Small Arteriovenous Malformations Research Articles

Genotypes and phenotypes of capillary malformation-arteriovenous malformation: characterization and correlation analysis.

Capillary malformation-arteriovenous malformation (CM-AVM) is a rare genetic disorder characterized by multiple small capillary malformations (CMs) and arteriovenous malformations (AVMs), which has been linked with pathogenic variants in RASA1 and EPHB4. However, more data are needed to explore the phenotypic characteristics and the association between genotypes and clinical phenotypes. Our aim was to investigate the phenotypic and genetic characteristics of CM-AVM in East Asians, identify potential unique phenotypes, and conduct genotype-phenotype association analyses. This is a single-center study prospectively collecting CM-AVM patients' clinical data, with genetic data from blood or tissue samples. A total of 59 patients were enrolled. Thirty-two individuals had a leading CM greater than Schobinger stage II. The trigeminal nerve branches and greater auricular, transverse cervical, and lesser occipital nerves' somatosensory innervation zones divided head and neck CMs into six zones: V1, V2, V3, GA, TC, and LO zones. GA, TC, and LO zones had a positive correlation with one another but a negative correlation with V2 zone involvement. The RASA1 and EPHB4 pathogenic variants were detected in 41 out of 59, which showed two types of variant allele frequency (VAF) distributions. VAF above 30% made RASA1 pathogenic variants more susceptible to multifocal CMs than those below 30%. Leading CMs in the head and neck exhibit two segmentation patterns, anterior and lateral, which may differ in ear involvement and progression. Germline RASA1 pathogenic variants increased multifocal CM risk more than the somatic variants.

Surgical treatment of small-sized S3 arterio-venous malformations with neo-adjuvant and adjuvant bleomycin

Arteriovenous Malformations are complex and challenging entities, and their treatment is often tailored on the patient. Interstitial sclerosing treatment with bleomycin is promising especially in cases where the aesthetical and/or functional burden of surgical intervention would be impactful as in the S3 AVM according to the SECg classification.We treated 15 patients presenting small (<10cm3) S3 arterio-venous malformations with 3 + 3 sessions of 15.000 IU of interstitial bleomycin. 9 patients presented moderate to good response to the first 3 sessions and thus surgical re-shaping was performed between the two cycles. US examination was done pre-treatment, before each session and every 3 months after the end of the protocol to assess the arterio-venous malformations.Fifteen of the seventeen patients concluded the protocol. 9 patients underwent surgical re-shaping while 6 skipped it because of their excellent response to the first 3 bleomycin injections. Major improvement in terms of appearance and symptoms (pulsations, ulcerations, bleeding or pain) were always achieved. There was a 20% of minor complications.The presented data are encouraging and seem to suggest that this may be a promising protocol to extend the use of bleomycin in arterio-venous malformations and reduce the impact of surgery.

Primary Embolization of Cerebral Arteriovenous Malformations With Intention to Cure: A Systematic Review of Literature and Meta-Analysis.

The treatment of brain arteriovenous malformations (AVMs) involves multiple approaches, including embolization, microsurgical resection, and radiosurgery. With the advent of new embolisates, dual-lumen balloon catheters, detachable tip microcatheters, and transvenous embolization, endovascular AVM obliteration has become more effective. Although adjuvant embolization and embolization are commonly used, the safety and effectiveness of curative embolization remain unclear. We conducted a systematic literature review using PubMed, Ovid Medline, and Web of Science to identify studies reporting outcomes in patients with AVMs who underwent primary embolization with the intention to cure. We collected data on patient characteristics, AVM features, complications, and radiographic and clinical outcomes for meta-analysis. We identified 25 studies with a total of 1425 patients with 1427 AVMs who underwent curative embolization. Of these patients, 70% were low grade (pooled = 61% [39-82]), 67% were <3 cm (pooled = 78% [60-92]), and 75% were in superficial locations (pooled = 80% [72-86]). At last radiographic follow-up (mean, 16.7 ± 10.9 months), the full obliteration rate was 52% (pooled = 61% [43-77]) and retreatment rate was 25% (pooled = 17% [8.3-27]). At last clinical follow-up (mean, 24.2 ± 13.3 months), the poor clinical outcome rate was 7.9% (pooled = 4.4% [1.3-8.7]) and symptomatic complication rate was 13% (pooled = 13% [8-19]). There was no significant difference in the rate of radiographic cure, need for retreatment, and poor outcomes between ruptured and unruptured AVMs. Symptomatic complications were more common in the treatment of unruptured AVMs. The primary outcomes showed high heterogeneity (I2 = 72%-94%). Curative embolization of AVM is primarily reserved for small and low-grade AVMs, with highly variable outcomes. Our findings suggest poor radiographic outcomes and increased risk of complications. Outcomes are highly dependent on patient selection and technique used. Large multicenter prospective studies are required to further guide patient selection, categorize clinical and radiographic outcomes, and identify subgroup of patients that may benefit from curative embolization.

