Postradiosurgery Hemorrhage Research Articles

Hemorrhagic Outcome of Brainstem Cavernous Malformations following Radiosurgery: Dose-Response Relationship

Introduction: This study aimed to assess the impact of gamma knife radiosurgery on brainstem cavernous malformations (CMs). Methods: A total of 85 patients (35 females; median age 41.0 years) who underwent gamma knife radiosurgery for brainstem CMs at our institute between 2006 and 2015 were enrolled in a prospective clinical observation trial. Risk factors for hemorrhagic outcomes were evaluated, and outcomes were compared across different margin doses. Results: The pre-radiosurgery annual hemorrhage rate (AHR) was 32.3% (44 hemorrhages during 136.2 patient-years). The median planning target volume was 1.292 cc. The median margin and maximum doses were 15.0 and 29.2 Gy, respectively, with a median isodose line of 50.0%. The post-radiosurgery AHR was 2.7% (21 hemorrhages during 769.9 patient-years), with a rate of 5.5% within the first 2 years and 2.0% thereafter. The post-radiosurgery AHR for patients with margin doses of ≤13.0 Gy (n = 15), 14.0–15.0 Gy (n = 50), and ≥16.0 Gy (n = 20) was 5.4, 2.7, and 0.6%, respectively. Correspondingly, transient adverse radiation effects were observed in 6.7 (1/15), 10.0 (5/50), and 30.0% (6/20) of cases, respectively. An increased margin dose per 1 Gy (hazard ratio: 0.530, 95% CI: 0.341–0.826, p = 0.005) was identified as an independent protective factor against post-radiosurgery hemorrhage. Margin doses of ≥16.0 Gy were associated with improved hemorrhagic outcomes (hazard ratio: 0.343, 95% confidence interval [CI]: 0.157–0.749, p = 0.007), but an increased risk of adverse radiation effects (odds ratio: 3.006, 95% CI: 1.041–8.677, p = 0.042). Conclusion: The AHR of brainstem CMs decreased following radiosurgery, and our study revealed a significant dose-response relationship. Margin doses of 14–15 Gy were recommended. Further studies are required to validate our findings.

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.

Venous Stenosis and Hemorrhage After Radiosurgery for Cerebral Arteriovenous Malformations

The risk of hemorrhage remains after radiosurgery for patients with arteriovenous malformations (AVMs), especially during the latency period. The effect of venous outflow stenosis on postradiosurgery AVM hemorrhage has been understudied. The present study sought to clarify the effect of venous stenosis on postradiation hemorrhage. We retrospectively reviewed the records of patients with AVM seen at our institution from 1990 to 2015. Patients who had undergone radiosurgery were included, and those without sufficient data were excluded. We performed multivariable Cox regression to evaluate the predictors of postradiosurgery hemorrhage, with specific emphasis on venous stenosis. Patients were censored from the first radiosurgery to hemorrhage or the last follow-up visit. The baseline and angiographic characteristics were compared between those with venous stenosis and those without to address potential confounders. The present study included 240 patients, of whom 29 (12.1%) had venous stenosis. The venous stenosis cohort included more patients with venous varices (P= 0.009) and fewer with deep venous drainage (P= 0.048) compared with those without venous stenosis. Most patients had grade III or higher AVMs (63.2%), with an obliteration rate of 32.9%. In an all-inclusive multivariable Cox regression, hemorrhage risk was associated with venous stenosis (hazard ratio [HR], 3.70; P= 0.034), age (HR, 1.05; P= 0.002), AVM volume (HR, 1.04; P= 0.004), and hemorrhage before treatment (HR, 4.11; P= 0.014). Male gender was protective (HR, 0.31; P= 0.036) against hemorrhage. We identified statistically significant risk factors for postradiosurgery AVM hemorrhage, which included advanced age, female gender, the presence of venous stenosis, a larger AVM volume, and previous hemorrhage. We recommend cautious selection of patients for radiosurgery with close follow-up after treatment, especially for patients with these risk factors.

373 Risk of Hemorrhage Following Radiosurgery for Cerebral Arteriovenous Malformations (AVMs) Is Associated with Venous Stenosis

