Long-term surveillance in an infant with spontaneous obliteration of pial arteriovenous malformation and large intranidal aneurysm: A unique case observation.

Background: Spontaneous obliteration of untreated cerebral arteriovenous malformations (AVMs) is rare, occurring in <1% of cases, and is even less common in pediatric populations. The mechanisms driving spontaneous regression of brain AVMs remain poorly understood, and long-term surveillance in pediatric patients is infrequently documented. Case Description: The authors reported a remarkably rare instance of spontaneous thrombosis in a pial AVM accompanied by a large intranidal aneurysm in a 10-month-old infant, initially presenting with a nocturnal seizure. Diagnostic imaging revealed a ruptured intranidal aneurysm causing acute hemorrhage in the left anterior interhemispheric subdural space, extending into adjacent areas. Further, magnetic resonance imaging (MRI) and magnetic resonance angiography delineated the AVM in the left superior frontal gyrus, associated with a thrombosed aneurysm and surrounding edema. Cerebral angiography confirmed the AVM's origin from the left anterior cerebral artery, displaying early venous drainage and small, indirect feeders not amenable to endovascular treatment. Over time, serial imaging showed the aneurysm's transition from partial to complete thrombosis. Subsequent MRIs and angiographic assessments up to age 10 confirmed complete resolution of the AVM and aneurysm, with focal hyperemia persisted until age 16, when recurrent AVM was identified. Conclusion: We document a rare spontaneous regression of a pial AVM with an intranidal aneurysm influenced by specific vascular factors. Despite this, spontaneous thrombosis should not replace vigilant long-term monitoring in pediatric neurovascular care.

Associations of Brain Arteriovenous Malformation-Related Factors with Epileptic Seizure Presentations.

BACKGROUND: Arteriovenous malformations (AVMs) are abnormal tangles of arteries and veins that connect directly without an intervening capillary bed. Epileptic seizures are the second most common symptom in patients with brain AVMs, occurring in 30 to 50% of cases. However, the exact mechanism of epileptic seizure development in AVMs remains unclear. In this study, we aimed to investigate the factors associated with epileptic seizures in patients with brain arteriovenous malformation (AVMs) in Kazakhstan. METHODS: A case-control study was conducted, which included 163 patients diagnosed with brain AVMs. Demographic and clinical data were collected and analyzed, and multivariate logistic regression was built to assess the factors associated with seizures in brain AVMs. RESULTS: from this rupture of vessels OR = 0.36 95% CI (0.14-0.91, a medium-to-high Spetzler-Martin score (III-V) OR = 6.16 (2.14-17.69) and OR = 3.05 (1.08-8.68), respectively), location in brain cortex (frontal lobe OR = 6.16 (2.04-18.54), parietal lobe OR = 9.37 (3.26-26.91), temporal lobe OR = 4.57 (1.56-13.36), occipital lobe OR = 0.27 (0.08-0.91), and the presence of hemiparesis OR = 0.12 (0.02-0.66) in adverse outcomes were statistically significantly associated with the presence of epileptic seizures in brain arteriovenous malformations patients. CONCLUSIONS: To conclude, this contributed to model factors associated with brain arteriovenous malformations that are linked to epileptic seizures.

Reliability of study endpoint adjudication in a pragmatic trial on brain arteriovenous malformations.

