A Randomized Trial Of Unruptured Brain Arteriovenous Malformations Research Articles

Treatment outcomes for ARUBA-eligible brain arteriovenous malformations: a comparison of real-world data from the NVQI-QOD AVM registry with the ARUBA trial

BackgroundSignificant controversy exists about the management of unruptured cerebral arteriovenous malformations (AVMs). Results from A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) suggested that intervention increases the risk of...

In Response to: Dicpinigaitis AJ, Ogulnick JV, Mayer AS, Gandhi CD, Al‐Mufti F. Increase in Ruptured Cerebral Arteriovenous Malformations and in the United States: Unintended Consequences of the ARUBA Trial? Stroke Vasc Interv Neurol . 2022;0:e000442. https://doi.org/10.1161/SVIN.122.000442

In Response to: Dicpinigaitis AJ, Ogulnick JV, Mayer AS, Gandhi CD, Al‐Mufti F. Increase in Ruptured Cerebral Arteriovenous Malformations and in the United States: Unintended Consequences of the ARUBA Trial? <i>Stroke Vasc Interv Neurol</i> . 2022;0:e000442. https://doi.org/10.1161/SVIN.122.000442

In Response to: Dicpinigaitis AJ, Ogulnick JV, Mayer AS, Gandhi CD, Al‐Mufti F. Increase in Ruptured Cerebral Arteriovenous Malformations and Mortality in the United States: Unintended Consequences of the ARUBA Trial

In Response to: Dicpinigaitis AJ, Ogulnick JV, Mayer AS, Gandhi CD, Al‐Mufti F. Increase in Ruptured Cerebral Arteriovenous Malformations and Mortality in the United States: Unintended Consequences of the ARUBA Trial

Stereotactic Radiosurgery for A Randomized Trial of Unruptured Brain Arteriovenous Malformations-Eligible Patients: A Meta-Analysis.

The outcomes of A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) were controversial, and they suggested that intervention is inferior to medical management for unruptured brain arteriovenous malformations (AVMs). However, several studies have shown that stereotactic radiosurgery (SRS) is an acceptable therapy for unruptured AVMs. To test the hypothesis that ARUBA intervention arm's SRS results are meaningfully inferior to those from similar populations reported by other studies. We performed a literature review to identify SRS studies of patients who met the eligibility criteria for ARUBA. Patient, AVM, treatment, and outcome data were extracted for statistical analysis. Regression analyses were pooled to identify factors associated with post-SRS obliteration and hemorrhage. The study cohort included 8 studies comprising 1620 ARUBA-eligible patients who underwent SRS. At the time of AVM diagnosis, 36% of patients were asymptomatic. The mean follow-up duration was 80 months. Rates of radiologic, symptomatic, and permanent radiation-induced changes were 45%, 11%, and 2%, respectively. The obliteration rate was 68% at last follow-up. The post-SRS hemorrhage and mortality rates were 8%, and 2%, respectively. Lower Spetzler-Martin grade (odds ratios [OR] = 0.84 [0.74-0.95], P = .005), lower radiosurgery-based AVM score (OR = 0.75 [0.64-0.95], P = .011), lower Virginia Radiosurgery AVM Scale (OR = 0.86 [0.78-0.95], P = .003), and higher margin dose (OR = 1.13 [1.02-1.25], P = .025) were associated with obliteration. SRS carries a favorable risk to benefit profile for appropriately selected ARUBA-eligible patients, particularly those with smaller volume AVMs. Our findings suggest that the results of ARUBA do not reflect the real-world safety and efficacy of SRS for unruptured AVMs.