Abstract INTRODUCTION Approximately 6% of all patients who undergo radiosurgery experience subsequent hemorrhage, even in those with obliterated lesions. Little information has been presented in existing literature about risk modifiers of post-radiosurgery hemorrhage. Associated aneurysms, venous drainage pattern, size of AVM and prescription dose were previously reported as risk factors. Here, we aim to elucidate the effect of venous stenosis on risk of hemorrhage after radiosurgery. METHODS We retrospectively reviewed medical records of all AVM patients evaluated at our institution from 1990–2015, and those who were treated with radiosurgery were included. We excluded patients without baseline or follow-up data, nor information about treatment and angiographic results. Baseline and angiographic characteristics were compared between those with venous stenosis and those without to elicit confounding factors. We then proceeded with univariable and multivariable Cox regression analysis looking at predictors of post-radiosurgery hemorrhage, with inclusion of confounding factors. Patients were censored from first radiosurgery to hemorrhage or to last follow-up. RESULTS &gt;We included 240 patients in this study. Twenty-nine (12.1%) had venous stenosis; there were more AVMs with venous varices(P = 0.009) and fewer with deep venous drainage (P = 0.048) compared to those without venous stenosis. Univariable analysis on post-radiosurgery hemorrhage showed age, gender, AVM volume, venous stenosis, and unrelated aneurysm were associated with increased risk of hemorrhage. In an all-inclusive model multivariable Cox regression, increased risk of hemorrhage was associated with venous stenosis (HR:3.70, P = 0.034), age (HR:1.05, P = 0.002), AVM volume (HR:1.04, P = 0.004), and hemorrhage before treatment (HR:4.11, P = 0.014). Male gender appears protective (HR:0.31, P = 0.036) against hemorrhage. CONCLUSION We found multiple factors associated with increased risk of AVM hemorrhage after radiosurgery. We recommend that selection of radiosurgery should proceed with caution with close follow-up after treatment, especially in patients with venous stenosis combined with advanced age, female gender, large AVM volume, and previous rupture.

Radiosurgery in treatment of cerebral arteriovenous malformation: Mid-term results of 388 cases from a single center.

Background and Objectives:The purpose of this study is to evaluate the outcome and risks of radiosurgery for patients with arteriovenous malformations (AVM) of the brain all treated in a single center in the 3rd world with all its limitations.Materials and Methods:We performed a retrospective analysis of 388 patients with AVM treated with radiosurgery during an 8-year period. Factors associated with increased chance of AVM obliteration or hemorrhages during the follow-up period were analyzed.Results:Among 388 cases included in our series, 74 were Spetzler-Martin (SM) grade IV or V. Forty-four patients (11.3%) experienced post-radiosurgery hemorrhage in their follow-up period. The number of feeders (one/multiple) and deep location of the AVM did not alter the chance of bleeding (P < 0.05). Higher SM grading of the AVM was associated with increased chance of hemorrhage and decreased obliteration rate (P > 0.05) in the mid-term follow up.Conclusions:Our case series showed that radiosurgery can be considered a viable alternative in the treatment of even large AVMs which might not be considered good candidates for surgery or endovascular treatment. Further data including large size lesions are warranted to further support our findings.

Radiosurgery for Unruptured Brain Arteriovenous Malformations: An International Multicenter Retrospective Cohort Study.

The role of intervention in the management of unruptured brain arteriovenous malformations (AVM) is controversial. To analyze in a multicenter, retrospective cohort study, the outcomes following radiosurgery for unruptured AVMs and determine predictive factors. We evaluated and pooled AVM radiosurgery data from 8 institutions participating in the International Gamma Knife Research Foundation. Patients with unruptured AVMs and ≥12 mo of follow-up were included in the study cohort. Favorable outcome was defined as AVM obliteration, no postradiosurgical hemorrhage, and no permanently symptomatic radiation-induced changes. The unruptured AVM cohort comprised 938 patients with a median age of 35 yr. The median nidus volume was 2.4 cm 3 , 71% of AVMs were located in eloquent brain areas, and the Spetzler-Martin grade was III or higher in 57%. The median radiosurgical margin dose was 21 Gy and follow-up was 71 mo. AVM obliteration was achieved in 65%. The annual postradiosurgery hemorrhage rate was 1.4%. Symptomatic and permanent radiation-induced changes occurred in 9% and 3%, respectively. Favorable outcome was achieved in 61%. In the multivariate logistic regression analysis, smaller AVM maximum diameter ( P = .001), the absence of AVM-associated arterial aneurysms ( P = .001), and higher margin dose ( P = .002) were found to be independent predictors of a favorable outcome. A margin dose ≥ 20 Gy yielded a significantly higher rate of favorable outcome (70% vs 36%; P < .001). Radiosurgery affords an acceptable risk to benefit profile for patients harboring unruptured AVMs. These findings justify further prospective studies comparing radiosurgical intervention to conservative management for unruptured AVMs.

Stereotactic radiosurgery for Spetzler-Martin Grade III arteriovenous malformations: an international multicenter study.

