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.

Predictive Factors of Radiation-Induced Changes Following Single-Session Gamma Knife Radiosurgery for Arteriovenous Malformations.

We evaluated for possible predictors of radiation-induced changes (RICs) after gamma knife radiosurgery (GKRS) for arteriovenous malformations (AVMs). We identified the nidal component within AVMs to analyze the correlation between the volume of brain parenchyma within the 50% isodose line (IDL) and RICs. We retrospectively reviewed patients with AVMs who underwent a single-session of GKRS at our institution between 2007 and 2017 with at least a 2-year minimum follow-up. Follow-up magnetic resonance images were evaluated for newly developed T2 signal changes and the proportions of nidus and intervening parenchyma were quantified. A total of 180 AVM patients (98 males and 82 females) with a median age of 34 years were included in the present study. The overall obliteration rate was 67.8%. The median target volume was 3.65 cc. The median nidus and parenchyma volumes within the 50% IDL were 1.54 cc and 2.41 cc, respectively. RICs were identified in 79 of the 180 patients (43.9%). AVMs associated with previous hemorrhages showed a significant inverse correlation with RICs. In a multivariate analysis, RICs were associated with a higher proportion of brain parenchyma within the 50% IDL (hazard ratio (HR) 169.033; p < 0.001) and inversely correlated with the proportion of nidus volume within the 50% IDL (HR 0.006; p < 0.001). Our study identified that a greater proportion of brain tissue between the nidus within the 50% IDL was significantly correlated with RICs. Nidus angioarchitectural complexity and the absence of a prior hemorrhage were also associated with RICs. The identification of possible predictors of RICs could facilitate radiosurgical planning and treatment decisions as well as the planning of appropriate follow-up after GKRS; this could minimize the risk of RICs, which would be particularly beneficial for the treatment of incidentally found asymptomatic AVMs.

A comparative outcomes analysis of patients treated for arteriovenous malformation with LINAC-based stereotactic radiosurgery by a standard frame-based technique or a frameless technique utilizing 3-dimensional rotational angiography.

Previous work at our institution treating arteriovenous malformation (AVM) with radiosurgery (RS) demonstrated superior nidus visualization and geometric accuracy with use of 3-dimensional rotational angiography (3DRA) compared to biplanar digital subtraction angiography. We have since adopted a unique radiosurgical protocol that utilizes 3DRA in the planning of linear accelerator (LINAC)-based RS delivered in a frameless manner. This study seeks to compare clinical outcomes between patients treated by this novel approach and those treated by our historic frame-based protocol. Clinical data were queried for all patients treated for AVM by single-fraction RS from 2003 to 2017. RICs were identified and classified as radiologic, symptomatic, or permanent. Excellent outcome was defined as nidus obliteration without intracranial hemorrhage (ICH) or symptomatic RIC. Clinical predictors of study outcomes were identified through univariate and multivariate logistic regression using backwards elimination to optimize a predictive model. 131 AVMs in 124 patients were included with a median follow-up of 88 months. 59 AVMs received frame-based RS and 72 AVMs received frameless RS. Rate of obliteration was 64% for frame-based RS and 61% for frameless RS (p = 0.70). Radiologic, symptomatic, and permanent RICs rates were 68%, 17%, and 8%, respectively, for frame-based cases, versus 40% (p < 0.01), 8% (p = 0.13), and 3% (p = 0.15), respectively, for frameless cases. Excellent outcome was achieved in 49% of frame-based cases and 53% of frameless cases (p = 0.68). These results illustrate the safety and effectiveness of frameless LINAC-based AVM RS utilizing 3DRA.

Stereotactic radiosurgery for pediatric brain arteriovenous malformations: long-term outcomes.

