Timing of microsurgical resection for ruptured brain arteriovenous malformations: a propensity score-matched analysis using prospective single-center registry data.

OBJECTIVE: The optimal microsurgical timing in ruptured brain arteriovenous malformations (AVMs) is not well understood and is surrounded by controversy. This study aimed to elucidate the impacts of microsurgical resection timing on clinical outcomes. METHODS: The authors retrieved and reviewed the records on all ruptured AVMs treated at their institution and registered in a nationwide multicenter prospective collaboration registry between August 2011 and August 2021. Patients were dichotomized into an early resection group (≤ 30 days from the last hemorrhagic stroke) and a delayed resection group (> 30 days after the last hemorrhagic stroke). Propensity score-matched analysis was used to compare long-term outcomes. The primary outcome was neurological status as assessed using the modified Rankin Scale (mRS). The secondary outcomes were complete obliteration rate, postoperative seizure, and postoperative hemorrhage. RESULTS: Of the 3649 consecutive AVMs treated at the authors' institution, a total of 558 ruptured AVMs were microsurgically resected and had long-term follow-up. After propensity score matching, 390 ruptured AVMs (195 pairs) were included in the comparison of outcomes. The mean (± standard deviation) clinical follow-up duration was 4.93 ± 2.94 years in the early resection group and 5.61 ± 2.56 years in the delayed resection group. Finally, as regards the distribution of mRS scores, short-term neurological outcomes were better in the delayed resection group (risk difference [RD] 0.3%, 95% CI -0.1% to 0.6%, p = 0.010), whereas long-term neurological outcomes were similar between the two groups (RD 0.0%, 95% CI -0.2% to 0.2%, p = 0.906). Long-term favorable neurological outcomes (early vs delayed: 90.8% vs 90.3%, p > 0.999; RD 0.5%, 95% CI -5.8% to 6.9%; RR 1.01, 95% CI 0.94-1.07) and long-term disability (9.2% vs 9.7%, p > 0.999; RD -0.5%, 95% CI -6.9% to 5.8%; RR 0.95, 95% CI 0.51-1.75) were also similar between these groups. In terms of secondary outcomes, postoperative seizure (early vs delayed: 8.7% vs 5.6%, p = 0.239; RD 3.1%, 95% CI -2.6% to 8.8%; RR 1.55, 95% CI 0.74-3.22), postoperative hemorrhage (1.0% vs 1.0%, p > 0.999; RD 0.0%, 95% CI -3.1% to 3.1%; RR 1.00, 95% CI 0.14-7.04), and hospitalization time (16.4 ± 8.5 vs 19.1 ± 7.9 days, p = 0.793) were similar between the two groups, whereas early resection had a lower complete obliteration rate (91.3% vs 99.0%, p = 0.001; RD -7.7%, 95% CI -12.9% to 3.1%; RR 0.92, 95% CI 0.88-0.97). CONCLUSIONS: Early and delayed resection of ruptured AVMs had similar long-term neurological outcomes. Delayed resection can lead to a higher complete obliteration rate, although the risk of rerupture during the resection waiting period should be vigilantly monitored.

Comparison of conservative management, microsurgery only, and microsurgery with preoperative embolization for unruptured arteriovenous malformations: A propensity score weighted prospective cohort study.

AIMS: To compare the efficacy and deficiency of conservative management (CM), microsurgery (MS) only, and microsurgery with preoperative embolization (E + MS) for unruptured arteriovenous malformations (AVMs). METHODS: We prospectively included unruptured AVMs undergoing CM, MS, and E + MS from our institution between August 2011 and August 2021. The primary outcomes were long-term neurofunctional outcomes and hemorrhagic stroke and death. In addition to the comparisons among CM, MS, and E + MS, E + MS was divided into single-staged hybrid and multi-staged E + MS for further analysis. Stabilized inverse probability of treatment weighting using propensity scores was applied to control for confounders by treatment indication across the three groups. RESULTS: Of 3758 consecutive AVMs admitted, 718 patients were included finally (266 CM, 364 MS, and 88 E + MS). The median follow-up duration was 5.4 years. Compared with CM, interventions (MS and E + MS) were associated with neurological deterioration. MS could lower the risk of hemorrhagic stroke and death. Multi-staged E + MS was associated with neurological deterioration and higher hemorrhagic risks compared with MS, but the hybrid E + MS operation significantly reduced the hemorrhage risk. CONCLUSION: In this study, unruptured AVMs receiving CM would expect better neurofunctional outcomes but bear higher risks of hemorrhage than MS or E + MS. The single-staged hybrid E + MS might be promising in reducing inter-procedural and subsequent hemorrhage.

Re-rupture in ruptured brain arteriovenous malformations: a retrospective cohort study based on a nationwide multicenter prospective registry.

