ARUBA Trial Research Articles

Systematic reviews and meta-analyses in the cerebrovascular space: essential domains for readers.

Systematic Review and Meta-Analysis (SRMAs) in neurosurgery have significantly increased. With approximately 1million patients affected by cerebrovascular disease annually, interpreting SRMAs necessitates a systematic approach. The objective of this review is to identify and describe four essential domains for SRMA interpretation. This review outlines the necessities of reviewing existing literature and methodological frameworks essential for interpreting cerebrovascular neurosurgery SRMAs. Each domain is to accurately assess study design variations, heterogeneity assessment methods, outcome comparability strategies, and the impact of technological advancements and time bias on study outcomes. Study design evaluation distinguishes between randomized controlled trials (RCTs) and non-randomized studies. RCTs provide high internal validity, but as seen in the ARUBA trial, can contain internal flaws that necessitate a deeper understanding before application to clinical practices. Non-randomized studies offer valuable real-world insights. A heterogeneity assessment involves readers and writers accurately using forest plots, Cochrane's Q test, Higgins I² statistics, subgroup analysis, and meta-regressions to understand a study's clinical findings. The expertise thresholds, as in the NASCET trial, significantly impact a study's external validity. Strategies such as the GRADE approach can assist in managing diverse outcome measures. Technological advancements, particularly in endovascular procedures and SRS, influence the accuracy of comparing studies across periods, and thus swiftly outdate older studies, lowering the applicability of SRMAs. Effective interpretation of cerebrovascular neurosurgery SRMAs requires attention to study design, heterogeneity, outcome comparability, and technological advancements. These domains collectively enable evidence-based clinical decision-making and optimized patient care in a dynamic field.

Changes in inpatient brain arteriovenous malformation management in the United States following the ARUBA trial: analysis of an interrupted time series design

The November 2013 online publication of ARUBA, the first multi-institutional randomized controlled trial for unruptured brain arteriovenous malformations (AVMs), has sparked over 100 publications in protracted debates MethodsThis study sought to examine inpatient management patterns of brain AVMs from 2009 to 2016 and observe if changes in U.S. inpatient management were attributable to the ARUBA publication using interrupted time series of brain AVM studies from the National Inpatient Sample data 2009–2016. Outcomes of interest were use of embolization, surgery, combined embolization and microsurgery, radiotherapy, and observation during that admission. An interrupted time series design compared management trends before and after ARUBA. Segmented linear regression analysis tested for immediate and long-term impacts of ARUBA on management. ResultsElective and asymptomatic patient admissions declined 2009–2016. In keeping with the ARUBA findings, observation for unruptured brain AVMs increased and microsurgery decreased. However, embolization, radiosurgery, and combined embolization and microsurgery also increased. For ruptured brain AVMs, treatment modality trends remained positive with even greater rates of observation, embolization, and combined embolization and microsurgery occurring after ARUBA (data on radiosurgery were scarce). None of the estimates for the change in trends were statistically significant. ConclusionsThe publication of ARUBA was associated with a decrease in microsurgery and increase in observation for unruptured brain AVMs in the US. However, inpatient radiotherapy, embolization, and combined embolization and surgery also increased, suggesting trends moved counter to ARUBA’s conclusions. This analysis suggested that ARUBA had a small impact as clinicians rejected ARUBA’s findings in managing unruptured brain AVMs.

Current perspectives and trends in the treatment of brain arteriovenous malformations: a review and bibliometric analysis.

