Prevalence and Predictors of Hereditary Hemorrhagic Telangiectasia and Capillary-Malformation Arteriovenous Malformation Syndrome Among Children with Neurovascular Malformations.

OBJECTIVE: To investigate the prevalence and predictors of hereditary hemorrhagic telangiectasia (HHT) and capillary-malformation arteriovenous malformation (CM-AVM) syndrome among children with no prior personal or family history of these diseases who presented with an arteriovenous shunt lesion. STUDY DESIGN: A retrospective chart review was completed on patients aged 0 through 21 years with arteriovenous shunt lesions evaluated at our Cerebrovascular Center. Diagnosis of definite or suspected HHT or CM-AVM was based on clinical features and genetic testing. Associations between final diagnosis and type and number of lesions, epistaxis, telangiectasias, CM, and pulmonary AVMs were assessed. RESULTS: Eighty-nine patients were included. Thirteen (14.6%) had definite HHT, 11 (12.4%) suspected HHT, and 4 (4.5%) definite CM-AVM. Having ≥2 episodes of epistaxis/year and ≥ 2 sites with telangiectasias were each associated with definite HHT (P < .001). Having ≥ 2 CM was associated with definite CM-AVM (P < .001). Pulmonary AVM was associated with increased odds of having definite HHT (OR = 6.3, 95% CI: 1.2-33.4). Multiple lesions (OR = 24.5, 95% CI: 4.5-134.8) and arteriovenous fistulas (OR = 6.2, 95% CI: 1.9-20.3) each increased the likelihood of having definite HHT or CM-AVM. Genetic testing was positive in 31% of patients tested. CONCLUSIONS: We recommend that children with neurovascular shunt lesions be offered genetic testing and undergo further evaluation for HHT and CM-AVM. Awareness and early diagnosis of these conditions is a critical step toward improving long-term outcomes and preventing disease-associated complications.

Second Report of the p.Leu874Pro Missense Variant in EPHB4 in a Family With Capillary Malformation-Arteriovenous Malformation Syndrome (CM-AVM) Syndrome.

Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is characterized by the presence of multiple small (1-2 cm in diameter) capillary malformations of the skin. This disorder has been described as two distinct entities: CM-AVM1 and CM-AVM2. The diagnosis of these disorders has been associated with pathogenic variants in the RASA1 gene for RASA1-CM-AVM, formerly known as CM-AVM1, and, more recently, the EPHB4 genes for EPHB4-CM-AVM, formerly known as CM-AVM2. Affected patients with either type may also have arteriovenous malformations and fistulas, which can cause life-threatening bleeding, congestive heart failure, or neurologic consequences such as stroke. These syndromes are typically either sporadic or inherited in an autosomal dominant manner with variable expressivity. We report a case series of a father and three daughters who have clinically diagnosed EPHB4-CM-AVM syndrome who were found to have a variant of uncertain significance (VUS) in EPHB4 that has only been reported once prior.

Management of Giant Type II Arteriovenous Malformation of the Neck With Heart Failure in a Pediatric Patient With Coil and NLE Embolization: A Case Report.

PURPOSE: Although arteriovenous malformations (AVMs) are typically benign lesions, massive ones can lead to severe complications, including heart failure. Notably, there is no standardized treatment for AVMs. Moreover, management of AVMs can be challenging when these lesions involve vital organ systems, such as the head and neck. In this report, we describe embolization of a massive cervical AVM in a pediatric patient with heart failure. CASE REPORT: A 10-year-old boy presented with severe heart failure secondary to a massive AVM in the neck (right side). Despite 3 unsuccessful arterial embolization procedures, venous embolization of the dominant outflow vein using a coil and n-butyl-2-cyanoacrylate, lipiodol, and ethanol proved effective, and symptoms, cerebral natriuretic peptide level (568-29 pg/mL), and echocardiography were significantly improved. Although residual AVM persisted in the right upper extremity for 6 months after surgery, his cardiac function remained preserved, and his activities of daily living have improved. CONCLUSION: Venous embolization is a valuable treatment modality for type II AVMs with a dominant outflow vein. However, considering the patient burden associated with large AVMs, multiple therapeutic interventions at appropriate intervals and long-term follow-up are important. CLINICAL IMPACT: We present a pediatric patient with a type II massive arteriovenous malformation (AVM) in the neck and severe heart failure. Despite undergoing 3 arterial embolization procedures, his condition remained unchanged. However, venous embolization of the dominant outflow vein resulted in a significant improvement in symptoms. This case emphasizes the importance of considering multiple and appropriately timed therapeutic interventions, particularly for massive AVMs, to optimize patient outcomes while minimizing treatment burden.

