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Background: Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening neurosurgical emergency with a high mortality rate. Delayed cerebral ischemia (DCI) and cerebral vasospasm (CVS) are delayed products of early brain injury (EBI), which may constitute the principal determinant of an unfavorable patient prognosis. Consequently, the mitigation of DCI and CVS assumes paramount significance in the pursuit of enhanced patient outcomes. However, except for oral nimodipine, there is no effective therapy available in the current guideline. Hence, the exigency arises to proffer novel treatment paradigms. The diversity of hydrogen therapeutic targets has been largely reported in basic research, unveiling its latent capacity to ameliorate EBI in aSAH patients., Methods: Early Hydrogen-Oxygen Gas Mixture Inhalation in Patients with Aneurysmal Subarachnoid Hemorrhage (HOMA), a single-center, prospective, open-labeled, randomized controlled clinical trial, endeavors to evaluate the efficacy and safety of hydrogen-oxygen gas mixture inhalation therapy in aSAH patients. A cohort of 206 patients will be randomized to either hydrogen-oxygen gas mixture inhalation group (8 h per day, 3 L/min, hydrogen concentration of 67%, oxygen concentration of 33%) or oxygen inhalation group (8 h per day, 3 L/min, oxygen concentration of 33%) within 72 h after aSAH and treated for 7 days in the ICU ward. The primary outcomes are the incidence of DCI and CVS during hospitalization., Discussion: The HOMA aims to evaluate the effectiveness of hydrogen-oxygen gas mixture inhalation therapy in preventing DCI or CVS and improving outcomes in aSAH patients. Notably, this is the first large-scale trial of hydrogen therapy in aSAH patients. Given that the Chinese population represents a significant portion of the global population and the increasing incidence of stroke due to aging, optimizing patient care is vital. Given the current challenges in aSAH patient outcomes, initiating more prospective clinical trials is essential. Recent research has shown hydrogen's therapeutic potential, aligning with EBI in aSAH, driving our exploration of hydrogen therapy's mechanisms in post-aneurysm rupture damage., Ethics and Dissemination: The protocol for the HOMA study was approved by the Ethics Committee of Beijing Tiantan Hospital, Capital Medical University (KY 2022-020-02). All results of the present study will be published in peer-reviewed journals and presented at relevant conferences., Trial Registration: ClinicalTrials.gov NCT05282836. Registered on March 16, 2022., (© 2024. The Author(s).)

Purpose: Early hypoperfusion changes exist in patients with aneurysmal subarachnoid hemorrhage (aSAH). We aimed to investigate a readily obtainable quantitative computed tomography perfusion (CTP) parameter that could assist in quickly identifying patients at risk of delayed cerebral ischemia (DCI) and poor 90-day functional outcomes on admission., Methods: We prospectively collected data between 2021.04 and 2022.12. Preoperative CTP data were post-processed using RAPID software. The cortical blood flow insufficiency (CBFI) was defined as Time-to-maximum > 4.0 s. Patients were categorized into four groups according to CBFI volume distribution. To minimize differences among the groups, we employed stabilized inverse probability of treatment weighting (sIPTW). The primary outcome was DCI and poor 90-day functional outcomes (modified Rankin Scale, 3-6) was the secondary outcome. Multivariable Cox or Logistic analysis were performed to estimate the association between CBFI volume and the study outcomes, both before and after sIPTW., Results: At baseline, the mean (SD) age of the 493 participants was 55.0 (11.8) years, and 299 (60.6%) were female. One hundred and seven participants with DCI and eighty-six participants with poor 90-day functional outcomes were identified. After sIPTW, CBFI volume demonstrated a significant association with DCI (Cox regression: Group 4 versus Group 1, HR 3.69, 95% CI 1.84-7.01) and poor 90-day functional outcomes (Logistic regression: Group 4 versus Group 1, OR 4.61, 95% CI 2.01-12.50)., Conclusion: In this study, an elevated preoperative CBFI volume was associated with adverse outcomes in aSAH patients. More well-designed studies are needed to confirm this association., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objective: Delayed cerebral ischemia (DCI)-induced cerebral infarction is a major cause of adverse neurological outcomes following aneurysmal subarachnoid hemorrhage (aSAH). This study aimed to investigate the relationship between postoperative serum electrolyte levels and DCI in patients with aSAH., Materials and Methods: We analyzed the data of patients with aSAH between 2015 and 2022. The patients were classified into two groups according to whether they experienced DCI. Electrolyte levels were categorized into three groups based on the normal ranges for electrolytes. Logistic regression models were used to study the relationship between electrolyte levels and DCI. Another logistic regression analysis was conducted to explore the relationship between the different severity levels of statistically significant indicators and DCI. A restrictive cubic spline model was adopted to assess the potential linear relationship between electrolytes and DCI. Subsequently, sensitivity analysis was performed to assess the impact of collinearity among ions. Finally, subgroup analysis was performed., Results: This study included 1,099 patients. Patients with hyperchloremia were more prone to DCI than those with normal chloride levels. Subsequently, excluding the population with hypochloremia, both mild and severe hyperchloremia were found to be associated with an increased risk of DCI compared with normal chloride levels. Within the framework of a restrictive cubic spline, our findings revealed an increased incidence of DCI (P for nonlinear = 0.735) as chloride levels increased. Sensitivity analysis revealed that patients with severe hyperchloremia were more susceptible to DCI., Conclusions: This study found that patients with aSAH and postoperative hyperchloremia are more prone to developing DCI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Objective: The aim of this study is to explore whether preoperative hemoglobin levels could serve as a prospective biomarker for early brain injury in patients with aneurysmal subarachnoid hemorrhage (aSAH). This investigation seeks to discern its association with postoperative complications and unfavorable clinical outcomes., Methods: We conducted a comprehensive analysis of data derived from the LongTeam registry, including patients with aSAH diagnosed between January 2015 and September 2021. These patients were stratified into three distinct groups based on their hemoglobin levels: anemic, standard, and elevated HGB. We employed logistic models featuring spline transformations