Deep Arteriovenous Malformations Research Articles

1133 Biologically Effective Dose and Prediction of Obliteration of Arteriovenous Malformations in Pediatric Patients Treated by Gamma Knife Radiosurgery

INTRODUCTION: Stereotactic radiosurgery (SRS) represents an effective treatment for pediatric arteriovenous malformations (AVMs). Biologic effective dose (BED) is recognized as a predictive variable for outcomes in the adult population, but its role has never been studied in pediatric outcomes. METHODS: Retrospective data for = 18 years old patients treated with single-session SRS for AVM was collected from 1989 – 2019. BED calculations were performed using an a/b ratio of 2.47. Kaplan-Meier analysis was used to evaluate obliteration, new hemorrhage, and radiation-induced changes (RIC). Cox-regression analysis was used for obliteration prediction using two models (margin dose versus BED). RESULTS: One-hundred-ninety-seven patients [median age = 13.1 years, Interquartile range (IQR) = 5.2] were included; 72.6% presented initially with spontaneous hemorrhage. A median margin dose of 22 Gy (IQ = 4.0) with a median BED of 183.2Gy (IQR = 70.54) was used to treat AVMs with a median volume of 2.8 cm3 (IQR = 2.9). Following SRS, obliteration was confirmed in 115 patients (58.4%) using MRI and angiography at a median follow-up of 2.85 years (IQR = 2.26). The cumulative obliteration probability was 43.6% (95% CI = 36.1-50.3), 60.5% (95% CI+=2.2-67.4), 66.0% (95% CI= 56.0-73.7) at 3, 5 and 10 years respectively. In multivariate analysis, a BED >180 Gy [HR = 2.11, 95% CI=1.30-3.40, p = 0.002] in model 1, and a margin dose >20 Gy [HR = 1.90, 95% CI = 1.15-3.13, p = 0.019] in model 2, were associated with obliteration. An AVM nidus volume >4 cm3 was associated with lower obliteration rates in both models. The probability of symptomatic RIC at 10 years was 8.6% (95% CI = 3.5-13.4). Neither BED nor margin dose were associated with RIC occurrence, with the only predictive factor being deep AVM location [HR = 3, 95% CI = 1-9.1, p = 0.048]. CONCLUSIONS: This study confirms BED as a predictor for pediatric AVM obliteration. Optimization of BED in pediatric AVM SRS planning may improve cumulative obliteration rates.

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.

Long-term outcomes of deep pediatric arteriovenous malformations.

Multimodality treatment has been shown to be the optimal management strategy for pediatric arteriovenous malformations (AVMs). Deep AVMs represent a subset of AVMs for which optimal management may be achieved with a combination of radiosurgery and highly selective embolization, in the absence of compelling features requiring operative intervention. The objective of this study was to identify predictors of good functional outcomes in pediatric patients with deep AVMs. A retrospective cohort study of the outcomes of 79 patients with deep AVMs from January 1988 through December 2021 was performed. Deep AVMs were defined as those with the majority of the nidus centered in the basal ganglia, thalamus, or brainstem. Collected data included patient demographics and presenting symptoms, presenting modified Rankin Scale (mRS) score, radiographic findings and outcomes, management strategy, complications, and clinical outcomes as indicated by follow-up mRS score. A good outcome was defined as a follow-up mRS score ≤ 2, while a poor outcome was defined as a follow-up mRS score ≥ 3. Statistical analysis was performed to identify factors associated with functional outcomes. With a mean follow-up duration of 85.6 months, there was a 72.2% angiographic obliteration rate, with 75.9% of patients having a good clinical outcome (mRS score ≤ 2). Presenting symptoms and radiographic characteristics were not significantly associated with long-term functional outcomes. There was a significantly higher rate of posttreatment hemorrhage in patients with a poor versus good outcome (11.8% vs 0%, p = 0.010). On multivariate logistic regression analysis, poor long-term functional outcome was only associated with poor presenting mRS score (p = 0.002). Satisfactory angiographic obliteration rates and good long-term functional outcomes can be achieved for deep AVMs, with stereotactic radiosurgery as the cornerstone of multimodality treatment.

