Unruptured Arteriovenous Malformations Research Articles

Abstract 52: Clinical Impairment in Patients Followed With or Without Interventional Therapy in a Randomized Trial of Unruptured Brain Avms (aruba)

Background and Purpose: A Randomized trial of Unruptured Brain Arteriovenous malformations (ARUBA) compared outcome after interventional treatment of unbled brain AVMs with medical management. Follow-up data to assess pre-specified functional impairment after primary outcome events by treatment group and exploratory analyses by Spetzler-Martin grade are presented. Methods: We examined functional impairment using the modified Rankin scale score (mRS ≥2) at the time of primary outcome (death or stroke) by treatment group, and an exploratory analysis with these outcomes by Spetzler-Martin Grade. Analyses were performed both by intention to treat (as randomized) and as treated. Results: After a median of 42 months of follow-up, the median post-primary outcome event mRS for those ‘ as randomized ’ to medical management (MM) was 2 (IQR: 1,4) versus 3 (IQR: 1,5) in the interventional therapy (IT) arm. Values for those ‘ as treated’ , were 1 (IQR: 1,5) versus 4 (IQR: 2,5). The risk of functional impairment, as measured by an mRS ≥2 after a primary outcome event, was significantly lower for patients ‘ as randomized’ to MM (8/110, 7%) compared to IT (27/116, 23%) (HR 0.26, 95%CI 0.12, 0.57), and even lower for those ‘as treated’ (4/122, 3% vs 31/104, 30%; HR 0.09, 95% CI 0.03,0.27). Spetzler-Martin Grade and primary outcome events were not associated in the medical arm (p=0.80) but were so with increasing grades in the interventional arm (p=0.0002). Conclusion: In ARUBA, a death or stroke with a significant increase in functional impairment was more common for patients undergoing preventive intervention compared to those randomized to medical management.

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.

Efficacy analysis of Onyx embolization in combination with gamma knife surgery for the treatment of intracranial arteriovenous malformation

Objective To investigate the effectiveness and safety of Onyx embolization in combination with gamma knife surgery for the treatment of intracranial arteriovenous malformations (AVMs). Methods A total of 86 patients with AVM admitted to the Neurological intervention Center, Beijing Neurosurgery Institute, Capital Medical University and treated with Onyx embolization in combination with gamma knife surgery from April 2004 to September 2011 were analyzed retrospectively. The related complications and clinical prognosis of embolization were counted and analyzed. During the embolization of AVMs, the combined high risk of bleeding (intracranial aneurysms, hemodynamic aneurysms, and AVM-related arteriovenous fistula) were assessed and embolized. According to the risk factors and embolization or not, the intracranial AVMs with high risk factors were divided into either a targeted embolization group or a non-targeted embolization group. The effect of targeted embolization on hemorrhage risk was assessed. Results The overall annual hemorrhage rate in patients with AVM was 1.66%, and the ruptured AVM was 2.26%, the unruptured AVM was 1.08%, and the annual mortality rate was 0.74%. One of 16 patients with embolization related complications had permanent neurological dysfunction. Twenty-four of 29 patients complicated with intranidal aneurysm underwent targeted embolization; 4 of 5 patients with hemodynamic aneurysm underwent targeted embolization; and 8 of 9 patients with arteriovenous fistula underwent targeted embolization. Chi square test showed that the hemorrhage complications of the targeted embolization group was significantly lower than that of the non-targeted embolization group (P<0.01). Conclusion The targeted embolization in combination with gamma knife surgery may decrease the risk of intracranial AVM hemorrhage, improve clinical prognosis and occur less permanent complications. This method is suitable for the treatment of intracranial AVMs of larger volume and those can not be cured with a single program. Key words: Intracranial arteriovenous malformations; Cerebral angiography; Radiotherapy; Hemorrhage; Postoperative complication

Involvement of the visual pathway is not a risk factor of visual field deficits in patients with occipital arteriovenous malformations: an fMRI study