Hereditary hemorrhagic telangiectasia: from signaling insights to therapeutic advances.

Hereditary hemorrhagic telangiectsia (HHT) is an inherited vascular disorder with highly variable expressivity, affecting up to 1 in 5,000 individuals. This disease is characterized by small arteriovenous malformations (AVMs) in mucocutaneous areas (telangiectases) and larger visceral AVMs in the lungs, liver, and brain. HHT is caused by loss-of-function mutations in the BMP9-10/ENG/ALK1/SMAD4 signaling pathway. This Review presents up-to-date insights on this mutated signaling pathway and its crosstalk with proangiogenic pathways, in particular the VEGF pathway, that has allowed the repurposing of new drugs for HHT treatment. However, despite the substantial benefits of these new treatments in terms of alleviating symptom severity, this not-so-uncommon bleeding disorder still currently lacks any FDA- or European Medicines Agency-approved (EMA-approved) therapies.

Stereotactic radiosurgery for brain arteriovenous malformations in patients with hereditary hemorrhagic telangiectasia

ObjectiveBrain arteriovenous malformations (AVMs) in patients with hereditary hemorrhagic telangiectasia (HHT) present different characteristics from sporadic AVMs, and they have lower initial bleeding rates. Conservative management is usually preferred for the treatment of these lesions. In this case study, we present the largest series of HHT patients treated with stereotactic radiosurgery to date.MethodsWe identified eight patients with HHT and 14 AVMs. We retrospectively collected clinical, radiographic, and treatment characteristics of the patients and each AVM.ResultsMost patients in our sample presented with small AVMs. The median volume of these AVMs was 0.22 cm3 (IQR 0.08–0.59). Three out of eight patients presented with initial intracerebral hemorrhage (ICH). The majority of lesions had low (12/14) Spetzler-Martin grades (I–II). Median maximum and margin doses used for treatment were 36.2 (IQR 35.25–44.4) and 20 (IQR 18–22.5) Gy, respectively. The overall obliteration rate after SRS was 11/14, and the median time to obliteration across all 11 obliterated AVMs was 35.83 months (IQR, 17–39.99). Neurological status was favorable with all patients having a mRS of 0 or 1 at the last follow-up. Symptomatic radiation-induced changes (RIC) after SRS were low (7.1%), and there were no permanent RIC.ConclusionsPatients with HHT who present with multiple brain AVMs are generally well served by SRS. Obliteration can be achieved in the majority of HHT patients and with a low complication rate. In the current study, initial hemorrhage rates prior to SRS were noticeable which supports the decision to treat these AVMs. Future studies are needed to better address the role of SRS for HHT patients harboring ruptured and unruptured AVMs.

Challenges in Identifying and Resecting Small Bowel Arteriovenous Malformation

Challenges in Identifying and Resecting Small Bowel Arteriovenous Malformation

Abstract 17520: Dynamic Intrapulmonary Shunting in the Setting of Amphetamine Use

