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BACKGROUND: To assess the long-term outcome of large brain arteriovenous malformations (AVMs) (volume > 10 ml) underwent combined embolization and stereotactic radiosurgery (E+SRS) versus SRS alone. METHODS: Patients were recruited from a nationwide multicenter prospective collaboration registry (MATCH study, August 2011-August 2021) and categorized into E+SRS and SRS alone cohorts. Propensity score-matched survival analysis was employed to control for potential confounding variables. The primary outcome was a composite event of non-fatal hemorrhagic stroke or death. Secondary outcomes were favorable patient outcomes, AVM obliteration, favorable neurological outcomes, seizure, worsened mRS score, radiation-induced changes (RIC), and embolization complications. Furthermore, the efficacy of distinct embolization strategies was evaluated. Hazard ratios (HRs) were computed utilizing Cox proportional hazard models. RESULTS: Among 1063 AVMs who underwent SRS with or without prior embolization, 176 patients met the enrollment criteria. Following propensity score matching, the final analysis encompassed 98 patients (49 pairs). Median (interquartile range) follow-up duration for primary outcomes spanned 5.4 (2.7-8.4) years. Overall, the E+SRS strategy demonstrated a trend toward reduced incidence of primary outcomes compared to the SRS alone strategy (1.44 vs 2.37 per 100 patient-years; HR, 0.58 [95 % CI, 0.17-1.93]). Regardless of embolization degree or strategy, stratified analyses further consistently revealed a similar trend, albeit without achieving statistical significance. Secondary outcomes generally exhibited equivalence, but the combined approach showed potential superiority in most measures. CONCLUSIONS: This study suggests a trend toward lower long-term non-fatal hemorrhagic stroke or death risks with the E+SRS strategy when compared to SRS alone in large AVMs (volume > 10 ml).

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This study by Sasahara et al. explores the role of ephrin A1 in brain arteriovenous malformations (AVM) using DNA microarray analysis, quantitative real-time RT-PCR, and immunohistochemistry. The research identifies significant upregulation of ephrin A1 in AVM, suggesting its potential involvement in the abnormal vascular architecture characteristic of this condition. The study's innovative methodology and thorough exploration of gene expression patterns contribute valuable insights into AVM pathogenesis, highlighting ephrin A1 as a potential therapeutic target. However, the study's limitations include clinical variability among patient samples and the use of draining veins as controls, which may affect the robustness of the findings. Future research should address these limitations by using more homogeneous samples and expanding the investigation to include other ephrin family members. This could provide a broader understanding of ephrin signaling in AVM and guide the development of targeted therapies.

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Background: Brain arteriovenous malformation (BAVM) is one of the most common causes of cerebral hemorrhage in children. The effectiveness of one-stop hybrid operation in the treatment of BAVM in adults has been widely confirmed, but there are few study for the case in children. The aim of this study was to retrospectively analyze of the role and significance of one-stop hybrid surgery versus microsurgery in the treatment of BAVM in children. Methods: A total of 57 children (≤18 years old) with BAVM who were admitted to The 900th Hospital and Fujian Children's Hospital between September 2018 and August 2022 were retrospectively analyzed. According to the inclusion and exclusion criteria, 38 patients were included, and they were divided into a microsurgical group (25 patients) and a hybrid operation group (13 patients) according to the treatment modality. The following clinical characteristics were observed: sex, age, initial symptoms, presence or absence of signs, Glasgow Coma Scale (GCS) score, Hunt-Hess grade, imaging characteristics such as the location of the BAVM, Spetzler-Martin (S-M) grade, presence of intraventricular hemorrhage, treatment and prognostic indicators such as intraoperative blood loss, operation time, imaging cure, postoperative complications, length of hospital stay, and 3- and 6-month modified Rankin score (mRS) after the operation. Results: The proportions of female patients (P=0.042), patients whose BAVM were located in the supratentorial region (P=0.034) and patients whose S-M grade was above grade III (P=0.003) were greater in the hybrid operation group than those in the microsurgical group. The intraoperative blood loss (P<0.001), operation time (P<0.001) and postoperative hospital stay (P=0.024) of patients in the microsurgical group were greater than those in the hybrid operation group. The presence of signs and the S-M grade may be relevant factors in predicting the surgical approach, and the probability of selecting a hybrid operation for each step of increasing the S-M grade was 3.046 times that of microsurgery. Conclusions: A one-stop hybrid operation is effective and safe for the treatment of BAVM in children. High S-M grades of BAVM are more suitable for hybrid operation.