Occipital arteriovenous malformations (AVMs) are still one of neurosurgery’s most intriguing and challenging pathologies. In this study, we reviewed our series of patients with occipital AVMs admitted in Beijing Tiantan Hospital from June 2013 through January 2015 and attempted to evaluate the risk factors of visual field deficits (VFDs) in these patients at presentation. Forty-two consecutive patients with occipital AVMs were included in our study. Patient parameters (age, sex, and history of hemorrhage) and AVM characteristics (size, side, venous drainage, Spetzler-Martin grade, and diffuseness) were collected. VFDs were quantified using an Octopus perimetry. Conventional MRI, blood oxygen level dependent fMRI (BOLD-fMRI) of the visual cortex, and diffusion tensor imaging (DTI) of the optic radiation were performed. The least distances from the AVM to the optic radiation (AVM-OR) and from the AVM to the visual cortex (AVM-VC) were measured. Univariate analyses were used to correlate initial VFDs with patient parameters, AVM characteristics, AVM-OR, and AVM-VC distances. VFDs were identified in 14 patients, among which 12 patients presented with a history of hemorrhage and 2 patients presented with nonhemorrhagic chronic headache. VFDs were more common (P = 0.000003) in patients with ruptured AVMs. VFD frequency was not associated with patient age, sex, and AVM characteristics (size, side, venous drainage, S-M grade, and diffuseness). Unlike other lesions involving the optic radiation and visual cortex, the frequency of VFDs in occipital AVMs did not correlate with the AVM-OR and AVM-VC distances (P = 0.640 and 0.638, respectively). A history of hemorrhage is an independent risk factor of VFDs in occipital AVMs. Most unruptured occipital AVMs may present with chronic headache and seizures other than VFDs. The distances from the AVMs to the optic radiation and the visual cortex are not associated with preexisting VFDs. Our results prompt us to probe into the plasticity of the visual pathway in patients with this congenital vascular anomaly.

Treatment of Brain AVMs (TOBAS): study protocol for a pragmatic randomized controlled trial.

BackgroundThe management of unruptured brain arteriovenous malformation (AVM) patients remains controversial. Furthermore, curative attempts to treat ruptured AVM patients have not been questioned so far, and there is a lack of prospective data on clinical results according to treatment modality. Endovascular treatment is often used aiming to improve the safety or efficacy of surgery or radiation therapy, but benefits have never been documented in a trial. A care trial context is needed to evaluate interventions at the same time they are practised.Methods/Trial designTOBAS is a pragmatic, prospective, multicenter, randomized, controlled trial and registry which offers a care trial context for brain AVM patients, including surgical resection, radiosurgery or endovascular embolization, alone or combined. The study includes two RCTs and a multimodality prospective registry. The objectives of the proposed study are to assess whether preventive interventions (surgery, embolization, radiation therapy, alone or combined), selected by the local treatment team and performed as locally practiced, randomly allocated and compared with conservative management, in unruptured brain AVM patients eligible for active or conservative management, can improve the proportion of patients having an independent outcome (modified Rankin Scale (mRS) < 3, as assessed by a standardized questionnaire administered by non-masked care personnel) at 10 years. All patients judged ineligible for randomized allocation are to be entered in a multimodal registry. The objective of a nested trial in patients with ruptured or unruptured AVMs to be treated by surgery or radiation therapy, is to assess whether pre-surgical or pre-radiation embolization, randomly allocated and compared with no embolization, can improve the proportion of patients with complete eradication of the AVM, as locally adjudicated, combined with a good clinical outcome (mRS < 3). The study will require up to 2000 patients in approximately 30 centers or more, followed for 10 years. TOBAS is registered at clinicaltrials.gov: NCT02098252 as of 25 March 2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-015-1019-0) contains supplementary material, which is available to authorized users.

Cerebral protection during neurosurgery and stroke.

