Risk of Brain Arteriovenous Malformation Hemorrhage Before and After Stereotactic Radiosurgery.

Background and Purpose- Understanding the hemorrhage risks associated with brain arteriovenous malformations (AVMs) before and after stereotactic radiosurgery (SRS) is important. The aims of this multicenter, retrospective cohort study are to evaluate and compare the rates of pre- and post-SRS AVM hemorrhage and identify risk factors. Methods- We pooled AVM SRS data from 8 institutions participating in the International Radiosurgery Research Foundation. Predictors of post-SRS hemorrhage were determined using a multivariate logistic regression model. Pre- and post-SRS hemorrhage rates were compared using Fisher exact test. Ruptured and unruptured AVMs were matched in a 1:1 ratio using propensity scores, and their outcomes were compared. Results- The study cohort comprised 2320 AVM patients who underwent SRS. Deep AVM location (odds ratio, 1.86; 95% CI, 1.19-2.92; P=0.007), the presence of an AVM-associated arterial aneurysm (odds ratio, 2.44; 95% CI, 1.63-3.66; P<0.001), and lower SRS margin dose (odds ratio, 0.93; 95% CI, 0.88-0.98; P=0.005) were independent predictors of post-SRS hemorrhage. The post-SRS hemorrhage rate was lower for obliterated versus patent AVMs (6.0 versus 22.3 hemorrhages/1000 person-years; P<0.001). The AVM hemorrhage rate decreased from 15.4 hemorrhages/1000 person-years before SRS to 11.9 after SRS ( P=0.001). The outcomes of the matched ruptured versus unruptured AVM cohorts were similar. Conclusions- SRS appears to reduce the risk of AVM hemorrhage, although this effect is predominantly driven by obliteration. Deep-seated AVMs are more likely to rupture during the latency period after SRS. AVM-associated aneurysms should be considered for selective occlusion before SRS of the nidus to ameliorate the post-SRS hemorrhage rate of these lesions.

Stereotactic Radiosurgery for Pediatric Versus Adult Brain Arteriovenous Malformations.

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.

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

BACKGROUND AND PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adverse radiation effects in volume-staged radiosurgery for large arteriovenous malformations: a multiinstitutional study.

OBJECTIVE: The optimal treatment paradigm for large arteriovenous malformations (AVMs) is controversial. One approach is volume-staged stereotactic radiosurgery (VS-SRS). The authors previously reported efficacy of VS-SRS for large AVMs in a multiinstitutional cohort; here they focus on risk of symptomatic adverse radiation effects (AREs). METHODS: This is a multicentered retrospective review of patients treated with a planned prospective volume staging approach to stereotactically treat the entire nidus of an AVM, with volume stages separated by intervals of 3-6 months. A total of 9 radiosurgical centers treated 257 patients with VS-SRS between 1991 and 2016. The authors evaluated permanent, transient, and total ARE events that were symptomatic. RESULTS: Patients received 2-4 total volume stages. The median age was 33 years at the time of the first SRS volume stage, and the median follow-up was 5.7 years after VS-SRS. The median total AVM nidus volume was 23.25 cm3 (range 7.7-94.4 cm3), with a median margin dose per stage of 17 Gy (range 12-20 Gy). A total of 64 patients (25%) experienced an ARE, of which 19 were permanent. Rather than volume, maximal linear dimension in the Z (craniocaudal) dimension was associated with toxicity; a threshold length of 3.28 cm was associated with an ARE, with a 72.5% sensitivity and a 58.3% specificity. In addition, parietal lobe involvement for superficial lesions and temporal lobe involvement for deep lesions were associated with an ARE. CONCLUSIONS: Size remains the dominant predictor of toxicity following SRS, but overall rates of AREs were lower than anticipated based on baseline features, suggesting that dose and size were relatively dissociated through volume staging. Further techniques need to be assessed to optimize outcomes.

Extracranial carotid artery stenting: the Puerto Rico medical center endovascular neurosurgery service experience.