Biologically Effective Dose and Prediction of Obliteration of Arteriovenous Malformations in Pediatric Patients Treated by Gamma Knife Radiosurgery.

Stereotactic radiosurgery (SRS) represents an effective treatment for pediatric arteriovenous malformations (AVMs). Biological effective dose (BED) has shown promising results in 2 previous studies as a predictive variable for outcomes in adults, but its role has never been studied in pediatric outcomes. Retrospective data for patients 18 years or younger treated with a single-session SRS for AVMs were collected from 1989 to 2019. BED calculations were performed using an α/β ratio of 2.47. Kaplan-Meier analysis was used to evaluate obliteration, new hemorrhage, and radiation-induced changes (RIC). Cox-regression analysis was used for obliteration prediction using 2 models (margin dose vs BED). One hundred ninety-seven patients (median age = 13.1 years, IQR = 5.2) were included; 72.6% (143/197) of them presented initially with spontaneous hemorrhage. A median margin dose of 22 Gy (IQR = 4.0) with a median BED of 183.2 Gy (IQR = 70.54) was used to treat AVM with a median volume of 2.8 cm 3 (IQR = 2.9). After SRS, obliteration was confirmed in 115/197 patients (58.4%) using magnetic resonance imaging and angiography at a median follow-up of 2.85 years (IQR = 2.26). The cumulative obliteration probability was 43.6% (95% CI = 36.1-50.3), 60.5% (95% CI+ = 2.2-67.4), and 66.0% (95% CI = 56.0-73.7) at 3, 5, and 10 years, respectively. In Cox multivariate analysis, a BED >180 Gy (hazard ratio [HR] = 2.11, 95% CI = 1.30-3.40, P = .002) in model 1 and a margin dose >20 Gy (HR = 1.90, 95% CI = 1.15-3.13, P = .019) in model 2 were associated with obliteration. An AVM nidus volume >4 cm 3 was associated with lower obliteration rates in both models. The probability of symptomatic RIC at 10 years was 8.6% (95% CI = 3.5-13.4). Neither BED nor margin dose was associated with RIC occurrence, with the only predictive factor being deep AVM location (HR = 3, 95% CI = 1-9.1, P = .048). This study confirms BED as a predictor for pediatric AVM obliteration. Optimization of BED in pediatric AVM SRS planning may improve cumulative obliteration rates.

Giant Brain Arteriovenous Malformation Managed by Staged Embolizations and Surgical Resection with Satisfactory Outcome

Spetzler-Martin grade V (>6 cm) arteriovenous malformations (AVMs) are traditionally considered inoperable. A 35-year-old man presented with repeated seizures for 7 years, and computed tomography arteriography and magnetic resonance imaging revealed left deep hemispheric AVM. A combination of embolization and surgical resection successfully achieved a cure of the patient. Well-equipped neurosurgery facilities can best manage selective Spetzler-Martin grade V AVMs with no neurologic deficits contrary to their traditionally inoperable concept. Successful surgery offers the patient a better quality of life.

Quantitative evaluation of the subsequent hemorrhage with arteriography-derived hemodynamic features in patients with untreated cerebral arteriovenous malformation.

Patients with untreated cerebral arteriovenous malformations (AVMs) are at risk of intracerebral hemorrhage. However, treatment to prevent AVM hemorrhage carries risks. This study aimed to analyze the AVM nidus-related hemodynamic features and identify the risk factors for subsequent hemorrhage. We retrospectively identified patients with untreated AVMs who were assessed at our institution between March 2010 and March 2021. Patients with ≥6 months of treatment-free and hemorrhage-free follow-up after diagnosed by digital subtraction angiography were included in subsequent examinations. The hemodynamic features were extracted from five contrast flow-related parameter maps. The Kaplan-Meier analyses and Cox proportional hazards regression models were used to find the potential risk factors for subsequent hemorrhage. Overall, 104 patients with a mean follow-up duration of 3.37 years (median, 2.42 years; range, 6-117 months) were included in study, and the annual risk of rupture was 3.7%. Previous rupture (hazard ratio [HR], 4.89; 95% confidence interval [CI], 1.16-20.72), deep AVM location (HR, 4.02; 95% CI, 1.01-15.99), higher cerebral blood volume (HR, 3.35; 95% CI, 1.15-9.74) in the nidus, and higher stasis index (HR, 1.54; 95% CI, 1.06-2.24) in the nidus were associated with subsequent hemorrhage in untreated AVMs. Higher cerebral blood volume and stasis index in the nidus suggest increased blood inflow and stagnant blood drainage. The combination of these factors may cause subsequent hemorrhage of AVMs.