BACKGROUND: This study aimed to investigate the natural history of re-rupture in ruptured brain arteriovenous malformations (AVMs) and to provide comprehensive insights into its associated factors and prevention. METHODS: This study included 1712 eligible ruptured AVMs from a nationwide multicenter prospective collaboration registry between August 2011 and September 2021. The natural rupture risk before intervention and the annual rupture risk after intervention were both assessed. Cox proportional hazard regression models and Kaplan-Meier survival curves were used to explore independent factors associated with AVM re-rupture. The correlation between these factors and AVM re-rupture was verified in multiple independent cohorts, and the prevention effect of intervention timing and intervention strategies on AVM re-rupture was further analyzed. RESULTS: The annual re-rupture risk in ruptured AVMs was 7.6%, and the cumulative re-rupture risk in the first 1, 3, 5, and 10 years following the initial rupture were 10%, 25%, 37.5%, and 50%, respectively. Cox proportional hazard regression analysis confirmed adult patients, ventricular system involvement, and any deep venous drainage as independent factors associated with AVM re-rupture. The intervention was found to significantly reduce the risk of AVM re-rupture (annual rupture risk 11.34% vs 1.70%, p<0.001), especially in those who underwent surgical resection (annual rupture risk 0.13%). CONCLUSIONS: The risk of re-rupture in ruptured AVMs is high. Adult patients, ventricular system involvement, and any deep venous drainage are independent risk factors for re-rupture. Applying the results universally to all ruptured AVM cases may be biased. Intervention could effectively reduce the risk of re-rupture.

Association of embolization with long-term outcomes in brain arteriovenous malformations: a propensity score-matched analysis using nationwide multicenter prospective registry data.

BACKGROUND: Brain arteriovenous malformations (AVMs) account for 25% of hemorrhagic strokes in young adults. Although embolization has been widely performed as a stand-alone procedure to cure brain AVM, it is undermined whether patients benefit from this treatment. This study aimed to compare the long-term outcome of hemorrhagic stroke or death in patients with either conservative management or stand-alone embolization for AVM. METHODS: The study population was derived from a nationwide multicenter prospective collaboration registry (the MATCH registry) between August 2011 and August 2021. The propensity score-matched survival analysis was performed in the overall and stratified AVM cases (unruptured and ruptured), respectively, to compare the long-term outcome of hemorrhagic stroke or death, and neurological status. The efficacy of distinct embolization strategies was also evaluated. Hazard ratios (HRs) with 95% CI were calculated using Fine-Gray competing risk models. RESULTS: Of the 3682 consecutive AVMs, 906 underwent either conservative management or embolization as the stand-alone management strategy. After propensity score matching, a total of 622 (311 pairs) patients constituted an overall cohort. The unruptured and ruptured subgroups were composed of 288 cases (144 pairs) and 252 cases (126 pairs), respectively. In the overall cohort, embolization did not prevent long-term hemorrhagic stroke or death compared with conservative management [2.07 vs. 1.57 per 100 patient-years; HR, 1.28 (95% CI, 0.81-2.04)]. Similar results were maintained in both unruptured AVMs [1.97 vs. 0.93 per 100 patient-years; HR, 2.09 (95% CI, 0.99-4.41)] and ruptured AVMs [2.36 vs. 2.57 per 100 patient-years; HR, 0.76 (95% CI, 0.39-1.48)]. Stratified analysis showed that the target embolization might be beneficial for unruptured AVMs [HR, 0.42 (95% CI, 0.08-2.29)], while the curative embolization improved the outcome of ruptured AVMs [HR, 0.29 (95% CI, 0.10-0.87)]. The long-term neurological status was similar between these two strategies. CONCLUSIONS: This prospective cohort study did not support a substantial superiority of embolization over conservative management for AVMs in preventing long-term hemorrhagic stroke or death.

Development and Validation of a Scoring System for Hemorrhage Risk in Brain Arteriovenous Malformations.

Importance: The dilemma between natural rupture risk and adverse outcomes of intervention is of major concern for patients with unruptured arteriovenous malformations (AVMs). The existing risk score for AVM rupture includes factors that are controversial and lacks prospective validation. Objective: To develop and robustly validate a reliable scoring system to predict the rupture risk of AVMs. Design, Setting, and Participants: This prognostic study developed a prediction model derived from a single-center cohort (derivation cohort) and validated in a multicenter external cohort (multicenter external validation cohort) and a cohort of patients receiving conservative treatment management (conservative treatment validation cohort). Patients were recruited from a nationwide multicenter prospective collaboration registry in China. A total of 4135 patients were enrolled in the registry between August 1, 2011, and September 1, 2021. Of those, 3962 patients were included in the study (3585 in the derivation cohort and 377 in the multicenter external validation cohort); 1028 patients from the derivation cohort who had time-to-event data and prerupture imaging results were included in the conservative treatment validation cohort. Data were analyzed from March 10 to June 21, 2022. Main Outcomes and Measures: A scoring system was developed based on risk factors identified from a literature review and a robust selection process. Patients were stratified into different risk groups based on scores to calculate hemorrhage-free probability in future years, and Kaplan-Meier curves were plotted to visualize risk stratification. Receiver operating characteristic curves were used to assess the discrimination of models. Univariable analyses (logistic regression analysis for descriptive data and Cox regression analysis for survival data) were used to compare baseline information and assess bias. Results: Among 3962 patients (2311 men [58.3%]; median [IQR] age, 26.1 [14.6-35.5] years), 3585 patients (2100 men [58.6%]; median [IQR] age, 25.9 [14.6-35.0] years) were included in the derivation cohort, and 377 patients (211 men [56.0%]; median [IQR] age, 26.4 [14.5-39.2] years) were included in the multicenter external validation cohort. Thirty-six hemorrhages occurred over a median (IQR) follow-up of 4.2 (0.3-6.0) years among 1028 patients in the conservative treatment validation cohort. Four risk factors were used to develop the scoring system: ventricular system involvement, venous aneurysm, deep location, and exclusively deep drainage (VALE). The VALE scoring system performed well in all 3 cohorts, with areas under the receiver operating characteristic curve of 0.77 (95% CI, 0.75-0.78) in the derivation cohort, 0.85 (95% CI, 0.81-0.89) in the multicenter external validation cohort, and 0.73 (95% CI, 0.65-0.81) in the conservative treatment validation cohort. The 10-year hemorrhage-free rate was 95.5% (95% CI, 87.1%-100%) in the low-risk group, 92.8% (95% CI, 88.8%-97.0%) in the moderate-risk group, and 75.8% (95% CI, 65.1%-88.3%) in the high-risk group; the model discrimination was significant when comparing these rates between the high-risk group and the low- and moderate-risk groups (P < .001 for both comparisons). Conclusions and Relevance: In this prognostic study, the VALE scoring system was developed to distinguish rupture risk among patients with AVMs. The stratification of unruptured AVMs may enable patients with low risk of rupture to avoid unnecessary interventions. These findings suggest that the scoring system is a reliable and applicable tool that can be used to facilitate patient and physician decision-making and reduce unnecessary interventions or unexpected AVM ruptures.