This article reviews the recent evidence on perioperative neuroprotection in patients undergoing brain surgery and in patients with acute stroke. With varying degrees of success, numerous pharmacological and nonpharmacological therapies have been employed to provide neuroprotection for patients during the perioperative period and after acute ischemic stroke (IAS). Recent studies have failed to demonstrate neuroprotective effects of intraoperative remifentanil or propofol use, although hypertonic saline may provide better brain relaxation than mannitol during elective intracranial surgery for tumor. Magnesium sulfate offers no improvement in neurological outcome at 90 days after stroke. Medical management alone may be superior to medical management with interventional therapy for the prevention of death or stroke in unruptured arteriovenous malformations. In patients with IAS with a proximal vessel occlusion, small infarct core, and moderate-to-good collateral circulation, rapid endovascular treatment resulted in improved functional outcomes and reduced mortality. For endovascular clot evacuation after IAS, conscious sedation may be safer than general anaesthesia. Recent evidence provides insufficient evidence of neuroprotective strategies to guide clinical management, and more randomized clinical trials are needed to optimize patient care.

The clinical characteristics and treatment of cerebral AVM in pregnancy.

Cerebral arteriovenous malformation (AVM) in pregnancy is a complex situation and there is no agreement on its hemorrhage risk and treatment. Although studies on bleeding risk of cerebral AVMs in pregnancy are very few and there are different results between them, pregnancy will increase the hemorrhagic risk of AVM, and ruptured cerebral AVM in pregnancy should be treated actively. After intracranial hemorrhage, cerebral angiography should be performed for pregnant women shielded correctly. Cerebral angiography could clearly demonstrate the characteristics of cerebral AVM. The results from the literature show that the radiation dose of endovascular and stereotactic radiotherapy for cerebral AVM in pregnancy is below the safety value and is safe. Unruptured AVM in pregnancy, if there is no bleeding factor, such as no coexisting aneurysm, smooth venous drainage, no venous ectasia, or high risk of treatment, should be observed conservatively.

Treatment of AVM-Associated Epilepsy and the Factors Influencing Outcomes

erebrovascular etiologies, including arteriovenous malformations (AVMs), account for up to 15% cases of C epilepsy (7). The risks of hemorrhage associated with these lesions have been well documented; however, the treatment of seizures in patients harboring cerebral AVMs is less well studied (16). Epilepsy is the most common clinical manifestation of unruptured AVMs and second only to hemorrhage in those with ruptures (12). Crawford et al. (4) studied the factors associated with AVMs that increase the likelihood of seizures and found that, overall, the incidence was low, with just 6% carrying a diagnosis of epilepsy before hemorrhage. This is in contrast to prior studies that cited an incidence of 17%e40% in unruptured AVMs (11, 13). Turjman et al. (16) reported their findings on seizure risk related to the angioarchitecture of the AVMs and found that superficial location with feeding by the external carotid artery, or a temporoparietal superficial location and feeding by the middle cerebral artery, were more predictive of epilepsy, an expected result when considering that proximity to cortex results in a more epileptogenic state. Most of these patients present with a first-time seizure; however, up to 43% of patients with newly diagnosed AVMs present with recurrent seizures (9).

Prognostic role of neutrophil-to-lymphocyte ratio in patients with brain arteriovenous malformations