391 Stereotactic Radiosurgery for Intermediate and High-Grade Arteriovenous Malformations: Outcomes Stratified by the Supplemented Spetzler-Martin Grading System

INTRODUCTION: The Supplemented Spetzler-Martin (Supp-SM) grading system is predictive of surgical risk for patients with brain arteriovenous malformations (AVM). METHODS: 219 patients had SRS from 1990 to 2016 for SM III (n = 154) or SM IV-V (n = 65) AVM. The Supp-SM grades were 4 (n = 14, 6%), 5 (n = 36, 16%), 6 (n = 67, 31%), 7 (n = 76, 35%), and 8-9 (n = 26, 12%). 60 patients (27%) had deep AVM (basal ganglia, thalamus, or brainstem). 39 patients (18%) had volume-staged SRS; 41 (19%) underwent repeat SRS. The median follow-up was 69 months for grade III AVM and 113 months for grade IV-V AVM. RESULTS: 163 patients (74%) had obliteration at a median of 38 months after initial SRS. The obliteration rates at 4 and 8 years were 59% and 76%, respectively. 31 patients (14%) had post-SRS deficits from hemorrhage (n = 7, 3%) or radiation injury (n = 24, 11%). 6 patients (3%) died after SRS (hemorrhage, n = 5; radiation injury, n = 1). The rates of neurologic decline or death at 4 and 8 years were 11% and 18%, respectively. Factors predictive of non-obliteration were deep location (HR 0.57, 95% CI 0.39-0.82, p = 0.003) and increasing AVM volume (HR 0.96, 95% CI 0.93-0.99, p = 0.002). Increasing AVM volume was the only factor associated with neurologic decline (HR 1.05, 95% CI 1.02-1.08, p = 0.002). The Supp-SM grading system did not correlate with obliteration (HR 0.94, 95% CI 0.82-1.09, p = 0.43) or neurologic decline (HR 1.15, 95% CI 0.84-1.56, p = 0.38). CONCLUSIONS: The Supp-SM grading system was not predictive of outcomes after SRS of intermediate or high-grade AVM. In a cohort which included a high percentage (47%) of “inoperable” AVM (Supp-SM ≥7), most patients had obliteration after SRS, although the chance of neurologic decline was significant.

Stereotactic radiosurgery for intermediate- and high-grade arteriovenous malformations: outcomes stratified by the supplemented Spetzler-Martin grading system.

The supplemented Spetzler-Martin (Supp-SM) grading system was developed to improve the predictive accuracy of surgical risk for patients with brain arteriovenous malformations (AVMs). The aim of this study was to apply the Supp-SM grading system to patients having stereotactic radiosurgery (SRS) for Spetzler-Martin (SM) intermediate- (grade III) or high-grade (grade IV-V) AVMs to enable comparison with published microsurgical series. In 219 patients who underwent SRS during the period from 1990 to 2016, the Supp-SM grade was calculated for SM grade III (n = 154) or SM grade IV-V (n = 65) AVMs. The Supp-SM grades in these patients were 4 (n = 14, 6%), 5 (n = 36, 16%), 6 (n = 67, 31%), 7 (n = 76, 35%), and 8-9 (n = 26, 12%). Sixty patients (27%) had deep AVMs (basal ganglia, thalamus, or brainstem). Thirty-nine patients (18%) had volume-staged SRS; 41 patients (19%) underwent repeat SRS. The median follow-up period was 69 months for SM grade III AVMs and 113 months for SM grade IV-V AVMs. AVM obliteration was confirmed in 163 patients (74%) at a median of 38 months after initial SRS. The obliteration rates at 4 and 8 years were 59% and 76%, respectively. Thirty-one patients (14%) had post-SRS deficits from hemorrhage (n = 7, 3%) or radiation injury (n = 24, 11%). Six patients (3%) died after SRS (hemorrhage, n = 5; radiation injury, n = 1). The rates of neurological decline or death at 4 and 8 years were 11% and 18%, respectively. Factors predictive of nonobliteration were deep location (HR 0.57, 95% CI 0.39-0.82, p = 0.003) and increasing AVM volume (HR 0.96, 95% CI 0.93-0.99, p = 0.002). Increasing AVM volume was the only factor associated with neurological decline (HR 1.05, 95% CI 1.02-1.08, p = 0.002). The Supp-SM grading score did not correlate with either obliteration (HR 0.94, 95% CI 0.82-1.09, p = 0.43) or neurological decline (HR 1.15, 95% CI 0.84-1.56, p = 0.38). The Supp-SM grading system was not predictive of outcomes after SRS of intermediate- or high-grade AVM. In a cohort that included a high percentage (47%) of "inoperable" AVMs according to Supp-SM grade (≥ 7), most patients had obliteration after SRS, although there was a high risk of neurological decline.

