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Dural arteriovenous fistulas (DAVFs) are a relatively rare intracranial vascular malformation. The various treatment options for DAVFs include observation, compression therapy, endovascular therapy, radiosurgery, or surgery. A combination of these therapies may also be used. The treatment choice for DAVFs depends on the type of fistula, the severity of symptoms, DAVF angioarchitecture, and the efficacy and safety of treatments. The use of stereotactic radiosurgery (SRS) in DAVFs started in the late 1970s. There is a delay before the fistula gets obliterated after SRS and there is a risk of hemorrhage from the fistula till the fistula gets obliterated. Initial reports described the role of SRS in small DAVFs without severe symptoms, which were inaccessible by endovascular or surgical measures or in combination with embolization in larger DAVFs. SRS can be appropriate for indirect cavernous sinus DAVF fistulas (Barrow type B, C, and D). Borden types II and III and Cognard types IIb-V DAVFs have a high risk of hemorrhage and are traditionally considered less favorable to be treated with SRS as immediate treatment is required to decrease the risk of hemorrhage. However, recently SRS has been tried in these high-grade DAVF as a monotherapy. Factors that have a positive impact on the obliteration rates of DAVF following SRS are the location of DAVF with the cavernous sinus DAVF having much better obliteration rates than DAVF located at other locations, Borden Type I or Cognard Types III or IV DAVFs, absence of CVD, hemorrhage at the time of initial presentation, and target volume lesser than 1.5 mL., Competing Interests: None

Objective: To determine whether biological effective dose (BED) was predictive of obliteration after stereotactic radiosurgery (SRS) for cerebral arteriovenous malformations (AVMs)., Patients and Methods: We studied patients undergoing single-session AVM SRS between January 1, 1990, and December 31, 2014, with at least 2 years of imaging follow-up. Excluded were patients with syndromic AVM, previous SRS or embolization, and patients treated with volume-staged SRS. Biological effective dose was calculated using a mono-exponential model described by Jones and Hopewell. The primary outcome was likelihood of total obliteration defined by digital subtraction angiography or magnetic resonance imaging (MRI). Variables were analyzed as continuous and dichotomous variables based on the maximum value of (sensitivity-[1-specificity])., Results: This study included 352 patients (360 AVM, median follow-up, 5.9 years). The median margin dose prescribed was 18.75 Gy (interquartile range [IQR]: 18 to 20 Gy). Two hundred fifty-nine patients (71.9%) had obliteration shown by angiography (n=176) or MRI (n=83) at a median of 36 months after SRS (IQR: 26 to 44 months). Higher BED was associated with increased likelihood of obliteration in univariate Cox regression analyses, when treated as either a dichotomous (≥133 Gy; hazard ratio [HR],1.52; 95% confidence interval [CI], 1.19 to 1.95; P<.001) or continuous variable (HR, 1.00, 95% CI, 1.0002 to 1.005; P=.04). In multivariable analyses including dichotomized BED and location, BED remained associated with obliteration (P=.001)., Conclusion: Biological effective dose ≥133 Gy was predictive of AVM obliteration after single-session SRS within the prescribed margin dose range 15 to 25 Gy. Further study is warranted to determine whether BED optimization should be considered as well as treatment dose for AVM SRS planning., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Background: The latency period from stereotactic radiosurgery (SRS) to obliteration of arteriovenous malformations (AVM) requires continuous imaging surveillance. Magnetic resonance (MR) perfusion is promising for noninvasive monitoring of AVMs after SRS. We studied longitudinal MR perfusion changes of brain AVMs treated with SRS., Methods: Consecutive patients treated for brain AVMs using SRS who had MR perfusion imaging studies performed before and at least once after SRS were studied. We estimated ipsilateral/contralateral brain hemisphere ratios of MR perfusion indexes, including regional cerebral blood flow (rCBF) and relative cerebral blood volume (rCBV), in the AVM nidus, perinidal region, and remote anterior and posterior brain regions., Results: Eleven patients (6 women; median age, 21 years) underwent SRS (median prescription dose, 18 Gy; range, 12-20 Gy) for brain AVMs (median Spetzler-Martin grade 2 and median volume 4.6 mL). Before the SRS, rCBV and rCBF ratios were significantly higher in the AVM nidus compared with other investigated brain regions (P < 0.001). Median time from SRS to the first and last post-SRS MR perfusion studies was 8 and 35 months, respectively. There was a statically significant decrease of rCBV (P = 0.043) and rCBF (P = 0.036) ratios in the AVM nidus, but not other brain regions, during post-SRS follow-up., Conclusions: There is a gradual decrease of rCBV and rCBF in the AVM nidus after SRS. MR perfusion imaging is promising for monitoring of hemodynamic changes of AVMs after SRS. Larger studies investigating clinical value of MR perfusion imaging for AVMs after SRS are warranted., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: High arteriovenous malformation (AVM) obliteration rates have been reported with stereotactic radiosurgery (SRS), and multiple factors have been found to be associated with AVM obliteration. These predictors have been inconsistent throughout studies. We aimed to analyze our experience with linear accelerator (LINAC)-based SRS for brain AVMs, evaluate outcomes, assess factors associated with AVM obliteration and review the various reported predictors of AVM obliteration., Methods: Electronic medical records were retrospectively reviewed to identify consecutive patients with brain AVMs treated with SRS over a 27-year period with at least 2 years of follow-up. Logistic regression analysis was performed to identify factors associated with AVM obliteration., Results: One hundred twenty-eight patients with 142 brain AVMs treated with SRS were included. Mean age was 34.4 years. Fifty-two percent of AVMs were associated with a hemorrhage before SRS, and 14.8% were previously embolized. Mean clinical and angiographic follow-up times were 67.8 months and 58.6 months, respectively. The median Spetzler-Martin grade was 3. Mean maximal AVM diameter was 2.8 cm and mean AVM target volume was 7.4 cm 3 with a median radiation dose of 16 Gy. Complete AVM obliteration was achieved in 80.3%. Radiation-related signs and symptoms were encountered in 32.4%, only 4.9% of which consisted of a permanent deficit. Post-SRS AVM-related hemorrhage occurred in 6.3% of cases. In multivariate analysis, factors associated with AVM obliteration included younger patient age (P = .019), male gender (P = .008), smaller AVM diameter (P = .04), smaller AVM target volume (P = .009), smaller isodose surface volume (P = .005), a higher delivered radiation dose (P = .013), and having only one major draining vein (P = .04)., Conclusions: AVM obliteration with LINAC-based radiosurgery was safe and effective and achieved complete AVM obliteration in about 80% of cases. The most prominent predictors of AVM success included AVM size, AVM volume, radiation dose, number of draining veins and patient age., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest., (Copyright © 2020. Published by Elsevier Inc.)