Hereditary haemorrhagic telangiectasia: A primer for the paediatrician.

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant condition characterised by small telangiectasias and larger multisystem arteriovenous malformations (AVMs). Common sites of AVMs include in the nose, lungs, brain and liver. These lesions are prone to rupture, leading to complications including recurrent epistaxis and significant haemorrhage. Pulmonary hypertension (PH) can also occur. This review presents an update on the genetics, clinical manifestations, management options, and screening recommendations for children with HHT.

Repeat single-session stereotactic radiosurgery for arteriovenous malformation: a systematic review and meta-analysis.

BACKGROUND: Stereotactic radiosurgery is the preferred option for treating brain arteriovenous malformation (AVM) when the risks associated with surgery outweigh the potential benefits. However, some patients require repeat radiosurgery due to residual AVM after the first procedure. This systematic review and meta-analysis aimed to investigate the safety and efficacy of repeated procedure of radiosurgery for AVM. METHOD: A systematic review was conducted according to the PRISMA guideline. The search was conducted on PubMed, Scopus, Embase, and Web of Science, using a pre-designed search string. Studies investigating the efficacy of repeat radiosurgery for residual AVM following initial single session radiosurgery were included. The risk of bias was assessed using the JBI tool. Meta-analysis and met-regression were performed to pool and inspect data. RESULTS: Our meta-analysis, with a mean follow-up of 45.57 months, reveals repeat radiosurgery as a viable option for arteriovenous malformations (AVMs), achieving a 60.82% obliteration rate with a mean time to obliteration of 33.18 months. Meta-regression identifies AVM volume and Spetzler-Martin (SM) grade as factors influencing obliteration, with smaller volume and lower SM grades associated with higher rates. Complications include 10.33% radiation-induced changes, 5.26% post-radiosurgery hemorrhage, 2.56% neurologic deficits, and 0.67% cyst formation. Heterogeneity in complications is primarily attributed to male proportion and SM grade, while factors influencing post-radiosurgery hemorrhage remain unclear. The type of radiosurgery, whether Gamma Knife Radiosurgery (GKRS) or LINAC, does not significantly impact outcomes. CONCLUSION: Repeat radiosurgery is a feasible, effective, and safe treatment for AVMs following failure of initial radiosurgery. When utilized in appropriate patient subgroups, it provides an acceptable risk-to-benefit profile. Feature studies are required to clarify its clear indications.

Elucidating the pathogenesis behind arteriovenous malformations of the central nervous system: a bibliometric analysis.

Arteriovenous malformations (AVMs) are vascular malformations of the central nervous system (CNS) with potential for significant consequences. The exact pathophysiologic mechanism of AVM formation is not fully understood. This study aims to evaluate bibliometric parameters and citations of the literature of AVMs to provide an overview of how the field has evolved. We performed an electronic search on Web of Science to identify the top 100 published and indexed articles with the highest number of citations discussing the pathogenesis of AVMs. This study yielded 1863 articles, of which the top 100 were selected based on the highest total citation count. These articles included 24% basic science, 46% clinical, and 30% review articles. The most-cited article was a clinical article from 2003, and the most recent was published in 2022. The median number of authors was 6, with the highest being 46 for a clinical article. The top 5 journals were identified, with the highest impact factor being 20.1. 13 countries were identified, with the US contributing the most articles (approximately 70%). Regarding genes of investigation, VEGF was one of the early genes investigated, while more interested in RAS/MAPK has been garnered since 2015. There is a growing interest in AVM genomics and pathogenesis research. While progress has been made in understanding clinical aspects and risk factors, the exact pathophysiological mechanisms and genetic basis of AVM formation remain incompletely understood. Further investigation of key genes in AVM pathogenesis can allow identification of potential therapeutic targets.

