Arteriovenous Malformations Patients Research Articles

Predictors of radiation-induced changes in arteriovenous malformation patients undergoing radiosurgery: Insights from a Malaysian linear accelerator cohort.

Radiation-induced changes (RICs) post-stereotactic radiosurgery (SRS) critically influence outcomes in arteriovenous malformation (AVM) treatments. This study aimed to identify predictors of RICs, described the types and severity of RICs, and assessed their impact on patient's functional outcomes to enhance risk assessment and treatment planning for AVM patients. This retrospective study analyzed 87 AVM patients who underwent SRS at Hospital Kuala Lumpur between January 2015 and December 2020. RICs were identified through detailed magnetic resonance imaging evaluations, and predictive factors were determined using multiple logistic regression. Functional outcomes were assessed with the modified Rankin scale (mRS). Among the cohort, 40.2% developed RICs, with radiological RICs in 33.3%, symptomatic RICs in 5.7%, and permanent RICs in 1.1%. Severity categorization revealed 25.3% as Grade I, 13.8% as Grade II, and 1.1% as Grade III. Notably, higher Pollock-Flickinger scores and eloquence location were significant predictors of RIC occurrence. There was a significant improvement in functional outcomes post-SRS, with a marked decrease in non-favorable mRS scores from 8.0% pre-SRS to 1.1% post-SRS (P = 0.031). The study identified the eloquence location and Pollock-Flickinger scores as predictors of RICs post-SRS. The significant reduction in non-favorable mRS scores post-SRS underscores the efficacy of SRS in improving patient outcomes. Their results highlighted the importance of personalized treatment planning, focusing on precise strategies to optimize patient outcomes in AVM management, reducing adverse effects while improving functional outcomes.

Surgical outcomes and risk factors for overall mortality in brain arteriovenous malformations patients: a retrospective analysis.

Brain arteriovenous malformations (AVMs) are challenging vascular lesions. Extensive follow-up studies are necessary to refine the therapeutic algorithm, and to improve long-term survival in these patients. The aim of the study was to assess surgical outcomes, and to evaluate overall long-term mortality in patients treated for brain AVMs. This retrospective single-center study included 191 patients with brain AVMs, admitted between 2012 and 2022. Clinical and angiographical particularities have been analyzed, to identify factors that might influence early outcome and overall long-term mortality. Out of 79 patients undergoing surgery, 51 had ruptured AVMs with total resection achieved in 68 cases (86.1%). Deep venous drainage was associated with incomplete resection. Female sex, admission modified Rankin Scale (mRS) > 2, and eloquent location were independent predictors of poor outcomes. Multiple venous drainage was associated with a higher risk of worsened early outcome. Eloquent brain region involvement, conservative treatment, increasing age, admission mRS > 2, and comorbidities significantly decrease survival in brain AVM patients. Patients treated with interventional treatments had significantly better survival than the conservatively managed ones, when adjusting for age and admission mRS. The study identified female sex, poor neurologic status on admission and eloquence as independent prognostic factors for a negative outcome after surgery. Patients who received interventional treatment had significantly better survival than patients managed conservatively. We recommend employing tailored, proactive management strategies as they significantly enhance long-term survival in brain AVM patients.

Machine Learning Approach for Analyzing 3-Year Outcomes of Patients with Brain Arteriovenous Malformation (AVM) after Stereotactic Radiosurgery (SRS).

A cerebral arteriovenous malformation (AVM) is a tangle of abnormal blood vessels that irregularly connects arteries and veins. Stereotactic radiosurgery (SRS) has been shown to be an effective treatment for AVM patients, but the factors associated with AVM obliteration remains a matter of debate. In this study, we aimed to develop a model that can predict whether patients with AVM will be cured 36 months after intervention by means of SRS and identify the most important predictors that explain the probability of being cured. A machine learning (ML) approach was applied using decision tree (DT) and logistic regression (LR) techniques on historical data (sociodemographic, clinical, treatment, angioarchitecture, and radiosurgery procedure) of 202 patients with AVM who underwent SRS at the Instituto de Radiocirugía del Perú (IRP) between 2005 and 2018. The LR model obtained the best results for predicting AVM cure with an accuracy of 0.92, sensitivity of 0.93, specificity of 0.89, and an area under the curve (AUC) of 0.98, which shows that ML models are suitable for predicting the prognosis of medical conditions such as AVM and can be a support tool for medical decision-making. In addition, several factors were identified that could explain whether patients with AVM would be cured at 36 months with the highest likelihood: the location of the AVM, the occupation of the patient, and the presence of hemorrhage.