OBJECTIVE: Contrary to the better described obliteration- and hemorrhage-related data after stereotactic radiosurgery (SRS) of brain arteriovenous malformations (AVMs) in pediatric patients, estimates of the rarer complications, including cyst and tumor formation, are limited in the literature. The aim of the present study was to assess the long-term outcomes and risks of SRS for AVMs in pediatric patients (age < 18 years). METHODS: The authors retrospectively analyzed the International Radiosurgery Research Foundation pediatric AVM database for the years 1987 to 2018. AVM obliteration, post-SRS hemorrhage, cyst formation, and tumor formation were assessed. Cumulative probabilities, adjusted for the competing risk of death, were calculated. RESULTS: The study cohort comprised 539 pediatric AVM patients (mean follow-up 85.8 months). AVM obliteration was observed in 64.3% of patients, with cumulative probabilities of 63.6% (95% CI 58.8%-68.0%), 77.1% (95% CI 72.1%-81.3%), and 88.1% (95% CI 82.5%-92.0%) over 5, 10, and 15 years, respectively. Post-SRS hemorrhage was observed in 8.4% of patients, with cumulative probabilities of 4.9% (95% CI 3.1%-7.2%), 9.7% (95% CI 6.4%-13.7%), and 14.5% (95% CI 9.5%-20.5%) over 5, 10, and 15 years, respectively. Cyst formation was observed in 2.1% of patients, with cumulative probabilities of 5.5% (95% CI 2.3%-10.7%) and 6.9% (95% CI 3.1%-12.9%) over 10 and 15 years, respectively. Meningiomas were observed in 2 patients (0.4%) at 10 and 12 years after SRS, with a cumulative probability of 3.1% (95% CI 0.6%-9.7%) over 15 years. CONCLUSIONS: AVM obliteration can be expected after SRS in the majority of the pediatric population, with a relatively low risk of hemorrhage during the latency period. Cyst and benign tumor formation after SRS can be observed in 7% and 3% of patients over 15 years, respectively. Longitudinal surveillance for delayed neoplasia is prudent despite its low incidence.

Stereotactic radiosurgery for arteriovenous malformations of the basal ganglia and thalamus: an international multicenter study.

OBJECTIVE: Arteriovenous malformations (AVMs) of the basal ganglia (BG) and thalamus are associated with elevated risks of both hemorrhage if left untreated and neurological morbidity after resection. Therefore, stereotactic radiosurgery (SRS) has become a mainstay in the management of these lesions, although its safety and efficacy remain incompletely understood. The aim of this retrospective multicenter cohort study was to evaluate the outcomes of SRS for BG and thalamic AVMs and determine predictors of successful endpoints and adverse radiation effects. METHODS: The authors retrospectively reviewed data on patients with BG or thalamic AVMs who had undergone SRS at eight institutions participating in the International Gamma Knife Research Foundation (IGKRF) from 1987 to 2014. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes (RICs). Multivariable models were developed to identify independent predictors of outcome. RESULTS: The study cohort comprised 363 patients with BG or thalamic AVMs. The mean AVM volume and SRS margin dose were 3.8 cm3 and 20.7 Gy, respectively. The mean follow-up duration was 86.5 months. Favorable outcome was achieved in 58.5% of patients, including obliteration in 64.8%, with rates of post-SRS hemorrhage and permanent RIC in 11.3% and 5.6% of patients, respectively. Independent predictors of favorable outcome were no prior AVM embolization (p = 0.011), a higher margin dose (p = 0.008), and fewer isocenters (p = 0.044). CONCLUSIONS: SRS is the preferred intervention for the majority of BG and thalamic AVMs. Patients with morphologically compact AVMs that have not been previously embolized are more likely to have a favorable outcome, which may be related to the use of a higher margin dose.

Effect of treatment period on outcomes after stereotactic radiosurgery for brain arteriovenous malformations: an international multicenter study.