BACKGROUND: The results of a clinical trial are given in terms of primary and secondary outcomes that are obtained for each patient. Just as an instrument should provide the same result when the same object is measured repeatedly, the agreement of the adjudication of a clinical outcome between various raters is fundamental to interpret study results. The reliability of the adjudication of study endpoints determined by examination of the electronic case report forms of a pragmatic trial has not previously been tested. METHODS: The electronic case report forms of 62/434 (14%) patients selected to be observed in a study on brain AVMs were independently examined twice (4 weeks apart) by 8 raters who judged whether each patient had reached the following study endpoints: (1) new intracranial hemorrhage related to AVM or to treatment; (2) new non-hemorrhagic neurological event; (3) increase in mRS ≥1; (4) serious adverse events (SAE). Inter and intra-rater reliability were assessed using Gwet's AC1 (κG) statistics, and correlations with mRS score using Cramer's V test. RESULTS: There was almost perfect agreement for intracranial hemorrhage (92% agreement; κG = 0.84 (95%CI: 0.76-0.93), and substantial agreement for SAEs (88% agreement; κG = 0.77 (95%CI: 0.67-0.86) and new non-hemorrhagic neurological event (80% agreement; κG = 0.61 (95%CI: 0.50-0.72). Most endpoints correlated (V = 0.21-0.57) with an increase in mRS of ≥1, an endpoint which was itself moderately reliable (76% agreement; κG = 0.54 (95%CI: 0.43-0.64). CONCLUSION: Study endpoints of a pragmatic trial were shown to be reliable. More studies on the reliability of pragmatic trial endpoints are needed.

Application of artificial intelligence in brain arteriovenous malformations: Angioarchitectures, clinical symptoms and prognosis prediction.

BACKGROUND: Artificial intelligence (AI) has rapidly advanced in the medical field, leveraging its intelligence and automation for the management of various diseases. Brain arteriovenous malformations (AVM) are particularly noteworthy, experiencing rapid development in recent years and yielding remarkable results. This paper aims to summarize the applications of AI in the management of AVMs management. METHODS: Literatures published in PubMed during 1999-2022, discussing AI application in AVMs management were reviewed. RESULTS: AI algorithms have been applied in various aspects of AVM management, particularly in machine learning and deep learning models. Automatic lesion segmentation or delineation is a promising application that can be further developed and verified. Prognosis prediction using machine learning algorithms with radiomic-based analysis is another meaningful application. CONCLUSIONS: AI has been widely used in AVMs management. This article summarizes the current research progress, limitations and future research directions.

Unruptured Brain Arteriovenous Malformations: A Systematic Review and Meta-Analysis of Mortality and Morbidity in Aruba-Eligible Studies.

BACKGROUND: Treating unruptured brain arteriovenous malformations (bAVMs) represent significant challenges, with numerous uncertainties still in debate. The ARUBA trial induced further investigation into optimal management strategies for these lesions. Here, we present a systematic-review and meta-analysis focusing on ARUBA-eligible studies, aiming to correlate patient data with outcomes and discuss key aspects of these studies. METHODS: Following PRISMA guidelines, we conducted a systematic-review. Variables analyzed included bAVM Spetzler-Martin (SM) grade, treatment modalities, and outcomes such as mortality and neurological deficits. We compared studies with a minimum of 50% cases classified as SM 1-2 lesions and those with less than 50% in this category. Similarly, a comparison between studies with at least 50% microsurgery-cases and those with less than 50% was performed. We examined correlations between mortality incidence, SM distribution, and treatment modalities. RESULTS: Our analysis included 16 studies with 2.417 patients. The frequency of bAVMs SM-grade 1-2 ranged from 44% to 76%, SM-grade 3 from 19% to 48%, and SM 4-5 from 5 to 23%. Notably, studies with more than 50% cases presenting lesions SM-grade 1-2 presented significantly lower mortality rates than those with less than 50% cases of SM 1-2 lesions (P < 0.001). No significant difference in mortality rates or neurological deficits was identified between studies with more than 50% of microsurgery-cases and those with less than 50%. CONCLUSIONS: The analysis revealed that studies with a higher proportion of bAVMs presenting SM 1-2 lesions were associated with lower mortality rates. Mortality did not show a significant association with treatment modalities.

Deep Learning Detection and Segmentation of Brain Arteriovenous Malformation on Magnetic Resonance Angiography.

