Pediatric cerebral cavernous malformations and stereotactic radiosurgery: an analysis of 50 cases from a multicentric study.

OBJECTIVE: Cerebral cavernous malformations (CCMs) are the second most common vascular anomaly affecting the CNS in children. Although stereotactic radiosurgery (SRS) has been proposed as an alternative to microsurgery in the management of selected cases in adults, there is a paucity of studies focusing on pediatric patients. The aim of this study was to present the outcomes and associated risks of SRS in this subgroup of patients. METHODS: This retrospective multicenter study included pediatric patients treated with single-session SRS for CCMs. The annual hemorrhage rate (AHR) was calculated before and after SRS in hemorrhagic lesions. The Engel classification was used to describe post-SRS epileptic control. Adverse radiation effects (AREs) and the occurrence of new neurological deficits were recorded. RESULTS: The study included 50 patients (median age 15.1 [IQR 5.6] years) harboring 62 CCMs. Forty-two (84%) and 22 (44%) patients had a history of hemorrhage or epilepsy prior to SRS, respectively. The AHR from diagnosis to SRS excluding the first hemorrhage was 7.19 per 100 CCM-years, dropping to 3.15 per 100 CCM-years after treatment. The cumulative risk of first hemorrhage after SRS was 7.4% (95% CI 0%-14.3%) at 5 years and 23.6% (95% CI 0%-42.2%) at 10 years. Eight hemorrhagic events involving 6 CCMs in 6 patients were recorded in the post-SRS follow-up period; 4 patients presented with transient symptoms and 4 with permanent symptoms. Of the 22 patients with pre-SRS seizures, 11 were seizure free at the last follow-up (Engel class I), 6 experienced improvement (Engel class II or III), 5 had no improvement (Engel class IVA or IVB), and 1 experienced worsening (Engel class IVC). Radiographic AREs were documented in 14.5% (9/62) of CCMs, with 4 being symptomatic. CONCLUSIONS: Single-session SRS reduces the CCM hemorrhage rate in the pediatric population and provides adequate seizure control.

Repeat stereotactic radiosurgery for persistent cerebral arteriovenous malformations in pediatric patients.

OBJECTIVE: The purpose of this study was to describe the long-term outcomes and associated risks related to repeat stereotactic radiosurgery (SRS) for persistent arteriovenous malformations (AVMs) in pediatric patients. METHODS: Under the auspices of the International Radiosurgery Research Foundation, this retrospective multicenter study analyzed pediatric patients who underwent repeat, single-session SRS between 1987 and 2022. The primary outcome variable was a favorable outcome, defined as nidus obliteration without hemorrhage or neurological deterioration. Secondary outcomes included rates and probabilities of hemorrhage, radiation-induced changes (RICs), and cyst or tumor formation. RESULTS: The cohort included 83 pediatric patients. The median patient age was 11 years at initial SRS and 15 years at repeat SRS. Fifty-seven children (68.7%) were managed exclusively using SRS, and 42 (50.6%) experienced hemorrhage prior to SRS. Median AVM diameter and volume were substantially different between the first (25 mm and 4.5 cm3, respectively) and second (16.5 mm and 1.6 cm3, respectively) SRS, while prescription dose and isodose line remained similar. At the 5-year follow-up evaluation from the second SRS, nidus obliteration was achieved in 42 patients (50.6%), with favorable outcome in 37 (44.6%). The median time to nidus obliteration and hemorrhage was 35.5 and 38.5 months, respectively. The yearly cumulative probability of favorable outcome increased from 2.5% (95% CI 0.5%-7.8%) at 1 year to 44% (95% CI 32%-55%) at 5 years. The probability of achieving obliteration followed a similar pattern and reached 51% (95% CI 38%-62%) at 5 years. The 5-year risk of hemorrhage during the latency period after the second SRS reached 8% (95% CI 3.2%-16%). Radiographically, 25 children (30.1%) had RICs, but only 5 (6%) were symptomatic. Delayed cyst formation occurred in 7.2% of patients, with a median onset of 47 months. No radiation-induced neoplasia was observed. CONCLUSIONS: The study results showed nidus obliteration in most pediatric patients who underwent repeat SRS for persistent AVMs. The risks of symptomatic RICs and latency period hemorrhage were quite low. These findings suggest that repeat radiosurgery should be considered when treating pediatric patients with residual AVM after prior SRS. Further study is needed to define the role of repeat SRS more fully in this population.

