Inhibition of BACE1 attenuates microglia-induced neuroinflammation after intracerebral hemorrhage by suppressing STAT3 activation.

Hematoma-induced neuroinflammation is the cause of poor prognosis in intracerebral hemorrhage (ICH); therefore, promoting blood clearance and blocking overactivated inflammation are rational approaches for ICH treatment. ß-site amyloid precursor protein (APP) lyase-1 (BACE1) is a key molecule regulating the microglial phenotype transition in neurodegenerative diseases. Therefore, the aim of this study was to investigate the role of BACE1 in microglial phagocytosis and inflammatory features in ICH. Here, we demonstrated the unique advantages of targeting BACE1 in microglia using an autologous blood model and primary microglia hemoglobin stimulation. When BACE1 was inhibited early in ICH, fewer residual hematomas remained, consistent with an increase in genetic features that favor phagocytosis and anti-inflammation. In addition, inhibition of BACE1 enhanced the secretion of anti-inflammatory cytokines and substantially reduced the expression of proinflammatory genes, which was regulated by signal transduction and phosphorylation of activator of transcription 3 (STAT3). Further pharmacological inhibition of STAT3 phosphorylation effectively blocked the proinflammatory and weak phagocytic phenotype of microglia due to BACE1 induction. In summary, BACE1 is the critical molecule regulating the inflammatory and phagocytic phenotypes of microglia after ICH, and targeted inhibition of the BACE1/STAT3 pathway is an important strategy for the future treatment of ICH-induced neurological injury.

Microsurgical revascularization of a symptomatic proximal vertebral artery: pilot experiences from a single center.

Background: Vertebral artery stenosis and occlusion (VASO) is a high-risk factor for posterior circulation stroke. Post-stent restenosis and drug tolerance have facilitated the exploration of microsurgical vascular reconstruction. This study aims to evaluate the safety and efficacy of microsurgical reconstruction of the proximal VA. Methods: Twenty-nine patients (25 men, aged 63.2 years) who had symptoms of posterior circulation ischemia underwent microsurgical revascularization for proximal VASO were retrospectively included in this study. Procedural complications and clinical and angiographic outcomes were reviewed. Results: Twelve, three, and five patients underwent VA endarterectomy, artery transposition, or both, respectively; seven patients underwent vertebral endarterectomy plus stent implantation; and two patients failed surgery because of the difficult exposure of the VA and the occurrence of vascular dissection. The perioperative period-related complications included seven cases of Horner's syndrome, five cases of hoarseness, and one case of chylothorax. No cases of perioperative stroke or death were reported. The mean follow-up period was 28.4 (8-62 months). Most patients improved clinically; however, the vertebrobasilar ischemia symptoms did not decrease significantly in two patients during the follow-up. Moreover, follow-up imaging was performed in all the patients, and no signs of anastomotic stenosis were reported. Conclusion: Microsurgical reconstruction is an alternative option that can effectively treat refractory proximal VASO disease and in-stent stenosis, with a high rate of postoperative vascular recirculation. Prospective cohort studies with larger sample sizes must be conducted to validate the above conclusions.

Reconstructive endovascular treatment for basilar artery trunk aneurysms: complications and clinical and angiography outcomes.

BACKGROUND: Basilar artery trunk aneurysms (BTAs) are rare intracranial aneurysms. We aim to investigate the procedural complications and clinical and angiographic outcomes of BTAs treated with reconstructive endovascular treatment (EVT). METHODS: We retrospectively reviewed the data of 111 patients with BTAs who underwent reconstructive EVT during 2013-2022. The factors associated with procedural complications and clinical and angiographic outcomes were analyzed. RESULTS: The study included 81 men and 30 women (median age 60 years). Overall, 26 (23.4%) cases presented with subarachnoid hemorrhage and 85 (76.6%) presented with unruptured aneurysms. Periprocedural ischemic and hemorrhagic complications occurred in 29 (26.1%) and 4 (3.6%) cases, respectively. The rate of favorable clinical outcomes was 83.8% (92/111) and the mortality rate was 14.4% (16/111). Angiographic follow-up data were available for 77/95 (81.1%) survivors; 57 (74.0%) and 20 (26%) aneurysms exhibited complete and incomplete obliteration, respectively. Old age, high Hunt and Hess grades (IV-V), hemorrhagic complications, and increased aneurysm size were independent risk factors for unfavorable clinical outcomes (p<0.05). Increased aneurysm size and incomplete aneurysm occlusion on immediate angiography were independent risk factors for incomplete occlusion during follow-up (p<0.05). CONCLUSION: Reconstructive EVTs are a feasible and effective treatment for BTAs but are associated with a high risk of ischemic and hemorrhagic complications and a high mortality rate. Larger aneurysms may predict unfavorable clinical outcomes and aneurysm recurrence during follow-up. Hemorrhagic complications may predict unfavorable clinical outcomes, whereas immediate complete aneurysm occlusion may predict total occlusion during follow-up.