OBJECTIVEThe role of and technique for stereotactic radiosurgery (SRS) in the management of arteriovenous malformations (AVMs) have evolved over the past four decades. The aim of this multicenter, retrospective cohort study was to compare the SRS outcomes of AVMs treated during different time periods.METHODSThe authors selected patients with AVMs who underwent single-session SRS at 8 different centers from 1988 to 2014 with follow-up ≥ 6 months. The SRS eras were categorized as early (1988-2000) or modern (2001-2014). Statistical analyses were performed to compare the baseline characteristics and outcomes of the early versus modern SRS eras. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes (RICs).RESULTSThe study cohort comprised 2248 patients with AVMs, including 1584 in the early and 664 in the modern SRS eras. AVMs in the early SRS era were significantly smaller (p < 0.001 for maximum diameter and volume), and they were treated with a significantly higher radiosurgical margin dose (p < 0.001). The obliteration rate was significantly higher in the early SRS era (65% vs 51%, p < 0.001), and earlier SRS treatment period was an independent predictor of obliteration in the multivariate analysis (p < 0.001). The rates of post-SRS hemorrhage and radiological, symptomatic, and permanent RICs were not significantly different between the two groups. Favorable outcome was achieved in a significantly higher proportion of patients in the early SRS era (61% vs 45%, p < 0.001), but the earlier SRS era was not statistically significant in the multivariate analysis (p = 0.470) with favorable outcome.CONCLUSIONSDespite considerable advances in SRS technology, refinement of AVM selection, and contemporary multimodality AVM treatment, the study failed to observe substantial improvements in SRS favorable outcomes or obliteration for patients with AVMs over time. Differences in baseline AVM characteristics and SRS treatment parameters may partially account for the significantly lower obliteration rates in the modern SRS era. However, improvements in patient selection and dose planning are necessary to optimize the utility of SRS in the contemporary management of AVMs.

Volume-staged versus dose-staged stereotactic radiosurgery outcomes for large brain arteriovenous malformations: a systematic review.

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 cm3) 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.

Cyst formation after stereotactic radiosurgery for brain arteriovenous malformations: a systematic review.

OBJECTIVE Cyst formation can occasionally occur after stereotactic radiosurgery (SRS) for brain arteriovenous malformations (AVMs). Given the limited data regarding post-SRS cyst formation in patients with AVM, the time course, natural history, and management of this delayed complication are poorly defined. The aim of this systematic review was to determine the incidence, time course, and optimal management of cyst formation after SRS for AVMs. METHODS A literature review was performed using PubMed to identify studies reporting cyst formation in AVM patients treated with SRS. Baseline and outcomes data, including the incidence and management of post-SRS cysts, were extracted from each study that reported follow-up duration. The mean time to cyst formation was calculated from the subset of studies that reported individual patient data. RESULTS Based on pooled data from 22 studies comprising the incidence analysis, the overall rate of post-SRS cyst formation was 3.0% (78/2619 patients). Among the 26 post-SRS cyst patients with available AVM obliteration data, nidal obliteration was achieved in 20 (76.9%). Of the 64 cyst patients with available symptomatology and management data, 21 (32.8%) were symptomatic; 21 cysts (32.8%) were treated with surgical intervention, whereas the remaining 43 (67.2%) were managed conservatively. Based on a subset of 19 studies reporting individual time-to-cyst-formation data from 63 patients, the mean latency period to post-SRS cyst formation was 78 months (6.5 years). CONCLUSIONS Cyst formation is an uncommon complication after SRS for AVMs, with a relatively long latency period. The majority of post-SRS cysts are asymptomatic and can be managed conservatively, although enlarging or symptomatic cysts may require surgical intervention. Long-term follow-up of AVM patients is crucial to the appropriate diagnosis and management of post-SRS cysts.

Early versus late arteriovenous malformation responders after stereotactic radiosurgery: an international multicenter study.

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.

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.

Gamma Knife surgical treatment for partially embolized cerebral arteriovenous malformations.

