral hemorrhage.

BACKGROUND AND OBJECTIVES: The prognosis of patients with spontaneous intracerebral hemorrhage (ICH) is often influenced by hematoma volume, a well-established predictor of poor outcome. However, the optimal intraventricular hemorrhage (IVH) volume cutoff for predicting poor outcome remains unknown. METHODS: We analyzed 313 patients with spontaneous ICH not undergoing evacuation, including 7 cases with external ventricular drainage (EVD). These patients underwent a baseline CT scan, followed by a 24-hour CT scan for measurement of both hematoma and IVH volume. We defined hematoma growth as hematoma growth > 33 % or 6 mL at follow-up CT, and poor outcome as modified Rankin Scale score≥3 at three months. Cutoffs with optimal sensitivity and specificity for predicting poor outcome were identified using receiver operating curves. RESULTS: The receiver operating characteristic analysis identified 6 mL as the optimal cutoff for predicting poor outcome. IVH volume> 6 mL was observed in 53 (16.9 %) of 313 patients. Patients with IVH volume>6 mL were more likely to be older and had higher NIHSS score and lower GCS score than those without. IVH volume>6 mL (adjusted OR 2.43, 95 % CI 1.13-5.30; P = 0.026) was found to be an independent predictor of poor clinical outcome at three months in multivariable regression analysis. CONCLUSIONS: Optimal IVH volume cutoff represents a powerful tool for improving the prediction of poor outcome in patients with ICH, particularly in the absence of clot evacuation or common use of EVD. Small amounts of intraventricular blood are not independently associated with poor outcome in patients with intracerebral hemorrhage. The utilization of optimal IVH volume cutoffs may improve the clinical trial design by targeting ICH patients that will obtain maximal benefit from therapies.

Intensive blood pressure control after endovascular thrombectomy for acute ischaemic stroke (ENCHANTED2/MT): a multicentre, open-label, blinded-endpoint, randomised controlled trial.

BACKGROUND: The optimum systolic blood pressure after endovascular thrombectomy for acute ischaemic stroke is uncertain. We aimed to compare the safety and efficacy of blood pressure lowering treatment according to more intensive versus less intensive treatment targets in patients with elevated blood pressure after reperfusion with endovascular treatment. METHODS: We conducted an open-label, blinded-endpoint, randomised controlled trial at 44 tertiary-level hospitals in China. Eligible patients (aged ≥18 years) had persistently elevated systolic blood pressure (≥140 mm Hg for >10 min) following successful reperfusion with endovascular thrombectomy for acute ischaemic stroke from any intracranial large-vessel occlusion. Patients were randomly assigned (1:1, by a central, web-based program with a minimisation algorithm) to more intensive treatment (systolic blood pressure target <120 mm Hg) or less intensive treatment (target 140-180 mm Hg) to be achieved within 1 h and sustained for 72 h. The primary efficacy outcome was functional recovery, assessed according to the distribution in scores on the modified Rankin scale (range 0 [no symptoms] to 6 [death]) at 90 days. Analyses were done according to the modified intention-to-treat principle. Efficacy analyses were performed with proportional odds logistic regression with adjustment for treatment allocation as a fixed effect, site as a random effect, and baseline prognostic factors, and included all randomly assigned patients who provided consent and had available data for the primary outcome. The safety analysis included all randomly assigned patients. The treatment effects were expressed as odds ratios (ORs). This trial is registered at ClinicalTrials.gov, NCT04140110, and the Chinese Clinical Trial Registry, 1900027785; recruitment has stopped at all participating centres. FINDINGS: Between July 20, 2020, and March 7, 2022, 821 patients were randomly assigned. The trial was stopped after review of the outcome data on June 22, 2022, due to persistent efficacy and safety concerns. 407 participants were assigned to the more intensive treatment group and 409 to the less intensive treatment group, of whom 404 patients in the more intensive treatment group and 406 patients in the less intensive treatment group had primary outcome data available. The likelihood of poor functional outcome was greater in the more intensive treatment group than the less intensive treatment group (common OR 1·37 [95% CI 1·07-1·76]). Compared with the less intensive treatment group, the more intensive treatment group had more early neurological deterioration (common OR 1·53 [95% 1·18-1·97]) and major disability at 90 days (OR 2·07 [95% CI 1·47-2·93]) but there were no significant differences in symptomatic intracerebral haemorrhage. There were no significant differences in serious adverse events or mortality between groups. INTERPRETATION: Intensive control of systolic blood pressure to lower than 120 mm Hg should be avoided to prevent compromising the functional recovery of patients who have received endovascular thrombectomy for acute ischaemic stroke due to intracranial large-vessel occlusion. FUNDING: The Shanghai Hospital Development Center; National Health and Medical Research Council of Australia; Medical Research Futures Fund of Australia; China Stroke Prevention; Shanghai Changhai Hospital, Science and Technology Commission of Shanghai Municipality; Takeda China; Hasten Biopharmaceutic; Genesis Medtech; Penumbra.