Stability of unruptured intracranial aneurysms in the anterior circulation: nomogram models for risk assessment.

OBJECTIVE: The probable stability of the lesion is critical in guiding treatment decisions in unruptured intracranial aneurysms (IAs). The authors aimed to develop multidimensional predictive models for the stability of unruptured IAs. METHODS: Patients with unruptured IAs in the anterior circulation were prospectively enrolled and regularly followed up. Clinical data were collected, IA morphological features were assessed, and adjacent hemodynamic features were quantified with patient-specific computational fluid dynamics modeling. Based on multivariate logistic regression analyses, nomograms incorporating these factors were developed in a primary cohort (patients enrolled between January 2017 and February 2018) to predict aneurysm rupture or growth within 2 years. The predictive accuracies of the nomograms were compared with the population, hypertension, age, size, earlier rupture, and site (PHASES) and earlier subarachnoid hemorrhage, location, age, population, size, and shape (ELAPSS) scores and validated in the validation cohort (patients enrolled between March and October 2018). RESULTS: Among 231 patients with 272 unruptured IAs in the primary cohort, hypertension, aneurysm location, irregular shape, size ratio, normalized wall shear stress average, and relative resident time were independently related to the 2-year stability of unruptured IAs. The nomogram including clinical, morphological, and hemodynamic features (C+M+H nomogram) had the highest predictive accuracy (c-statistic 0.94), followed by the nomogram including clinical and morphological features (C+M nomogram; c-statistic 0.89), PHASES score (c-statistic 0.68), and ELAPSS score (c-statistic 0.58). Similarly, the C+M+H nomogram had the highest predictive accuracy (c-statistic 0.94) in the validation cohort (85 patients with 97 unruptured IAs). CONCLUSIONS: Hemodynamics have predictive values for 2-year stability of unruptured IAs treated conservatively. Multidimensional nomograms have significantly higher predictive accuracies than conventional risk prediction scores.

A nomogram to predict the risk of postoperative intracranial rebleeding in patients with spontaneous intracranial hematoma.

The 30-day mortality rate of spontaneous cerebral hemorrhage (ICH) is approximately 30-50%. Surgery may improve the prognosis of patients with severe ICH. However, ICH survivors after surgery still face the risks of postoperative intracranial rebleeding (PIB), and clinical tools that accurately predict the risk of PIB occurrence are not available. Therefore, a retrospective study was performed. The population was divided into two groups according to the occurrence of PIB. Univariate and multivariate logistic regression analyses were performed to screen risk factors for PIB. Next, an early PIB risk nomogram prediction model was constructed. In addition, the impact of PIB on the prognosis of ICH was evaluated. In total, 150 ICH patients were continuously enrolled in this study; 21 patients suffered from PIB, and the overall incidence of PIB was 14.0% (21/150). Coronary heart disease history, a lower GCS score, and subarachnoid hemorrhage absence were screened as risk factors for early PIB. The early PIB risk nomogram showed good calibration and discrimination with a concordance index of 0.807 (95% confidence interval (CI), 0.715-0.899), which was confirmed to be 0.788 through bootstrapping validation. In addition, a significant difference in discharged GOS scores (P = 0.043) was observed between the PIB group and the n-PIB group. These results showed that a history of coronary heart disease, a lower GCS score, and absence of subarachnoid hemorrhage were risk factors for early PIB. In addition, the early PIB risk nomogram prediction model exhibits good discrimination and calibration. The occurrence of PIB could reduce the prognosis of ICH patients.

The Relationship of Morphological-Hemodynamic Characteristics, Inflammation, and Remodeling of Aneurysm Wall in Unruptured Intracranial Aneurysms.