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Arteriovenous malformation of the brain (bAVM) is a vascular phenotype related to brain defective angiogenesis. Involved vessels show impaired expression of vascular differentiation markers resulting in the arteriolar to venule direct shunt. In order to clarify aberrant gene expression occurring in bAVM, here we describe results obtained by methylome analysis performed on endothelial cells (ECs) isolated from bAVM specimens, compared to human cerebral microvascular ECs. Results were validated by quantitative methylation-specific PCR and quantitative realtime-PCR. Differential methylation events occur in genes already linked to bAVM onset, as RBPJ and KRAS. However, among differentially methylated genes, we identified EPHB1 and several other loci involved in EC adhesion as well as in EC/vascular smooth muscle cell (VSMC) crosstalk, suggesting that only endothelial dysfunction might not be sufficient to trigger the bAVM phenotype. Moreover, aberrant methylation pattern was reported for many lncRNA genes targeting transcription factors expressed during neurovascular development. Among these, the YBX1 that was recently shown to target the arteridin coding gene. Finally, in addition to the conventional CpG methylation, we further considered the role of impaired CHG methylation, mainly occurring in brain at embryo stage. We showed as differentially CHG methylated genes are clustered in pathways related to EC homeostasis, as well as to VSMC-EC crosstalk, suggesting as impairment of this interaction plays a prominent role in loss of vascular differentiation, in bAVM phenotype.

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Nosebleeds and intracranial hemorrhage from brain arteriovenous malformations (bAVMs) are among the most devastating symptoms of patients with hereditary hemorrhagic telangiectasis (HHT). All available managements have limitations. We showed that intravenous delivery of soluble FMS-related tyrosine kinase 1 using an adeno-associated viral vector (AAV9-sFLT1) reduced bAVM severity of endoglin deficient mice. However, minor liver inflammation and growth arrest in young mice were observed. To identify AAV variants and delivery methods that can best transduce brain and nasal tissue with an optimal transduction profile, we compared 3 engineered AAV capsids (AAV.cc47, AAV.cc84 and AAV1RX) with AAV9. A single-stranded CBA promoter driven tdTomato transgene was packaged in these capsids and delivered intravenously (i.v.) or intranasally (i.n.) to wild-type mice. A CMV promoter driven Alk1 transgene was packaged into AAV.cc84 and delivered to PdgfbiCre;Alk1 f/f mice through i.v. injection followed by brain AVM induction. Transduced cells in different organs, vessel density and abnormal vessels in the bAVMs, and liver inflammation were analyzed histologically. Liver and kidney function were measured enzymatically. Compared to other viral vectors, AAV.cc84, after i.v. delivery, transduced a high percentage of brain ECs and few hepatocytes; whereas after i.n. delivery, AAV.cc84 transduced ECs and perivascular cells in the brain, and ECs, epithelial cells, and skeletal muscles in the nose with minimum hepatocyte transduction. No changes to liver or kidney function were detected. Delivery of AAV.cc84-Alk1 through i.v. to PdgfbiCre;Alk1 f/f mice reduced bAVM severity. In summary, we propose that AAV.cc84-Alk1 is a promising candidate for developing gene therapy in HHT patients.