// Sunfu Zhang 1, * , Jing Zhang 1, * , Qingqing Ren 1, * , Min He 1, * , Baoyin Shan 1 , Yunhui Zeng 1 , Zhiyong Liu 1 , Hao Liu 1 and Jianguo Xu 1 1 Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, The First People&rsquo;s Hospital of Yibin, Sichuan, People&rsquo;s Republic of China * These authors contributed equally to this work Correspondence to: Jianguo Xu, email: jgx_2015@163.com Keywords: brain arteriovenous malformations; cerebral hemorrhage; neutrophils; lymphocytes; prognosis. Received: March 10, 2017&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: December 05, 2017&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Published: January 02, 2018 ABSTRACT Purpose: This study was to investigate the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in patients with brain arteriovenous malformations (AVMs). Materials and Methods: Patients with AVMs were retrospectively identified. A hemogram from peripheral venous blood samples was taken within 24 hours of admission. The occurrences of death or major disability were noted at the end point of 6 months and the outcome was assessed with a modified Rankin Scale score. Results: A total of 175 patients were enrolled. There were 97 (55%) patients in the ruptured AVMs group and 78 (45%) in the unruptured AVMs group. In patients with unruptured AVMs, NLR was an independent risk factor for poor outcome at 6 months ( p = .036), but not a significant predictor with a ROC area of 0.638. Whereas, NLR was higher in the patients with poor outcome in ruptured AVMs group ( p &lt; .001). The area under the curve was .864 ( P &lt; .001), and an NLR of 8.88 was identified the best discriminating variable and the best predictive cutoff value. Conclusions: NLR represented a reliable prognostic predictor for patients with ruptured AVMs. However, the NLR could not be a useful prognostic predictor for patients presented with unruptured AVMs.

Visual Field Preservation in Surgery of Occipital Arteriovenous Malformations: A Prospective Study

We reviewed our prospective study of patients with occipital arteriovenous malformations (AVMs) to assess whether the display of optic radiation diffusion tensor imaging (DTI) during neuronavigation-guided surgery can reduce the severity of postoperative visual field deficits (VFDs) and to evaluate the factors associated with visual field preservation. Forty-six consecutive patients with occipital AVMs were randomized in our study. DTI of the optic radiation was displayed during neuronavigation surgery in 24 patients. The other 22 patients were treated surgically without neuronavigation. Modified Rankin Scale (mRS) scores and visual fields were evaluated preoperatively, immediately after surgery, and at the last follow-up. The patients' baseline characteristics and AVM features were statistically similar between the 2 surgical groups. The postoperative obliteration rate was 100%. The postoperative mRS scores did not differ between the 2 groups (P > 0.05). Preexisting VFDs were more common (P = 0.00004) in patients who bled than in those with unruptured AVMs. The application of DTI-incorporated neuronavigation reduced the frequency and severity of postoperative VFDs (P = 0.013 and 0.001, respectively). Visual fields were more likely to be preserved in patients with an AVM >5 mm from the optic radiation (P = 0.025). A history of hemorrhage is an independent risk factor for VFDs associated with occipital AVMs. Although not showing superiority in postoperative mRS, functional MRI navigation-guided surgery may help to radically resect occipital AVMs and preserve patient visual fields. A 5-mm distance from the optic radiation may be a suitable safety margin for visual field preservation.

Acute rupture of a feeding artery aneurysm after embolization of a brain arteriovenous malformation

Staged endovascular embolization of large arteriovenous malformations (AVMs) is frequently performed to gradually reduce flow and prevent abrupt hemodynamic changes. While feeding artery aneurysms have been associated with increased risk of hemorrhage in the setting of AVMs, decisions regarding if and when to treat these aneurysms vary. Acute, fatal rupture of a feeding artery aneurysm following embolization of a large, unruptured AVM has been infrequently reported in the literature. A 69-year-old female presented with headache and mild left hemiparesis referable to a 5 cm right fronto-parieto-temporal AVM with surrounding vasogenic edema. The AVM was associated with numerous bilateral feeding artery aneurysms (the largest was a 2 cm right middle cerebral artery (MCA) bifurcation aneurysm). There was also a large, partially thrombosed venous varix. Staged embolization of the AVM was performed. Several hours after the third stage of her embolization, she became obtunded, with a fixed and dilated right pupil. Head computed tomography (CT) showed a large intraparenchymal hemorrhage with midline shift in the right sylvian fissure, remote from the AVM nidus. She was taken to surgery for a decompressive craniectomy and hematoma evacuation. The MCA aneurysm was confirmed to be the source of hemorrhage and it was clipped. Despite aggressive medical and surgical treatments, the patient died. An increase in AVM feeding artery pressure following endovascular embolization may contribute to the rupture of a feeding artery aneurysm. For this reason, treatment of large arterial aneurysms on feeding pedicles should be considered prior to embolization of the AVM nidus.