Description of Case: A 35-year-old female non-smoker with ADHD on amphetamine for the past 3 months and family history of hereditary hemorrhagic telangiectasia (HHT) presented with significant exertional dyspnea for 1 week. She was hypoxic to 82% while walking, with normal oxygen saturation at rest. Transthoracic echocardiogram with agitated saline revealed extracardiac right-to-left shunting with exercise and Valsalva. This was confirmed by dobutamine stress echocardiogram with agitated saline (Figure 1A). Transesophageal echocardiogram with agitated saline (Figure 1B) revealed no shunt through the foramen ovale, but it demonstrated bubbles entering from the left upper pulmonary vein, suggestive of an extracardiac shunt from a pulmonary arteriovenous malformation (AVM). Right heart catheterization and pulmonary angiogram revealed normal pressures, and no pulmonary abnormalities with normal pulmonary venous return. Supine right heart catheterization with exercise revealed normal pressures, although the initial pulmonary artery (PA) saturation was 28%; repeat PA saturation one minute later was 48%. Arterial saturation was 95%. Pulmonary function testing, ventilation perfusion scan, high-resolution CT chest, and coronary CT angiogram were unremarkable. The patient was instructed to avoid all stimulants, and to take a non-hormonal contraceptive. At her 3-month follow-up, she reported significant improvement in her symptoms. She underwent a 6-minute walk test, and her lowest oxygen saturation was 88%. Discussion: This patient presented with exertional hypoxia, normal saturations at rest, evidence of an extracardiac shunt only with exertion and absence of clear sources of the shunt on imaging. With her family history of HHT, this is suggestive of a small pulmonary AVM that opened by elevated PA pressures, likely triggered by amphetamine use, and its discontinuation led to symptom resolution.

Volume Fractionation Stereotactic Radiosurgery for Large Volume Intracranial Arteriovenous Malformations.

Arteriovenous malformations (AVMs) are common intracranial vascular anomalies. Common treatment modalities used to manage AVMs are surgical excision, embolization, and stereotactic radiosurgery (SRS). Large AVMs are defined as AVMs larger than 10 cm3 and pose a therapeutic challenge with high rates of treatment-related morbidity and mortality. Single-stage SRS is a good option for small AVMs but carries high risks of radiation-induced complications in large AVMs. Volume-staged SRS (VS-SRS) is a newer strategy used in large AVMs that allows one to deliver an optimal radiation dose to the AVMs while reducing the risk of radiation damage to the normal brain. It involves the division of AVM into multiple small sectors which are irradiated at different time intervals with high radiation doses. Good obliteration rates with less risk of radiation-induced complications have been described in the literature with VS-SRS.

Arteriovenous Malformations:Endovascular Techniques and Devices

Endovascular embolization using liquid materials is a safe and effective treatment option for cerebral arteriovenous malformations(AVM). Onyx and n-butyl cyanoacrylate, currently available in Japan, have specific features. Appropriate embolic agents should be selected based on their characteristics. Transarterial embolization(TAE)is the standard endovascular treatment approach. However, there have been some recent reports regarding the efficacy of transvenous embolization(TVE). TVE is potentially curative for small AVM with hemorrhagic onset, inaccessible arterial feeders, deep location, and/or a single draining vein. In specific cases, TVE may provide a higher chance of complete obliteration of the AVM than TAE. Some unsolved problems need further clarification, such as the relative positions of liquid embolization against direct surgery, dealing with unruptured AVM, and effective treatment for high-grade AVM.

Microsurgical resection of a ruptured right peri-ventricular brain arteriovenous malformation with preoperative embolization.

A 41-year-old female presented with a headache and left inferior quadrantanopia. Imaging demonstrated a clot spanning the atrium of the ventricle to the superior parietal lobule (SPL), with a small arteriovenous malformation (AVM) nidus outside the atrium of the ventricle. The nidus was supplied by parieto-occipital arterial (P4) feeders with a single atrial draining vein. Pre-operative embolization of a pedicle with Onyx provided a surgical marker. A parietal craniotomy was performed with a trans-cortical SPL approach. During AVM resection, the draining vein was injured, which was stabilized using a temporary clip to "spot weld" the defect and continue nidus dissection with patent venous outflow. After careful dissection, coagulation, and division of all the arterial feeders, the AVM was mobilized and the draining vein was clipped, coagulated, and divided. Follow-up indocyanine green angiography and cerebral angiography both confirmed complete resection of the AVM. The patient consented to the procedure and to publication.