Single dominant lesion in capillary malformation-arteriovenous malformation (CM-AVM) RASA1 syndrome.

We report two cases with localized vascular malformations clinically resembling the "dominant lesion" seen in capillary malformation-arteriovenous malformation (CM-AVM) syndrome, however, lacking germline RASA1 variants but presenting double somatic RASA1 variants in affected tissue. Both patients presented with localized and superficial high-flow vascular malformations were treated with surgery and laser therapy and showed partial resolution. The study underscores the rarity of somatic RASA1 variants, contributes to understanding the "second-hit" pathophysiology in vascular lesions, and emphasizes the significance of clinical distinctions and genotyping for accurate diagnoses, offering implications for diagnosis, prognosis, and genetic counseling.

Influence of preoperative embolisation on resection of brain arteriovenous malformations: cohort study.

PURPOSE: Preoperative endovascular embolisation is a widely used adjunct for the surgical treatment of brain arteriovenous malformations (AVMs). However, whether this improves completeness of AVM resection is unknown, as previous analyses have not adjusted for potential confounding factors. We aimed to determine if preoperative endovascular embolisation was associated with increased rate of complete AVM resection at first surgery, following adjustment for Spetzler-Martin grade items. METHODS: We identified a cohort of all patients undergoing first ever AVM resection in a specialist neurosciences unit in the NHS Lothian Health Board region of Scotland between June 2004 and June 2022. Data was prospectively extracted from medical records. Our primary outcome was completeness of AVM resection. We determined the odds of complete AVM resection using binomial logistic regression with adjustment for Spetzler-Martin grading system items: maximum nidus diameter, eloquence of adjacent brain and the presence of deep venous drainage. RESULTS: 88 patients (median age 40y [IQR 19-53], 55% male) underwent AVM resection. 34/88 (39%) patients underwent preoperative embolisation and complete resection was achieved at first surgery in 74/88 (84%). Preoperative embolisation was associated with increased adjusted odds of complete AVM resection (adjusted odds ratio [aOR] 8.6 [95% confidence interval (95% CI) 1.7-67.7]; p = 0.017). The presence of deep venous drainage was associated with reduced chance of complete AVM resection (aOR 0.18 [95% CI 0.04-0.63]; p = 0.009). CONCLUSIONS: Preoperative embolisation is associated with improved chances of complete AVM resection following adjustment for Spetzler-Martin grade, and should therefore be considered when planning surgical resection of AVMs.

Trans-radial artery microcatheter angiography-assisted juvenile ruptured brainstem arteriovenous malformation resection.

BACKGROUND: Due to their crucial functional location, surgical treatment of brainstem arteriovenous malformations (AVMs) has always been challenging. For unruptured AVMs, we can determine whether radiological therapy, interventional treatment, or surgical resection is feasible based on the AVM structure. However, for ruptured AVMs, microsurgical resection and interventional embolization are effective methods to prevent further rupture. In the microsurgical resection of AVMs, we usually use a hybrid operation to confirm the AVM structure and determine if the AVM is completely resected during the surgery. METHOD: We report a case of juvenile ruptured brainstem AVM resection. The right lateral position and left suboccipital retrosigmoid approach were used. We established an interventional approach via left radial artery and set a microcatheter in the feeding artery. Methylene blue injection via a microcatheter showed the AVM structure, and we totally resected the brainstem AVM under electrophysiological monitoring and navigation. Intraoperative angiography was performed to ensure complete resection without residual nidus. CONCLUSION: This case demonstrates that the trans-radial approach is convenient and safe for special positions in hybrid operations. Methylene blue injection via a microcatheter in the feeding artery provides clearer visualization of the AVM structure under the microscope.

