Perivascular macrophages (PVMs) are increasingly recognized as key players in maintaining brain homeostasis, yet their role in maintaining neurovascular-metabolic homeostasis has not been fully explored. We hypothesized that PVM depletion compromises cerebrospinal fluid-interstitial fluid exchange through glymphatic system (GS) dysfunction, thereby exacerbating cortical hyperexcitability manifested as increased epilepsy susceptibility and seizure intensity. Using clodronate liposomes (CLOs), we achieved >85% PVM depletion in mice. Following pentylenetetrazole (PTZ) challenge, PVM-depleted mice exhibited anxiety-like behaviors (reduced center time, p < 0.05), impaired working memory (decreased spontaneous alternation, p < 0.05), and increased cortical hyperexcitability, including shorter seizure latency and elevated EEG total power (p < 0.05). Mechanistically, PVM loss led to dysregulation of extracellular matrix components (increased laminin and collagen IV), impairing perivascular space integrity and GS function (reduced CSF tracer clearance, p < 0.05). AQP4 inhibition with TGN-020 further exacerbated PTZ-induced EEG abnormalities (increased total power, p < 0.05). Analysis of human epileptic tissue confirmed elevated collagen IV deposition in the seizure focus (p < 0.05) and a trend toward increased PVM density (p = 0.0638). These results highlight PVMs as essential modulators of the glymphatic-metabolic axis, linking vascular health to brain excitability. Targeting the PVM-GS interface offers therapeutic potential for disorders involving vascular dysfunction and neuronal hyperexcitability.

The optimal timing of surgery for aneurysmal subarachnoid hemorrhage (aSAH) remains controversial. This study aims to identify the optimal surgical window within 72 h of symptom onset. Patients with aSAH who underwent surgical treatment within 72 h of onset were identified from the Chinese Multicenter Cerebral Aneurysm Database (2017–2020). Multivariable Cox and logistic regression models with restricted cubic splines (RCS) were used to assess associations between onset-to-treatment time and all-cause mortality and 2-year dependent survival, respectively. A total of 3560 patients with aSAH were included. During a mean follow-up of 30.9 ± 22.5 months, 521 deaths were recorded, yielding a 2-year mortality rate of 12.9

Background:The efficacy of microsurgical treatment (MST) and endovascular treatment (EVT) in aneurysmal subarachnoid hemorrhage (aSAH) patients requiring external ventricular drainage (EVD) remains unclear. This study aims to comprehensively compare the outcomes of MST and EVT in this specific patient population. Methods:We consecutively enrolled surgical patients with aSAH requiring EVD from the Chinese Multicenter Aneurysm Database (CMAD) between January 2017 and December 2020. A 1:1 propensity score matching (PSM) was performed to balance baseline differences between the MST and EVT groups. Outcomes and complications were then compared between the matched groups. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). The Kaplan-Meier survival curves were used to compare survival between the MST and EVT groups. Results:A total of 197 aSAH patients met the inclusion criteria. After PSM, 45 patients who underwent MST were matched with 45 patients who received EVT. No significant differences were observed between the MST and EVT groups in terms of 2-year mortality (MST: 32.3%; EVT: 35.5%, p = 0.48), dependent survival at discharge (MST: 51.2%; EVT: 48.8%, OR 0.955, 95% CI 0.399-2.285, p = 0.917), or dependent survival at 2 years (MST: 70.8%; EVT: 29.2%, OR 1.080, 95% CI 0.253-4.607, p = 0.918). Compared with the EVT group, the MST group had a significantly higher incidence of intracranial infection (MST: 26.7%; EVT: 4.4%, OR 0.128, 95% CI 0.027-0.611, p = 0.010) and a lower incidence of pneumonia (MST: 22.2%; EVT: 42.2%, OR 2.558, 95% CI 1.021-6.409, p = 0.045). Conclusion:In aSAH patients requiring EVD, EVT did not demonstrate clear advantages over MST in terms of survival or functional outcomes. MST was associated with a higher incidence of intracranial infection, whereas EVT showed a relatively higher rate of pneumonia during hospitalization. Given the retrospective design and limited sample size, these findings should be interpreted with caution.

