Trial Of Unruptured Brain Arteriovenous Malformations Research Articles

Grades of brain arteriovenous malformations and risk of hemorrhage and death.

ObjectiveTo assess the relationship of the grade of unruptured and untreated Brain Arteriovenous Malformations (AVMs), with the risk of subsequent stroke and death during follow‐up.MethodsThis prospective study was drawn from a cohort of adult patients with unruptured AVMs, who participated in the conservative treatment arm (medical management only for headache or seizures) of the randomized clinical trial of unruptured brain AVMs (ARUBA study). The grade of AVMs (Spetzler–Martin scale) was dichotomized into categories: AVMs of grades I and II were considered low grade; AVMs of grades III and IV were considered high grade. There were no grade V AVM patients in ARUBA. The primary outcome was symptomatic stroke (hemorrhagic or ischemic – documented by imaging) or death.ResultsThe conservative treatment group had 123 patients (“as treated” analysis). 71 (57.7%) had lesions characterized for this analysis as low‐grade lesions and 52 (42.2%) as high grade. From the total of 10 (8.13%) primary outcomes, three occurred (4.22%) in low‐grade AVMs and seven (13.46%) in high‐grade AVMs (P = 0.0942).InterpretationStatistical analysis of the cohort of patients with unruptured and untreated AVMs from ARUBA study showed that the graduation categories (Spetzler–Martin grades) were not associated with the outcome of subsequent stroke or death.

Multicenter assessment of morbidity associated with cerebral arteriovenous malformation hemorrhages.

The optimal management strategy for unruptured cerebral arteriovenous malformations (AVMs) is controversial since the ARUBA trial (A Randomized trial of Unruptured Brain AVMs). An accurate understanding of the morbidity associated with AVM hemorrhages may help clinicians to formulate the best treatment strategy for unruptured AVMs. To determine the morbidity associated with initial cerebral AVM rupture in patients presenting to tertiary medical centers. Retrospective chart reviews from three tertiary academic medical centers were performed for the period between 2008 and 2014. All patients admitted with intracranial hemorrhage due to untreated AVMs were included in this study. Patient-specific variables, including demographics, imaging characteristics, neurologic examination results, and clinical outcome, were analyzed and recorded. 101 Patients met the inclusion criteria. Admission National Institutes of Health Stroke Scale (NIHSS) scores were 0, 1-9, and ≥10 in 26%, 29%, and 45% of patients, respectively. Hematoma locations were subarachnoid, intraventricular, intraparenchymal, and combined in 5%, 11%, 32%, and 52% of patients, respectively. Deep venous drainage was present in 43% of AVMs; AVM-associated aneurysms were present in 44% of patients. Emergent hematoma evacuations were performed in 37% of patients and 8% of patients died while in hospital. At discharge, of those who survived, NIHSS scores of ≥1 and ≥10 were found in 69% and 23%, respectively. At the 90-day follow-up, 34% had a modified Rankin Scale (mRS) score >2. Patients with admission NIHSS score ≥10 had significantly higher rates of midline shift, surgical hematoma evacuation, and follow-up mRS ≥3 (p<0.05). The morbidity associated with cerebral AVM rupture appeared to be higher in our study than previously reported. Morbidity from AVM rupture should be considered as an important factor, together with variables such as risk of AVM rupture and procedural risk, in determining the optimal treatment strategy for unruptured cerebral AVMs.