OBJECTIVE: Extracranial carotid artery stenting (CAS) represents a viable alternative for high-risk surgical patients. The aim of this study was to determine the clinical features and outcome of 25 patients that underwent CAS at the Puerto Rico Medical Center. METHODS: A retrospective review of a series of 25 high-risk surgical patients that underwent CAS from June 2005 to January 2010 was performed. Patients were followed-up at clinics with computed tomography angiography and/or digital subtraction angiography. RESULTS: Patient ages ranged from 52 to 88 years. Twenty-one of the patients had severe cervical carotid stenosis (more than 80%). Those with moderate stenosis (from 50% to 80%) were treated when they were symptomatic or when stenosis recurred after carotid endarterectomy. Among the 25 patients, only 2 presented with restenosis (more than 50% luminal diameter). Both had a history of radiation-induced disease, but neither required retreatment. Five patients required post-stenting angioplasty due to a less than 50% improvement in luminal diameter. There was 1 death, and 1 patient presented delayed neurocognitive deterioration. The combined long-term morbidity and mortality in the subgroup with at least two years of follow-up was 8.3%. There were no intracerebral hemorrhages or recurrent strokes/transient ischemic attacks. CONCLUSION: The restriction of post-stenting angioplasty to only those cases without significant revascularization appears to help reduce restenosis rates while ensuring a gradual increase in intracranial blood flow. The latter may not apply to patients with a prior history of radiotherapy.

Embolization of Brain Arteriovenous Malformations With Versus Without Onyx Before Stereotactic Radiosurgery.

BACKGROUND: Embolization of brain arteriovenous malformations (AVMs) using ethylene-vinyl alcohol copolymer (Onyx) embolization may influence the treatment effects of stereotactic radiosurgery (SRS) differently than other embolysates. OBJECTIVE: To compare the outcomes of pre-SRS AVM embolization with vs without Onyx through a multicenter, retrospective matched cohort study. METHODS: We retrospectively reviewed International Radiosurgery Research Foundation AVM databases from 1987 to 2018. Embolized AVMs treated with SRS were selected and categorized based on embolysate usage into Onyx embolization (OE + SRS) or non-Onyx embolization (NOE + SRS) cohorts. The 2 cohorts were matched in a 1:1 ratio using de novo AVM features for comparative analysis of outcomes. RESULTS: The matched cohorts each comprised 45 patients. Crude AVM obliteration rates were similar between the matched OE + SRS vs NOE + SRS cohorts (47% vs 51%; odds ratio [OR] = 0.837, P = .673). Cumulative probabilities of obliteration were also similar between the OE + SRS vs NOE + SRS cohorts (subhazard ratio = 0.992, P = .980). Rates of post-SRS hemorrhage, all-cause mortality, radiation-induced changes, cyst formation, and embolization-associated complications were similar between the matched cohorts. Sensitivity analysis for AVMs in the OE + SRS cohort embolized with Onyx alone revealed a higher rate of asymptomatic embolization-associated complications in this subgroup compared to the NOE + SRS cohort (36% vs 15%; OR = 3.297, P = .034), but the symptomatic complication rates were similar. CONCLUSION: Nidal embolization using Onyx does not appear to differentially impact the outcomes of AVM SRS compared with non-Onyx embolysates. The embolic agent selected for pre-SRS AVM embolization should reflect both the experience of the neurointerventionalist and target of endovascular intervention.

Stereotactic Radiosurgery With Versus Without Embolization for Brain Arteriovenous Malformations.