Aneurysm wall remodeling (AWR) is an important pathological characteristic in aneurysm wall, which was characterized by abnormal histological structure and inflammation infiltration. In the present study, the aim is to determine the relationships of morphological-hemodynamic characteristics, inflammation, and AWR in intracranial aneurysms (IAs), as well as the pathological basis of morphological-hemodynamic predictors to achieve IA development. For this end, 113 unruptured IAs were prospectively collected from 110 cases. In addition, patient-specific computational fluid dynamics and geometry were adopted to determine hemodynamic and morphological parameters. Moreover, Hematoxylin-Eosin staining was performed to identify the AWR. By performing immunofluorescence, the inflammatory markers were detected. Masson staining was conducted to characterize the characteristics of atherosclerosis in aneurysm wall. To demonstrate the parameters regarding the AWR, a multivariate logistic analysis was conducted. Besides, correlation analyses were conducted to verify the relationship between morphological-hemodynamic and pathological characteristics. For 113 unruptured IAs, no difference was identified in baseline information. AWR was demonstrated in 92 (81.4%) IAs. To be specific, the aneurysm size (odds ratio (OR), 2.63; confidence interval (CI), 1.04-6.67; P = 0.041), size ratio (SR; OR, 1.95; CI, 1.38-2.76; P < 0.001), normalized wall shear stress average (NWSSA; OR, 0.05; CI, 0.01-0.15; P = 0.007), and relative resident time (RRT; OR, 1.28; CI, 1.07-1.53; P = 0.007) were proved as the factors of AWR. As revealed from the results of immunofluorescence, aneurysm size, SR, NWSSA, and RRT were significantly correlated with the level of inflammation in IA tissues. Furthermore, Masson staining revealed that atherosclerosis area in IA tissues and NWSSA was correlated with RRT. In this study, SR, NWSSA, and RRT were demonstrated as the risk factors of AWR. The mentioned parameters could also reflect the characteristics of inflammation and atherosclerosis in aneurysm wall as well. This study revealed that biomechanical stress and inflammation in aneurysm wall are correlated, which might suggest the pathological evidence of morphological-hemodynamic predictors for IA development.

Impairment and Plasticity of Language-Related White Matter in Patients With Brain Arteriovenous Malformations.

BACKGROUND: Language dysfunction is rarely seen in patients with unruptured brain arteriovenous malformation (AVM) albeit the AVM nidus involving language areas, which provides a unique disease model to study language reorganization. The objective of this study was to investigate the impairment and reorganization patterns and characteristics of language-related white matter in AVMs located at different brain areas. METHODS: Thirty-three patients with AVMs involving language areas were prospectively enrolled. Patients were categorized into 3 groups according to the lesion locations: the frontal (14 patients), temporal (15 patients), and parietal groups (4 patients). Thirty age- and sex-matched healthy controls were enrolled as comparison. All participants underwent diffusion tensor imaging scans, and automated fiber quantification method was applied to quantitatively study the difference of segmented language-related white matter connectivity between 3 AVM groups and control group. RESULTS: Language functions were normal in all subjects according to Western Aphasia Battery test. In the frontal group, fractional anisotropy (FA) value decreased in the left arcuate fascicle and increased in left superior longitudinal fasciculus and uncinate fascicle; in the temporal group, FA values decreased in left inferior fronto-occipital fascicle and inferior longitudinal fascicle and increased in right anterior thalamic radiation and uncinate fascicle; in the parietal group, FA values decreased in left arcuate fascicle and inferior longitudinal fascicle and increased in bilateral anterior thalamic radiations and uncinate fascicles and right inferior fronto-occipital fascicle. In fascicles with decreased FA values, the increase of radial diffusivity was common, and fascicles with increased FA values usually presented along with increased axial diffusivity values. CONCLUSIONS: Remodeling of language-related white matter occurs when traditional language areas are involved by AVM nidus, and its reorganization patterns vary with locations of AVM nidus. Fascicle impairment is mainly caused by the myelin deficits, and its plasticity may be dominated by the axon remodeling procedure.

Rebleeding of Ruptured Intracranial Aneurysm After Admission: A Multidimensional Nomogram Model to Risk Assessment.