OBJECTIVE Because of the angioarchitectural diversity of Spetzler-Martin (SM) Grade III arteriovenous malformations (AVMs), the management of these lesions is incompletely defined. The aims of this multicenter, retrospective cohort study were to evaluate the outcomes after stereotactic radiosurgery (SRS) for SM Grade III AVMs and to determine the factors predicting these outcomes. METHODS The authors analyzed and pooled data from patients with SM Grade III AVMs treated with SRS at 8 institutions participating in the International Gamma Knife Research Foundation. Patients with these AVMs and a minimum follow-up length of 12 months were included in the study cohort. An optimal outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes (RICs). Data were analyzed by univariate and multivariate regression analyses. RESULTS The SM Grade III AVM cohort comprised 891 patients with a mean age of 34 years at the time of SRS. The mean nidus volume, radiosurgical margin dose, and follow-up length were 4.5 cm3, 20 Gy, and 89 months, respectively. The actuarial obliteration rates at 5 and 10 years were 63% and 78%, respectively. The annual postradiosurgery hemorrhage rate was 1.2%. Symptomatic and permanent RICs were observed in 11% and 4% of the patients, respectively. Optimal outcome was achieved in 56% of the patients and was significantly more frequent in cases of unruptured AVMs (OR 2.3, p < 0.001). The lack of a previous hemorrhage (p = 0.037), absence of previous AVM embolization (p = 0.002), smaller nidus volume (p = 0.014), absence of AVM-associated arterial aneurysms (p = 0.023), and higher margin dose (p < 0.001) were statistically significant independent predictors of optimal outcome in a multivariate analysis. CONCLUSIONS Stereotactic radiosurgery provided better outcomes for patients with small, unruptured SM Grade III AVMs than for large or ruptured SM Grade III nidi. A prospective trial or registry that facilitates a comparison of SRS with conservative AVM management might further clarify the authors' observations for these often high-risk AVMs.

International multicenter cohort study of pediatric brain arteriovenous malformations. Part 2: Outcomes after stereotactic radiosurgery.

OBJECTIVE Pediatric patients (age < 18 years) harboring brain arteriovenous malformations (AVMs) are burdened with a considerably higher cumulative lifetime risk of hemorrhage than adults. Additionally, the pediatric population was excluded from recent prospective comparisons of intervention versus conservative management for unruptured AVMs. The aims of this multicenter, retrospective cohort study are to analyze the outcomes after stereotactic radiosurgery for unruptured and ruptured pediatric AVMs. METHODS We analyzed and pooled AVM radiosurgery data from 7 participating in the International Gamma Knife Research Foundation. Patients younger than 18 years of age who had at least 12 months of follow-up were included in the study cohort. Favorable outcome was defined as AVM obliteration, no post-radiosurgical hemorrhage, and no permanently symptomatic radiation-induced changes (RIC). The post-radiosurgery outcomes of unruptured versus ruptured pediatric AVMs were compared, and statistical analyses were performed to identify predictive factors. RESULTS The overall pediatric AVM cohort comprised 357 patients with a mean age of 12.6 years (range 2.8-17.9 years). AVMs were previously treated with embolization, resection, and fractionated external beam radiation therapy in 22%, 6%, and 13% of patients, respectively. The mean nidus volume was 3.5 cm3, 77% of AVMs were located in eloquent brain areas, and the Spetzler-Martin grade was III or higher in 59%. The mean radiosurgical margin dose was 21 Gy (range 5-35 Gy), and the mean follow-up was 92 months (range 12-266 months). AVM obliteration was achieved in 63%. During a cumulative latency period of 2748 years, the annual post-radiosurgery hemorrhage rate was 1.4%. Symptomatic and permanent radiation-induced changes occurred in 8% and 3%, respectively. Favorable outcome was achieved in 59%. In the multivariate logistic regression analysis, the absence of prior AVM embolization (p = 0.001) and higher margin dose (p < 0.001) were found to be independent predictors of a favorable outcome. The rates of favorable outcome for patients treated with a margin dose ≥ 22 Gy vs < 22 Gy were 78% (110/141 patients) and 47% (101/216 patients), respectively. A margin dose ≥ 22 Gy yielded a significantly higher probability of a favorable outcome (p < 0.001). The unruptured and ruptured pediatric AVM cohorts included 112 and 245 patients, respectively. Ruptured AVMs had significantly higher rates of obliteration (68% vs 53%, p = 0.005) and favorable outcome (63% vs 51%, p = 0.033), with a trend toward a higher incidence of post-radiosurgery hemorrhage (10% vs 4%, p = 0.07). The annual post-radiosurgery hemorrhage rates were 0.8% for unruptured and 1.6% for ruptured AVMs. CONCLUSIONS Radiosurgery is a reasonable treatment option for pediatric AVMs. Obliteration and favorable outcomes are achieved in the majority of patients. The annual rate of latency period hemorrhage after radiosurgery for both ruptured and unruptured pediatric AVM patients conveys a significant risk until the nidus is obliterated.