Clinical Characteristics and Multimodality Therapy Outcomes in 304 Pediatric Patients with Cerebral Arteriovenous Malformations

Clinical follow-up data of pediatric patients with cerebral arteriovenous malformations (AVMs) are limited. This study investigated the characteristics of AVMs in children and analyzed the clinical outcomes of multimodality therapy in pediatric patients with AVMs at a single center. This retrospective study included consecutive patients diagnosed with AVMs at our institution between August 2008 and June 2018. Data on demographic characteristics, AVM features, and clinical outcomes were collected. Patients aged <18years at admission were defined as children. Overall, 1009 patients with AVMs were included, with 304 (30.1%) patients aged <18years. AVMs in pediatric patients were more likely to present with intracranial hemorrhage, mostly located in deep areas of the brain. A small nidus, exclusively deep drainage, and deep AVM location were associated with hemorrhage in children; Kaplan-Meier analysis revealed that patients with ruptured AVMs had a higher risk of developing a follow-up hemorrhage than those with unruptured AVMs. Among 290 children who were followed up, the multivariate regression analysis showed that a higher pretreatment modified Rankin Scale score, deep AVM location, and conservative treatment were significantly associated with unfavorable outcomes. In pediatric patients, AVMs were more likely to present with intracranial hemorrhage than that in adults. Hemorrhagic presentation in children was associated with a small nidus, exclusively deep drainage, and deep AVM location. Pediatric patients with ruptured AVMs had significantly higher risks of follow-up hemorrhage than those with unruptured AVMs. Our clinical results suggest that nonconservative treatment is better for pediatric patients with AVMs.

Predictive Factors for Arteriovenous Malformation Obliteration After Stereotactic Radiosurgery: A Single-Center Study

Stereotactic radiosurgery (SRS) is particularly useful for treatment of deep arteriovenous malformations (AVMs) in eloquent territory with a high associated surgical risk. Prior studies have demonstrated high rates of AVM obliteration with SRS (60%-80%) in a latency period of 2-4 years for complete obliteration. Studies have identified several factors associated with successful obliteration of the AVM nidus; however, these present inconsistent and conflicting data. The aim of this single-center study was to examine factors associated with successful obliteration of AVMs treated with SRS. A retrospective review was performed of 210 consecutive patients undergoing SRS for brain AVMs between 2010 and 2019. The χ2 test and logistic regression analysis were used to identify patient and AVM factors associated with successful obliteration. Younger age (P= 0.034) and prior embolization (P= 0.012) were associated with complete obliteration. The presence of coronary artery disease was associated with incomplete obliteration (P= 0.04). No AVM characteristics were statistically associated with complete obliteration, although superficial venous drainage (P= 0.08) and frontal location (P= 0.06) trended toward significance. Successful obliteration of the AVM nidus was significantly associated with younger age and prior embolization. The presence of coronary artery disease negatively affected obliteration rates. These results add to the mixed results seen in the literature and emphasize the need for continued studies to delineate more specific patient and AVM factors that contribute to successful obliteration.