OBJECTIVE: Rebleeding is recognized as the main cause of mortality after intracranial aneurysm rupture. Though timely intervention can prevent poor prognosis, there is no agreement on the surgical priority and choosing medical treatment for a short period after rupture. The aim of this study was to investigate the risk factors related to the rebleeding after admission and establish predicting models for better clinical decision-making. METHODS: The patients with ruptured intracranial aneurysms (RIAs) between January 2018 and September 2020 were reviewed. All patients fell to the primary and the validation cohort by January 2020. The hemodynamic parameters were determined through the computational fluid dynamics simulation. Cox regression analysis was conducted to identify the risk factors of rebleeding. Based on the independent risk factors, nomogram models were built, and their predicting accuracy was assessed by using the area under the curves (AUCs). RESULT: A total of 577 patients with RIAs were enrolled in this present study, 86 patients of them were identified as undergoing rebleeding after admission. Thirteen parameters were identified as significantly different between stable and rebleeding aneurysms in the primary cohort. Cox regression analysis demonstrated that six parameters, including hypertension [hazard ratio (HR), 2.54; P = 0.044], bifurcation site (HR, 1.95; P = 0.013), irregular shape (HR, 4.22; P = 0.002), aspect ratio (HR, 12.91; P < 0.001), normalized wall shear stress average (HR, 0.16; P = 0.002), and oscillatory stress index (HR, 1.14; P < 0.001) were independent risk factors related to the rebleeding after admission. Two nomograms were established, the nomogram including clinical, morphological, and hemodynamic features (CMH nomogram) had the highest predicting accuracy (AUC, 0.92), followed by the nomogram including clinical and morphological features (CM nomogram; AUC, 0.83), ELAPSS score (AUC, 0.61), and PHASES score (AUC, 0.54). The calibration curve for the probability of rebleeding showed good agreement between prediction by nomograms and actual observation. In the validation cohort, the discrimination of the CMH nomogram was superior to the other models (AUC, 0.93 vs. 0.86, 0.71 and 0.48). CONCLUSION: We presented two nomogram models, named CMH nomogram and CM nomogram, which could assist in identifying the RIAs with high risk of rebleeding.

The Potential Role of hsa_circ_0005505 in the Rupture of Human Intracranial Aneurysm.

Objective: Recently, abundant number of studies have revealed many functions of circular RNAs in multiple diseases, however, the role of circular RNA in the rupture of human intracranial aneurysm is still unknown. This study aims to explore the potential functions of circular RNA in the rupture of human intracranial aneurysms. Methods: The differentially expressed circular RNAs between un-ruptured intracranial aneurysms (n = 5) and ruptured intracranial aneurysms (n = 5) were analyzed with the Arraystar human circRNAs microarray. Quantitative real-time PCR (qPCR) was used to verify the results of the circRNA microarray. The role of circular RNA in intracranial aneurysm rupture was assessed in vitro. MTT assay, CCK-8 assay, Caspase3/7 assay, assay of cell apoptosis and Celigo wound healing was conducted to evaluate the relationship between circular RNA and the rupture of human intracranial aneurysms. Results: A total of 13,175 circRNA genes were detected. Among them 63 circRNAs upregulated and 54 circRNAs downregulated significantly in ruptured intracranial aneurysms compared with un-ruptured intracranial aneurysms (p < 0.05 Fold Change > 1.5). Five upregulated circRNAs were selected for further study (hsa_circ_0001947, hsa_circ_0043001, hsa_circ_0064557, hsa_circ_0058514, hsa_circ_0005505). The results of qPCR showed only hsa_circ_0005505 significantly upregulated (p < 0.05). The expression of hsa_circ_0005505 was higher in ruptured intracranial aneurysm tissues. And our in vitro data showed that hsa_circRNA_005505 promotes the proliferation, migration and suppresses the apoptosis of vascular smooth muscle cell. Conclusion: This study revealed an important role of hsa_circ_0005505 in the proliferation, migration and apoptosis of vascular smooth muscle cell, and indicated that hsa_circ_0005505 may associate with the pathological process of intracranial aneurysms.

The Effect of Preoperative Antiplatelet Therapy on Early Postoperative Rehemorrhage and Outcomes in Patients With Spontaneous Intracranial Hematoma.

BACKGROUND AND PURPOSE: The effect of antiplatelet therapy (APT) on early postoperative rehemorrhage and outcomes of patients with spontaneous intracerebral hemorrhage (ICH) is still unclear. This study is to evaluate the effect of preoperative APT on early postoperative rehemorrhage and outcomes in ICH patients. METHODS: This was a multicenter cohort study. ICH patients undergoing surgery were divided into APT group and no antiplatelet therapy (nAPT) group according to whether patients received APT or not. Chi-square test, t-test, and Mann-Whitney U test were used to compare the differences in variables, postoperative rehematoma, and outcomes between groups. Multivariate logistics regression analysis was used to correct for confounding variables, which were different in group comparison. RESULTS: One hundred fifty ICH patients undergoing surgical treatment were consecutively included in this study. Thirty five (23.33%) people were included in the APT group, while 115 (76.67%) people were included in the nAPT group. The incidence of early postoperative rehemorrhage in the APT group was significantly higher than that in the nAPT group (25.7% VS 10.4%, p = 0.047 < 0.05). After adjustment for age, ischemic stroke history, and ventricular hematoma, preoperative APT had no significant effect on early postoperative rehemorrhage (p = 0.067). There was no statistical difference between the two groups in early poorer outcomes (p = 0.222) at 14 days after surgery. After adjustment for age, ischemic stroke history, and ventricular hematoma, preoperative APT also had no significant effect on early poorer modified Rankin Scale (mRS) (p = 0.072). CONCLUSION: In conclusion, preoperative APT appears to be safe and have no significant effect on early postoperative rehematoma and outcomes in ICH patients.