Radiosurgery for Cerebral Arteriovenous Malformations with Associated Arterial Aneurysms

The radiosurgical outcomes for cerebral arteriovenous malformations (AVM) with AVM-associated arterial aneurysms (AAA) are poorly understood, because many AAAs are embolized before nidal intervention. The aim of this retrospective case-control study is to determine the effect of AAAs on AVM radiosurgery outcomes. We evaluated an institutional AVM radiosurgery database from 1989 to 2013. AAAs were classified as intranidal (type I) or prenidal (type II). The case cohort comprised AVMs with patent type I or II AAAs. The control cohort comprised AVMs without AAAs and matched 2:1 to the case cohort. The case cohort comprised 51 AVMs, including 23 with type I and 28 with type II AAAs. The control cohort comprised 102 AVMs without AAAs. The cumulative AVM obliteration, annual postradiosurgery hemorrhage, and radiologically evident radiation-induced changes rates were 67%, 3.3%, and 28%, respectively, for the case cohort, compared with 70%, 2.0%, and 35%, respectively, for the control cohort. The presence of an AAA was not significantly associated with obliteration (P = 0.293), postradiosurgery hemorrhage (P = 0.209), or radiation-induced changes (P = 0.323). The rates of type II AAA occlusion at 3, 5, and 10 years were 46%, 77%, and 95%, respectively. The type II AAA occlusion rate was significantly higher in obliterated AVMs (P = 0.002). Patent intranidal or prenidal AAAs do not significantly affect AVM radiosurgical outcomes. Occlusion of distal prenidal AAAs commonly occurs after radiosurgery. These findings may support a more conservative stance for embolization before radiosurgery for AVMs with AAAs.

Radiosurgery for Cerebral Arteriovenous Malformations in A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA)-Eligible Patients: A Multicenter Study.

The benefit of intervention for patients with unruptured cerebral arteriovenous malformations (AVMs) was challenged by results demonstrating superior clinical outcomes with conservative management from A Randomized Trial of Unruptured Brain AVMs (ARUBA). The aim of this multicenter, retrospective cohort study is to analyze the outcomes of stereotactic radiosurgery for ARUBA-eligible patients. We combined AVM radiosurgery outcome data from 7 institutions participating in the International Gamma Knife Research Foundation. Patients with ≥12 months of follow-up were screened for ARUBA eligibility criteria. Favorable outcome was defined as AVM obliteration, no postradiosurgery hemorrhage, and no permanently symptomatic radiation-induced changes. Adverse neurological outcome was defined as any new or worsening neurological symptoms or death. The ARUBA-eligible cohort comprised 509 patients (mean age, 40 years). The Spetzler-Martin grade was I to II in 46% and III to IV in 54%. The mean radiosurgical margin dose was 22 Gy and follow-up was 86 months. AVM obliteration was achieved in 75%. The postradiosurgery hemorrhage rate during the latency period was 0.9% per year. Symptomatic and permanent radiation-induced changes occurred in 11% and 3%, respectively. The rates of favorable outcome, adverse neurological outcome, permanent neurological morbidity, and mortality were 70%, 13%, 5%, and 4%, respectively. Radiosurgery may provide durable clinical benefit in some ARUBA-eligible patients. On the basis of the natural history of untreated, unruptured AVMs in the medical arm of ARUBA, we estimate that a follow-up duration of 15 to 20 years is necessary to realize a potential benefit of radiosurgical intervention for conservative management in unruptured patients with AVM.

Stereotactic Radiosurgery for Partially Resected Cerebral Arteriovenous Malformations

Incomplete microsurgical resection of cerebral arteriovenous malformations (AVM) occurs uncommonly. However, such patients harboring postoperative residual nidi remain exposed to the risk of AVM hemorrhage and are therefore reasonable candidates for further intervention. The goals of this retrospective case-control study are to analyze the radiosurgery outcomes for partially resected AVMs and determine the effect of prior resection on AVM radiosurgery outcomes. We evaluated a prospective database of AVM patients treated with radiosurgery from 1989-2013. Previously resected AVMs with radiologic follow-up ≥2 years or nidus obliteration were selected for analysis and matched, in a 1:1 fashion and blinded to outcome, to previously unresected AVMs. Statistical analyses were performed to assess relationship between prior resection and AVM radiosurgery outcomes. The matching process yielded 88 patients in each of the previously resected and unresected AVM cohorts. In the resected AVM cohort, the actuarial AVM obliteration rates at 3 and 5 years were 47% and 75%, respectively; the rates of radiologic and symptomatic radiation-induced changes (RICs) were 10% and 3%, respectively; and the annual postradiosurgery hemorrhage risk was 1.1%. The lack of prior AVM resection (P < 0.001) and superficial AVM location (P = 0.009) were independent predictors of radiologic RIC. The actuarial rates of obliteration (P = 0.849) and postradiosurgery hemorrhage (P = 0.548) were not significantly different between the resected and unresected AVM cohorts. Radiosurgery affords a reasonable risk-to-benefit profile for incompletely resected AVMs. For those with a small-volume residual nidus after resection, radiosurgery should be considered an effective alternative to repeat resection.