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

The benefit of intervention for patients with unruptured cerebral arteriovenous malformations (AVMs) was challenged by results demonstrating superior clinical outcomes with conservative management from A Randomized Trial of Unruptured Brain AVMs (ARUBA). The aim of this multicenter, retrospective cohort study is to analyze the outcomes of stereotactic radiosurgery for ARUBA-eligible patients. We combined AVM radiosurgery outcome data from 7 institutions participating in the International Gamma Knife Research Foundation. Patients with ≥12 months of follow-up were screened for ARUBA eligibility criteria. Favorable outcome was defined as AVM obliteration, no postradiosurgery hemorrhage, and no permanently symptomatic radiation-induced changes. Adverse neurological outcome was defined as any new or worsening neurological symptoms or death. The ARUBA-eligible cohort comprised 509 patients (mean age, 40 years). The Spetzler-Martin grade was I to II in 46% and III to IV in 54%. The mean radiosurgical margin dose was 22 Gy and follow-up was 86 months. AVM obliteration was achieved in 75%. The postradiosurgery hemorrhage rate during the latency period was 0.9% per year. Symptomatic and permanent radiation-induced changes occurred in 11% and 3%, respectively. The rates of favorable outcome, adverse neurological outcome, permanent neurological morbidity, and mortality were 70%, 13%, 5%, and 4%, respectively. Radiosurgery may provide durable clinical benefit in some ARUBA-eligible patients. On the basis of the natural history of untreated, unruptured AVMs in the medical arm of ARUBA, we estimate that a follow-up duration of 15 to 20 years is necessary to realize a potential benefit of radiosurgical intervention for conservative management in unruptured patients with AVM.

Current surgical results with low-grade brain arteriovenous malformations.

Resection is an appealing therapy for brain arteriovenous malformations (AVMs) because of its high cure rate, low complication rate, and immediacy, and has become the first-line therapy for many AVMs. To clarify safety, efficacy, and outcomes associated with AVM resection in the aftermath of A Randomized Trial of Unruptured Brain AVMs (ARUBA), the authors reviewed their experience with low-grade AVMs-the most favorable AVMs for surgery and the ones most likely to have been selected for treatment outside of ARUBA's randomization process. A prospective AVM registry was searched to identify patients with Spetzler-Martin Grade I and II AVMs treated using resection during a 16-year period. Of the 232 surgical patients included, 120 (52%) presented with hemorrhage, 33% had Spetzler-Martin Grade I, and 67% had Grade II AVMs. Overall, 99 patients (43%) underwent preoperative embolization, with unruptured AVMs embolized more often than ruptured AVMs. AVM resection was accomplished in all patients and confirmed angiographically in 218 patients (94%). There were no deaths among patients with unruptured AVMs. Good outcomes (modified Rankin Scale [mRS] score 0-1) were found in 78% of patients, with 97% improved or unchanged from their preoperative mRS scores. Patients with unruptured AVMs had better functional outcomes (91% good outcome vs 65% in the ruptured group, p = 0.0008), while relative outcomes were equivalent (98% improved/unchanged in patients with ruptured AVMs vs 96% in patients with unruptured AVMs). Surgery should be regarded as the "gold standard" therapy for the majority of low-grade AVMs, utilizing conservative embolization as a preoperative adjunct. High surgical cure rates and excellent functional outcomes in patients with both ruptured and unruptured AVMs support a dominant surgical posture for low-grade AVMS, with radiosurgery reserved for risky AVMs in deep, inaccessible, and highly eloquent locations. Despite the technological advances in endovascular and radiosurgical therapy, surgery still offers the best cure rate, lowest risk profile, and greatest protection against hemorrhage for low-grade AVMs. ARUBA results are influenced by a low randomization rate, bias toward nonsurgical therapies, a shortage of surgical expertise, a lower rate of complete AVM obliteration, a higher rate of delayed hemorrhage, and short study duration. Another randomized trial is needed to reestablish the role of surgery in unruptured AVM management.

Management of perisylvian arteriovenous malformations: a retrospective institutional case series and review of the literature.