Objective: Arteriovenous malformations (AVMs) present no pathologic tissue, and radiation dose is confined in a clear targeted volume. The authors retrospectively evaluated the role of the biologically effective dose (BED) after Gamma Knife radiosurgery (GKRS) for brain AVMs., Methods: A total of 149 consecutive cases of unruptured AVMs treated by upfront GKRS in Lille University Hospital, France, were included. The mean length of follow-up was 52.9 months (median 48, range 12-154 months). The primary outcome was obliteration, and the secondary outcome was complication appearance. The marginal dose was 24 Gy in a vast majority of cases (n = 115, 77.2%; range 18-25 Gy). The mean BED was 220.1 Gy2.47 (median 229.9, range 106.7-246.8 Gy2.47). The mean beam-on time was 32.3 minutes (median 30.8, range 9-138.7 minutes). In the present series, the mean radiation dose rate was 2.259 Gy/min (median 2.176, range 1.313-3.665 Gy/min). The Virginia score was 0 in 29 (19.5%), 1 in 61 (40.9%), 2 in 41 (27.5%), 3 in 18 (12.1%), and 4 in 0 (0%) patients, respectively. The mean Pollock-Flickinger score was 1.11 (median 1.52, range 0.4-2.9). Univariate (for obliteration and complication appearance) and multivariate (for obliteration only) analyses were performed., Results: A total of 104 AVMs (69.8%) were obliterated at the last follow-up. The strongest predictor for obliteration was BED (p = 0.03). A radiosurgical obliteration score is proposed, derived from a fitted multivariable model: (0.018 × BED) + (1.58 × V12) + (-0.013689 × beam-on time) + (0.021 × age) - 4.38. The area under the receiver operating characteristic curve was 0.7438; after internal validation using bootstrap methods, it was 0.7088. No statistically significant relationship between radiation dose rate and obliteration was found (p = 0.29). Twenty-eight (18.8%) patients developed complications after GKRS; 20 (13.4%) of these patients had transient adverse radiological effects (perilesional edema developed). Predictors for complication appearance were higher prescription isodose volume (p = 0.005) and 12-Gy isodose line volume (V12; p = 0.001), higher Pollock-Flickinger (p = 0.02) and Virginia scores (p = 0.003), and lower beam-on time (p = 0.03)., Conclusions: The BED was the strongest predictor of obliteration of unruptured AVMs after upfront GKRS. A radiosurgical score comprising the BED is proposed. The V12 appears as a predictor for both efficacy and toxicity. Beam-on time was illustrated as statistically significant for both obliteration and complication appearance. The radiation dose rate did not influence obliteration in the current analysis. The exact BED threshold remains to be established by further studies.