Multimodality treatment for brain arteriovenous malformation in Mainland China: design, rationale, and baseline patient characteristics of a nationwide multicenter prospective registry.

BACKGROUND: Brain arteriovenous malformation (AVM) is an important cause of hemorrhagic stroke in young adults, which can lead to severe neurological impairment. The registry of Multimodality treatment for brain ArTeriovenous malformation in mainland CHina (MATCH) is a national prospective registry to identify the natural history of AVMs in Asian population; to investigate traditional and emerging hemorrhagic predictors; and to explore the superiority of the multidisciplinary assessment in improving the long-term outcomes.  METHODS: Consecutive AVM patients will be enrolled from 52 participating hospitals in mainland China. Baseline demographic, clinical and imaging data will be collected prospectively. Conservation, microsurgery, embolization, stereotactic radiosurgery (SRS), and multimodal strategies are all included in this study. Patients will be divided into experimental and control group according to whether the treatment protocols are formulated by multidisciplinary team. Neurofunctional status, subsequent hemorrhage, seizure, and novel neurofunctional deficit will be queried at 3 months, annually (1 and 2 years), 3 years, and 10 years follow-up. RESULTS: Between August 2011 and April 2021, 3241 AVMs were enrolled in 11 participating sites. Among them, 59.0% were male with an average age of 28.4 ± 14.6 years, 61.2% had rupture history and 2268 hemorrhagic events occurred before admission. The median Spetzler-Martin grade and Lawton-Young grade was 3 and 5, respectively. Microsurgery is the dominant strategy (35.7%), with a similar proportion of embolization, SRS, and a combination of both (12.7%; 14.8%; 11.8%; respectively). Among them, 15.43% underwent multidisciplinary assessment and received standardized treatment. At the most recent follow-up, 7.8% were lost and the median follow-up duration was 5.6 years. CONCLUSIONS: The MATCH study is a large-sample nationwide prospective registry to investigate multimodality management strategy for AVMs. Data from this registry may also provide the opportunity for individualized risk assessment and the development of optimal individual management strategies. TRIAL REGISTRATION: ClinicalTrials.gov Registry ( NCT04572568 ).

Assessment of gamma knife radiosurgery for unruptured cerebral arterioveneus malformations based on multi-parameter radiomics of MRI.

OBJECTIVE: The treatment of Gamma knife radiosurgery (GKS) for unruptured Arteriovenous Malformations (AVM) remains controversial. A safe, effective and non-invasive method to predict outcome seems attractive for GKS. The purpose of this study was to develop and validate a MRI based multi-parameter radiomics model predicting the outcome of GKS for unruptured AVM. METHODS: Eighty-eight unruptured AVM patients who initial underwent GKS between January 2011 and December 2016 in our hospital were included in this retrospective study. Patients were divided into two groups named as favourable and unfavourable outcome, according to the clinical outcome. Favourable outcome was defined as obliteration without post-SRS hemorrhage or permanent radiation-induced changes (RIC). Multivariate logistic regression analysis was used to select appropriate clinical features and construct a clinical predicting model. In terms of radiomic model, manually segmentation and radiomics extracted were performed on each AVM lesions. Finally, 1684 radiomics features were extracted and Recursive Feature Elimination (RFE) method combined with Random forest classifier were used for feature selection and model construction. The performance of the radiomics model was evaluated by the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). In addition, the favourable group was further divided into early and late respond subgroup according to the time of obliteration evaluated by 2 years. The selected features were further compared according the respond time. RESULTS: The median duration of neuroimaging follow-up was 65 months, 56 patients showed favourable outcome and 17 patients were observed obliteration within 2 years. The radiomics model constructed by 12 selected features achieved significant higher AUC of 0.88 (95% confidence interval 0.87-0.90) than traditional scoring system for predicting AVM outcome. Two selected radiomics features named "Dependence Variance" and "firstorder-Skewness" were found significant difference between the patients with early or late-respond. CONCLUSIONS: The results suggest that the radiomics features could be successfully used for the pretreatment prediction of outcome for GKS in unruptured AVMs, which is helpful for decision-making process on unruptured AVM patients.

