Unruptured Brain Arteriovenous Malformations: A Systematic Review and Meta-Analysis of Mortality and Morbidity in Aruba-Eligible Studies.

BACKGROUND: Treating unruptured brain arteriovenous malformations (bAVMs) represent significant challenges, with numerous uncertainties still in debate. The ARUBA trial induced further investigation into optimal management strategies for these lesions. Here, we present a systematic-review and meta-analysis focusing on ARUBA-eligible studies, aiming to correlate patient data with outcomes and discuss key aspects of these studies. METHODS: Following PRISMA guidelines, we conducted a systematic-review. Variables analyzed included bAVM Spetzler-Martin (SM) grade, treatment modalities, and outcomes such as mortality and neurological deficits. We compared studies with a minimum of 50% cases classified as SM 1-2 lesions and those with less than 50% in this category. Similarly, a comparison between studies with at least 50% microsurgery-cases and those with less than 50% was performed. We examined correlations between mortality incidence, SM distribution, and treatment modalities. RESULTS: Our analysis included 16 studies with 2.417 patients. The frequency of bAVMs SM-grade 1-2 ranged from 44% to 76%, SM-grade 3 from 19% to 48%, and SM 4-5 from 5 to 23%. Notably, studies with more than 50% cases presenting lesions SM-grade 1-2 presented significantly lower mortality rates than those with less than 50% cases of SM 1-2 lesions (P < 0.001). No significant difference in mortality rates or neurological deficits was identified between studies with more than 50% of microsurgery-cases and those with less than 50%. CONCLUSIONS: The analysis revealed that studies with a higher proportion of bAVMs presenting SM 1-2 lesions were associated with lower mortality rates. Mortality did not show a significant association with treatment modalities.

Radiosurgery as a microsurgical adjunct: outcomes after microsurgical resection of intracranial arteriovenous malformations previously treated with stereotactic radiosurgery.

OBJECTIVE: Microsurgical resection of arteriovenous malformations (AVMs) can be aided by staged treatment consisting of stereotactic radiosurgery followed by resection in a delayed fashion. This approach is particularly useful for high Spetzler-Martin (SM) grade lesions because radiosurgery can reduce flow through the AVM, downgrade the SM rating, and induce histopathological changes that additively render the AVM more manageable for resection. The authors present their 28-year experience in managing AVMs with adjunctive radiosurgery followed by resection. METHODS: The authors retrospectively reviewed records of patients treated for cerebral AVMs at their institution between January 1990 and August 2019. All patients who underwent stereotactic radiosurgery (with or without embolization), followed by resection, were included in the study. Of 1245 patients, 95 met the eligibility criteria. Univariate and multivariate regression analyses were performed to assess relationships between key variables and clinical outcomes. RESULTS: The majority of lesions treated (53.9%) were high grade (SM grade IV-V), 31.5% were intermediate (SM grade III), and 16.6% were low grade (SM grade I-II). Hemorrhage was the initial presenting sign in half of all patients (49.5%). Complete resection was achieved among 84% of patients, whereas 16% had partial resection, the majority of whom received additional radiosurgery. Modified Rankin Scale (mRS) scores of 0-2 were achieved in 79.8% of patients, and 20.2% had poor (mRS scores 3-6) outcomes. Improved (44.8%) or stable (19%) mRS scores were observed among 63.8% of patients, whereas 36.2% had a decline in mRS scores. This includes 22 patients (23.4%) with AVM hemorrhage and 6 deaths (6.7%) outside the perioperative period but prior to AVM obliteration. CONCLUSIONS: Stereotactic radiosurgery is a useful adjunct in the presurgical management of cerebral AVMs. Multimodal therapy allowed for high rates of AVM obliteration and acceptable morbidity rates, despite the predominance of high-grade lesions in this series of patients.

The predictors of clinical outcomes in brainstem arteriovenous malformations after stereotactic radiosurgery.