Critical Appraisal of Randomized Controlled Trials on Unruptured Brain Arteriovenous Malformations

Brain arteriovenous malformations management remains controversial despite the numerous, available treatment options. Randomized controlled trials (RCTs) theoretically provide the strongest evidence for the assessment of any therapeutic intervention. However, poorly designed RCTs may be associated with biases, inaccuracies, and misleading conclusions. The purpose of our study is to assess reporting transparency and methodological quality of the existing RCTs. A search was performed in the PubMed, Scopus, Embase, clinicaltrials.gov, and Cochrane databases. The search was limited to English literature. We included all published RCTs reporting on the management of unruptured brain arteriovenous malformations. The eligible studies were evaluated by 5 blinded raters with the CONsolidated Standards of Reporting Trials 2010 statement and the risk-of-bias 2 tool. The inter-rater agreement was assessed with the Fleiss' Kappa. A randomized trial of unruptured brain arteriovenous malformations (ARUBA) and treatment of brain arteriovenous malformations (TOBAS) trials were evaluated. ARUBA achieved high CONsolidated standards of reporting trials compliance, while TOBAS showed a moderate one. In ARUBA the introduction, discussion, and other information sections reached the highest compliance rate (80%-86%). The lowest rates were recorded in the results and the methods (62% and 73%, respectively). The inter-rater agreement was moderate to substantial (54.1% to 78.4%). All the examined studies demonstrated a high risk of bias, mainly related to ill-defined intended interventions, missing outcome data, and selection of the reported results. Our study confirmed the high risk of bias mainly attributed to several protocol violations, deviations, minimal external validity and selection, attrition, and allocation biases of the ARUBA trial. Analysis of the TOBAS trial revealed a moderate overall reporting clarity and a high risk of bias.

Untangling the Modern Treatment Paradigm for Unruptured Brain Arteriovenous Malformations.

Brain arteriovenous malformations (AVMs) often present treatment challenges. Patients with unruptured AVMs must consider not only whether they want to be treated, but what treatment modality they would prefer. Vascular neurosurgeons, neurointerventional surgeons, and stereotactic radiosurgeons must in turn guide their patients through the most appropriate treatment course considering the risk of AVM rupture, an individual AVM’s characteristics, and patient preferences. In this review we will look at how the clinical trial “A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA)” has influenced the approach to unruptured brain AVMs and the treatment modalities available to clinicians to deal with these formidable lesions.

Upfront and Repeated Gamma-Knife Radiosurgery for Small (≤5 mL) Unruptured Brain Arteriovenous Malformation: A Cohort of 249 Consecutive Patients

According to A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA), conservative treatment seems to be superior to any intervention for unruptured brain arteriovenous malformations (AVMs). This study aims to evaluate safety and efficacy of upfront and repeated Gamma-Knife Radiosurgery (GKRS) in patients harboring small AVMs fulfilling the inclusion criteria of ARUBA. A retrospective study was conducted to evaluate outcomes of unruptured naive brain AVM with a volume ⩽ 5 mL eligible to ARUBA treated by GKRS with at least 3 years of follow-up. From 1992 to 2014, 249 patients fulfilled the inclusion criteria of this study. The median age was 36 years (range: 18-78 years). The median treated volume of the nidus was 1.3 mL (range: 0.4-5 mL) and 63% of the AVM were in eloquent areas. Radiosurgery-based AVM score was 1-1.8 (76%), the Spetzler-Martin grade was II-III (73%), and the Virginia Radiosurgery AVM scale was ≤1 point (75%). The overall AVM obliteration rate was 77.1% after up to 3 GKRS sessions. The median dose at the margin was 24 Gy (15-25 Gy) and the median follow-up was 45 months (range: 36-205 months). Eight patients (3.2%) experienced hemorrhage after GKRS, corresponding to a post-GKRS hemorrhage annual rate of 1.03%. Permanent symptomatic radio-induced changes rate was 2% (4 increased seizures, 1 neurologic deficit). The very low toxicity rate and the high occlusion rate suggest in favor of upfront and repeated GKRS for unruptured small AVMs (⩽5 mL).

Elective intervention for unruptured cranial arteriovenous malformations in relation to ARUBA trial: a National Inpatient Sample study.