Currently, there is a lack of intuitive analysis regarding the development trend, main authors, and research hotspots in the field of cerebral arteriovenous malformation treatment, as well as a detailed elaboration of possible research hotspots. A bibliometric analysis was conducted on data retrieved from the Web of Science core collection database between 2000 and 2022. The analysis was performed using R, VOSviewer, CiteSpace software, and an online bibliometric platform. A total of 1,356 articles were collected, and the number of publications has increased over time. The United States and the University of Pittsburgh are the most prolific countries and institutions in the field. The top three cited authors are Kondziolka D, Sheehan JP, and Lunsford LD. The Journal of Neurosurgery and Neurosurgery are two of the most influential journals in the field of brain arteriovenous malformation treatment research, with higher H-index, total citations, and number of publications. Furthermore, the analysis of keywords indicates that "aruba trial," "randomised trial," "microsurgery," "onyx embolization," and "Spetzler-Martin grade" may become research focal points. Additionally, this paper discusses the current research status, existing issues, and potential future research directions for the treatment of brain arteriovenous malformations. This bibliometric study comprehensively analyses the publication trend of cerebral arteriovenous malformation treatment in the past 20 years. It covers the trend of international cooperation, publications, and research hotspots. This information provides an important reference for scholars to further study cerebral arteriovenous malformation.

Abstract Number ‐ 210: Curative Embolization of Ruptured Pediatric Cerebral Arteriovenous Malformations

Introduction The incidence of ruptured cerebral arteriovenous malformations (AVMs) has increased as a consequence of the publication of the ARUBA trial. In the setting of ruptured AVMs, target embolization of high‐risk features can be considered to decrease the risk for recurrent hemorrhage. However, embolization with the intention to cure has not been well studied in ruptured AVMs. Furthermore, the role of primary curative embolization of pediatric AVMs is uncertain. Hence, we aimed to characterize the safety and efficacy of curative embolization for ruptured AVMs in pediatric patients. Methods Between 2010 and 2022, a retrospective analysis of all pediatric (≤18 years) patients who underwent curative embolization for ruptured AVMs was conducted in two institutions. Demographic data, clinical presentation, Spetzler‐Martin (SM) grade, associated high‐risk vascular structures, and procedural characteristics were retrieved. The safety (intraprocedural complications and mortality) and efficacy (complete angiographic obliteration after the last embolization session) were evaluated. Results Sixty‐eight patients (38 females; mean age 12.4 ± 3.4 years) underwent a total of 109 embolization sessions. The most frequent clinical presentation was headache (79%). There were 15 (22%) SM grade I lesions, 34 (51%) grade II, 14 (21%) grade III, and 4 (6%) grade IV. In 21 patients, twenty‐three high‐risk structures were observed (3 prenidal aneurysms, 12 intranidal aneurysms, 3 venous aneurysms, 2 varicose veins, 3 arteriovenous fistulae). Decompressive craniectomy with intracerebral hemorrhage evacuation was performed in 15 patients (22%). The mean number of sessions per patient was 1.6 (range 1 to 6) and n‐butyl cyanoacrylate was the most used embolic agent (30%). The transarterial approach was the most common (91%). The mean volume of embolic agents in each patient was 2.1 ml (range 0.1 to 6 ml). Seventeen intraprocedural complications (16% of procedures) were observed and no deaths were reported. In patients with high‐risk structures the rate of intraprocedural complications was 24%. The most common complication was microcatheter‐related vessel perforation (7%). Complete angiographic obliteration was achieved in 42 patients (62%). In 30 patients (44%) the AVM was occluded with a single embolization session. The rate of complete obliteration in patients with high‐risk structures was 62%. Conclusions Curative embolization of ruptured pediatric AVMs shows a high rate of intraprocedural complications, especially when high‐risk associated vascular structures are present. In addition, acceptable complete obliteration rates were found. Appropriate long‐term follow‐up in prospective studies tailored to the pediatric population are required to determine the best therapeutic approach.

Impact of ARUBA trial on trends and outcomes in symptomatic non-ruptured brain AVMs: A national sample analysis