Background: Gamma Knife radiosurgery (GKRS) in the treatment of arteriovenous malformations (AVMs) is still controversially discussed., Objective: To present long-term follow-up data on patients after Gamma Knife radiosurgery for cerebral AVMs., Methods: Overall, 516 patients received radiosurgery for cerebral AVMs between 1992 and 2018 at our department, of whom 265 received radiosurgery alone and 207 were treated with a combined endovascular-radiosurgical approach. Moreover, 45 patients were treated with a volume-staged approach. Two eras were analyzed, the pre-modern era between 1992 and 2002 and the modern era thereafter., Results: In GKRS-only treated patients, median time to nidus occlusion was 3.8 years. Spetzler-Ponce (SP) class was a significant predictor for time to obliteration in the whole sample. Median time to obliteration for the combined treatment group was 6.5 years. Patients in the pre-modern era had a significantly higher obliteration rate than those treated in the modern era. Overall, the calculated yearly hemorrhage risk in the observation period after first GKRS was 1.3%. Permanent post-radiosurgical complications occurred in 4.9% of cases but did not differ between the treatment groups or treatment eras. The obliteration rate was significantly lower and the hemorrhage rate was higher in volume-staged treated patients than in conventionally treated patients., Conclusion: GKRS is an effective treatment option for SP class A and B cerebral AVMs. After combined endovascular-radiosurgical treatment, the outcome of selected SP class C AVMs aligns with that of SP class B lesions. Both the combined therapy and radiosurgery alone constitute sound methods for treatment of cerebral AVMs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Brain arteriovenous malformations (AVMs) are congenital vascular anomalies characterized by arteriovenous shunting through a network of coiled and tortuous vessels. Because of this anatomy, the venous drainage of an AVM is hypothesized to contain more oxygenated, arterialized blood than healthy veins. By exploiting the paramagnetic properties of deoxygenated hemoglobin in venous blood using magnetic resonance imaging (MRI) quantitative susceptibility mapping (QSM), we aimed to explore venous density and oxygen saturation (SvO 2 ) in patients with a brain AVM. We considered three groups of subjects: patients with a brain AVM before treatment using gamma knife radiosurgery (GKR); patients three or more years post-GKR treatment; and healthy volunteers. First, we investigated the appearance of AVMs on QSM images. Then, we investigated whether QSM could detect increased SvO 2 in the veins draining the malformations. In patients before GKR, venous density, but not SvO 2 , was significantly larger in the hemisphere containing the AVM compared to the contralateral hemisphere (p = 0.03). Such asymmetry was not observed in patients after GKR or in healthy volunteers. Moreover, in all patients before GKR, the vein immediately draining the AVM nidus had a higher SvO 2 than healthy veins. Therefore, QSM can be used to detect SvO 2 alterations in brain AVMs. However, since factors such as flow-induced signal dephasing or the presence of hemosiderin deposits also strongly affect QSM image contrast, AVM vein segmentation must be performed based on alternative MRI acquisitions, e.g., time of flight magnetic resonance angiography or T 1 -weighted images. This is the first study to show, non-invasively, that AVM draining veins have a significantly larger SvO 2 than healthy veins, which is a finding congruent with arteriovenous shunting., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Arteriovenous malformations (AVMs) in pediatric patients exhibit remarkable differences in terms of management and outcomes. Owing to a paucity of relevant data pertaining to AVMs in pediatric patients, special interest and investigation are required for an improved understanding of the available evidence by clinicians., Objective: To determine the clinical outcomes of single-session stereotactic radiosurgery (SRS) for AVMs in pediatric patients., Methods: A systematic literature review was performed to identify studies that reported the outcomes of SRS for AVMs in pediatric patients. Data pertaining to variables such as obliteration rate, post-SRS new hemorrhage rate, post-SRS new neurological deficit rate, and mortality rate were extracted and analyzed using meta-analysis techniques., Results: Based on pooled data from 20 studies with 1212 patients, single-session SRS resulted in complete obliteration in 65.9% (95% confidence interval [CI], 60.5%-71.1%; I2 = 66.5%) patients. Overall complication rate (including new hemorrhage, new neurodeficit, and mortality) was 8.0% (95% CI, 5.1%-11.5%; I2 = 66.4%). Post-SRS new neurological deficit rate was 3.1% (95% CI, 1.3%-5.4%; I2 = 59.7%), and post-SRS hemorrhage rate was 4.2% (95% CI, 2.5%-6.3%; I2 = 42.7%). There was no significant difference between studies disaggregated by treatment method (Gamma Knife [Elekta AB] vs other), treatment year (before year 2000 vs after year 2000), median AVM volume reported (≥3 vs <3 cm3), median dose reported (≥20 vs <20 Gy), or follow-up period (≥36 vs <36 mo)., Conclusion: Single-SRS is a safe treatment alternative that achieves high obliteration rates and acceptable complication rates for AVMs in pediatric patients., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Objective: This study was conducted to achieve more conclusive evidence for the efficacy of stereotactic radiosurgery (SRS) for brainstem cavernous malformations (BSCMs)., Methods: A literature search of PubMed, EMBASE, and Web of Science was performed and studies reporting the outcomes of SRS for BSCMs were included. The primary outcome was the pre-SRS and post-SRS hemorrhage rates; the pooled incidence rate ratio (IRR) with 95% confidence interval was chosen as effect size. Lesion control, symptom change, and radiation-related complications were evaluated., Results: A total of 576 patients across 14 studies were included in this meta-analysis. The post-SRS hemorrhage rate was significantly decreased compared with the pre-SRS rate (IRR, 0.123; P < 0.001), and the hemorrhage rate 2 years after SRS was significantly lower than that within 2 years after SRS (IRR, 0.317; P < 0.001). Ten among 14 studies have shown that the symptoms were improved or stationary after SRS. Lesion volume was reduced in 47.3% of the patients and was stationary in 49.4% on the last follow-up images. Symptomatic adverse radiation effects (AREs) developed in 7.3% and permanent AREs were observed in 2.2%. In subgroup analysis, studies having mean marginal dose of ≤13 Gy showed statistically significantly lower development of symptomatic AREs than those having mean marginal dose of >13Gy (2.0% vs. 10.8%; P = 0.008)., Conclusions: SRS using a relatively low marginal dose can be a safe and effective treatment for BSCM. Further prospective studies are necessary to confirm the optimal radiation dose and efficacy of SRS for BSCMs., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to analyze serum levels of vascular endothelial growth factor (VEGF) and endostatin in patients with cerebral treated by stereotactic radiosurgery (SRS), and to assess their association with radiological radiation-induced changes (RICs)., Methods: To measure serum biomarkers, peripheral venous blood was collected before SRS and 1 week, 1 month, 3 months, and 6 months after SRS. To evaluate RICs, clinical and neuroimaging follow-up were performed concurrently every 6 months after SRS., Results: Twenty-seven patients were enrolled (11 in the group with RIC, 16 in the group without RIC). Serum VEGF and endostatin levels were positively correlated (P = 0.036, r = 0.405). In the group with RIC, the median serum VEGF 6 months after SRS (58.98 pg/mL) was significantly higher than that of the group without RIC (15.17 pg/mL) (P = 0.001). Multivariate analysis revealed that higher VEGF 6 months after SRS (P = 0.001, hazard ratio, 1.032; 95% confidence interval, 1.012-1.052) and lower endostatin 1 month after SRS (P = 0.007, hazard ratio, 0.964; 95% confidence interval, 0.935-0.993) were significantly associated with RICs., Conclusions: Our results show that serum levels of VEGF 6 months after SRS were higher in the group with RIC. Serum levels of VEGF 6 months and endostatin 1 month after SRS were associated with the radiological RICs. Thus, serial measurements of serum VEGF and endostatin after SRS might help predict RICs in patients with arteriovenous malformation treated by SRS., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Competing Interests: There are no conflicts of interest