Circular RNA circDUS2 Is a Potential Biomarker for Intracranial Aneurysm.

Background: CircRNAs have been found to play a crucial role in the pathological process of various kinds of diseases. However, the role of circRNAs in the formation and rupture of intracranial aneurysm is still unknown. Methods: Differentially expressed circRNAs profiles between superficial temporal arteries (n = 5) and intracranial aneurysms (n = 5) were analyzed using the Arraystar human circRNAs microarray. Quantitative real-time PCR was utilized to validate the differential expression of circDUS2. Fluorescence in situ hybridization (FISH) was meant for the location of circDUS2 in human brain vascular smooth muscle cell (HBVSMC). Structural analysis was used to speculate on the function of circDUS2. Results: Five hundred forty-three upregulated and 397 downregulated significantly in intracranial aneurysm as compared to superficial temporal arteries. Quantitative real-time PCR verified the elevated expression of the upregulated circDUS2. The FISH test revealed that circDUS2 is located in the cytoplasm of brain vascular smooth muscle cells. Conclusion: This study showed differential expression data of circRNAs between superficial temporal artery and intracranial aneurysm and revealed that circDUS2 is a potential molecular marker for intracranial aneurysm.

Multidimensional predicting model of intracranial aneurysm stability with backpropagation neural network: a preliminary study.

OBJECTIVES: The stability of intracranial aneurysms (IAs) may involve in multidimensional factors. Backpropagation (BP) neural network could be adopted to support clinical work. This preliminary study aimed to delve into the feasibility of BP neural network in assessing the risk of IA rupture/growth and to prove the advantage of multidimensional model over single/double-dimensional model. METHODS: Thirty-six IA patients were recruited from a prospective registration study (ChiCTR1900024547). All patients were followed up until aneurysm ruptured/grew or 36 months after being diagnosed with the IAs. The multidimensional data regarding clinical, morphological, and hemodynamic characteristics were acquired. Hemodynamic analyses were conducted with patient-specific models. Based on these characteristics, seven models were built with BP neural network (the ratio of training set to validation set as 8:1). The area under curves (AUC) was calculated for subsequent comparison. RESULTS: Forty-five characteristics were determined from 36 patients with 37 IAs. In the models based on the single dimension of IA characteristics, only morphological characteristics exhibited high performance in assessing 3-year IA stability (AUC = 0.703, P = 0.035). Among the models integrating two dimensions of IA characteristics, clinical-morphological (AUC = 0.731, P = 0.016), clinical-hemodynamic (AUC = 0.702, P = 0.036), and morphological-hemodynamic (AUC = 0.785, P = 0.003) models were capable of assessing the risk of 3-year IA rupture/growth. Moreover, the models including all three dimensions exhibited the maximum predicting significance (AUC = 0.811, P = 0.001). CONCLUSION: The present preliminary study reported that BP neural network might support assessing the 3-year stability of IAs. Models based on multidimensional characteristics could improve the assessment accuracy for IA rupture/growth.

Differentially Expressed Circular RNA Profile in an Intracranial Aneurysm Group Compared with a Healthy Control Group.

OBJECTIVE: Intracranial aneurysm (IA) is a fatal disease owing to vascular rupture and subarachnoid hemorrhage. Much attention has been given to circular RNAs (circRNAs) because they may be potential biomarkers for many diseases, but their mechanism in the formation of IA remains unknown. METHODS: circRNA expression profile analysis of blood samples was conducted between patients with IA and controls. Overall, 235 differentially expressed circRNAs were confirmed between IA patients and the control group. The reliability of the microarray results was demonstrated by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Of 235 differentially expressed genes, 150 were upregulated, while the other 85 were downregulated. Five miRNAs matched to every differential expression of circRNAs, and related MREs were predicted. We performed gene ontology (GO) analysis to identify the functions of their targeted genes, with the terms "Homophilic cell adhesion via plasma membrane adhesion molecules" and "Positive regulation of cellular process" showing the highest fold enrichment. CONCLUSIONS: This study demonstrated the role of circRNA expression profiling in the formation of IA and revealed that the mTOR pathway can be a latent therapeutic strategy for IA.