Induced Endothelial Cell Cycle Arrest Prevents Arteriovenous Malformations in Hereditary Hemorrhagic Telangiectasia.

Distinct endothelial cell cycle states (early G1 versus late G1) provide different "windows of opportunity" to enable the differential expression of genes that regulate venous versus arterial specification, respectively. Endothelial cell cycle control and arteriovenous identities are disrupted in vascular malformations including arteriovenous shunts, the hallmark of hereditary hemorrhagic telangiectasia (HHT). To date, the mechanistic link between endothelial cell cycle regulation and the development of arteriovenous malformations (AVMs) in HHT is not known. We used BMP (bone morphogenetic protein) 9/10 blocking antibodies and endothelial-specific deletion of activin A receptor like type 1 (Alk1) to induce HHT in Fucci (fluorescent ubiquitination-based cell cycle indicator) 2 mice to assess endothelial cell cycle states in AVMs. We also assessed the therapeutic potential of inducing endothelial cell cycle G1 state in HHT to prevent AVMs by repurposing the Food and Drug Administration-approved CDK (cyclin-dependent kinase) 4/6 inhibitor (CDK4/6i) palbociclib. We found that endothelial cell cycle state and associated gene expressions are dysregulated during the pathogenesis of vascular malformations in HHT. We also showed that palbociclib treatment prevented AVM development induced by BMP9/10 inhibition and Alk1 genetic deletion. Mechanistically, endothelial cell late G1 state induced by palbociclib modulates the expression of genes regulating arteriovenous identity, endothelial cell migration, metabolism, and VEGF-A (vascular endothelial growth factor A) and BMP9 signaling that collectively contribute to the prevention of vascular malformations. This study provides new insights into molecular mechanisms leading to HHT by defining how endothelial cell cycle is dysregulated in AVMs because of BMP9/10 and Alk1 signaling deficiencies, and how restoration of endothelial cell cycle control may be used to treat AVMs in patients with HHT.

Natural History and Histopathology of Expanding Cysts and Hematomas After Stereotactic Radiosurgery for Arteriovenous Malformations of the Brain: A Case Series

We reviewed the clinical course and histopathologic findings for cases involving the formation of expanding cysts and/or hematomas after gamma knife surgery (GKS) for arteriovenous malformations (AVMs). We report a single-center retrospective review of 18 patients who presented with cyst and/or hematoma expansion after GKS for AVMs between 1993 and 2023. Expanding cysts and hematomas were defined as well-demarcated cavities filled with fluid or well-marginated heterogenous hematomas presenting with expansion proximal to or in the location of the original AVM, respectively. Patient demographics, AVM characteristics, history of interventions and surgeries, and imaging and histopathologic features of expanding cysts and hematomas were collected for analysis. Among 1072 AVM patients treated using GKS, 18 presented with expanding cysts or hematomas during a total follow-up period of 16,757 patient-years (0.11 case/100 persons/patient-year). The time to cyst or hematoma identification was 4-13 years after initial GKS, with a mean duration of 8.6 years. Among the patients examined, 7 (38.9%) presented mainly with hematoma, 10 (55.6%) presented mainly with cysts, and 1 presented with approximately equal components of both. Among the 18 patients, 13 (72.2%) underwent craniotomy to treat cyst or hematoma expansion. All the specimens had similar histopathologic characteristics, including organizing hematoma with fresh and old hemorrhage, fibrinoid necrosis of the vessels, gliosis of normal brain tissue, infiltration of hemosiderin-laden histiocytes, and extravascular protein leakage. Our findings suggest that the formation of these 2 complications can be attributed to a common mechanism involving radiation-induced vascular damage in brain tissue adjacent to the AVM and subsequent chronic inflammation and capillary dilatation.

Pulmonary arteriovenous malformations in patients with previous brain abscess: a cross-sectional population-based study.