Microsurgical Treatment of Deep and Eloquent AVMs.

Over the past 30years, the treatment of deep and eloquent arteriovenous malformations (AVMs) has moved away from microneurosurgical resection and towards medical management and the so-called minimally invasive techniques, such as endovascular embolization and radiosurgery. The Spetzler-Martin grading system (and subsequent modifications) has done much to aid in risk stratification for surgical intervention; however, the system does not predict the risk of hemorrhage nor risk from other interventions. In more recent years, the ARUBA trial has suggested that unruptured AVMs should be medically managed. In our experience, although these eloquent regions of the brain should be discussed with patients in assessing the risks and benefits of intervention, we believe each AVM should be assessed based on the characteristics of the patient and the angio-architecture of the AVM, in particular venous hypertension, which may guide us to treat even high-grade AVMs when we believe we can (and need to) to benefit the patient. Advances in imaging and intraoperative adjuncts have helped us in decision making, preoperative planning, and ensuring good outcomes for our patients. Here, we present several cases to illustrate our primary points that treating low-grade AVMs can be more difficult than treating high-grade ones, mismanagement of deep and eloquent AVMs at the behest of dogma can harm patients, and the treatment of any AVM should be tailored to the individual patient and that patient's lesion.

Is there an Influence of Match and Mismatch of Venous Drainage Pattern on AVM Hemorrhagic Presentation?

To analyze whether there is an influence of match and mismatch of venous drainage patterns on arteriovenous malformation (AVM) hemorrhagic presentation. Consecutive 161 patients of AVM between 2014 and 2017 were retrospectively reviewed. Venous drainage was considered deep or superficial. Match of venous drainage pattern was defined as a superficial AVM with only superficial venous drainage or a deep AVM with deep venous drainage. Mismatch of venous drainage pattern was defined as a superficial AVM involving a deep venous drainage. Univariate analysis was used to assess the influence of match and mismatch of venous drainage pattern on AVM hemorrhagic presentation. AVM location and venous drainage were matched in 116 patients, including superficial location with superficial venous drainage or deep location with deep venous drainage, and were mismatched in 45 patients, including superficial location with deep venous drainage. The rupture proportion of mismatch venous drainage pattern was statistically comparable to that of deep location with deep drainage (P = 0.819). However, superficial location with deep venous drainage was statistically associated with a higher rupture percentage than that of superficial location with superficial venous drainage (P = 0.003). Mismatch venous drainage pattern or an exclusively deep venous drainage is associated with an initial clinical presentation with an AVM hemorrhage.

Comparison of management approaches in deep-seated intracranial arteriovenous malformations: Does treatment improve outcome?

Deep-seated intracranial arteriovenous malformations (AVMs) represent a subset of AVMs characterized by variably reported outcomes regarding the risk of hemorrhage, microsurgical complications, and response to stereotactic radiosurgery (SRS). We aimed to compare outcomes of microsurgery, SRS, endovascular therapy, and conservative follow-up in deep-seated AVMs. A prospectively maintained database of AVM patients (1990–2017) was queried to identify patients with ruptured and unruptured deep-seated AVMs (extension into thalamus, basal ganglia, or brainstem). Comparisons of hemorrhage-free survival and poor functional outcome (modified Rankin scale [mRS] > 2) were performed between conservative management, microsurgery (±pre-procedural embolization), SRS (±pre-procedural embolization), and embolization utilizing multivariable Cox and logistic regression analyses controlling for univariable factors with p < 0.05. Of 789 AVM patients, 102 had deep-seated AVMs (conservative: 34; microsurgery: 6; SRS: 54; embolization: 8). Mean follow-up time was 6.1 years and did not differ significantly between management groups (p = 0.393). Complete obliteration was achieved in 49% of SRS patients. Upon multivariable analysis controlling for baseline rupture with conservative management as a reference group, embolization was associated with an increased hazard of hemorrhage (HR = 6.2, 95%CI [1.1–40.0], p = 0.037), while microsurgery (p = 0.118) and SRS (p = 0.167) provided no significant protection from hemorrhage. Controlling for baseline mRS, microsurgery was associated with an increased risk of poor outcome (OR = 9.2[1.2–68.3], p = 0.030), while SRS (p = 0.557) and embolization (p = 0.541) did not differ significantly from conservative management. Deep AVMs harbor a high risk of hemorrhage, but the benefit from intervention Remains uncertain. SRS may be a relatively more effective approach if interventional therapy is indicated.

