NOTCH4 Single-Nucleotide Polymorphism Is Associated with Brain Arteriovenous Malformation in a Chinese Han Population.

INTRODUCTION: Brain arteriovenous malformations (BAVMs) are high-flow intracranial vascular malformations characterized by the direct connection of arteries to veins without an intervening capillary bed. They are one of the main causes of intracranial hemorrhage and epilepsy, although morbidity is low. Angiogenesis, heredity, inflammation, and arteriovenous malformation syndromes play important roles in BAVM formation. Animal experiments and previous studies have confirmed that NOTCH4 may be associated with BAVM development. Our study identifies a connection between NOTCH4 gene polymorphisms and BAVM in a Chinese Han population. METHODS: We enrolled 150 patients with BAVMs confirmed by digital subtraction angiography (DSA) in the Department of Neurosurgery, Zhujiang Hospital, Southern Medical University from June 2017 to July 2019. Simultaneously, 150 patients without cerebrovascular disease were confirmed by computed tomography angiography/magnetic resonance angiography/DSA. DNA was extracted from peripheral blood and NOTCH4 genotypes were identified by PCR-ligase detection reaction. The χ2 test or Fisher's exact test was used to evaluate the differences in allele and genotype frequencies between the BAVM group, control group, bleeding group, and other complications. RESULTS: Two single-nucleotide polymorphisms (SNPs), rs443198 and rs438475, were significantly associated with BAVM. No SNP genotypes were significantly associated with hemorrhage or epilepsy. SNPs rs443198_AA-SNP and rs438475_AA-SNP may be associated with a lower risk of BAVM (p = 0.011, odds ratio (OR) = 0.459, 95% confidence interval (CI): 0.250-0.845; p = 0.033, OR = 0.759, 95% CI: 0.479-1.204). CONCLUSION: NOTCH4 gene polymorphisms were associated with BAVM and may be a risk factor in a Chinese Han population.

Morphology-aware multi-source fusion-based intracranial aneurysms rupture prediction.

OBJECTIVES: We proposed a new approach to train deep learning model for aneurysm rupture prediction which only uses a limited amount of labeled data. METHOD: Using segmented aneurysm mask as input, a backbone model was pretrained using a self-supervised method to learn deep embeddings of aneurysm morphology from 947 unlabeled cases of angiographic images. Subsequently, the backbone model was finetuned using 120 labeled cases with known rupture status. Clinical information was integrated with deep embeddings to further improve prediction performance. The proposed model was compared with radiomics and conventional morphology models in prediction performance. An assistive diagnosis system was also developed based on the model and was tested with five neurosurgeons. RESULT: Our method achieved an area under the receiver operating characteristic curve (AUC) of 0.823, outperforming deep learning model trained from scratch (0.787). By integrating with clinical information, the proposed model's performance was further improved to AUC = 0.853, making the results significantly better than model based on radiomics (AUC = 0.805, p = 0.007) or model based on conventional morphology parameters (AUC = 0.766, p = 0.001). Our model also achieved the highest sensitivity, PPV, NPV, and accuracy among the others. Neurosurgeons' prediction performance was improved from AUC=0.877 to 0.945 (p = 0.037) with the assistive diagnosis system. CONCLUSION: Our proposed method could develop competitive deep learning model for rupture prediction using only a limited amount of data. The assistive diagnosis system could be useful for neurosurgeons to predict rupture. KEY POINTS: • A self-supervised learning method was proposed to mitigate the data-hungry issue of deep learning, enabling training deep neural network with a limited amount of data. • Using the proposed method, deep embeddings were extracted to represent intracranial aneurysm morphology. Prediction model based on deep embeddings was significantly better than conventional morphology model and radiomics model. • An assistive diagnosis system was developed using deep embeddings for case-based reasoning, which was shown to significantly improve neurosurgeons' performance to predict rupture.

A preliminary investigation of radiomics differences between ruptured and unruptured intracranial aneurysms.