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

BACKGROUND AND OBJECTIVES: 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. METHODS: 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/ß 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). RESULTS: 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). CONCLUSION: This study confirms BED as a predictor for pediatric AVM obliteration. Optimization of BED in pediatric AVM SRS planning may improve cumulative obliteration rates.

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

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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

BACKGROUND: To explore the therapeutic outcomes of CyberKnife based fractionated stereotactic radiotherapy (CKFRT) for patients with cerebral arteriovenous malformations (AVM). METHODS: Between 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 âˆ¼ 5 fractions). AVM obliteration following CKFRT was confirmed by magnetic resonance imaging or angiography. RESULTS: During 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. CONCLUSIONS: CKFRT is an effective primary treatment for patients with cerebral AVMs with a low hemorrhage risk.

Incorporation of Brain Connectomics for Stereotactic Radiosurgery Treatment Planning.

BACKGROUND AND IMPORTANCE: Neurosurgeons have integrated neuroanatomy-based tractography to avoid critical structures during dose planning. However, they have yet to integrate more comprehensive connectome networks for radiosurgical planning. CLINICAL PRESENTATION: A young man presented with a Spetzler-Martin Grade 3 right temporal arteriovenous malformation. DISCUSSION: As proof of concept, we incorporated connectomic networks including default mode network, optic radiation and central executive network into the Gamma Knife radiosurgical treatment planning workflow. Connectome networks were created from T1 anatomic and diffusion-weighted images magnetic resonance images using Quicktome software. The resulting networks were voxel-encoded in the magnetic resonance images, imported into GammaPlan, and segmented by image thresholding. The GammaPlan Lightning optimizer was used to create radiosurgical plans with a dose of 20 Gy to the 50% isodose line delivered to the arteriovenous malformation nidus both with and without treating these networks as risk structures. When taking into account the connectome networks, a maximum dose restriction of 14 Gy was placed on each network during lightning dose planning. With default mode network, optic radiation, and central executive network as risk structures, the maximum dose and V 12Gy were reduced by 23.4% and 88.3%, 20% and 34.3%, and 29.8% and 63.2%, respectively. CONCLUSION: We were able to incorporate connectomes into radiosurgical dose planning approaches. This allowed for dose reductions to the networks while still achieving delivery of a therapeutic dose to the target volume.

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

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Stereotactic radiosurgery outcome for deep-seated cerebral arteriovenous malformations in the brainstem and thalamus/basal ganglia: systematic review and meta-analysis.

Deep-seated unruptured AVMs located in the thalamus, basal ganglia, or brainstem have a higher risk of hemorrhage compared to superficial AVMs and surgical resection is more challenging. Our systematic review and meta-analysis provide a comprehensive summary of the stereotactic radiosurgery (SRS) outcomes for deep-seated AVMs. This study follows the guidelines set forth by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Statement. We conducted a systematic search in December 2022 for all reports of deep-seated arteriovenous malformations treated with SRS. Thirty-four studies (2508 patients) were included. The mean obliteration rate in brainstem AVM was 67% (95% CI: 0.60-0.73), with significant inter-study heterogeneity (tau2 = 0.0113, I2 = 67%, chi2 = 55.33, df = 16, p-value < 0.01). The mean obliteration rate in basal ganglia/thalamus AVM was 65% (95% CI: 0.58-0.72) with significant inter-study heterogeneity (tau2 = 0.0150, I2 = 78%, chi2 = 81.79, df = 15, p-value < 0.01). The presence of deep draining veins (p-value: 0.02) and marginal radiation dose (p-value: 0.04) were positively correlated with obliteration rate in brainstem AVMs. The mean incidence of hemorrhage after treatment was 7% for the brainstem and 9% for basal ganglia/thalamus AVMs (95% CI: 0.05-0.09 and 95% CI: 0.05-0.12, respectively). The meta-regression analysis demonstrated a significant positive correlation (p-value < 0.001) between post-operative hemorrhagic events and several factors, including ruptured lesion, previous surgery, and Ponce C classification in basal ganglia/thalamus AVMs. The present study found that radiosurgery appears to be a safe and effective modality in treating brainstem, thalamus, and basal ganglia AVMs, as evidenced by satisfactory rates of lesion obliteration and post-surgical hemorrhage.

Outcome Evaluation of Repeat Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations.

