Untreated Arteriovenous Malformations Research Articles

Rupture risk assessment in cerebral arteriovenous malformations: an ensemble model using hemodynamic and morphological features

BackgroundCerebral arteriovenous malformation (AVM) is a cerebrovascular disorder posing a risk for intracranial hemorrhage. However, there are few reliable quantitative indices to predict hemorrhage risk accurately. This study aimed to...

Quantitative evaluation of the subsequent hemorrhage with arteriography-derived hemodynamic features in patients with untreated cerebral arteriovenous malformation.

Patients with untreated cerebral arteriovenous malformations (AVMs) are at risk of intracerebral hemorrhage. However, treatment to prevent AVM hemorrhage carries risks. This study aimed to analyze the AVM nidus-related hemodynamic features and identify the risk factors for subsequent hemorrhage. We retrospectively identified patients with untreated AVMs who were assessed at our institution between March 2010 and March 2021. Patients with ≥6 months of treatment-free and hemorrhage-free follow-up after diagnosed by digital subtraction angiography were included in subsequent examinations. The hemodynamic features were extracted from five contrast flow-related parameter maps. The Kaplan-Meier analyses and Cox proportional hazards regression models were used to find the potential risk factors for subsequent hemorrhage. Overall, 104 patients with a mean follow-up duration of 3.37 years (median, 2.42 years; range, 6-117 months) were included in study, and the annual risk of rupture was 3.7%. Previous rupture (hazard ratio [HR], 4.89; 95% confidence interval [CI], 1.16-20.72), deep AVM location (HR, 4.02; 95% CI, 1.01-15.99), higher cerebral blood volume (HR, 3.35; 95% CI, 1.15-9.74) in the nidus, and higher stasis index (HR, 1.54; 95% CI, 1.06-2.24) in the nidus were associated with subsequent hemorrhage in untreated AVMs. Higher cerebral blood volume and stasis index in the nidus suggest increased blood inflow and stagnant blood drainage. The combination of these factors may cause subsequent hemorrhage of AVMs.

Risk for Hemorrhage the First 2 Years After Gamma Knife Surgery for Arteriovenous Malformations: An Update.

Knowledge about the natural course of brain arteriovenous malformations (AVMs) have increased during the past 20 years, as has the number of AVMs treated, especially larger ones. It is thus timely to again analyze the risk for hemorrhage after Gamma Knife Surgery (GKS). To confirm or contradict conclusions drawn 20 years ago regarding factors that affect the risk for post-GKS hemorrhage. The outcome after GKS was studied in 5037 AVM patients followed for up to 2 years. The relation between post-treatment hemorrhage rate and a number of patient, AVM, and treatment parameters was analyzed. The results were also compared with the results from our earlier study. The annual post-treatment hemorrhage rate was 2.4% the first 2 years after GKS. Large size, low treatment dose, and old age were independent risk factors for AVM hemorrhage. After having compensated for the factors above, peripheral AVM location and female sex, at least during their child bearing ages, were factors associated with a lower post-GKS hemorrhage rate. Large AVMs (>5 cm 3 ) treated with low doses (≤16 Gy) had higher and small AVMs treated with high doses a lower risk for hemorrhage as compared with untreated AVMs. This was detectable within the first 6 months after GKS. No difference in hemorrhage rate could be detected for the other AVMs. Based on our findings, it is advisable to prescribe >16 Gy to larger AVMs, assuming that the risk for radiation-induced complications can be kept at an acceptable level.