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Nosebleeds and intracranial hemorrhage from brain arteriovenous malformations (bAVMs) are among the most devastating symptoms of patients with hereditary hemorrhagic telangiectasis (HHT). All available managements have limitations. We showed that intravenous (i.v.) delivery of soluble Feline McDonough Sarcoma (FMS)-related tyrosine kinase 1 using an adeno-associated viral vector (AAV9-sFLT1) reduced bAVM severity of endoglin deficient mice. However, minor liver inflammation and growth arrest in young mice were observed. To identify AAV variants and delivery methods that can best transduce brain and nasal tissue with an optimal transduction profile, we compared 3 engineered AAV capsids (AAV.cc47, AAV.cc84, and AAV1RX) with AAV9. A single-stranded CBA promoter driven tdTomato transgene was packaged in these capsids and delivered i.v. or intranasally (i.n.) to wild-type mice. A CMV promoter driven Alk1 transgene was packaged into AAV.cc84 and delivered to PdgfbiCre;Alk1f/f mice through i.v. followed by bAVM induction. Transduced cells in organs, vessel density, abnormal vessels in the bAVMs, and liver inflammation were analyzed histologically. Liver and kidney function were measured enzymatically. Compared to other viral vectors, AAV.cc84, after i.v. delivery, transduced a high percentage of brain endothelial cells (ECs) and few hepatocytes; whereas after i.n. delivery, AAV.cc84 transduced ECs and perivascular cells in the brain, and ECs, epithelial cells, and muscles in the nose with minimum hepatocyte transduction. No changes to liver or kidney function were detected. The delivery of AAV.cc84-Alk1 through i.v. to PdgfbiCre;Alk1f/f mice reduced bAVM severity. In summary, we propose that AAV.cc84-Alk1 is a promising candidate for developing gene therapy in HHT patients.

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Microsurgical resection is an effective method to treat brain arteriovenous malformations (BAVMs). Functional magnetic resonance imaging (fMRI) can evaluate the spatial relationship of nidus and eloquent. Diffuse BAVMs are related to poor outcomes postoperatively. The role of fMRI in evaluating outcomes in patients with different nidus types remains unclear. BAVM patients received microsurgical resection were included from a prospective, multicenter cohort study. All patients underwent fMRI evaluation preoperatively and were regularly followed up postoperatively. Diffuse BAVM is radiologically identified as nidus containing normal brain tissue interspersing between malformed vessels. Lesion-to-eloquent distance (LED) was calculated based on the relationship between nidus and eloquent. The primary outcome was 180-day unfavorable neurological status postoperatively. The risk of primary outcome was investigated within different BAVM nidus types. The LED's performance to predict poor outcome was evaluated using area under curve (AUC). 346 BAVM patients were included in this study. 93 (26.9%) patients were found to have a 180-day unfavorable outcome. Multivariate logistic analysis demonstrated LED (odd ratio [OR], 0.44; 0.34-0.57; P < 0.001) and mRS at admission (OR, 2.59; 1.90-3.54; P < 0.001) as factors of unfavorable outcome. Subgroup analysis showed LED and mRS at admission as factors of unfavorable outcome for patients with compact BAVMs (all P < 0.05), but not for patients with diffuse BAVMs. Subsequent analysis showed that LED performed poorly to predict the unfavorable outcome for patients with diffuse BAVMs, compared with patients with compact BAVMs (AUC as 0.69 vs. 0.86, P < 0.05). A larger cutoff value of LED to unfavorable outcome was found in patients with diffuse BAVMs (15 mm) compared with patients with compact BAVMs (4.7 mm). Usage of LED to evaluate postoperative outcome of patients with diffuse BAVMs differs from its use in patients with compact BAVMs. Specific assessment strategy considering BAVM nidus types could help improve patients' outcome. MITASREAVM cohort (unique identifier: NCT02868008, https://clinicaltrials.gov/study/NCT02868008?term=NCT02868008&rank=1 ).