Hereditary hemorrhagic telangiectasia diagnosis: A case report.

This case report presents a 13-year-old patient with a lung nodule identified on a chest radiograph in the emergency department during an evaluation of knee and side pain after a fall. The patient had nosebleeds, family history of hereditary hemorrhagic telangiectasia (HHT) and after chest computed tomography with angiography, the nodule was defined as a single pulmonary arteriovenous malformation (PAVM). Neither parent nor patient had been evaluated for HHT, an autosomal dominant disease, despite the family history. This patient satisfied the clinical criteria for the diagnosis and had a confirmatory genetic test, which led to diagnosis in mother also. The patient's PAVMs were treated, decreasing the risk of life threatening complications. Diagnosing HHT in children is often delayed or missed, even in families with HHT, as in this case report. Without any physical signs or clinical symptoms, families and healthcare providers often dismiss the possibility of the diagnosis. Children with HHT are at the same risk for complications of stroke, anemia, hypoxemia, heart failure and increased morbidity as adults. It is essential to recognize the importance of family history when evaluating children in primary care and urgent settings, as this patient's diagnosis was delayed 13 years. Awareness of HHT signs and symptoms are essential to early referral to an HHT specialist, for diagnosis and management.

Investigation of the Genetic Determinants of Telangiectasia and Solid Organ Arteriovenous Malformation Formation in Hereditary Hemorrhagic Telangiectasia (HHT).

Telangiectases and arteriovenous malformations (AVMs) are the characteristic lesions of Hereditary Hemorrhagic Telangiectasia (HHT). Somatic second-hit loss-of-function variations in the HHT causative genes, ENG and ACVRL1, have been described in dermal telangiectasias. It is unclear if somatic second-hit mutations also cause the formation of AVMs and nasal telangiectasias in HHT. To investigate the genetic mechanism of AVM formation in HHT, we evaluated multiple affected tissues from fourteen individuals. DNA was extracted from fresh/frozen tissue of 15 nasal telangiectasia, 4 dermal telangiectasia, and 9 normal control tissue biopsies, from nine unrelated individuals with HHT. DNA from six formalin-fixed paraffin-embedded (FFPE) AVM tissues (brain, lung, liver, and gallbladder) from five individuals was evaluated. A 736 vascular malformation and cancer gene next-generation sequencing (NGS) panel was used to evaluate these tissues down to 1% somatic mosaicism. Somatic second-hit mutations were identified in three in four AVM biopsies (75%) or half of the FFPE (50%) samples, including the loss of heterozygosity in ENG in one brain AVM sample, in which the germline mutation occurred in a different allele than a nearby somatic mutation (both are loss-of-function mutations). Eight of nine (88.9%) patients in whom telangiectasia tissues were evaluated had a somatic mutation ranging from 0.68 to 1.96% in the same gene with the germline mutation. Six of fifteen (40%) nasal and two of four (50%) dermal telangiectasia had a detectable somatic second hit. Additional low-level somatic mutations in other genes were identified in several telangiectasias. This is the first report that nasal telangiectasias and solid organ AVMs in HHT are caused by very-low-level somatic biallelic second-hit mutations.

Endovascular approach to posterior spinal cord AV shunts via the anterior spinal artery.

Intradural spinal cord arteriovenous shunts are challenging vascular lesions with poor prognosis if left untreated. Therapeutic options include endovascular treatment, microsurgery or a combined approach. Surgical approaches are more complex if the lesions are located anteriorly and supplied by the anterior spinal artery (ASA). ASA can also vascularize shunts located on the posterior surface of the spinal cord either by transmedullary arteries, pial circumferential arteries or, if affecting the lower portions of the cord, by the anastomotic channels of the basket. Each of these vessels can be used for endovascular navigation to reach the shunts with good results if appropriate anatomical rules are followed. We describe here some technical considerations based on the anatomical analysis for the embolization of posterior spinal cord arteriovenous shunts vascularized by the anterior spinal artery.

Executive summary of the 14th HHT international scientific conference.

Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant vascular disorder characterized by small, dilated clustered vessels (telangiectasias) and by larger visceral arteriovenous malformations (AVMs), which directly connect the feeding arteries with the draining veins. These lesions are fragile, prone to rupture, and lead to recurrent epistaxis and/or internal hemorrhage among other complications. Germline heterozygous loss-of-function (LOF) mutations in Bone Morphogenic Protein 9 (BMP9) and BMP10 signaling pathway genes (endoglin-ENG, activin like kinase 1 ACVRL1 aka ALK1, and SMAD4) cause different subtypes of HHT (HHT1, HHT2 and HHT-juvenile polyposis (JP)) and have a worldwide combined incidence of about 1:5000. Expert clinicians and international scientists gathered in Cascais, Portugal from September 29th to October 2nd, 2022 to present the latest scientific research in the HHT field and novel treatment strategies for people living with HHT. During the largest HHT scientific conference yet, participants included 293 in person and 46 virtually. An impressive 209 abstracts were accepted to the meeting and 59 were selected for oral presentations. The remaining 150 abstracts were presented during judged poster sessions. This review article summarizes the basic and clinical abstracts selected as oral presentations with their new observations and discoveries as well as surrounding discussion and debate. Two discussion-based workshops were also held during the conference, each focusing on mechanisms and clinical perspectives in either AVM formation and progression or current and future therapies for HHT. Our hope is that this paper will represent the current progress and the remaining unanswered questions surrounding HHT, in order to serve as an update for those within the field and an invitation to those scientists and clinicians as yet outside of the field of HHT.

Longitudinal Assessment of Curaçao Criteria in Children with Hereditary Hemorrhagic Telangiectasia.

OBJECTIVE: To assess the utility of the Curaçao criteria by age over time in children with hereditary hemorrhagic telangiectasia (HHT). STUDY DESIGN: This was a single-center, retrospective analysis of patients attending the HHT clinic at the Hospital for Sick Children (Toronto, Canada) between 2000 and 2019. The evaluation of the Curaçao criteria was completed during initial and follow-up visits. Screening for pulmonary and brain arteriovenous malformations was completed at 5 yearly intervals. RESULTS: A total of 116 patients with genetic confirmation of HHT were included in the analysis. At initial screening at a median (IQR) age of 8.4 (2.8, 12.9) years, 41% met criteria for a definite clinical diagnosis (≥3 criteria). In children <6 years at presentation, only 23% fulfilled at least 3 criteria initially. In longitudinal follow-up, 63% reached a definite clinical diagnosis, with a median (IQR) follow-up duration of 5.2 (3.2, 7.9) years (P = .005). Specifically, more patients met the epistaxis and telangiectasia criteria at last visit compared with initial (79% vs 60%; P = .006; 47% vs 30%; P = .02) but not for the arteriovenous malformation criterion (59% vs 57%; P = .65). CONCLUSIONS: In the pediatric population, most patients do not meet definite clinical criteria of HHT at initial presentation. Although the number of diagnostic criteria met increased over time, mainly due to new onset of epistaxis and telangiectasia, accuracy remained low during follow-up visits. Relying solely on clinical criteria may lead to underdiagnosis of HHT in children.

Endovascular Treatment of Peripheral Arteriovenous Malformations (AVMs): Do Angiographic Outcomes Relate to the Quality of Life?