Long-term follow-up in patients with brain arteriovenous malformation based on the Quality of Life Scale and socioeconomic status

Intracranial haemorrhage (ICH) is associated with permanent neurological disability resulting in deterioration of the quality of life (QoL). Our study assesses QoL in patients with ruptured arteriovenous malformation (AVM) in long-term follow-up at least five years after ICH and compares their QoL with the QoL of patient with non-ruptured AVM. Using the Quality of Life Scale (QOLS), the Patient Health Questionnaire (PHQ-9) for depressive symptoms, and the socioeconomic status (SES), a prospective assessment was performed. The modified Rankin Scale (mRS) was assessed for outcome. Of 73 patients, 42 (57.5%) had ruptured (group 1) and 31 (42.5%) a non-ruptured AVM (group 2). Mean follow-up time was 8.6 ± 3.9years (8.5 ± 4.2years in group 1 and 8.9 ± 3.7years in group 2). Favourable outcome (mRS 0-1) was assessed in 60 (83.3%) and unfavourable in 12 (16.7%) patients. Thirty-one of 42 patients (73.8%) in group 1 and 29 of 30 patients in group 2 (96.7%) had favourable outcomes. Mean QOLS was 85.6 ± 14.1 (group 1 86.1 ± 15.9, group 2 84.9 ± 11.4). Patients in group 1 did not show a significant difference in QoL compared to patients in group 2 (p = 0.23). Additional analyses in group 2 (rho = - 0.73; p < 0.01) and in untreated AVM patients (rho = - 0.81; p < 0.01) showed a strong correlation between QOLS and PHQ-9. Long-term follow-up showed no difference in the QoL between patients with and without ICH caused by brain AVM. Outcome- and QoL-scores were high in both groups. Further studies are necessary to evaluate depression and anxiety symptoms in patients with AVM.

Living with a Brain AVM: A Quality of Life Assessment.

Brain arteriovenous malformations (AVM) are uncommon vascular lesions with the risk of hemorrhage, epileptic seizures, neurological deficits, and headache. Comparing the risks of the natural history and that of preventive treatment, a recent study has found observation more beneficial than treatment for unruptured AVMs. This study, however, did not consider the long-term impact of carrying a brain AVM on everyday activities. In this study we analyzed the Quality Of Life (QOL) of patients with untreated AVMs, a measure increasingly used in clinical trials to asses this kind of impact. We enrolled 36 patients with unruptured, untreated brain AVM from our hospital database and measured their QOL retrospectively using the EQ-5D-5L questionnaire. As a control group we used the results of the Research Report, a nationwide study based on the quality of life of 5534 healthy Hungarians in 2002. Due to the low number of cases, statistical analysis could not be made. Headache proved to be the most common AVM-related sign in our cohort (40%, n=17), with a female predominance; neurological deficit was detected in 33% (n=14), while epileptic seizures occurred in 26% (n=11), more commonly affecting male subjects. Anxiety and discomfort seemed to be the most prevalent influencing factors on QOL, especially in the youngest age group (18-34years). Female subjects showed a greater dependence than men in all age groups, though males had a more significant impairment in their usual activities. Older patients were affected more significantly in their self-care and usual activities compared with the younger population. Untreated AVMs have a significant negative impact on patients carrying unruptured brain AVMs, as proved by QOL assessment. Beside neurological deficits, this impact should also be considered in the therapeutic decision.

Hereditary Hemorrhagic Telangiectasia (HHT) and Survival: The Importance of Systematic Screening and Treatment in HHT Centers of Excellence.

Hereditary hemorrhagic telangiectasia (HHT), an autosomal dominant disease, is characterized by telangiectases and arteriovenous malformations (AVMs). Untreated AVMs, especially in the lungs—pulmonary AVMs (PAVMs)—can result in morbidity with a decreased life expectancy. We have investigated whether HHT patients, systematically screened for HHT-related organ involvement and treated if needed, have a similar survival as persons without HHT. We included all individuals screened for HHT between 2004 and 2016 with a genetically or clinically confirmed diagnosis (HHT group) or excluded diagnosis (non-HHT control group). The social security number was used to confirm status as dead or alive in December 2019. We included 717 HHT patients and 471 controls. There was no difference in survival between the HHT and the non-HHT control group. The HHT group had a life expectancy of 75.9 years (95% confidence interval (CI) 73.3–78.6), comparable to the control group (79.3 years, 95% CI 74.8–84.0, Mantel–Cox test: p = 0.29). In conclusion, the life expectancy of HHT patients systematically screened for HHT-related organ involvement and treated if needed in an HHT center of excellence was similar compared to their controls, justifying systematic screening and treatment in HHT patients.