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OBJECTIVE: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant disorder characterized by multiple vascular malformations. Brain arteriovenous malformations (bAVMs) are a significant manifestation of HHT. The surgical management of these lesions in patients with HHT remains debated, with limited literature on postoperative outcomes. The goal of this study was to evaluate the safety and efficacy of surgical treatment for bAVMs in patients with HHT and propose a treatment rationale based on a single-center experience. METHODS: This retrospective review included 20 patients diagnosed with HHT who underwent resection of 23 bAVMs at the Stanford University Medical Center between January 2007 and September 2023. Data were also collected on bAVMs treated conservatively, with embolization, or with radiosurgery at the authors' institution, for comparison. RESULTS: There were 16 Spetzler-Martin (SM) grade I, 6 SM grade II, and 1 SM grade IV bAVM. Six of the bAVMs presented with neurological symptoms (3 with hemorrhage and 3 with focal neurological deficits), while the rest were detected on routine screening. Complete excision was angiographically confirmed in all patients, with a mean overall hospital stay of 2.1 days and a mean follow-up of 36 months. Postoperative complications were limited to transient mild weakness in 2 patients, 1 of whom also had transient speech deficits, and visual field deficits in 3 patients, 2 of whom improved on long-term follow-up. CONCLUSIONS: In this most extensive surgical series published to date, resection of bAVMs in patients with HHT showed favorable outcomes with a low complication rate, suggesting that the benefits of surgery outweigh the risks, especially considering the potential cumulative lifetime risk of hemorrhage. MR arterial spin labeling was found to be the most sensitive noninvasive measure of detecting bAVMs in patients with HHT.

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Background: Few studies have investigated the safety of endovascular treatment (EVT) for brain arteriovenous malformations (BAVMs) via the anterior choroidal artery (AchA); therefore, this topic is worth studying further. Materials and methods: This was a retrospective study of 18 consecutive patients with BAVMs that were treated via the AchA with Onyx casting. Clinical and angiographic data were collected from the patients and analyzed. Results: The ages of the 18 patients ranged from 13 to 67 years (mean 39.2 ± 14.7 years), and eight patients were male (44.4%, 8/18). All patients had intracranial hemorrhages, including 2 with previous hemorrhages. All 18 BAVMs were mainly fed by the AchA and were treated via the AchA as the route for casting Onyx-18. Of the 13 single-trunk AchAs, after EVT, all proximal segments were preserved. For the 5 double-trunk AchAs, EVT was performed via the lower trunk; the proximal segments of the lower trunk were occluded for 2 of these AchAs. Among the 18 BAVMs, 16 niduses were embolized to different degrees, as were twelve associated aneurysms. Five (27.8%, 5/18) of the 18 patients experienced complications, and appropriate management was provided. During long-term follow-up, 14 (77.8%, 14/18) patients achieved good outcomes. Conclusion: EVT for BAVMs via the AchA has significant risks, but overall, good long-term outcomes were achieved in approximal 80% of the patients. This study highlights the potential of this technique for embolizing BAVMs via the AchA.

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We report a rare case of hereditary hemorrhagic telangiectasia (HHT) in a 4-month-old female infant with findings of child abuse. She presented with poor feeding, vomiting, and irritability after a short fall from the bed. Initial evaluation found subdural hematomas, persistent hypoxia, failure to thrive, a frenulum tear, facial lacerations, and bruising. The patient was admitted, and an extensive workup led to the diagnosis of brain and pulmonary arteriovenous malformations and finally the diagnosis of HHT. The subdural hematomas, cutaneous injuries, and oral injury were highly suspicious for child abuse and were reported to Child Protective Services and law enforcement for investigation simultaneous to the medical work-up. Her hospital course was complicated by progressive hypoxemia with radiographic evidence of several large pulmonary arteriovenous malformations, for which she underwent successful embolization. Her head injury was indeterminate for physical abuse in the setting of a medical condition predisposing to intracranial hemorrhage. A few weeks later, she was readmitted with repeat abusive injuries in the form of femur fractures. This case demonstrates the unique diagnostic dilemma when 2 diagnoses are occurring simultaneously-HHT and child abuse-and showcases the importance of a detailed family history, genetic testing, strong multidisciplinary collaboration with a holistic approach and medically informed Child Protective Services systems to ensure accurate diagnoses and safe disposition.