PURPOSE: Patients with arteriovenous malformations (AVMs) have a lower health-related quality of life (QoL) than the general population. QoL assessment of patients with peripheral AVMs after endovascular treatment is scarce in the literature. Radiologic and clinical outcomes are not always correlated in vascular malformation treatment. This study aimed to investigate the relationship between clinical outcomes, QoL, and angiographic outcomes. MATERIALS AND METHODS: Patients with peripheral AVM that underwent endovascular treatment between January 2009 and December 2021 in a single center were retrospectively evaluated. Patients' characteristics (age, sex), AVM characteristics (Schobinger classification, location, angiographic architecture), previous treatment, treatment characteristics (type of endovascular approach, embolizing agent and number of sessions), percentages of angiographic response, complications, and recurrence were evaluated. The angiographic architecture was evaluated according to the Yakes classification. The questionnaire was applied for evaluation of clinical response and QoL. Patients older than 12 years and those who can be contacted were included in clinical and QoL analysis. Clinical response was defined as improvement in the patient's most important pretreatment symptom. Treatment response was defined as clinical response plus >50% angiographic response. RESULTS: Eighty-six patients (41 males [47.7%], 45 females [52.3%]) were included in angiographic analysis. The mean age was 28.44±12.99 years (range=5-61). Forty-three patients (50%) had previous treatment. The median number of sessions was 2 (range 1-15, InterQuartile Range [IOR]=2). Sixty-one patients (30 males [49.2%], 31 females [50.8%]) were included in clinical analysis. The clinical response rate was 73.8%, 95% confidence interval (CI) [0.60, 0.84]. The treatment response rate was 45.9%, 95% CI [0.33, 0.59]. The complication rate was 8.2%. Before treatment, 48 patients (78.7%) reported a negative impact on their QoL. Thirty-three of 48 patients (68.8%) reported improvement on their QoL after treatment. Higher Schobinger stages were related to a negative impact on QoL before treatment (p<0.01). Yakes types were not related to QoL (p=0.065). Clinical response was related to improvement on QoL after treatment (p<0.01). Angiographic and treatment responses were not related to improved QoL after treatment (p=0.52 and p=0.055, respectively). CONCLUSION: Angiographic architecture and outcomes were not always reflected in QoL after endovascular treatment. CLINICAL IMPACT: This study's findings will help clinicians with what to focus on in AVM treatment and how to monitor patients with peripheral AVM after endovascular treatment. Rather than relying too much on the angiographic response, patients should be checked for symptoms and quality of life improvement. No clear data in the literature regarding the applicability of the Yakes Classification in patients with previous treatment. This study questioned the applicability of the Yakes Classification in patients with previous treatments. In this study, type 4 AVMs were more common in patients with previous treatment.

Multidisciplinary coordinated care of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease).

Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu disease, is a rare disorder with a case prevalence as high as one in 5000, causing arteriovenous malformations in multiple organ systems. HHT is familial with autosomal dominant inheritance, with genetic testing allowing confirmation of the diagnosis in asymptomatic kindreds. Common clinical manifestations are epistaxis and intestinal lesions causing anemia and requiring transfusions. Pulmonary vascular malformations predispose to ischemic stroke and brain abscess and may cause dyspnea and cardiac failure. Brain vascular malformations can cause hemorrhagic stroke and seizures. Rarely, liver arteriovenous malformations can cause hepatic failure. A form of HHT can cause juvenile polyposis syndrome and colon cancer. Specialists in multiple fields may be called to care for one or more aspects of HHT, but few are familiar with evidence-based guidelines for HHT management or see a sufficient number of patients to gain experience with the unique characteristics of the disease. Primary care physicians and specialists are often unaware of the important manifestations of HHT in multiple systems and the thresholds for their screening and appropriate management. To improve familiarity, experience, and coordinated multisystem care for patients with HHT, the Cure HHT Foundation, which advocates for patients and families with this disease, has accredited 29 centers in North America with designated specialists for the evaluation and care of patients with HHT. Team assembly and current screening and management protocols are described as a model for evidence-based, multidisciplinary care in this disease.

Endovascular treatment of spinal AVM: report of two cases with transvenous approach in combination with retrograde pressure cooker technique.

PURPOSE: Endovascular treatment of spinal AVMs is limited by low complete cure rates. Transarterial extensive treatment with liquid embolics carries the risk of clinically relevant ischemic complications. We report two cases of symptomatic spinal AVMs treated by a transvenous approach with retrograde pressure cooker technique. METHODS: In two selected cases, transvenous navigation aimed at retrograde pressure cooker embolization. RESULTS: Retrograde venous navigation was possible with two parallel microcatheters, and the pressure cooker technique with ethylenvinylalcohol-polymer was applicable in both cases. One AVM was occluded completely, and one subtotally due to a second draining vein. No clinical complications occurred. CONCLUSION: A transvenous approach for embolization with liquid embolics may offer advantages in treating certain spinal AVMs.