Intracranial Vascular Malformations and Epilepsy.

Among the spectrum of intracranial vascular malformations (IVMs), arteriovenous malformations (AVMs), and cavernous malformations (CCMs) are of particular importance for epilepsy. Seizures are a common mode of presentation for both conditions. Seizures may occur de novo or secondary to intracerebral hemorrhage. Timely imaging is thus crucial for patients with seizures and AVMs or CCMs. Patients with a first-ever AVM- or CCM-related seizure can now be considered to have epilepsy according to the International League Against Epilepsy criteria. Observational studies and case series suggest that between 45 to 78% of patients with AVM-related epilepsy and 47 to 60% of patients with CCM-related epilepsy may achieve seizure freedom through antiepileptic drugs (AEDs) alone. Invasive procedures are available although current evidence suggests that epilepsy-specific preintervention evaluations are underused. Randomized controlled trials and population-based studies have demonstrated worse short-term functional outcomes after routine intervention on unruptured AVMs or CCMs when compared with conservative management. The role of invasive therapy for IVM-related epilepsy has yielded mixed results. Case series have reported high estimates of seizure freedom although these results have not been replicated in controlled observational studies. Randomized controlled trials of immediate invasive therapy versus conservative management, in addition to usual care with AEDs and of different types of treatment and their timing, are warranted for AVMs and CCM-related epilepsy.

The clinical characteristics and treatment of cerebral AVM in pregnancy.

Cerebral arteriovenous malformation (AVM) in pregnancy is a complex situation and there is no agreement on its hemorrhage risk and treatment. Although studies on bleeding risk of cerebral AVMs in pregnancy are very few, and they provide different results, pregnancy will increase the hemorrhagic risk of AVM and ruptured cerebral AVM in pregnancy should be actively treated. After intracranial hemorrhage, cerebral angiography should be performed for pregnant women shielded correctly. Cerebral angiography could clearly demonstrate the characteristics of cerebral AVM. Results from the literature show that the radiation dose of endovascular and stereotactic radiotherapy for cerebral AVM in pregnancy was below the safety value and was safe. For an unruptured AVM in pregnancy, if there are no bleeding factors, e.g. no coexisting aneurysm, smooth venous drainage, no venous ectasia, or high risk of treatment, then it should be observed conservatively.

Silent arteriovenous malformation hemorrhage and the recognition of "unruptured" arteriovenous malformation patients who benefit from surgical intervention.

Arteriovenous malformation (AVM) patients present in 4 ways relative to hemorrhage: (1) unruptured, without a history or radiographic evidence of old hemorrhage (EOOH); (2) silent hemorrhage, without a bleeding history but with EOOH; (3) ruptured, with acute bleeding but without EOOH; and (4) reruptured, with acute bleeding and EOOH. We hypothesized that characteristics and outcomes in the unrecognized group of silent hemorrhage patients may differ from those of unruptured patients. Two hundred forty-two patients operated-on since 1997 were categorized by hemorrhage status and hemosiderin positivity in this cohort study: unruptured (group 1), silent hemorrhage (group 2), and ruptured/reruptured (group 3/4). Group 3/4 was combined because hemosiderin cannot distinguish acute hemorrhage from older silent hemorrhage. Hemosiderin was found in 45% of specimens. Seventy-five patients (31.0%) had unruptured AVMs, 30 (12.4%) had silent hemorrhage, and 137 (56.6%) had ruptured/reruptured AVMs. Deep drainage, posterior fossa location, preoperative modified Rankin Scale (mRS) score, outcome, and macrophage score were different across groups. Only the macrophage score was different between the groups without clinical hemorrhage. Outcomes were better in silent hemorrhage patients than in those with frank rupture (mean mRS scores of 1.2 and 1.7, respectively). One-third of patients present with silent AVM hemorrhage. No clinical or anatomic features differentiate these patients from unruptured patients, except the presence of hemosiderin and macrophages. Silent hemorrhage can be diagnosed using magnetic resonance imaging with iron-sensitive imaging. Silent hemorrhage portends an aggressive natural history, and surgery halts progression to rerupture. Good final mRS outcomes and better outcomes than in those with frank rupture support surgery for silent hemorrhage patients, despite the findings of ARUBA.

