Arteriovenous Malformations Volume Research Articles

Examining barriers to care: a retrospective cohort analysis investigating the relationship between hospital volume and outcomes in pediatric patients with cerebral arteriovenous malformations.

Comprehensive data on treatment patterns of pediatric cerebral arteriovenous malformations (AVMs) are lacking. The authors' aim was to examine national trends, assess the effect of hospital volume on outcomes, and identify variables associated with treatment at high-volume centers. Pediatric AVM admissions (for ruptured and unruptured lesions) occurring in the US in 2016 and 2019 were identified using the Kids' Inpatient Database. Demographics, treatment methods, costs, and outcomes were recorded. The effect of hospital AVM volume on outcomes and factors associated with treatment at higher-volume hospitals were analyzed. Among 2752 AVM admissions identified, 730 (26.5%) patients underwent craniotomy, endovascular treatment, or a combination. High-volume (vs low-volume) centers saw lower proportions of Black (8.7% vs 12.9%, p < 0.001) and lowest-income quartile (20.7% vs 27.9%, p < 0.001) patients, but were more likely to provide endovascular intervention (19.5%) than low-volume institutions (13.7%) (p = 0.001). Patients treated at high-volume hospitals had insignificantly lower numbers of complications (mean 2.66 vs 4.17, p = 0.105) but significantly lower odds of nonroutine discharge (OR 0.18 [95% CI 0.06-0.53], p = 0.009) and death (OR 0.13 [95% CI 0.02-0.75], p = 0.023). Admissions at high-volume hospitals cost more than at low-volume hospitals, regardless of whether intervention was performed ($64,811 vs $48,677, p = 0.001) or not ($64,137 vs $33,779, p < 0.001). Multivariable analysis demonstrated that Hispanic children, patients who received AVM treatment, and those in higher-income quartiles had higher odds of treatment at high-volume hospitals. In this largest study of US pediatric cerebral AVM admissions to date, higher hospital volume correlated with several better outcomes, particularly when patients underwent intervention. Multivariable analysis demonstrated that higher income and Hispanic race were associated with treatment at high-volume centers, where endovascular care is more common. The findings highlight the fact that ensuring access to appropriate treatment of patients of all races and socioeconomic classes must be a focus.

Comparison of Repeat Versus Initial Stereotactic Radiosurgery for Intracranial Arteriovenous Malformations: A Retrospective Multicenter Matched Cohort Study

BACKGROUND AND OBJECTIVES: Studies comparing neurological and radiographic outcomes of repeat to initial stereotactic radiosurgery (SRS) intracranial arteriovenous malformations are scarce. Our aim was to perform a retrospective matched comparison of patients initially treated with SRS with those undergoing a second radiosurgical procedure. METHODS: We collected data from arteriovenous malformations managed in 21 centers that underwent initial and repeated radiosurgery from 1987 to 2022. Based on arteriovenous malformations volume, margin dose, deep venous drainage, deep, and critical location, we matched 1:1 patients who underwent an initial SRS for treatment-naive arteriovenous malformations and a group with repeated SRS treatment. RESULTS: After the selection process, our sample consisted of 328 patients in each group. Obliteration in the initial SRs group was 35.8% at 3 and 56.7% at 5 years post-SRS, while the repeat SRS group showed obliteration rates of 33.9% at 3 years and 58.6% at 5 years, without statistically significant differences (P = .75 and P = .88, respectively). There were no statistically significant differences between the 2 groups for obliteration rates (hazard ratio = 0.93; 95% CI, 0.77-1.13; P = .5), overall radiation-induced changes (RIC) (OR = 1.1; 95% CI, 0.75-1.6; P = .6), symptomatic RIC (OR = 0.78; 95% CI, 0.4-1.5; P = .4), and post-SRS hemorrhage (OR = 0.68; 95% CI; P = .3). CONCLUSION: In matched cohort analysis, a second SRS provides comparable outcomes in obliteration and RIC compared with the initial SRS. Dose reduction on repeat SRS may not be warranted.