IntroductionThe real-world evolution of management and outcomes of patients with unruptured brain arteriovenous malformations (AVMs) has not been well-delineated following the ARUBA trial findings of no general advantage of initial interventional (surgical/endovascular/radiotherapy) vs. initial conservative medical therapy. MethodsWe analyzed the National Inpatient Sample from 2009-2018, capturing 20% of all admissions in the U.S. Validated ICD-9 and -10 codes defined brain AVMs, comorbidities, and the use of interventional modalities. Analyses were performed by year and for the dichotomized periods of pre-ARUBA (2009-2013) vs. post-ARUBA (2014-2018). ResultsAmong the national projected 88,037 AVM admissions, 72,812 (82.7%) were unruptured AVMs and 15,225 (17.3%) were ruptured AVMs. Among uAVMs, 51.4% admitted pre-ARUBA and 48.6% in post-ARUBA period. The post-ARUBA patients were mildly older (median age 53.3 vs. 51.8 (p = 0.001) and had more comorbidities including hypertension, diabetes, obesity, renal impairment, and smoking. Before the first platform report of ARUBA (2009-2012), rates of use of interventional treatments during uAVM admissions trended up from 31.8% to 35.4%. Thereafter, they declined significantly to 26.4% in 2018 (p = 0.02). The decline was driven by a reduction in the frequency of endovascular treatment from 18.8% to 13.9% and inpatient stereotactic radiosurgery from 0.5% to 0.1%. No change occurred in the frequency of microsurgery or combined endovascular and surgical approaches. Adjusted multivariable model of uAVMs showed increased odds of discharge to a long-term inpatient facility or in-hospital death [OR 1.14 (1.02-1.28), p = 0.020] in post-ARUBA. A significantly increased proportion of ruptured AVMs from 17.0% to 23.3% was observed consistently in post-ARUBA. ConclusionNationwide practice in the management of unruptured AVMs changed substantially with the publication of the ARUBA trial in a durable and increasing manner. Fewer admissions with the interventional treatment of unruptured AVMs occurred, and a corresponding increase in admission for ruptured AVMs transpired, as expected with a strategy of watchful waiting and treatment only after an index bleeding event. Further studies are needed to determine whether these trends can be considered to be ARUBA trial effect or are merely coincidental.

Understanding burden of proof and equipoise in the design of pragmatic clinical trials: An example from a trial on brain arteriovenous malformations

Background and purposeThe burden of proof principle is rarely discussed and poorly understood, but central to the proper design of pragmatic clinical trials. A better understanding of the principle could play an important role in the re-introduction of scientific methods within practice and in revising fundamental problems with the current research-care separation. MethodsWe analyze the design of the ARUBA trial on the management of unruptured brain arteriovenous malformations. We also review how the concept of clinical equipoise was introduced to address a misconceived problem of research ethics. ResultsThe ARUBA trial hypothesis in favour of conservative management of brain arteriovenous malformations failed to take into account the fact that the burden of proof was on surgery, endovascular treatment or radiation therapy. Thus, results remained inconclusive and other trials are needed. The equipoise notion fails to take into account that the burden of proof is on unvalidated medical or surgical interventions, if we want to provide outcome-based medical care that patients can trust. ConclusionThe burden of proof principle is essential to properly design pragmatic trials. This principle also explains why in certain circumstances optimal care is a randomized care trial.

Abstract 136: Long-term Impact Of Aruba Trial On Management And Outcomes Of Unruptured Intracranial Arteriovenous Malformations

Introduction: The real-world evolution of management and outcomes of patients with unruptured cerebral arteriovenous malformations (AVMs) has not been well-delineated following the ARUBA trial findings of no general advantage of initial interventional (surgical/endovascular/radiotherapy) vs initial conservative medical therapy. Methods: We analyzed from 2009-2018 the National Inpatient Sample of all AVM admissions in the United States. Analyses were performed by year and for the dichotomized periods of pre-ARUBA (2009-2013) vs. post-ARUBA (2014-2018). Joinpoint regression models with permutation model selection delineated yearly trends in intervention rate in uAVMs. Results: Among a total of 72,812 uAVMs, 35,420 were in the post-ARUBA and 37,392 in the pre-ARUBA period. Median age was 53.3 in post-ARUBA vs. 51.8 in the pre-ARUBA period (p=0.001) with no difference in female sex, 51.1% vs. 51.8% (p=0.44). The intervention rate was lower in the post- vs -pre-ARUBA period, 29.6% vs. 34.0% (p=0.006) (figure). Interventional rate decreased monotonically by -4.32% in the post-ARUBA period (figure). Among the post-ARUBA AVM patients, compared with pre-ARUBA, there were no differences in odds of in-hospital ischemic stroke [OR 1.05 (0.92-1.20), p=0.45] or in-hospital mortality [OR 0.88 (0.62-1.24), p=0.47] but the odds did increase for combined discharge to a facility or in-hospital mortality [OR 1.14 (1.02-1.28), p=0.020]. In addition, the frequency of admissions for ruptured AVMs accelerated in the post-ARUBA period (figure). Conclusion: Nationwide practice in management of unruptured AVMs changed substantially with the publication of the ARUBA trial, in a durable and increasing manner. Fewer admissions with interventional treatment of unruptured AVMs occurred and a corresponding increase in admission for ruptured AVMs transpired, as expected with a strategy of watchful waiting and treatment only after an index bleeding event.