OBJECTIVE: A combination of embolization and radiosurgery is used as a common strategy for the treatment of large and complex cerebral arteriovenous malformations (AVMs). This study presents the experiences of partially embolized cerebral AVMs followed by Gamma Knife surgery (GKS) and assesses predictive factors for AVM obliteration and hemorrhage. METHODS: The interventional neuroradiology database that was reviewed included 404 patients who underwent AVM embolization. Using this database, the authors retrospectively analyzed all partially embolized AVM cases followed by GKS for a residual nidus. Except for cases of complete AVM obliteration, the authors excluded all patients with radiological follow-up of less than 2 years. Logistic regression analysis was used to analyze the predictive factors related to AVM obliteration and hemorrhage following GKS. Kaplan-Meier analysis was used to evaluate the obliteration with a cutoff AVM nidus volume of 3 cm(3) and 10 cm(3). RESULTS: One hundred sixty-two patients qualified for the study. The median patient age was 26 years and 48.8% were female. Hemorrhage presented as the most common symptom (48.1%). The median preembolization volume of an AVM was 14.3 cm(3). The median volume and margin dose for GKS were 10.92 cm(3) and 16.0 Gy, respectively. The median radiological and clinical follow-up intervals were 47 and 79 months, respectively. The annual hemorrhage rate was 1.71% and total obliteration rate was 56.8%. Noneloquent area (p = 0.004), superficial location (p < 0.001), decreased volume (p < 0.001), lower Spetzler-Martin grade (p < 0.001), lower Virginia Radiosurgery AVM Scale (RAS; p < 0.001), lower Pollock-Flickinger score (p < 0.001), lower modified Pollock-Flickinger score (p < 0.001), increased maximum dose (p < 0.001), and increased margin dose (p < 0.001) were found to be statistically significant in predicting the probability of AVM obliteration in the univariate analysis. In the multivariate analysis, only volume (p = 0.016) was found to be an independent prognostic factor for AVM obliteration. The log-rank (Mantel-Cox) test of the Kaplan-Meier analysis (chi-square = 54.402, p < 0.001) showed a significantly decreased obliteration rate of different cutoff AVM volume groups of less than 3 cm(3), 3-10 cm(3), and more than 10 cm(3). No independent prognostic factor was found for AVM hemorrhage in multivariate analysis. CONCLUSIONS: Partially embolized AVMs are amenable to successful treatment with GKS. The volume of the nidus significantly influences the outcome of radiosurgical treatment. The Virginia RAS and Pollock-Flickinger score were found to be reliable scoring systems for selection of patient candidates and prediction of partially embolized AVM closure and complications for GKS.

Radiosurgery for temporal lobe arteriovenous malformations: effect of temporal location on seizure outcomes.

OBJECT: The temporal lobe is particularly susceptible to epileptogenesis. However, the routine use of anticonvulsant therapy is not implemented in temporal lobe AVM patients without seizures at presentation. The goals of this case-control study were to determine the radiosurgical outcomes for temporal lobe AVMs and to define the effect of temporal lobe location on postradiosurgery AVM seizure outcomes. METHODS: From a database of approximately 1400 patients, the authors generated a case cohort from patients with temporal lobe AVMs with at least 2 years follow-up or obliteration. A control cohort with similar baseline AVM characteristics was generated, blinded to outcome, from patients with non-temporal, cortical AVMs. They evaluated the rates and predictors of seizure freedom or decreased seizure frequency in patients with seizures or de novo seizures in those without seizures. RESULTS: A total of 175 temporal lobe AVMs were identified based on the inclusion criteria. Seizure was the presenting symptom in 38% of patients. The median AVM volume was 3.3 cm3, and the Spetzler-Martin grade was III or higher in 39% of cases. The median radiosurgical prescription dose was 22 Gy. At a median clinical follow-up of 73 months, the rates of seizure control and de novo seizures were 62% and 2%, respectively. Prior embolization (p = 0.023) and lower radiosurgical dose (p = 0.027) were significant predictors of seizure control. Neither temporal lobe location (p = 0.187) nor obliteration (p = 0.522) affected seizure outcomes. The cumulative obliteration rate was 63%, which was significantly higher in patients without seizures at presentation (p = 0.046). The rates of symptomatic and permanent radiation-induced changes were 3% and 1%, respectively. The annual risk of postradiosurgery hemorrhage was 1.3%. CONCLUSIONS: Radiosurgery is an effective treatment for temporal lobe AVMs. Furthermore, radiosurgery is protective against seizure progression in patients with temporal lobe AVM-associated seizures. Temporal lobe location does not affect radiosurgery-induced seizure control. The low risk of new-onset seizures in patients with temporal or extratemporal AVMs does not seem to warrant prophylactic use of anticonvulsants.