Radiosurgery for unruptured cerebral arteriovenous malformations in pediatric patients.

Unruptured cerebral arteriovenous malformations (AVMs) in pediatric patients (age <18 years) were excluded from A Randomized Trial of Unruptured AVMs (ARUBA). Therefore, the efficacy of radiosurgery for unruptured pediatric AVMs is poorly understood. The goal of this study is to determine the outcomes and define the predictors of obliteration following radiosurgery for unruptured AVMs in pediatric patients. We evaluated a prospective database, from 1989 to 2013, of AVM patients treated with radiosurgery at our institution. Patients with age less than 18 years at the time of radiosurgery, unruptured nidi, and at least 2 years of radiologic follow-up or AVM obliteration were selected for analysis. Statistical analyses were performed to determine actuarial obliteration rates and identify factors associated with obliteration. In the 51 unruptured pediatric AVM patients included for analysis, the median age was 13 years, and the most common presentation was seizure in 53 %. The median nidus volume and radiosurgical margin dose were 3.2 cm(3) and 21.5 Gy, respectively. The median radiologic follow-up was 45 months. The actuarial AVM obliteration rates at 3, 5, and 10 years were 29 %, 54 %, and 72 %, respectively. In the multivariate Cox proportional hazards regression analysis, higher margin dose (P = 0.002), fewer draining veins (P = 0.038), and lower Virginia Radiosurgery AVM Scale (P = 0.003) were independent predictors of obliteration. Obliteration rates were significantly higher with a margin dose of at least 22 Gy (P = 0.003) and for nidi with 2 or fewer draining veins (P = 0.001). The incidences of radiologically evident, symptomatic, and permanent radiation-induced changes were 55 %, 16 %, and 2 %, respectively. The annual post-radiosurgery hemorrhage rate was 1.3 %, and the incidence of post-radiosurgery cyst formation was 2 %. Radiosurgery affords a favorable risk to benefit profile for unruptured pediatric AVMs. Pediatric patients with unruptured AVMs merit further study to define an optimal management approach.

Radiosurgery for ruptured intracranial arteriovenous malformations

Ruptured intracranial arteriovenous malformations (AVMs) are at a significantly greater risk for future hemorrhage than unruptured lesions, thereby necessitating treatment in the majority of cases. In a retrospective, single-center study, the authors describe the outcomes after radiosurgery in a large cohort of patients with ruptured AVMs. From an institutional review board-approved, prospectively collected AVM radiosurgery database, the authors identified all patients with a history of AVM rupture. They analyzed obliteration rates in all patients in whom radiological follow-up data were available (n = 639). However, to account for the latency period associated with radiosurgery, only those patients with more than 2 years of radiological follow-up and those with earlier AMV obliteration were included in the analysis of prognostic factors related to obliteration and complications. This resulted in a cohort of 565 patients with ruptured AVMs for whom data were analyzed; these patients had a median radiological follow-up of 57 months and a median age of 29 years. Twenty-one percent of the patients underwent preradiosurgery embolization. The median volume and prescription dose were 2.1 cm(3) and 22 Gy, respectively. The Spetzler-Martin grade was III or higher in 56% of patients, the median radiosurgery-based AVM score was 1.08, and the Virginia Radiosurgery AVM Scale (RAS) score was 3 to 4 points in 44%. Survival and regression analyses were performed to determine obliteration rates over time and predictors of obliteration and complications. In the overall population of 639 patients with ruptured AVMs, the obliteration rate was 11.1% based on MRI only (71 of 639 patients), 56.0% based on angiography (358 of 639), and 67.1% based on combined modalities (429 of 639 patients). In the cohort of patients with 2 years of follow-up or an earlier AVM obliteration, the cumulative obliteration rate was 76% and the actuarial obliteration rates were 41% and 64% at 3 and 5 years, respectively. Multivariate analysis identified the absence of preradiosurgery embolization (p < 0.001), increased prescription dose (p = 0.001), the presence of a single draining vein (p = 0.046), no postradiosurgery-related hemorrhage (p = 0.007), and lower Virginia RAS score (p = 0.020) as independent predictors of obliteration. The annual risk of a hemorrhage occurring during the latency period was 2.0% and the rate of hemorrhage-related morbidity and mortality was 1.6%. Multivariate analysis showed that decreased prescription dose (p < 0.001) and multiple draining veins (p = 0.003) were independent predictors of postradiosurgery hemorrhage. The rates of symptomatic and permanent radiation-induced changes were 8% and 2.7%, respectively. In the multivariate analysis, a single draining vein (p < 0.001) and higher Virginia RAS score (p = 0.005) were independent predictors of radiation-induced changes following radiosurgery. Radiosurgery effectively treats ruptured AVMs with an acceptably low risk-to-benefit ratio. For patients with ruptured AVMs, favorable outcomes are more likely when preradiosurgical embolization is avoided and a higher prescription dose can be delivered.