Microsurgical Treatment of Deep and Eloquent AVMs.

Over the past 30years, the treatment of deep and eloquent arteriovenous malformations (AVMs) has moved away from microneurosurgical resection and towards medical management and the so-called minimally invasive techniques, such as endovascular embolization and radiosurgery. The Spetzler-Martin grading system (and subsequent modifications) has done much to aid in risk stratification for surgical intervention; however, the system does not predict the risk of hemorrhage nor risk from other interventions. In more recent years, the ARUBA trial has suggested that unruptured AVMs should be medically managed. In our experience, although these eloquent regions of the brain should be discussed with patients in assessing the risks and benefits of intervention, we believe each AVM should be assessed based on the characteristics of the patient and the angio-architecture of the AVM, in particular venous hypertension, which may guide us to treat even high-grade AVMs when we believe we can (and need to) to benefit the patient. Advances in imaging and intraoperative adjuncts have helped us in decision making, preoperative planning, and ensuring good outcomes for our patients. Here, we present several cases to illustrate our primary points that treating low-grade AVMs can be more difficult than treating high-grade ones, mismanagement of deep and eloquent AVMs at the behest of dogma can harm patients, and the treatment of any AVM should be tailored to the individual patient and that patient's lesion.

Treatment-Associated Stroke in Patients Undergoing Endovascular Therapy in the ARUBA Trial.

Since the publication of ARUBA trial (A Randomized Trial of Unruptured Brain Arteriovenous Malformations), outcomes in treated and untreated patients with unruptured arteriovenous malformation have been thoroughly compared. However, no prior analysis of ARUBA patients has sought to identify risk factors for perioperative stroke. Improved understanding of risks within the ARUBA cohort will help clinicians apply the study’s findings in a broader context. The National Institute of Neurological Disorders and Stroke database was queried for all data relating to ARUBA patients, including demographics, interventions undertaken, and timing of stroke. Retrospective cohort analysis was performed with the primary outcome of perioperative stroke in patients who underwent endovascular intervention, and stroke risk was modeled with multivariate analysis. A total of 64 ARUBA patients were included in the analysis. One hundred and fifty-ninth interventions were performed, and 26 (16%) procedures resulted in stroke within 48 hours of treatment. Posterior cerebral artery supply (adjusted odds ratio, 4.42 [95% CI, 1.23–15.9], P=0.02) and Spetzler-Martin grades 2 and 3 arteriovenous malformation (adjusted odds ratio, 7.76 [95% CI, 1.20–50.3], P=0.03; 9.64 [95% CI, 1.36–68.4], P=0.04, respectively) were associated with increased perioperative stroke risk in patients who underwent endovascular intervention. Patients treated in the United States or Germany had a significantly lower stroke risk than patients treated in other countries (adjusted odds ratio, 0.18 [95% CI, 0.04–0.82], P=0.02). Knowing patient and lesion characteristics that increase risk during endovascular treatment can better guide clinicians managing unruptured brain arteriovenous malformation. Our analysis suggests risk of perioperative stroke is dependent on Spetzler-Martin grade and posterior-circulation arterial supply. Differences in regional treatment paradigms may also affect stroke risk.

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.