OBJECTIVES: Prediction of intracranial aneurysm rupture is important in the management of unruptured aneurysms. The application of radiomics in predicting aneurysm rupture remained largely unexplored. This study aims to evaluate the radiomics differences between ruptured and unruptured aneurysms and explore its potential use in predicting aneurysm rupture. METHODS: One hundred twenty-two aneurysms were included in the study (93 unruptured). Morphological and radiomics features were extracted for each case. Statistical analysis was performed to identify significant features which were incorporated into prediction models constructed with a machine learning algorithm. To investigate the usefulness of radiomics features, three models were constructed and compared. The baseline model A was constructed with morphological features, while model B was constructed with addition of radiomics shape features and model C with more radiomics features. Multivariate analysis was performed for the ten most important variables in model C to identify independent risk factors. A simplified model based on independent risk factors was constructed for clinical use. RESULTS: Five morphological features and 89 radiomics features were significantly associated with rupture. Model A, model B, and model C achieved the area under the receiver operating characteristic curve of 0.767, 0.807, and 0.879, respectively. Model C was significantly better than model A and model B (p < 0.001). Multivariate analysis identified two radiomics features which were used to construct the simplified model showing an AUROC of 0.876. CONCLUSIONS: Radiomics signatures were different between ruptured and unruptured aneurysms. The use of radiomics features, especially texture features, may significantly improve rupture prediction performance. KEY POINTS: • Significant radiomics differences exist between ruptured and unruptured intracranial aneurysms. • Radiomics shape features can significantly improve rupture prediction performance over conventional morphology-based prediction model. The inclusion of histogram and texture radiomics features can further improve the performance. • A simplified model with two variables achieved a similar level of performance as the more complex ones. Our prediction model can serve as a promising tool for the risk management of intracranial aneurysms.

The role of wall shear stress in the parent artery as an independent variable in the formation status of anterior communicating artery aneurysms.

OBJECTIVES: The study aimed to determine which hemodynamic parameters independently characterize anterior communicating artery (AcomA) aneurysm formation and explore the threshold of wall shear stress (WSS) of the parent artery to better illustrate the correlation between the magnitude of WSS and AcomA aneurysm formation. METHODS: Eighty-one patients with AcomA aneurysms and 118 patients without intracranial aneurysms (control population), as confirmed by digital subtraction angiography (DSA) from January 2014 to May 2017, were included in this cross-sectional study. Three-dimensional-DSA was performed to evaluate the morphologic characteristics of AcomA aneurysms. Local hemodynamic parameters were obtained using transcranial color-coded duplex (TCCD). Multivariate logistic regression and a two-piecewise linear regression model were used to determine which hemodynamic parameters are independent predictors of AcomA aneurysm formation and identify the threshold effect of WSS of the parent artery with respect to AcomA aneurysm formation. RESULTS: Univariate analyses showed that the WSS (p < 0.0001), angle between the A1 and A2 segments of the anterior cerebral artery (ACA) (p < 0.001), hypertension (grade II) (p = 0.007), fasting blood glucose (FBG; > 6.0 mmol/L) (p = 0.005), and dominant A1 (p < 0.001) were the significant parameters. Multivariate analyses showed a significant association between WSS of the parent artery and AcomA aneurysm formation (p = 0.0001). WSS of the parent artery (7.8-12.3 dyne/cm2) had a significant association between WSS and aneurysm formation (HR 2.0, 95% CI 1.3-2.8, p < 0.001). CONCLUSIONS: WSS ranging between 7.8 and 12.3 dyne/cm2 independently characterizes AcomA aneurysm formation. With each additional unit of WSS, there was a one-fold increase in the risk of AcomA aneurysm formation. KEY POINTS: • Multivariate analyses and a two-piecewise linear regression model were used to evaluate the risk factors for AcomA aneurysm formation and the threshold effect of WSS on AcomA aneurysm formation. • WSS ranging between 7.8 and 12.3 dyne/cm 2 was shown to be a reliable hemodynamic parameter in the formation of AcomA aneurysms. The probability of AcomA aneurysm formation increased one-fold for each additional unit of WSS. • An ultrasound-based TCCD technique is a simple and accessible noninvasive method for detecting WSS in vivo; thus, it can be applied as a screening tool for evaluating the probability of aneurysm formation in primary care facilities and community hospitals because of the relatively low resource intensity.

Treatment of giant/large internal carotid aneurysms: parent artery occlusion or stent-assisted coiling.

PURPOSE: Treatment of giant/large internal carotid aneurysm is a challenge for neurologists. Previously, parent artery occlusion was the classic therapy; now the stent-assisted coil embolization has become available in recent years, but the optimal therapy is under debate. The goal of the present study was to compare two endovascular treatment modalities in terms of safety, efficacy and short-term outcomes. METHODS: All the patients were divided into two groups: Group A: patients who underwent parent artery occlusion, and Group B: patients who underwent stent-assisted coil embolization. Follow-up outcomes were evaluated using the modified Rankin Scale (mRS). RESULTS: After 12 months of follow-up, the favorable outcome (mRS: 0-2) had no statistical significance in both groups (p = 1.00). Patients in group A had greater ischemia compared with patients in group B, but the difference did not reach statistical significance (p = 0.421). In group B, patients had a higher rate of partial occlusion (p = 0.255) and recurrence (10% vs. 0%; p = 0.586). CONCLUSIONS: Stent-assisted coiling may not be superior to parent artery occlusion in selected patients after short-term follow-up. Parent artery occlusion is a simple, safe and effective treatment for large/giant internal carotid aneurysms.