Benefit of Advanced 3D DSA and MRI/CT Fusion in Neurovascular Pathology

Digital subtraction angiography provides excellent spatial and temporal resolution; however, it lacks the capability to depict the nonvascular anatomy of the brain and spinal cord.A review of the institutional database identified five patients in whom a new integrated fusion workflow of cross-sectional imaging and 3D rotational angiography (3DRA) provided important diagnostic information and assisted in treatment planning. These included two acutely ruptured brain arteriovenous malformations (AVM), a small superficial brainstem AVM after radiosurgery, a thalamic microaneurysm, and a spine AVM, and fusion was crucial for diagnosis and influenced further treatment.Fusion of 3DRA and cross-sectional imaging may help to gain a deeper understanding of neurovascular diseases. This is advantageous for planning and providing treatment and, most importantly, may harbor the potential to minimize complication rates. Integrating image fusion in the work-up of cerebrovascular diseases is likely to have a major impact on the neurovascular field in the future.

Prenatal diagnosis and characterization of extra-axial, supratentorial pial arteriovenous malformation using high-resolution transvaginal neurosonography.

Prenatal diagnosis and characterization of extra-axial, supratentorial pial arteriovenous malformation using high-resolution transvaginal neurosonography.

Spontaneous obliteration of brain arteriovenous malformations: illustrative cases.

Spontaneous angiographic obliteration of a brain arteriovenous malformation (AVM) is considered a rare outcome, with most cases in the literature related to prior hemorrhage in small brain AVMs. The authors present a prospective, single center, consecutive case series. The clinical course and radiographic features of four cases with spontaneous obliteration of brain AVM were analyzed. The median age of patients in this series was 47.6 years, with an equal gender split. The median maximum brain AVM diameter was 2 cm. The median time to spontaneous obliteration was 26 months, with hemorrhage preceding this in three out of four cases and a prolonged latency in the only case with a nidus size larger than 3 cm and no hemorrhage. The present study provides additional information to allow clinicians to counsel patients about the rare outcomes of conservative management. This work extends our understanding of when this phenomenon can occur by reporting on the differences associated with spontaneous obliteration of larger AVMs.

Risk for Hemorrhage the First 2 Years After Gamma Knife Surgery for Arteriovenous Malformations: An Update.

Knowledge about the natural course of brain arteriovenous malformations (AVMs) have increased during the past 20 years, as has the number of AVMs treated, especially larger ones. It is thus timely to again analyze the risk for hemorrhage after Gamma Knife Surgery (GKS). To confirm or contradict conclusions drawn 20 years ago regarding factors that affect the risk for post-GKS hemorrhage. The outcome after GKS was studied in 5037 AVM patients followed for up to 2 years. The relation between post-treatment hemorrhage rate and a number of patient, AVM, and treatment parameters was analyzed. The results were also compared with the results from our earlier study. The annual post-treatment hemorrhage rate was 2.4% the first 2 years after GKS. Large size, low treatment dose, and old age were independent risk factors for AVM hemorrhage. After having compensated for the factors above, peripheral AVM location and female sex, at least during their child bearing ages, were factors associated with a lower post-GKS hemorrhage rate. Large AVMs (>5 cm 3 ) treated with low doses (≤16 Gy) had higher and small AVMs treated with high doses a lower risk for hemorrhage as compared with untreated AVMs. This was detectable within the first 6 months after GKS. No difference in hemorrhage rate could be detected for the other AVMs. Based on our findings, it is advisable to prescribe >16 Gy to larger AVMs, assuming that the risk for radiation-induced complications can be kept at an acceptable level.

Intestinal arteriovenous malformations: a diagnostic and therapeutic challenge

Arteriovenous malformations (AVM) of the intestine are rare causes of gastrointestinal bleeding. Diagnosis depends upon accurate interpretation of imaging features and histopathology to differentiate them from other vascular malformations. Presentation of colonic AVM with mucous diarrhea and pain is rare and poses diagnostic challenges. Usually, patients presenting with bleed need surgical intervention. The current report discussed one patient with chronic liver disease, extrahepatic portal vein thrombosis with small bowel AVM and two patients with colonic AVM, highlighting management strategies adopted.

Curative Embolization of Small Brain Arteriovenous Malformations by Ethyl Vinyl Alcohol Copolymer: A Systematic Review and Meta-Analysis.