Microsurgical approach for symptomatic brain AVMs – single center experience

ABSTRACT Objectives: Brain arteriovenous malformations (AVMs) represent high-flow vascular lesions made up of a complex network of feeding arteries and draining veins interposed by a nidus and without a capillary bed. The management of the AVMs represents a challenge, and the optimal treatment should be considered based on the particularities of each AVM. This paper aims to provide outcome data for the cohort of patients with AVMs that underwent surgical treatment. Methods: A retrospective review of patients who presented with AVMs between 2001 and 2019 was conducted. Patients were included if they underwent surgery, preoperative and postoperative angiographic studies were available. Results: 91 patients were included. The SM grade was 1 in 16 cases (17,6%), 2 in 27 patients (29.7%), 3 in 29 patients (31,9%), 4 in 12 cases (13.2%) and grade 5 in 7 cases (7.7%). In 58 (63.7%) cases the AVMs were ruptured. Complete microsurgical resection was achieved in 82 cases (90.1%). Unruptured AVM (87.9% vs. 63.8% for ruptured AVMs; p = 0.015), low-grade AVM (86% vs. 60.4% for grade III–V AVMs; p = 0.006) and cortical location (79.5% vs. 30.8% for deep AVM; p < 0.0001) were the factors associated with a good outcome on mRS scale. Conclusions: Microsurgical resection is the curative treatment for AVMs and offers a good functional outcome if selection criteria are met.

Analysis of the Related Risk Factors of Cerebral AVM Hemorrhage and the Relationship Between EPCs and SDF-1 in Brain AVM

To explore the related risk factors of hemorrhage in human brain cerebral arteriovenous malformations (AVM) and the relationship between endothelial progenitor cells (EPCs) content and stromal cell-derived factor-1 (SDF-1) in different ages. A retrospective analysis was conducted on 130 patients with cerebral AVM who underwent surgical treatment from May 2012 to October 2018. Univariate and multivariate logistic analysis was used to investigate the related risk factors of cerebral AVM hemorrhage. Forty paraffin specimens of human brain AVM were harvested from 24 cases of cerebral hemorrhage patients and 16 cases of non-cerebral hemorrhage patients Paraffin samples of cerebral cortex from 8 patients with epilepsy during the same period were selected as control. Positive expression of CD34 and vascular endothelial growth factor receptor 2 (KDR2) in brain tissue samples of both groups were used to identify EPCs. Immunofluorescence double staining was used for KDR2 and CD34 positive localization to determine EPCs localization, and SDF-1 expression detection was performed. The size of brain AVM<3 cm, deep brain AVM and single venous drainage are independent risk factors for cerebral AVM hemorrhage. Immunohistochemical results showed that CD34 and KDR2 were expressed in cerebral AVM group, but not in the control group. Double immunofluorescence staining showed that EPCs mainly existed at the edge of vascular wall, while SDF-1 could co-stain with alpha-smooth muscle actin (α-SMA) positive cells and CD31 positive cells. SDF-1 expression in brain AVM tissue was higher than that in control group. There were significant differences in the number of EPCs among the patients of different ages ( P<0.05). There was no significant difference in EPCs between cerebral hemorrhage group and non-hemorrhage group ( P>0.05). Brain AVM (<3 cm), single venous drainage and deep brain AVM are independent risk factors for cerebral AVM hemorrhage. In human brain AVM, EPC appears high level but decrease with age, which may play a role in vascular remodeling in AVM.

Early obliteration of pediatric brain arteriovenous malformations after stereotactic radiosurgery: an international multicenter study.

