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Background: Language dysfunction is rarely seen in patients with unruptured brain arteriovenous malformation (AVM) albeit the AVM nidus involving language areas, which provides a unique disease model to study language reorganization. The objective of this study was to investigate the impairment and reorganization patterns and characteristics of language-related white matter in AVMs located at different brain areas. Methods: Thirty-three patients with AVMs involving language areas were prospectively enrolled. Patients were categorized into 3 groups according to the lesion locations: the frontal (14 patients), temporal (15 patients), and parietal groups (4 patients). Thirty age- and sex-matched healthy controls were enrolled as comparison. All participants underwent diffusion tensor imaging scans, and automated fiber quantification method was applied to quantitatively study the difference of segmented language-related white matter connectivity between 3 AVM groups and control group. Results: Language functions were normal in all subjects according to Western Aphasia Battery test. In the frontal group, fractional anisotropy (FA) value decreased in the left arcuate fascicle and increased in left superior longitudinal fasciculus and uncinate fascicle; in the temporal group, FA values decreased in left inferior fronto-occipital fascicle and inferior longitudinal fascicle and increased in right anterior thalamic radiation and uncinate fascicle; in the parietal group, FA values decreased in left arcuate fascicle and inferior longitudinal fascicle and increased in bilateral anterior thalamic radiations and uncinate fascicles and right inferior fronto-occipital fascicle. In fascicles with decreased FA values, the increase of radial diffusivity was common, and fascicles with increased FA values usually presented along with increased axial diffusivity values. Conclusions: Remodeling of language-related white matter occurs when traditional language areas are involved by AVM nidus, and its reorganization patterns vary with locations of AVM nidus. Fascicle impairment is mainly caused by the myelin deficits, and its plasticity may be dominated by the axon remodeling procedure.

Rationale: Brain arteriovenous malformations (bAVMs) are abnormal entanglement of blood vessels in brain, with direct connections from arteries to veins, lacking functional capillary bed. Although several somatic mutations were reported, the molecular mechanism and genetic disposition of bAVM remain poorly understood. Objective: We aim to identify transcriptional anomalies and critical functional pathways in bAVM lesions and explore their association with key de novo germline and somatic variants in bAVM patients. Methods and Results: We established a comprehensive bAVM dataset from 269 patients, by performing single-cell sequencing of 17 bAVM lesions, whole-exome sequencing of germline DNA from 60 case-unaffected-parental trios, and genomic/transcriptomic sequencing of 231 bAVM lesions. We found abnormal expression of endothelial and mesenchymal markers in bAVM at both bulk and single-cell level, which was validated by flow cytometric analysis and immunofluorescence staining, suggesting an involvement of endothelial-to-mesenchymal transition (EndMT) process in AVM (arteriovenous-malformation). Using data from the 60 trios, we identified nonsynonymous de novo germline mutations affecting 46 genes, including EXPH5 (detected in 2 independent cases), and vessel-related genes, such as EPAS1 and ENG . Interestingly, knockdown of epas1 in zebrafish embryo showed AVM-like phenotype exclusively in brain. Subsequent computational and experimental analyses demonstrated that expression of genes affected by de novo germline mutations was enriched in vascular cell types and was involved in EndMT-relevant behaviors including cell migration, angiogenesis, and cell marker transition. Moreover, we detected somatic KRAS mutations in 129 of 179 (72%) cases and showed that KRAS mutations were associated with bleeding as the first symptom ( P =0.0072). Following experimental studies demonstrated that KRAS mutations independently regulated EndMT features, consolidating the involvement of EndMT in this disease. Lastly, we showed that lovastatin reversed EndMT features in vitro and ex vivo. Conclusions: Our results suggest the convergent role of de novo germline mutations and somatic mutations in regulating EndMT in bAVM and provided a potential therapeutic option.