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.

Abstract 190: Hemorrhage of Cerebral Arteriovenous Malformations Significantly Alters Stereotactic Radiosurgery Outcomes

Introduction: Intracranial hemorrhage is simultaneously the most frequent and most debilitating manifestation of cerebral arteriovenous malformations (AVM), but its impact on success and complications of radiosurgery has not been rigorously assessed. In this case-control study, we define the effect of prior hemorrhage on AVM radiosurgery outcomes. Methods: From a prospective, institutional database of 1400 AVM patients treated with Gamma Knife radiosurgery, unruptured and ruptured AVMs were matched in a 1:1 fashion, blinded to outcome, based on patient demographics, prior embolization, AVM size (mean volume of unruptured AVMs 3.7 cm3 versus ruptured AVMs 3.5 cm3, P=0.195), Spetzler-Martin grade and radiosurgical treatment parameters (mean prescription dose for unruptured AVMs 20.9 Gy versus ruptured AVMs 21.0 Gy, P=0.837). There were 270 patients in each cohort. Matched statistical analyses were used to compare the baseline characteristics, obliteration rates, post-radiosurgery latency period hemorrhage risks, and incidences of radiation-induced changes (RIC) between the two cohorts. Results: The actuarial obliteration rates of the two cohorts were similar (unruptured AVMs: 38%, 58%, 76% at 3, 5, 10 years, respectively; ruptured AVMs: 40%, 60%, 73% at 3, 5, 10 years, respectively; P=0.592). However, for embolized AVMs, complete obliteration was more likely to be achieved in unruptured lesions (unruptured AVMs: 25%, 32%, 54% at 3, 5, 10 years, respectively; ruptured AVMs: 18%, 27%, 42% at 3, 5, 10 years, respectively; P=0.038). Prior AVM rupture resulted in a higher annual risk of post-radiosurgery latency period hemorrhage (ruptured AVMs 2.3% versus unruptured AVMs 1.1%, P=0.025) but a lower rate of cumulative and symptomatic RIC (cumulative RIC: ruptured AVMs 30.4% versus unruptured AVMs 48.9%, P&lt;0.0001; symptomatic RIC: ruptured AVMs 7.0% versus unruptured AVMs 12.2%, P=0.041, respectively). The rates of permanent RIC were similar between the unruptured (2.2%) and ruptured (1.9%) AVM cohorts (P=0.761). Conclusion: Prior AVM rupture significantly alters the risk of latency period hemorrhage and RIC following radiosurgery. These effects should be taken into consideration with the multidisciplinary management of AVM patients.

Abstract 192: Axonal Guidance Factors as Potential Pediatric AVM Urinary Biomarker

Introduction: Development of noninvasive biomarkers for pediatric arteriovenous malformations (AVMs) could improve diagnosis and identify potential therapeutic targets. The axonal guidance factor, EphrinB2, and its cognate receptor EphB4 have been implicated in AVM development. Here we report our initial experience with urinary EphrinB2 as a novel AVM-specific urinary biomarker. Hypothesis: We hypothesize that urinary and tissue levels of EphrinB2 will be elevated in patients with AVM and distinguish AVM from other cerebrovascular disease. Methods: Specimens were collected from 45 pediatric patients (0-21 years of age) including unruptured AVM (n=15), moyamoya (n=15) and age- and sex-matched controls (n=15), per an IRB-approved protocol. ELISA quantified levels of urinary EphrinB2. Matched AVM tissue from the same patient was subjected to immunohistochemistry to correlate source tissue expression with biomarker levels. Results: Statistical analysis revealed a statistically significant increase in EphrinB2 and AVM-specific biomarker fingerprints capable of discerning AVM both from controls and also from other types of vascular neurosurgical disease. Compared to controls, EphrinB2 was elevated with mean EphrinB2 (0.10 pg/ug vs. 0.019 pg/ug, p&lt;0.01) and compared to moyamoya patients mean EphrinB2 (0.10 pg/ug vs. 0.014, p&lt;0.01). Similarly, EphrinB2 and EphB4 staining was significantly increased in AVM tissue vs. normal blood vessels matched as controls. Conclusion: In conclusion, these data suggests potential utility of urinary biomarkers, specifically EphrinB2, as diagnostic tools for clinicians treating children with AVMs and demonstrates proof-of- principle results supporting the concept of hypothesis-driven biomarker “fingerprinting” for unique cerebrovascular disease, differentiating AVM from other vascular pathology. For the first time, these data correlate known aspects of AVM molecular biology with clinically relevant diagnostics.

