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

Background and Purpose: 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. Methods: 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. Results: 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, 1.23­15.9], P=0.02) and Spetzler-Martin grades 2 and 3 arteriovenous malformation (adjusted odds ratio, 7.76 [95% CI, 1.20­50.3], P=0.03; 9.64 [95% CI, 1.36­68.4], 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, 0.04­0.82], P=0.02). Conclusions: 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.

Risk of Seizures after Endovascular Management of Ruptured Intracranial Aneurysms: A Systematic Review and Meta-analysis.

Seizures in aneurysmal subarachnoid haemorrhage (aSAH) have been described secondary to SAH, changes in cortical function, vasospasm and as a result of treatment effects. Seizures are one of the important clinical determinants in neurological outcome of aSAH. Various studies support the notion of less risk of future seizures in endovascular treatment as compared to the microsurgical clipping, yet there is no conclusive evidence in favour or against the seizure occurrence in aSAH patients after endovascular treatment as compared to the microsurgical treatment. To carry out a systematic review and meta-analysis of the risk of seizures after endovascular management (coiling) of ruptured intracranial aneurysms. A literature search was performed in electronic database of PubMed, MEDLINE, Embase, and Scopus from inception to February 2020, using the terms Seizure, Intracranial aneurysms, embolization, with no constraints applied. Data were pooled using a random-effect model, results were abstracted as odds ratios (ORs) and 95% confidence interval (CI), and heterogeneity was reported as Chi-square. Five studies involving 3,077 patients were included in the meta-analysis. After endovascular management of aSAH, seizure risk was increased by a worse clinical severity (World Federation of Neurosurgery scale or Hunt and Hess) (OR, 3.34; 95% CI, 2.69-4.16; p<0.00001), severe vasospasm (OR, 2.20; 95% CI, 1.67-2.92; p<0.00001), cerebral infarction (OR, 5.19; 95% CI, 3.23-8.35; p<0.00001), and cerebral edema (OR, 1.79; 95% CI, 1.37-2.34; p<0.0000). Worse clinical severity, vasospasm, cerebral infarction and cerebral oedema are significant risk factors for the development of seizures after endovascular intervention in aSAH. The mechanism for this correlation is not clear.

Sex Differential in 15-Hydroxyprostaglandin Dehydrogenase Levels in the Lumen of Human Intracranial Aneurysms.

BACKGROUND: Aspirin is a promising medical therapy for the prevention of intracranial aneurysm (IA) rupture. Recently, we found that men have a better response to aspirin than women. The purpose of this study was to determine whether a sex differential exists in the level of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in the lumen of human IAs. METHODS AND RESULTS: Consecutive patients undergoing coiling or stent-assisted coiling for a saccular IA at our institution were enrolled. Two samples (A and B) were collected from IA lumens, and the plasma level of 15-PGDH was measured using an ELISA-based method. The study included 38 patients, with 20 women and 18 men. Women and men were comparable on baseline characteristics. The mean plasma concentration of 15-PGDH did not differ statistically between sample A (62.8±16.2 ng/mL) and sample B (61.8±17.9 ng/mL; 95% confidence interval -6.6 to 9.4). The mean plasma concentration of 15-PGDH in IA lumens of samples A and B was significantly higher in men (73.8±13.5 ng/mL) than women (49.6±7.8 ng/mL; P<0.0001). CONCLUSIONS: Higher enzyme levels of 15-PGDH exist in the lumen of IAs of men compared with women. This observation could explain why aspirin confers better protection against IA rupture in men than in women. The susceptibility of an individual to aspirin may differ according to the level of 15-PGDH.

Stereotactic Radiosurgery for ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations)-Eligible Spetzler-Martin Grade I and II Arteriovenous Malformations: A Multicenter Study.