Prehospital Ultra-Early Neurological Deterioration in Intracerebral Hemorrhage: Definition, Prevalence, and Association with Outcomes.

INTRODUCTION: The objective of this study was to define prehospital ultra-early neurological deterioration (UND) and to investigate the association with functional outcomes in patients with intracerebral hemorrhage (ICH). METHODS: We conducted a prospective cohort study of consecutive acute ICH patients. The stroke severity at onset and hospital admission was assessed using the Chongqing Stroke Scale (CQSS), and prehospital UND was defined as a CQSS increase of ≥2 points between symptoms onset and admission. Early neurological deterioration (END) was defined as the increase of ≥4 points in NIHSS score within the first 24 h after admission. Poor outcome was defined as a modified Rankin Scale (mRS) of 4-6 at 3 months. RESULTS: Prehospital UND occurred in 29 of 169 patients (17.2%). Patients with prehospital UND had a median admission NIHSS score of 17.0 as opposed to those without prehospital UND with a median NIHSS score of 8.5. There were three patterns of neurological deterioration: prehospital UND only in 21 of 169 patients (12.4%), END but without prehospital UND in 20 of 169 patients (11.8%), and continuous neurological deterioration in both phases in 8 patients (4.7%). Prehospital UND was associated with worse 3-month outcomes (median mRS score, 4.0 vs. 2.0, p = 0.002). After adjusting for age, time from onset to admission, END, and systolic blood pressure, prehospital UND was an independent predictor of poor outcome (odds ratio [OR] 3.27, 95% confidence interval [CI] 1.26-8.48, p = 0.015). CONCLUSION: Prehospital UND occurs in approximately 1 in 7 patients between symptom onset and admission and is associated with poor functional outcome in patients with ICH. Further research is needed to investigate the prehospital UND in the prehospital phase in the triage of patients with ICH.

Association of Intravenous Alteplase, Early Reperfusion, and Clinical Outcome in Patients With Large Vessel Occlusion Stroke: Post Hoc Analysis of the Randomized DIRECT-MT Trial.

BACKGROUND: The added value of intravenous alteplase in reperfusing ischemic brain tissue in patients undergoing endovascular treatment and directly presented to an endovascular treatment-capable hospital is uncertain. We conducted this post hoc analysis of a randomized trial (DIRECT-MT [Direct Intraarterial Thrombectomy in Order to Revascularize Acute Ischemic Stroke Patients With Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals: A Multicenter Randomized Clinical Trial]) to explore the association of intravenous alteplase, early (preendovascular treatment) reperfusion, and clinical outcome and to determine factors which may modify alteplase treatment effect on early reperfusion. METHODS: In this post hoc analysis of the DIRECT-MT randomized trial comparing intravenous alteplase before endovascular treatment versus endovascular treatment only, 623 of 656 randomized patients, with adequate angiographic evaluation for early reperfusion assessment, were included. The association of intravenous alteplase and early reperfusion (defined as expanded Thrombolysis in Cerebral Infarction score ≥2a on angiogram) was assessed using unadjusted comparisons and multivariable logistic regression. RESULTS: Among 623 patients included (317 received intravenous alteplase and 306 did not), early reperfusion occurred in 91 (15%) patients and was associated with better functional outcome (modified Rankin Scale score, 0-2 of 49/91 [54%] versus 178/531 [34%]; adjusted odds ratio, 1.92 [95% CI, 1.15-3.21]; P<0.001). Intravenous alteplase was independently associated with early reperfusion (59/317 [19%] versus 32/306 [10%]; adjusted odds ratio, 2.06 [95% CI, 1.27-3.33]; P=0.003), and the alteplase effect was modified by time from randomization to groin puncture (dichotomized by median, ≤33 minutes; adjusted odds ratio, 1.06 [95% CI, 0.53-2.10] versus >33 minutes; adjusted odds ratio, 4.07 [95% CI, 1.86-8.86]; Pinteraction=0.012). CONCLUSIONS: For patients with large vessel occlusion directly presenting to an endovascular treatment-capable hospital, intravenous alteplase increases early reperfusion when endovascular treatment gets delayed more than approximately half an hour. Thus, intravenous alteplase should be considered if endovascular treatment delays are anticipated by the treating medical team. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03469206.