Distal anterior cerebral artery aneurysms (DACA) associated with complex anatomical variations of the anterior cerebral artery (ACA) are exceptionally rare. We report a rare case of a 78-year-old woman with a rare ACA configuration characterized by three distinct A2 branches, in which a saccular aneurysm developed at the bifurcation of the middle branch. The patient was admitted with sudden onset of headache, dizziness, nausea, vomiting, and hypertension. Computed tomography (CT) revealed subarachnoid hemorrhage. Computed tomography angiography (CTA) and digital subtraction angiography (DSA) revealed three distinct A2 branches arising from the ACA complex, with an aneurysm originating from the middle branch. On the eighth day after hemorrhage, stent-assisted coil embolization was successfully performed. Considering the close anatomical relationship between the aneurysm neck and the right superior trunk, a stent was strategically deployed in the right superior trunk to preserve distal cerebral perfusion. The postoperative course was uneventful, and clinical follow-up demonstrated an excellent neurological outcome. This case highlights the critical role of precise preoperative imaging evaluation (CTA, DSA) and individualized treatment strategies in managing complex vascular variations and associated aneurysms.

ABSTRACT Background There is a lack of comparative studies between posterior circulation saccular aneurysms (SA) and dissecting aneurysms (DA). This study aims to comprehensively compare the clinical characteristics, treatment strategies, and outcomes of SA and DA. Methods We included all consecutive patients with posterior circulation aneurysmal subarachnoid hemorrhage (aSAH) who underwent surgical treatment between January 2017 and December 2020 from the Chinese Multicenter Cerebral Aneurysm Database (CMAD). Baseline data were retrospectively collected, and survival status and 2‐year mRS scores were prospectively assessed. Functional outcomes were categorized as favorable (mRS 0–2) and unfavorable (mRS 3–6). Logistic regression models were used to explore the association between aneurysm morphology and outcomes. Results Note that 406 patients with posterior circulation aSAH who underwent surgical treatment were included, comprising 314 (77.3%) with SA and 92 (22.7%) with DA. In unadjusted analyses, DA was associated with a lower rate of unfavorable outcomes at 2 years (17.1% vs. 34.8%, p = 0.003) but a higher rate of parent vessel sacrifice (22.8% vs. 8.0%, p < 0.001), while ischemic complications were comparable between groups. After further adjustment for covariates, DA showed a trend toward a lower risk of unfavorable outcomes in Model 3 (OR = 0.490, 95% CI 0.237–1.013, p = 0.054). In addition, the association between DA and a higher risk of parent vessel sacrifice remained consistent across all models (Model 1: OR = 3.419, 95% CI 1.811–6.456, p < 0.001; Model 2: OR = 2.737, 95% CI 1.415–5.293, p = 0.003; Model 3: OR = 2.899, 95% CI 1.463–5.747, p = 0.002). Conclusion DA may be associated with a trend toward better long‐term functional outcomes compared with SA. Although parent vessel sacrifice was more frequently required, it was not associated with an increased risk of ischemic complications.

Background:Cerebral small vessel disease (CSVD) is a major cause of vascular cognitive impairment. Glymphatic dysfunction has been implicated in cognitive decline, but its relationship with CSVD-related cognitive impairment, particularly with regard to potential hemispheric differences, remains unclear. Methods:Forty-eight CSVD patients and 56 matched healthy controls underwent brain MRI and cognitive assessment using the Montreal Cognitive Assessment (MoCA). Bilateral ALPS indices (ALPS-L and ALPS-R) were calculated to assess glymphatic function. Pearson and partial correlation analyses were performed to examine associations between ALPS indices and MoCA scores. Logistic regression models and receiver operating characteristic (ROC) analyses were used to evaluate the associations between hemispheric ALPS indices and cognitive impairment as measured by the MoCA and assess their performance in distinguishing CSVD patients from healthy controls. Results:Both ALPS-L and ALPS-R were significantly reduced in CSVD patients (p < 0.01). ALPS-L was positively correlated with MoCA scores (r = 0.307, p = 0.001), independent of demographic factors, whereas ALPS-R showed no significant association. ROC analyses demonstrated that incorporating ALPS indices improved the prediction of relatively lower cognitive performance measured by MoCA, with the model including ALPS-L showing higher predictive performance (AUC = 0.765) compared with the contrast model including ALPS-R (AUC = 0.737). The trend of these models in distinguishing CSVD from healthy controls is consistent. Conclusion:CSVD patients exhibit bilateral lymphatic dysfunction. The left ALPS index showed a lateralized association with MoCA-measured cognitive impairment and may represent a potential imaging marker associated with cognitive performance in CSVD.