Purpose: Arteriovenous malformations' (AVMs) obliteration depends on several factors; among the many factors that must be considered to obtain a high rate of obliteration and a low rate of complications, Flickinger-Pollock Score (FPS) seems to have an important role but still have to be validated in the pediatric population while Paddick-Conformity Index (PCI) still has no demonstration of its utility on the outcome and is considered only as a treatment quality marker., Methods: We retrospectively analyzed 33 consecutive children (2-18 years) with an AVM, treated with stereotactic radiosurgery Gamma Knife (SRS-GK) from 2001 to 2014 in our institution. We assess angiographic (DSA) Obliteration Rate (OR) as well FPS and PCI to draw conclusions., Results: DSA-OR was 60.6% with a rate of hemorrhage of 0%. median target volume (TV) was 3.60 cc (mean 4.32 ± 3.63; range 0.15-14.2), median PD was 22 Gy (mean 21.4 ± 2.6; range 16.5-25). Median percentage of coverage was 98% (mean 97 ± 3; range 84-100). The median modified FPS was 0.78 (mean 0.89 ± 0.52; range 0.21-2.1) and highly correlate with OR (p = 0.01). The median PCI was 0.65 (mean 0.65 ± 0.14; range 0.34-0.95) A PCI lower than 0.57 highly correlates with final OR (p = 0.02)., Conclusion: SRS-GK was safe and gradually effective in children. A prescription dose-like that used in adult population (i.e. > 18 and between 20 and 25 Gy) is essential to achieve obliteration. A PD of 23 Gy and 22 Gy did impact OR, respectively (p = 0.02) and (p = 0.05). FPS and PCI are valuable scores that seem to correlate with the OR also in the pediatric population although further prospective studies are needed to confirm these observations.

Gamma Knife radiosurgery (GKRS) of cerebral arteriovenous malformations (AVM) is an accepted treatment option that has been performed for more than 40 years. The goal of AVM GKRS is nidus obliteration to eliminate the risk of intracranial hemorrhage while minimizing the risk of short- and long-term adverse radiation effects (ARE). Nidus obliteration typically occurs between 1 and 5 years after GKRS. The most important factor associated with nidus obliteration is the prescribed radiation dose. The chance of obliteration ranges from 60 to 70% for margin doses of 15-16 Gy to 90% or more for margin doses of 20-25 Gy. Neurologic decline after GKRS can occur from either hemorrhage or ARE. Numerous studies have shown that the risk of AVM bleeding is either unchanged or decreased following GKRS. Advances in neuroimaging and dose-planning software have reduced the incidence of early ARE to <4%. Volume-staged procedures can be safely performed for large-volume AVM that were previously considered too large for GKRS. Late ARE (generally cyst formation) are common in patients who develop early MRI imaging changes (areas of high T2 signal) after GKRS, but most cases can be managed with either observation or resection of the thrombosed AVM., (© 2019 S. Karger AG, Basel.)