Treatment Outcomes of Unruptured Arteriovenous Malformations With a Subgroup Analysis of ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations)-Eligible Patients

The design and conclusions of A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) trial are controversial, and its structure limits analysis of patients who could potentially benefit from treatment. To analyze the results of a consecutive series of patients with unruptured brain arteriovenous malformations (BAVMs), including a subgroup analysis of ARUBA-eligible patients. One hundred five patients with unruptured BAVMs were treated over an 8-year period. From this series, 90 adult patients and a subgroup of 61 patients determined to be ARUBA eligible were retrospectively reviewed. A subgroup analysis for Spetzler-Martin grades I/II, III, and IV/V was performed. The modified Rankin Scale was used to assess functional outcome. Persistent deficits, modified Rankin Scale score deterioration, and impaired functional outcome occurred less frequently in ARUBA-eligible grade I/II patients compared with grade III to V patients combined (P = .04, P = .04, P = .03, respectively). Twenty-two of 39 patients (56%) unruptured grade I and II BAVMs were treated with surgery without and with preoperative embolization, and all had a modified Rankin Scale score of 0 to 1 at the last follow-up. All patients treated with surgery without and with preoperative embolization had radiographic cure at the last follow-up. The results of ARUBA-eligible and unruptured grade I/II patients overall show that excellent outcomes can be obtained in this subgroup of patients, especially with surgical management. Functional outcomes for ARUBA-eligible patients were similar to those of patients who were randomized to medical management in ARUBA. On the basis of these data, in appropriately selected patients, we recommend treatment for low-grade BAVMs.

Critical assessment of the morbidity associated with ruptured cerebral arteriovenous malformations

BackgroundAn accurate understanding of the morbidity and mortality associated with brain arteriovenous malformation (AVM) hemorrhage is important in determining the management of unruptured AVMs. Recent studies suggest this morbidity to...

Ruptured Arteriovenous Malformation Presenting with Kernohan's Notch.

AVMs are congenital lesions that predispose patients to intracranial hemorrhage and resultant neurological deficits. These deficits are often focal and due to the presence of local neurologic disruption from hemorrhage in the contralateral cerebral hemisphere. We present a rare case of a patient with ipsilateral neurological deficits due to Kernohan's Notch phenomenon resulting from hemorrhage from an AVM. A 31-year-old woman with seizures underwent MR and angiographic imaging which confirmed an unruptured left parietal AVM. The patient declined treatment and presented with obtundation 4 years later. Imaging revealed an acute left parietal ICH and SDH with significant mass effect. The patient underwent emergent hemicraniectomy and hematoma evacuation. Postoperatively, she made significant improvement and was following commands contralaterally with ipsilateral hemiplegia. MR imaging revealed right Kernohan's Notch. The patient had significant rehabilitation with neurological improvement. She eventually underwent elective embolization followed by subsequent surgical resection and bone replacement. Three years from the initial hemorrhage, the patient had only mild left-sided weakness and ambulates without assistance. A false localizing sign, Kernohan's Notch phenomenon, should be considered in the setting of AVM hemorrhage with paradoxical motor impairment and can be identified through MRI.