BACKGROUND:High-quality evidence comparing surgical strategies within 0-24 h and 24-72 h after aneurysmal subarachnoid hemorrhage (aSAH) remains limited. This study aimed to systematically evaluate surgical safety and long-term outcomes across these two critical time windows. METHODS:Patients with aSAH undergoing aneurysm surgery within 72 h were consecutively enrolled from 12 tertiary centers in northern China between January 2017 and December 2020. A 1:1 propensity score matching (PSM) adjusted for intergroup differences, and a generalized estimating equation (GEE) model accounted for hospital-level clustering. Outcomes were compared between the 0-24 h and 24-72 h groups. Kaplan-Meier curves assessed survival, Cox models identified mortality risk factors, and logistic regression determined predictors of 2-year dependency. RESULTS:A total of 3560 patients were included. After PSM, 1329 patients in the 0-24 h group were matched with 1329 in the 24-72 h group. There were no significant differences in 2-year mortality (12.3% vs 10.8%, p = 0.49), dependency at discharge (21.0% vs 18.4%; adjusted odds ratio (OR) = 0.815, 95% confidence interval (CI) = 0.649-1.024, p = 0.079), or 2-year dependency (10.6% vs 9.3%; adjusted OR = 0.896, 95% CI = 0.636-1.264, p = 0.533). Compared with the 0-24 h group, the 24-72 h group had lower in-hospital mortality (3.8% vs 1.1%; adjusted OR = 0.503, 95% CI = 0.349-0.723, p < 0.001), rebleeding (3.6% vs 1.9%; adjusted OR = 0.489, 95% CI = 0.299-0.801, p = 0.004), and stress ulcer bleeding (8.7% vs 4.9%; adjusted OR = 0.811, 95% CI = 0.713-0.922, p = 0.001). Risk factors for mortality and 2-year dependency differed between groups. CONCLUSION:Surgery within 24 h of onset showed similar long-term outcomes compared with treatment at 24-72 h, but in-hospital mortality and some hemorrhage-related complications differed. Risk factor analysis may provide guidance for individualized treatment strategies.

Background:Systematic investigations into the modifying effect of age on sex-related differences in postoperative outcomes after aSAH remain limited. This study aimed to clarify the role of age in the association between sex and poor outcomes. Methods:We retrospectively reviewed patients with aSAH who underwent surgical treatment and were consecutively admitted between January 2017 and December 2020 across 12 medical centers in four northern provinces of China. Multivariable logistic regression models were used to examine the association between sex and outcomes. Generalized additive models (GAMs) and segmented regression analyses were used to examine the nonlinear associations of sex and age with poor outcomes. Results:A total of 4865 patients were included in the analysis of sex and in-hospital outcomes, of whom 3979 completed follow-up and were included in the 2-year outcome analysis. Regarding 2-year outcomes, female patients exhibited significantly lower risks of poor outcomes (OR = 0.696, 95% CI: 0.564-0.859, P < 0.001) and mortality (OR = 0.558, 95% CI: 0.441-0.707, P < 0.001). Segmented logistic regression based on sex crossover points identified by the GAM at ages 42 and 78 revealed that within the 42-78-year age range, female patients had a significantly lower risk of poor outcomes compared with males (OR = 0.677, 95% CI: 0.543-0.844, P < 0.001). The GAM further indicated that the risk of poor outcomes in females began to increase notably after age 49. Using 49 years as a cutoff in segmented logistic regression, age prior to 49 was not significantly associated with 2-year poor outcomes in females (OR = 0.950, 95% CI: 0.883-1.021, P = 0.164), whereas age 49 and above was associated with a significant increase in risk (OR = 1.088, 95% CI: 1.071-1.105, P < 0.001). Conclusion:Age-related sex differences influence the risk of poor outcomes after aSAH, highlighting the importance of considering sex-age interactions in clinical decision-making.