Treatment of unruptured vertebral dissecting aneurysms: internal trapping or stent-assisted coiling.

PURPOSE: Endovascular treatment is an attractive approach for the treatment of unruptured vertebral dissecting aneurysms, and includes internal trapping and stent-assisted coil embolization. However, the optimal therapy remains debatable. We reviewed our experience with both endovascular treatment modalities and compared the safety, efficacy, and short-term outcomes for each approach. MATERIALS AND METHODS: We retrospectively reviewed 65 consecutive patients with unruptured vertebral dissecting aneurysms who underwent endovascular treatment between January 2003 and January 2014. 24 patients underwent endovascular internal trapping (group A) while 41 patients underwent stent-assisted coiling (group B). Thirteen patients underwent single stent with coiling while 28 patients underwent double or three stent-assisted coiling. Short-term outcomes were evaluated using the modified Rankin Scale. RESULTS: A favorable clinical outcome was achieved in 58 of 65 patients. Procedure-related complications included ischemic symptoms (n = 6) and recurrence (n = 4). There was no statistical difference in modified Rankin Scale scoring between groups. Group A patients had more ischemia symptoms compared with group B patients (p = 0.043), Group B patients had higher recurrence rates compared with group A patients, but the difference had no statistical significance (p = 1.00). However, recurrence only occurred in patients who underwent stent-assisted coiling alone (p = 0.046). CONCLUSION: Stent-assisted coiling for unruptured vertebral dissecting aneurysms may maintain artery patency. Multilayer disposition of stents with coils may decrease complications and facilitate aneurysm occlusion. Larger, prospective studies are necessary to determine the long-term outcomes of reconstructive therapy.

Comparative efficacy of Glubran and polyvinyl-alcohol particles in the embolization of meningiomas.

PURPOSE: Preoperative embolization of meningiomas decreases intraoperative bleeding and shortens operation time. However, in meningiomas predominantly vascularized by the internal carotid artery (ICA) or vertebral artery (VA) branches, embolization of external carotid artery feeder branches may lead to a hemodynamic increase in blood supply from the ICA or VA, whereas embolization of ICA or VA feeder branches with particle embolic agents may be associated with complications. This study investigated the safety and efficacy of Glubran, a liquid embolic agent, for the embolization of this type of meningioma compared with polyvinyl-alcohol (PVA) particles. MATERIALS AND METHODS: From January 2006 to June 2015, 157 consecutive patients (98 females; mean age = 48.3 years) who suffered from meningiomas and were preoperatively referred for embolization were retrospectively analyzed. Glubran (n = 40) and PVA (n = 55) were used to devascularize tumors. Sixty-two patients were not embolized because of dangerous anastomosis or other tumor characteristics. Intraoperative blood loss, intraoperative time, degree of angiographic devascularization and embolization-related complications were analyzed. RESULTS: The intraoperative blood loss and operative time were significantly lower in the Glubran-embolized versus non-embolized group. Furthermore, Glubran embolization significantly reduced intraoperative blood loss and operative time for meningiomas that received their primary blood supply from the ICA and/or VA compared with PVA embolization. CONCLUSIONS: Preoperative meningioma embolization with Glubran decreases intraoperative blood loss and operative time. Furthermore, embolization with Glubran produces more effective devascularization compared with PVA for meningiomas supplied by the ICA and/or VA. Thus, Glubran may represent a better embolic agent for this meningioma subtype.

Nefiracetam Attenuates Pro-Inflammatory Cytokines and GABA Transporter in Specific Brain Regions of Rats with Post-Ischemic Seizures.