to assess the relationship between HGB levels and in-hospital complications. Furthermore, a multivariate Cox proportional hazard model was employed to estimate the impact of elevated hemoglobin levels on the hazard function, which was elucidated through Kaplan-Meier curves., Results: Our study comprised a total of 988 patients, among whom 115 (11.6%) presented preoperative anemia, and 63 (6.4%) exhibited elevated preoperative HGB levels. Following adjustments for potential confounding factors, no significant disparity in risk was evident between anemic patients and those with standard HGB levels. However, individuals with elevated HGB levels displayed a heightened incidence and an increased risk of developing deep vein thrombosis (DVT, odds ratio [OR] = 2.39, 95% confidence interval [CI] = 1.16-4.91, p = 0.018; hazard ratio [HR] = 2.05, 95% CI 1.08-3.92, p = 0.015). Aberrant HGB concentrations did not demonstrate an association with other clinical outcomes., Conclusion: Our findings emphasize that abnormal HGB levels show no association with adverse outcomes at the 90 days mark after accounting for clinical confounding factors in patients with aSAH. Simultaneously, the study illuminates the potential of HGB as an early indicator for identifying patients at a heightened risk of developing DVT., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Objectives: Early fibrinolysis disorder exists in aneurysmal subarachnoid hemorrhage (aSAH). We aimed to investigate the association of markers of early fibrinolysis disorder with poor 90-day prognosis in patients with aSAH., Materials and Methods: A total of 693 consecutive aSAH patients from April 2020 to December 2022 were selected from the Long-term Prognosis of Emergency Aneurysmal Subarachnoid Hemorrhage (LongTEAM) trial. Poor 90-day prognosis was defined as a modified Rankin Scale 3-6 at 90 days after discharge. D-dimer (DD) and Fibrin degradation product (FDP) levels on admission were used to assess fibrinolysis disorder and patients were classified according to their quartiles. Multivariable logistic regression analysis was used to determine the association., Results: Of 693 patients included, 131 (18.9%) had poor 90-day prognosis. Patients in the highest quartile of DD and FDP levels had higher risk of poor 90-day prognosis than those in the first quartile (DD: adjusted odds ratio [aOR]=2.22, 95% confidence interval [CI], 1.13-4.36, p = 0.021; FDP: aOR=2.87, 95% CI, 1.48-5.58, p = 0.002), after adjusting for potential risk factors. Meanwhile, a linear dose-response relationship between DD and FDP and poor 90-day prognosis was found. Subgroup analysis showed that DD and FDP were consistently associated with poor 90-day prognosis across subgroups, and no intergroup interaction was found. Interestingly, the associations of DD and FDP with poor 90-day prognosis were more significant in low-grade aSAH patients., Conclusions: Elevated markers of early fibrinolysis disorder, including DD and FDP on admission, were associated with poor 90-day prognosis in aSAH patients., Competing Interests: Declaration of Competing Interest The authors have no personal, financial, or institutional interest in any of the materials or methods used in this study or the findings specified in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Objective: Our study aims to investigate the association between the Hounsfield unit (Hu) value of the insular cortex (IC) during emergency admission and the subsequent occurrence of post-operative neurocardiogenic injury (NCI) among patients afflicted with aneurysmal subarachnoid hemorrhage (aSAH)., Methods: Patients baseline characteristics were juxtaposed between those with and without NCI. The significant variables were incorporated into a multivariable stepwise logistic regression model. Receiver operating characteristic (ROC) curves were drafted for each significant variable, yielding cutoff values and the area under the curve (AUC). Subgroup and sensitivity analyses were performed to assess the predictive performance across various cohorts and ascertain result stability. Propensity score matching (PSM) was ultimately employed to redress any baseline characteristic disparities., Results: Patients displaying a right IC Hu value surpassing 28.65 exhibited an escalated risk of postoperative NCI upon confounder adjustment (p < 0.001). The ROC curve eloquently manifested the predictive capacity of right IC Hu in relation to NCI (AUC = 0.650, 95%CI, 0.591-0.709, p < 0.001). Further subgroup analysis revealed significant interactions between right IC Hu and factors such as age, history of heart disease, and Graeb 5-12 score. Sensitivity analysis further upheld the results' significant (p = 0.002). The discrepancy in NCI incidence between the two groups, both prior (p < 0.002) and post (p = 0.039) PSM, exhibited statistical significance. After PSM implementation, the likelihood of NCI displayed an ascending trend with increasing right IC Hu values, from the Hu 1 cohort onward, receding post the Hu 4 cohort., Conclusion: This study definitively establishes an elevated right IC Hu value in the early stages of emergency admission as an autonomous predictor for ensuing NCI subsequent to aSAH., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

This study aimed to identify the association between the platelet-to-white blood cell ratio (PWR) and outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). Data for patients diagnosed with aSAH and admitted from January 2015 to December 2020 were retrospectively analyzed. Multivariate logistic regression analysis was performed to identify factors that correlated with unfavorable outcomes at 3 months. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off value for the PWR to discriminate favorable and unfavorable outcomes at 3 months. The patients were then divided into two groups based on this cut-off value. To reduce selection bias, propensity score matching (PSM) was performed to balance the baseline characteristics. In total, 800 patients were enrolled in this study. The multivariate logistic regression analysis showed that the PWR (odds ratio, 1.05; 95% confidence interval, 1.00-1.09; p = 0.034) at admission was independently associated with unfavorable 3-month outcomes. ROC curve analysis identified 15.69 as the best cut-off PWR value for predicting clinical outcomes. After PSM, patients with a PWR < 15.69 exhibited a higher incidence of postoperative pneumonia (POP) (37.2% vs. 25.6%, p = 0.011) and unfavorable 3-month outcomes (19.3% vs. 12.1%, p = 0.043). These findings suggest that patients with aSAH showing a PWR < 15.69 at admission have a higher probability of developing POP, which may be the main factor causing unfavorable outcomes at 3 months., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Arteriovenous fistulas (AVFs) at the craniocervical junction (CCJ) are uncommon conditions with complex angioarchitecture. The objective