Intracerebral de novo arterio-venous malformations as a side effect of bevacizumab.

INTRODUCTION: Bevacizumab is a monoclonal antibody for the vascular endothelial growth factor receptor and is utilized in the treatment of various tumors. Gastrointestinal perforation/fistula, heart failure, hemorrhage, hypertension, proteinuria/nephrotic syndrome, thromboembolism, posterior reversible encephalopathy syndrome, and necrotizing fasciitis are serious side effects of bevacizumab. Bevacizumab associated de novo brain arterio-venous malformation formation has not been documented in the literature. CASE REPORT: Here, we presented a 35-year-old female patient with recurrent high-grade glial tumor who developed multiple supra- and infratentorial de novo arterio-venous malformations after receiving the last dose of bevacizumab. MANAGEMENT & OUTCOME: Intervention options for the adverse effect were limited. In fact, there was no chance of intervention because the patient died for another reason. DISCUSSION: Based on this experience, it can be hypothesized that bevacizumab may induce de novo arterio-venous malformations in the brain as a result of arterial and venous thrombotic effects. Additional studies should be done to clarify the causal relationship between bevacizumab and arterio-venous malformations in primary brain tumors.

Clinical features and outcome in pediatric arteriovenous malformation: institutional multimodality treatment.

PURPOSE: Intracranial arteriovenous-malformation (AVM) is a relatively rare condition in pediatrics, yet is a major cause of spontaneous intracranial hemorrhage with a risk of fatal hemorrhage reported to be between 4 and 29%. Little is known about vessel morphology and optimum treatment modalities including multimodality combination therapy and prognosis in children. METHODS: A retrospective review of all children presenting to our institution from 2006 to 2020 that had an AVM was undertaken. RESULTS: A total of 50 children were identified with median age of 11 (range 1-16) years. The mean follow-up was 7.6 years. Forty-one children presented as an emergency and of those, 40 had hemorrhage identified on initial brain imaging. The average nidus size was 25 mm, drainage was superficial in 51% of cases, and located in eloquent cortex in 56%. The supplemental Spetzler-Martin grading indicated 78% (39/50) were grade 4 and above (moderate to high risk). Primary treatment modalities included embolization in 50% (25) or SRS in 30% (15) and surgery in 20% (10).The AVM was obliterated on follow-up DSA in 66% children. Three children had post-treatment hemorrhage, two related to embolization and one the day following SRS, giving a re-bleed rate of 6%. The GOSE was available for 32 children at long term follow and 94% had a good outcome (GOSE 5-8). Two children died due to acute hemorrhage (4%). CONCLUSION: The majority of children with AVM present with hemorrhage. The rebleed rate during definitive treatment is low at 6% over the study period. The selective use of the 3 modalities of treatment has significantly reduced mortality and severe disability.

Bleeding pediatric AVM with negative pre-operative angiography: the first case report.

INTRODUCTION: Pediatric arteriovenous malformation (pAVM) is one of the most common vascular entities in non-traumatic intracerebral hemorrhage (ICH) in children. To diagnose arteriovenous malformation (AVM), digital subtraction angiography (DSA) is the gold standard investigation because it can provide sufficient dynamic information about the AVM. In extremely rare occasions, angiography is unable to detect an AVM because the AVM is spontaneously occluded. All reported cases found by authors in the literature had already been diagnosed with AVM by angiography or other vascular studies before the AVM occlusion. CASE PRESENTATION: We present a case of a 4-year-old girl who presented with left occipital ICH with atypical calcification. Based on history and investigation, pAVM was the most likely diagnosis. However, preoperative angiography was negative for pAVM and for shunting. Bleeding tumor was then suspected instead. After resection, pathological diagnosis confirmed pAVM. CONCLUSION: Our case demonstrates that DSA, despite being considered the gold standard, cannot always diagnose pAVM. The mechanism of spontaneous AVM occlusion remains unknown.