Hypofractionated stereotactic radiotherapy in Spetzler Martin grades 4 and 5 arteriovenous malformations in the pediatric population: Is it a viable alternative?

To analyze the outcomes of hypofractionated stereotactic radiotherapy (HFSRT) for Spetzler Martin grades 4 and 5 arteriovenous malformations (AVMs) in a pediatric population. Fourteen patients with Spetzler Martin (SM) grades IV and V large AVMs who underwent HFSRT between January 2013 and July 2019 were retrospectively reviewed. All patients received HFSRT at a dose of 30-36Gy in 5 to 6 fractions. They were followed up annually with clinical and imaging assessments to evaluate obliteration rates. The median age at presentation was 15years (range 8-21years). Ten (71%) were SM grade 4 AVMs and the rest were SM grade 5 AVMs. The majority presented with headache (8 [57%]), and 3 (21%) presented with bleeding. The median nidus volume was 39.4cc (IQR, 31.4-52.4). Two (14%) patients had infratentorial AVMs. All of them had deep venous drainage. The median clinical follow-up duration was 75months (range 31-107months). There was complete obliteration of the nidus in 3 (21%) patients with a median time to obliteration of 39months. HFSRT resulted in a reduction of the AVM volume to 12cc or less in nearly 70% of patients. None of the patients experienced re-bleeding. 79% reported an improvement in their symptoms. HFSRT is a highly effective treatment for high-grade AVMs in children, which can result in either complete elimination or significant reduction of the nidus volume or make it suitable for additional treatment, such as single-session stereotactic radiosurgery (SRS).

Feasibility of Gamma Knife Radiosurgery for Brain Arteriovenous Malformations According to Nidus Type.

Gamma Knife Radiosurgery (GKRS) is an effective and noninvasive treatment for high-risk arteriovenous malformations (AVMs). Since differences in GKRS outcomes by nidus type are unknown, this study evaluated GKRS feasibility and safety in patients with brain AVMs. This single-center retrospective study included patients with AVM who underwent GKRS between 2008 and 2021. Patients were divided into compact- and diffuse-type groups according to nidus characteristics. We excluded patients who performed GKRS and did not follow-up evaluation with MRI or DSA within 36 months from the study. We used univariate and multivariate analyses to characterize associations of nidus type with obliteration rate and GKRS-related complications. We enrolled 154 patients (mean age, 32.14±17.17 years; mean post-GKRS follow-up, 52.10±33.67 months) of whom 131 (85.1%) had compact- and 23 (14.9%) diffuse-type nidus AVMs. Of all AVMs, 89 (57.8%) were unruptured, and 65 (42.2%) had ruptured. The mean Spetzler-Martin AVM grades were 2.03±0.95 and 3.39±1.23 for the compact- and diffuse-type groups, respectively (p<0.001). During the follow-up period, AVM-related hemorrhages occurred in four individuals (2.6%), three of whom had compact nidi. Substantial radiation-induced changes and cyst formation were observed in 21 (13.6%) and 1 (0.6%) patients, respectively. The AVM complete obliteration rate was 46.1% across both groups. Post-GKRS complication and complete obliteration rates were not significantly different between nidus types. For diffuse-type nidus AVMs, larger AVM size and volume (p<0.001), lower radiation dose (p<0.001), eloquent area location (p=0.015), and higher Spetzler-Martin grade (p<0.001) were observed. GKRS is a safe and feasible treatment for brain AVMs characterized by both diffuse- and compact-type nidi.

Radiosurgery With Prior Embolization Versus Radiosurgery Alone for Intracranial Arteriovenous Malformations: A Systematic Review and Meta-Analysis.