of this study was to identify the angioarchitectural features of CCJ-AVF that were predictive of clinical presentation and neurological function. The study encompassed a total of 68 consecutive patients with CCJ-AVF at two neurosurgical centers between 2014 and 2022. Additionally, a systematic review was conducted, including 68 cases with detailed clinical data obtained via PubMed database spanning 1990 to 2022. Clinical and imaging data were collected and pooled together to analyze factors associated with subarachnoid hemorrhage (SAH), myelopathy, and modified Rankin scale (mRS) at presentation. The mean age of the patients was 54.5 ± 13.1 years, with 76.5% of them being male. The most common feeding arteries were V3-medial branches (33.1%), and drainage was frequently through the anterior or posterior spinal vein/perimedullary vein (72.8%). SAH was the most common presentation (49.3%), and an associated aneurysm was identified as a risk factor for SAH (adjusted OR, 7.44; 95%CI, 2.89-19.15). Anterior or posterior spinal vein/perimedullary vein (adjusted OR, 2.78; 95%CI, 1.00-7.72) and male gender (adjusted OR, 3.76; 95%CI, 1.23-11.53) were associated with higher risk for myelopathy. Myelopathy at presentation was an independent risk factor for unfavorable neurological status (adjusted OR per score, 4.73; 95%CI, 1.31-17.12) in untreated CCJ-AVF. The present study identifies risk factors associated with SAH, myelopathy, and unfavorable neurological status at presentation in patients with CCJ-AVF. These findings may help treatment decisions for these complex vascular malformations., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study aimed to establish a new scoring model based on the early brain injury (EBI) indicators to predict the 90-day functional outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). We retrospectively enrolled 825 patients and prospectively enrolled 108 patients with aSAH who underwent surgical clipping or endovascular coiling (derivation cohort = 640; validation cohort = 185; prospective cohort = 108) in our institute. We established a logistic regression model based on independent risk factors associated with 90-day unfavorable outcomes. The discrimination of the prognostic model was assessed by the area under the curve in a receiver operating characteristic curve analysis. The Hosmer-Lemeshow goodness-of-fit test and a calibration plot were used to evaluate the calibration of the prediction model. The developed scoring model named "TAPS" (total score, 0-7 points) included the following admission variables: age > 55 years old, WFNS grade of 4-5, mFS grade of 3-4, Graeb score of 5-12, white blood cell count > 11.28 × 10 9 /L, and surgical clipping. The model showed good discrimination with the area under the curve in the derivation, validation, and prospective cohorts which were 0.816 (p < 0.001, 95%CI = 0.77-0.86), 0.810 (p < 0.001, 95%CI = 0.73-0.90), and 0.803 (p < 0.001, 95%CI = 0.70-0.91), respectively. The model also demonstrated good calibration (Hosmer-Lemeshow goodness-of-fit test: X 2  = 1.75, df = 8, p = 0.988). Compared with other predictive models, TAPS is an easy handle tool for predicting the 90-day unfavorable outcomes of aSAH patients, which can help clinicians better understand the concept of EBI and quickly identify those patients at risk of poor prognosis, providing more positive treatment strategies. Trial registration: NCT04785976. Registered 5 March 2021-retrospectively registered, http://www.clinicaltrials.gov ., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: To assess differences in the clinical prognosis between different treatment timings in poor-grade (Hunt and Hess grade 4-5) aneurysmal subarachnoid hemorrhage patients., Methods: The treated 127 poor-grade aneurysmal subarachnoid hemorrhage patients were divided into three groups: early treatment within 2 days, treatment on days 3 to 10, and treatment for more than 10 days after the hemorrhage. Odd ratios with a 95% confidence interval were calculated in logistic regression for different timing strategies regarding delayed cerebral ischemia and poor prognosis at 3 months. Subgroup analyses were conducted to determine whether the different timing strategies affect the prognosis., Results: Patients who received the treatment on days 3 to 10 were prone to develop delayed cerebral ischemia and poor prognosis at 3 months. Postponing treatment in patients older than 55 years or diagnosed with an intraventricular hematoma on the initial computed tomography scan may lead to poor prognosis, with the early intervention group as a reference., Conclusions: Early intervention in poor-grade aneurysmal subarachnoid hemorrhage is suggested to be implemented. The treatment on 3 to 10 days harbored the highest risk of poor prognosis; patients might benefit more from early intervention, especially for ones older than 55 years or diagnosed with an intraventricular hematoma., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Small multiple intracranial aneurysms (SMIAs) are known to be more prone to rupture than are single aneurysms. However, specific recommendations for patients with small MIAs are not included in the guidelines of the American Heart Association and American Stroke Association. In this study, we aimed to evaluate the feasibility of machine learning-based cluster analysis for discriminating the risk of rupture of SMIAs., Methods: This multi-institutional cross-sectional study included 1,427 SMIAs from 660 patients. Hierarchical cluster analysis guided patient classification based on patient-level characteristics. Based on the clusters and morphological features, machine learning models were constructed and compared to screen the optimal model for discriminating aneurysm rupture., Results: Three clusters with markedly different features were identified. Cluster 1 (n = 45) had the highest risk of subarachnoid hemorrhage (SAH) (75.6%) and was characterized by a higher prevalence of familiar IAs. Cluster 2 (n = 110) had a moderate risk of SAH (38.2%) and was characterized by the highest rate of SAH history and highest number of vascular risk factors. Cluster 3 (n = 505) had a relatively mild risk of SAH (17.6%) and was characterized by a lower prevalence of SAH history and lower number of vascular risk factors. Lasso regression analysis showed that compared with cluster 3, clusters 1 (odds ratio [OR], 7.391; 95% confidence interval [CI], 4.074-13.150) and 2 (OR, 3.014; 95% CI, 1.827-4.970) were at a higher risk of aneurysm rupture. In terms of performance, the area under the curve of the model was 0.828 (95% CI, 0.770-0.833)., Conclusions: An unsupervised machine learning-based algorithm successfully identified three distinct clusters with different SAH risk in patients with SMIAs. Based on the morphological factors and identified clusters, our proposed model has good discrimination ability for SMIA ruptures., (© 2023. The Author(s).)