OBJECTIVE: ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations) found better short-term outcomes after conservative management compared with intervention for unruptured arteriovenous malformations (AVMs). However, because Spetzler-Martin (SM) grade I-II AVMs have the lowest treatment morbidity, sufficient follow-up of these lesions may show a long-term benefit from intervention. The aim of this multicenter, retrospective cohort study is to assess the outcomes after stereotactic radiosurgery (SRS) for ARUBA-eligible SM grade I-II AVMs. METHODS: We pooled SRS data for patients with AVM from 7 institutions and selected ARUBA-eligible SM grade I-II AVMs with ≥12 months follow-up for analysis. Favorable outcome was defined as AVM obliteration, no post-SRS hemorrhage, and no permanently symptomatic radiation-induced changes. RESULTS: The ARUBA-eligible SM grade I-II AVM cohort comprised 232 patients (mean age, 42 years). The mean nidus volume, SRS margin dose, and follow-up duration were 2.1 cm3, 22.5 Gy, and 90.5 months, respectively. The actuarial obliteration rates at 5 and 10 years were 72% and 87%, respectively; annual post-SRS hemorrhage rate was 1.0%; symptomatic and permanent radiation-induced changes occurred in 8% and 1%, respectively; and favorable outcome was achieved in 76%. Favorable outcome was significantly more likely in patients treated with a margin dose >20 Gy (83%) versus ≤20 Gy (62%; P < 0.001). Stroke or death occurred in 10% after SRS. CONCLUSIONS: For ARUBA-eligible SM grade I-II AVMs, long-term SRS outcomes compare favorably with the natural history. SRS should be considered for adult patients harboring unruptured, previously untreated low-grade AVMs with a minimum life expectancy of a decade.

Intervention for A randomized trial of unruptured brain arteriovenous malformations (ARUBA) - Eligible patients: An evidence-based review.

While intervention for ruptured arteriovenous malformations (AVMs) of the brain is typically warranted, the management of unruptured AVMs remains controversial. Despite numerous retrospective studies, only one randomized controlled trial has been conducted, comparing the role of medical management alone to medical management plus surgical and/or radiosurgical intervention in patients with unruptured AVMs: A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA). To great controversy, ARUBA concluded that medical management alone was superior to intervention for unruptured AVMs, which was subsequently challenged by various single-institution and multi-center studies analyzing outcomes of ARUBA-eligible patients. This review summarizes studies returned from a PubMed database search querying, 'ARUBA,' 'ARUBA-eligible,' 'surgery unruptured AVM,' and "radiosurgery unruptured AVM". The rates of the primary endpoint of symptomatic stroke or death were low among the analyzed studies (0-12.2%, mean 8.0%) and similar to the medically managed arm of ARUBA (10.1%). Likewise, the percentage of patients with impaired functional outcomes (modified Rankin score ≥2) in the reviewed studies was low (5.9%-13.1%; mean: 9.9%) and comparable to the 14.0% observed in the medically management arm of ARUBA. The key findings of ARUBA and subsequent work in its aftermath are overviewed and analyzed for the role of surgery and/or radiosurgery in patients with unruptured AVMs.

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

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

Treatment of small ruptured intracranial aneurysms: comparison of surgical and endovascular options.

BACKGROUND: Small intracranial aneurysms pose significant challenges to endovascular therapy. Surgical clipping is considered by many to be the preferred treatment for these lesions. We present the results of the first study comparing the 2 treatment modalities in small ruptured aneurysms. METHODS AND RESULTS: Between 2004 and 2011, 151 patients with small ruptured aneurysms (≤3 mm) were treated in our institution: 91 (60.3%) with endovascular therapy and 60 (39.7%) with surgical clipping. The surgical and endovascular groups were generally comparable with regard to baseline demographics, with the exception of larger mean aneurysm size in the endovascular group versus the surgical group (2.8 versus 2.5 mm, respectively; P<0.001) and a higher proportion of posterior circulation aneurysms in the endovascular group. Endovascular treatment failed in 9.9% of patients. Procedure-related complications occurred in 23.3% of surgical patients versus 9.8% of endovascular patients (P=0.01). Only 3.7% of patients undergoing endovascular therapy experienced an intraprocedural aneurysm rupture. There were no procedural deaths or rehemorrhages in either group. The rates of aneurysm recanalization and retreatment after endovascular therapy were 18.2% and 12.7%, respectively. Favorable outcomes (moderate, mild, or no disability) were not statistically different between the endovascular (67.1%) and surgical (56.7%) groups (P=0.3). CONCLUSIONS: Surgical clipping was associated with a higher rate of periprocedural complications, but overall disability outcomes were similar. Endovascular therapy, if technically feasible, might be a preferred option in this setting. Inclusion of patients with small aneurysms in randomized controlled trials seems feasible and will be needed to provide definitive information on the best therapeutic approach. (J Am Heart Assoc. 2012;1:e002865 doi: 10.1161/JAHA.112.002865.).