The addition of adjuvant embolization to radiosurgery has been proposed as a means of improving treatment outcomes of intracranial arteriovenous malformations (AVMs). However, the relative efficacy and safety of radiosurgery with adjuvant embolization vs radiosurgery alone remain uncertain. Moreover, previous systematic reviews and meta-analyses have included a limited number of studies and did not consider the effects of baseline characteristics, including AVM volume, on the outcomes. This systematic review aimed to evaluate the efficacy of preradiosurgery embolization for intracranial AVMs with consideration to matching status between participants in each treatment group. A systematic review and meta-analysis were conducted by searching electronic databases, including PubMed, Scopus, and Cochrane Library, up to January 2023. All studies evaluating the utilization of preradiosurgery embolization were included. A total of 70 studies (9 matched and 71 unmatched) with a total of 12 088 patients were included. The mean age of the included patients was 32.41 years, and 48.91% of the patients were female. Preradiosurgery embolization was used for larger AVMs and patients with previous hemorrhage ( P < .01, P = .02, respectively). The obliteration rate for preradiosurgery embolization (49.44%) was lower compared with radiosurgery alone (61.42%, odds ratio = 0.56, P < .01), regardless of the matching status of the analyzed studies. Although prior embolization was associated higher rate of cyst formation ( P = .04), it lowered the odds of radiation-induced changes ( P = .04). The risks of minor and major neurological deficits, postradiosurgery hemorrhage, and mortality were comparable between groups. This study provides evidence that although preradiosurgery embolization is a suitable option to reduce the AVM size for future radiosurgical interventions, it may not be useful for same-sized AVMs eligible for radiosurgery. Utilization of preradiosurgery embolization in suitable lesions for radiosurgery may result in the added cost and burden of an endovascular procedure.

Effect of Cobalt-60 Treatment Dose Rate on Arteriovenous Malformation Obliteration After Stereotactic Radiosurgery With Gamma Knife.

Stereotactic radiosurgery (SRS) marginal dose is associated with successful obliteration of cerebral arteriovenous malformations (AVM). SRS dose rate-how old the cobalt-60 sources are-is known to influence outcomes for some neurological conditions and benign tumors. The objective of this study was to determine the association between cobalt-60 treatment dose rate and cerebral AVM obliteration in patients treated with SRS. We performed a retrospective cohort study of 361 patients undergoing 411 AVM-directed SRS treatments between 2005 and 2019 at a single institution. Lesion characteristics, SRS details, obliteration dates, and post-treatment toxicities were recorded. Univariate and multivariate regression analyses of AVM outcomes regarding SRS dose rate (range 1.3-3.7 Gy, mean = 2.4 Gy, median = 2.5 Gy) were performed. At 10 years post-SRS, 68% of AVMs were obliterated on follow-up imaging. Dose rates >2.9 Gy/min were found to be significantly associated with AVM obliteration compared with those <2.1 Gy/min ( P = .034). AVM size, biologically effective dose, and SRS marginal dose were also associated with obliteration, with obliteration more likely for smaller lesions, higher biologically effective dose, and higher marginal dose. Higher dose rates were not associated with the development of post-SRS radiological or symptomatic edema, although larger AVM volume was associated with both types of edema. Patients with cerebral AVMs treated with higher SRS dose rates (from newer cobalt-60 sources) experience higher incidences of obliteration without a significant change in the risk of post-treatment edema.

Effect of Cobalt-60 Calibration Dose-Rate on Arteriovenous Malformation Obliteration after Stereotactic Radiosurgery