A Machine Learning Model Predicts the Outcome of SRS for Residual Arteriovenous Malformations after Partial Embolization: A Real-World Clinical Obstacle.

OBJECTIVE: To propose a machine learning (ML) model predicting the favorable outcome of stereotactic radiosurgery (SRS) for residual brain arteriovenous malformation (bAVM) after partial embolization. METHODS: One hundred and thirty bAVM patients who underwent partial embolization followed by SRS were reviewed retrospectively. Patients were split at random split into training datasets (n = 100) and testing datasets (n = 30). Radiomics and dosimetric features were extracted from pre-SRS treatment images. Feature selection was performed to select appropriate radiomics and dosimetric features. Three ML algorithms were applied to construct models using selected features respectively. A total of 9 models were trained to predict favorable outcomes (obliteration without complication) of bAVMs. The efficacy of these models was evaluated on the testing dataset using mean accuracy (ACC) and area under the receiver operating characteristic curve (AUC). RESULTS: The obliteration rate of this cohort was 70.77% (92 of 130) with a mean follow-up of 43.8 months (range, 12-108 months). Favorable outcomes were achieved in 89 patients (68.46%). Four radiomics features and 7 dosimetric features were selected for ML model construction. The dosimetric support vector machines (SVM) model showed the best performance on the training dataset, with an ACC of 0.74 and AUC of 0.78. The dosimetric SVM model also showed the best performance on the testing dataset, with an ACC of 0.83 and AUC of 0.77. CONCLUSIONS: Dosimetric features are good predictors of prognosis for patients with partially embolized bAVM followed by SRS therapy. The use of ML models is an innovative method for predicting favorable outcomes of partially embolized bAVM followed by SRS therapy.

Stereotactic Radiosurgery With vs. Without Prior Embolization for Brain Arteriovenous Malformations: A Propensity Score Matching Analysis.

Objective: Whether partial embolization could facilitate the post-stereotactic radiosurgery (SRS) obliteration for brain arteriovenous malformations (bAVMs) remains controversial. We performed this study to compare the outcomes of SRS with and without prior embolization for bAVMs. Methods: We retrospectively reviewed the Beijing Tiantan AVMs prospective registration research database from September 2011 to October 2014. Patients were categorized into two groups, combined upfront embolization and SRS (Em+SRS group) and SRS alone (SRS group), and we performed a propensity score matching analysis based on pre-embolization baseline characteristics; the matched groups each comprised 76 patients. Results: The obliteration rate was similar between SRS and Em+SRS (44.7 vs. 31.6%; OR, 1.754; 95% CI, 0.905-3.401; p = 0.096). However, the SRS group was superior to the Em+SRS group in terms of cumulative obliteration rate at a follow-up of 5 years (HR,1.778; 95% CI, 1.017-3.110; p = 0.033). The secondary outcomes, including functional state, post-SRS hemorrhage, all-cause mortality, and edema or cyst formation were similar between the matched cohorts. In the ruptured subgroup, the SRS group could achieve higher obliteration rate than Em+SRS group (56.5 vs. 31.9%; OR, 2.773; 95% CI, 1.190-6.464; p = 0.018). The cumulative obliteration rate at 5 years was also higher in the SRS group (64.5 vs. 41.3%; HR, 2.012; 95% CI, 1.037-3.903; p = 0.038), and the secondary outcomes were also similar between the matched cohorts. Conclusion: Although there was no significant difference in the overall obliteration rate between the two strategies, this study suggested that pre-SRS embolization may have a negative effect on post-SRS obliteration. Furthermore, the obliteration rates of the SRS only strategy was significantly higher than that of the Em+SRS strategy in the ruptured cohort, while no such phenomenon was found in the unruptured cohort.

Chinese Cerebrovascular Neurosurgery Society and Chinese Interventional & Hybrid Operation Society, of Chinese Stroke Association Clinical Practice Guidelines for Management of Brain Arteriovenous Malformations in Eloquent Areas.

Aim: The aim of this guideline is to present current and comprehensive recommendations for the management of brain arteriovenous malformations (bAVMs) located in eloquent areas. Methods: An extended literature search on MEDLINE was performed between Jan 1970 and May 2020. Eloquence-related literature was further screened and interpreted in different subcategories of this guideline. The writing group discussed narrative text and recommendations through group meetings and online video conferences. Recommendations followed the Applying Classification of Recommendations and Level of Evidence proposed by the American Heart Association/American Stroke Association. Prerelease review of the draft guideline was performed by four expert peer reviewers and by the members of Chinese Stroke Association. Results: In total, 809 out of 2,493 publications were identified to be related to eloquent structure or neurological functions of bAVMs. Three-hundred and forty-one publications were comprehensively interpreted and cited by this guideline. Evidence-based guidelines were presented for the clinical evaluation and treatment of bAVMs with eloquence involved. Topics focused on neuroanatomy of activated eloquent structure, functional neuroimaging, neurological assessment, indication, and recommendations of different therapeutic managements. Fifty-nine recommendations were summarized, including 20 in Class I, 30 in Class IIa, 9 in Class IIb, and 2 in Class III. Conclusions: The management of eloquent bAVMs remains challenging. With the evolutionary understanding of eloquent areas, the guideline highlights the assessment of eloquent bAVMs, and a strategy for decision-making in the management of eloquent bAVMs.

Radiosurgery-Based AVM Scale Is Proposed for Combined Embolization and Gamma Knife Surgery for Brain Arteriovenous Malformations.