Radiosurgery for unruptured brain arteriovenous malformations in the pre-ARUBA era: long-term obliteration rate, risk of hemorrhage and functional outcomes

The management of non-hemorrhagic arteriovenous malformations (AVMs) remains a subject of debate, even more since the ARUBA trial. Here, we report the obliteration rate, the risk of hemorrhage and the functional outcomes after Gamma Knife radiosurgery (GKRS) as first-line treatment for non-hemorrhagic AVMs treated before the ARUBA publication, in a reference university center with multimodal AVM treatments available. We retrospectively analyzed data from a continuous series of 172 patients harboring unruptured AVMs treated by GKRS as first-line treatment in our Lille University Hospital, France, between April 2004 and December 2013. The primary outcome was obliteration rate. Secondary outcomes were the hemorrhage rate, the modified Rankin Scale (mRS), morbidity and epilepsy control at last follow-up. The minimal follow-up period was of 3 years. Median age at presentation was 40 years (IQR 28; 51). Median follow-up was 8.8 years (IQR 6.8; 11.3). Median target volume was 1.9 cm3 (IQR 0.8–3.3 cm3), median Spetzler-Martin grade: 2 (IQR 1–2), median Pollock-Flickinger score: 1.07 (IQR 0.82–2.94), median Virginia score: 1 (IQR 1–2). Median treatment dose was 24 Gy at 50% isodose line. Twenty-three patients underwent a second GKRS after a median time of 58 months after first GKRS. The overall obliteration rate was of 76%, based primarily on cerebral angiography and/or rarely only upon MRI. Hemorrhage during the post-treatment follow-up was reported in 18 (10%) patients (annual risk of 1.1%). Transient post-GKRS morbidity was reported in 14 cases (8%) and persistent neurological deficit in 8 (4.6%) of patients. At last follow-up, 86% of patients had a mRS ≤ 1. Concerning patients with pretherapeutic epilepsy, 84.6% of them were seizure-free at last follow-up. GKRS as first-line therapeutic option for unruptured cerebral AVMs achieves high obliteration rates (76%) while maintaining a high-level patient’s autonomy. All hemorrhagic events occurred during the first 4 years after the initial GKRS. In cases with epilepsy, there was 84.6% seizure free at last follow-up. Permanent morbidity was reported in only 4.6%.

Predictors of Stroke Following Initial Intervention in the ARUBA Trial

Predictors of Stroke Following Initial Intervention in the ARUBA Trial

Decision-Making for Patients With Cerebral Arteriovenous Malformations.

Cerebral arteriovenous malformations (AVMs) are a complex and heterogeneous pathology which require an understanding of the natural history of these lesions, as well as the potential treatment options in order to manage them safely. While treatment is the agreed upon strategy for most ruptured AVMs, the management of unruptured AVMs continues to be debated. More recently, this debate has been fueled by the A Randomized Trial of Unruptured Arteriovenous Malformations (ARUBA) trial which attempts to define the natural history and treatment risk of AVMs. However, the trial has significant shortcomings which limit its broad applicability. In addition, the breadth, efficacy, and safety of potential treatment options continue to improve. This review focuses on defining the natural history of cerebral AVMs, an overview of the ARUBA trial, and the most current treatment paradigm for cerebral AVMs.

Longitudinal Findings from ARUBA Trial for Unruptured AVM Still Favor Medical Management over Interventional Therapy

Longitudinal Findings from ARUBA Trial for Unruptured AVM Still Favor Medical Management over Interventional Therapy

Liquid embolic agent Fe3O4-EVOH for endovascular arteriovenous malformation embolisation: Preliminary evaluation in an in vivo swine rete mirabile model.

Arteriovenous malformation (AVM) embolisation is in peril after the ARUBA trial. Advancements that are needed to reduce procedural risk are better control and visualisation during micro-catheter injection of liquid embolic material. The injectability, radiographic visualisation, mechanical stability and biocompatibility of the embolic agent Fe3O4-EVOH was evaluated in an in vivo swine AVM model. The swine AVM model is the rete mirabile (RM). Nine swine AVM models were embolised with the embolic agent Fe3O4-EVOH by using a 1.5 F micro-catheter. Procedure times, embolisation success (defined as complete embolisation of the nidus), volume of embolic agent and histopathology were assessed. Six swine underwent embolisation of one side rete, and three underwent embolisation of both sides. We did not experience any technical complication during embolisation of each rete. The micro-catheter was easy to retrieve. Fluoroscopic visualisation of the Fe3O4-EVOH cast was adequate. The mean embolisation time for each RM was 7.5 minutes. The median volume of the embolic agent for each RM was 0.52 mL. At one, four and eight weeks following injection, microscopic and histological analysis demonstrated minimal inflammatory changes in the perivascular tissues and permanent occlusion of the embolised vasculature. Fe3O4-EVOH embolic agent is an effective endovascular occlusion material, providing the initial in vivo characteristics of stability and biocompatibility.