Aneurysmal subarachnoid hemorrhage (aSAH) is the most devastating form of stroke. Up to now, little is known about the effect of sex differences on complications and outcomes. We retrospectively reviewed aSAH patients admitted to our institution between January 2015 and December 2020. The functional outcomes at discharge and 90 days after discharge were assessed using the modified Rankin Scale (mRS). Baseline characteristics, in-hospital complications, and outcomes were compared after 1:1 propensity score matching (PSM). The area under the curve (AUC) in the receiver operating characteristic curve (ROC) analysis was calculated to measure each independent risk factor's prediction ability. A total of 833 patients were included. After PSM, 109 male patients were compared with 109 female patients. Female patients had a higher incidence of anemia (47/109 [43.1%] vs. 30/109 [27.5%], p = 0.016) than male patients, while male patients had a higher incidence of pneumonia (36/109 [33.0%] vs. 19/109 [17.4%], p = 0.008) than female patients. No significant differences were found in the rate of unfavorable outcomes at discharge and 90-day outcomes (40/109 [36.7%] vs. 50/109 [45.9%], p = 0.169; 15/109 [13.8%] vs. 19/107 [17.8%], p = 0.420) between female and male patients. Pneumonia (AUC = 0.749, 95% confidence interval [CI] = 0.623-0.875, p < 0.001) and anemia (AUC = 0.753, 95% CI = 0.632-0.873, p = 0.002) showed good ability to predict 90-day unfavorable outcomes in male and female patients, respectively. Female patients had a higher incidence of anemia but a lower incidence of pneumonia during hospitalization. However, differences in in-hospital complications did not result in differences in outcomes between women and men. Clinical Trial Registration: NCT04785976. 2021/03/05, retrospectively registered., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Hemoglobin (HGB), a potent spasmogen, may cause irreversible damage to the brain after aneurysm rupture. However, there is no clinical evidence to reveal the relationship between blood HGB concentrations on admission and the prognosis of patients with aneurysmal subarachnoid hemorrhage (aSAH). We retrospectively reviewed all aSAH patients admitted to our institution between January 2015 and December 2020. Functional outcome was assessed at 90 days after discharge using the modified Rankin scale (mRS). Independent risk factors associated with 90-day unfavorable outcomes were derived from a forward stepwise multivariate analysis. Receiver operating characteristic curve analysis was conducted to identify the best cutoff value of HGB to discriminate 90-day unfavorable outcomes. Then, patients were divided into two groups according to the cutoff value of HGB, and to account for imbalances in baseline characteristics, propensity score matching (PSM) was carried out to assess the impact of HGB on in-hospital complications. A total of 800 aSAH patients without anemia on admission were retrospectively enrolled in this study. Elevated blood HGB (OR = 1.02, 95% CI = 1.00-1.03, p = 0.018) on admission was identified as an independent risk factor associated with 90-day unfavorable outcomes, and the cutoff value was 149.5 g/L. After PSM, patients with an HGB > 149.5 g/L had a higher incidence of in-hospital delayed cerebral ischemia (DCI) (33.9% vs. 22.0%, p = 0.013) and deep vein thrombosis (DVT) (11.9% vs. 4.0%, p = 0.006). Patients with a blood HGB > 149.5 g/L on admission might develop more DCI and DVT during hospitalization, leading to 90-day unfavorable outcomes in aSAH patients. ClinicalTrials.gov Identifier: NCT04785976. 2021/03/05, retrospectively registered., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Controlling blood pressure levels is critical to preventing intracranial aneurysm rupture, and a summary review of induced rupture events allows better health education for patients. We retrospectively reviewed all medical records of consecutive patients with aneurysmal subarachnoid hemorrhage (aSAH) admitted to Beijing Tiantan Hospital from 2015 to 2020. We collected patients' demographic information, aneurysm morphology, blood pressure level on admission, time to onset, and events at the time of aneurysm rupture to analyze the factors precipitating aneurysmal rupture. A total of 764 patients were enrolled for analysis, including 461 (60.3%) female patients and 303 (39.7%) male patients. The mean age of onset in this cohort was 55, and 465 (60.9%) patients had hypertension history. Autumn (245/764 [32.1%]) was the most frequent season for aneurysm rupture, and 07:00-12:59 (277/764 [36.3%]) was the most frequent time frame for aneurysm rupture. The five most prevalent events when aneurysm rupture happened were: (1) daily behaviors that may induce hypertension (181/764 [23.7%]), especially defecation or micturition (116/181 [64.1%]); (2) sporting (162/764 [21.2%]), especially high-intensity sports (108/162 [66.7%]); (3) mood and mental factors (112/764 [14.7%]), especially arguing or quarreling (61/112 [54.5%]); (4) sudden postural changes (93/764 [12.2%]), especially getting up (69/93 [74.2%]); and (5) sleeping (72/764 [9.4%]). Patients should avoid behaviors that may cause fluctuations in blood pressure, including keeping warm during seasonal alternation, keeping their urine and defecation unobstructed, avoiding high intensity physical exercise, maintaining a happy mood, avoiding sudden postural changes, and should not bathe with too cold or too hot water., (© 2022 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background and Purpose: Approximately 15%-45% of patients with unruptured intracranial aneurysms have multiple intracranial aneurysms (MIAs). Determining which one is most likely to rupture is extremely important for treatment decision making for MIAs patients. This study aimed to develop and validate a nomogram to evaluate the per-aneurysm rupture risk of MIAs patients., Methods: A total of 1671 IAs from 700 patients with MIAs were randomly dichotomised into derivation and validation sets. Multivariate logistic regression analysis was used to select predictors and construct a nomogram model for aneurysm rupture risk assessment in the derivation set. The discriminative accuracy, calibration performance and clinical usefulness of this nomogram were assessed. We also developed a multivariate model for a subgroup of 158 subarachnoid haemorrhage (SAH) patients and compared its performance with the nomogram model., Results: Multivariate analyses identified seven variables that were significantly associated with IA rupture (history of SAH, alcohol consumption, female sex, aspect ratio >1.5, posterior circulation, irregular shape and bifurcation location). The clinical and morphological-based MIAs (CMB-MIAs) nomogram model showed good calibration and discrimination (derivation set: area under the curve (AUC)=0.740 validation set: AUC=0.772). Decision curve analysis demonstrated that the nomogram was clinically useful. Compared with the nomogram model, the AUC of multivariate model developed from SAH patients had lower value of 0.730., Conclusions: This CMB-MIAs nomogram for MIAs rupture risk is the first to be developed and validated in a large multi-institutional cohort. This