BACKGROUND Pediatric brain arteriovenous malformations (AVMs) are a significant cause of morbidity but the role of multimodal therapy in the treatment of these lesions is not well understood. OBJECTIVE To compare the outcomes of stereotactic radiosurgery (SRS) with and without prior embolization for pediatric AVMs. METHODS We retrospectively evaluated the International Radiosurgery Research Foundation pediatric AVM database. AVMs were categorized, based on use of pre-embolization (E + SRS) or lack thereof (SRS-only). Outcomes were compared in unadjusted and inverse probability weight (IPW)-adjusted models. Favorable outcome was defined as obliteration without post-SRS hemorrhage or permanent radiation-induced changes (RIC). RESULTS The E + SRS and SRS-only cohorts comprised 91 and 448 patients, respectively. In unadjusted models, the SRS-only cohort had higher rates of obliteration (68.5% vs 43.3%

Importance Postpartum hemorrhage (PPH) is an emergent obstetric complication and the leading cause of maternal mortality. Pelvic arterial embolization (PAE) is an effective treatment for intractable PPH. However, a unique protocol has not been accepted in obstetrical practice. Objective To evaluate its efficiency, safety, complications, and outcomes, we conducted a systematic review and meta-analysis of PAE for PPH in the literature. Evidence Acquisition The Medline, the database of abstract of reviews, the index to allied health literature, and the Chinese database Sino-Med were searched on March 31, 2020, for studies on PAE for PPH. The data for PAE indication, agents, arteries, success rate, complications, and outcomes were extracted and syncretized for meta-analysis. Results From 1075 identified articles, 113 abstracts or full articles were retrieved and 43 studies were finally identified as meeting the including criteria. The results demonstrated that the indications for PAE were as follows: uterine atony, placental abnormality, delivery tract injury, disseminated intravascular coagulation, arteriovenous malformation, and vaginal hematoma. The embolization agents mostly in order were gelatin sponge particles, polyvinyl alcohol particles, Gelfoam, N-butyl cyanoacrylate, microcoil, and glue; for arteries, they were mostly uterine artery and internal iliac artery. The clinical success rate was 90.5%, whereas the technical success rate was 99.3%. The most common complications of PAE were postembolization syndrome and menstrual abnormality. Conclusions and Relevance The emergent PAE is a safe and effective method with high success rate in life-threatening PPH management. Gelatin sponge granules measuring 500 to 1000 μm in diameter have safe results. Pelvic arterial embolization may affect the recovery of menses and increase PPH in the subsequent pregnancy, but there was no noted correlation with fetal growth restriction. Target Audience Obstetricians and gynecologist, family physicians Learning Objectives After participating in this activity, physicians should be better able to explain the causes of PPH; identify which arteries should be chosen for embolization; and describe the advantages of PAE for PPH management.

Background: The aim of this study was to examine the efficacy and safety of treating large or eloquently located intracranial arteriovenous malformations (AVMs) with fractionated stereotactic radiosurgery (FSRS). Materials and Methods: Eighteen patients with AVM treated with FSRS between March 2006 and August 2018 were retrospectively evaluated. The nidus obliteration, volume reduction, rate of rebleeding, newly onset neurological deficit, and signal change in magnetic resonance imaging (MRI) were evaluated. Results: With a median follow-up of 88 months (range: 24–154), 6 of the 18 lesions (33.3%) had a complete obliteration. All obliteration occurred in patients received the total treatment dose of 21 Gy (6 of 9 patients, 66.7%). The median time to complete obliteration was 38 months (range: 12–53). The mean volume reduction after FSRS in the 25 Gy group was 30.2% ± 20.9% and that in the 21 Gy group was 87.7% ± 24.2%. During the follow-up period, 4 of 18 (22.2%) lesions revealed T2 signal change in the MRI. No FSRS-related complication was noted clinically or radiologically. Conclusion: According to the present results, FSRS could be an effective and safe treatment alternative for complicated AVMs. Delayed toxicity after treatment is not noticed in the current study, but long-term follow-up is required. A higher dose in total and each fraction is likely needed when treating larger lesions.

Spinal epidural hematoma (SEH) is a rare disease and may lead to spinal cord compression. It could be caused by trauma, including iatrogenic procedures such as spinal surgery or spinal anesthesia or by spontaneous events related to coagulopathy or arteriovenous malformation. Once SEH is suspected clinically and confirmed by image modalities, it should be emergently decompressed by surgical intervention. Prognosis depends on the rate of symptoms development, interval from symptom onset to surgery, level of spinal involvement, and degree of neurological deficits. Here, we report the case of a 79-year-old female who sustained a fall months before admission, presented with a 3-day history of back and bilateral lower limbs weakness. Radiography and magnetic resonance imaging demonstrated epidural hematomas at the level of T12 to L2 without associated vertebral fracture. An urgent decompressive laminectomy with blood clot removal was performed immediately. Postoperatively, her neurologic deficits improved significantly except for residual numbness.