ABSTRACT: The brainstem arteriovenous malformations (BS-AVMs) have a high morbidity and mortality and stereotactic radiosurgery (SRS) has been widely used to treat BS-AVMs. However, no consensus is reached in the explicit predictors of obliteration for BS-AVMs after SRS.To identify the predictors of clinical outcomes for BS-AVMs treated by SRS, we performed a retrospective observational study of BS-AVMs patients treated by SRS at our institution from 2006 to 2016. The primary outcomes were obliteration of nidus and favorable outcomes (AVM nidus obliteration with mRS score ≤2). For getting the outcomes more accurate, we also pooled the results of previous studies as well as our study by meta-analysis.A total of 26 patients diagnosed with BS-AVMs, with mean volume of 2.6 ml, were treated with SRS. Hemorrhage presentation accounted for 69% of these patients. Overall obliteration rate was 42% with mean follow-up of more than five years and two patients (8%) had a post-SRS hemorrhage. Favorable outcomes were observed in 8 patients (31%). Higher margin dose (>15Gy) was associated with higher obliteration (P = .042) and small volume of nidus was associated with favorable outcomes (P = .036). After pooling the results of 7 studies and present study, non-prior embolization (P = .049) and higher margin dose (P = .04) were associated with higher obliteration rate, in addition, the lower Virginia Radiosurgery AVM Scale (VRAS) was associated with favorable outcomes (P = .02) of BS-AVMs after SRS.In the BS-AVMs patients treated by SRS, higher margin dose (19-24Gy) and non-prior embolization were the independent predictors of higher obliteration rate. In addition, smaller volume of nidus and lower VRAS were the potential predictors of long-term favorable outcomes for these patients.

Treatments of unruptured brain arteriovenous malformations: A systematic review and meta-analysis.

BACKGROUND: The best therapeutic option for unruptured brain arteriovenous malformations (bAVMs) patients is disputed. OBJECTIVE: To assess the occurrence of obliteration and complications of patients with unruptured bAVMs after various treatments. METHODS: A systematic literature search was performed in PubMed, EMBASE, Web of Science, and so on to identify studies fulfilling predefined inclusion criteria. Baseline, treatment, and outcomes data were extracted for statistical analysis. RESULTS: We identified 28 eligible studies totaling 5852 patients. The obliteration rates were 98% in microsurgery group (95% confidence interval (CI): 96%-99%, I2 = 74.5%), 97% in surgery group (95%CI: 95%-99%, I2 = 18.3%), 87% in endovascular treatment group (95%CI: 80%-93%, I2 = 0.0%), and 68% in radiosurgery group (95%CI: 66%-69%, I2 = 92.0%). The stroke or death rates were 1% in microsurgery group (95%CI: 0%-2%, I2 = 0.0%), 0% in surgery group (95%CI: 0%-1%, I2 = 0.0%), 4% in endovascular treatment group (95%CI: 0%-8%, I2 = 85.8%), and 3% in radiosurgery group (95%CI: 3%-4%, I2 = 82.9%). In addition, the proportions of hemorrhage were 2% in microsurgery group (95%CI: 1%-4%, I2 = 0.0%), 23% in endovascular treatment group (95%CI: 7%-39%), and 12% in radiosurgery group (95%CI: 12%-13%, I2 = 99.2%). As to neurological deficit, the occurrence was 9% in microsurgery group (95%CI: 6%-11%, I2 = 94.1%), 20% in surgery group (95%CI: 13%-27%, I2 = 0.0%), 14% in endovascular treatment group (95%CI: 10%-18%, I2 = 64.0%), and 8% in radiosurgery group (95%CI: 7%-9%, I2 = 66.6%). CONCLUSIONS: We found that microsurgery might provide lasting clinical benefits in some unruptured bAVMs patients for its high obliteration rates and low hemorrhage. These findings are helpful to provide a reference basis for neurosurgeons to choose the treatment of patients with unruptured bAVMs.

Unruptured Arteriovenous Malformations: Do We Have an Answer After the Final Follow-Up of ARUBA? A Bayesian Viewpoint.