Sylvian arteriovenous malformations (sAVMs) are challenging lesions of the central nervous system. The natural history of these unique lesions as well as clinical outcomes following treatment of sAVMs has been limited to case series owing to the rarity of these lesions. The authors present their experience with sAVMs and review the literature. In accordance with the Henry Ford Institutional Review Board, medical records of patients with sAVMs treated from 2000 to 2012 were reviewed. Clinical data were retrospectively collected to calculate pre- and posttreatment modified Rankin Scale scores for all patients. The authors identified 15 patients with sAVMs who received treatment. Of these, 12 were female and 3 were male, and the average age at presentation was 39.6 ± 12.94 years (± SD). Two patients (13.3%) had Spetzler-Martin Grade I lesions, 6 patients (40%) had Grade II lesions, 5 patients (33.3%) had Grade III lesions, and another 2 (13.3%) harbored Grade IV arteriovenous malformations (AVMs). According to the Sugita classification, 6 patients (40%) had medial lesions, 6 (40%) had lateral lesions, 2 (13.3%) had deep lesions, and 1 patient (6.67%) had a pure sAVM. Eight patients (53.3%) underwent stereotactic radiosurgery while 7 patients (46.7%) had microsurgical resection; 1 patient underwent surgical extirpation after incomplete response following radiosurgery. After treatment, 9 patients were unchanged from pretreatment (60%), 3 patients worsened, and 2 patients had improved functional outcome (20% and 13.3%, respectively). The authors' literature search yielded 348 patients with sAVMs, most of them harboring Spetzler-Martin Grade II and III lesions. Approximately 98% of the patients underwent resection with excellent outcomes. While the ideal choice of therapeutic modality for cerebral AVMs remains controversial in light of the recent publication of the ARUBA (A Randomized trial of Unruptured Brain AVMs) trial, a multidisciplinary treatment approach for the management of sAVMs can lead to acceptable neurological outcome.

Treatment of arteriovenous malformations of the brain

The treatment of ruptured and unruptured brain arteriovenous malformations (AVMs) is driven by the need to prevent incident or recurrent intracranial hemorrhages. Improving feasibility of the rapidly developing endovascular, neurosurgical, and radiotherapeutic procedures leads to invasive treatment of an increasing number of neurologically intact patients with accidentally diagnosed AVMs. Recent data confirm that the natural history risk of unruptured AVMs is significantly lower than the risk of those presenting with rupture, and the treatment risk of invasive management of unruptured AVMs seems higher than their natural history risk. The treatment decision algorithm for these patients remains unsettled, as no randomized clinical trial data exist on the benefit of invasive AVM treatment for patients with bled or with unbled AVMs. The recently launched study A Randomized Trial of Unruptured Brain AVMs (ARUBA) will be the first trial randomizing patients with nonhemorrhaged AVMs to invasive versus conservative management.

Invasive treatment of unruptured brain arteriovenous malformations is experimental therapy

Brain arteriovenous malformations (AVMs) are currently being treated in a variety of ways, including medical management, endovascular procedures, neurosurgery and radiotherapy. The widespread diffusion of these various treatment approaches is partially driven by the existence of variations in the perception about the risks of rupture, and how devastating such events would be. Data from the most recent studies suggest the majority of AVM patients are diagnosed without signs of hemorrhage, further, that the natural history risk for the unruptured cohort is far more benign than for those presenting with rupture. In cases where hemorrhage occurs, the clinical syndrome is significantly less disabling than in patients with non-AVM related hemorrhage. For unruptured AVMs, current morbidity data suggest a higher risk for invasive management than for the natural history of untreated patients. No randomized clinical trial data exist on the benefit of invasive AVM treatment, and the most contentious issue at present is whether intervention should be considered for AVMs that have not bled. In a scientific sense, invasive treatment for unruptured brain AVMs may be considered experimental therapy awaiting the results from 'A Randomized Trial of Unruptured Brain AVMs' (ARUBA), which is currently underway.

ARUBA – A Randomized Trial of Unruptured Brain AVMs

Rationale: Current invasive treatment for brain arteriovenous malformations (AVMs) is varied and includes endovascular procedures, neurosurgery, and radiotherapy alone and in combination, largely dependent on the decisions of the local clinical team. However, no controlled treatment data on invasive AVM therapy exist and recent data raise serious doubt about the treatment benefit for unruptured brain AVMs. We propose a randomized treatment trial testing the hypothesis that medical management improves long-term outcomes of patients with unruptured AVMs compared to invasive treatment.