Radiosurgery for Unruptured Intervention-Naïve Pediatric Brain Arteriovenous Malformations.

Long-term data regarding stereotactic radiosurgery (SRS) as a standalone therapy for unruptured pediatric brain arteriovenous malformations (AVMs) are incompletely defined. To evaluate, in a multicenter, retrospective cohort study, the outcomes after SRS for unruptured, intervention-naïve pediatric AVMs. To retrospectively analyze the International Radiosurgery Research Foundation pediatric AVM database from 1987 to 2018. Pediatric patients with unruptured, previously untreated AVMs who underwent SRS were included. The primary endpoint was a composite of hemorrhagic stroke, death, or permanently symptomatic radiation-induced changes. The study cohort comprised 101 patients (mean follow-up 80.8 mo). The primary endpoint occurred in 14%, comprising hemorrhagic stroke, death, and permanent radiation-induced changes in 6%, 3%, and 8%, respectively. Estimated probabilities of the primary endpoint were 5.2%, 10.8%, and 23.0% at 2, 5, and 10 yr, respectively. Estimated probabilities of AVM obliteration at 5 and 10 yr were 64% and 82%, respectively. Single SRS treatment (P=.007) and higher margin dose (P=.005) were predictors of obliteration. Subgroup analysis of Spetzler-Martin grade I-III AVMs estimated primary endpoint probabilities of 3.7%, 8.4%, and 18.7% at 2, 5, and 10 yr, respectively. Treatment of unruptured, intervention-naïve AVMs in the pediatric population with SRS carries an approximately 2% annual risk of morbidity and mortality, which appears to plateau after 10 yr. The poorly described natural history of pediatric AVMs renders any comparison of SRS vs conservative management imperfect.

Clinical outcome following cerebral AVM hemorrhage.

A significant difference exists between the published results reporting the clinical outcome following brain arteriovenous malformation (AVM) ruptures. Information about the outcome following hemorrhage in an AVM population treated with radiosurgery could provide additional information to assess the risk of mortality and morbidity following an AVM hemorrhage. Clinical outcome was studied in 383 patients, the largest patient population yet studied, who suffered from a symptomatic hemorrhage after Gamma Knife® surgery (GKS) but before confirmed AVM obliteration. The impact of different patient, AVM, and treatment parameters on the clinical outcome was analyzed. The aim was to generate outcome predictions by comparing our data to and combining them with earlier published results. No relation was found between clinical outcome and treatment parameters, indicating that the results are applicable also on untreated AVMs. Twenty-one percent of the patients died, 45% developed or experienced worsening of neurological sequelae, and 35% recovered completely after the hemorrhage. Old age was a predictor of poor outcome. Sex, AVM location, AVM volume, and history of prior hemorrhage did not influence the outcome. The mortality rate was comparable to earlier published prospective data, but higher than that found in retrospective studies. The mortality rates in earlier published retrospective series as well as in studies focusing on clinical outcome following AVM hemorrhage significantly underestimate the risk for a mortal outcome following an AVM hemorrhage. Based on our findings, an AVM rupture has around 20% likelihood to result in mortality, 45% likelihood to result in a minor or major deficit, and 35% likelihood of complete recovery. The findings are probably applicable also for AVM ruptures in general. The cumulative mortality and morbidity rates 25years after diagnosis were estimated to be around 40% in a patient with a patent AVM.

