Arteriovenous Malformations Hemorrhage Research Articles

In-room assessment of intravascular velocity from time-resolved rotational angiography in patients with arteriovenous malformation: a pilot study

BackgroundTime-resolved rotational angiography (t-RA) enables interventionists to better comprehend complex arteriovenous malformations (AVMs), thereby facilitating endovascular treatment. However, its use in evaluating hemodynamic changes has rarely been explored.ObjectiveThis study uses...

124 Repeat Stereotactic Radiosurgery for Incompletely Obliterated Arteriovenous Malformations

Abstract INTRODUCTION To evaluate the outcomes and risks of repeat stereotactic radiosurgery (SRS) for incompletely obliterated cerebral arteriovenous malformations (AVM). METHODS Six participating centers of the International Gamma Knife Research Foundation (IGKRF) identified 335 patients who had incompletely obliterated AVMs at a median follow-up of 45.6 months after initial SRS (range, 15–283 months). The median AVM target volume at initial SRS was 4.3 cc but was reduced to 1.4cc at the time of the second procedure. The median margin dose at both initial SRS and repeat SRS was 20 Gy. The median follow-up after repeat SRS was 64 months (range, 6–218 months). RESULTS >The actuarial rate of total obliteration by angiography or MRI after repeat SRS was 31%, 50%, 61%, and 80% at 3, 4, 5, and 10 years, respectively. Factors associated with a higher rate of AVM obliteration were smaller residual AVM target volume, and >50% of volume reduction after the initial procedure. The cumulative actuarial rates of new AVM hemorrhage after repeat SRS were 1.8%, 4.5%, 6.6%, 8.9% and 14.9% at 1, 2, 3, 5, and 10 years. Factors associated with a higher risk of hemorrhage after repeat SRS were a larger number of a prior hemorrhages, larger AVM target volume, and initial AVM volume reduction <50%. Symptomatic adverse radiation effect (ARE) developed in 29 patients (8.6%) after initial SRS and 27 patients (8.1%) after repeat SRS. CONCLUSION Repeat SRS for incompletely obliterated AVMs increases the eventual obliteration rate but patients remain at risk of hemorrhage until obliteration occurs. The best results for incompletely obliterated AVMs were seen in patients with a smaller residual AVM volume and no prior hemorrhages.

373 Risk of Hemorrhage Following Radiosurgery for Cerebral Arteriovenous Malformations (AVMs) Is Associated with Venous Stenosis

Abstract INTRODUCTION Approximately 6% of all patients who undergo radiosurgery experience subsequent hemorrhage, even in those with obliterated lesions. Little information has been presented in existing literature about risk modifiers of post-radiosurgery hemorrhage. Associated aneurysms, venous drainage pattern, size of AVM and prescription dose were previously reported as risk factors. Here, we aim to elucidate the effect of venous stenosis on risk of hemorrhage after radiosurgery. METHODS We retrospectively reviewed medical records of all AVM patients evaluated at our institution from 1990–2015, and those who were treated with radiosurgery were included. We excluded patients without baseline or follow-up data, nor information about treatment and angiographic results. Baseline and angiographic characteristics were compared between those with venous stenosis and those without to elicit confounding factors. We then proceeded with univariable and multivariable Cox regression analysis looking at predictors of post-radiosurgery hemorrhage, with inclusion of confounding factors. Patients were censored from first radiosurgery to hemorrhage or to last follow-up. RESULTS >We included 240 patients in this study. Twenty-nine (12.1%) had venous stenosis; there were more AVMs with venous varices(P = 0.009) and fewer with deep venous drainage (P = 0.048) compared to those without venous stenosis. Univariable analysis on post-radiosurgery hemorrhage showed age, gender, AVM volume, venous stenosis, and unrelated aneurysm were associated with increased risk of hemorrhage. In an all-inclusive model multivariable Cox regression, increased risk of hemorrhage was associated with venous stenosis (HR:3.70, P = 0.034), age (HR:1.05, P = 0.002), AVM volume (HR:1.04, P = 0.004), and hemorrhage before treatment (HR:4.11, P = 0.014). Male gender appears protective (HR:0.31, P = 0.036) against hemorrhage. CONCLUSION We found multiple factors associated with increased risk of AVM hemorrhage after radiosurgery. We recommend that selection of radiosurgery should proceed with caution with close follow-up after treatment, especially in patients with venous stenosis combined with advanced age, female gender, large AVM volume, and previous rupture.