BACKGROUND: The delineation of brain arteriovenous malformations (bAVMs) is crucial for subsequent treatment planning. Manual segmentation is time-consuming and labor-intensive. Applying deep learning to automatically detect and segment bAVM might help to improve clinical practice efficiency. PURPOSE: To develop an approach for detecting bAVM and segmenting its nidus on Time-of-flight magnetic resonance angiography using deep learning methods. STUDY TYPE: Retrospective. SUBJECTS: 221 bAVM patients aged 7-79 underwent radiosurgery from 2003 to 2020. They were split into 177 training, 22 validation, and 22 test data. FIELD STRENGTH/SEQUENCE: 1.5 T, Time-of-flight magnetic resonance angiography based on 3D gradient echo. ASSESSMENT: The YOLOv5 and YOLOv8 algorithms were utilized to detect bAVM lesions and the U-Net and U-Net++ models to segment the nidus from the bounding boxes. The mean average precision, F1, precision, and recall were used to assess the model performance on the bAVM detection. To evaluate the model's performance on nidus segmentation, the Dice coefficient and balanced average Hausdorff distance (rbAHD) were employed. STATISTICAL TESTS: The Student's t-test was used to test the cross-validation results (P < 0.05). The Wilcoxon rank test was applied to compare the median for the reference values and the model inference results (P < 0.05). RESULTS: The detection results demonstrated that the model with pretraining and augmentation performed optimally. The U-Net++ with random dilation mechanism resulted in higher Dice and lower rbAHD, compared to that without that mechanism, across varying dilated bounding box conditions (P < 0.05). When combining detection and segmentation, the Dice and rbAHD were statistically different from the references calculated using the detected bounding boxes (P < 0.05). For the detected lesions in the test dataset, it showed the highest Dice of 0.82 and the lowest rbAHD of 5.3%. DATA CONCLUSION: This study showed that pretraining and data augmentation improved YOLO detection performance. Properly limiting lesion ranges allows for adequate bAVM segmentation. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 1.

A simple but effective solution for proximal mark absence on some microcatheters in intracranial aneurysm embolization: Technical note.

Background: Endovascular coil embolization is increasingly being used for the treatment of intracranial aneurysms and other pathologies such as arteriovenous (AV) malformations and AV fistulas. Appropriate embolization technique requires a microcatheter with two radiopaque marks, one proximal and one distal. We present an alternative coils deployment technique for intracranial aneurysms, using a microcatheter without a proximal radiopaque mark. Methods: We describe the technique for embolization that was used in a 36-year-old female patient, in which we used a microcatheter without a proximal radiopaque mark for coil embolization of an intracranial aneurysm. Results: We used a Headway Duo flow directed microcatheter for a coiling embolization of an intracranial aneurysm, solving the absence of the proximal radiopaque mark by cannulating the microcatheter with a Traxcess 0.014 microguidewire, and placing an external mark on the screen in the proximal portion of the microguidewire 30 mm radiopaque tip to indirectly mark the proximal mark of the microcatheter. Conclusion: There is scarce evidence supporting the use of microcatheters with no proximal radiopaque mark for coil embolization. This report attempts to disclose how an easy and simple technique can be used as a rescue method to solve the proximal radiopaque mark absence during endovascular coil release procedures. To the best of our knowledge, this technique has not been previously described; therefore, its use is not widespread among neurointerventionists.

Management of Adult Unruptured Brain Arteriovenous Malformations: An Updated Network Meta-Analysis.