Pulmonary arteriovenous malformations (PAVMs) may cause recurrent brain abscess. The primary aim was to determine the prevalence of PAVM amongst survivors of brain abscess. The proportion with cardiac right-to-left shunts was also assessed post hoc. This was a cross-sectional population-based study of adult (≥18 years) survivors of cryptogenic bacterial brain abscess in Denmark from 2007 through 2016. Patients were invited for bubble-echocardiography to detect vascular right-to-left shunting and, if abnormal, subsequent computed tomography thorax for diagnosis of PAVM. Data are presented as n/N (%) or median with interquartile range (IQR). Study participation was accepted by 47/157 (30%) eligible patients amongst whom two did not appear for scheduled bubble-echocardiography. The median age of participants was 54 years (IQR 45-62) and 19/57 (33%) were females compared with 59 years (IQR 48-68, p = 0.05) and 41/85 females (48%, p = 0.22) in non-participants. Bubble-echocardiography was suggestive of shunt in 10/45 (22%) participants and PAVM was subsequently confirmed by computed tomography in one patient with grade 1 shunting. The corresponding prevalence of PAVM was 2% (95% confidence interval 0.06-11.8) amongst all examined participants. Another 9/45 (20%) were diagnosed with patent in persistent foramen ovale (n = 8) or atrial septum defect (n = 1), which is comparable with the overall prevalence of 25% amongst adults in the Danish background population. Undiagnosed PAVM amongst adult survivors of cryptogenic bacterial brain abscess is rare but may be considered in select patients. The prevalence of cardiac right-to-left shunts amongst brain abscess patients corresponds to the prevalence in the general population.

Effect of cerebral arteriovenous malformation location on outcomes of repeat, single-fraction stereotactic radiosurgery: a matched-cohort analysis.

Patients with deep-seated arteriovenous malformations (AVMs) have a higher rate of unfavorable outcome and lower rate of nidus obliteration after primary stereotactic radiosurgery (SRS). The aim of this study was to evaluate and quantify the effect of AVM location on repeat SRS outcomes. This retrospective, multicenter study involved 505 AVM patients managed with repeat, single-session SRS. The endpoints were nidus obliteration, hemorrhage in the latency period, radiation-induced changes (RICs), and favorable outcome. Patients were split on the basis of AVM location into the deep (brainstem, basal ganglia, thalamus, deep cerebellum, and corpus callosum) and superficial cohorts. The cohorts were matched 1:1 on the basis of the covariate balancing score for volume, eloquence of location, and prescription dose. After matching, 149 patients remained in each cohort. The 5-year cumulative probability rates for favorable outcome (probability difference -18%, 95% CI -30.9 to -5.8%, p = 0.004) and AVM obliteration (probability difference -18%, 95% CI -30.1% to -6.4%, p = 0.007) were significantly lower in the deep AVM cohort. No significant differences were observed in the 5-year cumulative probability rates for hemorrhage (probability difference 3%, 95% CI -2.4% to 8.5%, p = 0.28) or RICs (probability difference 1%, 95% CI -10.6% to 11.7%, p = 0.92). The median time to delayed cyst formation was longer with deep-seated AVMs (deep 62 months vs superficial 12 months, p = 0.047). AVMs located in deep regions had significantly lower favorable outcomes and obliteration rates compared with superficial lesions after repeat SRS. Although the rates of hemorrhage in the latency period and RICs in the two cohorts were comparable, delayed cyst formation occurred later in patients with deep-seated AVMs.

GPRASP1 loss-of-function links to arteriovenous malformations by endothelial activating GPR4 signals.