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In the field of cerebrovascular neurosurgery, intracranial aneurysms (IAs) have been occasionally associated with brain arteriovenous malformations (BAVMs), indicating a more aggressive clinical course, and increased rates of hemorrhage and rehemorrhage. Treatment of flow-related IAs in BAVMs remains debatable, with considerations for preventive intervention versus concurrent BAVM treatment. Managing such situations might be challenging, especially in determining which of the IAs or BAVMs should be treated first, and which treatment strategy would be most appropriate for each situation. A precise identification of the rupture site is required, whether it is the AVM nidus or the IA, for choosing the best treatment plans. We present a case of a 29-year-old male patient diagnosed with several intracranial vascular conditions: a ruptured anterior communicating artery (ACoA) aneurysm and an unruptured ophthalmic artery aneurysm, associated with a frontal BAVM. Moreover, we discussed the possible scenarios regarding the association of these conditions, highlighting their manifestations and the most suitable therapeutic approach for each. Thus, our exploration of the challenges and considerations involved in treating these intricate neurovascular conditions underscores the need for a customized approach for each patient's situation.

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The November 2013 online publication of ARUBA, the first multi-institutional randomized controlled trial for unruptured brain arteriovenous malformations (AVMs), has sparked over 100 publications in protracted debates METHODS: This study sought to examine inpatient management patterns of brain AVMs from 2009 to 2016 and observe if changes in U.S. inpatient management were attributable to the ARUBA publication using interrupted time series of brain AVM studies from the National Inpatient Sample data 2009-2016. Outcomes of interest were use of embolization, surgery, combined embolization and microsurgery, radiotherapy, and observation during that admission. An interrupted time series design compared management trends before and after ARUBA. Segmented linear regression analysis tested for immediate and long-term impacts of ARUBA on management. RESULTS: Elective and asymptomatic patient admissions declined 2009-2016. In keeping with the ARUBA findings, observation for unruptured brain AVMs increased and microsurgery decreased. However, embolization, radiosurgery, and combined embolization and microsurgery also increased. For ruptured brain AVMs, treatment modality trends remained positive with even greater rates of observation, embolization, and combined embolization and microsurgery occurring after ARUBA (data on radiosurgery were scarce). None of the estimates for the change in trends were statistically significant. CONCLUSIONS: The publication of ARUBA was associated with a decrease in microsurgery and increase in observation for unruptured brain AVMs in the US. However, inpatient radiotherapy, embolization, and combined embolization and surgery also increased, suggesting trends moved counter to ARUBA's conclusions. This analysis suggested that ARUBA had a small impact as clinicians rejected ARUBA's findings in managing unruptured brain AVMs.

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Current treatments of brain arteriovenous malformation (BAVM) are associated with considerable risks and at times incomplete efficacy. Therefore, a clinically consistent animal model of BAVM is urgently needed to investigate its underlying biological mechanisms and develop innovative treatment strategies. Notably, existing mouse models have limited utility due to heterogenous and untypical phenotypes of AVM lesions. Here we developed a novel mouse model of sporadic BAVM that is consistent with clinical manifestations in humans. Mice with BrafV600E mutations in brain ECs developed BAVM closely resembled that of human lesions. This strategy successfully induced BAVMs in mice across different age groups and within various brain regions. Pathological features of BAVM were primarily dilated blood vessels with reduced vascular wall stability, accompanied by spontaneous hemorrhage and neuroinflammation. Single-cell sequencing revealed differentially expressed genes that were related to the cytoskeleton, cell motility, and intercellular junctions. Early administration of Dabrafenib was found to be effective in slowing the progression of BAVMs; however, its efficacy in treating established BAVM lesions remained uncertain. Taken together, our proposed approach successfully induced BAVM that closely resembled human BAVM lesions in mice, rendering the model suitable for investigating the pathogenesis of BAVM and assessing potential therapeutic strategies.