Brain arteriovenous malformations (bAVMs) are vascular lesions that carry significant morbidity and mortality risk upon rupture. bAVM rupture causes either intracerebral or intraventricular hemorrhage, or both. In 2014, the first results of the ARUBA trial (A Randomized Trial of Unruptured Brain Arteriovenous Malformations) were published in The Lancet, causing a paradigm shift in clinical practice and suggesting the superiority of medical treatment in terms of mortality or stroke compared with any intervention designed to obliterate the AVM. In 2020, the final results of the ARUBA trial were published. In this Viewpoint, we critically review the clinical equipoise behind the trial, highlight issues regarding external validity, and place the results of the trial in the context of other results in scientific literature of bAVMs using Bayesian inference. ARUBA is a trial of decision-making, and only proper knowledge of the nuances of its interpretation within the broader context of bAVM research can lead to proper decision-making when confronted with patients with unruptured bAVMs.

Morbidity and mortality associated with sequential flow reduction embolization technique of cerebral arteriovenous malformations using n-butyl cyanoacrylate.

BACKGROUND: Endovascular embolization of cerebral arteriovenous malformations (AVM) with liquid n-butyl cyanoacrylate (n-BCA) serves multiple purposes including AVM occlusion and flow reduction in preparation for other treatment modalities. The objective was to study the clinical, structural, and angiographic factors affecting complications associated with AVM treatment by sequential n-BCA embolizations for nidal occlusion versus quantitative flow reduction in preparation for surgical resection or radiosurgery. METHODS: We performed a retrospective review of all patients who underwent endovascular embolization of cerebral AVM at our institution between 1998 and 2019, during which time the technique of traditional embolization evolved to a strategy of targeted sequential flow reduction guided by serial flow imaging based on quantitative magnetic resonance angiography, in conjunction with a shift away from nidal penetration. RESULTS: Among 251 patients, 47.8% of patients presented with ruptured AVM. On average, each patient underwent 2.4 embolizations, for a total of 613 sessions. Major morbidity related to embolization occurred in 18 (7.2%) patients, but this occurred disproportionately in the traditional embolization strategy (n=16, 8%) in contrast with the flow-targeting strategy (n=2, 3.8%). Four patients (1.6%) died in the overall group, and these all occurred with the traditional embolization strategy (2% of 199 patients); no deaths occurred in the flow-targeting strategy (n=52). CONCLUSION: Embolization with n-BCA targeted to sequential flow reduction and feeder occlusion with limited nidal penetration prior to definitive surgical or radiosurgical treatment can be safely performed with low overall morbidity and mortality.

Non-Traumatic Intracerebral Hematoma in the Young: Findings from a Tertiary Hospital in the Philippines.

BACKGROUND: There is geographic variability in the clinical profile and outcomes of non-traumatic intracerebral hematoma (ICH) in the young, and data for the Philippines is lacking. We aimed to describe this in a cohort from the Philippines, and identify predictors of mortality. METHODS: We performed a retrospective study of all patients aged 19-49 years with radiographic evidence of non-traumatic ICH admitted in our institution over five years. Data on demographics, risk factors, imaging, etiologies, surgical management, in-hospital mortality, and discharge functional outcomes were collected. Multivariate logistic regression analysis was done to determine factors predictive of mortality. RESULTS: A total of 185 patients were included, which had a mean age of 40.98 years and a male predilection (71.9%). The most common hematoma location was subcortical, but it was lobar for the subgroup of patients aged 19-29 years. Overall, the most common etiology was hypertension (73.0%), especially in patients aged 40-49. Conversely, the incidence of vascular lesions and thrombocytopenia was higher in patients aged 19-29. Surgery was done in 7.0% of patients. The rates of mortality and favorable functional outcome at discharge were 8.7% and 35.1%, respectively. Younger age (p = 0.004), higher NIHSS score on admission (p=0.01), higher capillary blood glucose on admission (p=0.02), and intraventricular extension of hematoma (p = 0.01) predicted mortality. CONCLUSIONS: In the Philippines, the most common etiology of ICH in young patients was hypertension, while aneurysms and AVM's were the most common etiology in the subgroup aged 19 - 29 years. Independent predictors of mortality were identified.

Medical management with interventional therapy versus medical management alone for unruptured brain arteriovenous malformations (ARUBA): final follow-up of a multicentre, non-blinded, randomised controlled trial.