Stereotactic radiosurgery (SRS) is a treatment option for pediatric brain arteriovenous malformations (AVMs), and early obliteration could encourage SRS utilization for a subset of particularly radiosensitive lesions. The objective of this study was to determine predictors of early obliteration after SRS for pediatric AVMs. The authors performed a retrospective review of the International Radiosurgery Research Foundation AVM database. Obliterated pediatric AVMs were sorted into early (obliteration ≤ 24 months after SRS) and late (obliteration > 24 months after SRS) responders. Predictors of early obliteration were identified, and the outcomes of each group were compared. The overall study cohort was composed of 345 pediatric patients with obliterated AVMs. The early and late obliteration cohorts were made up of 95 (28%) and 250 (72%) patients, respectively. Independent predictors of early obliteration were female sex, a single SRS treatment, a higher margin dose, a higher isodose line, a deep AVM location, and a smaller AVM volume. The crude rate of post-SRS hemorrhage was 50% lower in the early (3.2%) than in the late (6.4%) obliteration cohorts, but this difference was not statistically significant (p = 0.248). The other outcomes of the early versus late obliteration cohorts were similar, with respect to symptomatic radiation-induced changes (RICs), cyst formation, and tumor formation. Approximately one-quarter of pediatric AVMs that become obliterated after SRS will achieve this radiological endpoint within 24 months of initial SRS. The authors identified multiple factors associated with early obliteration, which may aid in prognostication and management. The overall risks of delayed hemorrhage, RICs, cyst formation, and tumor formation were not statistically different in patients with early versus late obliteration.

Risk of Brain Arteriovenous Malformation Hemorrhage Before and After Stereotactic Radiosurgery.

Background and Purpose- Understanding the hemorrhage risks associated with brain arteriovenous malformations (AVMs) before and after stereotactic radiosurgery (SRS) is important. The aims of this multicenter, retrospective cohort study are to evaluate and compare the rates of pre- and post-SRS AVM hemorrhage and identify risk factors. Methods- We pooled AVM SRS data from 8 institutions participating in the International Radiosurgery Research Foundation. Predictors of post-SRS hemorrhage were determined using a multivariate logistic regression model. Pre- and post-SRS hemorrhage rates were compared using Fisher exact test. Ruptured and unruptured AVMs were matched in a 1:1 ratio using propensity scores, and their outcomes were compared. Results- The study cohort comprised 2320 AVM patients who underwent SRS. Deep AVM location (odds ratio, 1.86; 95% CI, 1.19-2.92; P=0.007), the presence of an AVM-associated arterial aneurysm (odds ratio, 2.44; 95% CI, 1.63-3.66; P<0.001), and lower SRS margin dose (odds ratio, 0.93; 95% CI, 0.88-0.98; P=0.005) were independent predictors of post-SRS hemorrhage. The post-SRS hemorrhage rate was lower for obliterated versus patent AVMs (6.0 versus 22.3 hemorrhages/1000 person-years; P<0.001). The AVM hemorrhage rate decreased from 15.4 hemorrhages/1000 person-years before SRS to 11.9 after SRS ( P=0.001). The outcomes of the matched ruptured versus unruptured AVM cohorts were similar. Conclusions- SRS appears to reduce the risk of AVM hemorrhage, although this effect is predominantly driven by obliteration. Deep-seated AVMs are more likely to rupture during the latency period after SRS. AVM-associated aneurysms should be considered for selective occlusion before SRS of the nidus to ameliorate the post-SRS hemorrhage rate of these lesions.

Characteristics and Long-Term Outcome of 127 Children With Cerebral Arteriovenous Malformations

Population-based long-term data on pediatric patients with cerebral arteriovenous malformations (AVMs) are limited. To clarify the characteristics and long-term outcome of pediatric patients with AVM. A retrospective analysis was performed on 805 consecutive brain AVM patients admitted to a single center between 1942 and 2014. The patients were defined as children if they were under 18 yr at admission. Children were compared to an adult cohort. Changing patterns of presentation were also analyzed by decades of admission. The patients comprised 127 children with a mean age of 12 yr. The mean follow-up time was 21 yr (range 0-62). Children presented more often with intracerebral hemorrhage (ICH) but less often with epilepsy than adults. Basal ganglia, cerebellar, and posterior paracallosal AVMs were more common in pediatric than in adult patients. Frontal and temporal AVMs, in contrast, were more common in adult than in pediatric patients. As the number of incidentally and epilepsy-diagnosed AVMs increased, ICH rates dropped in both cohorts. In total, 22 (82%) pediatric and 108 (39%) adult deaths were assessed as AVM related. After multivariate analysis, small AVM size and surgical treatment correlated with a favorable long-term outcome. Hemorrhagic presentation was more common in children than in adults. This was also reflected as lower prevalence of epileptic presentation in the pediatric cohort. Lobar and cortical AVM locations were less frequent, whereas deep and cerebellar AVMs were more common in children. Hemorrhagic presentation correlated negatively with incidentally and epilepsy-diagnosed AVMs. In children, AVM was a major cause of death, but in adults, other factors contributed more commonly to mortality.