BACKGROUND: Repeat stereotactic radiosurgery (SRS) for persistent cerebral arteriovenous malformation (AVM) has generally favorable patient outcomes. However, reporting studies are limited by small patient numbers and single-institution biases. The purpose of this study was to provide the combined experience of multiple centers, in an effort to fully define the role of repeat SRS for patients with arteriovenous malformation. METHODS: This multicenter, retrospective cohort study included patients treated with repeat, single-fraction SRS between 1987 and 2022. Follow-up began at repeat SRS. The primary outcome was a favorable patient outcome, defined as a composite of nidus obliteration in the absence of hemorrhage or radiation-induced neurological deterioration. Secondary outcomes were obliteration, hemorrhage risk, and symptomatic radiation-induced changes. Competing risk analysis was performed to compute yearly rates and identify predictors for each outcome. RESULTS: The cohort comprised 505 patients (254 [50.3%] males; median [interquartile range] age, 34 [15] years) from 14 centers. The median clinical and magnetic resonance imaging follow-up was 52 (interquartile range, 61) and 47 (interquartile range, 52) months, respectively. At last follow-up, favorable outcome was achieved by 268 (53.1%) patients (5-year probability, 50% [95% CI, 45%-55%]) and obliteration by 300 (59.4%) patients (5-year probability, 56% [95% CI, 51%-61%]). Twenty-eight patients (5.6%) experienced post-SRS hemorrhage with an annual incidence rate of 1.38 per 100 patient-years. Symptomatic radiation-induced changes were evident in 28 (5.6%) patients, with most occurring in the first 3 years. Larger nidus volumes (between 2 and 4 cm3, subdistribution hazard, 0.61 [95% CI, 0.44-0.86]; P=0.005; >4 cm3, subdistribution hazard, 0.47 [95% CI, 0.32-0.7]; P<0.001) and brainstem/basal ganglia involvement (subdistribution hazard, 0.6 [95% CI, 0.45-0.81]; P<0.001) were associated with reduced probability of favorable outcome. CONCLUSIONS: Repeat SRS confers reasonable obliteration rates with a low complication risk. With most complications occurring in the first 3 years, extending the latency period to 5 years generally increases the rate of favorable patient outcomes and reduces the necessity of a third intervention.

Stereotactic Radiosurgery or Fractionated Stereotactic Radiotherapy for Arteriovenous Malformation.

BACKGROUND: The best management for AVM, particularly high-grade ones and those that have been ruptured before, is still unknown. Data from prospective data lacks support for the best approach. METHODS: We retrospectively review patients with AVM at a single institution that were treated with radiation or a combination of radiation and embolization. These patients were divided into two groups based on radiation fractionation: SRS and fSRS. RESULTS: One-hundred and thirty-five (135) patients were first assessed and 121 met study criteria. Mean age at treatment was 30.5 years, and most patients were male. The groups were otherwise balanced, except for nidus size. SRS group had smaller lesions (P > 0.005). SRS correlates to better chance of nidus occlusion and lesser chance of retreatment. Complications such as radionecrosis (5%) and bleeding after nidus occlusion (1 patient) were rare. CONCLUSIONS: Stereotactic radiosurgery plays an important role on the treatment of AVM. Whenever possible, SRS should be preferred. Data from prospective trials about larger and previously ruptured lesions are needed.

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

BACKGROUND AND OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Gamma Knife Radiosurgery for Spetzler-Martin Grade III Brain Arteriovenous Malformations.

BACKGROUND: Spetzler-Martin (SM) grade III arteriovenous malformations (AVMs) show angioarchitecture heterogeneity and lack a clearly defined treatment strategy. This study aims to evaluate outcomes after treatment of SM grade III AVMs with Gamma Knife radiosurgery (GKRS). METHODS: A single-institution retrospective analysis was conducted of 307 patients with SM grade III AVMs undergoing GKRS between October 2006 and December 2020 with follow-up times of at least 24 months. SM grade III AVMs were classified into 4 subtypes: IIIA (S1E1V1), IIIB (S2E0V1), subtype IIIC (S2E1V0), and IIID (S3E0V0). RESULTS: Over a median follow-up time of 50.3 months, complete AVM obliteration was achieved in 211 patients (68.7%). Complete obliteration rates in subtypes IIIA, IIIB, IIIC, and IIID were 80.8%, 55.4%, 53.4%, and 25.0%, respectively. Annual post-GKRS hemorrhage risk was 0.8%. Significant radiosurgery-induced imaging changes occurred in 7 patients (2.3%). Three variables were identified as predictors of obliteration in final forward stepwise regression models, including volume of AVM (B = -0.011; P < 0.001), age (B = -0.004; P = 0.024), and previous AVM hemorrhage (B = 0.187; P = 0.077). CONCLUSIONS: GKRS is a safe and effective treatment for SM grade III AVMs, particularly subtype IIIA (S1E1V1). AVM volume is the key predictor of post-GKRS obliteration.