Effect of Occlusion Site on the Safety and Efficacy of Intravenous Alteplase Before Endovascular Thrombectomy: A Prespecified Subgroup Analysis of DIRECT-MT.

BACKGROUND AND PURPOSE: Recent trials showed thrombectomy alone was comparable to bridging therapy in patients with anterior circulation large vessel occlusion eligible for both intravenous alteplase and endovascular thrombectomy. We performed this study to examine whether occlusion site modifies the effect of intravenous alteplase before thrombectomy. METHODS: This is a prespecified subgroup analysis of a randomized trial evaluating risk and benefit of intravenous alteplase before thrombectomy (DIRECT-MT [Direct Intra-Arterial Thrombectomy in Order to Revascularize AIS Patients With Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals]). Among 658 randomized patients, 640 with baseline occlusion site information were included. The primary outcome was the score on the modified Rankin Scale at 90 days. Multivariable ordinal logistic regression analysis with an interaction term was used to estimate treatment effect modification by occlusion location (internal carotid artery versus M1 versus M2). We report the adjusted common odds ratio for a shift toward better outcome on the modified Rankin Scale after thrombectomy alone compared with combination treatment adjusted for age, the National Institutes of Health Stroke Scale score at baseline, the time from stroke onset to randomization, the modified Rankin Scale score before stroke onset, and collateral score per the DIRECT-MT statistical analysis plan. RESULTS: The overall adjusted common odds ratio was 1.08 (95% CI, 0.82-1.43) with thrombectomy alone compared with combination treatment, and there was no significant treatment-by-occlusion site interaction (P=0.47). In subgroups based on occlusion location, we found the following adjusted common odds ratios: 0.99 (95% CI, 0.62-1.59) for internal carotid artery occlusions, 1.12 (95% CI, 0.77-1.64) for M1 occlusions, and 1.22 (95% CI, 0.53-2.79) for M2 occlusions. No treatment-by-occlusion site interactions were observed for dichotomized modified Rankin Scale distributions and successful reperfusion (extended thrombolysis in Cerebral Infarction score ≥2b) before thrombectomy. Differences in symptomatic hemorrhage rate were not significant between occlusion locations (internal carotid artery occlusion: 7.02% in bridging therapy versus 7.14% for thrombectomy alone, P=0.97; M1 occlusion: 5.06% versus 2.48%, P=0.22; M2 occlusion: 9.09% versus 4.76%; P=0.78). CONCLUSIONS: In this prespecified subgroup of a randomized trial, we found no evidence that occlusion location can inform intravenous alteplase decisions in endovascular treatment eligible patients directly presenting at endovascular treatment capable centers. Future studies are needed to confirm our findings. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03469206.

Braided stents assisted coiling for endovascular management of posterior cerebral artery aneurysms: a preliminary mid-term experience.

PURPOSE: Posterior cerebral artery (PCA) aneurysms are rare. This study is to evaluate the preliminary experience of braided stents applied in PCA aneurysms treatment. METHODS: Angiographic and clinical data of 28 PCA patients treated with braided stents from July 2016 and September 2020 were retrospectively analyzed. RESULTS: A total of 28 PCA aneurysms were enrolled. 22 (78.6%) aneurysms were dissecting aneurysms, while 6 (21.4%) aneurysms were saccular aneurysms. Thirty-five braided stents were implanted with dual stents implanted in 7 cases. Immediate angiographic results show that Raymond class I was obtained in 13 patients (46.4%), Raymond class II was obtained in 4 patients (14.3%), and Raymond class III was obtained in 11 patients (39.3%). Perioperative hemorrhagic events occurred in 1 patient (3.6%). Twenty-four patients (85.7%) received angiographic follow-up, and the mean follow-up time was 11.2 ± 4.9 months. Two patients (8.3%) were confirmed with IA neck recurrence, and 3 patients (12.5%) were confirmed asymptomatic parent artery occlusion (PAO). The other 19 patients were confirmed promoted occlusion with 18 Raymond class I (75%) and 1 Raymond class II (4.2%). Twenty-seven patients (96.4%) received clinical follow-up, and the mean follow-up time was 32.2 ± 13.5 months. One patient (3.7%) confirmed the death event 2 weeks after discharge. The other 27 patients (96.3%) got favorable clinical outcomes with an mRS score of 0-2. CONCLUSIONS: Braided stent-assisted coiling with a high occlusion rate and relatively low complication rate provides an alternative strategy in treating PCA aneurysms. Long-term outcomes need further randomized study with larger case numbers.