BACKGROUND: Prior comparisons of brain arteriovenous malformations (AVMs) treated using stereotactic radiosurgery (SRS) with or without embolization were inherently flawed, due to differences in the pretreatment nidus volumes. OBJECTIVE: To compare the outcomes of embolization and SRS, vs SRS alone for AVMs using pre-embolization malformation features. METHODS: We retrospectively reviewed International Radiosurgery Research Foundation AVM databases from 1987 to 2018. Patients were categorized into the embolization and SRS (E + SRS) or SRS alone (SRS-only) cohorts. The 2 cohorts were matched in a 1:1 ratio using propensity scores. Primary outcome was defined as AVM obliteration. Secondary outcomes were post-SRS hemorrhage, all-cause mortality, radiologic and symptomatic radiation-induced changes (RIC), and cyst formation. RESULTS: The matched cohorts each comprised 101 patients. Crude AVM obliteration rates were similar between the matched E + SRS vs SRS-only cohorts (48.5% vs 54.5%; odds ratio = 0.788, P = .399). Cumulative probabilities of obliteration at 3, 4, 5, and 6 yr were also similar between the E + SRS (33.0%, 46.4%, 56.2%, and 60.8%, respectively) and SRS-only (32.9%, 46.2%, 56.0%, and 60.6%, respectively) cohorts (subhazard ratio (SHR) = 1.005, P = .981). Cumulative probabilities of radiologic RIC at 3, 4, 5, and 6 yr were lower in the E + SRS (25.0%, 25.7%, 26.7%, and 26.7%, respectively) vs SRS-only (45.3%, 46.2%, 47.8%, and 47.8%, respectively) cohort (SHR = 0.478, P = .004). Symptomatic and asymptomatic embolization-related complication rates were 8.3% and 18.6%, respectively. Rates of post-SRS hemorrhage, all-cause mortality, symptomatic RIC, and cyst formation were similar between the matched cohorts. CONCLUSION: This study refutes the prevalent notion that AVM embolization negatively affects the likelihood of obliteration after SRS.

A proposal for a new arteriovenous malformation grading scale for neuroendovascular procedures and literature review.

BACKGROUND: Traditionally, decisions regarding treatment and outcomes for patients with cerebral arteriovenous malformations (AVM) have made use of the Spetzler-Martin grading scale. The latter has withstood the test of time in clinical practice for AVM patients managed surgically and even when comparing studies involving other modalities of treatment. Recent awareness on the applicability of the grading system for risk assessment and outcome determination in cases of treatment by neuroendovascular means has emerged. We propose a preliminary grading system for neuroendovascular procedures based on a revision of the available literature. METHODS: A literature search using the keywords 'arteriovenous malformation', 'embolization' and 'outcome' was done. Articles studying the factors involved in complications and outcome determination for endovascular cerebral AVM patients were reviewed. These were tabulated and those dealing with anatomical, radiological and hemodynamic descriptions that were noted as significant determinants of risk or clinical outcome were used for development of a preliminary grading system to be used in a follow-up validation study. RESULTS: A grading system similar to the Spetzler-Martin grading scale was developed using factors deemed in the literature as significant determinants of outcome. The classification includes the number of feeding vessels into the AVM, the eloquence of adjacent areas, and the presence of fistulous components. Follow-up study is underway at our institution to validate our proposal. Yet, significant evidence exists in the literature validating those factors as stand alone determinants of outcome and risk, suggesting that this grading scale may well be applicable to endovascular embolization procedures. CONCLUSIONS: A grading scale similar to the Spetzler-Martin grading system for use in risk assessment and outcome determination in brain AVM patients treated by endovascular techniques seems adequate and clinically feasible. Studies on applicability and validation are underway.

Stereotactic Radiosurgery for Cavernous Sinus Versus Noncavernous Sinus Dural Arteriovenous Fistulas: Outcomes and Outcome Predictors.