Volume Fractionation Stereotactic Radiosurgery for Large Volume Intracranial Arteriovenous Malformations.

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

First use of radiation for the treatment of arteriovenous malformation.

In 1921, Norwegian neurosurgeon Vilhelm Magnus (1871-1929) described the first use of radiation for the treatment of an arteriovenous malformation (AVM) in his monograph, Bidrag til hjernechirurgiens klinik og resultater. Seeing as this monograph has never been widely translated nor digitized, the authors discuss the impact of Magnus' original work and the ethics surrounding its citation. The senior author of this paper gained access to and directly translated key sections of Magnus' publication. Without Norwegian language skills, reading and understanding Magnus' text would have been impossible. Magnus described the use of radiation therapy in a single patient found to have an AVM (or "angioma"). He states that she was "well" 8 years later. No other information on that treatment is given, but for good reason Magnus has been given credit in the literature for the first use of radiation of any kind to treat a person with AVM. Most papers that have referenced Magnus' monograph cite it even though it is probable that the authors did not see it, let alone read its contents. While it is appropriate that his innovation has been properly credited, the authors discuss the limits of citing publications sight unseen.

Age-Dependent Hemorrhage Risk and Obliteration Benefit After Radiosurgery for Brain Arteriovenous Malformation.

PURPOSE: Because patients with untreated brain arteriovenous malformations (BAVMs) are at variable risks of cerebral hemorrhage and associated mortality and morbidity, it is essential to identify patient populations who benefit most from prophylactic interventions. This study aimed to examine age-dependent differences in the therapeutic effect of stereotactic radiosurgery (SRS) on BAVMs. METHODS AND MATERIALS: This retrospective observational study enrolled patients with BAVMs who underwent SRS at our institution between 1990 and 2017. The primary outcome was post-SRS hemorrhage, and the secondary outcomes included nidus obliteration, post-SRS early signal changes, and mortality. To investigate age-related differences in outcomes after SRS, we performed age-stratified analyses using the Kaplan-Meier analysis and weighted logistic regression with the inverse probability of censoring weighting (IPCW). To address significant differences in patient baseline characteristics, we also performed inverse probability of treatment weighting (IPTW) adjusted for possible confounders to investigate age-related differences in outcomes after SRS. RESULTS: A total of 735 patients with 738 BAVMs were stratified by age. Age-stratified analysis using a weighted logistic regression model with IPCW showed a direct correlation between patient age and post-SRS hemorrhage (odds ratio [OR], 95% confidence interval [CI], and P value: 2.20, 1.34-3.63, and .002 at 18 months; 1.86, 1.17-2.93, and .008 at 36 months; and 1.61, 1.05-2.48, and .030 at 54 months, respectively). The age-stratified analysis also showed an inverse relationship between age and obliteration over the first 42 months after SRS (OR, 95% CI, and P value: 0.05, 0.02-0.12, and <.001 at 6 months; 0.55, 0.44-0.70, and <.001 at 24 months; and 0.76, 0.63-0.91, and .002 at 42 months, respectively). These results were also confirmed with the IPTW analyses. CONCLUSIONS: Our analysis demonstrated that patients' age at SRS is significantly associated with hemorrhage and the nidus obliteration rate after treatment. In particular, younger patients are more likely to exhibit reduced cerebral hemorrhages and achieve earlier nidus obliteration compared with older patients.

Radiation-Induced Changes Associated with Obliteration of Brain AVMs after Repeat Radiosurgery.

BACKGROUND AND PURPOSE: Radiation-induced changes can occur after stereotactic radiosurgery for brain AVMs, potentially causing symptomatic complications. We evaluated the incidence of such changes and the efficacy of repeat gamma knife radiosurgery for incompletely obliterated AVMs. MATERIALS AND METHODS: We retrospectively evaluated 150 patients who underwent gamma knife radiosurgery for AVMs between 2002 and 2020; twenty-five underwent further radiosurgical procedures for incompletely obliterated AVMs. We recorded the median margin doses at the first (median, 20 Gy; range, 12-23 Gy; AVM volume, 0.026-31.3 mL) and subsequent procedures (median, 18 Gy; range, 12-23 Gy; AVM volume, 0.048-9.2 mL). RESULTS: After the first treatment, radiologic radiation-induced changes developed in 48 (32%) patients, eight of whom had symptomatic changes. After repeat gamma knife radiosurgery, 16 of 25 patients achieved complete AVM obliteration (64%). The development of radiation-induced changes after the first treatment was significantly associated with successful obliteration by subsequent radiosurgery (OR = 24.0, 95% CI 1.20-483, P = .007). Radiation-induced changes occurred in only 5 (20%) patients who underwent a second gamma knife radiosurgery, one of whom experienced transient neurologic deficits. Between the first and repeat gamma knife radiosurgery procedures, there was no significant difference in radiologic and symptomatic radiation-induced changes (P = .35 and P = 1.0, respectively). CONCLUSIONS: Radiation-induced changes after the first gamma knife radiosurgery were associated with AVM obliteration after a repeat procedure. The risk of symptomatic radiation-induced changes did not increase with retreatment. When the first procedure fails to achieve complete AVM obliteration, a favorable outcome can be achieved by a repeat gamma knife radiosurgery, even if radiation-induced changes occur after the first treatment.