Background and purpose: To evaluate whether a radiosurgery-based arteriovenous malformation (AVM) scale (RBAS) could be used to predict obliteration of brain arteriovenous malformations (bAVMs) supposed for combined endovascular embolization (EMB) and gamma knife surgery (GKS) treatment. Methods: bAVM patients who underwent GKS with or without previous EMB from January 2011 to December 2016 at our institution were retrospectively reviewed. The patients were categorized into a combined treatment group and a GKS group. A 1:1 propensity score matching (PSM) was used to match the two groups. Pre-EMB and pre-GKS RBAS were assessed for every patient. Multivariate analysis was performed to find factors associated with complete obliteration in the combined treatment group. Survival analysis based on sub-groups according to RBAS was performed to compare obliteration rate and find cutoffs for appropriate treatment modalities. Results: A total of 96 patients were involved, and each group comprised 48 patients. There was no difference between the two groups in terms of obliteration rate (75.0 vs. 83.3%, p = 0.174). Pre-EMB RBAS (p = 0.010) and the number of feeding arteries (p = 0.014) were independent factors associated with obliteration rate in the combined treatment group. For the combined treatment patients, sub-group analysis according to pre-EMB RBAS (score <1.0, 1.0-1.5, and >1.5) showed statistical difference in obliteration rate (p = 0.002). Sub-group analysis according to RBAS between the two groups showed that the obliteration rate of the GKS group is significantly higher than the combined group when RBAS >1.5 (47.4 vs. 66.7%, p = 0.036). Conclusions: The RBAS is proposed to be efficient in predicting obliteration of bAVMs supposed to receive combined EMB and GKS treatment. Patients with RBAS >1.5 are inclined to be more suitable for GKS instead of the combined treatment.

Long-Term Outcomes of Elderly Brain Arteriovenous Malformations After Different Management Modalities: A Multicenter Retrospective Study.

Background: More and more elderly patients are being diagnosed with arteriovenous malformation (AVM) in this global aging society, while the treatment strategy remains controversial among these aging population. This study aimed to clarify the long-term outcomes of elderly AVMs after different management modalities. Methods: The authors retrospectively reviewed 71 elderly AVMs (>60 years) in two tertiary neurosurgery centers between 2011 and 2019. Patients were divided into four groups: conservation, microsurgery, embolization, and stereotactic radiosurgery (SRS). The perioperative complications, short-term and long-term neurological outcomes, obliteration rates, annualized rupture risk, and mortality rates were compared among different management modalities in the ruptured and unruptured subgroups. Kaplan-Meier survival analysis was employed to compare the death-free survival rates among different management modalities. Logistic regression analyses were conducted to calculate the odds ratios (ORs) and 95% confidence intervals (CI) for predictors of long-term unfavorable outcomes (mRS > 2). Results: A total of 71 elderly AVMs were followed up for an average of 4.2 ± 2.3 years. Fifty-four (76.1%) presented with hemorrhage, and the preoperative annualized rupture risk was 9.4%. Among these patients, 21 cases (29.6%) received conservative treatment, 30 (42.3%) underwent microsurgical resection, 13 (18.3%) received embolization, and 7 (9.9%) underwent SRS. In the prognostic comparison, the short-term and long-term neurological outcomes were similar between conservation and intervention both in the ruptured and unruptured subgroups (ruptured: p = 0.096, p = 0.904, respectively; unruptured: p = 0.568, p = 0.306, respectively). In the ruptured subgroup, the intervention cannot reduce long-term mortality (p = 0.654) despite the significant reduction of subsequent hemorrhage than conservation (p = 0.014), and the main cause of death in the intervention group was treatment-related complications (five of seven, 71.4%). In the logistic regression analysis, higher admission mRS score (OR 3.070, 95% CI 1.559-6.043, p = 0.001) was the independent predictor of long-term unfavorable outcomes (mRS>2) in the intervention group, while complete obliteration (OR 0.146, 95% CI 0.026-0.828, p = 0.030) was the protective factor. Conclusions: The long-term outcomes of elderly AVMs after different management modalities were similar. Intervention for unruptured elderly AVMs was not recommended. For those ruptured, we should carefully weigh the risk of subsequent hemorrhage and treatment-related complications. Besides, complete obliteration should be pursued once the intervention was initiated. Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT04136860.

Long-term outcomes of brainstem arteriovenous malformations after different management modalities: a single-centre experience.