Developmental venous anomaly with radiation-induced arteriovenous malformation.

Developmental venous anomaly (DVA) is considered a congenital vascular anatomic variation with normal draining function. Limited cases of DVA with arteriovenous malformation (AVM) in the territory of DVA have been reported, and the etiology of de novo AVM formation remains unknown and speculative. In this case, it is continuously observed that the inappropriate radiosurgery involving the DVA draining veins led to the disruption of DVA radicles and the secondary formation of de novo AVM and hemodynamic aneurysm. This sequential process exhibited in the present case verified that outflow disturbance underlay the potential etiology of AVM formation drained by adjoining DVA. Meanwhile, it also manifested the importance of preserving the integrity of the collecting veins when treating the DVA by any means.

The development and understanding of intracranial aneurysm based on rabbit model.

In modern society, intracranial aneurysms have seriously affected people's life. To better study and treat intracranial aneurysm, animal models are ideal candidates to perform biological research and preclinical endovascular device testing. Rabbit aneurysm model is one of the most commonly used animal models, and the rabbit aneurysms share similarities in histology, morphology, and hemodynamic aspects with human intracranial aneurysms, which is an ideal model for intracranial aneurysm pre-clinical and basic research. In this review, we will summarize the main methods of establishing rabbit aneurysms model and will further discuss the current biological mechanisms of intracranial aneurysms based on rabbit model. Further improvements of rabbit aneurysm model and more deep studies based on this model are needed to provide new insights into studying and clinical treating intracranial aneurysm.

Textbook Outcomes Among Patients with Aneurysmal Subarachnoid Hemorrhage Following Endovascular Treatment.

INTRODUCTION: The case fatality rate among patients with aneurysmal subarachnoid hemorrhage (aSAH) has decreased progressively, with numerous patients subjected to contemporary paradigms that minimize the use of agonizing therapeutic processes. The concept of the "Textbook Outcome" (TO), a composite outcome that highlights numerous favorable outcomes, was developed in the context of gastrointestinal tumor surgeries and expeditiously extended across diverse surgical spheres. The aim of this study was to explore the factors hindering the achievement of optimal prognoses in postinterventional aSAH patients, employ textbook outcomes, and establish predictive models. METHODS: We conducted a retrospective review of data from 1270 aSAH patients who received endovascular treatment between 2012 and 2018. We delineated an exemplary TO within the aSAH domain, characterized by favorable clinical results, minimal complications, and the absence of retreatments. This TO-oriented approach is explained within the manuscript. RESULTS: The findings revealed that preoperative intraventricular hemorrhage (IVH), preoperative Hunt and Hess grade (H&H) ≥ 3, World Federation of Neurosurgical Societies (WFNS) grade ≥ 3, the presence of blebs on the aneurysm, aneurysms situated at branching sites, and non-stent-assisted endovascular intervention were the strongest risk factors for not achieving textbook outcomes (non-"Textbook Outcome" [N-TO]). Decision curve analysis and calibration analyses revealed strong concordance between the predictions of the N-TO nomogram model and the actual observations. CONCLUSIONS: Treatment Outcomes hold significant practical value in clinical studies of aSAH patients receiving endovascular treatment. The likelihood of N-TOs was predicted by IVH, H&H grade ≥ 3, WFNS grade ≥ 2, presence o f bleb on the aneurysm, and aneurysms located at branching sites.

Effect of Clot Burden Score on Safety and Efficacy of Intravenous Alteplase Prior to Mechanical Thrombectomy in Acute Ischemic Stroke: A Subgroup Analysis of a Randomized Phase 3 Trial.