Microsurgery for Unruptured Cerebral Arteriovenous Malformations in the National Inpatient Sample is More Common Post-ARUBA

The ARUBA trial (A Randomized Trial of Unruptured Brain Arteriovenous Malformations) was the first randomized control trial to investigate unruptured cerebral arteriovenous malformation (cAVM) treatments and concluded that medical management was superior to interventional therapy for the treatment of unruptured cAVMs. This conclusion generated considerable controversy and was followed by rebuttals and meta-analyses of the ARUBA methodology and results. We sought to determine whether the ARUBA results altered treatment trends of cAVMs within the United States. Using the National Inpatient Sample, the largest all-payer inpatient care database within the United States, we isolated patients who were admitted on an elective basis for cAVM treatment and determined the treatment modality undergone by these patients. The cohort was dichotomized separately at 2 ARUBA time points: the European Stroke Conference presentation in May 2013, and The Lancet publication in February2014. We found that the overall treatment rate of unruptured cAVMs decreased after both time points. However, the rate of surgical excision alone, relative to other modalities, was significantly increased, and endovascular intervention demonstrated a nonsignificant decrease. Our findings suggest that the ARUBA trial has influenced unruptured cAVM treatment patterns within the United States. Although the overall treatment rate has decreased, unruptured cAVMs, when treated post-ARUBA, are most commonly approached with surgical excision alone.

Basic research and surgical techniques for brain arteriovenous malformations.

Arteriovenous malformations (AVMs) are hemorrhagic vascular diseases in which arteries and veins are directly connected with no capillary bed between the two. We herein introduce the results of basic research of this disease and surgical techniques based on our data and experiences. The results obtained from our research show that cell death- and inflammation-related molecules changed or became activated compared with control specimens. These findings indicate that chronic inflammation occurs in and around the nidus of AVMs. Various molecules are involved in the mechanisms of cell death and angiogenesis during this process. Confirmation of blood flow in the nidus is very important to avoid hemorrhagic complications during surgical removal of the nidus. The risk of hemorrhage increases when the blood flow in the nidus is not reduced. We reported the advantages of serial indocyanine green videoangiography, which is used to assess the blood flow during AVM nidus removal. Since publication of the ARUBA trial and Scottish Audit, treatments with high morbidity have not been allowed. It is especially important for neurosurgeons to treat low Spetzler-Martin grade AVMs with low morbidity. J. Med. Invest. 67 : 222-228, August, 2020.

The NASSAU (New ASSessment of cerebral Arteriovenous Malformations yet Unruptured) Analysis: Are the Results From The ARUBA Trial Also Applicable to Unruptured Arteriovenous Malformations Deemed Suitable for Gamma Knife Surgery?

The optimal management of unruptured brain arteriovenous malformations (AVMs) is controversial after the ARUBA trial. To confirm or repudiate the ARUBA conclusion that "medical management only is superior to medical management with interventional therapy for unruptured brain arteriovenous malformations." Data were collected from 1351 patients treated with Gamma Knife Surgery (GKS; Elekta AB, Stockholm, Sweden) for unruptured and untreated AVMs The follow-up was 8817 yr (median 5.0 and mean 6.5). The results of the analyses were compared to that found in patients randomized to medical management only in the ARUBA trial and extrapolated to a 10-yr time period. Our data were also compared to the natural course in a virtual AVM population for a 25-yr time period. The incidence of stroke was similar among ARUBA and our patients for the first 5 yr. Thereafter, the longer the follow-up, the relatively better outcome following treatment. Both the mortality rate and the incidence of permanent deficits in patients with small AVMs were the same as in untreated patients for the first 2 to 3 yr after GKS, after which GKS patients did better. Patients with large AVMs had a higher incidence of neurological deficits in the first 3 yr following GKS. The difference decreased thereafter, but the time until break even depended on the analysis method used and the assumed risk for hemorrhage in patent AVMs. The ARUBA trial conclusion that medical management is superior to medical management with interventional therapy for all unruptured AVMs could be repudiated.