nomogram could be used in decision-making and risk stratification in MIAs patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: It remains unclear whether the additive effect of coexisting intracranial aneurysms increases the risk of subarachnoid hemorrhage (SAH) in patients with multiple intracranial aneurysms. We have performed a tentative analysis for the additive effect of coexisting aneurysms., Methods: This multi-institutional cross-sectional study included 1781 aneurysms from 746 patients with multiple intracranial aneurysms. Using the generalized linear mixed model, we analyzed risk factors associated with individual aneurysm rupture and assessed the additive risk of SAH for each patient., Results: The coexisting aneurysms number was not significantly associated with individual intracranial aneurysm rupture, both in unadjusted and adjusted analyses. Patient-level analysis found that an increased number of coexisting aneurysms was significantly associated with a greater estimated additive risk ( P <0.001). Estimated additive risks of patients with 2, 3, and 4 or more coexisting intracranial aneurysms were 25.9%, 31.8%, and 38.1%, respectively, which are comparable to the actual incidence of SAH in those patients (26.6%, 29.5%, and 36.5%, respectively), with a Spearman correlation coefficient of 1.000 ( P <0.001). Compared with aneurysm-related factors, the estimated additive effect had better discrimination power for SAH risk, with areas under the receiver operating characteristic curve of 0.821., Conclusions: We found that a greater number of coexisting aneurysms did not increase rupture risk of individual aneurysms, but the potential additive effect might increase SAH risk in patients with multiple intracranial aneurysms.

Objective: To study clinical outcome of giant intracranial aneurysms (diameter ≥25 mm) treated with different surgical modalities and to analyze factors affecting prognosis., Methods: A retrospective analysis was performed of 204 consecutive patients with giant intracranial aneurysms who underwent surgical treatment in our department from 1995 to 2008. Clinical outcome was evaluated with the Glasgow Outcome Scale., Results: Surgical modalities included direct aneurysm neck clipping in 102 patients (50.0%), parent artery reconstruction in 51 patients (25.0%), proximal artery ligation in 23 patients (11.3%; 4 patients combined with revascularization), trapping in 26 patients (12.7%), and wrapping in 2 patients (1.0%). Follow-up data were available for 181 patients (88.7%), with a mean follow-up period of 62 months (range, 12-164 months). A good outcome (Glasgow Outcome Scale score 5) was observed in 114 patients (63.0%), and a poor outcome (Glasgow Outcome Scale score 1-4) was observed in 67 patients (37.0%). Independent factors that affected prognosis were age and location of aneurysm. Older age (≥50 years) and location of aneurysm in posterior circulation were associated with poor outcome. In 85 patients with preoperative subarachnoid hemorrhage, patients with a higher Hunt and Hess grade (≥3) had a worse outcome compared with patients with a low Hunt and Hess grade (1 or 2). Surgical modalities and other factors were not significantly associated with clinical outcome., Conclusions: Giant intracranial aneurysms are effectively treated with craniotomy and surgical treatment. Older age, aneurysm location in posterior circulation, and higher Hunt and Hess grade are risk factors affecting prognosis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Poor-grade aneurysmal subarachnoid hemorrhage (aSAH) is associated with increased intracranial pressure, and these patients are unstable with a high risk of rebleeding. Computed tomography angiography (CTA) has been proposed as an examination tool for the rapid detection of ruptured aneurysms. We aimed to determine the safety and efficacy of CTA alone for surgical treatment of poor-grade aSAH compared with digital subtraction angiography (DSA)., Methods: We conducted a multicenter retrospective analysis of 144 patients with poor-grade aSAH who underwent surgical treatment for 2 different cohorts. Patients were grouped into CTA alone and DSA groups. Baseline characteristics, postoperative complications, and clinical outcomes at discharge and at last follow-up were compared between the 2 groups. Multivariate logistic regression models were used to assess the association between CTA alone and clinical outcomes after we adjusted for potential confounders., Results: Of the 116 patients included, 42 (36.2%) patents received CTA alone and 74 patients (63.7%), including 12 patients with CTA and DSA and 62 patients with DSA alone, received DSA before surgical treatment. Patients with larger ruptured aneurysms (P = 0.006), aneurysm sizes of larger than 5 mm (P = 0.025), presence of single aneurysms (P = 0.018), and presence of intraventricular hemorrhage (P = 0.019) more often received CTA alone. All ruptured aneurysms were clipped successfully during surgery. There were no statistically significant differences in postoperative complications and clinical outcomes between the 2 groups., Conclusions: Although CTA alone can be safely and effectively used in most patients requiring surgical treatment, additional DSA may be considered in patients with smaller ruptured aneurysms or in those with multiple aneurysms., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: There is no consensus regarding the optimal timing for surgery for poor-grade aneurysmal subarachnoid hemorrhage., Objective: To retrospectively evaluate variation in patient characteristics and outcomes between early and delayed surgery groups., Methods: Poor-grade aneurysmal subarachnoid hemorrhage was defined as a World Federation of Neurosurgical Societies grade of IV or V after resuscitation. Early surgery was defined as surgery performed within 72 hours of ictus, and delayed surgery was defined as surgery after 72 hours. Outcomes were assessed by modified Rankin score. The mean time of follow-up was 12.5 ± 3.4 months., Results: Of the 118 patients included in the study, 80 (68%) underwent early surgery and 38 (32%) underwent delayed surgery. Patients with brain herniation (P < .001) and a lower Fisher grade (P = .02) more often underwent early surgery. Patients in the early group more often underwent decompressive craniectomy (P < .001). Postoperative complications and length of hospital stay did not differ, and outcomes were similar between the 2 groups. Forty (34%) patients had an excellent outcome (modified Rankin score 0-1). Multivariate analysis showed a slight trend toward an excellent outcome in the early surgery group. Younger age, World Federation of Neurosurgical Societies grade IV after resuscitation, and middle cerebral artery aneurysms were independent predictors of an excellent outcome., Conclusion: Although patients with brain herniation and a lower Fisher grade were more likely to undergo early surgery, there was a slight trend toward an excellent outcome in the early surgery group. Patients with a younger age, World Federation of Neurosurgical Societies grade IV after resuscitation, and middle cerebral artery aneurysms were more likely to experience an excellent outcome.