Utility of indocyanine green videoangiography in subcortical arteriovenous malformation resection.

Subcortical arteriovenous malformations (AVMs) are surgically challenging. Localization is crucial for eloquent areas, and complete resection evaluation is uncertain. Indocyanine green videoangiography (ICG-VA) can assist this surgery. An illustrative video of a subcortical frontoparietal bleeding AVM resection assisted by ICG-VA is presented. A bleeding arterial feeder aneurysm was embolized in the acute phase to protect against rebleeding. ICG-VA helped to detect the AVM's superficial arterialized draining vein, distinguishing it from normal cortical veins. This enabled a customized sulcus approach. ICG-VA showed normalized flow through the previously arterialized vein, confirming the AVM's complete resection. This applies when there is a single drainage remaining. The video can be found here: https://youtu.be/L7yJEE66kV0 .

Radiosurgery in treatment of cerebral arteriovenous malformation: Mid-term results of 388 cases from a single center.

Background and Objectives:The purpose of this study is to evaluate the outcome and risks of radiosurgery for patients with arteriovenous malformations (AVM) of the brain all treated in a single center in the 3rd world with all its limitations.Materials and Methods:We performed a retrospective analysis of 388 patients with AVM treated with radiosurgery during an 8-year period. Factors associated with increased chance of AVM obliteration or hemorrhages during the follow-up period were analyzed.Results:Among 388 cases included in our series, 74 were Spetzler-Martin (SM) grade IV or V. Forty-four patients (11.3%) experienced post-radiosurgery hemorrhage in their follow-up period. The number of feeders (one/multiple) and deep location of the AVM did not alter the chance of bleeding (P < 0.05). Higher SM grading of the AVM was associated with increased chance of hemorrhage and decreased obliteration rate (P > 0.05) in the mid-term follow up.Conclusions:Our case series showed that radiosurgery can be considered a viable alternative in the treatment of even large AVMs which might not be considered good candidates for surgery or endovascular treatment. Further data including large size lesions are warranted to further support our findings.

Hemorrhage Risk of Brain Arteriovenous Malformations During Pregnancy and Puerperium in a North American Cohort.

Conclusions reached in existing literature about risk of arteriovenous malformation (AVM) hemorrhage during pregnancy are controversial. This study compares the risk of hemorrhage in pregnant and nonpregnant female patients with AVM in a North American cohort. We retrospectively reviewed female patients with AVM evaluated from 1990 to 2015. Exposure period for pregnancy and puerperium was calculated as 40 and 6 weeks, respectively, for each full-term pregnancy and 6 weeks for each abortion. Hemorrhage events and patient-years were calculated during an exposure period (pregnancy and puerperium), and a nonexposure period defined as either the interval from birth until AVM obliteration or until last follow-up after subtracting exposure period. Poisson rate ratio test was used to compare rate of hemorrhage between exposure and nonexposure periods. For 270 female patients with AVM, mean age was 35.0±19.6 years, and race distribution was white (n=165, 61.1%), black (n=59, 21.9%), Hispanic (n=9, 3.3%), Asian (n=6, 2.2%), and other (n=31, 11.5%). From 191 total pregnancies occurring before AVM obliteration, there were 175 (91.6%) term deliveries and 16 (8.4%) abortions. Overall annual hemorrhage rate for 149 total hemorrhages during an average of 11 097 patient-years was 1.34%. There were 140 hemorrhages in nonexposed women and 9 hemorrhages in pregnant women, translating to an annual hemorrhage rate of 1.3% in nonpregnant women versus 5.7% in pregnant women (P<0.001). Identical analysis for reproductive age patients (15-50) demonstrated a rate of 1.3% versus 7.0% (P<0.001). Our results conflict with those from a recent study describing no increased rate of rupture during pregnancy. This difference may reflect unique population attributes influencing brain AVM hemorrhage during pregnancy.

