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.

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.

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.

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.

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.

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.

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.

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.

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

BACKGROUND AND PURPOSE: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Early Rebleeding after Brain Arteriovenous Malformation Rupture, Clinical Impact and Predictive Factors: A Monocentric Retrospective Cohort Study.

BACKGROUND: Brain arteriovenous malformations (BAVMs) are a leading cause of intracranial hemorrhage in young adults. This study aimed to identify individual predictive factors of early rebleeding after BAVM rupture and determine its impact on prognosis. METHODS: Early rebleeding was defined as a spontaneous intracranial hemorrhage within 30 days of BAVM rupture in patients with nonobliterated BAVMs. One hundred fifty one patients with 158 BAVM hemorrhagic events admitted to a tertiary care center during 14 years were included. Univariate followed by multivariate logistic regression was performed to assess the impact of early rebleeding on in-hospital mortality and modified Rankin Scale (mRS) score beyond 3 months and to identify independent predictors of early rebleeding. RESULTS: Eight early rebleeding events were observed, 6 of which occurred during the first 7 days. Early rebleeding was independently and significantly associated with poor outcome (mRS ≥3 beyond 3 months, p = 0.004) but not with in-hospital mortality (p = 0.9). Distal flow-related aneurysms (p = 0.009) and altered consciousness with a Glasgow coma scale score of 3 (p = 0.01) were independently associated with early rebleeding. CONCLUSIONS: Early rebleeding is a severe complication that can occur after BAVM-related hemorrhage. Distal flow-related aneurysms and initial altered consciousness are associated with early rebleeding.

Outcome of microsurgical excision of unruptured brain arteriovenous malformations in ARUBA-eligible patients.

OBJECTIVES: To determine the outcome of microsurgical excision of selected unruptured brain arteriovenous malformations (AVMs), and to compare the results with those of the ARUBA trial. METHODS: Prospective data collection for all patients undergoing microsurgical excision of unruptured brain AVMs by two neurovascular surgeons. Outcome measures similar to those assessed in the ARUBA trial (death and stroke) as well as modified Rankin scores (mRS) at 6 months were assessed. RESULTS: Between September 2004 and September 2014, 45 patients with unruptured brain AVMs underwent microsurgical excision. 11 patients (eight children and three with mRS >2 at presentation) were excluded to match ARUBA eligibility criteria. 34 patients were included in this study. AVM characteristics closely matched those in the ARUBA trial with 70.5% Spetzler-Martin (SM) grade I or II AVMs, 68% AVM size <3 cm. However, compared to ARUBA, a larger proportion of our patients presented with seizures, and a lower proportion with headaches. 8(23%) had preoperative embolization. There were no deaths and no strokes (as defined in ARUBA). 5 (14.7%) had permanent neurological deficit related to surgery within/near eloquent cortex. At 6 months follow-up, 32 (94%) had mRS score of 0-1. Two (6%) had mRS 2 and none had mRS> 2. Postoperative digital DSA confirmed complete AVM excision in all cases. None of the patients have suffered intracranial hemorrhage during the follow-up period of 6-126 (median 69) months. CONCLUSIONS: Microsurgical excision of unruptured brain AVMs can be performed with low morbidity in selected cases. Our study has limitations particularly the small number of patients with selected AVMs for microsurgical excision. However, our results suggest that ARUBA results may not be applicable to microsurgical excision when cases are appropriately selected for this treatment modality.

Stereotactic radiosurgery of intracranial arteriovenous malformations and the use of the K index in determining treatment dose.

OBJECT: The appropriate dose during stereotactic radiosurgery (SRS) of cerebral arteriovenous malformations (AVMs) remains a matter of debate. In the present study, the authors retrospectively evaluated the association of using a prescribed dose calculated utilizing the K index with the obliteration rate of cerebral AVMs after SRS. METHODS: The authors performed a retrospective analysis of the Cleveland Clinic SRS database. All patients undergoing Gamma Knife radiosurgery for cerebral AVMs from 1997 to 2010 were selected. Regression techniques and Kaplan-Meier analyses were used to investigate the effect of divergence from the optimal K index dose on the rate of AVM obliteration. RESULTS: In the study period 152 patients (mean age 43.6 years; 53.9% of treatments were performed in females) underwent 165 Gamma Knife radiosurgery treatments for AVMs. In a univariate analysis Spetzler-Martin grade (OR 0.63 [95% CI 0.42-0.93]), higher AVM score (OR 0.43 [95% CI 0.27-0.70]), larger AVM volume (OR 0.88 [95% CI 0.82-0.94]), and higher maximum diameter (OR 0.56 [95% CI 0.41-0.77]) were associated with a lower rate of AVM obliteration. Higher margin dose (OR 1.16 [95% CI 1.08-1.24]) and higher maximum dose (OR 1.08 [95% CI 1.04-1.13]) were associated with a higher obliteration rate. To further examine the effect of prescribed dose divergence from the calculated K index dose, cases were classified to groups depending on the AVM volume and dose variance from the ideal K index dose. Contingency tables and Kaplan-Meier curves were then created, and no significant differences in rates of obliteration were noted among the different groups. CONCLUSIONS: Gamma Knife radiosurgery for cerebral AVMs remains an effective and safe treatment modality. Smaller AVMs may receive doses less than the calculated K index dose without an apparent effect on obliteration rates.