The management of unruptured brain arteriovenous malformations (ubAVMs) is a complex challenge to neurovascular practitioners. This meta-analysis aimed to identify the optimal management of ubAVMs comparing conservative management, embolization, radiosurgery, microsurgical resection, and multimodality. The search strategy was developed a priori according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the Ovid Medline, Embase, Web of Science, and Cochrane Library databases to identify relevant papers. Using R version 4.1.1., a frequentist network meta-analysis was conducted to compare different management modalities for the ubAVMs. Overall, the conservative group had the lowest risk of rupture (P-score=0.77), and the lowest rate of complications was found in the conservative group (P-score=1). Among different interventions, the multimodality group had the highest rupture risk (P-score=0.34), the lowest overall complications (P-score=0.75), the best functional improvement (P-score=0.65), and the lowest overall mortality (P-score=0.8). However, multimodality treatment showed a significantly higher risk of rupture (odds ratio [OR]=2.13; 95% confidence interval [95% CI]=1.18-3.86) and overall complication rate (OR=5.56; 95% CI=3.37-9.15) compared to conservative management; nevertheless, there were no significant differences in overall mortality or functional independence when considered independently. Conservative management is associated with the lowest rupture risk and complication rate overall. A multimodal approach is the best option when considering mortality rates and functional improvement in the context of existing morbidity/symptoms. Microsurgery, embolization, and radiosurgery alone are similar to the natural history in terms of functional improvement and mortality, but have higher complication rates.

Brain arteriovenous malformations of the middle cerebral artery region: image characteristics and endovascular treatment based on a new classification system.

BACKGROUND: To date, few studies have investigated the use of endovascular treatment (EVT) for brain arteriovenous malformations (BAVMs) in the supplying area of the middle cerebral artery (MCA). Moreover, no suitable classification was aimed at EVT for MCA-BAVMs. Therefore, this study proposed a new classification. METHODS: This study retrospectively collected 135 MCA­BAVMs. They were classified into four types: Type I BAVMs located above the M1 segment; Type II BAVMs located in the region around the Sylvian fissure; and Type III BAVMs located in the supplying region of the M4 segment and subdivided into types IIIa and IIIb. The relevance of various types of MCA-BAVMs and their imaging characteristics and EVT outcomes was analyzed by ordinary one-way ANOVA, Tukey's multiple comparisons test and the chi-square test. RESULTS: The 135 patients averaged 33.8 ± 14.7 years and included 75 females (55.6%, 75/135). Among them, 15 (11.1%, 15/135), 16 (11.9%, 16/135), 54 (40%, 54/135), and 50 (37%, 50/135) MCA-BAVMs were type I, II, IIIa and IIIb, respectively. After EVT, a good outcome was achieved in 97% of patients. Statistical analysis showed that type I BAVMs were smaller than type II and IIIb BAVMs (P value < 0.05), and type IIIb BAVMs were larger than type I and IIIa BAVMs (P value < 0.05). Deep vein involvement in type I and IIIb BAVMs was more common than in other types (P value < 0.05), and intraventricular hemorrhage (IVH) was also more common (P value < 0.05). The normal morphology in type IIIb was less than that in the other types (P value < 0.05). Type IIIa BAVMs had a higher degree than other types (P value < 0.05). CONCLUSION: The present study demonstrated that the new classification of MCA-BAVMs can be used to evaluate imaging characteristics and EVT outcomes in different types. In addition, EVT may be a safe treatment modality for MCA­BAVMs.

Exosomal miR-3131 derived from endothelial cells with KRAS mutation promotes EndMT by targeting PICK1 in brain arteriovenous malformations.

AIMS: To explore the underlying mechanism by which low-frequency KRAS mutations result in extensive EndMT occurrence. METHODS: Exosomes derived from primarily cultured brain arteriovenous malformation (bAVMs) and human umbilical vein endothelial cells (HUVECs) transfected with KRASG12D , KRASWT , or KRASNC lentiviruses were isolated, and their effects on HUVECs were identified by western blotting and immunofluorescence staining. The expression levels of exosomal microRNAs (miRNAs) were evaluated by miRNA microarray, followed by functional experiments on miR-3131 and detection of its downstream target, and miR-3131 inhibitor in reversing the EndMT process induced by KRASG12D -transfected HUVECs and bAVM endothelial cells (ECs) were explored. RESULTS: Exosomes derived from KRASG12D bAVM ECs and KRASG12D -transfected HUVECs promoted EndMT in HUVECs. MiR-3131 levels were highest in the exosomes of KRASG12D -transfected HUVECs, and HUVECs transfected with the miR-3131 mimic acquired mesenchymal phenotypes. RNA-seq and dual-luciferase reporter assays revealed that PICK1 is the direct downstream target of miR-3131. Exosomal miR-3131 was highly expressed in KRASG12D bAVMexos compared with non-KRAS-mutant bAVMexos or HUVECexos . Finally, a miR-3131 inhibitor reversed EndMT in HUVECs treated with exosomes or the supernatant of KRASG12D -transfected HUVECs and KRASG12D bAVM ECs. CONCLUSION: Exosomal miR-3131 promotes EndMT in KRAS-mutant bAVMs, and miR-3131 might be a potential biomarker and therapeutic target in KRASG12D -mutant bAVMs.