BACKGROUND: Dural arteriovenous fistulas (DAVFs) can be categorized based on location. OBJECTIVE: To compare stereotactic radiosurgery (SRS) outcomes between cavernous sinus (CS) and non-CS DAVFs and to identify respective outcome predictors. METHODS: This is a retrospective study of DAVFs treated with SRS between 1988 and 2016 at 10 institutions. Patients' variables, DAVF characters, and SRS parameters were included for analyses. Favorable clinical outcome was defined as angiography-confirmed obliteration without radiological radiation-induced changes (RIC) or post-SRS hemorrhage. Other outcomes were DAVFs obliteration and adverse events (including RIC, symptomatic RIC, and post-SRS hemorrhage). RESULTS: The overall study cohort comprised 131 patients, including 20 patients with CS DAVFs (15%) and 111 patients with non-CS DAVFs (85%). Rates of favorable clinical outcome were comparable between the 2 groups (45% vs 37%, P = .824). Obliteration rate after SRS was higher in the CS DAVFs group, even adjusted for baseline difference (OR = 4.189, P = .044). Predictors of favorable clinical outcome included higher maximum dose (P = .014) for CS DAVFs. Symptomatic improvement was associated with obliteration in non-CS DAVFs (P = .005), but symptoms improved regardless of whether obliteration was confirmed in CS DAVFs. Non-CS DAVFs patients with adverse events after SRS were more likely to be male (P = .020), multiple arterial feeding fistulas (P = .018), and lower maximum dose (P = .041). CONCLUSION: After SRS, CS DAVFs are more likely to obliterate than non-CS ones. Because these 2 groups have different total predictors for clinical and radiologic outcomes after SRS, they should be considered as different entities.

Dose response and architecture in volume staged radiosurgery for large arteriovenous malformations: A multi-institutional study.

BACKGROUND: Optimal treatment paradigm for large arteriovenous malformations (AVMs) is controversial. Volume-staged stereotactic radiosurgery (VS-SRS) provides an effective option for these high-risk lesions, but optimizing treatment for these recalcitrant and rare lesions has proven difficult. METHODS: This is a multi-centered retrospective review of patients treated with a planned prospective volume staging approach to stereotactically treat the entire nidus of an AVM with volume stages separated by intervals of 3-6 months. A total of 9 radiosurgical centers treated 257 patients with VS-SRS between 1991 and 2016. We evaluated near complete response (nCR), obliteration, cure, and overall survival. RESULTS: With a median age of 33 years old at the time of first SRS volume stage, patients received 2-4 total volume stages and a median follow up of 5.7 years after VS-SRS. The median total AVM nidus volume was 23.25 cc (range: 7.7-94.4 cc) with a median margin dose per stage of 17 Gy (range: 12-20 Gy). Total AVM volume, margin dose per stage, compact nidus, lack of prior embolization, and lack of thalamic location involvement were all associated with improved outcomes. Dose >/= 17.5 Gy was strongly associated with improved rates of nCR, obliteration, and cure. With dose >/= 17.5 Gy, 5- and 10-year cure rates were 33.7% and 76.8% in evaluable patients compared to 23.7% and 34.7% of patients with 17 Gy and 6.4% and 20.6% with <17 Gy per volume-stage (p = 0.004). Obliteration rates in diffuse nidus architecture with <17 Gy were particularly poor with none achieving obliteration compared to 32.3% with doses >/= 17 Gy at 5 years (p = 0.007). Comparatively, lesions with a compact nidus architecture exhibited obliteration rates at 5 years were 10.7% vs 9.3% vs 26.6% for dose >17 Gy vs 17 Gy vs >/=17.5 Gy. CONCLUSION: VS-SRS is an option for upfront treatment of large AVMs. Higher dose was associated with improved rates of nCR, obliteration, and cure suggesting that larger volumetric responses may facilitate salvage therapy and optimize the chance for cure.

Stereotactic radiosurgery with versus without prior Onyx embolization for brain arteriovenous malformations.