OBJECTIVE:Despite advancements in neurosurgery and intensive care that reduce overall mortality, poor-grade aneurysmal subarachnoid hemorrhage (aSAH; patients with World Federation of Neurosurgical Societies [WFNS] grades IV and V) remains a significant clinical challenge and is associated with persistently high mortality rates. The aim of this study was to assess the long-term outcomes of patients with poor-grade aSAH and to identify factors influencing patient prognosis to guide clinical management. METHODS:A multicenter, observational cohort study was conducted across 12 regional centers in northern China. The study included patients with poor-grade aSAH admitted from 2017 to 2020. The baseline data included demographics, clinical presentation, aneurysm characteristics, and treatment modalities. Outcome data, including survival status, mortality along with its associated causes and timing, and modified Rankin scale (mRS) scores, were collected prospectively at the last medical follow-up. Changes in case fatality over time were quantified with weighted linear regression. Survival analysis was performed to estimate survival and hazard ratios for death. Binary logistic regression was performed to estimate the odds ratio for dependency (mRS scores 3-5). RESULTS:Among the 1589 enrolled patients, 1339 were successfully followed up, with a mean follow-up of 26.37 months. Among them, 61.5% (824/1339) were dependent or died. The overall mortality rate was 51.1% (684/1339), and 21.4% (140/655) of the survivors were dependent. The risk factors for mortality included age ≥ 65 years, previous history of stroke, and WFNS grade V. Additionally, conservative treatment and endovascular treatment were identified as risk factors and protective factors, respectively, compared with surgical treatment. WFNS grade V and middle cerebral artery aneurysms were independent risk factors for dependency. CONCLUSIONS:Although there has been a downward trend in recent years, the long-term mortality rate for patients with poor-grade aSAH has remained significantly high at 51.1%, with 21.4% of survivors being dependent. Active aneurysm treatment, to the extent possible, is crucial for improving the prognosis of these patients.

BACKGROUND:Ruptured intracranial aneurysm (RIA) combined with internal carotid artery occlusion (ICAO) is a rare and serious vascular condition. We aimed to describe the clinical characteristics and outcomes of these patients. METHODS:We retrospectively analyzed cases of RIA with concurrent spontaneous ICAO from the Chinese Multicenter Aneurysm Database (CMAD). Logistic regression analysis was used to identify independent risk factors associated with patient prognosis. Cox proportional hazards model was performed to determine predictors of cumulative mortality. RESULTS:We analyzed 52 cases of RIA with ICAO, including 41 unilateral and 11 bilateral cases. Among unilateral ICAO cases, aneurysms were ipsilateral in 8, contralateral in 16, and midline in 17. Treatment included coiling (31 cases), clipping (6 cases), and conservative management (15 cases). Prognosis was favorable in 26 cases and unfavorable in 17, including 12 deaths. Logistic regression identified Hunt-Hess grade IV-V, conservative treatment, and symptomatic cerebral infarction as independent risk factors for unfavorable outcome. Cox proportional hazards model found Hunt-Hess grade IV-V to be a predictor of mortality during the 2-year follow-up. CONCLUSION:Hunt-Hess grade, treatment, and in-hospital cerebral infarction independently predict unfavorable outcome, with grades IV-V linked to early death. ICAO may increase the risk of aneurysm rupture, highlighting the importance of aneurysm location and its related hemodynamic mechanisms in clinical management.

BACKGROUND: Posterior cerebral artery (PCA) aneurysms are rare but clinically significant due to their critical location and complex management. The risk factor of the PCA aneurysms rupture remains unclear. This study aimed to investigate the associated factor of PCA aneurysms rupture in a large Chinese cohort. METHODS: We conducted a cross-sectional study including patients diagnosed with PCA aneurysms between January 2017 and December 2020. The study population comprised 143 patients, with 95 in the ruptured group and 48 in the unruptured group. Data on demographic characteristics, aneurysm features, medical history, and treatment outcomes were collected and analyzed using SPSS 27.0. Univariate and multivariate logistic regression analyses were performed to identify associated factors for PCA aneurysm rupture. RESULTS: The presence of coexisting internal carotid artery occlusion (ICAO) was identified as an independent associated factor for PCA aneurysm rupture (odds ratio [OR] = 4.74, 95% confidence interval [CI] 1.22-18.42, P = 0.03). Ischemic stroke (OR=0.44, 95% CI: 0.20-0.97, P = 0.02) and multiple aneurysms (OR=0.41, 95% CI: 0.19-0.87, P = 0.04) were found to be potential protective factors against rupture. The study also revealed a higher incidence of ICAO in the ruptured group (18.9%) compared to the unruptured group (6.3%), indicating a significant association with aneurysm rupture. CONCLUSIONS: This is the first multicenter study to highlight the coexistence of ICAO as a major associated factor for PCA aneurysm rupture in the Chinese population.