Stereotactic radiosurgery (SRS) dose rate - how old the cobalt-60 sources are - is known to influence outcomes for some neurologic conditions and benign tumors, but it is not known if SRS dose rate influences arteriovenous malformation (AVM) obliteration. The objective of this study is to determine the association between cobalt-60 calibration dose rate and cerebral AVM obliteration in patients treated with SRS. Our hypothesis is that higher SRS dose rates are associated with increased incidence of cerebral AVM obliteration. We performed a retrospective study of 361 patients undergoing 411 AVM-directed SRS treatments between 2005 and 2019 at a single institution. Obliteration was confirmed with digital subtraction angiogram or MRI (if patient refused angiography). Lesion characteristics, SRS treatment details, and post-treatment obliteration and toxicities were recorded. Univariate and multivariate proportional hazards regression models of AVM outcomes with regard to SRS dose rate were performed, controlling for factors such as Spetzler-Martin Grade, maximum AVM extent, prior hemorrhage and prior embolization. At 10 years post-SRS, 68% of AVMs were obliterated on follow-up imaging. Dose rates >2.9 Gy/min were found to be significantly associated with AVM obliteration compared to those <2.1 Gy/min (p = 0.034, Gray's test). AVM size or Spetzler-Martin grade were also associated with obliteration, with obliteration more likely for smaller lesions, particularly those <3 cm in maximal diameter, or with lower Spetzler-Martin grade. Higher dose rates were not associated with development of post-SRS radiologic or symptomatic edema, though larger AVM volume was associated with both types of edema. Patients with cerebral AVMs treated with higher SRS dose rates (from fresh cobalt-60 sources) experience higher incidences of obliteration, without a significant change in the risk of post-treatment edema. These findings suggest that clinics offering SRS for AVMs should regularly renew cobalt-60 radiation sources to maintain high therapeutic dose rates.

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.

Correlation Between Post-Radiosurgery Perinidal Hyperintensity and AVM Obliteration Following LINAC-Based Stereotactic Radiosurgery

We studied the correlation between new-onset perinidal hyperintensity (PH) on T2-weighted magnetic resonance imaging and obliteration of intracranial arteriovenous malformation (AVM) after stereotactic radiosurgery (SRS). A retrospective study of 148 patients with an intracranial AVM who underwent SRS between September 2005 and June 2018 and had ≥1 radiological follow-up (early magnetic resonance imaging) 12-18 months after SRS was performed to analyze the correlation between PH (graded from 0 to 2) and AVM obliteration. Of the 148 patients, 95 were male. The mean patient age was 27.7 ± 12.4 years. Of the 148 AVMs, 105 (70.9%) were obliterated at a median follow-up of 27 months (interquartile range, 14-48 months). The cumulative 3-, 5-, 10-year obliteration rate was 51.8%, 70.8%, and 91.8%, respectively. New-onset PH was observed in 58 AVMs (39.2%; 50 obliterated and 8 not obliterated). No association was found between the pretreatment variables or dose delivered and the development of PH. Grade 2 PH was associated with the risk of symptoms developing compared with grade 1 PH (37.5% vs. 4%; P= 0.002). Symptomatic PH was more likely to develop in patients with a larger AVM (P= 0.05). On multivariate analysis, the presence of a single draining vein (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.3-6.8), a lower median AVM volume (OR, 0.97; 95% CI, 0.6-0.89), a mean marginal radiation dose (OR, 1.29; 95% CI, 1.02-1.64), and the presence of PH (OR, 3.16; 95% CI, 1.29-7.71) were independent predictors of AVM obliteration. The incidence of PH after SRS for AVM was 39.2%. PH was an independent predictor of AVM obliteration after SRS. Grade 2 PH and a larger AVM volume were associated with symptomatic PH.

Quantitative Analysis of Parenchymal Effects and Flow of Large Arteriovenous Malformations Managed With Stereotactic Radiosurgery.

Stereotactic radiosurgery (SRS) of larger arteriovenous malformations (AVM) is associated with an elevated incidence of adverse radiation effects (ARE). To date, volume-response and dose-response models have been used to predict such effects. To understand radiological outcomes and their hemodynamic effects on the regional brain. A retrospective analysis was conducted at our institution using a prospective registry of patients managed between 2014 and 2020. We included patients with AVM with a nidus larger than 5 cc who received either single-session or volume-staged Gamma Knife radiosurgery. AVM volume changes, volumes of parenchymal response, and obliteration were analyzed and correlated with transit times and diameters of feeding arteries and draining veins. Sixteen patients underwent single-session SRS, and 9 patients underwent volume-staged SRS. The average AVM volume was 12.6 cc (5.5-23). The AVM locations were predominantly lobar (80%) and 17 (68%) were in critical locations. The mean margin dose was 17.2 Gy (15-21), and the median V12Gy was 25.5 cc. Fourteen (56%) AVMs had a transit time shorter than 1 second. The median vein-artery ratio (sum diameter of the veins/sum diameter of feeding arteries) was 1.63 (range, 0.60-4.19). Asymptomatic parenchymal effects were detected in 13 (52%) patients and were symptomatic in 4 (16%) patients. The median time to ARE was 12 months (95% CI 7.6-16.4). On univariate analysis, significant predictors of ARE were lower vein-artery ratio ( P = .024), longer transit time ( P = .05), higher mean dose ( P = .028), and higher D95 ( P = .036). Transit times and vessel diameters are valuable predictors of the subsequent parenchymal response after SRS. A more quantitative understanding of blood flow is critical for predicting the effects on the regional brain after AVM radiosurgery.