OBJECTIVE: Investigations of the combined effects of neoadjuvant Onyx embolization and stereotactic radiosurgery (SRS) on brain arteriovenous malformations (AVMs) have not accounted for initial angioarchitectural features prior to neuroendovascular intervention. The aim of this retrospective, multicenter matched cohort study is to compare the outcomes of SRS with versus without upfront Onyx embolization for AVMs using de novo characteristics of the preembolized nidus. METHODS: The International Radiosurgery Research Foundation AVM databases from 1987 to 2018 were retrospectively reviewed. Patients were categorized based on AVM treatment approach into Onyx embolization (OE) and SRS (OE+SRS) or SRS alone (SRS-only) cohorts and then propensity score matched in a 1:1 ratio. The primary outcome was AVM obliteration. Secondary outcomes were post-SRS hemorrhage, all-cause mortality, radiological and symptomatic radiation-induced changes (RICs), and cyst formation. Comparisons were analyzed using crude rates and cumulative probabilities adjusted for competing risk of death. RESULTS: The matched OE+SRS and SRS-only cohorts each comprised 53 patients. Crude rates (37.7% vs 47.2% for the OE+SRS vs SRS-only cohorts, respectively; OR 0.679, p = 0.327) and cumulative probabilities at 3, 4, 5, and 6 years (33.7%, 44.1%, 57.5%, and 65.7% for the OE+SRS cohort vs 34.8%, 45.5%, 59.0%, and 67.1% for the SRS-only cohort, respectively; subhazard ratio 0.961, p = 0.896) of AVM obliteration were similar between the matched cohorts. The secondary outcomes of the matched cohorts were also similar. Asymptomatic and symptomatic embolization-related complication rates in the matched OE+SRS cohort were 18.9% and 9.4%, respectively. CONCLUSIONS: Pre-SRS AVM embolization with Onyx does not appear to negatively influence outcomes after SRS. These analyses, based on de novo nidal characteristics, thereby refute previous studies that found detrimental effects of Onyx embolization on SRS-induced AVM obliteration. However, given the risks incurred by nidal embolization using Onyx, this neoadjuvant intervention should be used judiciously in multimodal treatment strategies involving SRS for appropriately selected large-volume or angioarchitecturally high-risk AVMs.

Treatment of intracranial aneurysms with the Enterprise stent: a multicenter registry.

OBJECT: The development of self-expanding stents dedicated to intracranial use has significantly widened the applicability of endovascular therapy to many intracranial aneurysms that would otherwise have been untreatable by endovascular techniques. Recent Food and Drug Administration approval of the Enterprise Vascular Reconstruction Device and Delivery System (Cordis) has added a new option for self-expanding stent-assisted intracranial aneurysm coiling. METHODS: The authors established a collaborative registry across multiple institutions to rapidly provide largevolume results regarding initial experience in using the Enterprise in real-world practice. Ten institutions (University at Buffalo, Thomas Jefferson University, University of Florida, Cleveland Clinic, Northwestern University, West Virginia University, University of Puerto Rico, Albany Medical Center Hospital, the Neurological Institute of Savannah, and the Barrow Neurological Institute) have provided consecutive data regarding their initial experience with the Enterprise. RESULTS: In total, 141 patients (119 women) with 142 aneurysms underwent 143 attempted stent deployments. The use of Enterprise assistance with aneurysm coiling was associated with a 76% rate of > or = 90% occlusion. An inability to navigate or deploy the stent was experienced in 3% of cases, as well as a 2% occurrence of inaccurate deployment. Procedural data demonstrated a 6% temporary morbidity, 2.8% permanent morbidity, and 2% mortality (0.8% unruptured, 12% ruptured). CONCLUSIONS: The authors report initial results of the largest series to date in using the Enterprise for intracranial aneurysm treatment. The Enterprise is associated with a high rate of successful navigation and low occurrence of inaccurate stent deployment. The overall morbidity and mortality rates were low; however, caution should be exercised when considering Enterprise deployment in patients with subarachnoid hemorrhage as the authors' experience demonstrated a high rate of associated hemorrhagic complications leading to death.

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.

Seizure Presentation in Patients with Brain Arteriovenous Malformations Treated with Stereotactic Radiosurgery: A Multicenter Study.