Radiosurgery for low-grade intracranial arteriovenous malformations

Low-grade, or Spetzler-Martin (SM) Grades I and II, arteriovenous malformations (AVMs) are associated with lower surgical morbidity rates than higher-grade lesions. While radiosurgery is now widely accepted as an effective treatment approach for AVMs, the risks and benefits of the procedure for low-grade AVMs, as compared with microsurgery, remain poorly understood. The authors of this study present the outcomes for a large cohort of low-grade AVMs treated with radiosurgery. From an institutional radiosurgery database comprising approximately 1450 AVM cases, all patients with SM Grade I and II lesions were identified. Patients with less than 2 years of radiological follow-up, except those with complete AVM obliteration, were excluded from analysis. Univariate and multivariate Cox proportional-hazards and logistic regression analyses were used to determine factors associated with obliteration, radiation-induced changes (RICs), and hemorrhage following radiosurgery. Five hundred two patients harboring low-grade AVMs were eligible for analysis. The median age was 35 years, 50% of patients were male, and the most common presentation was hemorrhage (47%). The median AVM volume and prescription dose were 2.4 cm(3) and 23 Gy, respectively. The median radiological and clinical follow-up intervals were 48 and 62 months, respectively. The cumulative obliteration rate was 76%. The median time to obliteration was 40 months, and the actuarial obliteration rates were 66% and 80% at 5 and 10 years, respectively. Independent predictors of obliteration were no preradiosurgery embolization (p < 0.001), decreased AVM volume (p = 0.005), single draining vein (p = 0.013), lower radiosurgery-based AVM scale score (p = 0.016), and lower Virginia Radiosurgery AVM Scale (Virginia RAS) score (p = 0.001). The annual postradiosurgery hemorrhage rate was 1.4% with increased AVM volume (p = 0.034) and lower prescription dose (p = 0.006) as independent predictors. Symptomatic and permanent RICs were observed in 8.2% and 1.4% of patients, respectively. No preradiosurgery hemorrhage (p = 0.011), a decreased prescription dose (p = 0.038), and a higher Virginia RAS score (p = 0.001) were independently associated with postradiosurgery RICs. Spetzler-Martin Grade I and II AVMs are very amenable to successful treatment with stereotactic radiosurgery. While patient, physician, and institutional preferences frequently dictate the final course of treatment, radiosurgery offers a favorable risk-to-benefit profile for the management of low-grade AVMs.

Radiosurgery for Spetzler-Martin Grade III arteriovenous malformations

Intracranial arteriovenous malformations (AVMs) are most commonly classified based on their Spetzler-Martin grades. Due to the composition of the Spetzler-Martin grading scale, Grade III AVMs are the most heterogeneous, comprising 4 distinct lesion subtypes. The management of this class of AVMs and the optimal treatment approach when intervention is indicated remain controversial. The authors report their experience with radiosurgery for the treatment of Grade III AVMs in a large cohort of patients. All patients with Spetzler-Martin Grade III AVMs treated with radiosurgery at the University of Virginia over the 20-year span from 1989 to 2009 were identified. Patients who had less than 2 years of radiological follow-up and did not have evidence of complete obliteration during that period were excluded from the study, leaving 398 cases for analysis. The median patient age at treatment was 31 years. The most common presenting symptoms were hemorrhage (59%), seizure (20%), and headache (10%). The median AVM volume was 2.8 cm(3), and the median prescription dose was 20 Gy. The median radiological and clinical follow-up intervals were 54 and 68 months, respectively. Univariate and multivariate Cox proportional hazards and logistic regression analysis were used to identify factors associated with obliteration, postradiosurgery radiation-induced changes (RIC), and favorable outcome. Complete AVM obliteration was observed in 69% of Grade III AVM cases at a median time of 46 months after radiosurgery. The actuarial obliteration rates at 3 and 5 years were 38% and 60%, respectively. The obliteration rate was higher in ruptured AVMs than in unruptured ones (p < 0.001). Additionally, the obliteration rate for Grade III AVMs with small size (< 3 cm diameter), deep venous drainage, and location in eloquent cortex was higher than for the other subtypes (p < 0.001). Preradiosurgery AVM rupture (p = 0.016), no preradiosurgery embolization (p = 0.003), increased prescription dose (p < 0.001), fewer isocenters (p = 0.006), and a single draining vein (p = 0.018) were independent predictors of obliteration. The annual risk of postradiosurgery hemorrhage during the latency period was 1.7%. Two patients (0.5%) died of hemorrhage during the radiosurgical latency period. The rates of symptomatic and permanent RIC were 12% and 4%, respectively. Absence of preradiosurgery AVM rupture (p < 0.001) and presence of a single draining vein (p < 0.001) were independent predictors of RIC. Favorable outcome was observed in 63% of patients. Independent predictors of favorable outcome were no preradiosurgery hemorrhage (p = 0.014), increased prescription dose (p < 0.001), fewer isocenters (p = 0.014), deep location (p = 0.014), single draining vein (p = 0.001), and lower Virginia radiosurgery AVM scale score (p = 0.016). Radiosurgery for Spetzler-Martin Grade III AVMs yields relatively high rates of obliteration with a low rate of adverse procedural events. Small and ruptured lesions are more likely to become obliterated after radiosurgery than large and unruptured ones.