BACKGROUND:There is no multicenter comparative study of microsurgical treatment (MST) and endovascular treatment (EVT) for unruptured intracranial aneurysms (UIAs) in China. The aim of this article is to comprehensively analyze the impact of differences in treatment modalities on the prognosis of patients with UIAs in northern China. METHOD:We analyzed data on surgically treated unruptured intracranial aneurysms (UIAs) from the Chinese Multicenter Cerebral Aneurysm Database (January 2017-December 2020). After 1:1 propensity score matching (PSM) to adjust for potential confounders, in-hospital complications and long-term outcomes were compared between MST and EVT cohorts. A generalized estimating equation (GEE) model, with hospital as the clustering variable and an exchangeable correlation structure, was used to evaluate the association between treatment modality and outcomes. Kaplan-Meier survival curves were applied to assess survival, while Cox proportional hazards regression identified mortality risk factors. Logistic regression was used to determine predictors of 2-year dependency. RESULTS:A total of 1953 patients with UIAs were included (MST: 416; EVT: 1537). After PSM, 2-year cumulative mortality differed significantly between the MST and EVT groups. Compared with the EVT group, MST patients had longer hospital stays and higher rates of cerebral ischemia, intracranial infection, hypoproteinemia, pneumonia, and deep vein thrombosis (DVT), but a lower rate of intraoperative rupture. CONCLUSION:EVT demonstrates advantages in terms of long-term mortality, in-hospital complications, length of hospital stay, and functional outcomes.

OBJECTIVE:There is currently no clear consensus on the optimal treatment strategy for multiple intracranial aneurysms (MIAs). This study aimed to systematically compare the clinical outcomes of one-stage treatment of all aneurysms versus treatment of only the responsible aneurysm in patients with ruptured MIAs. METHODS:We included patients with ruptured MIAs who underwent surgical treatment in the Chinese Multicenter Cerebral Aneurysm Database (CMAD). 1:1 propensity score matching (PSM) was applied to balance baseline differences between groups and to compare outcomes and complications between one-stage treatment of all aneurysms and treatment of the responsible aneurysm only. The association between treatment modality and inhospital complications was assessed using a generalized estimating equation model. Survival was analyzed using Kaplan-Meier curves, and Cox proportional hazards models were used to identify risk factors for mortality in patients with ruptured MIAs. RESULTS:A total of 811 patients with ruptured MIAs were initially enrolled in this study. After PSM, 316 patients who underwent one-stage treatment were matched with 316 patients who received treatment for the responsible aneurysm only, resulting in 632 patients included in the final analysis. Although no statistically significant difference in mortality was observed between the groups, the survival curve trend favored one-stage treatment, with a lower 2-year mortality rate (11.2% vs. 16.2%; HR 1.368, 95% CI: 0.920-2.032, p = 0.121). No significant differences were found between the groups in terms of functional outcomes or inhospital complications. Multivariable Cox proportional hazards analysis identified age, previous stroke, and Hunt-Hess grade IV-V as independent risk factors for mortality. Endovascular treatment (EVT) was found to be a protective factor. CONCLUSION:In this cohort, one-stage treatment of ruptured MIAs appeared feasible and showed no evident excess risk compared with treating only the responsible aneurysm. Patient selection remains critical, and the identified mortality risk factors may provide useful guidance for clinical risk assessment and preventive strategies.