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.

The risk of stroke or clinical impairment after stereotactic radiosurgery for ARUBA-eligible patients.

BACKGROUND AND PURPOSE: The best management of patients with unruptured brain arteriovenous malformations (BAVM) is controversial. In this study, we analyzed the stroke rate and functional outcomes of patients having stereotactic radiosurgery (SRS) for unruptured BAVM using the same eligibility criteria and primary end points as the ARUBA trial. METHODS: Retrospective observational study of 174 ARUBA-eligible patients having SRS from 1990 to 2005. RESULTS: The median follow-up after SRS was 64 months. Fifteen patients (8.7%) had a hemorrhagic stroke at a median of 21 months after SRS. Six patients (3.5%) had a focal neurological deficit and 4 patients died (2.3%). The risk of stroke or death was 10.3% at 5 years and 11.5% at 10 years. Twelve additional patients (6.9%) had a focal neurological deficit from either radiation-related complications (n=7) or subsequent resection (n=5). The risk of patients' having clinical impairment (modified Rankin Score ≥ 2) was 8.4% at 5 years and 12.0% at 10 years. Increasing BAVM volume was associated with both stroke or death (hazard ratio=1.06; 95% confidence interval, 1.0-1.11; P=0.04) and clinical impairment (hazard ratio=1.06; 95% confidence interval, 1.01-1.09; P=0.01). The 10-year risk of stroke or death and clinical impairment for patients with BAVM ≤ 5.6 cm(3) was 5% and 4%, respectively. CONCLUSIONS: The observed risk of stroke or death after SRS was approximately 2% per year for the first 5 years after SRS, declining to 0.2% annually for years 6 to 10. Patients with small volume BAVM may benefit from SRS compared with the natural history of unruptured BAVM over the planned follow-up interval of the ARUBA trial (5-10 years).

Venous angioarchitectural features of intracranial dural arteriovenous shunt and its relation to the clinical course.

INTRODUCTION: The aim of this study is to assess the relationship between the venous angioarchitectural features and the clinical course of intracranial dural arteriovenous shunt (DAVS) with cortical venous reflux (CVR). METHODS: With institutional review board approval, 41 patients (M:F = 24:17; median age, 52 years (range, 1-72 years), median follow-up; 1.5 years; partial treatment, n = 36) with persistent CVR were included. We evaluated the initial presentation and the incidence of annual morbidity (hemorrhage or new/worsened nonhemorrhagic neurological deficit (NHND)) according to the venous angiographic patterns-isolated venous sinus, occlusion of the draining sinus, direct pial venous drainage, pseudophlebitic pattern, venous ectasia, brisk venous drainage, and length of pial vein reflux-on digital subtraction angiography. Cox regression was performed to identify independent factors for clinical course. RESULTS: During 111.9 patient-years of follow-up, the overall annual morbidity rate was 11.6 % (mortality; n = 3, rate; 2.6 %/year). Hemorrhage occurred in five patients (12.2 %, rate; 4.5 %/year) and new/worsened NHND occurred in eight patients (19.5 %, rate; 7.2 %/year). Patients with isolated venous sinus, direct pial venous drainage, and pseudophlebitic pattern were associated with initial aggressive presentation. Venous ectasia was associated with initial hemorrhagic presentation. Brisk venous drainage was associated with initial benign presentation. Patients with isolated venous sinus showed a poor clinical course with a higher annual incidence of hemorrhage or new/worsened NHND (91.2 %/year vs 9.2 %/year; hazard ratio, 6.681; p = 0.027). CONCLUSIONS: Venous angioarchitectural features may be predictive of the clinical course of DAVSs. DAVS patients with isolated venous sinus may be especially at high risk for future aggressive clinical course.

Long-term results of radiosurgery for cerebral arteriovenous malformations.