Abstract 127: Radiosurgery for Unruptured Intervention-Naïve Pediatric Brain Arteriovenous Malformations

Background and Purpose: To evaluate, in a multicenter, retrospective cohort study, the outcomes after stereotactic radiosurgery (SRS) for unruptured, intervention-naïve pediatric brain arteriovenous malformations (AVM). Methods: We retrospectively analyzed the International Radiosurgery Research Foundation pediatric AVM database from 1987-2018. Pediatric patients with unruptured, previously untreated AVMs who underwent SRS were included. The primary endpoint was a composite of hemorrhagic stroke, death, or permanently symptomatic radiation-induced changes (RIC). Results: The study cohort comprised 101 patients (mean follow-up 80.8 months). The primary endpoint occurred in 14%, comprising hemorrhage stroke, death, and permanent RIC in 6%, 3%, and 8%, respectively. Estimated probabilities of the primary endpoint were 5.2%, 10.8%, and 23.0% at 2, 5, and 10 years, respectively (Figure 1). Estimated probabilities of AVM obliteration at 5 and 10 years were 64% and 82%, respectively (Figure 2). Single SRS treatment (p=0.007) and higher margin dose (p=0.005) were predictors of obliteration. Subgroup analysis of Spetzler-Martin grade I-III AVMs estimated primary endpoint probabilities of 3.7%, 8.4%, and 18.7% at 2, 5 and 10 years, respectively. Conclusion: Treatment of unruptured, intervention-naïve AVMs in the pediatric population with SRS carries an approximately 2% annual risk of morbidity and mortality, which appears to plateau after 10 years. The poorly described natural history of pediatric AVMs makes any comparison of SRS versus conservative management imperfect. However, due to the young age at diagnosis and excessive cumulative life hemorrhage risk of an untreated AVM in a child, SRS is likely to have a favorable long-term risk-benefit profile for appropriately selected unruptured pediatric AVMs.

Incidence of Spontaneous Obliteration in Untreated Brain Arteriovenous Malformations.

Spontaneous obliteration (SpO) of untreated arteriovenous malformations (AVMs) is rare with fewer than 100 cases reported. The incidence and predisposing factors of SpO remain unclear, impeding our understanding of lesion progression in untreated patients. To determine the incidence rate and predisposing factors of SpO in a North American cohort. AVMs were retrospectively evaluated at our institution for over 25 yr. Untreated AVMs were divided into 2 groups: SpO-AVMs and non-SpO-AVMs. All statistical results were based on univariate analyses. Incidence was generated from counts of SpO over the untreated interval in patient years from birth until obliteration, treatment, or last follow-up. One hundred fifty-four patients had untreated AVMs; SpO was observed in 4. Average ages were 49.0±23.6 and 48.7±20.4 yr in the SpO-AVM and non-SpO-AVM group, respectively (P=.98). Average AVM sizes were 2.0±1.8 cm (SpO-AVMs) and 3.7±2.6 cm (non-SpO-AVMs, P=.25). All SpO-AVMs and 40 (27.0%) non-SpO-AVMs had a ruptured presentation (P=.006). A single draining vein was observed in all SpO-AVMs and 39 (32.8%) non-SpO-AVMs (P=.01). Deep venous drainage was not observed in any SpO-AVMs, but in 81 (57.9%) non-SpO-AVMs (P=.04). Mean follow-up time was 37.0±42.6 and 75.6±161.7 mo in SpO-AVM and non-SpO-AVMs patients, respectively. Of the 2 SpO-AVM patients with postobliteration follow-up, 1 experienced recanalization. From a 672-patient cohort, the incidence of SpO over 28 961 patient years was 0.014%. SpO-AVMs have an annual incidence rate of approximately 0.014% and tend to present with rupture, a single draining vein, and superficial venous drainage. Expectation of SpO for untreated AVMs is not justified, and patients should anticipate life-long hemorrhagic risk for untreated AVMs.

The NASSAU (New ASSessment of cerebral Arteriovenous Malformations yet Unruptured) Analysis: Are the Results From The ARUBA Trial Also Applicable to Unruptured Arteriovenous Malformations Deemed Suitable for Gamma Knife Surgery?