BACKGROUND: In A Randomized trial of Unruptured Brain Arteriovenous malformations (ARUBA), randomisation was halted at a mean follow-up of 33·3 months after a prespecified interim analysis showed that medical management alone was superior to the combination of medical management and interventional therapy in preventing symptomatic stroke or death. We aimed to study whether these differences persisted through 5-years' follow-up. METHODS: ARUBA was a non-blinded, randomised trial done at 39 clinical centres in nine countries. Adults (age ≥18 years) diagnosed with an unruptured brain arteriovenous malformation, who had never undergone interventional therapy, and were considered by participating clinical centres to be suitable for intervention to eradicate the lesion, were eligible for inclusion. Patients were randomly assigned (1:1) by a web-based data collection system, stratified by clinical centre in a random permuted block design with block sizes of two, four, and six, to medical management alone or with interventional therapy (neurosurgery, embolisation, or stereotactic radiotherapy, alone or in any combination, sequence, or number). Although patients and investigators at a given centre were not masked to treatment assignment, investigators at other centres and those in the clinical coordinating centre were not informed of assignment or outcomes at any of the centres. The primary outcome was time to death or symptomatic stroke confirmed by imaging, assessed by a neurologist at each centre not involved in the management of participants' care, and monitored by an independent committee using an adaptive approach with interim analyses. Enrolment began on April 4, 2007, and was halted on April 15, 2013, after which follow-up continued until July 15, 2015. All analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, NCT00389181. FINDINGS: Of 1740 patients screened, 226 were randomly assigned to medical management alone (n=110) or medical management plus interventional therapy (n=116). During a mean follow-up of 50·4 months (SD 22·9), the incidence of death or symptomatic stroke was lower with medical management alone (15 of 110, 3·39 per 100 patient-years) than with medical management with interventional therapy (41 of 116, 12·32 per 100 patient-years; hazard ratio 0·31, 95% CI 0·17 to 0·56). Two patients in the medical management group and four in the interventional therapy group (two attributed to intervention) died during follow-up. Adverse events were observed less often in patients allocated to medical management compared with interventional therapy (283 vs 369; 58·97 vs 78·73 per 100 patient-years; risk difference -19·76, 95% CI -30·33 to -9·19). INTERPRETATION: After extended follow-up, ARUBA showed that medical management alone remained superior to interventional therapy for the prevention of death or symptomatic stroke in patients with an unruptured brain arteriovenous malformation. The data concerning the disparity in outcomes should affect standard specialist practice and the information presented to patients. The even longer-term risks and differences between the two therapeutic approaches remains uncertain. FUNDING: National Institute of Neurological Disorders and Stroke for the randomisation phase and Vital Projects Fund for the follow-up phase.

Updates in arteriovenous malformation management: the post-ARUBA era.

Brain arteriovenous malformations (AVMs) are complex and heterogeneous lesions that can rupture, causing significant morbidity and mortality. While ruptured lesions are usually treated, the management of unruptured AVMs remains unclear. A Randomized trial of Unruptured Brain Arteriovenous Malformations (ARUBA) was the first trial conducted to compare the effects of medical and interventional therapy. Although it concluded that medical therapy was superior in preventing stroke and death over a follow-up period of 33 months, the findings were met with intense criticism regarding several aspects of study design, progression, and analysis/conclusion. Namely, the increased use of stand-alone embolisation relative to microsurgery in a cohort with predominantly low-grade lesions combined with a short follow-up period amplified treatment risk. Subsequently, several observational studies were conducted on ARUBA-eligible patients to investigate the safety and efficacy of microsurgery, radiosurgery, and endovascular embolisation over longer follow-up periods. These reports showed that favourable safety profiles and cure rates can be achieved with appropriate patient selection and judicious use of different treatment modalities in multidisciplinary centres. Since large prospective randomised trials on AVMs may not be feasible, it is important to make use of practice-based data beyond the flawed ARUBA study to optimise patients' lifetime outcomes.