External validation of the Ruptured Arteriovenous Malformation Grading Scale (RAGS) in a multicenter adult cohort.

PURPOSE: While Ruptured Arteriovenous Malformation Grading Scale (RAGS) has recently been validated in children, the literature lacks validation on adults exclusively. Therefore, we aimed to determine the validity of RAGS on the external multicenter adult cohort and compare its accuracy with other scales. METHODS: A retrospective analysis was performed in five neurosurgical departments to extract patients who presented with the first episode of acute brain arteriovenous malformation (bAVM) rupture between 2012 and 2019. Standard logistic regression and area under the receiver operating curve (AUROC) calculations were performed to determine the value of the following scales: intracerebral hemorrhage (ICH), AVM-associated ICH (AVICH), Spetzler-Martin (SM), Supplemented SM (Supp-SM), Hunt and Hess (HH), Glasgow Coma Scale (GCS), World Federation of Neurological Surgeons (WFNS), and RAGS to predict change in categorical and dichotomized modified Rankin Scale (mRS) across three follow-up periods: within the 6 months, 6 months to 1 year, and above 1 year. RESULTS: Sixty-one individuals with a mean age of 43.6 years were included. The RAGS outperformed other grading scales during all follow-up time frames. It showed AUROC of 0.78, 0.74, and 0.71 at the first 6 months, between 6 and 12 months, and after 12 months of follow-up, respectively, when categorized mRS was applied, while corresponding values were 0.79, 0.76, and 0.73 for dichotomized mRS, respectively. CONCLUSION: The RAGS constitutes a reliable scale predicting clinical outcomes following bAVM rupture among adults. Furthermore, the RAGS proved its generalizability across medical centers with varying treatment preferences.

Unruptured brain arteriovenous malformations causing seizures localize to one common brain network.

Seizures are a frequent symptom of unruptured brain arteriovenous malformations (bAVMs). However, the brain regions responsible for these seizures remain unclear. To identify the brain regions causally involved in bAVM-related seizures, we retrospectively reviewed 220 patients with unruptured bAVMs. Using voxel-based lesion-symptom mapping (VLSM) analyses, we tested whether individual brain regions were associated with unruptured bAVM-related seizures. The result revealed that unruptured bAVMs causing seizures are anatomically heterogeneous at the voxel level. Subsequently, lesion network mapping (LNM) analyses was performed to determine whether bAVMs causing seizures belonged to a distributed brain network. LNM analyses indicated that these lesions were located in a functional network characterized by connectivity to the left caudate and precuneus. Moreover, the discrimination performance of the identified seizure network was evaluated in discovery set by calculating the individualized network damage score and was tested in validation set. Based on the calculated network damage scores, patients were divided into low-, medium-, and high-risk groups. The prevalence of seizures significantly differed among the three risk categories in both discovery (p = .003) and validation set (p = .004). Finally, we calculated the percentage of voxels in the canonical resting-state networks that overlapped with the seizure-susceptible brain regions to investigate the involvement of resting-state networks. With an involvement percentage over 50%, the frontoparietal control (82.9%), limbic function (76.7%), and default mode network (69.3%) were considered to be impacted in bAVM-related seizures. Our study identified the seizure-susceptible brain regions for unruptured bAVMs, which could be a plausible neuroimaging biomarker in predicting possible seizures.