Background: The landmark discovery of the meningeal lymphatic system (MLS) has revolutionized our understanding of CNS waste clearance and immune surveillance. Despite a decade of transformative research since its identification in 2015, a comprehensive analysis of its developmental trajectory, current research landscape, and future directions is lacking. This bibliometric study systematically analyzes the first decade of MLS research (2015-2025), with a particular emphasis on neurorestoration potential. Methods: We retrieved relevant publications from the Web of Science Core Collection (WoSCC) between 2015 and 2025. Data were processed using Microsoft Excel, while collaborative networks among countries, institutions, journals, and authors were analyzed via VOSviewer, CiteSpace, GraphPad Prism, Web of Science, and the online bibliometric platform (http://bibliometric.com/). The key metrics included article types, research trends, citation patterns, and keyword frequency. Results: A total of 449 publications from 2546 authors across 703 institutions in 46 countries published in 230 academic journals were identified. Nature communications contributed the largest number of MLS-related articles, whereas Nature was the most cocited journal. The majority of publications focused on immunology and cell biology. The United States and China emerged as leading contributors, with the University of Virginia producing the largest number of publications. Kipnis Jonathan was the most prolific author, whereas Louveau Antoine received the greatest number of cocitations. Keyword co-occurrence and reference analysis revealed that the "glymphatic system" and "meningeal lymphatic vessels" were central research themes. Notably, neurodegenerative diseases emerged as a rapidly growing research hotspot in MLS studies. Conclusion: This decade-spanning analysis reveals the potential of MLS research for clinically relevant neurorestorative applications. The recognition of MLS as a regulator of immune function and neural repair has positioned them as compelling therapeutic targets. Our study highlights key trends and predicts future directions in MLS research. These insights will help prioritize research efforts to harness MLS biology for central nervous system repair paradigms.

Poor-grade aneurysmal subarachnoid hemorrhage (aSAH), defined as World Federation of Neurosurgical Societies (WFNS) grades IV–V on admission, is associated with high mortality and disability. Although treatment initiation within 72 h is commonly recommended, the differential efficacy of specific subintervals during this therapeutic window (e.g., < 12 h, 12–24 h, and 24–72 h) has not been established. This study aims to determine the optimal timing of treatment of poor-grade aSAH using a large multicenter cohort. This cohort study included 990 cases of poor-grade (defined as WFNS grades IV–V on admission) aSAH identified retrospectively across 12 centers. Patients were classified into three different treatment time windows: < 12 h (n = 320), 12–23 h (n = 220), and ≥ 24 h (n = 450) after symptom onset. Outcomes included mortality, unfavorable outcome (modified Rankin scale [mRS] scores 3–6), and dependency (mRS scores 3–5) at follow-up. Cox proportional hazards regression models and competing risk analyses were used to assess the association between treatment delay and outcomes. During a median follow-up of 34.3 months, mortality rates were 46.6

BACKGROUND:The prognostic implications of a prior ischemic stroke in patients undergoing neurosurgical treatment for aneurysmal subarachnoid hemorrhage (aSAH) have not been fully established. This study sought to systematically investigate the outcomes of this population, with the aim of clarifying the impact of previous ischemic stroke on postoperative prognosis. METHOD:This study used the Chinese Multicenter Cerebral Aneurysm Database (CMAD) and included patients with a previous ischemic stroke who underwent neurosurgical treatment between 2017 and 2020. Patients without a previous ischemic stroke were selected as the control group using propensity score matching (PSM). The Generalized Estimating Equation model, with hospital as the clustering variable, was used to assess associations between previous ischemic stroke and outcomes. Prognosis and in-hospital complications were compared between the two groups, and overall survival was analyzed using Kaplan-Meier curves and stratified Cox regression, with hazard ratios (HRs) and 95 percent confidence intervals (CIs). RESULTS:Among the 4960 patients who underwent aneurysm surgery, 314 (6.3%) had a history of ischemic stroke, of whom 17 (0.3%) had pre-stroke dependency. The 2-year mortality was significantly higher in patients with prior ischemic stroke than in those without (25.5% vs. 11.0%, P < 0.001). Notably, the mortality rate reached 49.7% among patients with pre-stroke dependency. After PSM, 313 patients with a history of ischemic stroke were matched to 313 patients without. Compared with controls, patients with previous ischemic stroke had significantly higher risks of poor 2-year outcomes [modified Rankin Scale (mRS) 3-6: 31.5% vs. 29.8%, adjusted odds ratio (aOR) 1.736, 95% CI 1.337-2.253, P < 0.001], postoperative cerebral ischemia (21.4% vs. 10.9%, aOR 2.112, 95% CI 1.179-3.785, P = 0.012) and seizures (2.9% vs. 0.6%, aOR, 4.469 95% CI 1.314-15.199, P = 0.017). However, no significant differences were observed in survival with functional dependency (mRS 3-5). CONCLUSION:Patients with a history of ischemic stroke had more than double the 2-year cumulative mortality following aSAH surgery compared with those without, with an especially high mortality observed in the subgroup with pre-stroke dependency.