BACKGROUND/AIMS: Prior studies demonstrated that pro-inflammatory cytokines (PICs) including IL-1ß, IL-6 and TNF-α contribute to regulation of epilepsy-associated pathophysiological processes in the specific brain regions, namely the parietal cortex, hippocampus and amygdala. Moreover, GABA transporter type 1 and 3 (GAT-1 and GAT-3) modulating extracellular GABA levels are engaged in the role played by PICs in epileptogenesis. Note that brain ischemic injury also elevates cerebral PICs. Thus, in this report we examined the effects of nefiracetam (NEF), a pyrrolidone derivative, on the levels of IL-1ß, IL-6 and TNF-α, and expression of GAT-1 and GAT-3 in the parietal cortex, hippocampus and amygdala using a rat model of post-ischemic nonconvulsive seizure (NCS). METHODS: NCS was evoked by the middle cerebral artery occlusion (MCAO). ELISA and Western Blot analysis were employed to determine the levels of PICs and GAT-1/GAT-3, respectively. RESULTS: MCAO significantly increased IL-1ß, IL-6 and TNF-α in the parietal cortex, hippocampus and amygdala as compared with sham control animals (P<0.05 vs. control rats). Also, in these specific brain regions expression of GAT-1 and GAT-3 was amplified; and the levels of GABA were decreased in rats following MCAO (P<0.05 vs. control rats). Systemic administration of NEF significantly attenuated the elevated PICs, amplified GAT-1 and GAT-3 as well as impaired GABA. NEF also attenuated the number of NCS events following MCAO. CONCLUSION: our data demonstrate that NEF improves post-ischemia evoked-NCS by altering PICs, GABA transporters thereby alleviating GABA in the parietal cortex, hippocampus and amygdala. This support a role for PICs and GABA in engagement of the adaptive responses associated with epileptic activity, but also suggests that NEF has anti-epileptic effects via PICs-GABA mechanisms, having pharmacological implications to target the specific PICs for neuronal dysfunction and vulnerability related to post-ischemic seizures and cognitive impairment.

Predictors of Favorable Outcome of Intracranial Basilar Dissecting Aneurysm.

BACKGROUND: Management of intracranial basilar dissecting aneurysms has been controversial and challenging, and surgical and conservative treatments usually have a bad prognosis. Our study aimed at evaluating the outcomes of endovascular treatment for these lesions and exploring the predictors of favorable outcome. METHODS: We retrospectively reviewed 50 consecutive patients with basilar dissecting aneurysms from January 2006 to January 2013. Twenty-four patients underwent stent-assisted coiling whereas 26 patients underwent conservative treatment. Follow-up outcomes were evaluated using modified Rankin Scale (mRS) score. RESULTS: Of the patients treated with stent-assisted coiling, 20 patients had a favorable outcome (mRS score, 0-1), post-treatment recurrence occurred in 3 patients, 1 had rebleeding, and 2 had no rebleeding. Of the patients treated with conservative therapy (observation or anticoagulation), 10 patients had an unfavorable outcome, 2 patients with ruptured aneurysms developed rebleeding, and 8 patients had poor outcome because of infarct progression. Stent-assisted coiling group had a more favorable outcome than the conservatively treated group (83.3% versus 55.2%, P = .019). Initial complete obliteration was related to the favorable outcome in endovascular-treated group (P = .042). Stent placement was the only independent predictor of favorable outcome in the logistic regression analysis (P = .030; odds ratio = 5.828; 95% confidence interval, 1.192-28.503). CONCLUSIONS: Patients with basilar artery dissecting aneurysms treated with stent-assisted coiling had a more favorable outcome than the conservatively treated patients. Stent placement and initial complete occlusion were the favorable factors in patients with basilar dissecting aneurysm.

Endovascular Treatment of Dissecting Aneurysms of the Posterior Inferior Cerebellar Artery and Predictors of Outcome.

BACKGROUND: Isolated dissecting aneurysms of the posterior inferior cerebellar artery (PICA) are rare lesions, which carry high risk of rebleeding and mortality. However, the existing literature concerning predictors of outcome after endovascular treatment is limited and controversial. Our present study retrospectively reviewed and analyzed the clinical outcome of endovascular treatment-ruptured PICA-dissecting aneurysms and explored the predictors of outcome. METHODS: We retrospectively reviewed 17 consecutive patients with ruptured PICA dissecting aneurysms that underwent endovascular treatment from January 2003 to January 2014. Nine patients underwent selective coiling, whereas 7 patients underwent parent artery occlusion and 1 patient underwent stent-assisted coiling. Follow-up outcomes were evaluated using the modified Rankin Scale. The clinical outcomes of patients were categorized as favorable (modified Rankin Scale [mRS] score 0-1) or unfavorable (mRS score 2-6). RESULTS: Favorable outcomes (mRS score 0-1) were obtained in 13 of 17 patients. Post-treatment recurrence occurred in 1 patient with selective coiling in the 15-month follow-up, and the patient received stent-assisted coiling. The only patients with stent-assisted coiling developed PICA occlusion during follow-up. Aneurysm located in distal segment usually presented with intraventricular hemorrhage (P = .015). Hypertension, coexisting hydrocephalus, and time to operation (latter than 2 weeks) were associated with unfavorable outcome. CONCLUSIONS: Endovascular treatment of isolated dissecting aneurysm of PICA had excellent clinical outcomes, hypertension, coexisting hydrocephalus, and time to operation (latter than 2 weeks), which were associated with unfavorable outcome. Long-term follow-ups are necessary to provide stronger conclusions.