The right choice in treating small (Spetzler-Ponce grade A) brain arteriovenous malformations (AVMs) is a matter of debate with varying views from neurology, neurosurgery, and interventional neuroradiology points of view. The Spetzler-Martin 1 and 2 brain AVMs, especially those in eloquent and deep areas that are difficult to access by micro-neurosurgery, are most suitable for a complete cure by endovascular embolization with ethyl vinyl alcohol (EVOH)-based agents.A literature search was done with keywords such as endovascular embolization of small brain AVM. Data from 13 articles are included in the study based on predetermined inclusion and exclusion criteria.Meta-analysis for the complete cure rate was done, publication bias was removed, and regression analysis showed a 76% cure rate with a 95% confidence interval (CI). Major complications were hemorrhage and neurological deficit, which ranged from 0-20% and 0-16% with a mean proportion of 0.11 and 0.09, respectively. Long-term (3-6 months) follow-up data showed 0-4% recurrence at three months, 0-8% recurrence at six months, and 2-10% permanent disability. The mortality rate ranged from 3% to 4%. Three illustrative cases with data from the author’s institute are included in the article. To conclude, endovascular embolization for small brain AVMs is a satisfactory treatment modality, however, prospective registries and randomized controlled trials involving embolization versus neurosurgery and/or stereotactic radiosurgery (SRS) may validate the role of embolization in small brain AVMs as curative treatment.

Analysis of results determination of level of vascular endothelial growth factor, receptor for vascular endothelial growth factor and big endotelin-1 in structure of arteriovenous malformations

Objective ‒ to assess the diagnostic significance of angiogenesis factors based on the study of the level of angiogenesis factors (vascular endothelial growth factor (VEGF-A), specific receptor for vascular endothelial growth factor (VEGFR-1), endothelial inflammation factor (Big Endothelin-1)) in arterial and venous blood of patients with arteriovenous malformations (AVM) and healthy individuals without AVM. Materials and methods. In 2019–2021 a study according to the data of enzyme-linked immunosorbent assay the level of VEGF-A, VEGFR-1 and Big Endothelin-1 in the plasma of arterial and venous blood of 50 (19 (38.0 %) men and 31 (62.0 % women)) with AVM of different localization was carried out. The age of patients ranged from 3 to 51 years, the mean age ‒ (27.79 ± 2.19) years. The control group consisted of 35 healthy individuals (20 men and 15 women) without AVM. Patients with AVMs were divided into two groups: with small and medium-sized AVM in the stage of compensation (n=32) and with large and giant AVM in the stage of subcompensation or decompensation (n=18). Results. A significant (p &lt; 0.05) difference was proved between the concentration of VEGF-A, VEGFR-1, Big Endothelin-1 in the plasma of arterial and venous blood of patients with AVM. This fact proves that the processes of pathological angiogenesis occur precisely in the structure of AVM. The value of VEGF-A, VEGFR-1 and BE-1 in patients with small and medium AVM was higher than in healthy individuals. The VEGF-A level was significantly (p &lt; 0.05) in 2.4 times higher than in the control group, the VEGFR-1 level ‒ in 1.4 times, and the ET-1 level ‒ in 1.5 times. The value of VEGF-A, VEGFR-1 and BE-1 level in patients with large and giant AVM was significantly (p &lt; 0.05) higher than in healthy individuals: VEGF-A ‒ in 7.2 times, VEGFR-1 ‒ in 2.36 times, and BE-1 ‒ in 1.7 times. Conclusions. The data obtained make it possible to statistically reliably state that the processes of pathological angiogenesis occur directly in the structure of AVM. A statistically significant dependence of the level of VEGF-A, VEGFR-1 and BE-1 in the blood plasma of patients on the size of the AVM and the stage of its compensation was revealed.

Facilitation of Pediatric Posterior Fossa Vascular Malformation Resection Using Virtual Reality Platform: 2-Dimensional Operative Video.