BACKGROUND AND PURPOSE: Whether thrombus burden in acute ischemic stroke modify the effect of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) remains uncertain. We aim to investigate the treatment effect of stratified clot burden score (CBS) on the efficacy and safety of direct versus bridging MT. MATERIALS AND METHODS: This is an exploratory subgroup analysis of a randomized trial evaluating the effect of CBS on clinical outcome in the DIRECT-MT trial. CBS was divided into 3 groups (0-3, 4-6, and 7-10) based on preoperative CTA, where higher scores indicated a lower clot burden. We report the adjusted common odds ratio for a shift toward better outcomes on the mRS after thrombectomy alone compared with combination treatment by stratified CBS groups. RESULTS: No modification effect of mRS distribution was observed by CBS subgroups (CBS 0-3: adjusted common ratio odds 1.519 [95% CI, 0.928-2.486]; 4-6: 0.924 [0.635-1.345]; 7-10: 1.040 [0.481-2.247]). Patients with CBS 4-6 had a higher rate of early reperfusion (adjusted OR (aOR), 0.3 [95% CI, 0.1-0.9]), final reperfusion (aOR 0.5 [95% CI, 0.3-0.9]), and fewer thrombectomy attempts (aOR 0.4 [95% CI, 0.1-0.7]). Patients with CBS 7-10 had a higher rate of asymptomatic intracranial hemorrhage (14.9% versus 36.8%, P = .0197) for bridging MT. No significant difference was observed in other safety outcomes by trichotomized CBS. CONCLUSIONS: The subgroup analysis of DIRECT-MT suggested that thrombus burden did not alter the treatment effect of IVT before MT on functional outcomes in CBS subgroups.

Antioxidants and the risk of stroke: results from NHANES and two-sample Mendelian randomization study.

BACKGROUND: Stroke is the second leading cause of death worldwide, and observational studies have suggested a correlation between antioxidants and reduced stroke risk. However, it remains unclear whether causal relationships exist. METHODS: This study first performed a cross-sectional study of the association between the Composite Dietary Antioxidant Index (CDAI) and stroke using data from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. Second, a two-sample univariable Mendelian Randomization (MR) was performed to analyze the causal effect of circulating levels of antioxidants on different subtypes of stroke. RESULTS: The cross-sectional study included a total of 24,892 participants representing more than 200 million US non-institutionalized residents, a multivariable logistic regression model revealed that the risk of stroke decreased by 3.4% for each unit increase in CDAI (P = 0.017), with a non-linear association found, indicating a reduction in stroke risk before an inflection point of 3.078. MR analysis revealed that genetically determined levels of retinol had a suggestive protective effect on subarachnoid hemorrhage (SAH) (OR = 0.348, P = 0.025), and genetically determined levels of selenium had a suggestive protective effect against SAH (OR = 0.826, P = 0.007). However, no causal relationship was found between antioxidants and ischemic stroke or intracranial hemorrhage risk. CONCLUSIONS: Evidence suggests that diet-derived antioxidants may reduce the risk of stroke, as indicated by the protective effects of retinol and selenium against SAH. However, more research is needed to fully understand how antioxidants prevent stroke.

Clinical Outcomes On Tubridge Flow Diverter in Treatmenting Intracranial Aneurysms: a Retrospective Multicenter Registry Study.

PURPOSE: In China, the application of nitinol Tubridge flow diverter (TFD) has become popular for treating intracranial aneurysms (IAs). In this study, we investigated the safety outcomes of the application of TFD for treating IAs in real-world scenarios. METHODS: We retrospectively analyzed aneurysms treated with TFD in 235 centers throughout China between April 2018 and April 2020. The primary endpoint was the event-free survival rate at 12 months, defined as the occurrence of morbidity (spontaneous rupture, intraparenchymal hemorrhage (IPH), ischemic stroke, and permanent cranial neuropathy) or death. Univariate and multivariate analyses were performed to assess the risk factors. A good outcome was defined as a modified Rankin Score (mRS) of 0-2. RESULTS: We included 1281 unruptured aneurysms treated with TFD. The overall neurological morbidity and death rates after 12 months were 5.4 and 2.8%, respectively. Ischemic strokes were the most common complication (4.2%, P < 0.001). Cranial neuropathy, IPH, and spontaneous rupture occurred in 0.3%, 0.3%, and 0.5% of aneurysms, respectively. Univariate and multivariate analyses indicated that the male gender, older age, larger aneurysm diameter, and aneurysm located on BA were the independent risk factors for neurologic events. Aneurysm located on BA was the independent risk factor for ischemic strokes. Most patients (1222) had access to the mRS, and 93.2% of them achieved good outcomes. CONCLUSION: Treatment of IAs with TFD was associated with low morbidity and mortality, most of which were ischemic events. Large posterior aneurysms might be associated with a higher complication rate. TRIAL REGISTRATION: Retrospectively registered.