Objective: To determine factors and outcomes associated with ultra-early surgery for poor-grade aneurysmal subarachnoid haemorrhage (aSAH)., Design: A multicentre retrospective analysis, observational study., Setting: High-volume teaching hospitals (more than 150 aSAH cases per year)., Participants: 118 patients with World Federation of Neurosurgical Societies (WFNS) grades IV and V underwent surgical treatment. Ultra-early surgery was defined as surgery performed within 24 h of aSAH, and delayed surgery as surgery performed after 24 h. Outcome was assessed by modified Rankin Scale (mRS). The mean time of follow-up was 12.5±3.4 months (range 6-28 months)., Results: 47 (40%) patients underwent ultra-early surgery, and 71 (60%) patients underwent delayed surgery. Patients with WFNS grade V (p=0.011) and brain herniation (p=0.004) more often underwent ultra-early surgery. Postoperative complications were similar in ultra-early and delayed surgery groups. Adjusted multivariate analysis showed the outcomes were similar between the two groups. Multivariate analysis of predictors of poor outcome, ultraearly surgery was not an independent predictor of poor outcome, while advanced age, postresuscitation WFNS V grade, intraventricular haemorrhage, brain herniation and non-middle cerebral artery (MCA) aneurysms were associated with poor outcome., Conclusions: Although patients with WFNS grade V and brain herniation more often undergo ultra-early surgery, postoperative complications and outcomes in selected patients were similar in the two groups. Patients of younger age, WFNS grade IV, absence of intraventricular haemorrhage, absence of brain herniation and MCA aneurysms are more likely to have a good outcome. Ultra-early surgery could improve outcomes in carefully selected patients with poor-grade aSAH., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: The APOE-E4 allele has been identified as a risk factor for Alzheimer's disease and unfavorable outcomes after brain injuries. The purpose of this study was to confirm that APOE allele polymorphism also represents a risk factor for unfavorable outcomes following aneurysmal subarachnoid hemorrhage (SAH)., Methods: A total of 104 patients with aneurysmal SAH were studied. Computed tomography (CT) scan findings of SAH were assessed by Fisher's grade and clinical neurologic assessment was performed using the Hunt and Hess (H&H)grading system. Serum lipids were also analyzed. Outcomes at 3 months after SAH were determined using the Glasgow Outcome Scale., Results: The distributions of APOE genotypes and alleles of patients were matched with those of control subjects. That 5 of 18 patients with APOE-E4 allele (28%) had an unfavorable outcome was significantly different from those without APOE-E4 (8%, chi2, p = 0.032; OR = 4.34, 95% CI 1.20-15.75). However, the presence or absence of E2 or E3 alleles had no significant difference. The relative hazard of APOE-E4 for unfavorable outcome exited after adjustment for clinical assessment (OR = 6.95, 95% CI 1.21-39.75). Total serum cholesterol, low-density lipoprotein and apolipoprotein B were elevated in patients with unfavorable rather than favorable outcomes., Conclusion: Our findings confirmed that the patients with APOE-E4 allele were predisposed to unfavorable outcomes after aneurysmal SAH even though an association between APOE and incidence of the SAH may not exist. The effect of APOE on neurobiology and lipoprotein metabolism seems to partially explain the difference in outcomes and deserves further study.