In 2014, A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) concluded that medical management alone for cranial arteriovenous malformations (AVMs) had better clinical outcomes than interventional treatment. The impact of the ARUBA study on changes in the rates of intervention and outcomes is unknown. Thus, we investigated whether the conclusions from ARUBA may have influenced treatment modalities and outcomes of unruptured AVMs. The National Inpatient Sample (NIS) was queried between 2006 and 2018, for adult patients with an AVM who were admitted on an elective basis. Interventions included open, endovascular, and stereotactic surgeries. Join-point regression was used to assess differences in slopes of treatment rate for each modality before and after the time-point. Logistic regression was used to assess the odds of non-routine discharge and hemorrhage between the two time-points for each treatment modality. Linear regression was used to assess the mean length of stay (LOS) for each treatment modality between the two time-points. A total of 40,285 elective admissions for AVMs were identified between 2006 and 2018. The rate of intervention was higher pre-ARUBA (n = 15,848; 63.8%) compared to post-ARUBA (n = 6985; 45.2%; difference in slope - 8.24%, p < 0.001). The rate of open surgery decreased, while endovascular and stereotactic surgeries remained the same, after the ARUBA trial time-point (difference in slopes - 8.24%, p < 0.001; - 1.74%, p = 0.055; 0.20%, p = 0.22, respectively). For admissions involving interventions, the odds of non-routine discharge were higher post-ARUBA (OR 1.24; p = 0.043); the odds of hemorrhage were lower post-ARUBA (OR 0.69; p = 0.025). There was no statistical difference in length of stay between the two time-points (p = 0.22). The rate of intervention decreased, the rate of non-routine discharge increased, and rate of hemorrhage decreased post-ARUBA, suggesting that it may have influenced treatment practices for unruptured AVMs.

Changes in Clinical Presentation and Treatment Over Time in Patients with Unruptured Intracranial Arteriovenous Malformations

Treatment of unruptured intracranial arteriovenous malformations (AVMs) has become controversial since the ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations) study was published in 2014. We sought to analyze changes in the demographics, clinical presentation, and treatment strategies in 2 patient cohorts from the same institution separated by 40 years. We retrospectively reviewed the electronic medical records for a consecutive series of patients with unruptured intracranial AVMs seen at the Mayo Clinic between 2003 and 2017 and compared them with a previously published historical cohort from the same institution seen between 1974 and1985. There were 273 patients in the contemporary cohort, of which discovery of the AVM was incidental in 123 (45.1%), a 3.5-fold increase compared with the 13.1% out of 168 patients in the historical cohort (P < 0.0001). Consequently, the percentage of patients with seizures as the presenting symptom leading to the diagnosis of AVM decreased from 57.7% in the historical cohort to 28.9% in the contemporary cohort (P < 0.0001). Interventional treatment was utilized in 220 (81.5%) contemporary patients compared with 49 (29.2%) historical patients (P < 0.0001). Compared to 40 years ago, more patients are presenting with incidentally discovered intracranial AVMs and are undergoing interventional treatment. Better understanding of the natural history, developments in endovascular therapy, and stereotactic radiosurgery, as well as improvements in microsurgical techniques have led to a substantial increase in patients undergoing invasive treatment.

Treatment Outcomes of Endovascular Embolization Only in Patients with Unruptured Brain Arteriovenous Malformations: A Subgroup Analysis of ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations).

Endovascular embolization only has been advocated for treatment of brain arteriovenous malformations in recent trials. Our aim was to evaluate the results of embolization only in a cohort of patients who were enrolled in the A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) study at 39 clinical sites in 9 countries. We analyzed the rates and severity of stroke and death in patients who underwent embolization only. Events were identified through in-person neurologic follow-up visits performed at 6-month intervals during the first 2 years and annually, with telephone contact every 6 months thereafter. All event-related data were reviewed by independent adjudicators. Among 30 patients who had embolization planned, 26 underwent embolization only. A total of 13 stroke events were reported in the follow-up period among 26 subjects (ischemic, hemorrhagic, or both in 4, 7, and 2 subjects, respectively). The adverse event occurred after the first embolization in 11 of 13 patients. One patient had a major motor deficit, and 2 patients developed major visual field deficits. One event was fatal. The modified Rankin Scale score was 0-2 at last follow-up in 11 of the 12 stroke survivors. Estimated stroke-free survival was 46% at 12 months. Although the rates of stroke and/or death were high in patients treated with embolization only in ARUBA, the rates of favorable outcomes following stroke were high during follow-up.