Surgical treatment for antiplatelet intracerebral hemorrhage (SAP-ICH): protocol for a prospective cohort study of emergency surgery for severe spontaneous intracerebral hemorrhage patients on long-term oral antiplatelet treatment.

BACKGROUND: Despite the capability of emergency surgery to reduce the mortality of severe spontaneous intracranial hemorrhage (SSICH) patients, the effect and safety of surgical treatment for severe spontaneous intracranial hemorrhage (SSICH) patients receiving long-term oral antiplatelet treatment (LOAPT) remains unclear. In consideration of this, the cohort study is aimed at figuring out the effect and safety of emergency surgery for SSICH patients on LOAPT. METHODS: As a multicenter and prospective cohort study, it will be conducted across 7 representative clinical centers. Starting in September 2019, the observation is scheduled to be completed by December 2022, with a total of 450 SSICH patients recruited. The information on clinical, radiological, and laboratory practices will be recorded objectively. All of the patients will be monitored until death or 6 months after the occurrence of primary hemorrhage. RESULTS: In this study, two comparative cohorts and an observational cohort will be set up. The primary outcome is the effect of emergency surgery, which is subject to assessment using the total mortality and comparison in the survival rate of SSICH patients on LOAPT between surgical treatment and conservative treatment. The second outcome is the safety of surgery, with the postoperative hemorrhagic complication which is compared between the operated SSICH patients on and not on LOAPT. Based on the observation of the characteristics and outcome of SSICH patients on LOAPT, the ischemic events after discontinuing LOAPT will be further addressed, and the coagulation function assessment system for operated SSICH patients on LOAPT will be established. CONCLUSIONS: In this study, we will investigate the effect and safety of emergency surgery for SSICH patients on LOAPT, which will provide an evidence for management in the future. ETHICS AND DISSEMINATION: The research protocol and informed consent in this study were approved by the Institutional Review Board of Beijing Tiantan Hospital (KY2019-096-02). The results of this study are expected to be disseminated in peer-reviewed journals in 2023. TRIAL REGISTRATION: Name: Effect and safety of surgical intervention for severe spontaneous intracerebral hemorrhage patients on long-term oral antiplatelet treatment. ChiCTR1900024406 . Date of registration is July 10, 2019.

A scoring system to discriminate blood blister-like aneurysms: a multidimensional study using patient-specific model.

Presurgical discrimination of blood blister-like aneurysms (BBAs) can assist neurosurgeons in clinical decision-making. The aim of this study was to investigate the characteristics of BBAs and construct a useful tool to distinguish BBAs. This study reviewed patients with small/median, hemispherical, and wide-necked aneurysms of the internal carotid artery in our institution. BBAs were identified via their intraoperative findings. A hemodynamic analysis was performed using a patient-specific model. The independent risk factors of BBAs were investigated using a logistic analysis. A scoring system was then established to discriminate BBAs, in which its predicting value was analyzed using receiver operating characteristic (ROC) analysis. A total of 67 aneurysms comprising 21 BBAs were enrolled. Comparing features between BBAs and non-BBAs, statistical significances were found in the aspect ratio (AR), height-to-width ratio, aneurysm angle (AA), wall shear stress gradient (WSSG), and normalized wall shear stress average. A multivariate logistic analysis identified AR (OR = 0.29, p = 0.021), WSSG (OR = 1.54, p = 0.017) and AA (OR = 2.49, p = 0.039) as independent risk factors for BBAs. A scoring system was constructed using these parameters, effectively distinguishing BBAs (AUC = 0.931, p < 0.01). Our multidimensional scoring system may effectively assist in the discrimination of BBAs from wide-necked non-BBAs.

Emergency surgery is an effective way to improve the outcome of severe spontaneous intracerebral hemorrhage patients on long-term oral antiplatelet therapy.