The comorbidity of aneurysmal subarachnoid hemorrhage (aSAH) with intracranial atherosclerotic stenosis (ICAS) has been suggested to increase the risk of postoperative ischemic stroke. Logistic regression models were established to explore the association between computed tomography perfusion (CTP) parameters and 3-month neurological outcomes and delayed cerebral ischemia (DCI). Prognostic-related perfusion parameters were added to the existing prognostic prediction models to evaluate model performance improvement. Tmax > 4.0 s volume > 0 mL was significantly associated with 3-month unfavorable neurological outcomes after adjusting for potential confounders (OR 3.90, 95% CI 1.11–13.73), whereas the stenosis degree of ICAS was not. Although the cross-validated area under the curve (AUC) was similar after the addition of the Tmax > 4.0 s volume > 0 mL (SAHIT: p = 0.591; TAPS: p = 0.379), the continuous net reclassification index (cNRI) and integrated discrimination index (IDI) showed that the perfusion parameters significantly improved the performance of the two models (p < 0.001 for all comparisons). Patients with coexistent aSAH and ICAS, Tmax > 4.0 s volume > 0 mL is an independent factor of 3-month neurological outcomes. A quantitative assessment of cerebral perfusion may help accurately screen patients with poor outcomes due to the coexistence of aSAH and ICAS. [ABSTRACT FROM AUTHOR]

An inflammatory response after an aneurysmal subarachnoid hemorrhage (aSAH) has always been in the spotlight. However, few studies have compared the prognostic impact of inflammatory biomarkers. Moreover, why these inflammatory biomarkers contribute to a poor prognosis is also unclear. We retrospectively reviewed aSAH patients admitted to our institution between January 2015 and December 2020. The 90-day unfavorable functional outcome was defined as a modified Rankin scale (mRS) of ≥ 3. Independent inflammatory biomarker-related risk factors associated with 90-day unfavorable outcomes were derived from a forward stepwise multivariate analysis. Receiver operating characteristic curve analysis was conducted to identify the best cut-off value of inflammatory biomarkers. Then, patients were divided into two groups according to each biomarker's cut-off value. To eliminate the imbalances in baseline characteristics, propensity score matching (PSM) was carried out to assess the impact of each biomarker on in-hospital complications. A total of 543 patients were enrolled in this study and 96 (17.7%) patients had unfavorable 90-day outcomes. A multivariate analysis showed that the white blood cell (WBC) count, the systemic inflammation response index, the neutrophil count, the neutrophil-to-albumin ratio, the monocyte count, and the monocyte-to-lymphocyte ratio were independently associated with 90-day unfavorable outcomes. The WBC count showed the best predictive ability (area under the curve (AUC) = 0.710, 95% CI = 0.652–0.769, p < 0.001). After PSM, almost all abnormal levels of inflammatory biomarkers were associated with a higher incidence of pneumonia during hospitalization. The WBC count had the strongest association with poor outcomes. Similar to nearly all other inflammatory biomarkers, the cause of poor prognosis may be the higher incidence of in-hospital pneumonia. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to explore the relationship between white blood cells (WBCs) at admission and clinical outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). Patients and Methods: We analyzed data from patients with aSAH between January 2015 and September 2021 who were included in the LongTEAM (Long-term Prognosis of Emergency Aneurysmal Subarachnoid Hemorrhage) registry study. WBC is classified into four groups according to the quartile. We used the logistic model for in-hospital complications, mortality, modified Rankin scale (mRS) at discharge and 90 days to examine the relationship between WBC and clinical outcomes. We used WBC levels near odds ratio (OR) = 1 (Q1) in restricted cubic splines as the reference to evaluate whether there is a nonlinear relationship between WBC and clinical outcomes. Another Kaplan–Meier method was used to analyze the relationship between WBC levels and the risk of developing pneumonia. Results: Of the 988 patients included, the results showed that compared with patients in the Q1 group, patients in the highest quartile (Q4) had an increased incidence of 90-day unfavorable outcomes after adjusting the confounders (adjusted OR = 1.81, 95% CI = 1.02– 3.20, p = 0.042), which may be caused by the increased incidence and risk of pneumonia (adjusted OR = 2.06, 95% CI = 1.30– 3.29, p = 0.002; adjusted hazard ratio [HR]=1.63, 95% CI = 1.13– 2.36, p < 0.001). The restricted cubic spline indicated that the incidence of developing pneumonia and 90-day unfavorable outcomes rises with increasing WBC levels (p for nonlinear = 0.135 and 0.113). Conclusion: Patients with higher WBC at admission were associated with an increased incidence of 90-day unfavorable outcomes, which might be related to pneumonia. [ABSTRACT FROM AUTHOR]

Objective: Elevated ICP is a well-recognized phenomenon in aneurysmal subarachnoid hemorrhage (aSAH) that has been demonstrated to lead to poor outcomes. Delayed cerebral ischemia (DCI) is the most important reason for a poor clinical outcome after a subarachnoid hemorrhage. DCI is understood as a multifactorial process that evolves over time, largely caused by the sequelae of increased intracranial pressure (ICP). The study aimed to assess how to better define the association between ICP and DCI, and whether rational ICP management can improve the outcome of aSAH patients. Methods: We prospectively reviewed patients diagnosed with aSAH and received microsurgery clipping at our department from December 2019 to January 2021. Subdural ICP monitoring devices were kept to monitor the ICP. The ICP values were recorded every 1-h epochs. ICP -guided dehydration treatments were routinely performed to control the ICP level of patients after surgery. To evaluate whether the subdural ICP-directed management improved the prognosis of the aSAH patients, we compared the outcome data of the patients in our cohort with those treated at another ward of our hospital at the same period. Results: In total, 144 consecutive aSAH patients received microsurgery clipping at our department, 68 of whom underwent ICP monitoring. A total of 11,424 1-h ICP measurements were recorded for the included patients (1.30 years of recordings). Of 68 patients with ICP monitoring, 27 (27/68, 39.7%) patients developed DCI. Univariate analysis showed that higher Hunt-Hess grade (OR 2.138, 95% CI 1.025–4.459, p = 0.043), higher preoperative modified Rankin Scale score (OR 1.534, 95% CI 1.033–2.276, p = 0.034), and the max ICP value of each day value >28.5 mmHg (OR 4.442, 95% CI 1.509–13.082, p = 0.007) were associated with DCI. Also, patients with ICP-directed treatment showed a significantly lower DCI incidence than patients without ICP monitoring. Conclusion: Our study suggests that I less than 15 mmHg possibly constitute normal values and that 28.5 mmHg is the ICP threshold most strongly associated with the occurrence of DCI in aSAH patients. Patients who received the ICP-directed treatment presented a lower incidence of DCI. Our findings provide a basis for the recommendation of ICP-directed treatment after aSAH. Trial Registration Number: NCT04785976. [ABSTRACT FROM AUTHOR]