Gamma Knife Radiosurgery for ARUBA-Eligible Patients with Unruptured Brain Arteriovenous Malformations.

BACKGROUND: A randomized trial of unruptured brain arteriovenous malformations (ARUBA) reported superior outcomes in conservative management compared to interventional treatment. There were numerous limitations to the study. This study aimed to investigate the efficacy of gamma knife radiosurgery (GKS) for patients with brain arteriovenous malformations (AVMs) by comparing its outcomes to those of the ARUBA study. METHODS: We retrospectively reviewed ARUBA-eligible patients treated with GKS from June 2002 to September 2017 and compared against those in the ARUBA study. AVM obliteration and hemorrhage rates, and clinical outcomes following GKS were also evaluated. RESULTS: The ARUBA-eligible cohort comprised 264 patients. The Spetzler-Martin grade was Grade I to II in 52.7% and III to IV in 47.3% of the patients. The mean AVM nidus volume, marginal dose, and follow-up period were 4.8 cm³, 20.8 Gy, and 55.5 months, respectively. AVM obliteration was achieved in 62.1%. The annual hemorrhage rate after GKS was 3.4%. A stroke or death occurred in 14.0%. The overall stroke or death rate of the ARUBA-eligible cohort was significantly lower than that of the interventional arm of the ARUBA study (P < 0.001) and did not significantly differ from that of the medical arm in the ARUBA study (P = 0.601). CONCLUSION: GKS was shown to achieve a favorable outcome with low procedure-related morbidity in majority of the ARUBA-eligible patients. The outcome after GKS in our patients was not inferior to that of medical care alone in the ARUBA study. It is suggested that GKS is rather superior to medical care considering the short follow-up duration of the ARUBA study.

Effect of A Randomized trial of Unruptured Brain Arteriovenous Malformation on Interventional Treatment Rates for Unruptured Arteriovenous Malformations.

BACKGROUND: In 2013, investigators from A Randomized Trial of Unruptured Brain Arteriovenous Malformations (AVM; ARUBA) reported that interventions to obliterate unruptured AVMs caused more morbidity and mortality than medical management. OBJECTIVE: We sought to determine whether interventions for unruptured AVM decreased after publication of ARUBA results. METHODS: We used the Nationwide Readmissions Database to assess trends in interventional AVM management in patients ≥18 years of age from 2010 through 2015. Unruptured brain AVMs were identified using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code 747.81 and excluding any patient with a diagnosis of intracranial hemorrhage. Our primary outcome was interventional AVM treatment, identified using ICD-9-CM procedure codes for surgical resection, endovascular therapy, and stereotactic radiosurgery. Join-point regression was used to assess trends in the incidence of interventional AVM management among adults from 2010 through 2015. RESULTS: There was no significant U.S. population level change in unruptured brain AVM intervention rates before versus after ARUBA (p = 0.59), with the incidence of AVM intervention ranging from 8.0 to 9.2 per 10 million U.S. residents before the trial publication to 7.7-8.3 per 10 million afterwards. CONCLUSIONS: In a nationally representative sample, we found no change in rates of interventional unruptured AVM management after publication of the ARUBA trial results.

S100B Serum Elevation Predicts In-Hospital Mortality After Brain Arteriovenous Malformation Rupture.

Background and Purpose- S100B protein serum elevation has been associated with poor prognosis in neurologically ill patients. The purpose of this study is to determine whether elevation of S100B is associated with increased in-hospital mortality after brain arteriovenous malformation rupture. Methods- This is a retrospective study of patients admitted for brain arteriovenous malformation rupture. The study population was divided into derivation and validation cohorts. Univariate followed by multivariate logistic regression was used to determine whether elevation of S100B serum levels above 0.5 µg/L during the first 48 hours after admission (S100Bmax48) was associated with in-hospital mortality. Results- Two hundred and three ruptures met inclusion criteria. Twenty-three led to in-hospital mortality (11%). Mean S100Bmax48 was 0.49±0.62 µg/L. In the derivation cohort (n=101 ruptures), multivariate analysis found Glasgow coma scale score ≤8 (odds ratio, 21; 95% CI, 2-216; 0.001) and an S100Bmax48>0.5 µg/L (odds ratio, 19; 95% CI, 2-188; P=0.001) to be associated with in-hospital mortality. When applied to the validation cohort (n=102 ruptures), the same model found only S100Bmax48>0.5 µg/L (odds ratio, 8; 95% CI, 1.5-44; P=0.01) to be associated with in-hospital mortality. Conclusions- Elevated S100B protein serum level is strongly associated with in-hospital mortality after brain arteriovenous malformation rupture.