Multimodal cerebral arteriovenous malformation treatment: a 12-year experience and comparison of key outcomes to ARUBA.

Curative treatment of unruptured brain arteriovenous malformations (AVMs) remains controversial after the only randomized controlled trial, A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA), was halted prematurely because interim analysis revealed superiority of the medical management group. In contrast, meta-analyses of retrospective cohorts suggest that intervention is much safer than was found in ARUBA. The authors retrospectively analyzed 318 consecutive adult patients with brain AVMs treated at their institution with embolization, surgery, and/or proton beam radiosurgery. Analysis was performed in 142 ARUBA-eligible patients (baseline modified Rankin Scale [mRS] score 0-1, no history of hemorrhage), and results were compared to primary and secondary outcomes from ARUBA, as well as to natural history cohorts. The annualized stroke rate (hemorrhagic or ischemic) in this cohort was 1.8%, 4.9% in the first 12 months and 0.8% after the first 12 months, which was lower than in natural history studies and the ARUBA medical management arm (p = 0.001). The primary ARUBA endpoint of symptomatic stroke was reached in 13 patients (9.2%), which compares favorably to the ARUBA intervention arm (39.6%, p = 0.0001) and is similar to the ARUBA medical management arm (9.2%, p = 1.0). The secondary ARUBA endpoint (mRS score ≥ 2 at 5 years of follow-up) was reached in 14.3% of patients, compared to 40.5% in the ARUBA intervention arm (p = 0.002) and 16.7% in the ARUBA medical management arm (p = 0.6). This multimodal approach to the selection and treatment of patients with brain AVMs yields good clinical outcomes with key safety endpoints (stroke, death, and mRS score 0-1) better than the ARUBA intervention arm and similar to the ARUBA medical arm at 5 years of follow-up. Results compare favorably to natural history cohorts at longer follow-up times. This suggests that tertiary care centers with integrated programs, expertise in patient selection, and individualized treatment approaches may allow for better clinical outcomes than reported in ARUBA. It supports current registry studies and merits consideration of future randomized controlled trials in patients with brain AVMs.

Interventions for treating brain arteriovenous malformations in adults.