Arteriovenous malformations (AVMs) are fast-flow vascular malformations and refer to important causes of intracerebral haemorrhage in young adults. Getting deep insight into the genetic pathogenesis of AVMs is necessary. Herein, we identified two vital missense variants of G protein-coupled receptor (GPCR) associated sorting protein 1 (GPRASP1) in AVM patients for the first time and congruously determined to be loss-of-function variants in endothelial cells. GPRASP1 loss-of-function caused endothelial dysfunction in vitro and in vivo. Endothelial Gprasp1 knockout mice suffered a high probability of cerebral haemorrhage, AVMs and exhibited vascular anomalies in multiple organs. GPR4 was identified to be an effective GPCR binding with GPRASP1 to develop endothelial disorders. GPRASP1 deletion activated GPR4/cAMP/MAPK signalling to disturb endothelial functions, thus contributing to vascular anomalies. Mechanistically, GPRASP1 promoted GPR4 degradation. GPRASP1 enabled GPR4 K63-linked ubiquitination, enhancing the binding of GPR4 and RABGEF1 to activate RAB5 for conversions from endocytic vesicles to endosomes, and subsequently increasing the interactions of GPR4 and ESCRT members to package GPR4 into multivesicular bodies or late endosomes for lysosome degradation. Notably, the GPR4 antagonist NE 52-QQ57 and JNK inhibitor SP600125 effectively rescued the vascular phenotype caused by endothelial Gprasp1 deletion. Our findings provided novel insights into the roles of GPRASP1 in AVMs and hinted at new therapeutic strategies.

CyberKnife based fractionated stereotactic radiotherapy as an upfront treatment for cerebral arteriovenous malformation

BackgroundTo explore the therapeutic outcomes of CyberKnife based fractionated stereotactic radiotherapy (CKFRT) for patients with cerebral arteriovenous malformations (AVM). MethodsBetween January 2008 and October 2020, 45 patients underwent CKFRT for cerebral AVMs as a first treatment. The delineation of AVM targets included AVM nidus. The mean target volume was 4.07 cm3, and 9 lesions (20%) were larger than 10.0 cm3. The mean marginal dose was 24 Gy (range, 20–35 Gy). CKFRT was delivered in median 3 fractions (range, 2 ∼ 5 fractions). AVM obliteration following CKFRT was confirmed by magnetic resonance imaging or angiography. ResultsDuring a median follow-up of 47 (5–148) months, complete obliteration and partial obliteration of AVM after CKFRT were obtained in 23 (51%) and 13 (29%) patients, respectively. Median time to complete obliteration was 39 (15–63) months. The cumulative probability of complete obliteration rate at 3 years was 47%. Complete obliteration rate of AVM was associated with Radiosurgery-based AVM score, which was consisted of AVM volume, patients age, and AVM location. One (2%) patient had hemorrhage during the follow-up period. ConclusionsCKFRT is an effective primary treatment for patients with cerebral AVMs with a low hemorrhage risk.

A Success Story of Cerebral Arteriovenous Malformation (AVM) Treated with Stereotactic Radiosurgery (SRS) in Bangladesh

Purpose: To share a case of cerebral Arteriovenous Malformation (AVM) patient, treated with Stereotactic Radiosurgery (SRS) at Evercare Hospital Dhaka, treatment process and successful outcome. Background: Arteriovenous malformation is an anomaly, mostly congenital due to a misfit in vasculogenic, where arteries and veins come to a direct connection. Treatment options include observation, embolization, microsurgery, Stereotactic Radiosurgery (SRS) either alone or in combination. This report describes our experience in treating a patient of AVM by SRS. Stereotactic Radiosurgery is an established modality to achieve desired nidus obliteration, excellent compliance being noninvasive, and reduced treatment-related morbidity. This case report also reviewed the literature in detail. After a thorough literature search, to the best of our knowledge, this shall be the first published case report of AVM successfully treated with SRS in Bangladesh. Case Presentation: In March 2019, 25-years old male presented in Radiation Oncology OPD as a diagnosed case of AVM, having complaints of headache for two years. Headache was occasional and often associated with vertigo and dizziness. He had no neurologic deficit. A radiological assessment revealed a large (4.6x4.4cm) AVM in the left parieto-occipital lobe showing serpiginous enhancement with IV contrast. After routine workup, he underwent stereotactic Radiosurgery in March’2019. A dose of 23Gy was delivered to the malformation, including all nidus. Acute radiation toxicity was noted as transient hair loss only over the irradiated area and no other side effect. Radiological Assessment was done at six months, 1year, and 2.5 years. After having a stable size at six months, complete nidus obliteration was achieved at one year. His last visit to our OPD was in July 2021, with radiologically complete nidus obliteration without any significant clinical symptoms. Conclusions: Linear Accelerator-based SRS is an excellent treatment option for AVM, encouraging clinical outcomes for carefully selected patients. Bang. J Neurosurgery 2022; 12(1): 53-64

Early Treatment of Ruptured Cerebral Arteriovenous Malformations: Analysis of Neurological Outcomes and Health Care Costs.