BACKGROUND: Adequate surgical planning includes a precise understanding of patient-specific anatomy and is a necessity for neurosurgeons. Although the use of virtual reality (VR) technology is emerging in surgical planning and education, few studies have examined the effectiveness of immersive VR during surgical planning using a modern head-mounted display. OBJECTIVE: To investigate if and how immersive VR aids presurgical discussions of cerebrovascular surgery. METHODS: A multiuser immersive VR system, BananaVision(TM), was developed and used during presurgical discussions in a prospective patient cohort undergoing cerebrovascular surgery. A questionnaire/interview was administered to multiple surgeons after the surgeries to evaluate the effectiveness of the VR system compared to conventional imaging modalities. An objective assessment of the surgeon's knowledge of patient-specific anatomy was also conducted by rating surgeons' hand-drawn presurgical illustrations. RESULTS: The VR session effectively enhanced surgeons' understanding of patient-specific anatomy in the majority of cases (83.3%). An objective assessment of surgeons' presurgical illustrations was consistent with this result. The VR session also effectively improved the decision-making process regarding minor surgical techniques in 61.1% of cases and even aided surgeons in making critical surgical decisions about cases involving complex and challenging anatomy. The utility of the VR system was rated significantly higher by trainees than by experts. CONCLUSION: Although rated as more useful by trainees than by experts, immersive 3D VR modeling increased surgeons' understanding of patient-specific anatomy and improved surgical strategy in certain cases involving challenging anatomy.

Background Embolization of brain arteriovenous malformations (AVMs) using ethylene-vinyl alcohol copolymer (Onyx) embolization may influence the treatment effects of stereotactic radiosurgery (SRS) differently than other embolysates. Objective To compare the outcomes of pre-SRS AVM embolization with vs without Onyx through a multicenter, retrospective matched cohort study. Methods We retrospectively reviewed International Radiosurgery Research Foundation AVM databases from 1987 to 2018. Embolized AVMs treated with SRS were selected and categorized based on embolysate usage into Onyx embolization (OE + SRS) or non-Onyx embolization (NOE + SRS) cohorts. The 2 cohorts were matched in a 1:1 ratio using de novo AVM features for comparative analysis of outcomes. Results The matched cohorts each comprised 45 patients. Crude AVM obliteration rates were similar between the matched OE + SRS vs NOE + SRS cohorts (47% vs 51%; odds ratio [OR] = 0.837, P = .673). Cumulative probabilities of obliteration were also similar between the OE + SRS vs NOE + SRS cohorts (subhazard ratio = 0.992, P = .980). Rates of post-SRS hemorrhage, all-cause mortality, radiation-induced changes, cyst formation, and embolization-associated complications were similar between the matched cohorts. Sensitivity analysis for AVMs in the OE + SRS cohort embolized with Onyx alone revealed a higher rate of asymptomatic embolization-associated complications in this subgroup compared to the NOE + SRS cohort (36% vs 15%; OR = 3.297, P = .034), but the symptomatic complication rates were similar. Conclusion Nidal embolization using Onyx does not appear to differentially impact the outcomes of AVM SRS compared with non-Onyx embolysates. The embolic agent selected for pre-SRS AVM embolization should reflect both the experience of the neurointerventionalist and target of endovascular intervention.

Undiagnosed significant hydrocephalus is an uncommon finding at forensic autopsy as many cases present in life with complex neurological symptoms. We present a case of a 46-year-old man with no neurological deficits or history of head trauma that was incidentally found to have a massive hydrocephalus at autopsy. This was found to be associated with an unruptured arteriovenous malformation completely confined to the choroid plexus as well as complete agenesis of the corpus callosum. The arteriovenous malformation was found to form a calcified obstruction at the foramen of Monro analogous to a mass lesion, such as a colloid cyst of the third ventricle. The association of this malformation and agenesis of the corpus callosum has never been described. Histologic examination of the brain confirmed significant loss of white matter tracts and thinning of the cortical ribbon due to pressure atrophy of the ependymal lining without significant gliosis, cortical dysplasia, or evidence of other developmental malformations. Autopsy is a vital tool in the evaluation of such rare cases, enhances epidemiologic data, and increases the understanding of these pathophysiological associations.