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Brain arteriovenous malformations (bAVMs) are aberrant arteriovenous shunts through a vascular nidus with no intervening capillary beds. They are one of the commonest causes of spontaneous intracranial haemorrhage in children and may be associated with significant morbidity and mortality in cases of rupture. Treatment strategies include microsurgical resection, endovascular embolisation, stereotactic radiosurgery, multimodality treatment with a combination thereof, and particularly in high-grade bAVMs, conservative management. Clinicians involved in treating bAVMs need to have familiarity with the natural history pertaining to bAVMs in terms of risk of rupture, risk factors elevating rupture risk as well as understanding the clinical manifestations of bAVMs. This invited review serves to provide a synthesis on natural history and clinical presentation of bAVMs with particular focus in children to inform decision-making pertaining to management.

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BACKGROUND: Approximately 10% of people with hereditary hemorrhagic telangiectasia (HHT) have brain vascular malformations (VMs). Few reports describe de novo brain VM formation. International HHT Guidelines recommend initial brain VM screening upon HHT diagnosis in children but do not address rescreening. We aimed to confirm whether brain VMs can form de novo in patients with HHT. METHODS: The Brain Vascular Malformation Consortium HHT project is a 17-center longitudinal study enrolling patients since 2010. We analyzed the database for de novo VMs defined as those detected (1) on follow-up neuroimaging in a patient without previous brain VMs or (2) in a location distinct from previously identified brain VMs and reported those in whom a de novo VM could be confirmed on central neuroimaging review. RESULTS: Of 1909 patients enrolled, 409 (21%) had brain VMs. Seven patients were recorded as having de novo brain VMs, and imaging was available for central review in four. We confirmed that three (0.7% of individuals with brain VMs) had de novo brain VMs (two capillary malformations, one brain arteriovenous malformation) with intervals of six, nine, and 13 years from initial imaging. Two with de novo brain VMs were <18 years. The fourth patient, a child, did not have a de novo brain VM but had a radiologically confirmed increase in size of an existing brain arteriovenous malformation. CONCLUSIONS: Brain VMs can, albeit rarely, form de novo in patients with HHT. Given the potential risk of hemorrhage from brain VMs, regular rescreening in patients with HHT may be warranted.

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Brain Arteriovenous Malformations (bAVMs) are rare but high-risk developmental anomalies of the vascular system. Microsurgery through craniotomy is believed to be the mainstay standard treatment for many grades of bAVMs. However, a significant challenge emerges in the existing body of clinical studies on open surgery for bAVMs: the lack of reproducibility and comparability. This study aims to assess the quality of studies reporting clinical and surgical outcomes for bAVMs treated by open surgery and develop a reporting guideline checklist focusing on essential elements to ensure comparability and reproducibility. This is a systematic literature review that followed the PRISMA guidelines with the search in Medline, Embase, and Web of Science databases, for studies published between January 1, 2018, and December 1, 2023. Included studies were scrutinized focusing on seven domains: (1) Assessment of How Studies Reported on the Baseline Characteristics of the Patient Sample; (2) Assessment and reporting on bAVMs grading, anatomical characteristics, and radiological aspects; (3) Angioarchitecture Assessment and Reporting; (4) Reporting on Pivotal Concepts Definitions; (5) Reporting on Neurosurgeon(s) and Staff Characteristics; (6) Reporting on Surgical Details; (7) Assessing and Reporting Clinical and Surgical Outcomes and AEs. A total of 47 studies comprising 5,884 patients were included. The scrutiny of the studies identified that the current literature in bAVM open surgery is deficient in many aspects, ranging from fundamental pieces of information of methodology to baseline characteristics of included patients and data reporting. Included studies demonstrated a lack of reproducibility that hinders building cumulative evidence. A bAVM Open Surgery Reporting Guideline with 65 items distributed across eight domains was developed and is proposed in this study aiming to address these shortcomings. This systematic review identified that the available literature regarding microsurgery for bAVM treatment, particularly in studies reporting clinical and surgical outcomes, lacks rigorous scientific methodology and quality in reporting. The proposed bAVM Open Surgery Reporting Guideline covers all essential aspects and is a potential solution to address these shortcomings and increase transparency, comparability, and reproducibility in this scenario. This proposal aims to advance the level of evidence and enhance knowledge regarding the Open Surgery treatment for bAVMs.