Clinical features and endovascular treatment of intracranial arteriovenous malformations in pediatric patients.

PURPOSE: The purpose of this study was to characterize clinical features and evaluate the clinical outcome of endovascular embolization treatment intracranial arteriovenous malformations in pediatric patients. METHODS: A cohort of children (age ≤ 18 years) with arteriovenous malformations (AVMs) from 2000 to 2012 was included. Predictors studied included patient gender, age, and angioarchitectural features, including AVM location, nidus morphology and size, venous drainage, and associated aneurysms. Treatment method, complications and outcomes were recorded. The features of AVMs were evaluated before the treatment. RESULTS: One hundred twenty-seven children (77 males, mean age 13.2 years) were included; 90/127 (70.9 %) children were presented with hemorrhage. AVM size and deep venous drainage were independently associated with hemorrhage; 66/127 patients (52 %) treated with endovascular embolization. Complete obliteration at the end of all endovascular procedures was achieved in 14/66 patients (21.2 %), with an average of 78 % (range, 20-100 %) volume reduction. A mean of 2.9 (range, 1-9) feeding pedicles was embolized per patient. Overall, nine complications occurred in a total of 123 procedures (7.3 %). There was no procedure-related death in this study population. There was no significant difference between patients with and without complications in terms of AVM grade, demographic characteristics, or embolization features. CONCLUSIONS: AVM size and deep venous drainage were independently associated with hemorrhage in pediatric patients. Endovascular procedure is feasible and safe for pediatric AVMs, and complete embolization can be achieved in small AVMs, while large AVMs can be adequately reduced in size for additional microsurgery or stereotactic radiosurgery.

The recovery time of traumatic carotid-cavernous fistula-induced oculomotor nerve paresis after endovascular treatment with detachable balloons.

PURPOSE: The recovery time of traumatic carotid-cavernous fistula-induced oculomotor nerve paresis (ONP) after endovascular embolization with detachable balloons has not yet been adequately evaluated. This study was performed to make a deep analysis of the factors, which affect the prognosis of ONP after endovascular treatment of traumatic carotid-cavernous fistula (TCCF). MATERIALS AND METHODS: We retrospectively evaluated the clinical characteristics and the outcome of oculomotor nerve function in a series of 98 consecutive patients with ONP due to traumatic carotid-cavernous fistula which were endovascular treated with detachable balloons. Univariate analysis was applied to test the association between the time of ONP recovery and clinical variables. RESULTS: Ninety-eight consecutive patients (62 males, 36 females, mean age 34.2±12.7years) having presented with ONP underwent endovascular treatment with detachable balloons were enrolled in this study. ONP was complete in 22 (22.4%) patients and partial in 76 (77.6%) patients. Ninety (91.8%) patients were successfully occluded by single-session endovascular embolization. Retreatments by transarterial routes had to be performed in 8 (8.2%) patients because of recurrent fistula having occurred within 4weeks after embolization. ONP was recovered completely in all the patients, among who 4 (4.1%) were treated with occlusion of internal carotid artery. Factors showing significant association with the recovery time of ONP were the location of the fistula (P=0.007), the degree of preoperative ONP (P=0.003), the number of detachable balloon used (P=0.000) and the length of ONP before endovascular treatment (P=0.000). CONCLUSION: Endovascular treatment of traumatic carotid-cavernous fistula-induced ONP with detachable balloons is a safe and effective method. The length of ONP before endovascular treatment, the location of the fistula, the degree of preoperative ONP, the number of detachable balloons used were the statistically significant predictors of the length of ONP complete recovery.

Comparison of Pipeline embolization device versus Tubridge embolization device in unruptured intracranial aneurysms: a multicenter, propensity score matched study.