Gekko Coil System for Intracranial Aneurysms Treatment in China (GREAT-China): A Prospective Randomized Controlled Open-Label Noninferiority Trial.

OBJECTIVE: This study aimed to evaluate the safety and efficacy of the Gekko coil system in treating intracranial aneurysms (IAs) in clinical practice. METHODS: A prospective multicenter randomized open-label parallel positive control noninferiority trial was conducted by 11 centers in China. Patients with a target IA were randomized 1:1 to coiling with either Gekko or Axium coils. The primary outcome was successful aneurysm occlusion at 6 months postoperative follow-up, whereas the secondary outcomes included the successful occlusion aneurysm rate in the immediate postoperative period, recanalization rate at the 6 months follow-up, and technical success and security. RESULTS: Between May 2018 and September 2020, 256 patients were enrolled and randomized. Per-protocol analysis showed that the successful aneurysm occlusion rate at 6 months was 96.08% for the Gekko coil group compared with 96.12% in the Axium coil group, with a difference of -0.04% (P = 0.877). The successful immediate aneurysm occlusion rates were 86.00% and 77.45% in the Gekko coil group and the Axium coil group, respectively, showing no significant difference between the 2 groups (P = 0.116), whereas the recanalization rates during the 6 months follow-up were 2.02% and 1.96% in the Gekko and Axium coil groups, respectively, which was not statistically significant (P = 1.000). CONCLUSIONS: This trial showed that the Gekko coil system was noninferior to the Axium coil system in terms of efficacy and safety for IA embolization. In clinical practice, the Gekko coil system can be considered safe and effective for treating patients with IA.

Impact of early cognitive impairment on outcome trajectory in patients with intracerebral hemorrhage.

OBJECTIVE: To assess the prevalence and factors associated with early cognitive impairment in intracerebral hemorrhage (ICH) patients and to describe short-term recovery trajectories among ICH patients with early cognitive impairment. METHODS: We prospectively enrolled ICH patients without baseline dementia in our institutions. Cognitive function was assessed using mini-mental state examination (MMSE), and functional outcome was evaluated at discharge, 3, and 6 months after symptoms onset using the modified Rankin Scale (mRS). We used multinomial logistic regression models to investigate potential risk factors and generalized linear models to analyze the functional outcome data. RESULTS: Out of 181 patients with ICH, 167 were included in the final analysis. Early cognitive impairment occurred in 60.48% of patients with ICH. Age (odds ratio [OR] per 1-year increase, 1.037; 95% confidence interval [CI], 1.003-1.071; p = 0.034), National Institutes of Health Stroke Scale (NIHSS) score (OR per 1-point increase, 1.146; 95% CI, 1.065-1.233; p < 0.001) and lobar ICH location (OR, 4.774; 95% CI, 1.810-12.593; p = 0.002) were associated with early cognitive impairment in ICH patients. Patients with ≥10 years of education were less likely to experience early cognitive impairment (OR, 0.323; 95% CI, 0.133-0.783; p = 0.012). Participants with early cognitive impairment had a higher risk of poor outcome (OR, 4.315; 95% CI, 1.503-12.393; p = 0.005) than those without. Furthermore, there was a significantly faster functional recovery rate for those without early cognitive impairment compared with those with at 3 and 6 months (p < 0.05). INTERPRETATION: Early cognitive impairment was prevalent and associated with poor outcomes in ICH patients, which decelerated short-term functional recovery.

Prevalence of small vessel disease and incidental DWI-positive lesions in patients with aneurysmal subarachnoid hemorrhage versus intracerebral hemorrhage.