BACKGROUND: Stereotactic radiosurgery (SRS) is known to safely result in a high obliteration rate for small and medium sized arteriovenous malformations (AVM). OBJECTIVE: To evaluate the long-term outcome of patients treated with SRS, with special emphasis given to obliteration and toxicity rates. METHODS: We performed a review of 43 cerebral AVM patients, treated from 1998 to 2008 with a single SRS dose ranging from 21-25 Gy. Of these, 37 had a minimal follow-up of one year. Medical files were reviewed to assess patient and AVM characteristics, the SRS treatment, therapy prior to SRS, the obliteration rate and toxicities. Whenever necessary, outcome data was supplemented by telephone interviews with the patient or treating physician. RESULTS: AVM size was ≥3cm in diameter in 21% of patients. Five patients (11.6%) underwent surgery prior to SRS and 31 patients (72.1%) received one or more embolizations prior to SRS. Of the patients followed with angiography ≥1 year post-SRS, 89% (33/37) had a complete obliteration of the nidus, after a median time of 24.7 months post-treatment. Embolization prior to SRS was not predictive of outcome. One patient suffered a non-fatal haemorrhage between treatment and obliteration. The rate of symptomatic radiation-induced radiological changes was 8.1%. CONCLUSION: Our study shows both obliteration and complication rates in the upper limit of those reported in the literature. SRS seems an attractive treatment option for small AVMs. Unlike other reports, the prior use of embolization did not impact negatively on obliteration rates.

Age-dependent lethality in novel transgenic mouse models of central nervous system arteriovenous malformations.

BACKGROUND AND PURPOSE: The lack of an appropriate animal model has been a limitation in studying hemorrhage from arteriovenous malformations (AVMs) in the central nervous system. METHODS: Novel mouse central nervous system AVM models were generated by conditionally deleting the activin receptor-like kinase (Alk1; Acvrl1) gene with the SM22-Cre transgene. All mice developed AVMs in their brain and/or spinal cord, and >80% of them showed a paralysis or lethality phenotype due to internal hemorrhages during the first 10 to 15 weeks of life. The mice that survived this early lethal period, however, showed significantly reduced lethality rates even though they carried multiple AVMs. RESULTS: The age-dependent change in hemorrhage rates allowed us to identify molecular factors uniquely upregulated in the rupture-prone AVM lesions. CONCLUSIONS: Upregulation of angiopoietin 2 and a few inflammatory genes were identified in the hemorrhage-prone lesions, which may be comparable with human pathology. These models will be an exceptional tool to study pathophysiology of AVM hemorrhage.

Microsurgical treatment of the interhemispheric arteriovenous malformations.

From a total of 364 patients who underwent surgery for AVMs, 46 (12.63%) had lesions located interhemispherically. The majority of patients have entered the 4th and 5th age decade. The youngest operated patient was 18 years old and the oldest was 64. The most frequent clinical signs encountered were headaches (13 - 28.2%), epilepsy (21 - 45.65%), motor deficits (12 - 26.08%), sensitivity disorders (8 - 17.39%), speech disabilities (4 - 8.69%), visual field deficits (3 - 6.52%), mental disorders (5 - 10.85%) and alteration of consciousness (4 - 8.69%).The initial imagistic examination consisted of a noncontrast computed tomographic scan, followed by a magnetic resonance angiography (MRA) and a digital subtraction angiography. We included the 46 patients into the Spatzler-Martin scale based on the location, the proximity to the eloquent areas, as well as on the type of the venous drainage. Next we show the number of patients included in every grade of the scale. Grade I - 7 (15.21%) patients, Grade II - 17 (36.95%) patients, Grade III - 19 (41.30%) patients and Grade IV - 3 (6.52%) patients. An interhemispheric surgical approach was used for these AVMs. Excellent and good postoperative results has been obtained in 37 (80.43%) patients, fair results in 5 (10.86%), poor in 2 (4.34%) and 2 (4.34%) patients have died. One of the 2 deaths was caused by a haematoma in the bed of the AVM and the other was caused by a pulmonary embolism.

[Microsurgical treatment of cerebral arteriovenous malformations in Burdenko Neurosurgical Institute (recent experience)].

Recently the number of AVM resections in Burdenko Neurosurgical Institute has been increased dramatically. Aim of this study was to assess the results of open surgery in our clinic in modern neurosurgical era. Consecutive series if 160 patients with AVM treated using microsurgical technique since 2009 till 2011 was analyzed. Spetzler-Martin score distribution was: grade I--29 (18.1%) cases, grade II--84 (52.5%), grade III--38 (23.8%), grade IV--9 (5.6%). Patients with grade V AVMs were not operated. Treatment options included: AVM resection in 143 (89.4%) cases, embolization followed by resection in 15 (9.3%) and clipping of afferents in 2 (1.3%). Glasgow outcome scale score distribution was the following: V (good recovery)--70 (43.7%), IV (moderate disability)--71 (44.4%), III (severe disability)--16 (10%), II (vegetative state)--1 (0.6%) and I (death)--2 (1.3%). Microsurgery remains the primary option for radical treatment of cerebral AVMs. Careful selection of patients and planning of surgery are crucial for good outcomes.