BACKGROUND: Flow diverter devices (FDs) are increasingly used for treating unruptured intracranial aneurysms (UIAs), but limited studies compared different FDs. OBJECTIVE: To conduct a propensity score matched analysis comparing the Pipeline embolization device (PED) and Tubridge embolization device (TED) for UIAs. METHODS: Patients with UIAs treated with either PED or TED between July 2016 and July 2022 were included. Propensity score matching was performed to adjust for age, sex, comorbidities, smoking, drinking, aneurysm size, morphology, neck, location, parent artery diameter, adjunctive coiling, and angiographic follow-up duration. Perioperative complications and clinical and angiographic outcomes were compared after matching. RESULTS: 735 patients treated by PED and 290 patients treated by TED were enrolled. Compared with the PED group, patients in the TED group had a greater number of women and patients with ischemia, a smaller proportion of vertebrobasilar and non-saccular aneurysms, a smaller size and neck, and fewer adjunctive coils and overlapping stents, but a larger parent artery diameter and lumen disparities. After adjusting for these differences, 275 pairs were matched. No differences were found in perioperative complications (4.4% vs 2.5%, P=0.350), in-stent stenosis (16.0% vs 15.6%, P>0.999), or favorable prognosis (98.9% vs 98.5%, P>0.999). However, PED showed a trend towards better complete occlusion over a median 8-month angiographic follow-up (81.8% vs 75.3%, P=0.077). CONCLUSION: Compared with PED, TED provides a comparable rate of perioperative and short-term outcomes. Nevertheless, a better occlusion status in the PED group needs to be further verified over a longer follow-up period.

Surgical cannulation of the superior ophthalmic vein for the treatment of previously embolized cavernous sinus dural arteriovenous fistulas: serial studies and angiographic follow-up.

OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of transorbital puncture for the retreatment of previously embolized cavernous sinus dural arteriovenous fistulas (DAVFs) via a superior ophthalmic vein (SOV) approach. MATERIALS AND METHODS: During a 12-year period, 9 consecutive patients with previously embolized cavernous sinus DAVFs underwent retreatment via the transorbital SOV approach. RESULTS: All of the nine cases of previously embolized cavernous sinus DAVFs were successfully embolized. Clinical follow-ups were conducted in all nine cases at the duration of 17-141 months (61.22 ± 39.13 months). No recanalization occurred during the follow-up period. A subtle ptosis appeared in two patients and disappeared in one of the two cases after a 4-year follow-up. One patient suffered from paroxysmal positional vertigo and bruit for nearly 2 years after the treatment, but the follow-up angiography demonstrated no recurrence. One patient had persistent visual impairment caused by the initial venous stasis retinopathy. One patient with a history of a procedure-related transient decrease in visual acuity had it return to the normal level. The remaining four cases had clear improvement in the ocular symptoms and became completely asymptomatic during the follow-up period. No patient worsened or developed new symptoms. CONCLUSION: The approach of surgical cannulation of the SOV for the retreatment of previously embolized cavernous sinus DAVFs was proved feasible and efficient, especially when the transarterial and transfemoral venous approaches were inaccessible. However, if the SOV is not dilated enough or is located deeply in the orbit, transorbital venous puncture access may not be possible.

Evaluation of aneurysm rupture risk based upon flowrate-independent hemodynamic parameters: a multi-center pilot study.

BACKGROUND: Specifying generic flow boundary conditions in aneurysm hemodynamic simulations yields a great degree of uncertainty for the evaluation of aneurysm rupture risk. Herein, we proposed the use of flowrate-independent parameters in discriminating unstable aneurysms and compared their prognostic performance against that of conventional absolute parameters. METHODS: This retrospective study included 186 aneurysms collected from three international centers, with the stable aneurysms having a minimum follow-up period of 24 months. The flowrate-independent aneurysmal wall shear stress (WSS) and energy loss (EL) were defined as the coefficients of the second-order polynomials characterizing the relationships between the respective parameters and the parent-artery flows. Performance of the flowrate-independent parameters in discriminating unstable aneurysms with the logistic regression, Adaboost, and support-vector machine (SVM) methods was quantified and compared against that of the conventional parameters, in terms of sensitivity, specificity, and area under the curve (AUC). RESULTS: In discriminating unstable aneurysms, the proposed flowrate-independent EL achieved the highest sensitivity (0.833, 95% CI 0.586 to 0.964) and specificity (0.833, 95% CI 0.672 to 0.936) on the SVM, with the AUC outperforming the conventional EL by 0.133 (95% CI 0.039 to 0.226, p=0.006). Likewise, the flowrate-independent WSS outperformed the conventional WSS in terms of the AUC (difference: 0.137, 95% CI 0.033 to 0.241, p=0.010). CONCLUSION: The flowrate-independent hemodynamic parameters surpassed their conventional counterparts in predicting the stability of aneurysms, which may serve as a promising set of hemodynamic metrics to be used for the prediction of aneurysm rupture risk when physiologically real vascular boundary conditions are unavailable.