Brain arteriovenous malformations (AVMs) are the single most common cause of intracerebral haemorrhage in young adults. Brain AVMs also cause seizure(s) and focal neurological deficits (in the absence of haemorrhage, migraine or an epileptic seizure); approximately one-fifth are incidental discoveries. Various interventions are used in an attempt to eradicate brain AVMs: neurosurgical excision, stereotactic radiosurgery, endovascular embolization, and staged combinations of these interventions. This is an update of a Cochrane Review first published in 2006, and last updated in 2009. To determine the effectiveness and safety of the different interventions, alone or in combination, for treating brain AVMs in adults compared against either each other, or conservative management, in randomized controlled trials (RCTs). The Cochrane Stroke Group Information Specialist searched the Cochrane Stroke Group Trials Register (last searched 7 January 2019), the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 1) in the Cochrane Library, MEDLINE Ovid (1980 to 14 January 2019), and Embase OVID (1980 to 14 January 2019). We searched international registers of clinical trials, the contents pages of relevant journals, and bibliographies of relevant articles (November 2009). We also contacted manufacturers of interventional treatments for brain AVMs (March 2005). We sought RCTs of any intervention for brain AVMs (used alone or in combination), compared against each other or against conservative management, with relevant clinical outcome measures. One author screened the results of the updated searches for potentially eligible RCTs for this updated review. Both authors independently read the potentially eligible RCTs in full and confirmed their inclusion according to the inclusion criteria. We resolved disagreement by discussion. We assessed the risk of bias in included studies and applied GRADE. We included one trial with 226 participants: A Randomized trial of Unruptured Brain Arteriovenous Malformations (ARUBA), comparing intervention versus conservative management for unruptured brain AVMs (that had never bled). The quality of evidence was moderate because we found just one trial that was at low risk of bias other than a high risk of performance bias due to participants and treating physicians not being blinded to allocated treatment. Data on functional outcome and death at a follow-up of 12 months were provided for 218 (96%) of the participants in ARUBA. In this randomized controlled trial (RCT), intervention compared to conservative management increased death or dependency (modified Rankin Scale score ≥ 2, risk ratio (RR) 2.53, 95% confidence interval (CI) 1.28 to 4.98; 1 trial, 226 participants; moderate-quality evidence) and the proportion of participants with symptomatic intracranial haemorrhage (RR 6.75, 95% CI 2.07 to 21.96; 1 trial, 226 participants; moderate-quality evidence), but there was no difference in the frequency of epileptic seizures (RR 1.14, 95% CI 0.63 to 2.06; 1 trial, 226 participants; moderate-quality evidence). Three RCTs are ongoing. We found moderate-quality evidence from one RCT including adults with unruptured brain AVMs that conservative management was superior to intervention with respect to functional outcome and symptomatic intracranial haemorrhage over one year after randomization. More RCTs will help to confirm or refute these findings.

Cognitive performance in patients with cerebral arteriovenous malformation.

A cerebral arteriovenous malformation (cAVM) can change over time and cause symptoms, but clinical studies tend to define only the patients with ruptured cAVMs as symptomatic and do not consider neurocognitive aspects prior to neurosurgical intervention. The objective of this study was to describe the neurocognitive function of patients with ruptured and unruptured cAVMs according to the Spetzler-Martin (SM) grade, flow status, and anatomical topography. In this blinded cross-sectional study, 70 patients of both sexes and ages 18-60 years were evaluated using the Brazilian Brief Neuropsychological Assessment Battery Neupsilin. Of the 70 patients with cAVMs, 50 (71.4%) demonstrated deficits in at least one of the eight neurocognitive domains surveyed, although they did not exhibit neurological deficits. cAVMs in the temporal lobe were associated with memory deficits compared with the general population. The SM grade was not significantly associated with the results of patients with unruptured cAVMs. However, among patients with ruptured cAVMs, there were deficits in working memory in those with high-grade (SM grade) cAVMs and deficits in executive function (verbal fluency) in those with low-grade cAVMs (p < 0.001). This study indicates that patients with untreated cAVMs, either ruptured or unruptured, already exhibit neurocognitive deficits, even the patients without other neurological symptoms. However, the scales used to evaluate disability in the main clinical studies, such as A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA), do not assess neurocognitive alterations and therefore disregard any deficits that may affect quality of life. The authors' finding raises an important question about the effects of interventional treatment because it reinforces the hypothesis that cognitive alterations may be preexisting and not determined by interventions.

Rates and Predictors of Stroke in Medically Managed Patients with Unruptured Arteriovenous Malformations in ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations) (S2.004)

Rates and Predictors of Stroke in Medically Managed Patients with Unruptured Arteriovenous Malformations in ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations) (S2.004)

Treatment Outcomes of Primary Endovascular Embolization in Patients Randomized in Unruptured Arteriovenous Malformations with a Subgroup Analysis of ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations) (P3.9-007)

Treatment Outcomes of Primary Endovascular Embolization in Patients Randomized in Unruptured Arteriovenous Malformations with a Subgroup Analysis of ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations) (P3.9-007)

Abstract TP586: Rates and Predictors of Stroke in Medically Managed Patients With Unruptured Arteriovenous Malformations in ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations)