New approaches for brain arteriovenous malformations-related epilepsy.

BACKGROUND: The purpose of this review is to present the current literature and to highlight the most recent findings in brain arteriovenous malformations (bAVM)-related epilepsy research. METHODS: We searched Medline, PubMed, Biblioinserm, Cochrane Central to study the latest research reports about the different factors that could be responsible for the genesis of bAVM-related epilepsy. We analyzed if epileptogenesis has any characteristics traits and its relation with the vascular malformation. The results of different treatments on epilepsy were considered. Typical errors that may lead towards incorrect or worse management of the seizures for these patients were also examined. RESULTS: The development of bAVM results from multifactorial etiologies and bAVM-related epileptogenesis is likely specific for this pathology. Different types of evidence demonstrate a bidirectional relationship between bAVM and epilepsy. Currently, there is not enough published data to determine what may be the right management for these patients. CONCLUSIONS: A better understanding of epileptogenesis in conjunction with knowledge of the complex alterations of structures and functions following bAVM-related seizures is necessary. Identification of biomarkers that can identify subgroups most likely to benefit from a specific intervention are needed to help guide clinical management. A new concept for the treatment of epilepsy related to an unruptured bAVM that cannot be treated invasively is proposed as well as new therapeutic perspectives. The next necessary step will be to propose additional algorithms to improve the development of future trials.

State of the Art in the Role of Endovascular Embolization in the Management of Brain Arteriovenous Malformations-A Systematic Review.

As a significant cause of intracerebral hemorrhages, seizures, and neurological decline, brain arteriovenous malformations (bAVMs) are a rare group of complex vascular lesions with devastating implications for patients' quality of life. Although the concerted effort of the scientific community has improved our understanding of bAVM biology, the exact mechanism continues to be elucidated. Furthermore, to this day, due to the high heterogeneity of bAVMs as well as the lack of objective data brought by the lack of evaluative and comparative studies, there is no clear consensus on the treatment of this life-threatening and dynamic disease. As a consequence, patients often fall short of obtaining the optimal treatment. Endovascular embolization is an inherent part of multidisciplinary bAVM management that can be used in various clinical scenarios, each with different objectives. Well-trained neuro-interventional centers are proficient at curing bAVMs that are smaller than 3 cm; are located superficially in noneloquent areas; and have fewer, larger, and less tortuous feeding arteries. The transvenous approach is an emerging effective and safe technique that potentially offers a chance to cure previously untreatable bAVMs. This review provides the state of the art in all aspects of endovascular embolization in the management of bAVMs.

Brain AVMs-Related microRNAs: Machine Learning Algorithm for Expression Profiles of Target Genes.

INTRODUCTION: microRNAs (miRNAs) are a class of non-coding RNAs playing a myriad of important roles in regulating gene expression. Of note, recent work demonstrated a critical role of miRNAs in the genesis and progression of brain arteriovenous malformations (bAVMs). Accordingly, here we examine miRNA signatures related to bAVMs and associated gene expression. In so doing we expound on the potential prognostic, diagnostic, and therapeutic significance of miRNAs in the clinical management of bAVMs. METHODS: A PRISMA-based literature review was performed using PubMed/Medline database with the following search terms: "brain arteriovenous malformations", "cerebral arteriovenous malformations", "microRNA", and "miRNA". All preclinical and clinical studies written in English, regardless of date, were selected. For our bioinformatic analyses, miRWalk and miRTarBase machine learning algorithms were employed; the Kyoto Encyclopedia of Genes and Genomes (KEGG) database was quired for associated pathways/functions. RESULTS: four studies were ultimately included in the final analyses. Sequencing data consistently revealed the decreased expression of miR-18a in bAVM-endothelial cells, resulting in increased levels of vascular endodermal growth factor (VEGF), Id-1, matrix metalloproteinase, and growth signals. Our analyses also suggest that the downregulation of miR-137 and miR-195* within vascular smooth muscle cells (VSMCs) may foster the activation of inflammation, aberrant angiogenesis, and phenotypic switching. In the peripheral blood, the overexpression of miR-7-5p, miR-629-5p, miR-199a-5p, miR-200b-3p, and let-7b-5p may contribute to endothelial proliferation and nidus development. The machine learning algorithms employed confirmed associations between miRNA-related target networks, vascular rearrangement, and bAVM progression. CONCLUSION: miRNAs expression appears to be critical in managing bAVMs' post-transcriptional signals. Targets of microRNAs regulate canonical vascular proliferation and reshaping. Although additional scientific evidence is needed, the identification of bAVM miRNA signatures may facilitate the development of novel prognostic/diagnostic tools and molecular therapies for bAVMs.