The optimal management of unruptured brain arteriovenous malformations (AVMs) is controversial after the ARUBA trial. To confirm or repudiate the ARUBA conclusion that "medical management only is superior to medical management with interventional therapy for unruptured brain arteriovenous malformations." Data were collected from 1351 patients treated with Gamma Knife Surgery (GKS; Elekta AB, Stockholm, Sweden) for unruptured and untreated AVMs The follow-up was 8817 yr (median 5.0 and mean 6.5). The results of the analyses were compared to that found in patients randomized to medical management only in the ARUBA trial and extrapolated to a 10-yr time period. Our data were also compared to the natural course in a virtual AVM population for a 25-yr time period. The incidence of stroke was similar among ARUBA and our patients for the first 5 yr. Thereafter, the longer the follow-up, the relatively better outcome following treatment. Both the mortality rate and the incidence of permanent deficits in patients with small AVMs were the same as in untreated patients for the first 2 to 3 yr after GKS, after which GKS patients did better. Patients with large AVMs had a higher incidence of neurological deficits in the first 3 yr following GKS. The difference decreased thereafter, but the time until break even depended on the analysis method used and the assumed risk for hemorrhage in patent AVMs. The ARUBA trial conclusion that medical management is superior to medical management with interventional therapy for all unruptured AVMs could be repudiated.

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

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

Abstract TMP99: Assessment of Management and Outcomes of a First Hemorrhage in Patients With Untreated Arteriovenous Malformations

Introduction: Invasive interventions are commonly used to prevent re-rupture of ruptured arteriovenous malformations (AVMs), but are controversial for managing unruptured AVMs. This study uses a retrospective design to identify influential factors and outcomes in our multimodal treatment program for AVMs following a first rupture. Methods: We reviewed data from a single institution for 89 patients aged 18 years or older, with a first intracranial hemorrhage due to untreated AVMs between 2002 and 2015. We analyzed patient-specific variables and initial modified Rankin Scale (mRS) score groups (A, 0-2; B, 3-5) to compare group differences. Group outcomes were also assessed via multivariate regression. Results: Locations of Hemorrhage were as follows: 43 (48.3%) intraparenchymal, 16 (18.0%) intraventricular, 6 (6.7%) subarachnoid, and 24 (27.0%) combined. Spetzler-Martin grades included 50 grade I/II, 26 grade III, and 13 grade IV/V AVMs. Interventions were utilized in 79 patients (20 surgical resection, 28 Gamma Knife surgery [GKS], and 31 combined with embolization), and conservative management in 10. Mean follow-up was 77.2±45.4 months. Peri-interventional morbidity was 5.1% and the mortality rate was zero. Re-bleeding was observed in 2 patients before intervention and 3 patients after GKS. The group A (N=69) was significantly younger (44.1±16.7 vs. 53.3±13.1, P=0.02), more likely to have a nidus fed by a perforator (30.4% vs. 5.3%, P=0.02), and more likely to undergo GKS with or without embolization (56.5% vs. 25.5%, P=0.01) than the group B (N=19). Significantly more patients in the group A had final mRS scores ≤2 than the group B (95.5% vs. 36.8%, P&lt;0.0001). Multivariate analyses indicated that a nidus fed by a perforator was the only independent pre-hemorrhagic factor for an initial mRS 0-2, which was the only independent pre-treatment factor for a good outcome. Conclusion: Although our treatment results seemed favorable, initial severity influenced the outcome after an untreated AVM-related first intracranial hemorrhage. Further analyses of the factors associated with severe hemorrhage of AVMs may improve both the outcome of ruptured AVMs and the management of unruptured AVMs.

The benefit of radiosurgery for ARUBA-eligible arteriovenous malformations: a practical analysis over an appropriate follow-up period.