OBJECTIVE: The aims of this study are to clarify the long-term outcomes of brainstem arteriovenous malformations (AVMs) after different management modalities. METHODS: The authors retrospectively reviewed 61 brainstem AVMs in their institution between 2011 and 2017. The rupture risk was represented by annualised haemorrhagic rate. Patients were divided into five groups: conservation, microsurgery, embolisation, stereotactic radiosurgery (SRS) and embolisation+SRS. Neurofunctional outcomes were evaluated by the modified Rankin Scale (mRS). Subgroup analysis was conducted between different management modalities to compare the long-term outcomes in rupture or unruptured cohorts. RESULTS: All of 61 brainstem AVMs (12 unruptured and 49 ruptured) were followed up for an average of 4.5 years. The natural annualised rupture risk was 7.3%, and the natural annualised reruptured risk in the ruptured cohort was 8.9%. 13 cases were conservative managed and 48 cases underwent intervention (including 6 microsurgery, 12 embolisation, 21 SRS and 9 embolisation+SRS). In the selection of interventional indication, diffuse nidus were often suggested conservative management (p=0.004) and nidus involving the midbrain were more likely to be recommended for intervention (p=0.034). The risk of subsequent haemorrhage was significantly increased in partial occlusion compared with complete occlusion and conservative management (p<0.001, p=0.036, respectively). In the subgroup analysis, the follow-up mRS scores of different management modalities were similar whether in the rupture cohort (p=0.064) or the unruptured cohort (p=0.391), as well as the haemorrhage-free survival (p=0.145). In the adjusted Bonferroni correction analysis of the ruptured cohort, microsurgery and SRS could significantly improve the obliteration rate compared with conservation (p<0.001, p=0.001, respectively) and SRS may have positive effect on avoiding new-onset neurofunctional deficit compared with microsurgery and embolisation (p=0.003, p=0.003, respectively). CONCLUSIONS: Intervention has similar neurofunctional outcomes as conservation in these brainstem AVM cohorts. If intervention is adopted, partial obliteration should be avoided because of the high subsequent rupture risk. TRIAL REGISTRATION NUMBER: NCT04136860.

Factors Affecting Volume Reduction Velocity for Arteriovenous Malformations After Treatment With Dose-Stage Stereotactic Radiosurgery.

BACKGROUND AND PURPOSE: The purpose of this study was to identify morphologic and dosimetric features associated with volume reduction velocity for arteriovenous malformation (AVM) after dose-stage stereotactic radiosurgery (DS-SRS). METHODS: Thirty patients with intracranial AVM were treated with DS fractionated SRS at Beijing Tiantan Hospital from 2011 to 2019. The AVM nidus was automatically segmented from DICOMRT files using the 3D Slicer software. The change in lesion volume was obtained from the decrease in the planning target volume (PTV) between the two treatment sessions. The volume reduction velocity was measured by the change in volume divided by the time interval between treatments. Fourteen morphologic features of AVM prior to treatment were extracted from the PTV using 'Pyradiomics' implemented in Python. Along with other dosimetric features, univariate and multivariate analyses were performed to explore predictors of the volume reduction velocity. RESULTS: Among the 15 male (50.0%) and 15 female (50.0%) patients enrolled in this study, 17 patients (56.7%) initially presented with hemorrhage. The mean treatment interval between the initial and second SRS was 35.73 months. In multivariate analysis, the SurfaceVolumeRatio was the only independent factor associated with the volume reduction velocity (p=0.010, odds ratio=0.720, 95% confidence interval: 0.560-0.925). The area under the curve of this feature for predicting the volume reduction velocity after the initial treatment of DS-SRS was 0.83. (p=0.0018). CONCLUSIONS: The morphologic features correlated well with the volume reduction velocity in patients with intracranial AVM who underwent DS-SRS treatment. The SurfaceVolumeRatio could predict the rate of volume reduction of AVMs after DS-SRS.

Contemporary management of brain arteriovenous malformations in mainland China: a web-based nationwide questionnaire survey.

BACKGROUND: In the benefit of the large population and rapid economic growth, the interventional techniques and equipment for brain arteriovenous malformations (bAVMs) in mainland China have been rapidly improved. Chinese neurosurgical cerebrovascular physicians have accumulated rich experience and made pioneering explorations. This study aims to summarize the experience and treatment progress of bAVMs in mainland China. METHODS: We performed a web-based nationwide questionnaire survey among 67 tertiary neurosurgical institutions that had acknowledged treating bAVMs in the primary survey. Our questionnaire included clinical characteristics, radiological findings, intervention indications/contraindications, intervention timing, and intraoperative management of different treatment modalities. RESULTS: A total of 63 participants from 49 (73.1%) tertiary neurosurgical institutions responded to our questionnaire. Forty-two (66.7%) were neurosurgeons, 13 (20.6%) were neurointerventionists, and 8 (12.7%) were radiosurgeons. Approximately 3500 to 4000 cases of bAVMs were treated annually in these 49 departments. All participants agreed that the conclusions of ARUBA are debatable. Flow-related aneurysms, deep venous drainage, and arteriovenous fistula were considered as common hemorrhagic risk factors. Unruptured SM IV-V bAVMs, giant bAVMs, pediatric bAVMs, elderly bAVMs, and eloquent bAVMs were not absolute contraindications to intervention. Maximum lesion occlusion and minimal functional impairment were the principles of intervention management. Most of the neurosurgeons and neurointerventionists recommended early intervention (< 30 days) for ruptured bAVMs, and the radiosurgeons suggested intervention in the chronic phase or recovery phase (P < 0.01) and preferably 3 months after bleeding. Multi-modality strategies were thought effective for complex bAVMs, and more exploration of individualized intraoperative management was necessary. CONCLUSIONS: Intervention was acceptable for specific selected unruptured bAVMs in mainland China, especially in patients with hemorrhagic risk factors. The application of multidisciplinary cerebrovascular team and multicenter large-sample international registry study might be the next work for Chinese neurosurgical cerebrovascular physicians.

Weighted single-step GWAS identified candidate genes associated with semen traits in a Duroc boar population.