Background: Primary endovascular embolization has been advocated for treatment of brain arteriovenous malformations (BAVM) in recent trials. We performed this analysis to identify the rate and predictors of incident stroke in a cohort of unruptured BAVM patients recruited in a multicenter trial. Methods: We analyzed adult patients (≥18 years) with an unruptured BAVM were enrolled into Randomised trial of Unruptured Brain Arteriovenous malformations (ARUBA) at 39 clinical sites in nine countries who were randomized to medical treatment. We identified the rates of stroke ascertained by in-person neurological follow-up visits were performed at 6 month intervals during the first 2 years and annually, with telephone contacts every 6 months thereafter. The effect of baseline clinical and neuroimaging characteristics on incident stroke were determined. Results: A stroke event had occurred for 11 (10·1%) of the 109 patients randomized to medical management with a mean follow-up 33·3 months [SD 19·7]) with an annual incidence of 10.1%. Patients with unrelated intracranial aneurysms and higher systolic blood pressure were at higher risk. The mean systolic blood pressure was significantly higher among patients with stroke event (mean 142.3 ± SD 20.3 versus 124.8 ± 14.8, p=.03). There was a linear increase in the risk of stroke event with increasing systolic blood pressure in the logistic regression model (OR 1.1, 95% 1.0 - 1.11, p=.047) There was a trend towards lower incidence of stroke events in BAVM located in the occipital lobe (p=.099). Patient’s age, initial lesion size, and Spetzler Martin grade were not associated with stroke events. Conclusions: A low rate of stroke events was seen in patients with unruptured BAVM with the potential preventive role of aggressive systemic blood pressure treatment.

Treatment of Unruptured Brain Arteriovenous Malformations: A Single-Center Experience of 86 Patients and a Critique of the A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) Trial

The A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) trial has received fierce criticism, including considerable selection bias, poor generalizability, questionable clinical practices (only 15.8% underwent surgical resection, the gold standard for arteriovenous malformation [AVM] treatment), and short follow-up (33 months) for a disease process that carries a life-long risk. In this study, we sought to present our own experience treating unruptured brain AVMs to provide supporting evidence of the ARUBA trial criticism. All cases of treated brain AVMs from 2004 to 2017 at our institution were retrospectively reviewed and included in the analysis if they met ARUBA trial inclusion criteria. The primary outcome was symptomatic stroke or death. Secondary outcomes included AVM obliteration, long-term clinical impairment (modified Rankin Scale score >1), and new major or minor postoperative deficit. Of the 245 reviewed cases, 86 met the ARUBA trial criteria. Treatment included microsurgical resection alone (2.3%), preoperative embolization followed by microsurgical resection (62.8%), stereotactic radiosurgery alone (10.5%), embolization followed by stereotactic radiosurgery (15.1%), and embolization alone (9.3%). The primary outcome was met in 8.3%, new perioperative major and minor complications occurred in 5.8% and 12.8%, and long-term clinical impairment in 4.5%. AVM obliteration was observed in 92.4% overall and in 100% of patients who underwent surgical resection. The criticism of the ARUBA trial is warranted, as our study found that treatment of unruptured brain AVMs has an acceptable safety profile when approached in a multidisciplinary manner at an experienced institution, using surgical resection as the primary treatment modality when applicable.

Treatment Outcomes of A Randomized Trial of Unruptured Brain Arteriovenous Malformation-Eligible Unruptured Brain Arteriovenous Malformation Patients.