BACKGROUND: Seizures are the second most common clinical presentation in patients with brain arteriovenous malformations (AVMs) and the most common presentation of unruptured AVMs. The aim of the present multicenter, retrospective cohort study was to identify the predictors of seizure presentation in patients with AVM who had undergone stereotactic radiosurgery (SRS). METHODS: We performed a retrospective review of patients with AVM who had been treated with SRS at 8 participating International Radiosurgery Research Foundation sites. The patient and AVM characteristics were compared between those with and without seizure presentation in univariable and multivariable models. A subgroup analysis of patients with cortical AVMs was performed. RESULTS: The study cohort included 2333 patients with AVM, including 419 (18%) with and 1914 (82%) without a seizure presentation. Previous AVM resection (odds ratio [OR], 7.65; P = 0.001), a lack of previous AVM hemorrhage (OR, 0.004; P < 0.001), a cortical AVM location (OR, 1559.42; P < 0.001), a lower Spetzler-Martin grade (OR, 0.51; P = 0.007), and a higher Virginia radiosurgery AVM score (OR, 1.46; P = 0.008) were independent predictors of seizure presentation. The rate of seizure presentation in patients with cortical AVMs was 27%. Previous AVM resection (OR, 8.36; P < 0.001), a lack of previous AVM hemorrhage (OR, 0.004; P < 0.001), and temporal AVM location (OR, 4.15; P < 0.001) were independent predictors of seizure presentation for cortical AVMs. CONCLUSION: We identified multiple factors associated with seizure presentation in patients with AVM to undergo SRS. Previous AVM resection, a cortical AVM location, and a lack of previous AVM hemorrhage were the strongest predictors of pre-SRS seizures. The Spetzler-Martin grade and Virginia radiosurgery AVM score might have a role in seizure risk stratification. For cortical AVMs, a temporal lobe location was predictive of seizure presentation.

Hemorrhage risk of cerebral dural arteriovenous fistulas following Gamma Knife radiosurgery in a multicenter international consortium.

OBJECTIVE: The authors performed a study to evaluate the hemorrhagic rates of cerebral dural arteriovenous fistulas (dAVFs) and the risk factors of hemorrhage following Gamma Knife radiosurgery (GKRS). METHODS: Data from a cohort of patients undergoing GKRS for cerebral dAVFs were compiled from the International Radiosurgery Research Foundation. The annual posttreatment hemorrhage rate was calculated as the number of hemorrhages divided by the patient-years at risk. Risk factors for dAVF hemorrhage prior to GKRS and during the latency period after radiosurgery were evaluated in a multivariate analysis. RESULTS: A total of 147 patients with dAVFs were treated with GKRS. Thirty-six patients (24.5%) presented with hemorrhage. dAVFs that had any cortical venous drainage (CVD) (OR = 3.8, p = 0.003) or convexity or torcula location (OR = 3.3, p = 0.017) were more likely to present with hemorrhage in multivariate analysis. Half of the patients had prior treatment (49.7%). Post-GRKS hemorrhage occurred in 4 patients, with an overall annual risk of 0.84% during the latency period. The annual risks of post-GKRS hemorrhage for Borden type 2-3 dAVFs and Borden type 2-3 hemorrhagic dAVFs were 1.45% and 0.93%, respectively. No hemorrhage occurred after radiological confirmation of obliteration. Independent predictors of hemorrhage following GKRS included nonhemorrhagic neural deficit presentation (HR = 21.6, p = 0.027) and increasing number of past endovascular treatments (HR = 1.81, p = 0.036). CONCLUSIONS: Patients have similar rates of hemorrhage before and after radiosurgery until obliteration is achieved. dAVFs that have any CVD or are located in the convexity or torcula were more likely to present with hemorrhage. Patients presenting with nonhemorrhagic neural deficits and a history of endovascular treatments had higher risks of post-GKRS hemorrhage.

Evaluation of stereotactic radiosurgery for cerebral dural arteriovenous fistulas in a multicenter international consortium.