Radiation-Induced Changes After Stereotactic Radiosurgery for Brain Arteriovenous Malformations: A Systematic Review and Meta-Analysis.

Radiation-induced changes (RICs) are the most common complication of stereotactic radiosurgery (SRS) for brain arteriovenous malformations (AVMs), and they appear as perinidal T2-weighted hyperintensities on magnetic resonance imaging, with or without associated neurological symptoms. To determine the rates of RIC after AVM SRS and identify risk factors. A literature review was performed using PubMed and MEDLINE to identify studies reporting RIC in AVM patients treated with SRS. RICs were classified as radiologic (any neuroimaging evidence), symptomatic (any associated neurological deterioration, regardless of duration), and permanent (neurological decline without recovery). Baseline, treatment, and outcomes data were extracted for statistical analysis. Based on pooled data from 51 studies, the overall rates of radiologic, symptomatic, and permanent RIC after AVM SRS were 35.5% (1143/3222 patients, 32 studies), 9.2% (499/5447 patients, 46 studies), and 3.8% (202/5272 patients, 39 studies), respectively. Radiologic RIC was significantly associated with lack of prior AVM rupture (odds ratio [OR]=0.57; 95% confidence interval [CI]: 0.47-0.69; P<.001) and treatment with repeat SRS (OR=6.19; 95% CI: 2.42-15.85; P<.001). Symptomatic RIC was significantly associated with deep AVM location (OR=0.38; 95% CI: 0.21-0.67; P<.001). Approximately 1 in 3 patients with AVMs treated with SRS develop radiologically evident RIC, and of those with radiologic RIC, 1 in 4 develop neurological symptoms. Lack of prior AVM hemorrhage and repeat SRS are risk factors for radiologic RIC, and deep nidus location is a risk factor for symptomatic RIC.

Contralateral Transfalcine Versus Ipsilateral Anterior Interhemispheric Approach for Midline Arteriovenous Malformations: Surgical and Anatomical Assessment

The contralateral anterior interhemispheric approach (CAIA) is considered to provide surgical advantages to access deep midline lesions: wider working angle, gravity enhanced dissection and retraction, more efficient lighting, and ergonomics. Our team has previously published on the merits of using a contralateral trajectory for medial frontoparietal arteriovenous malformations (AVMs) compared with the conventional anterior interhemispheric approach (IAIA). In this article, we compare the IAIA and CAIA for the resection of medial frontoparietal AVMs using quantitative surgical and anatomical analysis. Two models were designed mimicking the most common features of midline AVMs. The CAIA and IAIA were performed bilaterally in 10 specimens. Variables to compare technical feasibility (surgical window [SW] and surgical freedom [SF], target exposure, and angle of attack) were independently assessed using stereotactic navigation. The average SW, SF, and angle of attack were compared with the Student t test. Significance threshold was set at 0.05. The CITA and IAIA were similar in terms of SW, target exposure, and SF in the superior aspect of the AVM. In the depth of the interhemispheric fissure, the CAIA was significantly superior to IAIA in both AVM models: 77% wider AA for the inferior aspect of the AVM (P < 0.01) and greater SF for the draining vein (54%, P= 0.01), ipsilateral (98%, P= 0.02), and contralateral ACA (117%, P < 0.01). This study suggests technical superiority of the CAIA for the resection of deep midline AVMs. No objective difference was noted in the superficial areas of our models, denoting that IAIA is a safer choice for superficial AVMs. Our results set the foundation for further clinical analysis comparing both approaches.