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.

Gamma Knife Radiosurgery in Partially Embolised Arteriovenous Malformations: Management Dilemmas and Outcomes.

The role of Gamma Knife radiosurgery (GKRS) in partially embolized arteriovenous malformations (AVMs) has always remained a subject of debate. The aim of this study was to evaluate the efficacy of GKRS in partially embolized AVMs and to analyze factor that influence its obliteration. This was a retrospective study from a single institute performed over a period of 12 years (2005-2017). It included all patients who underwent GKRS for partially embolized AVMs. Demographic characteristics, treatment profiles, and clinical and radiological data were obtained during treatment and follow-up. Obliteration rates and factors affecting the same were sought and analyzed. A total of 46 patients with a mean age of 30 years (range: 9-60 years) were included in the study. Follow-up imaging was available for 35 patients either by digital subtraction angiography (DSA) or magnetic resonance imaging (MRI). We found complete AVM obliteration in 21 patients (60%): one had near total obliteration (>90% obliteration), 12 had subtotal obliteration (<90%), and one had no change in the volume following GKRS. Following embolization alone, an average of 67% of the AVM volume was obliterated which resulted in an average 79% final obliteration rate after Gamma Knife radiosurgery. Mean duration to complete obliteration was found to be 3.45 years (range: 1-10 years). There was a significant difference (P = 0.04) in the mean interval between embolization and GKRS among cases with complete obliteration (12 months) and those with incomplete obliteration (36 months). There was no significant difference (P = 0.49) in the average obliteration rate between the ARUBA-eligible unruptured AVMs (79.22%) and ruptured AVMs (79.04%). Bleeding after GKRS during the latency period had a negative impact on obliteration (P = 0.05). Other factors like age, sex, Spetzler-Martin (SM)-grade, Pollock Flickinger score (PF-score), nidus volume, radiation dose, or presentation before embolization had no significant influence on obliteration. Three patients had permanent neurological deficits after embolization and none after radiosurgery. Six out of nine patients (66%) presenting with seizures were seizure-free after the treatment. Hemorrhage was noted in three patients following combined treatment and were managed non-surgically. Obliteration rates in partially embolized AVM after Gamma Knife are inferior when compared to Gamma Knife alone; moreover with volume staging and/or dose staging being increasingly plausible due to the new ICON machine, embolization may be completely replaced. However we have shown that in complicated and carefully chosen AVMs, embolization followed by GKRS is a valid modality of management. This study represents a real-world picture of individualized AVM treatment depending on patient choices and resources available.

Brain arteriovenous malformation flow after stereotactic radiosurgery: Role of quantitative MRA.

Stereotactic radiosurgery (SRS) is a current therapeutic option for treatment of arteriovenous malformations (AVMs) located in deep or eloquent brain regions. Obliteration usually occurs in a delayed fashion, with an expected latency of 3-5 years. Here, we assess how AVM flow correlates with volume before and after SRS treatment. Patients with supratentorial AVM treated with SRS at our institution between 2012-2022 were retrospectively reviewed. Patients were included if Quantitative Magnetic Resonance Angiography (QMRA) study was performed at baseline and at least at the first follow-up. Correlation between AVM flow and volume before and after treatment was evaluated. AVM flow and volume were additionally assessed for obliteration using the non-parametric receiver operating characteristic (ROC) curve. Twelve patients with radiologic follow-up imaging were included. Eight patients presented AVM rupture, one of which occurred after radiosurgical treatment. Three patients underwent embolization prior SRS. Mean AVM initial volume was 3.8 cc (0.1-12.4 cc), mean initial flow 174 ml/min (11-604 ml/min), both variables showed progressive reduction at follow-up (range 3-57 months); and flow decreased with volume reduction (p < 0.001). Area under the ROC was 0.914 for both AVM flow and volume with obliteration (p = 0.019). AVM flow significantly decreased after SRS treatment, reflecting volume reduction. Baseline AVM flow and volume both predicted obliteration. QMRA provides additional non-invasive information to monitor patients after radiosurgical treatment.