OBJECTIVE: In this multicenter study, the authors reviewed the results obtained in patients who underwent Gamma Knife radiosurgery (GKRS) for dural arteriovenous fistulas (dAVFs) and determined predictors of outcome. METHODS: Data from a cohort of 114 patients who underwent GKRS for cerebral dAVFs were compiled from the International Gamma Knife Research Foundation. Favorable outcome was defined as dAVF obliteration and no posttreatment hemorrhage or permanent symptomatic radiation-induced complications. Patient and dAVF characteristics were assessed to determine predictors of outcome in a multivariate logistic regression analysis; dAVF-free obliteration was calculated in a competing-risk survival analysis; and Youden indices were used to determine optimal radiosurgical dose. RESULTS: A mean margin dose of 21.8 Gy was delivered. The mean follow-up duration was 4 years (range 0.5-18 years). The overall obliteration rate was 68.4%. The postradiosurgery actuarial rates of obliteration at 3, 5, 7, and 10 years were 41.3%, 61.1%, 70.1%, and 82.0%, respectively. Post-GRKS hemorrhage occurred in 4 patients (annual risk of 0.9%). Radiation-induced imaging changes occurred in 10.4% of patients; 5.2% were symptomatic, and 3.5% had permanent deficits. Favorable outcome was achieved in 63.2% of patients. Patients with middle fossa and tentorial dAVFs (OR 2.4, p = 0.048) and those receiving a margin dose greater than 23 Gy (OR 2.6, p = 0.030) were less likely to achieve a favorable outcome. Commonly used grading scales (e.g., Borden and Cognard) were not predictive of outcome. Female sex (OR 1.7, p = 0.03), absent venous ectasia (OR 3.4, p < 0.001), and cavernous carotid location (OR 2.1, p = 0.019) were predictors of GKRS-induced dAVF obliteration. CONCLUSIONS: GKRS for cerebral dAVFs achieved obliteration and avoided permanent complications in the majority of patients. Those with cavernous carotid location and no venous ectasia were more likely to have fistula obliteration following radiosurgery. Commonly used grading scales were not reliable predictors of outcome following radiosurgery.

Evaluation of pediatric patients with vascular malformations managed with endovascular and radiosurgical techniques using a modified Rankin Disability Scale.

BACKGROUND: Pre- and postoperative evaluation of the pediatric patient with a cerebrovascular malformation can be cumbersome. This may be due to several factors, including age and ability to verbalize. Functional evaluation scales have been devised, yet application to a retrospective study, where information can be limited, may not be possible. Simpler scales, serving the purpose of functional description and categorization would be beneficial in these cases. METHODS: Between December 1997 and December 2003, 24 patients between the ages of 4 months to 17 years old underwent endovascular treatment for cerebrovascular lesions at our institution. The majority of the arteriovenous malformation cases underwent further radiosurgical treatment. Mean follow-up period from the time of the last endovascular or radiosurgical intervention was 22 months. A pediatric modification of the Rankin Disability Scale was used for evaluation of pre-procedural and post-procedural functional status. RESULTS: Combined embolization/radiosurgical approach had 4% mortality and 4% morbidity rates. This combined technique achieved a 46% cure in a variety of pediatric vascular anomalies. Overall improvement in disability using the pediatric modification of the Rankin Scale was noted for all of the cases, and a tendency for improvement was noted in the arteriovenous malformation subgroup though not statistically significant, p = 0.0547. CONCLUSIONS: These results indicate that a pediatric modification of the Rankin Disability Scale can be used for functional evaluation in this population. Although other functional evaluation scales are available and validated, using a Rankin Disability Scale modification is straightforward, and it can provide functional categorization in retrospective studies.

Effect of Advanced Age on Stereotactic Radiosurgery Outcomes for Brain Arteriovenous Malformations: A Multicenter Matched Cohort Study.