A Prospective Study Comparing the Three-Dimensional Rotational Angiography and Two-Dimensional Digital Subtraction Angiography in Evaluation of Brain Arteriovenous Malformations.

Background: Complex angioarchitecture of brain arteriovenous malformations (BAVM) are often difficult to evaluate with standard imaging technique of digital subtraction angiography (DSA). These details are better provided by 3D rotational angiography (3D-RA). Objective: The aim of the study is to compare two-dimensional digital subtraction angiography (2D-DSA) and 3D rotational angiography in the evaluation of BAVM angiographic architecture. Materials and Methods: 2D-DSA and 3D-RA of 167 consecutive patients with BAVM were analyzed for arterial feeders, nidal patterns, and detection of flow-related aneurysms, arteriovenous fistulous components, venous drainage, and draining vein stenosis. Results: 3D-RA detected a significantly higher number of aneurysms and draining venous stenoses (P < 0.001). The detected number of true intranidal aneurysms was significantly higher with 3D-RA (n = 94) vs 2D-DSA (n = 34) (P < 0.001). 2D-DSA has low sensitivity (43.1%) and specificity (73.4%) for detecting intranidal aneurysms. 3D-RA detected a significantly higher number (12.6%) of BAVM patients with feeding artery aneurysms as compared to 2D-DSA (8.4%), P value of 0.004. 3D-RA accurately depicted the distal course of dominant arterial feeders and fistulous sites in BAVMs. Direct arteriovenous communications were evident in 31.1% with 3D-RA, as compared to 2D-DSA (15%) with P value < 0.0001. A significantly higher number of draining vein stenosis was detected with 3D-RA (21.6%) as compared to 2D-DSA (13.2%), P value < 0.001. Conclusion: 3D-RA is better than 2D-DSA for detecting BAVM-associated flow-related aneurysms, distal course of the dominant arterial feeders, direct visualization of the fistulous components, deep venous drainage, and draining venous stenosis; findings imperative for making a prudent therapeutic decision.

Molecular and genetic mechanisms in brain arteriovenous malformations: new insights and future perspectives.

Brain arteriovenous malformations (bAVMs) are rare vascular lesions made of shunts between cerebral arteries and veins without the interposition of a capillary bed. The majority of bAVMs are asymptomatic, but some may be revealed by seizures and potentially life-threatening brain hemorrhage. The management of unruptured bAVMs remains a matter of debate. Significant progress in the understanding of their pathogenesis has been made during the last decade, particularly using genome sequencing and biomolecular analysis. Herein, we comprehensively review the recent molecular and genetic advances in the study of bAVMs that not only allow a better understanding of the genesis and growth of bAVMs, but also open new insights in medical treatment perspectives.

Cellular loci involved in the development of brain arteriovenous malformations.