BACKGROUND: In the pig production industry, artificial insemination (AI) plays an important role in enlarging the beneficial impact of elite boars. Understanding the genetic architecture and detecting genetic markers associated with semen traits can help in improving genetic selection for such traits and accelerate genetic progress. In this study, we utilized a weighted single-step genome-wide association study (wssGWAS) procedure to detect genetic regions and further candidate genes associated with semen traits in a Duroc boar population. Overall, the full pedigree consists of 5284 pigs (12 generations), of which 2693 boars have semen data (143,113 ejaculations) and 1733 pigs were genotyped with 50 K single nucleotide polymorphism (SNP) array. RESULTS: Results show that the most significant genetic regions (0.4 Mb windows) explained approximately 2%~ 6% of the total genetic variances for the studied traits. Totally, the identified significant windows (windows explaining more than 1% of total genetic variances) explained 28.29, 35.31, 41.98, and 20.60% of genetic variances (not phenotypic variance) for number of sperm cells, sperm motility, sperm progressive motility, and total morphological abnormalities, respectively. Several genes that have been previously reported to be associated with mammal spermiogenesis, testes functioning, and male fertility were detected and treated as candidate genes for the traits of interest: Number of sperm cells, TDRD5, QSOX1, BLK, TIMP3, THRA, CSF3, and ZPBP1; Sperm motility, PPP2R2B, NEK2, NDRG, ADAM7, SKP2, and RNASET2; Sperm progressive motility, SH2B1, BLK, LAMB1, VPS4A, SPAG9, LCN2, and DNM1; Total morphological abnormalities, GHR, SELENOP, SLC16A5, SLC9A3R1, and DNAI2. CONCLUSIONS: In conclusion, candidate genes associated with Duroc boars' semen traits, including the number of sperm cells, sperm motility, sperm progressive motility, and total morphological abnormalities, were identified using wssGWAS. KEGG and GO enrichment analysis indicate that the identified candidate genes were enriched in biological processes and functional terms may be involved into spermiogenesis, testes functioning, and male fertility.

Evaluation of a simple off-the-shelf bi-layered vascular scaffold based on poly(L-lactide-co-ε-caprolactone)/silk fibroin in vitro and in vivo.

Purpose: In the field of small-caliber vascular scaffold research, excellent vascular remodeling is the key to ensuring anticoagulant function. We prepared an off-the-shelf bi-layered vascular scaffold with a dense inner layer and a loose outer layer and evaluated its remodeling capabilities by in vivo transplantation. Materials and Methods: Based on poly(L-lactide-co-ε-caprolactone) (PLCL), silk fibroin(SF), and heparin (Hep), PLCL/SF/Hep bi-layered scaffolds and PLCL/Hep bi-layered scaffolds were prepared by electrospinning. The inner layer was a PLCL/SF/Hep or PLCL/Hep nanofiber membrane, and the outer layer was PLCL/SF nano yarn. The in vitro tests included a hydrophilicity test, mechanical properties test, and blood and cell compatibility evaluation. The in vivo evaluation was conducted via single rabbit carotid artery replacement and subsequent examinations, including ultrasound imaging, immunoglobulin assays, and tissue section staining. Results: Compared to the PLCL/Hep nanofiber membrane, the hydrophilicity of the PLCL/SF/Hep nanofiber membrane was significantly improved. The mechanical strength met application requirements. Both the blood and cell compatibility were optimal. Most importantly, the PLCL/SF/Hep scaffolds maintained lumen patency for 3 months after carotid artery transplantation in live rabbits. At the same time, CD31 and α-SMA immunofluorescence staining confirmed bionic endothelial and smooth muscle layers remodeling. Conclusion: Using this hybrid strategy, PLCL and SF were combined to manufacture bi-layered small-caliber vascular scaffolds; these PLCL/SF/Hep scaffolds showed satisfactory vascular remodeling.

Long-Term Follow-Up Studies of Gamma Knife Radiosurgery for Postsurgical Nonfunctioning Pituitary Adenomas.

OBJECTIVE: The aim of this study was to evaluate the long-term clinical outcomes of Gamma Knife radiosurgery (GKRS) for residual and recurrent nonfunctioning pituitary adenomas (NFPAs) after surgery and the role of GKRS in the management of NFPAs. METHODS: Between January 2000 and December 2010, 204 patients with residual or recurrent NFPAs undergoing GKRS were enrolled in this study according to the inclusion criteria. The median age of the patients was 48 years (mean, 48 years; range, 14-79 years). The median tumor volume was 3.3 mL (mean, 5.2 mL; range, 0.3-26.4 mL). The median margin dose was 14 Gy (mean, 14 Gy; range, 9-18 Gy). The median maximum dose was 31 Gy (mean, 30 Gy; 20-40 Gy). The median duration of follow-up was 86 months (mean, 88 months; range, 12-213 months). RESULTS: Of these 204 patients, the latest follow-up magnetic resonance imaging studies showed tumor regression in 102 patients (50%), tumor stability in 81 patients (40%), and tumor enlargement in 21 patients (10%). The tumor control rate of this cohort was 90%. The cumulative progression-free survival at 3, 5, 8, 10, and 15 years was 97%, 95%, 92%, 92%, and 81%, respectively. Thirty-seven patients (18%) developed new-onset hypopituitarism, with 1 patient experiencing panhypopituitarism. Five patients (2.5%) presented with new or worsening visual dysfunction without tumor growth. No new cranial nerve dysfunction was shown and no second brain tumor was identified. CONCLUSIONS: GKRS provided high tumor control and a low complication rate in our long-term follow-up. We recommend that early GKRS should be considered the routine adjuvant treatment for residual NFPAs approximately 6 months after subtotal surgical resection.