Outcomes following single-session radiosurgery for high-grade intracranial arteriovenous malformations

Introduction. The management of Spetzler–Martin Grade-IV and -V arteriovenous malformations (AVMs) is controversial due to their uncertain natural history, the high rate of morbidity and mortality associated with microsurgical resection, and the relatively low rate of successful obliteration from less invasive approaches such as radiosurgery and embolization. We present our radiosurgical results for high-grade AVMs. Methods. We identified all patients with Spetzler–Martin Grade-IV and -V AVMs treated with single-session radiosurgery at the University of Virginia between 1989 and 2009. Patients with less than 2 years of follow-up without obliteration were excluded. This yielded 110 patients with a median age 27.6 years. The median AVM volume was 5.7 cc and prescription dose was 19 Gy. The median radiographic and clinical follow-up intervals were 88 and 97 months, respectively. Results. Complete AVM obliteration was identified on MRI only in 11 patients (10%) and confirmed by DSA in 38 patients (34%) for a cumulative obliteration rate of 44%. The actuarial rates of obliteration at 3 and 5 years were 10% and 23%, respectively. The mean and median times to obliteration were 60 months and 43 months, respectively. Significant independent predictors of obliteration were no pre-radiosurgery embolization (P = 0.008), superficial location (P = 0.001), and higher prescription dose (P = 0.028). The annual rate of post-radiosurgery hemorrhage was 3.0%, and symptomatic RIC was observed in 12% of patients. Unruptured AVMs were more likely to have RIC (P = 0.005). The rates of temporary and permanent post-radiosurgery clinical deterioration were 9% and 10%, respectively. Conclusion. Single-session radiosurgery is an acceptable treatment option for select patients harboring high-grade AVMs for which microsurgery or conservative management are associated with an unacceptably high risk of adverse outcomes.

Radiosurgery for Primary Motor and Sensory Cortex Arteriovenous Malformations

Eloquent intracranial arteriovenous malformations (AVMs) located in the primary motor or somatosensory cortex (PMSC) carry a high risk of microsurgical morbidity. To evaluate the outcomes of radiosurgery on PMSC AVMs and compare them with radiosurgery outcomes in a matched cohort of noneloquent lobar AVMs. Between 1989 and 2009, 134 patients with PMSC AVMs underwent Gamma Knife radiosurgery with a median radiographic and clinical follow-up of 64 and 80 months, respectively. Seizure (40.3%) and hemorrhage (28.4%) were the most common presenting symptoms. Pre-radiosurgery embolization was performed in 33.6% of AVMs. Median AVM volume was 4.1 mL (range, 0.1-22.6 mL), and prescription dose was 20 Gy (range, 7-30 Gy). Cox regression analysis was performed to identify factors associated with obliteration. The overall obliteration rate, including magnetic resonance imaging and angiography, after radiosurgery was 63%. Obliteration was achieved in 80% of AVMs with a volume less than 3 mL compared with 55% for AVMs larger than 3 mL. No previous embolization (P = .002) and a single draining vein (P = .001) were independent predictors of obliteration on multivariate analysis. The annual post-radiosurgery hemorrhage risk was 2.5%. Radiosurgery-related morbidity was temporary and permanent in 14% and 6% of patients, respectively. Comparing PMSC AVMs with matched noneloquent lobar AVMs, the obliteration rates and clinical outcomes after radiosurgery were not statistically different. For patients harboring PMSC AVMs, radiosurgery offers a reasonable chance of obliteration with a relatively low complication rate. Eloquent location does not appear to confer the same negative prognostic value for radiosurgery that it does for microsurgery.

A practical grading scale for predicting outcome after radiosurgery for arteriovenous malformations: analysis of 1012 treated patients