BACKGROUND: The effect of age on adult brain arteriovenous malformation (AVM) outcomes after stereotactic radiosurgery (SRS) remains unclear. The aim of this study is to compare AVM outcomes between elderly (age ≥60 years) and nonelderly adult patients. METHODS: We retrospectively reviewed pooled data comprising patients who underwent SRS for AVMs between 1987 and 2014 at 8 centers participating in the International Gamma Knife Research Foundation. Adult (age ≥18 years) patients with ≥12 months follow-up were dichotomized into elderly and nonelderly cohorts, and matched in a 1:1 ratio. Favorable outcome was AVM obliteration without permanent symptomatic radiation-induced changes (RIC) or post-SRS hemorrhage. RESULTS: The study cohort consisted of 1845 patients (188 elderly vs. 1657 nonelderly) who met the inclusion criteria, and subsequent matching resulted in 181 patients in each cohort. In the matched cohorts, rates of obliteration (54.7% vs. 64.6%; P = 0.054) favorable outcome (51.4% vs. 61.3%; P = 0.056) were no different between the elderly and nonelderly cohorts. The rates of post-SRS hemorrhage (9.9% vs. 5.5%; P = 0.115), RIC (26.5% vs. 30.9%; P = 0.353), symptomatic RIC (9.4% vs. 9.4%; P = 1.000), and permanent symptomatic RIC (3.3% vs. 2.2%; P = 0.750) were also not significantly different between the elderly and nonelderly cohorts. Elderly patients with AVM did have a significantly higher rate of all-cause mortality (27.7% vs. 5.5%; P < 0.001). CONCLUSIONS: Advanced age does not seem to significantly affect obliteration or complication rates after SRS for AVMs. Although the decision to recommend intervention for AVMs in the elderly population is multifactorial, SRS may be a viable modality when treatment is deemed appropriate.

Stereotactic radiosurgery for Spetzler-Martin Grade IV and V arteriovenous malformations: an international multicenter study.

OBJECTIVE Due to the complexity of Spetzler-Martin (SM) Grade IV-V arteriovenous malformations (AVMs), the management of these lesions remains controversial. The aims of this multicenter, retrospective cohort study were to evaluate the outcomes after single-session stereotactic radiosurgery (SRS) for SM Grade IV-V AVMs and determine predictive factors. METHODS The authors retrospectively pooled data from 233 patients (mean age 33 years) with SM Grade IV (94.4%) or V AVMs (5.6%) treated with single-session SRS at 8 participating centers in the International Gamma Knife Research Foundation. Pre-SRS embolization was performed in 71 AVMs (30.5%). The mean nidus volume, SRS margin dose, and follow-up duration were 9.7 cm3, 17.3 Gy, and 84.5 months, respectively. Statistical analyses were performed to identify factors associated with post-SRS outcomes. RESULTS At a mean follow-up interval of 84.5 months, favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes (RIC) and was achieved in 26.2% of patients. The actuarial obliteration rates at 3, 7, 10, and 12 years were 15%, 34%, 37%, and 42%, respectively. The annual post-SRS hemorrhage rate was 3.0%. Symptomatic and permanent RIC occurred in 10.7% and 4% of the patients, respectively. Only larger AVM diameter (p = 0.04) was found to be an independent predictor of unfavorable outcome in the multivariate logistic regression analysis. The rate of favorable outcome was significantly lower for unruptured SM Grade IV-V AVMs compared with ruptured ones (p = 0.042). Prior embolization was a negative independent predictor of AVM obliteration (p = 0.024) and radiologically evident RIC (p = 0.05) in the respective multivariate analyses. CONCLUSIONS In this multi-institutional study, single-session SRS had limited efficacy in the management of SM Grade IV-V AVMs. Favorable outcome was only achieved in a minority of unruptured SM Grade IV-V AVMs, which supports less frequent utilization of SRS for the management of these lesions. A volume-staged SRS approach for large AVMs represents an alternative approach for high-grade AVMs, but it requires further investigation.

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.