Traditional outcome measures after stereotactic radiosurgery (SRS) for cerebral arteriovenous malformations (AVMs) have focused predominantly on angiographic obliteration and general neurologic complications. Several grading scales attempting to predict the outcome for specific patients have previously been proposed and validated, and are outlined here. These have largely been based on both AVM and patient characteristics and attempt to predict obliteration. However, the most practical and clinically oriented goal in the management of AVMs is the prospective avoidance of neurological sequelae manifesting in the form of stroke or death, regardless of AVM obliteration. Long-term outcomes following SRS have demonstrated stroke or death rates of 1.5-2.0% per year for the first 5 years after SRS, followed by 0.2-0.4% annual risk thereafter. This focus on the avoidance of stroke or death is additionally crucial for direct comparisons to non-interventional natural history data. Here, we discuss the history of outcomes data on radiosurgery for AVMs and propose a re-evaluation of clinical outcome that is of most utility to the patient., (© 2019 S. Karger AG, Basel.)

Objective: Seizures are the second-most common presenting symptom in patients with lobar arteriovenous malformations (AVMs). However, few studies have assessed the long-term effect of stereotactic radiosurgery (SRS) on seizure control. The authors of this study assess the outcome of SRS for these patients to identify prognostic factors associated with seizure control., Methods: Patients with AVM who presented with a history of seizure and underwent SRS at the authors' institution between 1987 and 2012 were retrospectively assessed. The total cohort included 155 patients with a mean follow-up of 86 months (range 6-295 months). Primary outcomes assessed were seizure frequency, antiepileptic drug regimen, and seizure freedom for 6 months prior to last follow-up., Results: Seizure-free status was achieved in 108 patients (70%), with an additional 23 patients (15%) reporting improved seizure frequency as compared to their pre-SRS status. The median time to seizure-free status was estimated to be 12 months (95% CI 0-27 months) as evaluated via Kaplan-Meier survival analysis. The mean seizure frequency prior to SRS was 14.2 (95% CI 5.4-23.1) episodes per year. Although not all patients tried, the proportion of patients successfully weaned off all antiepileptic drugs was 18% (28/155 patients). On multivariate logistic regression, focal impaired awareness seizure type (also known as complex partial seizures) and superficial venous drainage were significantly associated with a decreased odds ratio for seizure-free status at last follow-up (OR 0.37 [95% CI 0.15-0.92] for focal impaired awareness seizures; OR 0.36 [95% CI 0.16-0.81] for superficial venous drainage). The effects of superficial venous drainage on seizure outcome were nonsignificant when excluding patients with < 2 years of follow-up. AVM obliteration did not correlate with long-term seizure freedom (p = 0.202, chi-square test)., Conclusions: This study suggests that SRS improves long-term seizure control and increases the likelihood of being medication free, independently of AVM obliteration. Patients with focal impaired awareness seizures were less likely to obtain long-term seizure relief.

Objective: Of cavernous malformations (CMs) treated with radiosurgery (RS), 5% bleed after 2-year initial latency period. This rate is similar to failure rate of RS for other pathologies, which often require repeat RS for favorable outcome. The aim of this pilot study was to define failure of CM RS and to assess safety of second RS., Methods: Retrospective analysis was performed of 7 of 345 CMs retreated with RS; 6 CMs were deep-seated, and 1 was superficial. Median time between the 2 treatments was 8 years (range, 3-16 years), and median follow-up time after second RS was 3 years (range, 1-9 years)., Results: Following the 2-year latency period after RS, 6% of deep-seated and 5% of hemispheric CMs, and 6% of deep-seated and 2% of hemispheric lesions caused transient neurologic deficits without hemorrhage. A second treatment was indicated for rebleed in 5 cases and for recurrent transient neurologic deficits in 2 cases. Prescribed dose was 15 Gy (range, 12-20 Gy) at first treatment and 12 Gy (range, 12-18 Gy) at second treatment. Target volumes were 692 mm 3 (range, 54-2400 mm 3 ) and 935 mm 3 (range, 150-1550 mm 3 ) at first and second treatments, respectively, and treatment volumes were 811 mm 3 (range, 79-2500 mm 3 ) and 962 mm 3 (range, 194-1750 mm 3 ), respectively. Differences in treatment parameters were not significant. Reason for failure was inaccurate target definition in only 2 cases. There were no bleeds, morbidity, or mortality after second RS., Conclusions: Second RS applied to previously treated CMs is safe and may be effective. Further investigations are needed to verify these findings and assess long-term benefit of second RS., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: The aim of this study is to report the pattern, timing, responsible radiation parameters, and dosimetric results on the outcome of alopecia following gamma knife radiosurgery (GKRS) for various intracranial pathologies. A literature review of radiation-induced alopecia and observation of this complication with GKRS are also included., Materials and Methods: The authors report 6 cases of GKRS-induced focal temporary alopecia without dermal fibrosis or clinical scarring and with no long-term squeal., Results: In all the cases, the scalp received ≥3 Gy radiation exposure. Post GKRS alopecia is a temporary, noncicatricial, focal, reversible phenomenon observed within 2 weeks of the treatment. This acute complication is dose-dependent and reflects damage to the hair follicle. It is only seen with treated volumes in the superficial location. Hair regrowth occurs within two months with no long-term complications and change in hair quality being noted., Conclusion: Compared to whole brain radiotherapy, chances of alopecia are significantly less after GKRS. Despite a sharp dose fallout, a single fraction high-dose radiosurgery with GKRS may expose the skin appendages to more than 3 Gy radiation exposures, which may injure the hair follicles irrespective of the growth phase (anagen, telogen, or catagen) they are in. A careful planning that includes sparing of the dermal appendages and hair roots up to 4-6 mm depth in the skin may prevent this complication. Patients with superficial lesions should be well informed about the reversible nature of this possible complication, with near-normal hair growth being established within 2 months of treatment., Competing Interests: There are no conflicts of interest