Susceptibility weighted imaging for qualitative grading of persistent arteriovenous shunting in deep-seated arteriovenous malformations after stereotactic radiation surgery.

BACKGROUND AND PURPOSE: To investigate Susceptibility Weighted Imaging (SWI) signal changes in the draining vein of deep-seated arterio-venous malformations (AVMs) following stereotactic radiosurgery (SRS). METHODS AND MATERIALS: This is a retrospective study of 32 patients with deep-seated AVMs who were treated with SRS. Pre-SRS treatment and post-SRS treatment MRI were performed at 6, 12, and 24-month intervals. Deep-seated AVMs were classified based on their anatomical location and venous drainage pattern. AVM nidal volume (cm3) was estimated using the ABC/2 method. AV shunting of the AVM draining veins were graded according to its SWI signal intensity: hyperintense (grade III), mixed signal intensity (grade II), hypointense (grade I) and absent (grade 0). Conventional time-of-flight (TOF)-MRA and contrast enhanced (CE)-MRA sequences were performed to document the patency of the vein. RESULTS: Pre-SRS treatment AVM draining veins were either grade III 18/32 (56%) or grade II 14/32 (44%). Using mixed effects analysis, we demonstrate that each month following the SRS treatment nidal volumes decreased at the rate of 0.51 cm3/per month (CI -0.61 to (-0.40)) p =.00. Following the treatment, there was a clinically significant relationship between the signal and nidal volume: signal 0 corresponded with average nidal volume of 1.81 cm3 (CI 1.40-2.21), signal 1 with nidal volume of 2.06 cm3 (CI 1.69-2.44), signal 2 with nidal volume 2.73 cm3 (CI 2.35-3.11) and signal 3 with nidal volume 3.13 cm3 (CI 2.70-3.56) p = .00. CONCLUSION: Post-SRS AVM draining veins shows a stepwise regression of the SWI signal grades which can be reliably used as a surrogate to monitor the reduction of AV shunting.

Compactness index: a radiosurgery outcome predictor for patients with unruptured brain arteriovenous malformations.

OBJECTIVE: The goal of the study was to define and quantify brain arteriovenous malformation (bAVM) compactness and to assess its effect on outcomes after Gamma Knife radiosurgery (GKRS) for unruptured bAVMs. METHODS: Unsupervised machine learning with fuzzy c-means clustering was used to differentiate the tissue constituents of bAVMs on T2-weighted MR images. The percentages of vessel, brain, and CSF were quantified. The proposed compactness index, defined as the ratio of vasculature tissue to brain tissue, categorized bAVM morphology into compact, intermediate, and diffuse types according to the tertiles of this index. The outcomes of interest were complete obliteration and radiation-induced changes (RICs). RESULTS: A total of 209 unruptured bAVMs treated with GKRS were retrospectively included. The median imaging and clinical follow-up periods were 49.2 and 72.3 months, respectively. One hundred seventy-three bAVMs (82.8%) achieved complete obliteration after a median latency period of 43.3 months. The rates of RIC and permanent RIC were 76.1% and 3.8%, respectively. Post-GKRS hemorrhage occurred in 14 patients (6.7%), resulting in an annual bleeding risk of 1.0%. Compact bAVM, smaller bAVM volume, and exclusively superficial venous drainage were independent predictors of complete obliteration. Diffuse bAVM morphology, larger bAVM volume, and higher margin dose were independently associated with RICs. CONCLUSIONS: The compactness index quantitatively describes the compactness of unruptured bAVMs. Moreover, compact bAVMs may have a higher obliteration rate and a smaller risk of RICs than diffuse bAVMs. This finding could help guide decision-making regarding GKRS treatment for patients with unruptured bAVMs.