Preoperative flow analysis of arteriovenous malformations and obliteration response after stereotactic radiosurgery.

Morphological and angioarchitectural features of cerebral arteriovenous malformations (AVMs) have been widely described and associated with outcomes; however, few studies have conducted a quantitative analysis of AVM flow. The authors examined brain AVM flow and transit time on angiograms using direct visual analysis and a computer-based method and correlated these factors with the obliteration response after Gamma Knife radiosurgery. A retrospective analysis was conducted at a single institution using a prospective registry of patients managed from January 2013 to December 2019: 71 patients were analyzed using a visual method of flow determination and 38 were analyzed using a computer-based method. After comparison and validation of the two methods, obliteration response was correlated to flow analysis, demographic, angioarchitectural, and dosimetric data. The mean AVM volume was 3.84 cm3 (range 0.64-19.8 cm3), 32 AVMs (45%) were in critical functional locations, and the mean margin radiosurgical dose was 18.8 Gy (range 16-22 Gy). Twenty-seven AVMs (38%) were classified as high flow, 37 (52%) as moderate flow, and 7 (10%) as low flow. Complete obliteration was achieved in 44 patients (62%) at the time of the study; the mean time to obliteration was 28 months for low-flow, 34 months for moderate-flow, and 47 months for high-flow AVMs. Univariate and multivariate analyses of factors predicting obliteration included AVM nidus volume, age, and flow. Adverse radiation effects were identified in 5 patients (7%), and 67 patients (94%) remained free of any functional deterioration during follow-up. AVM flow analysis and categorization in terms of transit time are useful predictors of the probability of and the time to obliteration. The authors believe that a more quantitative understanding of flow can help to guide stereotactic radiosurgery treatment and set accurate outcome expectations.

Ischemia-induced inflammation in arteriovenous malformations.

The pathophysiology of development, growth, and rupture of arteriovenous malformations (AVMs) is only partially understood. However, inflammation is known to play an essential role in many vascular diseases. This feasibility study was conducted to investigate the expression of enzymes (cyclooxygenase 2 [COX-2] and NLRP3 [NOD-, LRR-, and pyrin domain-containing protein 3]) in the AVM nidus that are essential in their inflammatory pathways and to explore how these influence the pathophysiology of AVMs. The study group comprised 21 patients with partially thrombosed AVMs. The cohort included 8 ruptured and 13 unruptured AVMs, which had all been treated microsurgically. The formaldehyde-fixed and paraffin-embedded samples were immunohistochemically stained with a monoclonal antibody against COX-2 and NLRP3 (COX-2 clone: CX-294; NLRP3: ab214185). The authors correlated MRI and clinical data with immunohistochemistry, using the Trainable Weka Segmentation algorithm for analysis. The median AVM volume was 2240 mm3. The proportion of NLRP3-positive cells was significantly higher (26.23%-83.95%), compared to COX-2 positive cells (0.25%-14.94%, p < 0.0001). Ruptured AVMs had no higher expression of NLRP3 (p = 0.39) or COX-2 (p = 0.44), compared to nonruptured AVMs. Moreover, no patient characteristics could be reported that showed significant correlations to the enzyme expression. NLRP3 consistently showed an approximately 10-fold higher expression level than COX-2, making the inflammatory process in AVMs appear to be mainly associated with ischemic (NLRP3)-driven rather than with mechanical (COX-2)-driven inflammatory pathways. No direct associations between NLRP3 and COX-2 expression and radiological, standard histopathological, or patient characteristics were found in this cohort.