Abstract TP446: Predictors of Hemorrhagic Severity in Arteriovenous Malformation Patients

Introduction: One of the most frequent causes of non-traumatic intracerebral hemorrhage (ICH) in young adults is from a brain arteriovenous malformation (AVM) rupture. Understanding the potential spectrum of AVM outcomes is crucial in assessing treatment options. Although ICH mortality from ruptured brain AVMs is less frequent than for primary ICH, the severity of brain AVM hemorrhage is not well documented. We aimed to identify the clinical and anatomical variables associated with: (1) ICH volume and (2) intraventricular hemorrhage (IVH) presence to better prognosticate eventual clinical hemorrhage severity in brain AVM patients. Methods: ICH volume and presence of IVH (outcomes) were retrospectively assessed based on CT images for 150 patients admitted with ruptured AVMs and prospectively enrolled in our AVM database between 2000-2015. Parenchymal hemorrhage volumes were calculated using the ABC/2 method. Regression analysis was performed to assess the relationship between clinical and anatomical factors and ICH volume (proportional increase, PI) and presence of IVH (odds ratio, OR). Results: Older patients were less likely to have IVH (p=0.036). Exclusively deep venous drainage was associated with both smaller hemorrhage volumes (p&lt;0.001) and an increased likelihood of IVH (p&lt;0.001). Lobar AVM locations were associated with larger hemorrhage volumes (p&lt;0.001). Venous stenosis, based on a 5-point grading scale (5 = complete occlusion), was associated with larger hemorrhage volumes (p=0.006) and a decreased likelihood of IVH (p=0.014). Exclusively deep venous drainage (PI=0.29, 95% CI: 0.19 - 0.44), lobar location (PI=2.18, 95% CI: 1.47 - 3.24), and venous stenosis (PI=1.34, 95% CI: 1.09 - 1.64) remained significant independent predictors of hemorrhage volume in a multi-predictor model (P&lt;0.05). Similarly, exclusively deep venous drainage (OR=7.51, 95% CI: 2.69 – 21.00) and venous stenosis (OR=0.61, 95% CI: 0.41 – 0.90) remained significantly associated with IVH (P&lt;0.05). Conclusions: With the lack of a widely adopted AVM natural history score, our study provides further information regarding potential hemorrhage severity in addition to the current knowledge of hemorrhagic risk to better scrutinize patients with unruptured AVMs.

Letter: Lower Risk of Intracranial Arteriovenous Malformation Hemorrhage in Patients With Hereditary Hemorrhagic Telangiectasia.

Letter: Lower Risk of Intracranial Arteriovenous Malformation Hemorrhage in Patients With Hereditary Hemorrhagic Telangiectasia.

Invasive pneumococcal disease caused by mucoid serotype 3 Streptococcus pneumoniae: a case report and literature review

BackgroundAmong the different serotypes of Streptococcus pneumoniae, serotype 3 has received global attention. We report the fatal case of a 76-year-old Japanese man who had an invasive pneumococcal disease associated with pneumonia caused by serotype 3 S. pneumoniae.Case presentationThe patient had a history of hypertension, laryngeal cancer, chronic obstructive pulmonary disease, and type 2 diabetes mellitus. Following a cerebral arteriovenous malformation hemorrhage, he underwent surgery to remove the hematoma and began rehabilitation. On day 66 of hospitalization, he suddenly developed a fever, and coarse crackles and wheezes were heard in his right lung. A diagnosis of hospital-acquired aspiration pneumonia was made, and initial treatment with piperacillin/tazobactam was started. Teicoplanin was added after S. pneumoniae was isolated from the blood culture, however, the patient died 5 days later. The S. pneumoniae detected in the sputum smear was serotype 3, showed mucoid colonies and susceptibility to penicillins, cephalosporins, carbapenems, and levofloxacin, but resistance to erythromycin.ConclusionWe experienced a fatal case of pneumonia caused by mucoid serotype 3 S. pneumoniae with a thick capsule. Serotype 3-associated pneumonia may develop a wider pulmonary infiltrative shadow, a prolonged therapeutic or hospitalization course, and a poor outcome. Careful observation and intervention are required, and the use of additional antibiotics or intravenous immunoglobulins should be considered in such cases. Pneumococcal immunization is also an important public health measure to minimize the development of severe infections caused by serotype 3 strains.

Determination of Predictive Anatomic Parameters for Bleeding of Brain Arteriovenous Malformations by Multidetector CT Angiography.