The timing of surgical resection is controversial when managing ruptured arteriovenous malformations (AVMs) and varies considerably among centers. To retrospectively analyze clinical outcomes and hospital costs associated with delayed treatment in a ruptured cerebral AVM patient cohort. Patients undergoing surgical treatment for a ruptured cerebral AVM (January 1, 2015-December 31, 2020) were retrospectively analyzed. Patients who underwent emergent treatment of a ruptured AVM because of acute herniation were excluded, as were those treated >180 days after rupture. Patients were stratified by the timing of surgical intervention relative to AVM rupture into early (postbleed days 1-20) and delayed (postbleed days 21-180) treatment cohorts. Eighty-seven patients were identified. The early treatment cohort comprised 75 (86%) patients. The mean (SD) length of time between AVM rupture and surgical resection was 5 (5) days in the early cohort and 73 (60) days in the delayed cohort ( P < .001). The cohorts did not differ with respect to patient demographics, AVM size, Spetzler-Martin grade, frequency of preoperative embolization, or severity of clinical presentation ( P ≥ .15). Follow-up neurological status was equivalent between the cohorts ( P = .65). The associated mean health care costs were higher in the delayed treatment cohort ($241 597 [$99 363]) than in the early treatment cohort ($133 989 [$110 947]) ( P = .02). After adjustment for length of stay, each day of delayed treatment increased cost by a mean of $2465 (95% CI = $967-$3964, P = .002). Early treatment of ruptured AVMs was associated with significantly lower health care costs than delayed treatment, but surgical and neurological outcomes were equivalent.

Untargeted plasma metabolome identifies biomarkers in patients with extracranial arteriovenous malformations.

Objective: This study aimed to investigate the plasma metabolic profile of patients with extracranial arteriovenous malformations (AVM). Method: Plasma samples were collected from 32 AVM patients and 30 healthy controls (HC). Ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) was employed to analyze the metabolic profiles of both groups. Metabolic pathway enrichment analysis was performed through Kyoto Encyclopedia of Genes and Genomes (KEGG) database and MetaboAnalyst. Additionally, machine learning algorithms such as Least Absolute Shrinkage and Selection Operator (LASSO) and random forest (RF) were conducted to screen characteristic metabolites. The effectiveness of the serum biomarkers for AVM was evaluated using a receiver-operating characteristics (ROC) curve. Result: In total, 184 differential metabolites were screened in this study, with 110 metabolites in positive ion mode and 74 metabolites in negative mode. Lipids and lipid-like molecules were the predominant metabolites detected in both positive and negative ion modes. Several significant metabolic pathways were enriched in AVMs, including lipid metabolism, amino acid metabolism, carbohydrate metabolism, and protein translation. Through machine learning algorithms, nine metabolites were identify as characteristic metabolites, including hydroxy-proline, L-2-Amino-4-methylenepentanedioic acid, piperettine, 20-hydroxy-PGF2a, 2,2,4,4-tetramethyl-6-(1-oxobutyl)-1,3,5-cyclohexanetrione, DL-tryptophan, 9-oxoODE, alpha-Linolenic acid, and dihydrojasmonic acid. Conclusion: Patients with extracranial AVMs exhibited significantly altered metabolic patterns compared to healthy controls, which could be identified using plasma metabolomics. These findings suggest that metabolomic profiling can aid in the understanding of AVM pathophysiology and potentially inform clinical diagnosis and treatment.

Preradiosurgical Embolization of Arteriovenous Malformations Reduces Target Volume – The Main Determinant for Complete Obliteration