BACKGROUND:There is no universally recognized optimal cerebrospinal fluid (CSF) drainage strategy. This study aimed to comprehensively compare the efficacy and safety of external ventricular drainage (EVD) and lumbar drainage (LD) in the management of aneurysmal subarachnoid hemorrhage (aSAH). METHODS:We consecutively included aSAH patients who underwent surgical treatment with CSF drainage between January 2017 and December 2020 in the Chinese Multicenter Cerebral Aneurysm Database (CMAD). After 1:1 propensity score matching (PSM), intergroup outcomes and in-hospital complications were compared between the EVD and LD groups. The Generalized Estimating Equation (GEE) model was used to assess the relationship between the drainage method and intergroup outcomes. Kaplan-Meier curves were used to analyze survival, and Cox proportional hazard modeling was performed to identify risk factors for mortality. RESULTS:952 aSAH patients were initially included. After PSM, 167 patients receiving EVD were matched with 167 patients receiving LD, resulting in a total of 334 patients for the matched analysis. Patients receiving EVD had higher 2-year mortality (27.1% vs 15.1%, p = 0.011) and worse functional outcomes at discharge (45.5% vs 34.0%, adjusted OR: 0.567 95% CI: 0.324-0.991, p = 0.046). However, functional outcomes at 2 years did not show significant differences (23.4% vs 22.0%, adjusted OR: 0.811 95% CI: 0.375-1.754, p = 0.594). No differences were observed in in-hospital complication rates between the two groups. Multivariable Cox proportional hazard modeling identified WFNS Grade IV-V as a risk factor for mortality in the EVD group. In the LD group, mortality risk factors included age ⩾ 65 years, and diabetes. CONCLUSION:LD demonstrated significant advantages in short-term functional outcomes, and long-term survival outcomes, but did not demonstrate significant differences in long-term functional outcomes and in-hospital complications. Risk factors identified in the prognostic analysis may inform clinical decision-making.

Intracranial aneurysms combined with spontaneous internal carotid artery occlusion (ICAO) are a rare and serious vascular disorder. Currently, there is only limited information available on the clinical characteristics of these patients and the risk factors for aneurysm rupture. Our objective is to describe the clinical features of these patients and predict the risk factors for the rupture of unruptured intracranial aneurysms (UIAs) combined with ICAO. We retrospectively analyzed cases of intracranial aneurysms with concurrent spontaneous ICAO from the Chinese Multicenter Aneurysm Database(CMAD). We collected population demographic characteristics and clinical data using a standardized case questionnaire from CMAD. Binary logistic regression analysis was used to identify risk factors for rupture of UIA associated with combined ICAO. We identified 93 patients with intracranial aneurysms combined with ICAO, including 38 females and 55 males, with an average age of 60.7 ± 9.5 years (ranging from 32 to 79 years old). Among those with ICAO, 52 had ruptured intracranial aneurysms (RIAs) and 41 had UIAs. Specifically, there were 81 cases of unilateral ICAO, with 16 aneurysms located on the same side as the ICAO, 22 in the midline (AcomA, Basilar tip), and 43 on the opposite side of the ICAO; 12 cases were bilateral ICAO. Binary logistic regression analysis indicated that risk factors associated with the rupture of UIAs with ICAO included bilateral internal carotid artery occlusion and aneurysms in the posterior circulation. Furthermore, multivariate analysis showed that posterior circulation aneurysms are an independent risk factor for the rupture of UIAs with ICAO. We have described and analyzed the clinical characteristics and risk factors influencing the rupture of intracranial aneurysms in patients with ICAO. The study found that the location of the aneurysm is an important risk factor for the rupture of UIAs combined with ICAO.