Patients with brain arteriovenous malformation (AVM) have a certain risk to bleed, and the goal of this study was to examine the effect of radiological and clinical predictive characteristics of AVM hemorrhage using multidetector computed tomographic (MDCT) angiography. The study included a series of 57 patients, mean age 35.46 years, who were diagnosed during their hospitalization at Clinical Department of Neurosurgery, Clinical Center of Serbia, in the period from January 2008 to March 2016. In all patients, the diagnosis was made using MDCT angiography. Two groups of patients were observed. The first group included patients who did not initially present with hemorrhage, while the second group initially presented with hemorrhage. Both groups were treated with medical therapy or a combination of medical therapy with embolization/surgery/radiotherapy. Deep venous drainage (p<0.05), combined arterial supply from different basins (p<0.05) with a length <60 mm, venous dilatation present in the drainage vein (p<0.01), and the angle of casting sup-ply arteries in the nidus (p<0.01) carry a risk of repeated bleeding. In the group of patients who had initial hemorrhage, the mean value of the casting angle size was 130°, while in the group that did not have initial bleeding the mean value of the measured angle size was 103.81° with standard deviation of 17.21° (p<0.01). In conclusion, AVMs with deep venous drainage from the carotid and vertebrobasilar basin, the length of the feeding arteries <60 mm, the angle of the casting feeding arteries in the nidus ≥130° and dilatation and/or venous aneurysm of drainage vessel are predictive for clinical presenting by hemorrhage.

Chapter 2 - The natural history of cerebral arteriovenous malformations

Cerebral arteriovenous malformations (AVMs) are composed of a complex tangle of abnormal arteries and veins and are a significant source of cerebral hemorrhage and consequent morbidity and mortality in young adults, representing a diagnostic and therapeutic challenge. Current natural-history studies of cerebral AVMs report overall annual rates of 1% and 3% for the risk of epilepsy and hemorrhage, respectively. Unruptured AVMs have an annual hemorrhage rate of 2.2% while ruptured lesions have an annual hemorrhage rate of 4.5%. These hemorrhage rates are can change over time, particularly for hemorrhagic lesions, with the rebleed rate ranging from 6% to 15.8% in the first year after rupture across several studies. Besides hemorrhage, other significant risk factors for AVM hemorrhage include deep location, deep venous drainage, associated aneurysms, and pregnancy. Other factors include patient age, sex, and small AVM size, which are not currently considered significant risk factors for AVM hemorrhage. In addition to hemorrhage risk and seizure risk, the natural history of an AVM also encompasses the daily psychologic burden that a patient must endure knowing that he or she possesses an untreated AVM. This chapter reviews the epidemiology, clinical features, and natural history of cerebral AVMs.

Chapter 7 - Radiosurgery for the management of cerebral arteriovenous malformations

Cerebral arteriovenous malformations (AVMs) are rare, unstable vascular lesions which spontaneously rupture at a rate of approximately 2-4% annually. Stereotactic radiosurgery is a minimally invasive treatment for AVMs, with a favorable risk-to-benefit profile in most patients, with respect to obliteration, hemorrhage, and seizure control. Radiosurgery is ideally suited for small to medium-sized AVMs (diameter <3cm or volume <12cm3) located in deep or eloquent brain regions. Obliteration is ultimately achieved in 70-80% of cases and is directly associated with nidus volume and radiosurgical margin dose. Adverse radiation effects, which appear as T2-weighted hyperintensities on magnetic resonance imaging, develop in 30-40% of patients after AVM radiosurgery, are symptomatic in 10%, and fail to clinically resolve in 2-3%. The risk of AVM hemorrhage may be reduced by radiosurgery, but the hemorrhage risk persists during the latency period between treatment and obliteration. Delayed postradiosurgery cyst formation occurs in 2% of cases and may require surgical treatment. Radiosurgery abolishes or ameliorates seizure activity in the majority of patients with AVM-associated epilepsy and induces de novo seizures in 1-2% of those without preoperative seizures. Strategies for the treatment of large-volume AVMs include neoadjuvant embolization and either dose- or volume-staged radiosurgery.

International multicenter cohort study of pediatric brain arteriovenous malformations. Part 1: Predictors of hemorrhagic presentation.