Embolization and stereotactic radiosurgery (SRS) have increasingly been used to treat complex arteriovenous malformations (AVMs). We studied outcomes of AVM patients treated through a multidisciplinary approach, examined the effect of embolization on SRS success, and analyzed predictors of treatment failure. We retrospectively reviewed a prospectively maintained database of patients with AVMs treated with Gamma Knife (Leksell) SRS over an 11-year period. Patients with incomplete medical records and follow-up <2years were excluded. Demographics, clinical presentation, previous rupture history, angiographic nidus size, Spetzler-Martin (S-M) grade, adjunctive endovascular embolization and microsurgical resection, radiologic evidence of obliteration and hemorrhage, and clinical outcomes (modified Rankin Scale [mRS] scores) were recorded. Radiosurgery-related details including nidus volume and number of sessions and radiosurgery-, embolization-, and resection-associated complications were also recorded. Eighty-three patients (mean age, 41.0 ± 21.3years) were included. Mean reduction in AVM nidus target volume with endovascular embolization was 66.0 ± 19.7%. S-M grade reduction was achieved in 51.6% cases. Total obliteration after SRS was achieved in 56 AVMs (67.5%) after 2years, and in 38 (86.4%) after 4years. Two (2.4%) patients had rehemorrhage after SRS. Overall complication rate was 3.6%. Median angiographic follow-up was 55.5months. Favorable outcomes (mRS=0-2) were seen in 77.1%. SRS target volume was an independent predictor of treatment failure regardless of pre-SRS embolization. High AVM obliteration rates were achieved with judicious use of radiosurgery alone or with embolization. Embolization reduced target nidus volume by an average of 66%. SRS target volume was an independent predictor of treatment failure.

Cerebral AVM segmentation from 3D rotational angiography images by convolutional neural networks

Background and objective3D rotational angiography (3DRA) provides high quality images of the cerebral arteriovenous malformation (AVM) nidus that can be reconstructed in 3D. However, these reconstructions are limited to only 3D visualization without possible interactive exploration of geometric characteristics of cerebral structures. Refined understanding of the AVM angioarchitecture prior to treatment is mandatory and vascular segmentation is an important preliminary step that allow physicians analyze the complex vascular networks and can help guide microcatheters navigation and embolization of AVM. MethodsA deep learning method was developed for the segmentation of 3DRA images of AVM patients. The method uses a fully convolutional neural network with a U-Net-like architecture and a DenseNet backbone. A compound loss function, combining Cross Entropy and Focal Tversky, is employed for robust segmentation. Binary masks automatically generated from region-growing segmentation have been used to train and validate our model. ResultsThe developed network was able to achieve the segmentation of the vessels and the malformation and significantly outperformed the region-growing algorithm. Our experiments were performed on 9 AVM patients. The trained network achieved a Dice Similarity Coefficient (DSC) of 80.43%, surpassing other U-Net like architectures and the region-growing algorithm on the manually approved test set by physicians. ConclusionsThis work demonstrates the potential of a learning-based segmentation method for characterizing very complex and tiny vascular structures even when the training phase is performed with the results of an automatic or a semi-automatic method. The proposed method can contribute to the planning and guidance of endovascular procedures.

Language function of the superior longitudinal fasciculus in patients with arteriovenous malformation as evidenced by automatic fiber quantification.

The superior longitudinal fasciculus (SLF) is a major fiber tract involved in language processing and has been used to investigate language impairments and plasticity in many neurological diseases. The SLF is divided into four main branches that connect with different cortex regions, with two branches (SLF II, SLF III) being directly related to language. However, most white matter analyses consider the SLF as a single bundle, which may underestimate the relationship between these fiber bundles and language function. In this study, we investigated the differences between branches of the SLF in patients with arteriovenous malformation (AVM), which is a unique model to investigate language reorganization. We analyzed diffusion tensor imaging data of AVM patients and healthy controls to generate whole-brain fiber tractography, and then segmented the SLF into SLF II and III based on their distinctive waypoint regions. The SLF, SLF II, and III were further quantified, and four diffusion parameters of three branches were compared between the AVMs and controls. No significant diffusivity differences of the whole SLF were observed between two groups, however, the right SLF II and III in AVMs showed significant reorganization or impairment patterns as compared to the controls. Results demonstrating the need to subtracting SLF branches when studying structure-function relationship in neurological diseases that have SLF damage.