The necessity of emergency surgery for severe spontaneous intracerebral hemorrhage (SSICH) patients on long-term oral antiplatelet therapy (LOAPT) remains unclear. The aim of this study was to investigate the effect and safety of emergency surgery for SSICH patients on LOAPT (SSICH-LOAPT patients). In this study, a retrospective review of patients admitted to our institution for SSICH from January 2012 to December 2018 was conducted. The collected data included demographic, clinical, and surgical information. The outcome was recorded at 3 months after primary hemorrhage. The outcome of SSICH-LOAPT patients receiving emergency surgery and conservative treatment were compared. The risk of postoperative intracranial bleeding (PIB) in operated SSICH-LOAPT patients was further investigated. A total of 522 SSICH patients were retrospectively reviewed, including 181 SSICH-LOAPT patients and 269 operated patients. The total mortality and in-hospital mortality were 40.6% and 19.3%, respectively. As compared with SSICH-LOAPT patients receiving conservative treatment, the operated SSICH-LOAPT patients showed a lower total (p = 0.043) and in-hospital mortality (p = 0.024). When compared with operated patients not on LOAPT, the operated patients on LOAPT exhibited a higher rate of PIB (OR, 2.34; 95% CI 1.14-4.79; p = 0.018). As demonstrated by the multivariate logistic analysis, dual antiplatelet therapy were independent risk factors associated with PIB in operated SSICH-LOAPT patients (OR, 3.42; CI, 1.01-11.51; p = 0.047). Despite of increasing risk of PIB, emergency surgery could improve the outcome of SSICH-LOAPT patients as it could be effective in reducing mortality. Dual antiplatelet therapy was the independent risk factor related to the PIB in operated SSICH-LOAPT patients.

Perinidal Angiogenesis Is a Predictor for Neurovascular Uncoupling in the Periphery of Brain Arteriovenous Malformations: A Task-Based and Resting-State fMRI Study.

BACKGROUND: Potential neurovascular uncoupling (NVU) related to perinidal angiogenesis (PA) of brain arteriovenous malformations (AVMs) may cause inappropriate presurgical mapping using functional magnetic resonance imaging (fMRI), resulting in overconfident resection and postoperative morbidity. PURPOSE: To evaluate the potential impact of PA upon fMRI blood oxygen level-dependent signal in the periphery of AVMs. STUDY TYPE: Prospective. POPULATION: Twenty-one patients with AVMs located in the primary sensorimotor cortex (SM1) undergoing task-based fMRI (hand motor), and 19 patients with supratentorial AVMs undergoing resting-state fMRI. FIELD STRENGTH/SEQUENCE: 3.0T, echo-planar, time-of-flight, and magnetization-prepared rapid gradient-echo. ASSESSMENT: The presence of PA was determined by three observers (Y.C., J.W., and X.C.) according to digital subtraction angiography and MR angiography. Interhemispheric asymmetry of fMRI activations contralateral to hand movements was evaluated with the interhemispheric ratio of the average t-value within ipsilesional SM1 to contralesional SM1. Regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFF) were extracted from ring-shaped perinidal regions and contralateral homologous regions, and the corresponding interhemispheric ratios were calculated. The effect of PA on the interhemispheric asymmetry of motor activations, ReHo, and fALFF was estimated. STATISTICAL TESTS: Pearson analysis, paired and independent t-test, multiple linear regression, Friedman test, and factorial analysis of variance were used. RESULTS: Motor activations were significantly reduced in ipsilesional SM1 compared to contralesional SM1 (P < 0.05). The presence of PA was the independent predictor of activation loss in ipsilateral SM1(P < 0.05). Furthermore, perinidal regions exhibited reduced ReHo compared to the homologous regions (P < 0.05). PA was significantly associated with the decline of ReHo and fALFF in perinidal regions (P < 0.05, for both). DATA CONCLUSION: The presence of PA can predict perinidal NVU that may confound the interpretation of both task-based and resting-state fMRI, highlighting the importance of alternative approaches of brain functional localization in improving treatment of AVMs. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Corpus Callosum Diffusion Anisotropy and Hemispheric Lateralization of Language in Patients with Brain Arteriovenous Malformations.

Background: The corpus callosum (CC) plays a key role in mediating interhemispheric connectivity and developing functional hemispheric asymmetries. The purpose of this study was to investigate the changes in CC microstructure accompanying interhemispheric language reorganization in patients with brain arteriovenous malformations (AVMs). Methods: Forty-one patients with an unruptured AVM located in anatomically defined language areas underwent functional magnetic resonance imaging and diffusion tensor imaging. Hemispheric dominance in Broca's area (BA) and Wernicke's area (WA) was assessed separately. Right-sided or bilateral language dominance was classified as atypical lateralization. The CC was segmented into five subregions, and the mean fractional anisotropy (FA) was extracted. The relationship between callosal FA and language lateralization patterns was statistically analyzed. Results: We observed atypical language lateralization in 16 (39.0%) patients. Patients with atypical lateralization exhibited significantly higher mean FA values in the total CC (p = 0.002) and the anterior (p = 0.047), midanterior (p = 0.001), and midposterior (p = 0.043) subregions. Significant interaction effects of BA and WA lateralization were found for FA values in the total CC (p = 0.005) and the midanterior subregion (p = 0.004). Conclusions: These results indicate that AVM patients with atypical language lateralization exhibit higher callosal FA values, reflecting greater interhemispheric connectivity. Our findings contribute additional insights into the understanding of functional and structural plasticity of the human brain under pathological states. Impact statement Brain arteriovenous malformations (AVMs) are congenital lesions that frequently lead to interhemispheric language reorganization. In this study, by combining diffusion tensor imaging and functional magnetic resonance imaging, we investigated the relationship between callosal fractional anisotropy (FA) and language reorganization in patients with AVMs. We found that callosal FA was significantly higher in patients with atypical language lateralization, especially in those with crossed lateralization of Broca's and Wernicke's areas. This study demonstrated the remodeling of the corpus callosum microstructure accompanying language reorganization in AVM patients, providing insights into the structural and functional plasticity of the human brain associated with congenital cerebrovascular disease.