Long-term follow-up studies of Gamma Knife surgery for patients with neurofibromatosis Type 2.

OBJECT: The aim of this study was to evaluate long-term clinical outcomes after Gamma Knife surgery (GKS) for patients with neurofibromatosis Type 2 (NF2) and the role of GKS in the management of NF2. METHODS: From December 1994 through December 2008, a total of 46 patients (21 male, 25 female) with NF2 underwent GKS and follow-up evaluation for at least 5 years at the Gamma Knife Center of the Beijing Neurosurgical Institute. GKS was performed using the Leksell Gamma Knife Models B and C. The mean age of the patients was 30 years (range 13-59 years). A family history of NF2 was found for 9 (20%) patients. The NF2 phenotype was thought to be Wishart for 20 (44%) and Feiling-Gardner for 26 (56%) patients. Among these 46 patients, GKS was performed to treat 195 tumors (73 vestibular schwannomas and 122 other tumors including other schwannomas and meningiomas). For vestibular schwannomas, the mean volume was 5.1 cm(3) (median 3.6 cm(3), range 0.3-27.3 cm(3)), the mean margin dose was 12.9 Gy (range 10-14 Gy), and the mean maximum dose was 27.3 Gy (range 16.2-40 Gy). For other tumors, the mean volume was 1.7 cm(3) (range 0.3-5.5 cm(3)), the mean margin dose was 13.3 Gy (range 11-14 Gy), and the mean maximum dose was 26.0 Gy (range 18.0-30.4 Gy). The median duration of follow-up was 109 months (range 8-195 months). RESULTS: For the 73 vestibular schwannomas that underwent GKS, the latest follow-up MR images demonstrated regression of 30 (41%) tumors, stable size for 31 (43%) tumors, and enlargement of 12 (16%) tumors. The total rate of tumor control for bilateral vestibular schwannomas in patients with NF2 was 84%. Of the 122 other types of tumors that underwent GKS, 103 (85%) showed no tumor enlargement. The rate of serviceable hearing preservation after GKS was 31.9% (15/47). The actuarial rates for hearing preservation at 3 years, 5 years, 10 years, and 15 years were 98%, 93%, 44%, and 17%, respectively. Of the 46 patients, 22 (48%) became completely bilaterally deaf, 17 (37%) retained unilateral serviceable hearing, and 7 (15%) retained bilateral serviceable hearing. The mean history of the disease course was 12 years (range 5-38 years). CONCLUSIONS: GKS was confirmed to provide long-term local tumor control for small- to medium-sized vestibular schwannomas and other types of tumors, although vestibular schwannomas in patients with NF2 responded less well than did unilateral sporadic vestibular schwannomas. Phenotype is the most strongly predictive factor of final outcome after GKS for patients with NF2. The risk for loss of hearing is high, whereas the risk for other cranial nerve complications is low.

Clinical and pathological analysis of benign brain tumors resected after Gamma Knife surgery.

OBJECT: The goal of this study was to assess the clinical and pathological features of benign brain tumors that had been treated with Gamma Knife surgery (GKS) followed by resection. METHODS: In this retrospective chart review, the authors identified 61 patients with intracranial benign tumors who had undergone neurosurgical intervention after GKS. Of these 61 patients, 27 were male and 34 were female; mean age was 49.1 years (range 19-73 years). There were 24 meningiomas, 18 schwannomas, 14 pituitary adenomas, 3 hemangioblastomas, and 2 craniopharyngiomas. The interval between GKS and craniotomy was 2-168 months, with a median of 24 months; for 7 patients, the interval was 10 years or longer. For 21 patients, a craniotomy was performed before and after GKS; in 9 patients, pathological specimens were obtained before and after GKS. A total of 29 patients underwent GKS at the Beijing Tiantan Hospital. All specimens obtained by surgical intervention underwent histopathological examination. RESULTS: Most patients underwent craniotomy because of tumor recurrence and/or exacerbation of clinical signs and symptoms. Neuroimaging analyses indicated tumor growth in 42 patients, hydrocephalus in 10 patients with vestibular schwannoma, cystic formation with mass effect in 7 patients, and tumor hemorrhage in 13 patients, of whom 10 had pituitary adenoma. Pathological examination demonstrated that, regardless of the type of tumor, GKS mainly induced coagulative necrosis of tumor parenchyma and stroma with some apoptosis and, ultimately, scar formation. In addition, irradiation induced vasculature stenosis and occlusion and tumor degeneration as a result of reduced blood supply. GKS-induced vasculature reaction was rarely observed in patients with pituitary adenoma. Pathological analysis of tumor specimens obtained before and after GKS did not indicate increased tumor proliferation after GKS. CONCLUSIONS: Radiosurgery is effective for intracranial benign tumors of small size and deep location and for tumor recurrence after surgical intervention; it is not effective for intracranial tumors with symptomatic mass effect. The radiobiological effects of stereotactic radiosurgery on the benign tumors are mainly caused by cellular and vascular mechanisms. Among the patients in this study, high-dose irradiation did not increase tumor proliferation. GKS can induce primary and secondary effects in tumors, which could last more than 10 years, thereby warranting long-term follow-up after GKS.