BackgroundThe natural course of unruptured intracranial aneurysms (UIAs) has been well described in developed countries, but there is a lack of large studies on UIAs in China. This article aims to fill this gap by detailing the current status and natural course of UIAs in China and identifying the major risk factors for their rupture, providing a basis for clinical decision-making.MethodsWe included all patients with UIAs consecutively admitted to 12 tertiary care centers in 4 provinces in northern China between January 2017 and December 2020. The mean follow-up was 3.1 years (range 0–7.3 years). The current status of UIA patients in China was described in detail. Risk ratios for rupture were analyzed using the Cox proportional hazards model, and Kaplan–Meier curves were analyzed for long-term rupture rates.ResultsIn this study, among the 1,475 patients, 33.4% declined surgical treatment. Of the 1,189 patients who completed follow-up, 10.3% initially received conservative treatment but later underwent surgery. A total of 1,337 patients with UIAs who met the criteria were included in the statistical analysis. The annual rupture rate was 1.75%. Cox proportional hazards model identified the following risk factors for rupture: age over 70 years (HR 2.136, 95% CI 1.302–3.504, p = 0.003), aneurysm size of 10–20 mm (HR 3.543, 95% CI 1.501–8.363, p = 0.004) and ≥20 mm (HR 4.455, 95% CI 1.034–19.187, p = 0.045). ICA (HR 0.427, 95% CI 0.203–0.897, p = 0.025) was a protective factor.ConclusionIn China, treatment options for UIA patients are unique, with a low willingness to undergo surgery leading to a higher rupture rate. A significant percentage of Chinese patients refuse treatment, and those who initially choose conservative management are unlikely to opt for surgical intervention later. Advanced age, specific locations, and size are associated with UIA rupture. This study has important implications for clinical decision-making, public awareness of UIAs, and the development of health policies.

BACKGROUND Genetic susceptibility is a major determinant in intracranial aneurysm (IA) formation and rupture, yet the underlying mechanisms linking genetic variation to vascular dysfunction remain largely unknown. We have identified mutations in ARHGEF17, a guanine nucleotide exchange factor that regulates RhoA activation and cytoskeletal organization, as potential risk variants for IA. Given ARHGEF17’s regulatory role in endothelial barrier integrity and actin remodeling, we hypothesized that ARHGEF17 deficiency promotes IA pathogenesis through dysregulation of the RhoA/ROCK2/MLC signaling axis, leading to endothelial dysfunction and vascular wall instability. METHODS CRISPR–Cas9–mediated ARHGEF17 knockout (ARHGEF17⁻/⁻) mice and morpholino-based ARHGEF17-deficient zebrafish were established to assess the in vivo vascular effects of ARHGEF17 loss. An intracranial aneurysm model combining elastase injection and deoxycorticosterone acetate (DOCA)–induced hypertension was used to evaluate aneurysm incidence, rupture rate, and survival. Structural remodeling of the Circle of Willis (CoW) was assessed by Victoria Blue, EVG, and Picrosirius Red staining, as well as immunofluorescence for α-SMA, OPN, CD31, and inflammatory markers. Complementary in vitro studies were performed in HUVECs using lentiviral ARHGEF17 silencing (three shRNAs of varying efficiency) to examine endothelial proliferation, migration, tube formation, and barrier function (TEER). Activation of RhoA/ROCK2/MLC signaling was quantified by G-LISA and Western blotting. The ROCK inhibitor Y-27632 (10 μM) was applied to determine pathway dependence. RESULTS ARHGEF17⁻/⁻ mice exhibited a significantly higher incidence and rupture rate of intracranial aneurysms, accompanied by fragmentation of elastic fibers, loss of collagen organization, vascular smooth muscle cell dedifferentiation, and robust inflammatory activation in the CoW. Zebrafish lacking ARHGEF17 showed frequent intracranial hemorrhage and compromised vascular wall integrity, further confirming ARHGEF17’s role in cerebrovascular stability. In ECs, ARHGEF17 knockdown impaired proliferation, migration, tube formation, and barrier integrity in a silencing-efficiency–dependent manner. Mechanistically, ARHGEF17 deficiency activated the RhoA/ROCK2/MLC pathway, leading to increased phosphorylation of MLC and MYPT1 and disorganization of F-actin and junctional proteins. Pharmacological inhibition with Y-27632 restored endothelial function, normalized cytoskeletal structure, and re-established junctional continuity, indicating a ROCK2-dependent mechanism. CONCLUSIONS Our findings establish ARHGEF17 as a critical regulator of cerebrovascular integrity and identify RhoA/ROCK2/MLC mediated cytoskeletal remodeling as the mechanistic link between ARHGEF17 deficiency and aneurysm pathogenesis. Loss of ARHGEF17 compromises endothelial barrier function, triggers vascular inflammation, and promotes aneurysm formation and rupture. Importantly, ROCK inhibition rescues endothelial dysfunction, highlighting the RhoA/ROCK2/MLC axis as a promising therapeutic target for ARHGEF17 mutation–associated intracranial aneurysms. ### Competing Interest Statement The authors have declared no competing interest.