Background Distal transradial catheterization in the anatomic snuffbox is an alternate route of access that has started to gain consideration for neuroendovascular procedures. Objective To assess the feasibility and outcomes and present our institution's experience in performing neuroendovascular procedures via distal transradial access (dTRA). Methods We conducted a retrospective analysis and identified 120 patients who underwent consecutive neuroendovascular procedures via dTRA in the anatomic snuffbox. Data collection was performed on indication for procedure, sheath size, number of vessels selectively catheterized, fluoroscopy time, procedure duration, radiation exposure, conversion to femoral approach, access site complication, and procedure success. Results Of 120 patients with an average age of 54.7 yr ± 14.7, 73 (60.8%) underwent diagnostic angiograms, 38 (31.7%) underwent follow-up angiograms, and 9 (7.5%) underwent therapeutic procedures. The overall mean number of vessels catheterized was 2.5 ± 0.1 per procedure, the mean procedure time was 68.3 min ± 43.4, the mean fluoroscopy time was 10.8 min ± 7.6, the mean contrast dose was 70.6 mL ± 39.1, and the mean radiation exposure was 27 672.2 mGycm2 ± 42 728.4. Successfully completed therapeutic procedures included aneurysm 1 (0.8%), arteriovenous malformation (AVM)/arteriovenous fistula/carotid cavernous fistula 7 (5.8%), and 1 (0.8%) other treatment. Three patients (2.5%) required adjunct transfemoral endovenous access for AVM embolization. Two minor complications (1.67%) were a local wrist hematoma and a radial artery vasospasm without any sequelae. Conclusion Distal radial artery catheterization in the anatomic snuffbox is a safe and effective access site to perform neuroendovascular procedures. Complications and conversion rate are low making it a safe alternative.

Author(s): Graffeo, Christopher S; Sahgal, Arjun; De Salles, Antonio; Fariselli, Laura; Levivier, Marc; Ma, Lijun; Paddick, Ian; Regis, Jean Marie; Sheehan, Jason; Suh, John; Yomo, Shoji; Pollock, Bruce E | Abstract: BackgroundNo guidelines have been published regarding stereotactic radiosurgery (SRS) in the management of Spetzler-Martin grade I and II arteriovenous malformations (AVMs).ObjectiveTo establish SRS practice guidelines for grade I-II AVMs on the basis of a systematic literature review.MethodsPreferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant search of Medline, Embase, and Scopus, 1986-2018, for publications reporting post-SRS outcomes in ≥10 grade I-II AVMs with a follow-up of ≥24 mo. Primary endpoints were obliteration and hemorrhage; secondary outcomes included Spetzler-Martin parameters, dosimetric variables, and "excellent" outcomes (defined as total obliteration without new post-SRS deficit).ResultsOf 447 abstracts screened, 8 were included (n = 1, level 2 evidence; n = 7, level 4 evidence), representing 1102 AVMs, of which 836 (76%) were grade II. Obliteration was achieved in 884 (80%) at a median of 37 mo; 66 hemorrhages (6%) occurred during a median follow-up of 68 mo. Total obliteration without hemorrhage was achieved in 78%. Of 836 grade II AVMs, Spetzler-Martin parameters were reported in 680: 377 were eloquent brain and 178 had deep venous drainage, totaling 555/680 (82%) high-risk SRS-treated grade II AVMs.ConclusionThe literature regarding SRS for grade I-II AVM is low quality, limiting interpretation. Cautiously, we observed that SRS appears to be a safe, effective treatment for grade I-II AVM and may be considered a front-line treatment, particularly for lesions in deep or eloquent locations. Preceding publications may be influenced by selection bias, with favorable AVMs undergoing resection, whereas those at increased risk of complications and nonobliteration are disproportionately referred for SRS.