OBJECTIVE Brain arteriovenous malformations (AVMs) are the most common cause of spontaneous intracranial hemorrhage in pediatric patients (age < 18 years). Since the cumulative lifetime risk of AVM hemorrhage is considerable in children, an improved understanding of the risk factors influencing hemorrhagic presentation may aid in the management of pediatric AVMs. The aims of this first of a 2-part multicenter, retrospective cohort study are to evaluate the incidence and determine the predictors of hemorrhagic presentation in pediatric AVM patients. METHODS The authors analyzed pooled AVM radiosurgery data from 7 institutions participating in the International Gamma Knife Research Foundation (IGKRF). Patients younger than 18 years at the time of radiosurgery and who had at least 12 months of follow-up were included in the study cohort. Patient and AVM characteristics were compared between unruptured and ruptured pediatric AVMs. RESULTS A total of 357 pediatric patients were eligible for analysis, including 112 patients in the unruptured and 245 patients in the ruptured AVM cohorts (69% incidence of hemorrhagic presentation). The annual hemorrhage rate prior to radiosurgery was 6.3%. Hemorrhagic presentation was significantly more common in deep locations (basal ganglia, thalamus, and brainstem) than in cortical locations (frontal, temporal, parietal, and occipital lobes) (76% vs 62%, p = 0.006). Among the factors found to be significantly associated with hemorrhagic presentation in the multivariate logistic regression analysis, deep venous drainage (OR 3.2, p < 0.001) was the strongest independent predictor, followed by female sex (OR 1.7, p = 0.042) and smaller AVM volume (OR 1.1, p < 0.001). CONCLUSIONS Unruptured and ruptured pediatric AVMs have significantly different patient and nidal features. Pediatric AVM patients who possess 1 or more of these high-risk features may be candidates for relatively more aggressive management strategies.

Angioarchitectural Characteristics Associated With the Risk of Hemorrhage in Intracranial Arteriovenous Malformations

Angioarchitectural Characteristics Associated With the Risk of Hemorrhage in Intracranial Arteriovenous Malformations

Prevalence and characteristics of brain arteriovenous malformations in hereditary hemorrhagic telangiectasia: a systematic review and meta-analysis.

OBJECTIVE Patients with hereditary hemorrhagic telangiectasia (HHT) are known to suffer from high rates of cerebral arteriovenous malformations (AVMs). The authors performed a systematic review and meta-analysis of the literature examining prevalence rates, characteristics, and clinical presentation of cerebral AVMs in the HHT population. METHODS To identify studies on AVM prevalence and characteristics in the HHT population, 4 databases (MEDLINE, EMBASE, Scopus and Web of Science) were searched by a reference librarian with over 30 years experience in systematic reviews and meta-analysis. The search period was January 1, 1990-March 2016. The following search terms were used: hereditary hemorrhagic telangiectasia, Osler-Weber-Rendu syndrome, AVM, brain AVM, arteriovenous malformation, arteriovenous fistula, prevalence, and epidemiology. The authors identified studies that examined the prevalence rates, characteristics, and clinical presentation of cerebral AVMs in patients with HHT. They assessed overall AVM prevalence rates as well as prevalence rates by age, sex, HHT type, and country/region. They also systematically reviewed the characteristics of AVMs, including rupture status, location, clinical presentation, angioarchitecture, and Spetzler-Martin grade. Data were analyzed using a random-effects meta-analysis model. RESULTS Thirty-nine studies were included in this meta-analysis. Thirty studies examined brain AVM prevalence rates in various HHT patient populations, and 18 studies examined AVM clinical and angiographic characteristics (9 studies examined both prevalence rates and AVM characteristics). The prevalence of brain AVMs in HHT patients was 10.4% (95% CI 7.9%-13.0%) with no significant difference between males (8.5%, 95% CI 4.9%-12.0%) and females (11.0%, 95% CI 5.9%-16.1%). Patients with HHT Type 1 (HHT1) had a significantly higher brain AVM prevalence (13.4%, 95% CI 9.5%-17.4%) compared with those with HHT Type 2 (HHT2) (2.4%, 95% CI 1.0%-3.8%) (p < 0.0001). In 55.2% (95% CI 38.3%-72.1%) of cases, the AVMs were symptomatic. Spetzler-Martin grade was 2 or less in 86.9% (95% CI 67.5%-95.2%) of patients. CONCLUSIONS The prevalence of brain AVMs in the HHT population is about 10%. HHT1 patients are significantly more likely to have brain AVMs than HHT2 patients. Most AVMs in the HHT population are symptomatic. The Spetzler-Martin grade for these lesions is 2 or less in nearly 90% of patients.