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (aSAH) and intracerebral hemorrhage (ICH) are main forms of hemorrhagic stroke. Data regarding cerebral small vessel disease (SVD) burden and incidental small lesions on diffusion-weighted imaging (DWI) following aSAH are sparse. PATIENTS AND METHODS: We retrospectively analyzed a prospective cohort of aSAH and ICH patients with brain MRI within 30 days after onset from March 2015 to January 2023. White matter hyperintensity (WMH), lacune, perivascular space, cerebral microbleed (CMB), total SVD score, and incidental DWI lesions were assessed and compared between aSAH and ICH. Clinical and radiological characteristics associated with small DWI lesions in aSAH were investigated. RESULTS: We included 180 patients with aSAH (median age [IQR] 53 [47-61] years) and 299 with ICH (63 [53-73] years). DWI lesions were more common in aSAH than ICH (47.8% vs 14.4%, p < 0.001). Higher total SVD score was associated with ICH versus aSAH irrespective of hematoma location, whereas DWI lesions and strictly lobar CMBs were correlated with aSAH. Multivariable analysis showed that shorter time from onset to MRI, anterior circulation aneurysm rupture, CMB ⩾ 5, and total SVD score were associated with DWI lesions in aSAH. DISCUSSION AND CONCLUSION: Incidental DWI lesions and strictly lobar CMBs were more frequent in aSAH versus ICH whereas ICH had higher SVD burden. Incidental DWI lesions in aSAH were associated with multiple clinical and imaging factors. Longitudinal studies to investigate the dynamic change and prognostic value of the covert hemorrhagic and ischemic lesions in aSAH seem justified.

Blood-Based Biomarkers in Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is one of the most lethal subtypes of stroke, associated with high morbidity and mortality. Prevention of hematoma growth and perihematomal edema expansion are promising therapeutic targets currently under investigation. Despite recent improvements in the management of ICH, the ideal treatments are still to be determined. Early stratification and triage of ICH patients enable the adjustment of the standard of care in keeping with the personalized medicine principles. In recent years, research efforts have been concentrated on the development and validation of blood-based biomarkers. The benefit of looking for blood candidate markers is obvious because of their acceptance in terms of sample collection by the general population compared to any other body fluid. Given their ease of accessibility in clinical practice, blood-based biomarkers have been widely used as potential diagnostic, predictive, and prognostic markers. This review identifies some relevant and potentially promising blood biomarkers for ICH. These blood-based markers are summarized by their roles in clinical practice. Well-designed and large-scale studies are required to validate the use of all these biomarkers in the future.

Managing non-acute subdural hematoma using liquid materials: a Chinese randomized trial of middle meningeal artery treatment (MAGIC-MT)-protocol.

BACKGROUND: The conventional treatments for non-acute subdural hematoma (SDH) are facing the challenge of high hematoma recurrence and progression. A novel treatment of middle meningeal artery (MMA) embolization showed the potential role in decreasing the recurrence and progression rate of SDH compared to conventional treatments in multiple cohort studies. A randomized controlled trial is warranted to determine the effectiveness and safety of MMA embolization for non-acute hematoma and whether MMA embolization is superior to conventional treatments to lower the symptomatic recurrence and progression rate of non-acute SDH. METHODS: This is an investigator-initiated, multi-center, prospective, open-label parallel group trial with blinded outcome assessment (PROBE design) assessing superiority of MMA embolization compared to conventional treatments. A total of 722 patients are planned to be randomized 1:1 to receive MMA embolization (intervention) or conventional treatments (control). The primary outcome is the symptomatic SDH recurrence/progression rate within 90 ± 14 days post-randomization. DISCUSSION: This trial will clarify whether MMA embolization could reduce the recurrence or progression rate of symptomatic non-acute SDH compared to conventional treatment. TRIAL REGISTRATION: ClinicalTrials.gov. Identifier: NCT04700345, Registered on 7 January 2021.

Activation of BMP4-pSmad1/5 pathway impairs the function of VSMCs in intracranial aneurysms.

Intracranial aneurysms (IAs) are characterized by abnormal dilatation of the cerebral vessels. Vascular smooth muscle cells (VSMCs) are implicated in maintaining vascular homeostasis. Disordered VSMCs are one of the most common causes for occurrence and development of IAs. The bone morphogenetic protein 4 (BMP4) signalling pathway is involved in regulating cell proliferation, apoptosis, and differentiation. This study aimed to investigate the effects of BMP4 on VSMCs and its underlying mechanisms. BMP4 was upregulated in the VSMCs of IAs and caused apoptosis of VSMCs through Smad1/5 phosphorylation. In addition, BMP4 overexpression significantly promoted the proliferation and migration of VSMCs and induced a phenotypic transformation from contractile to inflammatory. Our findings facilitate further understanding of the occurrence and development of IAs and provide a potential therapeutic target.