303 Frameless Angiography-Based Gamma Knife Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations

INTRODUCTION: Traditional GammaKnife radiosurgery (GKRS) of brain arteriovenous malformations (AVMs) using digital subtraction angiography requires head immobilization using a stereotactic frame. METHODS: This is a retrospective review of unruptured AVM patients who underwent frameless GKRS. Thin-cut magnetic resonance imaging and 3-dimensional DSA were obtained without a stereotactic frame for all patients. The imaging studies were merged for contouring of the AVM nidus. During GKRS treatment, patients were immobilized using an individually molded thermoplastic mask. RESULTS: Thirty-one patients were included in the analysis. The median age is 45.0 years (IQR 28.0-55.0). The median nidus size is 3.0 cm (IQR 2.0-3.4). One patient had a Spetzler-Martin grade I, 11 had a grade II, 11 had a grade III, 6 had a grade IV, and 2 had a grade IV AVM. Eleven patients underwent pre-radiosurgical embolization, two patients had previous microsurgical resection, and one patient had prior radiosurgery. The median administered dose was 20 Gy (IQR 18.0-21.0). Twenty-three patients were treated in a single fraction, 6 in 3 fractions, and two patients received 5 fractions. All patients completed their treatment with the planned radiation dose without complications. CONCLUSIONS: This is the first study that integrates digital subtraction angiography in the treatment planning of brain AVMs using GKRS without utilizing a stereotactic head frame. Frameless GKRS provides numerous advantages over frame-based techniques including improved patient experience, the capability of fractionation, thus, expanding the eligibility of more AVMs for radiosurgery, while maintaining high spatial resolution of the AVM using angiography data.

Germline genetic mutations in pediatric cerebrovascular anomalies: a multidisciplinary approach to screening, testing, and management.

Genetic alterations are increasingly recognized as etiologic factors linked to the pathogenesis and development of cerebrovascular anomalies. Their identification allows for advanced screening and targeted therapeutic approaches. The authors aimed to describe the role of a collaborative approach to care and genetic testing in pediatric patients with neurovascular anomalies, with the objectives of identifying what genetic testing recommendations were made, the yield of genetic testing, and the implications for familial screening and management at present and in the future. The authors performed a descriptive retrospective cohort study examining pediatric patients genetically screened through the Pediatric Neurovascular Program of a single treatment center. Patients 18 years of age and younger with neurovascular anomalies, diagnosed radiographically or histopathologically, were evaluated for germline genetic testing. Patient demographic data and germline genetic testing and recommendation, clinical, treatment, and outcome data were collected and analyzed. Sixty patients were included; 29 (47.5%) were female. The mean age at consultation was 11.0 ± 4.9 years. Diagnoses included cerebral arteriovenous malformations (AVMs) (n = 23), cerebral cavernous malformations (n = 19), non-neurofibromatosis/non-sickle cell moyamoya (n = 8), diffuse cerebral proliferative angiopathy, and megalencephaly-capillary malformation. Of the 56 patients recommended to have genetic testing, 40 completed it. Genetic alterations were found in 13 (23%) patients. Four patients with AVMs had RASA1, GDF2, and ACVRL1 mutations. Four patients with cavernous malformations had Krit1 mutations. One with moyamoya disease had an RNF213 mutation. Three patients with megalencephaly-capillary malformation had PIK3CA mutations, and 1 patient with a cavernous sinus lesion had an MED12 mutation. The majority of AVM patients were treated surgically. Patients with diffuse cerebral proliferative angiopathy were treated medically with sirolimus. At-risk relatives of 3 patients positive for genetic anomalies had also been tested. This study demonstrates a role for exploring genetic alterations in the identification and treatment of pediatric neurovascular disease pathogenesis. Germline genetic mutations were found in almost one-quarter of the patients screened in this study, results that helped to identify medically targeted treatment modalities for some pediatric neurovascular patients. Insight into the genetic etiology of vascular anomalies may provide broader clinical implications for risk assessment, family screening, follow-up surveillance, and medical management.

Resting-state functional alterations in patients with brain arteriovenous malformations involving language areas.