The guideline for treating unruptured brain arteriovenous malformations (ubAVMs) remains controversial. A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) reported lower risk of stroke or death with conservative management compared to interventional treatment. There were numerous limitations to the study, including short follow-up period and disproportionate number of patients treated with surgery and embolization. To evaluate whether treatment of ARUBA-eligible patients have acceptable outcomes at our institution. Retrospective analysis was performed on 673 patients with brain AVMs treated at our institution between 2001 and 2014. One hundred five patients were ARUBA eligible and included in the study. Patients were divided into the microsurgery or Gamma Knife Radiosurgery (GKS; Elekta, Stockholm, Sweden) arm depending on their final treatment. Mean follow-up period was 43 mo (range 4-136 mo). Primary outcome was stroke or death. A total of 8 (7.6%) patients had a stroke or died. The overall risk of stroke or death was 11.4% (5 of 44 patients) for the microsurgery arm and 4.9% (3 of 61 patients) for the GKS arm. The annual rates of stroke or death were 2.1%, 4.0%, and 1.2% for the entire patient cohort, microsurgery arm, and GKS arm, respectively. AVM obliteration rates at the end of the follow-up period were 95.5% and 47.5% for the microsurgery and GKS arms, respectively. We report a lower overall risk of stroke or death in our ARUBA-eligible patients following treatment than ARUBA. Our results suggest that microsurgery and GKS may be appropriate treatments for patients with ubAVM.

Unruptured Brain Arteriovenous Malformations: Primary ONYX Embolization in ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations)-Eligible Patients.

In light of evidence from ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations), neurovascular specialists had to reconsider deliberate treatment of unruptured brain arteriovenous malformations (uBAVMs). Our objective was to determine the outcomes of uBAVM treated with primary embolization using ethylene vinyl alcohol (ONYX). Patients with uBAVM who met the inclusion criteria of ARUBA and were treated with primary Onyx embolization were assigned to this retrospective study. The primary outcome was the modified Rankin Scale score. Secondary outcomes were stroke or death because of uBAVM or intervention and uBAVM obliteration. Sixty-one patients (mean age, 38 years) were included. The median observation period was 60 months. Patients were treated by embolization alone (41.0%), embolization and radiosurgery (57.4%), or embolization and excision (1.6%). Occlusion was achieved in 44 of 57 patients with completed treatment (77.2%). Forty-seven patients (77.1%) had no clinical impairment at the end of observation (modified Rankin Scale score of <2). Twelve patients (19.7%) reached the outcome of stroke or death because of uBAVM or intervention. Treatment-related mortality was 6.6% (4 patients). In uBAVM, Onyx embolization alone or combined with stereotactic radiosurgery achieves a high occlusion rate. Morbidity remains a challenge, even if it seems lower than in the ARUBA trial.

Functional impairments for outcomes in a randomized trial of unruptured brain AVMs.

To investigate the effects of medical vs interventional management on functional outcome in A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA). We used the initial results of a nonblinded, randomized, controlled, parallel-group trial involving adults ≥18 years of age with an unruptured brain arteriovenous malformation (AVM) to compare the effects of medical management (MM) with or without interventional therapy (IT) on functional impairment, defined by a primary outcome of death or symptomatic stroke causing modified Rankin Scale (mRS) score ≥2. ARUBA closed recruitment on April 15, 2013. After a median of 33.3 months of follow-up (interquartile range 16.3-49.8 months), of the 223 enrolled in the trial, those in the MM arm were less likely to experience primary outcomes with an mRS score ≥2 than those who underwent IT. The results applied for both those as randomized (MM n = 109 vs IT n = 114) (hazard ratio [HR] 0.25, 95% confidence interval [CI] 0.11-0.57, p = 0.001) and as treated (MM n = 125 vs IT n = 98) (HR 0.10, 95% CI 0.04-0.28, p < 0.001). Functional impairment for the outcomes showed no significant difference by Spetzler-Martin grade for MM but was more frequent with increasing grades for IT (p < 0.001). Death or stroke with functional impairment in ARUBA after a median follow-up of 33 months was significantly lower for those in the MM arm both as randomized and as treated compared with those with IT. Functional severity of outcomes was lower in the MM arm, regardless of Spetzler-Martin grades. NCT00389181. This study provides Class II evidence that for adults with unruptured brain AVMs, interventional management compared to MM increases the risk of disability and death over ≈3 years.