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OBJECTIVE: Reducing the incidence of delayed postoperative hemorrhage (DPH) is one of the challenges in the surgical treatment of patients with brain arteriovenous malformations (bAVMs). This study aimed to identify several risk factors for DPH after bAVM resection and evaluate the impact of these risk factors in patients with bAVMs. METHODS: The authors retrospectively reviewed consecutive patients with bAVMs who underwent microsurgical resection between August 2011 and September 2021. Patients were divided into either the DPH group or non-DPH group based on whether they experienced a postoperative intracerebral hemorrhage into the bAVM bed within 14 days after bAVM resection. Factors associated with DPH were assessed using multivariate logistic regression analyses. RESULTS: A total of 1284 consecutive patients with bAVMs were evaluated; DPH events occurred in 18 patients (1.4%). There were several differences in vascular architecture between the two cohorts. A giant nidus, a nidus involved in the eloquent area, a periventricular nidus, and a nidus accompanied by venous ectasia were more likely to be associated with DPH events. The multivariate analysis identified two independent factors associated with DPH: maximum diameter (OR 1.44 per 1-cm increase, 95% CI 1.13-1.83) and periventricular lesion (OR 4.10, 95% CI 1.33-12.59). The area under the receiver operating characteristic curve for the maximum lesion diameter and development of DPH was 0.71 (95% CI 0.58-0.84). The cutoff value for the maximum bAVM diameter was 4.15 cm. Furthermore, patients with a giant bAVM, of which the maximum diameter was ≥ 4.15 cm, had a higher DPH risk after surgery (HR 5.79, 95% CI 2.01-16.67; p < 0.01). The incidence rates of DPH for patients with periventricular lesions were higher than those for patients without periventricular lesions (HR 4.50, 95% CI 1.77-11.40; p < 0.01). CONCLUSIONS: Patients with giant bAVMs or periventricular lesions are at higher risk for DPH after surgery. Strategies such as blood pressure control, preoperative embolization, intraoperative monitoring, and careful patient selection should be considered to reduce the risk of DPH in high-risk patients.

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OBJECTIVE: The brain arteriovenous malformation (BAVM) nidus compactness score (CS), determined on angiography, predicts BAVM recurrence after surgical resection among children with sporadic BAVMs. We measured the angiographic CS for BAVMs among children with hereditary hemorrhagic telangiectasia (HHT) to determine CS characteristics in this population. METHODS: A pediatric interventional neuroradiologist reviewed angiograms to determine the CS of BAVMs in children with HHT recruited to the BVMC. CS is based on overall nidus and perinidal anomalous vessel compactness. CS categories included 1 = diffuse nidus, 2 = intermediate nidus, and 3 = compact nidus. RESULTS: Forty-eight of 78 children (61.5%) with HHT and brain vascular malformations had a conventional angiogram; 47 (97.9%) angiograms were available. Fifty-four BAVMs were identified in 40 of these 47 children (85.1%). Of 54 BAVMs in children with HHT, CS was 1 in 7 (13%), 2 in 29 (53.7%), and 3 in 18 BAVMs (33.3%) compared with CS of 1 in six (26.1%), 2 in 15 (65.2%), and 3 in 2 BAVMs (8.7%) among 23 previously reported children with sporadic BAVMs, p = 0.045 (Fisher's exact). Seven children with HHT had intracranial hemorrhage: 4 had CS = 3, 1 had CS = 2, and 2 had CS = 1. CONCLUSIONS: A range of CSs exists across HHT BAVMs, suggesting it may be an angiographic measure of interest for future studies of BAVM recurrence and hemorrhage risk. Children with HHT may have more compact niduses compared to children with sporadic BAVMs. Additional research should determine whether CS affects hemorrhage risk or post-surgical recurrence risk in HHT-associated BAVMs, which could be used to direct BAVM treatment.