Gamma Knife Radiosurgery for Brain Arteriovenous Malformations: A 15-Year Single-Center Experience in Southern Vietnam

In the present study, we aimed to identify the obliteration outcomes, complications, and predictors in gamma knife radiosurgery (GKRS) treatment of brain arteriovenous malformations (AVMs) at a tertiary center in a developing country in a 15-year experience. We retrospectively reviewed the clinical data and GKRS procedures of patients who had undergone GKRS from 2006 to 2011 (cohort 1) and from 2011 to 2020 (cohort 2) at Cho Ray Hospital, Vietnam. The exclusion criteria included patients with <24 months of follow-up without obliteration or AVM-related hemorrhage during the study period. A total of 870 patients were included in the final analysis. The patients in cohort 1 had had significantly smaller AVMs (8.4 ± 11.6 cm3 vs. 11.2 ± 12.8 cm3; P< 0.001), and the AVMs were less frequently located in eloquent locations (46.6% vs. 65.5%; P < 0.001) than in cohort 2. The mean follow-up time was 49.6 ± 22.6 months (range, 5.9-102.6). The overall AVM obliteration rate was 66.6%. Cohort 1 had a significantly higher rate of complete obliteration compared with cohort 2 (81.0% vs. 55.1%; P<0.001). The post-GKRS annual hemorrhage risk was 1.0%. Significant radiosurgery-induced brain edema and radiosurgery-induced cyst formation was reported in 24 (2.6%) and 4 (0.5%) patients in cohorts 1 and 2, respectively. Using multivariate analysis, we identified prior AVM hemorrhage (hazard ratio [HR], 1.430; 95% confidence interval [CI], 1.182-1.729), a higher margin dose (HR, 1.136; 95% CI, 1.086-1.188), a noneloquent location (HR, 0.765; 95% CI, 0.647-0.905), and smaller AVM volume (HR, 0.982; 95% CI, 0.968-0.997) as predictive factors for obliteration. GKRS is a safe and effective treatment of brain AVMs. The lack of prior AVM hemorrhage, an eloquent location, and higher AVM were unfavorable predictors for post-GKRS obliteration.

Case Series for Gamma Knife Surgery for Arteriovenous Malformation Associated Intracranial Aneurysms

Abstract Objective The incidence of aneurysms coexisting with arteriovenous malformations (AVMs) ranges between 2.7% and 16.7%. The anatomical relationship between AVM and aneurysm is critical in deciding the best management. Methods Between October 1994 and August 2017, gamma knife surgery (GKS) was performed in six patients with AVMs and associated aneurysms. The patients consisted of four men and two women with a mean age of 37.8 years (range, 18−57 years). The mean follow-up was 34.2 months (range, 13−84 months). The mean maximal dose was 35.9 Gy and the mean margin dose to AVM was 18 Gy. Coil embolization was performed in one of the aneurysms prior to GKS. In our study, GKS was performed in six AVM-associated aneurysms. Of the six aneurysms, four were intranidal and two were pedicular. The mean volume of AVMs was 3.6 cm3 (range, 1.6−6.5 cm3). Results The locations of aneurysms are as follows: four on posterior cerebral artery (PCA), one on posterior inferior cerebellar artery (PICA), and one on middle cerebral artery (MCA). Sublocation sites were MCA M3 above, PCA P3 above, and PICA distal. There were no GKS-related complications. Complete obliteration of AVM and aneurysm was documented in all four patients with intranidal aneurysm-associated AVMs. Both the aneurysm and AVM were completely obliterated in the two patients with proximal pedicular aneurysms. Conclusion GKS is a possible treatment for AVM with associated intranidal or pedicular aneurysms located above P3 or M3, etc., in which there is less turbulent flow and jet flow.

Chronic encapsulated expanding hematomas after stereotactic radiosurgery for intracranial arteriovenous malformations.