Extravasation of contrast (Spot Sign) predicts in-hospital mortality in ruptured arteriovenous malformation.

BACKGROUND AND PURPOSE: The spot sign is a highly specific and sensitive predictor of hematoma expansion in following primary intracerebral hemorrhage (ICH). Rare cases of the spot sign have been documented in patients with intracranial hemorrhage secondary to arteriovenous malformation (AVM). The purpose of this retrospective study is to assess the accuracy of spot sign in predicting clinical outcomes in patients with ruptured AVM. MATERIALS AND METHODS: A retrospective analysis of a prospectively maintained database was performed for patients who presented to West China Hospital with ICH secondary to AVM in the period between January 2009 and September 2016. Two radiologists blinded to the clinical data independently assessed the imaging data, including the presence of spot sign. Statistical analysis using univariate testing, multivariate logistic regression testing, and receiver operating characteristic curve (AUC) analysis was performed. RESULTS: A total of 116 patients were included. Overall, 18.9% (22/116) of subjects had at least 1 spot sign detected by CT angiography, 7% (8/116) died in hospital, and 27% (31/116) of the patients had a poor outcome after 90 days. The spot sign had a sensitivity of 62.5% and specificity of 84.3% for predicting in-hospital mortality (p = .02, AUC 0.734). No correlation detected between the spot sign and 90-day outcomes under multiple logistic regression (p = .19). CONCLUSIONS: The spot sign is an independent predictor for in-hospital mortality. The presence of spot sign did not correlate with the 90 day outcomes in this patient cohort. The results of this report suggest that patients with ruptured AVM with demonstrated the spot sign on imaging must receive aggressive treatment early on due to the high risk of mortality.

The Unique Features and Outcomes of Microsurgically Resected Cerebellar Arteriovenous Malformations.

BACKGROUND: Cerebellar arteriovenous malformations (CAVMs) are challenging to treat given their close proximity to the brain stem, greater propensity for rupture, and greater rates of morbidity and mortality than other brain arteriovenous malformations. The present investigation sought to describe and characterize the features of these rare and unique lesions. METHODS: A retrospective review of CAVM cases treated at 2 tertiary medical centers was performed. Patients surgically treated at institution 1 from September 1999 to February 2013 and institution 2 from October 2008 to October 2015 were included. RESULTS: A total of 120 patients had been treated. Of the 120 patients, 85 (70.8%) had initially presented with hemorrhage, 45 (37.5%) of whom experienced hemorrhage requiring emergent surgery. A favorable neurological outcome was observed in 76 patients (63.3%; modified Rankin Scale score <3). The perioperative mortality was 2.5% (n = 3). The long-term mortality rate was 7.5% (n = 9). The mean follow-up time was 1.82 years. On average, the patients with large CAVMs (≥3 cm; P ≤ 0.001), who had received embolization before surgery (P = 0.04), did not have an associated aneurysm (P ≤ 0.001), or had a residual CAVM after surgery (P = 0.008) were significantly younger. Female patients had fewer CAVMs with deep venous drainage (54.3% vs. 72.3%; P = 0.049), experienced decreased mortality (1.4% vs. 16.7%; P = 0.003), and were less likely to have worse neurological status after treatment (P = 0.003). CONCLUSIONS: CAVMs are rare lesions that exhibit unique disease characteristics. Although most patients will experience a favorable outcome, CAVMs frequently present with hemorrhage, result in high rates of morbidity and mortality, and characteristically differ depending on patient age and gender.

Multimodal Interventional Treatment and Outcomes for Unruptured Arteriovenous Malformations.