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BACKGROUND AND OBJECTIVE: Brain arteriovenous malformations (bAVMs) carry a risk of hemorrhage. We aim to identify factors associated with subsequent hemorrhages. METHODS: Systematic searches were conducted across the ScienceDirect, Medline, and Cochrane databases. Assessed risk factors included bAVM size, bAVM volume, hemorrhage and seizure presentations, presence of deep venous drainage, deep-seated bAVMs, associated aneurysms, and Spetzler-Martin grade. Subgroup analyses were conducted on prior treatments, hemorrhage presentation, AVM size, and type of management. RESULTS: The meta-analysis included 8 cohort studies and 2 trials, with 4,240 participants. Initial hemorrhage presentation (HR 2.41; 95% CI 1.94-2.98; p < 0.001), any deep venous drainage (HR 1.52; 95% CI 1.09-2.13; p = 0.01), and associated aneurysms (HR 1.78; 95% CI 1.41-2.23; p < 0.001) increased secondary hemorrhage risk. Conversely, higher Spetzler-Martin grades (HR 0.77; 95% CI 0.68-0.87; p < 0.001) and larger malformation volumes (HR 0.87; 95% CI 0.76-0.99; p = 0.04) reduced risk. Subgroups showed any deep venous drainage in patients without prior treatment (HR 1.64; 95% CI 1.25-2.15; p < 0.001), bAVM > 3 cm (HR 1.79; 95% CI 1.15-2.78; p = 0.01), and multimodal interventions (HR 1.69; 95% CI 1.12-2.53; p = 0.01) increased risk. The reverse effect was found for patients initially presented without hemorrhage (HR 0.79; 95% CI 0.67-0.93; p = 0.01). Deep bAVM was a risk factor in > 3 cm cases (HR 2.72; 95% CI 1.61-4.59; p < 0.001) and multimodal management (HR 2.77; 95% CI 1.66-4.56; p < 0.001). Kaplan-Meier analysis revealed increased hemorrhage risk for initial hemorrhage presentation, while cumulative survival was higher in intervened patients over 72 months. CONCLUSION: Significant risk factors for bAVMs hemorrhage include initial hemorrhage, any deep venous drainage, and associated aneurysms. Deep venous drainage involvement is a risk factor in cases without prior treatment, those with bAVM > 3 cm, and cases managed with multimodal interventions. Deep bAVM involvement also emerges as a risk factor in cases > 3 cm and those managed with multimodal approaches.

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Background: The increase in the collagen I (COL I)/COL III ratio enhances vessel wall stiffness and renders vessels less resistant to blood flow and pressure changes. Activated microglia enhance inflammation-induced fibrosis. Hypotheses: The COL I/COL III ratio in human and mouse brain arteriovenous malformations (bAVMs) is associated with bAVM hemorrhage, and the depletion of microglia decreases the COL I/COL III ratio and hemorrhage. Method: COL I, COL III, and hemorrhages were analyzed in 12 human bAVMs and 6 control brains, and mouse bAVMs induced in three mouse lines with activin receptor-like kinase 1 (n = 7) or endoglin (n = 7) deleted in the endothelial cells or brain focally (n = 5). The controls for the mouse study were no-gene-deleted litter mates. Mouse bAVMs were used to test the relationships between the Col I/Col III ratio and hemorrhage and whether the transient depletion of microglia reduces the Col I/Col III ratio and hemorrhage. Results: The COL I/COL III ratio was higher in the human and mouse bAVMs than in controls. The microhemorrhage in mouse bAVMs was positively correlated with the Col I/Col III ratio. Transient depletion of microglia reduced the Col I/Col III ratio and microhemorrhage. Conclusions: The COL I/COL III ratio in the bAVMs was associated with bAVM hemorrhage. The depletion of microglia reduced the bAVM Col I/Col III ratio and hemorrhage.

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