Nonlinear Association of Glycosylated Hemoglobin With Single Intracranial Aneurysm Rupture in Patients With Diabetes Mellitus: A Cross-Sectional Study.

Background: The published literature linking diabetes mellitus (DM) to intracranial aneurysm (IA) ruptured has been controversial and limited by methodology. Thus, this study was performed to examine whether hyperglycemia control status is independently associated with single IA rupture in patients with DM. Methods: We conducted a cross-sectional study on two Chinese hospitals between January 2010 and November 2017. Medical records of 223 patients with single IA and DM were reviewed and analyzed. We used glycosylated hemoglobin (GHB) as the independent variable of interest, and the outcome variable was ruptured status of IA. Covariates included data on demographics, morphological parameters, lifestyle habits, clinical features, and comorbidities. Results: Multivariable adjusted binary logistic regression and sensitivity analyses indicated that GHB was not associated with IA rupture (odds ratio OR, = 1.07, 95% CI 0.84-1.35). A nonlinear association between GHB and IA rupture was observed, whose inflection points were 5.5 and 8.9. The OR values (95% confidence intervals) were 0.38 (0.16-0.9) at the range of 1.88-5.5% of GHB, 1.6 (1.03, 2.5) at the range of 5.5-8.9%, and 0.56 (0.06-5.34) at the range of 8.9-10.1, respectively. Conclusion: The independent correlation between GHB and risk of IA rupture presented is nonlinear. The good glycemic control in single IA patients with DM can reduce the risk of IA rupture, and vice versa.

A deep learning-based automatic system for intracranial aneurysms diagnosis on three-dimensional digital subtraction angiographic images.

BACKGROUND: Intracranial aneurysms (IAs) are a life-threatening disease. Their rupture can lead to hemorrhagic stroke. Most studies applying deep learning for the detection of aneurysms are based on angiographic images. However, critical diagnostic information such as morphology and aneurysm location are not captured by deep learning algorithms and still require manual assessments. PURPOSE: Digital subtraction angiography (DSA) is the gold standard for aneurysm diagnosis. To facilitate the fully automatic diagnosis of aneurysms, we proposed a comprehensive system for the detection, morphology measurement, and location classification of aneurysms on three-dimensional DSA images, allowing automatic diagnosis without further human input. METHODS: The system comprised three neural networks: a network for aneurysm detection, a network for morphology measurement, and a network for aneurysm location identification. A cross-scale dual-path transformer module was proposed to effectively fuse local and global information to capture aneurysms of varying sizes. A multitask learning approach was also proposed to allow an accurate localization of aneurysm neck for morphology measurement. RESULTS: The cross-scale dual-path transformer module was shown to outperform other state-of-the-art network architectures, improving segmentation, and classification accuracy. The detection network in our system achieved an F2 score of 0.946 (recall 93%, precision 100%), better than the winning team in the Cerebral Aneurysm Detection and Analysis challenge. The measurement network achieved a relative error of less than 10% for morphology measurement, at the same level as human operators. Perfect accuracy (100%) was achieved on aneurysm location classification. CONCLUSIONS: We have demonstrated that a comprehensive system can automatically detect, measure morphology and report the aneurysm location of aneurysms without human intervention. This can be a potential tool for the diagnosis of IAs, improving radiologists' performance and reducing their workload.

Elucidating the Synergistic Effect of Multiple Chinese Herbal Prescriptions in the Treatment of Post-stroke Neurological Damage.