Background and Purpose- The aim of this international, multicenter, retrospective matched cohort study is to directly compare the outcomes after stereotactic radiosurgery (SRS) for brain arteriovenous malformations (AVM) in pediatric versus adult patients. Methods- We performed a retrospective review of patients with AVM who underwent SRS at 8 institutions participating in the International Gamma Knife Research Foundation from 1987 to 2014. Patients were categorized into pediatric (<18 years of age) and adult (≥18 years of age) cohorts and matched in a 1:1 ratio using propensity scores. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes. Results- From a total of 2191 patients who were eligible for inclusion in the overall study cohort, 315 were selected for each of the matched cohorts. There were no significant differences between matched pediatric versus adult cohorts with respect to the rates of favorable outcome (59% versus 58%; P=0.936), AVM obliteration (62% versus 63%; P=0.934), post-SRS hemorrhage (9% versus 7%; P=0.298), radiological radiation-induced changes (26% versus 26%; P=0.837), symptomatic radiation-induced changes (7% versus 9%; P=0.383), or permanent radiation-induced changes (2% versus 3%; P=0.589). The all-cause mortality rate was significantly lower in the matched pediatric cohort (3% versus 10%; P=0.003). Conclusions- The outcomes after SRS for comparable AVMs in pediatric versus adult patients were not found to be appreciably different. SRS remains a reasonable treatment option for appropriately selected pediatric patients with AVM, who harbor a high cumulative lifetime hemorrhage risk. Age seems to be a poor predictor of AVM outcomes after SRS.

Arteriovenous malformations (AVMs) are rare congenital vascular pathologies. The reported overall annual hemorrhage rate is 3.0%, for unruptured AVMs it is 2.2%, and for ruptured AVMs, 4.5%. The main goal of AVM treatment is to prevent intracerebral hemorrhage. This is achieved by complete nidus eradication. Interventional treatment options include microsurgery, embolization and radiosurgery, as well as multimodal approaches. Radiosurgery is a safe and effective alternative to surgery or embolization, especially for AVMs located in deep or eloquent brain regions, where invasive treatment cannot be performed. With the introduction of the Leksell Gamma Knife, AVMs became one of the most common indications for radiosurgical interventions (nearly 30% of the first 15-year experience). The current review discusses the role of radiosurgery in the treatment of AVMs, with a focus on outcome predictors and a discussion of the relevant literature.

OBJECTIVE Several recent studies have improved our understanding of the outcomes of volume-staged (VS) and dose-staged (DS) stereotactic radiosurgery (SRS) for the treatment of large (volume > 10 cm 3 ) brain arteriovenous malformations (AVMs). In light of these recent additions to the literature, the aim of this systematic review is to provide an updated comparison of VS-SRS and DS-SRS for large AVMs. METHODS A systematic review of the literature was performed using PubMed to identify cohorts of 5 or more patients with large AVMs who had been treated with VS-SRS or DS-SRS. Baseline data and post-SRS outcomes were extracted for analysis. RESULTS A total of 11 VS-SRS and 10 DS-SRS studies comprising 299 and 219 eligible patients, respectively, were included for analysis. The mean obliteration rates for VS-SRS and DS-SRS were 41.2% (95% CI 31.4%-50.9%) and 32.3% (95% CI 15.9%-48.8%), respectively. Based on pooled individual patient data, the outcomes for patients treated with VS-SRS were obliteration in 40.3% (110/273), symptomatic radiation-induced changes (RICs) in 13.7% (44/322), post-SRS hemorrhage in 19.5% (50/256), and death in 7.4% (24/323); whereas the outcomes for patients treated with DS-SRS were obliteration in 32.7% (72/220), symptomatic RICs in 12.2% (31/254), post-SRS hemorrhage in 10.6% (30/282), and death in 4.6% (13/281). CONCLUSIONS Volume-staged SRS appears to afford higher obliteration rates than those achieved with DS-SRS, although with a less favorable complication profile. Therefore, VS-SRS or DS-SRS may be a reasonable treatment approach for large AVMs, either as stand-alone therapy or as a component of a multimodality management strategy.