Cerebral arteriovenous malformations (AVMs) are rare cerebral vascular lesions that are associated with high morbidity and mortality from hemorrhage; however, stereotactic radiosurgery (SRS) is a well-validated treatment modality. Few reports have delineated a subgroup of patients who develop delayed chronic encapsulated expanding hematomas (CEEHs) despite angiographic evidence of AVM obliteration following radiosurgery. In this report, the authors performed a retrospective review of more than 1000 radiosurgically treated intracranial AVM cases to delineate the incidence and management of this rare entity. Between 1988 and 2019, 1010 patients with intracranial AVM underwent Gamma Knife SRS at the University of Pittsburgh Medical Center. In addition to a review of a prospective institutional database, the authors performed a retrospective chart review of the departmental AVM database to specifically identify patients with CEEH. Pertinent clinical and radiological characteristics as well as patient outcomes were recorded and analyzed. Nine hundred fifty patients with intracranial AVM (94%) had sufficient clinical follow-up for analysis. Of these, 6 patients with CEEH underwent delayed resection (incidence rate of 0.0045 event per person-year). These patients included 4 males and 2 females with a mean age of 45.3 ± 13.8 years at the time of initial SRS. Four patients had smaller AVM volumes (4.9-10 cm3), and 3 of them were treated with a single SRS procedure. Two patients had larger-volume AVMs (55 and 56 cm3), and both underwent multimodal management that included staged SRS and embolization. Time to initial recognition of the CEEH after initial SRS ranged between 66 and 243 months. The time between CEEH recognition and resection ranged from 2 to 9 months. Resection was required because of progressive neurological symptoms that correlated with imaging evidence of gradual hematoma expansion. All 6 patients had angiographically confirmed obliteration of their AVM. Pathology revealed a mixed chronicity hematoma with areas of fibrosed blood vessels and rare areas of neovascularization with immature blood vessels but no evidence of a persistent AVM. All 6 patients reported persistent clinical improvement after hematoma resection. CEEH after SRS for AVM is a rare complication with an incidence rate of 0.0045 event per person-year over the authors' 30-year experience. When clinical symptoms progress and imaging reveals progressive enlargement over time, complete resection of a CEEH results in significant clinical recovery. Knowledge of this rare entity facilitates timely detection and eventual surgical intervention to achieve optimal outcomes.

The factors associated with obliteration following stereotactic radiosurgery in patients with brain arteriovenous malformations: a meta-analysis.

Various factors have been reported to affect the obliteration of brain arteriovenous malformations (AVM) following stereotactic radiosurgery (SRS). This meta-analysis was conducted to identify the factors potentially associated with AVM obliteration after SRS. We comprehensively searched databases and included studies that evaluated predictors of AVM obliteration after SRS using Cox proportional hazard regression analysis. Hazard ratios (HRs) with 95% confidence intervals (CIs) were utilized as effect estimates. Twelve studies, involving 4415 AVM cases, were included. According to combined estimates on univariate (UV) and multivariate (MV) analysis, age, gender and prior haemorrhage did not affect the closure probability. The following factors showed a significant and independent association with increased AVM obliteration: smaller AVMs maximal diameter (MV, HR: 1.32), smaller AVM volume (MV, HR: 1.05), AVM volume <10-15 cc (MV, HR: 1.55), higher margin dose (MV, HR: 1.05), margin dose ≥17-18 Gy (MV, HR: 3.71) and early treatment period (MV, HR: 1.78). Previous embolization and deep-seated AVM were independently negative predictors of obliteration whereas deep venous drainage was a positive predictor. Prior surgery, compactness of nidus, lower grading scores and higher SRS maximum dose were associated factors subject to confounding factors. Multiple factors associated with obliteration should be taken into consideration for selection of candidates with AVMs for SRS. AVM volume and radiation dose are the most prominent factor in assessing obliteration after SRS. Age, gender and prior haemorrhage may not affect the consideration of SRS treatment. Cautious use of SRS is needed for previously embolized AVM patients.