Relationship of pulsatility and resistance indices to cerebral arteriovenous malformation angioarchitectural features and hemorrhage

The role that hemodynamics plays in the pathophysiology of cerebral arteriovenous malformation (AVM) hemorrhage remains unclear. Here, we examine the relationship of pulsatility and resistance indices to AVM angioarchitectural features and hemorrhage. Records of patients with cerebral AVMs evaluated at our institution between 2007–2014 and with flows obtained before treatment using quantitative magnetic resonance angiography (QMRA) were retrospectively reviewed. Flow volume rate and flow velocity were measured in primary arterial feeders and compared to their contralateral counterparts. Pulsatility index (PI)=[(systolic flow velocity−diastolic flow velocity)/mean flow velocity] and resistance index (RI)=[(systolic flow velocity−diastolic flow velocity)/systolic flow velocity] were calculated for each feeder and compared to the normal contralateral vessel. Relationships between PI, RI and AVM clinical and angioarchitectural features were assessed using linear regression. Seventy-two patients with a total of 101 feeder arteries were included. PI and RI were significantly lower in AVM arterial feeders compared to normal vessels, thereby resulting in significantly higher flow volume rates and flow velocities in feeder vessels. There was no significant association of PI and RI with hemorrhagic presentation, exclusive deep venous drainage, venous stenosis, single draining vein, or deep location. In conclusion, PI and RI can be measured using QMRA and are lower in AVM arterial feeders compared to normal vessels. Although we found no significant correlation between PI, RI, and AVM angioarchitectural characteristics thought to be associated with increased hemorrhage risk, future studies with larger sample sizes may better elucidate this relationship.

163 - Apixaban Use in LVAD Patient with Recurrent GI Bleeding and Recent Embolic Stroke

Background: Left ventricular assist devices (LVAD) have been shown to improve quality of life and decrease mortality in patients with advanced heart failure. GI bleeding and pump thrombosis are major complications associated with LVAD therapy. Warfarin is the mainstay of anticoagulation for these patients. However, warfarin therapy can be challenging due to a narrow therapeutic window, drug/food interactions and need for frequent monitoring. The direct oral anticoagulants (DOACs) have been shown to be non-inferior or superior to warfarin for preventing stroke and reducing the risk of bleeding in patients with AF. As a result, DOACs are an enticing option for LVAD patients intolerant of warfarin anticoagulation. Summary: In this case report, we describe the use of apixaban in an LVAD patient with recurrent, severe GI bleeding, a recent embolic stroke and possible pump thrombosis (reflected by a rising LDH). KB was a 58 year-old male with a history of AF and systolic HF (EF 20%) who underwent HeartMate II LVAD implantation on 12/12/13. Warfarin was initiated POD #1. On POD #14, he had melena and Hgb drop with an INR of 2.5. ASA and warfarin were held and IV pantoprazole initiated. Upper endoscopy (EGD) revealed multiple bleeding arteriovenous malformations (AVMs) treated with epinephrine injection and clipping. He was discharged home POD #22 on warfarin with an INR (goal 1.8–2.2). ASA was held. At two and six weeks post-discharge, the patient was readmitted with recurrent melena and severe anemia due to bleeding AVMs that were cauterized. After the 3rd GI bleed, the decision was made to stop warfarin. ASA 81 was restarted. Hgb subsequently stabilized. Four months later, readmitted with memory deficits and apraxia due to suspected CVA. Head CT was negative. Hgb 14 g/dl. LDH 420 (Baseline 300). He was treated with heparin and discharged on apixaban 2.5 bid/ASA 81 mg. LDH and Hgb again remained stable as an outpatient. One month later, readmitted for scheduled transplant work-up. Hgb 12. LDH 700. Apixaban stopped. Treated with heparin × 48 hours for possible pump thrombosis. Apixaban 5 mg bid started. LDH 300 on discharge. One month later, listed status IA for transplant. Apixaban stopped. Warfarin restarted. Two weeks later he had recurrent melena. Hgb 7.5 g/dl. INR 3.0. He was transfused and underwent heart transplantation one week later but died due to post-op respiratory failure. Conclusion: DOACs may be a suitable anticoagulation alternative for LVAD patients intolerant of warfarin.