Background Long-term data regarding stereotactic radiosurgery (SRS) as a standalone therapy for unruptured pediatric brain arteriovenous malformations (AVMs) are incompletely defined. Objective To evaluate, in a multicenter, retrospective cohort study, the outcomes after SRS for unruptured, intervention-naive pediatric AVMs. Methods 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. Results 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. Conclusion Treatment of unruptured, intervention-naive 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.

A patient with multiple episodes of gastrointestinal bleeding underwent Tc-labeled red blood cell scintigraphy to detect the source of bleeding, which showed a focally increased activity in the upper midabdomen. SPECT/CT demonstrated that the activity was located in the pancreatic head. Angiography confirmed the diagnosis of pancreatic arteriovenous malformation. After transarterial embolization therapy, the patient no longer had bleeding episode. Based on the present case, pancreatic arteriovenous malformation should be included as differential diagnosis during Tc-red blood cell scintigraphy.

A 30-year-old woman presented with diplopia after resection of an intracranial cavernous malformation. Fundus examination showed an asymptomatic intraocular cavernous hemangioma of the retina. Clinicians should be aware of the potential coexistence of intraocular and intracranial cavernous malformations; the presence of both should suggest familial etiology. As with other intracranial and intraocular vascular lesions (e.g., arteriovenous malformation in Wyburn-Mason syndrome, retinal hemangioblastoma in von Hippel Lindau disease, and choroidal hemangioma in Sturge-Weber syndrome), the presence of a vascular lesion in either location should prompt evaluation for additional pathology.

Objectives This article discusses the diagnosis, imaging workup, and management of a rare cause of pulsatile tinnitus: intraparotid arteriovenous malformation. Patient A single patient with a superficial temporal arteriovenous malformation diagnosed by carotid duplex causing pulsatile tinnitus that failed initial surgical management. Repeat imaging failed to identify a cause for the persistent tinnitus. Intervention Reoperation with a parotid approach based on physical exam findings. Results Removal of a more proximal arteriovenous malformation in the parotid gland resulted in long-term resolution of the patient's pulsatile tinnitus. Conclusions Physical examination is essential in the workup and management of pulsatile tinnitus. Imaging is a useful adjunct in the diagnosis of pulsatile tinnitus but should not be solely relied upon.

Background Gamma Knife radiosurgery (GKRS) obliterates 65% to 82% of brain arteriovenous malformations (BAVMs). Objective To explore the impact of hemodynamics on GKRS outcomes. Methods We retrospectively (2011-2017) included 98 patients with BAVMs who had received GKRS alone. Two evaluators, blinded to the outcomes, analyzed the pre-GKRS angiography and magnetic resonance images to obtain the morphological characteristics and quantitative digital subtraction angiography (QDSA) parameters. The venous stasis index was defined as the inflow gradient divided by the absolute value of the outflow gradient. Patients' follow-up magnetic resonance or digital subtraction angiography images were evaluated for the presence of complete obliteration (CO). Cox regression and Kaplan-Meier analyses were conducted to determine the correlations between the parameters and outcomes. Results Among the 98 patients, 63 (63.4%) achieved CO after GKRS at a median latency period of 31 mo. In multivariable analyses with adjustments for age and sex, increased BAVM volume (hazard ratio (HR) 0.949, P = .022) was an independent characteristic predictor, and venous stenosis (HR 2.595, P = .009), venous rerouting (HR 0.375, P = .022), and larger stasis index (HR 1.227, P = .025) were independent angiographic predictors of CO. BAVMs with a stasis index of >1.71 had a higher 36-mo probability of CO than those with a stasis index of ≤1.71 (61.1% vs 26.7%, P Conclusion BAVMs with a larger stasis index, indicating more stagnant venous outflow, may predict obliteration after GKRS. QDSA analysis may help in predicting BAVM treatment outcomes and making therapeutic decisions.