Seizure and anticonvulsant outcomes following stereotactic radiosurgery for intracranial arteriovenous malformations.

OBJECT: Epilepsy associated with arteriovenous malformations (AVMs) has an unclear course after stereotactic radiosurgery (SRS). Neither the risks of persistent seizures nor the requirement for postoperative antiepileptic drugs (AEDs) are well defined. METHODS: The authors performed a retrospective review of all patients with AVMs who underwent SRS at the University of Virginia Health System from 1989 to 2012. Seizure status was categorized according to a modified Engel classification. The effects of demographic, AVM-related, and SRS treatment factors on seizure outcomes were evaluated with logistic regression analysis. Changes in AED status were evaluated using McNemar's test. RESULTS: Of the AVM patients with pre- or post-SRS seizures, 73 with pre-SRS epilepsy had evaluable data for subsequent analysis. The median patient age was 37 years (range 5-69 years), and the median follow-up period was 65.6 months (range 12-221 months). Sixty-five patients (89%) achieved seizure remission (Engel Class IA or IB outcome). Patients presenting with simple partial or secondarily generalized seizures were more likely to achieve Engel Class I outcome (p = 0.045). Twenty-one (33%) of 63 patients tapered off of pre-SRS AEDs. The incidence of freedom from AED therapy increased significantly after SRS (p < 0.001, McNemar's test). Of the Engel Class IA patients who continued AED therapy, 54% had patent AVM nidi, whereas only 19% continued AED therapy with complete AVM obliteration (p = 0.05). CONCLUSIONS: Stereotactic radiosurgery is an effective treatment for long-term AVM-related epilepsy. Seizure-free patients on continued AED therapy were more likely to have residual AVM nidi. Simple partial or secondarily generalized seizure type were associated with better seizure outcomes following SRS.

Volume-staged versus dose-staged radiosurgery outcomes for large intracranial arteriovenous malformations.

OBJECT: The aim in this paper was to compare the outcomes of dose-staged and volume-staged stereotactic radio-surgery (SRS) in the treatment of large (> 10 cm(3)) arteriovenous malformations (AVMs). METHODS: A systematic literature review was performed using PubMed. Studies written in the English language with at least 5 patients harboring large (> 10 cm(3)) AVMs treated with dose- or volume-staged SRS that reported post-treatment outcomes data were selected for review. Demographic information, radiosurgical treatment parameters, and post-SRS outcomes and complications were analyzed for each of these studies. RESULTS: The mean complete obliteration rates for the dose- and volume-staged groups were 22.8% and 47.5%, respectively. Complete obliteration was demonstrated in 30 of 161 (18.6%) and 59 of 120 (49.2%) patients in the dose- and volume-staged groups, respectively. The mean rates of symptomatic radiation-induced changes were 13.5% and 13.6% in dose- and volume-staged groups, respectively. The mean rates of cumulative post-SRS latency period hemorrhage were 12.3% and 17.8% in the dose- and volume-staged groups, respectively. The mean rates of post-SRS mortality were 3.2% and 4.6% in dose- and volume-staged groups, respectively. CONCLUSIONS: Volume-staged SRS affords higher obliteration rates and similar complication rates compared with dose-staged SRS. Thus, volume-staged SRS may be a superior approach for large AVMs that are not amenable to single-session SRS. Staged radiosurgery should be considered as an efficacious component of multimodality AVM management.

Radiosurgery for ruptured intracranial arteriovenous malformations.

OBJECT: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

OBJECT: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.