OBJECTIVE The authors of this study found that, given the latency period required for arteriovenous malformation (AVM) obliteration after stereotactic radiosurgery (SRS), a study with limited follow-up cannot assess the benefit of SRS for unruptured AVMs. METHODS The authors reviewed their institutional experience with "ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations)-eligible" AVMs treated with SRS between 1987 and 2016, with the primary outcome defined as stroke (ischemic or hemorrhagic) or death (AVM related or AVM unrelated). Patients with at least 3 years of follow-up in addition to those who experienced stroke or died during the latency period were included. Secondary outcome measures included obliteration rates, patients with new seizure disorders, and those with new focal deficits without stroke. RESULTS Of 233 patients included in this study, 32 had a stroke or died after SRS over the mean 8.4-year follow-up (14%). Utilizing the 10% stroke or death rate at a mean 2.8-year follow-up for untreated AVMs in ARUBA, the rate in the authors' study is significantly lower than that anticipated at the 8.4-year follow-up for an untreated cohort (14% vs 30%, p = 0.0003). Notwithstanding obliteration, in this study, annualized rates of hemorrhage and stroke or death after 3 years following SRS were 0.4% and 0.8%, respectively. The overall obliteration rate was 72%; new seizure disorders, temporary new focal deficits without stroke, and permanent new focal deficits without stroke occurred in 2% of patients each. CONCLUSIONS After a sensible follow-up period exceeding the latency period, there is a lower rate of stroke/death for patients with treated, unruptured AVMs with SRS than for patients with untreated AVMs.

Optimization of the Surgical Approach in AVMs Using MRI and 4D DSA Fusion Technique : Atechnical note.

Previously published data demonstrated the possibility of displaying the angioarchitecture of intracranial vascular malformations using time-resolved 3D imaging (4D digital subtraction angiography [DSA]). The purpose of our study was to prove the technical feasibility of creating fused images of time-resolved 3D reconstructions and MPRAGE MRI data sets and to check the reliability of the correct anatomical display of the angioma nidus and the venous drainage in the fused images of patients with intracranial arteriovenous malformations (AVM). In this study 20patients with intracranial AVM underwent pretherapeutic DSA and time-resolved 3D DSA in addition to MRI including MPRAGE sequences. The images were post-processed with the fusion software tool on adedicated research workstation. The fusion of both imaging modalities was done semi-automatically with automatic co-registration software followed by amanual co-registration. Co-registered DSA/MRI data sets of 20 untreated AVMs were evaluated independently by two reviewers. Image fusion was successful in all 20cases with an acceptable additional set-up time. The fused images were highly scored by the two raters in respect to their congruency of the dedicated regions. Precise anatomical localization of the nidus, the feeding arteries and the draining veins were possible with the merged images. Creating fused images of time-resolved 3D DSA and contrast-enhanced T1-weighted MPRAGE MR images might be beneficial for the preoperative and intrasurgical workflow in patients with AVMs. This new software tool fulfils the required quality and accuracy of the merged images. The clinical validation has to be proven in further studies.

Safety of Intraventricular rt-PA for Pan-Ventricular IVH Caused by a Ruptured AVM: A Case Report.

Intraventricular recombinant tissue plasminogen activator (IVT rt-PA) has improved outcomes for intraventricular hemorrhage (IVH). Patients with suspected or untreated arteriovenous malformations (AVMs) have been excluded from clinical trials. We present a patient with IVH secondary to a ruptured AVM safely treated with IVT rt-PA. A 48-year-old Hispanic male with a history of dermatomyositis presented to the emergency department with sudden left-sided weakness. En route to computed tomography (CT), he became lethargic. Computed tomography revealed extensive IVH with acute hydrocephalus, which was treated with the placement of external ventricular drain with clinical improvement. Computed tomography angiogram performed did not reveal AVM. Cerebral digital subtraction angiogram (DSA) was planned due to suspicion of AVM. Prior to DSA, patient became acutely lethargic. Computed tomography imaging revealed worsening hydrocephalus. External ventricular drain was noted to be draining. Repeat CT revealed improved hydrocephalus but with left lateral ventricle dilatation. Risks and benefits of IVT rt-PA were discussed with the family and a decision was made to treat. Three doses of 1 mg IVT rt-PA were administered with resolution of midline blood and lateral ventricular dilatation with clinical improvement. Digital subtraction angiogram revealed early draining vein on right internal carotid artery injection draining into the inferior sagittal sinus representing ruptured AVM without clear nidus. Repeat DSA with possible embolization was planned after discharge. In spite of additional in-hospital complications, the patient gradually improved and was ultimately discharged home. Our case supports the idea that the use of IVT rt-PA following an IVH caused by an underlying AVM could be further explored in carefully designed clinical trials.