Background Arteriovenous malformation (AVM) rupture is highly morbid. Outcomes after AVM rupture differ from other types of brain hemorrhage. There are no specific widely used grading systems designed to predict clinical outcome after AVM rupture. Objective To develop an all-comers scoring system to grade patients with AVM rupture and predict clinical outcome more accurately than grading systems currently in use. Methods We retrospectively reviewed patients who presented to our institution with a ruptured AVM. Using change in modified Rankin Score (mRS) as our response variable, we generated an ordinal logistic regression model to test for significant predictor variables. The full model was sequentially condensed until the simplest model with the highest area under the receiver operating curve (AUROC) was achieved. Results A total of 115 patients who presented with ruptured AVMs were included in the study, with a mean follow-up time of 4 yr. The Ruptured AVM Grading Scale (RAGS) consists of the Hunt and Hess (HH) score (1-5), patient age ( 70 = 2), deep venous drainage (1), and eloquence (1). The RAGS score outperformed other neurosurgical grading scales in predicting change in mRS, with an AUROC greater than 0.80 across all follow-up periods. Conclusion The RAGS score is a simple extension of the HH scale that predicts clinical outcome after AVM rupture more accurately than other grading systems.

BACKGROUND Single-session stereotactic radiosurgery (SRS) for large arteriovenous malformations (AVMs) ≥10 mL remains controversial, which is considered as the current size limitation. OBJECTIVE To reconsider the size limitation of SRS for AVMs by profoundly analyzing dose-volume relationship. METHODS Data on 610 consecutive patients with AVM treated with SRS using regular (18-22 Gy) or low (

Background and Purpose— The management of unruptured brain arteriovenous malformations remains unclear. Using a large cohort to determine risk factors predictive of hemorrhagic presentation of arteriovenous malformations, this study aims to develop a predictive tool that could guide hemorrhage risk stratification. Methods— A database of 789 arteriovenous malformation patients presenting to our institution between 1990 and 2017 was used. A hold-out method of model validation was used, whereby the data was randomly split in half into training and validation data sets. Factors significant at the univariable level in the training data set were used to construct a model based on multivariable logistic regression. Model performance was assessed using receiver operating curves on the training, validation, and complete data sets. The predictors and the complete data set were then used to derive a risk prediction formula and a practical scoring system, where every risk factor was worth 1 point except race, which was worth 2 points (total score varies from 0 to 6). The factors are summarized by R 2 eD arteriovenous malformation (acronym: R 2 eD AVM). Results— In 755 patients with complete data, 272 (36%) presented with hemorrhage. From the training data set, a model was derived containing the following risk factors: nonwhite race (odds ratio [OR]=1.8; P =0.02), small nidus size (OR=1.47; P =0.14), deep location (OR=2.3; P< 0.01), single arterial feeder (OR=2.24; P< 0.01), and exclusive deep venous drainage (OR=2.07; P =0.02). Area under the curve from receiver operating curve analysis was 0.702, 0.698, and 0.685 for the training, validation, and complete data sets, respectively. In the entire study population, the predicted probability of hemorrhagic presentation increased in a stepwise manner from 16% for patients with no risk factors (score of 0) to 78% for patients having all the risk factors (score of 6). Conclusions— The final model derived from this study can be used as a predictive tool that supplements clinical judgment and aids in patient counseling.

Background and Purpose— Understanding the hemorrhage risks associated with brain arteriovenous malformations (AVMs) before and after stereotactic radiosurgery (SRS) is important. The aims of this multicenter, retrospective cohort study are to evaluate and compare the rates of pre- and post-SRS AVM hemorrhage and identify risk factors. Methods— We pooled AVM SRS data from 8 institutions participating in the International Radiosurgery Research Foundation. Predictors of post-SRS hemorrhage were determined using a multivariate logistic regression model. Pre- and post-SRS hemorrhage rates were compared using Fisher exact test. Ruptured and unruptured AVMs were matched in a 1:1 ratio using propensity scores, and their outcomes were compared. Results— The study cohort comprised 2320 AVM patients who underwent SRS. Deep AVM location (odds ratio, 1.86; 95% CI, 1.19–2.92; P =0.007), the presence of an AVM-associated arterial aneurysm (odds ratio, 2.44; 95% CI, 1.63–3.66; P P =0.005) were independent predictors of post-SRS hemorrhage. The post-SRS hemorrhage rate was lower for obliterated versus patent AVMs (6.0 versus 22.3 hemorrhages/1000 person-years; P P =0.001). The outcomes of the matched ruptured versus unruptured AVM cohorts were similar. Conclusions— SRS appears to reduce the risk of AVM hemorrhage, although this effect is predominantly driven by obliteration. Deep-seated AVMs are more likely to rupture during the latency period after SRS. AVM-associated aneurysms should be considered for selective occlusion before SRS of the nidus to ameliorate the post-SRS hemorrhage rate of these lesions.