The authors performed a study to review outcomes following Gamma Knife radiosurgery for cerebral arteriovenous malformations (AVMs) and to create a practical scale to predict long-term outcome. Outcomes were reviewed in 1012 patients who were followed up for more than 2 years. Favorable outcome was defined as AVM obliteration and no posttreatment hemorrhage or permanent, symptomatic, radiation-induced complication. Preradiosurgery patient and AVM characteristics predictive of outcome in multivariate analysis were weighted according to their odds ratios to create the Virginia Radiosurgery AVM Scale. The mean follow-up time was 8 years (range 2-20 years). Arteriovenous malformation obliteration occurred in 69% of patients. Postradiosurgery hemorrhage occurred in 88 patients, for a yearly incidence of 1.14%. Radiation-induced changes occurred in 387 patients (38.2%), symptoms in 100 (9.9%), and permanent deficits in 21 (2.1%). Favorable outcome was achieved in 649 patients (64.1%). The Virginia Radiosurgery AVM Scale was created such that patients were assigned 1 point each for having an AVM volume of 2-4 cm(3), eloquent AVM location, or a history of hemorrhage, and 2 points for having an AVM volume greater than 4 cm(3). Eighty percent of patients who had a score of 0-1 points had a favorable outcome, as did 70% who had a score of 2 points and 45% who had a score of 3-4 points. The Virginia Radiosurgery AVM Scale was still predictive of outcome after controlling for predictive Gamma Knife radiosurgery treatment parameters, including peripheral dose and number of isocenters, in a multivariate analysis. The Spetzler-Martin grading scale and the Radiosurgery-Based Grading Scale predicted favorable outcome, but the Virginia Radiosurgery AVM Scale provided the best assessment. Gamma Knife radiosurgery can be used to achieve long-term AVM obliteration and neurological preservation in a predictable fashion based on patient and AVM characteristics.

Radiosurgery for patients with unruptured intracranial arteriovenous malformations

The appropriate management of unruptured intracranial arteriovenous malformations (AVMs) remains controversial. In the present study, the authors evaluate the radiographic and clinical outcomes of radiosurgery for a large cohort of patients with unruptured AVMs. From a prospective database of 1204 cases of AVMs involving patients treated with radiosurgery at their institution, the authors identified 444 patients without evidence of rupture prior to radiosurgery. The patients' mean age was 36.9 years, and 50% were male. The mean AVM nidus volume was 4.2 cm(3), 13.5% of the AVMs were in a deep location, and 44.4% were at least Spetzler-Martin Grade III. The median radiosurgical prescription dose was 20 Gy. Univariate and multivariate Cox regression analyses were used to determine risk factors associated with obliteration, postradiosurgery hemorrhage, radiation-induced changes, and postradiosurgery cyst formation. The mean duration of radiological and clinical follow-up was 76 months and 86 months, respectively. The cumulative AVM obliteration rate was 62%, and the postradiosurgery annual hemorrhage rate was 1.6%. Radiation-induced changes were symptomatic in 13.7% and permanent in 2.0% of patients. The statistically significant independent positive predictors of obliteration were no preradiosurgery embolization (p < 0.001), increased prescription dose (p < 0.001), single draining vein (p < 0.001), radiological presence of radiation-induced changes (p = 0.004), and lower Spetzler-Martin grade (p = 0.016). Increased volume and higher Pittsburgh radiosurgery-based AVM score were predictors of postradiosurgery hemorrhage in the univariate analysis only. Clinical deterioration occurred in 30 patients (6.8%), more commonly in patients with postradiosurgery hemorrhage (p = 0.018). Radiosurgery afforded a reasonable chance of obliteration of unruptured AVMs with relatively low rates of clinical and radiological complications.

Postradiosurgery Hemorrhage Rates of Arteriovenous Malformations of the Brain

The long-term benefit of radiosurgery of brain arteriovenous malformations (AVM), especially nonhemorrhagic cases, is controversial. We calculated hemorrhage rates pre- and posttreatment and analyzed the risk factors for bleeding based on cases followed at our site. One hundred eight patients, age 36 ± 17 years, 56 men. The mean follow-up was 65 ± 44 months (median, 54; interquartile range, 33-94). Most AVMs were small (74.1% <3 cm in diameter); 48.1% were located in an eloquent area, 27.8% had deep drainage, and 39.8% presented with hemorrhage. The annual hemorrhage rate for any undiagnosed AVM was 1.2%, and 3.3% for AVMs with hemorrhagic presentation. Older patients, cortical or subcortical AVMs, and cases with multiple draining veins were less likely to present with bleeding. During the first 36 months postradiosurgery, hemorrhagic AVMs had a rebleeding rate of 2.1%, and a rate of 1.1% from 3 years onwards. Nonhemorrhagic AVMs had a hemorrhage rate of 1.4% during the first 3 years and 0.3% afterward. Arterial hypertension and nidus volume were independent predictors of bleeding after treatment. Mean nidus obliteration time was 37 ± 18 months (median, 32; interquartile range, 25-40), with hemorrhage rate of 1.3% before and 0.6% after obliteration, and 1.9% for AVMs that were not closed at the end of follow-up. Both hemorrhagic and nonhemorrhagic AVMs benefit from radiosurgical therapy, with gradual decrease in their bleeding rates over the years. Albeit small, the risk of hemorrhage persists during the entirety of follow-up, being higher for cases with hemorrhagic presentation and nonobliterated AVM.