BACKGROUND: This study aimed to evaluate the selection and outcomes of multimodal interventional treatment for unruptured brain arteriovenous malformations (uAVMs) in ARUBA-eligible patients in a single institution. METHODS: We retrospectively reviewed the data of 94 patients with uAVMs treated between 2002 and 2014. They were divided into an intervention group and a conservative group. The primary outcome was defined as the composite of death or symptomatic stroke. Functional outcome was assessed using the modified Rankin Scale (mRS). RESULTS: The intervention and conservative groups included 75 and 19 patients, respectively, with mean follow-up periods of 59.2 ± 41.6 and 72.8 ± 39.2 months (P = 0.20), among whom the primary outcome occurred in 9 (12.3%) and 3 (17.6%) patients, respectively (P = 0.91). The proportion of patients with an mRS score ≥ 2 at last follow-up was not significantly different between the two groups (6.9% vs. 11.7%). In the intervention group, the incidence of death or stroke was lower and functional outcomes were better among patients with grade I/II AVMs than among patients with grade III AVMs. CONCLUSION: For patients with uAVMs, interventional treatment is not inferior to medical treatment alone, and careful selection should be made for patients with grade III AVMs.

Reimagining ARUBA: Theoretical Optimization of the Treatment of Unruptured Brain Arteriovenous Malformations.

BACKGROUND AND PURPOSE: The results of the A Randomized Trial of Unruptured Brain Arteriovenous (ARUBA) study, indicating that conservative medical management of unruptured brain arteriovenous malformations (UBAVM) is superior to interventional therapy, have generated debates that have hampered their application into clinical practice. Irrespectively of study conclusions, it seems reasonable to explore how much better interventional therapy would have to be to become competitive with conservative medical management. METHODS: We conducted an exploratory analysis to replicate the original data from ARUBA. The functional form of the replicated ARUBA data, according to their Weibull distribution, allowed estimation of parameters. We carried out Monte Carlo simulations while introducing theoretical reductions of interventional risk, and the results were used to construct theoretical and example Kaplan-Meier curves from simulations. RESULTS: The "ARUBA Replication" analysis showed results nearly identical to those published in the study, with an estimated hazard ratio of 0.27 (95% CI: 0.14-0.55). At 50% interventional risk reduction, the simulations showed an estimated event rate of 14.9%, and the protective effect of conservative medical management was no longer statistically significant. Greater risk reductions hastened the time to benefit for interventional therapy, and an 80% risk reduction demonstrated superiority of interventional therapy at just over 2 years Hazard Ratio (HR: 1.44, 95% CI: 0.55-4.92). CONCLUSIONS: Reduction in risk of interventional therapy by 50%-80% results in more competitive clinical outcomes, equating or surpassing the benefit of conservative medical management of UBAVM. This conjecture should be taken into consideration in the design of future studies of this patient population, particularly because it is supported by recent observational studies.

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.

Review of de novo cerebral arteriovenous malformation: haemorrhage risk, treatment approaches and outcomes.

Objective A small number of patients has been reported to develop a completely new or de novo arteriovenous malformation (AVM) after brain surgery, haemorrhage, head trauma or ischaemic stroke. The natural history of these lesions is unknown. In this review, both ruptured and unruptured de novo AVMs and their treatments were reviewed. Methods Published literature in the PubMed database citing 'de novo cerebral arteriovenous malformation' was reviewed. Additional studies were identified through reference searches in each reviewed article. A review was performed using all published cases, the treatment approaches and outcomes. Results A total of 38 patients, including 37 de novo AVMs reported from 1988 to 17 November 2017 and our one patient, was collected. The age at AVM diagnosis was 5-73 years (mean ± SD, 27.6 ± 20.5 years). The duration time, from negative examination to AVM diagnosis, was 2 months to 25 years (mean ± SD, 6.6 ± 4.9 years). The presentation of de novo AVM was headaches in three (7.9%) patients, bleedings in 12 (31.6%), incidental in 14 (36.8%) and seizure in nine (23.7%). The estimated risk of haemorrhage was 4.8% per year. Seventeen (44.7%) patients were treated with surgical resection, 10 (26.3%) were conservatively observed, nine (23.7%) were treated with radiosurgery and two (5.3%) were endovascularly embolised. The morbidity and mortality were reported as 5.3% and 7.9%, respectively. Conclusion Post-natal de novo AVMs have been reported. Their annual haemorrhage risk is 4.8%. Most of them are treated by surgical resection and are associated with morbidity and mortality.