Purpose: Radiosurgery is an established technique to treat cerebral arteriovenous malformations (AVMs). Obliteration of larger AVMs (> 10-15 cm 3 or diameter > 3 cm) in a single session is challenging with current radiosurgery platforms due to toxicity. We present a novel technique of multistage stereotactic radiosurgery (SRS) for large intracranial arteriovenous malformations (AVM) using the Gamma Knife system., Materials/methods: Eighteen patients with large (> 10-15 cm 3 or diameter > 3 cm) AVMs, which were previously treated using a staged SRS technique on the Cyberknife platform, were retrospectively selected for this study. The AVMs were contoured and divided into 3-8 subtargets to be treated sequentially in a staged approach at half to 4 week intervals. The prescription dose ranged from 15 Gy to 20 Gy, depending on the subtarget number, volume, and location. Gamma Knife plans using multiple collimator settings were generated and optimized. The coordinates of each shot from the initial plan covering the total AVM target were extracted based on their relative positions within the frame system. The shots were regrouped based on their location with respect to the subtarget contours to generate subplans for each stage. The delivery time of each shot for a subtarget was decay corrected with 60 Co for staging the treatment course to generate the same dose distribution as that planned for the total AVM target. Conformality indices and dose-volume analysis were performed to evaluate treatment plans., Results: With the shot redistribution technique, the composite dose for the multistaged treatment of multiple subtargets is equivalent to the initial plan for total AVM target. Gamma Knife plans resulted in an average PTV coverage of 96.3 ± 0.9% and a PITV of 1.23 ± 0.1. The resulting Conformality indices, V 12Gy and R 50 dose spillage values were 0.76 ± 0.05, 3.4 ± 1.8, and 3.1 ± 0.5 respectively., Conclusion: The Gamma Knife system can deliver a multistaged conformal dose to treat large AVMs when correcting for translational setup errors of each shot at each staged treatment., (© 2017 American Association of Physicists in Medicine.)

OBJECTIVE Cerebellar arteriovenous malformations (AVMs) represent the majority of infratentorial AVMs and frequently have a hemorrhagic presentation. In this multicenter study, the authors review outcomes of cerebellar AVMs after stereotactic radiosurgery (SRS). METHODS Eight medical centers contributed data from 162 patients with cerebellar AVMs managed with SRS. Of these patients, 65% presented with hemorrhage. The median maximal nidus diameter was 2 cm. Favorable outcome was defined as AVM obliteration and no posttreatment hemorrhage or permanent radiation-induced complications (RICs). Patients were followed clinically and radiographically, with a median follow-up of 60 months (range 7-325 months). RESULTS The overall actuarial rates of obliteration at 3, 5, 7, and 10 years were 38.3%, 74.2%, 81.4%, and 86.1%, respectively, after single-session SRS. Obliteration and a favorable outcome were more likely to be achieved in patients treated with a margin dose greater than 18 Gy (p < 0.001 for both), demonstrating significantly better rates (83.3% and 79%, respectively). The rate of latency preobliteration hemorrhage was 0.85%/year. Symptomatic post-SRS RICs developed in 4.5% of patients (n = 7). Predictors of a favorable outcome were a smaller nidus (p = 0.0001), no pre-SRS embolization (p = 0.003), no prior hemorrhage (p = 0.0001), a higher margin dose (p = 0.0001), and a higher maximal dose (p = 0.009). The Spetzler-Martin grade was not found to be predictive of outcome. The Virginia Radiosurgery AVM Scale score (p = 0.0001) and the Radiosurgery-Based AVM Scale score (p = 0.0001) were predictive of a favorable outcome. CONCLUSIONS SRS results in successful obliteration and a favorable outcome in the majority of patients with cerebellar AVMs. Most patients will require a nidus dose of higher than 18 Gy to achieve these goals. Radiosurgical and not microsurgical scales were predictive of clinical outcome after SRS.

OBJECTIVE The goal of stereotactic radiosurgery (SRS) for arteriovenous malformation (AVM) is complete nidus obliteration, thereby eliminating the risk of future hemorrhage. This outcome can be observed within the first 18 months, although documentation of AVM obliteration can extend to as much as 5 years after SRS is performed. A shorter time to obliteration may impact the frequency and effect of post-SRS complications and latency hemorrhage. The authors' goal in the present study was to determine predictors of early obliteration (18 months or less) following SRS for cerebral AVM. METHODS Eight centers participating in the International Gamma Knife Research Foundation (IGKRF) obtained institutional review board approval to supply de-identified patient data. From a cohort of 2231 patients, a total of 1398 patients had confirmed AVM obliteration. Patients were sorted into early responders (198 patients), defined as those with confirmed nidus obliteration at or prior to 18 months after SRS, and late responders (1200 patients), defined as those with confirmed nidus obliteration more than 18 months after SRS. The median clinical follow-up time was 63.7 months (range 7-324.7 months). RESULTS Outcome parameters including latency interval hemorrhage, mortality, and favorable outcome were not significantly different between the 2 groups. Radiologically demonstrated radiation-induced changes were noted more often in the late responder group (376 patients [31.3%] vs 39 patients [19.7%] for early responders, p = 0.005). Multivariate independent predictors of early obliteration included a margin dose > 24 Gy (p = 0.031), prior surgery (p = 0.002), no prior radiotherapy (p = 0.025), smaller AVM nidus (p = 0.002), deep venous drainage (p = 0.039), and nidus location (p < 0.0001). Basal ganglia, cerebellum, and frontal lobe nidus locations favored early obliteration (p = 0.009). The Virginia Radiosurgery AVM Scale (VRAS) score was significantly different between the 2 responder groups (p = 0.039). The VRAS score was also shown to be predictive of early obliteration on univariate analysis (p = 0.009). For early obliteration, such prognostic ability was not shown for other SRS- and AVM-related grading systems. CONCLUSIONS Early obliteration (≤ 18 months post-SRS) was more common in patients whose AVMs were smaller, located in the frontal lobe, basal ganglia, or cerebellum, had deep venous drainage, and had received a margin dose > 24 Gy.