Pediatric posterior fossa arteriovenous malformations (AVMs) are rare entities that pose significant cumulative lifetime risk of rupture and require treatment. Microsurgical resection remains a good option for definitively treating posterior fossa AVMs in one setting. The drawback of endovascular embolization is the lower rates of nidus obliteration. Although stereotactic radiosurgery is a safe alternative, it takes several years to achieve the treatment goal all the while predisposing the patient to the risk of AVM rupture.1,2 Accurate localization and visualization remain challenging for microsurgical treatment of posterior fossa AVMs.3-5 Small size of a nidus, prone position, and proximity to eloquent areas make these lesions particularly difficult to localize and resect. We present the operative case of a 6-year-old boy with a small, ruptured posterior fossa AVM. After undergoing hematoma evacuation, the patient underwent microsurgical resection of a small right vermian AVM assisted by the virtual reality platform, Surgical Theater (Gates Mills, OH). Our video demonstrates the utility of a virtual augmented reality platform for addressing the challenges posed by a small posterior fossa AVM with respect to the need for precise three-dimensional localization of small lesions. The patient consented to the procedure. The participants and any identifiable individuals consented to publication of his/her image.

Curative Embolization for Pediatric Spetzler-Martin Grade III Cerebral Arteriovenous Malformations

Spetzler-Martin (SM) grade III arteriovenous malformations (AVMs) represent a gray zone due to their high variability in location, size, and angioarchitecture. In addition, there is a lack of information on curative embolization in the pediatric population, especially in this subgroup of lesions. Here we present our experience treating grade III AVMs by curative embolization in pediatric patients. Clinical and angiographic data from pediatric patients with grade III SM AVMs were retrospectively collected between 2011 and 2020 in a referral institution. We grouped the AVMs into subtypes according to size (S), venous drainage (V), and eloquence (E) and obtained subtypes: IIIA (S1V1E1), IIIB (S2V1E0), IIIC (S2V0E1), and IIID (S3V0E0). A total of 61 embolization sessions were performed in 35 pediatric patients. There were 25 females (64%), and the mean age was 12.2 years (range 5-18). Complete angiographic occlusion was achieved in 16 patients (47%). In 13 patients (37%), the AVM was occluded with a single embolization session and most (12/13) had small lesions (IIIA subtype). Among the 19 patients with incomplete occlusion, most (58%) had large lesions (IIIB, IIIC, and IIID). Large AVMs (IIIB, IIIC, and IIID) underwent 36 sessions; however, only 3 patients (21%) achieved complete occlusion in 11 sessions. Eight intraoperative complications (13% procedures) occurred mainly in ruptured AVMs (7/8) and eloquent zones (7/8). Curative embolization for SM grade III AVMs in children carries a high complication rate, especially in small, ruptured, and eloquent lesions. In addition, acceptable immediate complete angiographic occlusion rates were achieved, especially in small AVMs.

Клинический случай артериовенозной мальформации

Arteriovenous malformation (AVM) is a congenital malformation of cerebral vessels, associated with an abnormal connection of arteries and veins. The altered locations of the cerebral vascula-ture form a conglomerate that is a direct arteriovenous shunting without intermediate capillaries. The incidence of the disease is 4 cases per 100 thousand population. Clinically, AVM debuts mainly at the age of 20 to 40, and is accompanied by intracranial hemorrhages in 50% to 60% of patients; mortality is 35%. In 27% to 70% of individuals, AVM are manifested by epileptic seizures of various focal origins. In diagnostics, X-ray computed tomography is used to detect hemorrhage in case of a ruptured malformation; magnetic resonance imaging, including angiography, to assess the AVM node, afferent vessels and venous drainage. Currently, the only radical treatment for AVM is surgical removal of the malformation. This is feasible for small and medium-sized AVMs of cerebral vessels (36% to 50% of patients), since removal of large AVMs and AVMs located in functionally important areas, even microsurgically, is associated with a high risk of death and disability. A clinical case of a 30-year-old young patient with an acute onset of the disease characterized by sudden loss of consciousness and an episode of seizures is presented. Based on the data of clinical and instrumental examination, an AVM of the left parietal lobe with parenchymal-ventricular hemorrhage was revealed. On the day of admission to the hospital in Ryazan, a surgical intervention was performed: external ventriculostomy on the left side. After 4 months the second surgical intervention, removal of AVM of the left parietal region using neurophysiological control was carried out at Burdenko Neurosurgical Hospital in Moscow, Russia. The successful surgical approach has completely eliminated the life-threatening pathology. Subsequently, the patient underwent rehabilitation in a neurological hospital at the place of residence. CONCLUSION: The topic of AVM is of great practical interest not only for neurosurgeons, but also for neurologists and radiologists, since timely diagnosis and treatment effectiveness directly depend on the coordinated work of these specialists.