Brain arteriovenous malformations (AVMs) may involve language areas but usually do not lead to aphasia. This study evaluated resting-state functional alterations and investigated the language reorganization mechanism in AVM patients. Thirty-nine patients with AVMs involving language areas and 32 age- and sex-matched healthy controls were prospectively enrolled. The AVM patients were categorized into three subgroups according to lesion location: the frontal (15 patients), temporal (14 patients), and parietal subgroups (10 patients). All subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI), and the amplitude of low-frequency fluctuation (ALFF) approach was applied to analyze rs-fMRI data. Language abilities were normal in all participants based on the Western Aphasia Battery. Compared with those of healthy subjects, ALFF values significantly increased (FDR corrected p < .01) in the anterior part of the right putamen in the frontal AVM subgroup, in the posterior part of the right inferior and middle temporal gyrus in the temporal AVM subgroup, and in the inferior lateral part of the left cerebellar hemisphere (lobule VIII) and the right inferior parietal lobule in the parietal AVM subgroup. Functional annotation using Neurosynth indicated that the ALFF t-map was only significantly positively associated with the language-related domain (FDR corrected p < .01). In patients with AVMs involving the language cortex, language network reorganization occurs to maintain normal language abilities. The brain areas recruited into the reorganized language network were located in the right cerebral and left cerebellar hemispheres, both of which are nondominant hemispheres. Differences in lesion location led to distinct reorganization patterns.

A complex approach to the treatment of arteriovenous IV-V degree malformations according to Spetzler‒Martin scale. Clinical case

Four therapeutic approaches have been developed for the treatment of arteriovenous malformations (AVMs): microsurgery, radiosurgery, embolization, and conservative treatment. The lack of consensus regarding the choice of treatment method and the different specializations of the doctor who are onvolved to the patient with AVM often determine the wrong treatment strategy. We performed a prospective analysis of the results of AVM of the IV degree according to Spetzler‒Martin scale, 4–5 points on the Buffalo scale complex treatment, based on clinical and tomographic data after the use of partial endovascular embolization and radical microsurgical removal of the AVM node assisted by cell saving technology. According to cerebral angiography 4 months follow-up there is no visible AVM vessels, the malformation was completely resected.Treatment of large and giant AVMs (IV and V degrees according to the Spetzler‒Martin scale) requires tailored surgical treatment approache using endovascular, microsurgical and radiosurgical techniques, but in many cases without achieving a radical result. The use of cell saver technology is necessary to reduce the risks of intraoperative complications associated with blood loss during microsurgical intervention, and enables radical removal of the AVM and recovery of the patient. The role of cell saver technology is crucial in vascular microsurgical interventions, which are often accompanied by a significant volume of blood loss, ensuring rapid autologous hemotransfusion and restoration of circulating blood volume. Endovascular embolization is a necessary step to reduce the risks of intraoperative complications during microsurgical intervention, which, together with the use of cell saver technology, makes it possible to achieve radical AVM removal and patient recovery.

External validation of the R2eD AVM scoring system to assess rupture risk in pediatric AVM patients.

The assessment of hemorrhagic risk is of central importance in the management of pediatric brain arteriovenous malformations (AVMs). A recently published scoring system, the R2eD AVM (race, exclusive deep location or not, AVM size < 3 or ≥ 3, venous drainage exclusively deep or not, and monoarterial feeding or >1 arterial feeders) considers patient race and AVM location, size, venous drainage, and arterial supply and was successfully externally validated for use in adults to predict the risk of AVM hemorrhagic presentation. In this study the authors sought to externally validate the R2eD AVM score for prediction of hemorrhagic risk in the pediatric AVM population. A pediatric database at Boston Children's Hospital was retrospectively reviewed for all patients with a diagnosis of intracranial AVM. Exclusion criteria included age > 21 years, multiple AVMs, and incomplete clinical/radiographic data. Demographic data and R2eD AVM score calculations were collected for all patients. Univariate binary logistic regression and multivariate stepwise backward elimination models were used to determine factors associated with hemorrhagic presentation. A total of 212 AVMs were identified in 212 patients with vascular anomalies from 1995 to 2021, and 144 patients met the inclusion criteria (74 [51.4%] male, 111 [77.1%] White), of whom 87 (60.4%) patients presented with rupture and 122 (84.7%) underwent resection. The mean age at surgery was 12 years (range 3 months to 20 years). The R2eD AVM scoring system was applied to each patient. The score components of size < 3 cm and exclusive deep venous drainage were significantly associated with rupture risk (p < 0.05). The complete model for the R2eD AVM score had an area under the curve of 0.671 (95% CI 0.586-0.757). This study demonstrated poor external validity of the R2eD AVM score in predicting pediatric AVM rupture risk. The results suggest that future studies are warranted to determine a better scoring method to capture pediatric rupture risk, given the significant differences in clinical presentation in pediatric compared with adult AVM patients.