Objective: Paediatric aneurysms are rare and difficult to treat. Studies on the long-term angiographic and clinical outcomes conducted within the past decade are lacking. We aimed to investigate the clinical and radiographic outcomes of paediatric aneurysms treated with different strategies in a contemporary series. Methods: We performed a retrospective medical record review of paediatric patients examined at our institution between 2011 and 2018. Patient charts were retrospectively reviewed for age, presentation, type and location of the aneurysm, modalities of treatment, complications, and clinical and angiographic outcomes. The rates of aneurysm recurrence and de novo formation were determined. Results: We evaluated 61 patients (mean age, 11.6 years; 23 females, 38 males) with 69 intracranial aneurysms. Their presentations included headache, neurological deficits, aneurysmal subarachnoid haemorrhage, incidental aneurysm, and traumatic subarachnoid haemorrhage. Of the aneurysms, 30 (49.2%) were giant. Forty-five (73.8%) patients underwent treatment for their aneurysms, and 16 (26.2%) patients were managed conservatively. The perioperative morbidity rate was 17.8%. There were no deaths. The long-term morbidity rate was 4.6%. The clinical outcomes were favourable in 82.2 and 95.3% at discharge and follow-up, respectively (mean, 41.5 months; range, 1.5–9 years). For treated aneurysms, 2/43 (4.6%) risk of aneurysm recurrence, 1/43 (2.3%) risk of aneurysm bleeding, 1/43 (2.3%) risk of de novo aneurysm formation. The annual bleeding, recurrence, and de novo formation or growth risk were 0.7, 1.4, and 0.7%, respectively. Conclusions: In neurovascular centres where microsurgical and endovascular options are available, most children with intracranial aneurysms can be successfully treated with low morbidity and mortality. However, they have higher rates of recurrence and a greater risk of de novo formation or growth than their adult counterparts, which mandates lifelong follow-up. [ABSTRACT FROM AUTHOR]

Background and Purpose: The utilization of flow diversion for ruptured intracerebral aneurysms (IAs) is still limited. We aimed to demonstrate our multicenter experience using the pipeline embolization device (PED) for ruptured IAs that were difficult to treat by clipping and coiling. Methods: Thirty-eight patients with ruptured IAs who underwent PED treatment from 2015 to 2020 were retrospectively reviewed. Factors associated with procedure-related stroke (ischemic and hemorrhagic) and clinical and angiography outcomes were analyzed. Results: There were 14 (36.8%) saccular IAs, 12 (31.6%) blister-like IAs, and 12 (31.6%) dissecting IAs. Perforator involvement was noted in 10 (26.3%) IAs. Early PED placement (≤ 15 days) and adjunctive coiling treatment were performed in 27 (71.1%) and 22 (57.9%) cases, respectively. The overall rate of stroke-related complications was 31.6% (12/38) (including rates of 10.5% for procedure-related hemorrhagic complications and 15.8% for procedure-related infarction). The mortality rate was 13.2% (5/38), and 84.2% of patients (32/38) had favorable outcomes. Thirty-two (84.2%) patients underwent follow-up angiographic evaluations; of these, 84.4% (27 patients) had complete occlusion and 15.6% had incomplete obliteration. Multivariate analysis revealed that early PED placement was not associated with a high risk of procedure-related stroke or an unfavorable outcome. Adjunctive coiling exhibited an association with procedure-related stroke (p = 0.073). Procedure-related hemorrhagic complications were significantly associated with an unfavorable outcome (p = 0.003). Immediate contrast stasis in the venous phase was associated with complete occlusion during follow-up (p = 0.050). Conclusion: The PED is a feasible and effective treatment to prevent rebleeding and achieve aneurysm occlusion, but it is associated with a substantial risk of periprocedural hemorrhage and ischemic complications in acute ruptured IAs. Therefore, the PED should be used selectively for acutely ruptured IAs. Additionally, adjunctive coiling might increase procedure-related stroke; however, it may reduce aneurysm rebleeding in acutely ruptured IAs. Patients with immediate contrast stasis in the venous phase were more likely to achieve total occlusion. A prospective study with a larger sample size should be performed to verify our results. [ABSTRACT FROM AUTHOR]

Object: Patients with aneurysmal subarachnoid hemorrhage (aSAH) have an increased incidence of cardiac events and short-term unfavorable neurological outcomes during the acute phase of bleeding. We studied whether troponin I elevation after ictus can predict future major adverse cardiac events (MACEs) and long-term neurological outcomes after 2 years. Methods: Consecutive aSAH patients within 3 days of bleeding were eligible for review from a prospective observational cohort (ClinicalTrials.gov Identifier: NCT04785976). Potential predictors of future MACEs and unfavorable long-term neurological outcomes were calculated by Cox and logistic regression analyses. Additional Kaplan–Meier curves were performed. Results: A total of 213 patients were enrolled with an average follow-up duration of 34.3 months. Individuals were divided into two groups: elevated cTnI group and unelevated cTnI group. By the last available follow-up, 20 patients had died, with an overall all-cause mortality rate of 9.4% and an annual all-cause mortality rate of 3.8%. Patients with elevated cTnI had a significantly higher risk of future MACEs (10.6 vs. 2.1%, p = 0.024, and 95% CI: 1.256–23.875) and unfavorable neurological outcomes at discharge, 3-month, 1-, 2-years, and last follow-up (p = 0.001, p < 0.001, p = 0.001, p < 0.001, and p < 0.001, respectively). In the Cox analysis for future MACE, elevated cTnI was the only independent predictor (HR = 5.980; 95% CI: 1.428–25.407, and p = 0.014). In the multivariable logistic analysis for unfavorable neurological outcomes, peak cTnI was significant (OR = 2.951; 95% CI: 1.376–6.323; p = 0.005). Kaplan–Meier analysis indicated that the elevated cTnI was correlated with future MACE (log-rank test, p = 0.007) and subsequent death (log-rank test, p = 0.004). Conclusion: cTnI elevation after aSAH could predict future MACEs and unfavorable neurological outcomes. [ABSTRACT FROM AUTHOR]