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.

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.

Abstract 55: Selection and Outcomes of Multimodality Interventional Treatment for Unruptured Arteriovenous Malformations in a Single Institution

Objective: The present study aimed to evaluate the selection and outcomes of multimodal interventional treatment for unruptured brain arteriovenous malformations (AVMs) in A Randomised trial of Unruptured Brain Arteriovenous malformations (ARUBA)-eligible patients in a single institution. Methods: We retrospectively reviewed the data of 94 patients with unruptured and untreated AVMs, who had modified Rankin scale (mRS) scores of 0 or 1 at our institution between 2002 and 2014. The patients were divided into an intervention group and a conservative group, and the outcomes were compared. Similar to ARUBA, we defined the primary outcome as the composite endpoint of death or symptomatic stroke. The mRS was used to assess the functional outcome. Results: Of the 94 patients, 75 were included in the intervention group and 19 were included in the conservative group. Additionally, among the 94 patients, 58, 29, and 7 patients had Spetzler-Martin grade I/II, III, and IV/V AVMs, respectively. The number of male patients and the mean age of the patients were significantly lower in the intervention group than in the conservative group (58.6% vs. 84.2%, P=0.03 and 40.8±13.9 vs. 48.4±18.4 years, P=0.04, respectively). However, no significant difference in the proportion of patients with grade I/II AVMs was noted between the groups (65.3% vs. 47.3%). In the intervention and conservative groups, the mean follow-up periods were 59.2±41.6 and 72.8±39.2 months, respectively (P=0.20), and the primary outcome occurred in 9 (12.3%) and 3 (17.6%) patients, respectively (P=0.56). The proportion of patients with a 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 (4.1% vs. 20%, P=0.003 and 2.0% vs. 15.7%, P=0.04, respectively). Conclusion: The present study found that for patients with unruptured AVMs, interventional treatment is not inferior to medical treatment alone. Multimodal interventional treatment is associated with good outcomes in patients with grade I/II AVMs. However, careful selection should be considered for patients with grade III AVMs.

Abstract WMP116: Multi-center Assessment of Morbidity After Cerebral Arteriovenous Malformation Rupture

Background: Previously published single center studies suggest the morbidity associated with brain arteriovenous malformations (AVM) hemorrhage to be lower than assumed. Given the recent controversy over the appropriate management of unruptured brain AVMs, we performed a multi-center critical assessment of the morbidity associated with ruptured brain AVMs. Methods: A retrospective chart review from tertiary care, urban, academic medical centers was performed. Inclusion criteria consisted of patients admitted for intracranial hemorrhage caused by a previously untreated AVM. Thirty-seven variables were analyzed, including patient demographics, imaging findings, clinical course and clinical exams. Results: 101 patients from three medical centers dating from 2008-2014 met the inclusion criteria. Admission NIHSS scores of 0, 1-9 and ≥10 were 26%, 29% and 45% respectively. Hematoma location was parenchymal in 32%, intraventricular in 11%, subarachnoid in 5%, and combined in 52%. Deep venous drainage was present in 43% of cases, and associated aneurysms were present in 44%. Thirty-seven percent underwent emergent hematoma evacuation while 8 patients expired during their admission. At discharge, of those that survived, 69% had a NIHSS ≥ 1, and 23% had a NIHSS ≥ 10. At 90 day follow-up, 27% had a mRS ≥ 3. Patients with admission NIHSS ≥ 10 had significantly higher rates of midline shift, surgical hematoma evacuation, and follow-up mRS ≥ 3( p &lt; 0.05). Conclusion: This multicenter critical assessment of the morbidity associated with brain AVM rupture suggests poorer clinical outcomes than previously assumed and reported. Rupture morbidity should be considered alongside rupture risk and procedural risk when considering preventative anatomic treatment of unruptured brain AVMs.