Treatment of Cerebral Arteriovenous Malformations with Radiosurgery or Hypofractionated Stereotactic Radiotherapy in a Consecutive Pooled Linear Accelerator Series

To review outcomes after linear accelerator stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (hfSRT) of arteriovenous malformations (AVMs) from a consecutive and pooled series of 2 Novalis centers and to analyze the influence of AVM size, Spetzler-Martin (SM) grade, pretreatment, and hemorrhagic versus nonhemorrhagic presentation. A subgroup analysis of A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA)-eligible patients also was performed. Prospectively collected treatment and outcome data were supplemented by retrospectively collected follow-up data for 93.8% of all patients. A total of 129 patients with AVM had SRS or hfSRT between 2000 and 2014 with the same linear accelerator system in 2 centers. Data analysis included initial presentation, SM grade, occlusion rates assessed by magnetic resonance and/or digital subtraction angiography, neurologic and therapeutic complications, and pretreatments. Statistical analysis was performed for patient demographic data and for factors potentially influencing outcome. Initial presentation was hemorrhage in 43.8% or seizures/neurologic deficits in 46.2%. The series included 6 SM grade I (5%), 26 SM II (21.5%), 55 SM III (45.5%), 28 SM IV (23%), and 6 SM V cases (5%). Pre-embolization was used in 36 patients (29.8%), 8 patients had previous surgery (6.6%), and 6 patients were irradiated before elsewhere (5%); 5 patients (4.2%) received multimodal pretreatment. Mean follow-up was 43 months. The occlusion rate for the total series was 71.1%, for SM I/II cases 80.6%, and 67.4% for the SM ≥ subgroup. The occlusion rate was 75.0% for the small volume (<4 cc) and 55.6% for the large volume (>10 cc) subgroup. There was no statistical difference between the occlusion rate of patients with or without pretreatment if taken all modalities together (72.7% and 69.7%, respectively). There was only a trend of a belated occlusion of pre-embolized AVMs. The occlusion rate for hemorrhagic AVM was with 77.4% better than for nonhemorrhagic (66.2%) or ARUBA-eligible AVMs (64.8%) but without reaching statistical significance. Neurologic deterioration was seen in 13.2% of the patients. There were 2 re-bleedings within 17-18 months (1.7%), 1 of them without a new neurologic deficit and total occlusion after re-SRS. One patient with pre-existing epilepsy died a sudden unexpected death (mortality rate: 0.8%). Overall SRS and hfSRT are valuable therapy options, especially in symptomatic patients with AVM, with a low rate of morbidity and mortality and an acceptable overall complete occlusion rate of >70% and >80% for SM I/II AVMs.

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.

Stereotactic radiosurgery for cerebral arteriovenous malformations: evaluation of long-term outcomes in a multicenter cohort.

OBJECTIVE In this multicenter study, the authors reviewed the results following Gamma Knife radiosurgery (GKRS) of cerebral arteriovenous malformations (AVMs), determined predictors of outcome, and assessed predictive value of commonly used grading scales based upon this large cohort with long-term follow-up. METHODS Data from a cohort of 2236 patients undergoing GKRS for cerebral AVMs were compiled from the International Gamma Knife Research Foundation. Favorable outcome was defined as AVM obliteration and no posttreatment hemorrhage or permanent symptomatic radiation-induced complications. Patient and AVM characteristics were assessed to determine predictors of outcome, and commonly used grading scales were assessed. RESULTS The mean maximum AVM diameter was 2.3 cm, with a mean volume of 4.3 cm3. A mean margin dose of 20.5 Gy was delivered. Mean follow-up was 7 years (range 1-20 years). Overall obliteration was 64.7%. Post-GRKS hemorrhage occurred in 165 patients (annual risk 1.1%). Radiation-induced imaging changes occurred in 29.2%; 9.7% were symptomatic, and 2.7% had permanent deficits. Favorable outcome was achieved in 60.3% of patients. Patients with prior nidal embolization (OR 2.1, p < 0.001), prior AVM hemorrhage (OR 1.3, p = 0.007), eloquent location (OR 1.3, p = 0.029), higher volume (OR 1.01, p < 0.001), lower margin dose (OR 0.9, p < 0.001), and more isocenters (OR 1.1, p = 0.011) were more likely to have unfavorable outcomes in multivariate analysis. The Spetzler-Martin grade and radiosurgery-based AVM score predicted outcome, but the Virginia Radiosurgery AVM Scale provided the best assessment. CONCLUSIONS GKRS for cerebral AVMs achieves obliteration and avoids permanent complications in the majority of patients. Patient, AVM, and treatment parameters can be used to predict long-term outcomes following radiosurgery.