Objective: Cerebellar arteriovenous malformation (C-AVM) is poorly tolerated because of its aggressive natural history. The aim of this study was to delineate long-term outcomes of Gamma Knife stereotactic radiosurgery (GKRS) for C-AVM., Methods: The outcomes of 45 patients who underwent GKRS for C-AVMs at our institution were retrospectively analyzed. Event-free survival was defined as free from any neurologic deficits caused by AVMs or adverse phenomena from the treatment., Results: The median age and follow-up were 41 years (range, 6-77 years) and 120 months (range, 5-291 months), respectively. The median volume and Pollock-Flickinger radiosurgical AVM score were 1.3 cm 3 (range, 0.1-8.3 cm 3 ) and 1.26 (range, 0.5-2.06), respectively. Actuarial obliteration rates were 46%, 75%, and 90% at 3, 5, and 6 years, respectively. Multivariate analysis showed that the maximal diameter ≤15 mm (P = 0.021) and margin dose >20 Gy (P = 0.0008) were significantly associated with better obliteration. Four patients experienced posttreatment hemorrhages, and annual hemorrhage rates were 1.9% and 0.30% before and after obliteration, respectively. One patient died because of hemorrhage, whereas the other 3 patients spontaneously recovered. Perifocal edema was confirmed in 8 (16%); however, no symptomatic edema was observed. Overall, neurologic deteriorations were noted in 4 patients; 3 were because of posttreatment hemorrhage, and 1 was because of pretreatment angiography. The event-free survival rates were 96%, 93%, and 93% at 4, 10, and 15 years, respectively., Conclusions: GKRS is a reasonable intervention for C-AVMs. Symptomatic complications are rare, and the long-term outcomes are favorable., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Intracranial dural arteriovenous malformations (DAVFs) are relatively uncommon vascular lesions characterized by the direct connection of dural arteries into dural venous sinuses or leptomeningeal veins. Strategies for the treatment of these complex lesions have evolved significantly over the past three decades, and include open surgical disconnection, endovascular embolization, stereotactic radiosurgery (SRS), or a combination of these approaches. Radiosurgical intervention is unique in offering significant benefits to patients while exposing them to few of the risks associated with more invasive interventions. In this chapter we provide an overview of DAVFs and discuss the features of these lesions that affect management. We focus, in particular, on radiosurgical management of these lesions, describing present treatment paradigms, the procedure for the treatment of DAVFs with SRS, and expected clinical outcomes using SRS., (© 2017 Elsevier B.V. All rights reserved.)

Stereotactic radiosurgery is a well-known treatment tool for arteriovenous malformations (AVMs). The method has high validity and minimal invasiveness, but late-onset problems involving tumor formation and vasculopathy induced by radiation have been reported. We present a rare case of a radiation-induced ruptured de novo aneurysm following Gamma Knife surgery (GKS) for an AVM. A 17-year-old, right-handed male underwent GKS for AVM at the left parietal lobe. After 3 years, a follow-up angiogram showed a residual AVM at the angular gyrus. Then, a 2nd GKS was performed for the residual lesion. Six years after the 1st GKS, the AVM disappeared on the angiogram. Seven years later, he suffered a sudden onset of headache. A left carotid angiogram revealed a ruptured aneurysm at the M2-M3 junction of the middle cerebral artery parietal branch. Coil embolization was performed, and the aneurysm was occluded. The patient was discharged without any neurologic deficits., (© 2017 S. Karger AG, Basel.)

Background and Purpose: A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) indicated the superiority of medical management in reducing the risks for strokes and other neurological deficits over observation alone. The aim of our study was to verify the rationale for stereotactic radiosurgery (SRS) for small unruptured arteriovenous malformation., Methods: A retrospective review was performed for 292 patients with unruptured arteriovenous malformations referred for SRS. The risks for cerebral hemorrhages were statistically compared before and after SRS., Results: Of the 292 patients in whom arteriovenous malformation was found unruptured at initial diagnosis, 17 sustained hemorrhages in the period between the diagnosis and the initial therapeutic intervention (annual bleeding rate, 2.1%; 95% confidence interval [CI], 1.2%-3.4%). Of the remaining 275 patients, 240 were initially treated with SRS, and 16 sustained a hemorrhage after SRS (annual bleeding rate, 1.1%; 95% CI, 0.6%-1.8%), but only 2 sustained a hemorrhage after angiographic obliteration (annual bleeding rate, 0.3%; 95% CI, 0.04%-1.2%). Comparing the risk of hemorrhage between the periods before and after SRS, a 53% risk reduction was achieved after SRS (hazard ratio, 0.47; 95% CI, 0.24-0.94; P=0.03), and 85% reduction was achieved after angiographic obliteration (hazard ratio, 0.15; 95% CI, 0.02-0.53; P=0.002)., Conclusions: SRS can significantly reduce the risk of stroke in the patients with small unruptured arteriovenous malformations. To definitively determine the clinical benefits of SRS, a longer follow-up will be necessary. However, based on our results, we can recommend SRS for patients who face a latent risk for stroke from this intractable vascular disease., (© 2016 American Heart Association, Inc.)