Brain arteriovenous malformations (bAVMs) are abnormal vessels that are prone to rupture, causing life-threatening intracranial bleeding. The mechanism of bAVM formation is poorly understood. Nevertheless, animal studies revealed that gene mutation in endothelial cells (ECs) and angiogenic stimulation are necessary for bAVM initiation. Evidence collected through analyzing bAVM specimens of human and mouse models indicate that cells other than ECs also are involved in bAVM pathogenesis. Both human and mouse bAVMs vessels showed lower mural cell-coverage, suggesting a role of pericytes and vascular smooth muscle cells (vSMCs) in bAVM pathogenesis. Perivascular astrocytes also are important in maintaining cerebral vascular function and take part in bAVM development. Furthermore, higher inflammatory cytokines in bAVM tissue and blood demonstrate the contribution of inflammatory cells in bAVM progression, and rupture. The goal of this paper is to provide our current understanding of the roles of different cellular loci in bAVM pathogenesis.

Transvenous embolization of hemorrhagic brain arteriovenous malformations: Case reports and literature review.

Introduction: Transvenous embolization (TVE) has been proven to be safe and feasible as an alternative management of brain arteriovenous malformations (AVMs). We presented four patients with a hemorrhagic brain AVM who underwent TVE and reviewed the relevant literature. Methods: Four patients underwent TVE of a hemorrhagic brain AVM in our center between July 2019 and July 2020. We retrospectively collected and analyzed the clinical and imaging data of these patients and those reported in previously published studies. Results: Four patients with a hemorrhagic brain AVM were included. Nidus sizes ranged from 0.79 to 2.56 cm. Spetzler-Martin grade ranged from grade II to grade III. The AVM nidus was located in a deep brain region in three patients. One patient underwent TVE alone and three underwent combined transarterial and transvenous approaches. Digital subtraction angiography (DSA) demonstrated complete obliteration of the vascular malformation after embolization in all four patients. Three patients were independent [modified Rankin Scale (mRS) score ≤ 2] at discharge. All four patients were independent at the last follow-up. AVM obliteration was confirmed in all four patients at the last angiographic follow-up. Conclusion: Transvenous embolization can be used as an alternative treatment for contemporary management of brain AVMs, appropriate patient selection is essential to achieve a good clinical outcome.

Critical Appraisal of Randomized Controlled Trials on Unruptured Brain Arteriovenous Malformations.

OBJECTIVE: Brain arteriovenous malformations management remains controversial despite the numerous, available treatment options. Randomized controlled trials (RCTs) theoretically provide the strongest evidence for the assessment of any therapeutic intervention. However, poorly designed RCTs may be associated with biases, inaccuracies, and misleading conclusions. The purpose of our study is to assess reporting transparency and methodological quality of the existing RCTs. METHODS: A search was performed in the PubMed, Scopus, Embase, clinicaltrials.gov, and Cochrane databases. The search was limited to English literature. We included all published RCTs reporting on the management of unruptured brain arteriovenous malformations. The eligible studies were evaluated by 5 blinded raters with the CONsolidated Standards of Reporting Trials 2010 statement and the risk-of-bias 2 tool. The inter-rater agreement was assessed with the Fleiss' Kappa. RESULTS: A randomized trial of unruptured brain arteriovenous malformations (ARUBA) and treatment of brain arteriovenous malformations (TOBAS) trials were evaluated. ARUBA achieved high CONsolidated standards of reporting trials compliance, while TOBAS showed a moderate one. In ARUBA the introduction, discussion, and other information sections reached the highest compliance rate (80%-86%). The lowest rates were recorded in the results and the methods (62% and 73%, respectively). The inter-rater agreement was moderate to substantial (54.1% to 78.4%). All the examined studies demonstrated a high risk of bias, mainly related to ill-defined intended interventions, missing outcome data, and selection of the reported results. CONCLUSIONS: Our study confirmed the high risk of bias mainly attributed to several protocol violations, deviations, minimal external validity and selection, attrition, and allocation biases of the ARUBA trial. Analysis of the TOBAS trial revealed a moderate overall reporting clarity and a high risk of bias.