Abstract TP587: Microsurgery Treatment Rate for Unruptured Cerebral Arteriovenous Malformations is Increased post-ARUBA

Background: The ARUBA trial reported medical management was superior to intervention for unruptured cerebral arteriovenous malformations (cAVMs); however, open excision was underrepresented in the intervention arm. We investigated whether the ARUBA trial results influenced treatment modality rates for unruptured cAVMs within the United States. Methods: We queried the National Inpatient Sample (NIS), the largest all-payer inpatient care database in the United States, and identified 2,028 patients that underwent treatment for unruptured cAVMs between January 2011 and September 2015. All screened subjects had AVM ICD-9-CM diagnosis code 747.81 (anomalies of cerebrovascular system) and were excluded based on hemorrhage codes 430 (SAH) and/or 431 (ICH). ICD-9-CM principal procedure codes were used to identify treatment modalities: endovascular (39.72), open excision (01.59), and stereotactic radiosurgery (SRS) (92.30-.39). Univariate logistic regression was used to compare treatment rates for each modality before and after two ARUBA time points: 1) European Stroke Conference (ESC) presentation May 2013 and 2) The Lancet publication February 2014. Results: When unruptured cAVMs were treated, the rate of open excision was greater after, compared to before, the May 2013 ARUBA presentation (OR 1.22, p<0.05). Additionally, a trend for open excision was noted using the February 2014 publication date (OR 1.20, p=0.054). Endovascular and SRS did not show significant differences in treatment rates at either time point. Conclusions: Unruptured cAVMs within the NIS database that underwent treatment had open excision significantly more after, compared to before, the ARUBA results were presented at the ESC. When using The Lancet publication date, a non-significant trend for open excision was noted but likely resulted from insufficient numbers in the post-Lancet publication group. Our findings suggest that the ARUBA trial has influenced current treatment modality rates for unruptured cAVMs captured within the NIS.

Uptake and radiological findings of screening cerebral magnetic resonance scans in patients with hereditary haemorrhagic telangiectasia.

Hereditary haemorrhagic telangiectasia (HHT) results in arteriovenous malformations (AVMs), most commonly in the lungs, liver and brain. Discussion of cerebral vascular malformations is an important element of patient management. The current study objectives were to examine uptake and results of screening cerebral magnetic resonance (MR) scans, excluding symptomatic patients requiring neurological investigations. The remaining non-symptomatic individuals received formal pretest counselling that differed according to family history. For the 603 patients with no neurological symptoms of concern, screening scan uptake was higher after publication of the ARUBA trial. Patients with a family history of cerebral haemorrhage were 4 to 14-fold more likely to have a screening scan than patients with no such family history. For patients without neurological symptoms suggesting cerebral AVMs, none of the 59 screening scans performed at our institution demonstrated a cerebral AVM. Four scans (6.8%) demonstrated small aneurysms. The most common abnormality was cerebral infarction (20/59, 33.9%), predominantly identified in patients with pulmonary AVMs. Of 29 pulmonary AVM patients with no previous history of clinical stroke, 16 (55.2%) had between one and five silent infarcts. For HHT patients with pulmonary AVMs, the most frequently affected sites were the cerebellum (40%) and thalamus (14.3%), and the age-adjusted odds ratio for an infarct was 21.6 (95% confidence intervals 3.7, 126), p = 0.001. We concluded that for cerebral screening programmes in HHT, the findings support informed patient choice incorporating understanding that cerebral AVMs are rare in non-symptomatic HHT patients, but that screening scans commonly detect silent cerebral infarction due to pulmonary AVMs.