Retrospective study of long-term outcome after brain arteriovenous malformation rupture: the RAP score.

OBJECTIVE The authors aimed to design a score for stratifying patients with brain arteriovenous malformation (BAVM) rupture, based on the likelihood of a poor long-term neurological outcome. METHODS The records of consecutive patients with BAVM hemorrhagic events who had been admitted over a period of 11 years were retrospectively reviewed. Independent predictors of a poor long-term outcome (modified Rankin Scale score ≥ 3) beyond 1 year after admission were identified. A risk stratification scale was developed and compared with the intracranial hemorrhage (ICH) score to predict poor outcome and inpatient mortality. RESULTS One hundred thirty-five patients with 139 independent hemorrhagic events related to BAVM rupture were included in this analysis. Multivariate logistic regression followed by stepwise analysis showed that consciousness level according to the Glasgow Coma Scale (OR 6.5, 95% CI 3.1-13.7, p < 10-3), hematoma volume (OR 1.8, 95% CI 1.2-2.8, p = 0.005), and intraventricular hemorrhage (OR 7.5, 95% CI 2.66-21, p < 10-3) were independently associated with a poor outcome. A 12-point scale for ruptured BAVM prognostication was constructed combining these 3 factors. The score obtained using this new scale, the ruptured AVM prognostic (RAP) score, was a stronger predictor of a poor long-term outcome (area under the receiver operating characteristic curve [AUC] 0.87, 95% CI 0.8-0.92, p = 0.009) and inpatient mortality (AUC 0.91, 95% CI 0.85-0.95, p = 0.006) than the ICH score. For a RAP score ≥ 6, sensitivity and specificity for predicting poor outcome were 76.8% (95% CI 63.6-87) and 90.8% (95% CI 81.9-96.2), respectively. CONCLUSIONS The authors propose a new admission score, the RAP score, dedicated to stratifying the risk of poor long-term outcome after BAVM rupture. This easy-to-use scoring system may help to improve communication between health care providers and consistency in clinical research. Only external prospective cohorts and population-based studies will ensure full validation of the RAP scores' capacity to predict outcome after BAVM rupture.

Treatment of Brain Arteriovenous Malformations with Hemodynamic Aneurysms: A Series of 131 Consecutive Cases.

BACKGROUND: The natural history of hemodynamic aneurysms (HAs) associated with brain arteriovenous malformations (AVMs) remains controversial, with no single approach to treatment. The purpose of this study was to justify preventive treatment tactics for HAs that pose an increased risk of rupture based on hemodynamic studies demonstrating hypertension in the afferent bed after AVM exclusion. METHODS: This retrospective analysis included 131 of 1740 patients (8%) with brain AVMs and at least 1 aneurysm treated at Burdenko Neurosurgical Institute between 2000 and 2016. Treatment consisted of microsurgery, endovascular interventions, or a combination of modalities. Patients were evaluated with the modified Rankin Scale before and after treatment. RESULTS: A total of 205 aneurysms were discovered. Multiple HAs were found in 46 patients (35%), and were significantly more often associated with posterior fossa AVMs; in addition, most were distally located. There was no difference in the incidence of hemorrhage between proximal and distal HAs. Microsurgical treatment was marked by high radicalism; 85% of HAs and 94% of AVMs were totally excluded based on control studies. In 10 cases, aneurysms were found after AVM removal, including 4 de novo aneurysms. In 1 case, the aneurysm regressed after AVM treatment. The mortality rate was 2.3%. CONCLUSIONS: Preoperative imaging should be carefully examined for associated aneurysms before and after surgical treatment. Our data suggests that HA exclusion, either as the first step or simultaneously with AVM treatment, is most beneficial to patients.