Metabolic Disorder of Extracellular Matrix Mediated by Decorin Upregulation Is Associated With Brain Arteriovenous Malformation Diffuseness.

BACKGROUND AND OBJECTIVE: Diffuse brain arteriovenous malformations (BAVMs) are mixed up with normal brain parenchyma and therefore increase the difficulty of surgical resection, leading to poor surgical prognosis. Since the mechanism underlying BAVM diffuseness remains unknown, a quantitative proteomic analysis was performed to investigate the altered expression of proteins in diffuse BAVMs compared to compact ones. METHODS: We performed proteomic analysis on five diffuse BAVMs and five compact BAVMs. Bioinformatics analysis was conducted to identify potential signals related to BAVM diffuseness. Candidate proteins were then investigated in BAVM specimens using immunofluorescence and Western blot analysis. Tube formation assays were used to investigate the effects of candidate proteins on the angiogenesis of human umbilical endothelial cells (HUVECs). Finally, Masson, Sirius red staining, and immunofluorescence were used to evaluate the characteristics of extracellular matrix (ECM) in BAVM tissues. RESULTS: A total of 58 proteins were found to be differentially expressed between diffuse and compact BAVMs via proteomic analysis. TGF-ß (transforming growth factor-beta) signaling pathway, ECM-receptor pathway, relaxin signaling pathway, and several other pathways were associated with BAVM diffuseness. The TGF-ß signaling pathway is associated with angiogenesis; the role of this pathway in the formation of diffuse BAVMs was investigated, and the decorin (DCN) upregulation played an important role in this process. Immunofluorescence showed that DCN was significantly upregulated within and around the malformed vessels of diffuse BAVMs. Functional assays showed that exogenous DCN could promote the tube formation ability of HUVECs through inhibiting the TGF-ß signaling pathway and overproducing ECM. Histological staining demonstrated the overproduction of ECM in diffuse BAVMs. CONCLUSION: TGF-ß signaling pathway inhibited by DCN in vascular endothelial cells is related to BAVM diffuseness. The metabolic disorder of ECM caused by DCN upregulation may significantly contribute to the formation of diffuse BAVMs.

Evaluating the safety of early surgery for ruptured intracranial aneurysms in patients with long-term aspirin use: a propensity score matching study.

BACKGROUND: Early microsurgical clipping is recommended for ruptured intracranial aneurysms to prevent rebleeding. However, dilemma frequently occurs when managing patients with current acetylsalicylic acid (aspirin) use. This study aimed to examine whether aspirin use was associated with worse outcomes after early surgery for aneurysmal subarachnoid hemorrhage (aSAH). METHODS: We retrieved a consecutive series of 215 patients undergoing early microsurgical clipping within 72 h after aneurysmal rupture from 2012 to 2018 in the neurosurgery department of Beijing Tiantan Hospital. The medical records of each case were reviewed. Twenty-one patients had a history of long-term aspirin use before the onset of aSAH, and 194 patients did not. To reduce confounding bias, propensity score matching (PSM) was performed to balance some characteristics of the two groups. The intraoperative blood loss, postoperative hemorrhagic events, postoperative hospital stay, and functional outcome at discharge were compared between aspirin and non-aspirin group. RESULTS: We matched all the 21 patients in aspirin group with 42 patients in non-aspirin group (1:2). Potential confounding factors were corrected between the two groups by PSM. No hospital mortality occurred after surgery. No significant differences were found in intraoperative blood loss (P = 0.540), postoperative hemorrhagic events (P > 0.999), postoperative hospital stay (P = 0.715), as well as functional outcome at discharge (P = 0.332) between the two groups. CONCLUSIONS: Our preliminary results showed that long-term low-dose aspirin use was not associated with worse outcomes. Early surgery can be safe for ruptured intracranial aneurysms in patients with long-term aspirin use.