Background: Traditional Chinese medicine (TCM) has been widely used in the treatment of human diseases. However, the synergistic effects of multiple TCM prescriptions in the treatment of stroke have not been thoroughly studied. Objective of the study: This study aimed to reveal the mechanisms underlying the synergistic effects of these TCM prescriptions in stroke treatment and identify the active compounds. Methods: Herbs and compounds in the Di-Tan Decoction (DTD), Xue-Fu Zhu-Yu Decoction (XFZYD), and Xiao-Xu-Ming Decoction (XXMD) were acquired from the TCMSP database. SEA, HitPick, and TargetNet web servers were used for target prediction. The compound-target (C-T) networks of three prescriptions were constructed and then filtered using the collaborative filtering algorithm. We combined KEGG enrichment analysis, molecular docking, and network analysis approaches to identify active compounds, followed by verification of these compounds with an oxygen-glucose deprivation and reoxygenation (OGD/R) model. Results: The filtered DTD network contained 39 compounds and 534 targets, the filtered XFZYD network contained 40 compounds and 508 targets, and the filtered XXMD network contained 55 compounds and 599 targets. The filtered C-T networks retained approximately 80% of the biological functions of the original networks. Based on the enriched pathways, molecular docking, and network analysis results, we constructed a complex network containing 3 prescriptions, 14 botanical drugs, 26 compounds, 13 targets, and 5 pathways. By calculating the synergy score, we identified the top 5 candidate compounds. The experimental results showed that quercetin, baicalin, and ginsenoside Rg1 independently and synergistically increased cell viability. Conclusion: By integrating pharmacological and chemoinformatic approaches, our study provides a new method for identifying the effective synergistic compounds of TCM prescriptions. The filtered compounds and their synergistic effects on stroke require further research.

Expression of cytokines in rat brain with focal cerebral ischemia after grafting with bone marrow stromal cells and endothelial progenitor cells.

BACKGROUND AIMS: This study aimed to observe nine factors expressed in rat ischemic brain after transplantation of bone marrow stromal cells (BMSC) and/or endothelial progenitor cells (EPC). These factors were vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 (SDF-1), basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF-l), transforming growth factor-ß (TGF-ß), platelet-derived growth factor-BB (PDGF-BB), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF). METHODS: Adult Wistar rats were divided randomly into four groups: a vehicle group, BMSC group, EPC group and BMSC combined with EPC group. The rats were subjected to middle cerebral artery occlusion (MCAO) then implanted intravenously with 3 × 10(6) BMSC, EPC, BMSC/EPC or phosphate-buffered saline (PBS) 24 h after MCAO. Neurologic functional deficits were measured on days 1, 7, 14, 28 after transplantation. On day 7 after transplantation, quantitative reverse transcription (qRT)-polymerase chain reaction (PCR) and Western blot were employed to detect the expression of VEGF, SDF-1, bFGF, IGF-l, TGF-ß, PDGF-BB, BDNF, GDNF and NGF. RESULTS: The neurologic evaluation found that the neurologic severity scores were no different between the four groups on day 1, and the scores of rats in the BMSC/EPC group were significantly lower than those of rats in the other groups on days 7, 14 and 28 after transplantation. The expressions of bFGF, VEGF and BNDF were significantly higher in the BMSC/EPC group compared with the other groups. CONCLUSIONS: The intravenous transplantation of BMSC combined with EPC could promote the functional rehabilitation of rats with focal cerebral ischemia, and the mechanism may be related to the enhanced expression of factors.

[Effect of electro-needling at acupoints of the yangming meridian on the expression of PAC-1 and lower limb functions in acute cerebral infarction patients].

OBJECTIVE: To observe the effect of electro-needling at acupoints of the yangming meridian on the expression of platelet associated complement-1 (PAC-1) and lower limb functions in acute cerebral infarction (ACI) patients. METHODS: 58 ACI patients were randomly assigned to the treatment group and the control group. Conventional therapies were given to all patients. Additionally, the electro-needling at acupoints of the yangming meridian was given to patients in the treatment group. Changes of PAC-1 were detected using flow cytometry. Effect of lower limbs functions of ACI patients before and after electro-needling was assessed using Fugl-Meyer Index. Meanwhile, 20 healthy subjects were selected for reference value. RESULTS: In the acute stage, the PAC-1 level in ACI patients were significantly higher than that in healthy subjects (P<0.05). The PAC-1 level in the electro-needling group was obviously lowered after treatment (P<0.01). There was no significant difference in the control group between before and after treatment. Significant difference was found in Fugl-Meyer index in the same group between before and after two-week treatment (P<0.05). It was higher in the electro-needling group than in the control group, showing significant difference (P<0.01). CONCLUSIONS: Platelet activation exists in the acute stage of ACI. Electro-needling at acupoints of the yangming meridian showed obvious inhibition on PAC-1 levels, could improve lower limbs functions of ACI patients. It was inferred that electro-needling at acupoints of the yangming meridian promoted the recovery of paralyzed lower limbs at the early stage mainly by regulating PAC-1 levels, thus postponing the progress of ACI.