BACKGROUND Arteriovenous malformations (AVMs) in pediatric patients exhibit remarkable differences in terms of management and outcomes. Owing to a paucity of relevant data pertaining to AVMs in pediatric patients, special interest and investigation are required for an improved understanding of the available evidence by clinicians. OBJECTIVE To determine the clinical outcomes of single-session stereotactic radiosurgery (SRS) for AVMs in pediatric patients. METHODS A systematic literature review was performed to identify studies that reported the outcomes of SRS for AVMs in pediatric patients. Data pertaining to variables such as obliteration rate, post-SRS new hemorrhage rate, post-SRS new neurological deficit rate, and mortality rate were extracted and analyzed using meta-analysis techniques. RESULTS Based on pooled data from 20 studies with 1212 patients, single-session SRS resulted in complete obliteration in 65.9% (95% confidence interval [CI], 60.5%-71.1%; I2 = 66.5%) patients. Overall complication rate (including new hemorrhage, new neurodeficit, and mortality) was 8.0% (95% CI, 5.1%-11.5%; I2 = 66.4%). Post-SRS new neurological deficit rate was 3.1% (95% CI, 1.3%-5.4%; I2 = 59.7%), and post-SRS hemorrhage rate was 4.2% (95% CI, 2.5%-6.3%; I2 = 42.7%). There was no significant difference between studies disaggregated by treatment method (Gamma Knife [Elekta AB] vs other), treatment year (before year 2000 vs after year 2000), median AVM volume reported (≥3 vs

Embolization is a well-established method of treatment of arteriovenous malformations. Most procedures are performed under general anesthesia due to the painful nature of some sclerosing agents, procedure duration, and need for immobilization to allow precise injection. Familiarity with the possible side effects of these agents is important for the anesthesiologist to facilitate timely and successful management of intra- and postprocedural complications. This case report describes an unusual presentation of systemic migration of glue-lipiodol mixture during embolization of a calf arteriovenous malformation in an adolescent that resulted in accelerated idioventricular rhythm and its successful management leading to complete resolution.

Background 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. Objective To determine the incidence rate and predisposing factors of SpO in a North American cohort. Methods 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. Results 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%. Conclusion 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.

Purpose The clinical significance of postoperative pseudomeningocele formation following optic nerve sheath fenestration (ONSF) has not been fully characterized. A literature review identifies 9 previously published cases the authors believe demonstrate pseudomeningocele formation and approximately 19 other similar findings that were either transient or less defined blebs. This study was undertaken to more clearly define the clinical, radiographic, and histopathologic features associated with this entity. Methods Sixteen-year, single-center, retrospective chart review of all ONSF cases performed by 2 surgeons. Clinical data, intracranial pressure, radiographic imaging, and histopathology of clinically detected pseudomeningoceles after ONSF were reviewed. Results Eighty-six eyes in 57 patients underwent ONSF (28 unilateral, 12 bilateral sequential, 17 bilateral simultaneous). Forty-nine of 57 patients had elevated intracranial pressure preoperatively (41 idiopathic intracranial hypertension, 4 venous thrombosis, 2 meningitis, 1 arteriovenous malformation, and 1 sarcoid). In 32 patients undergoing postoperative imaging, 4 eyes (4.7%) in 4 patients developed well-defined pseudomeningoceles, of which 3 were symptomatic and 2 required surgical revision. Each pseudomeningocele developed in the setting of elevated preoperative intracranial pressure (350, 360, 430, 500 mm H20). Magnetic resonance imaging and/or computed tomography revealed sharply demarcated fluid-filled sacs adjacent to the optic nerve. The contents of these sacs were hypointense on T1-weighted imaging, hyperintense on T2-weighting, variably enhanced with contrast, and hypointense on fluid attenuated inversion recovery, and were thus consistent with cerebrospinal fluid. Histopathologic analysis of one of these outpouchings demonstrated an acellular, fibrocollagenized lining consistent with pseudomeningocele. Three eyes in 3 additional patients had less well-defined findings on imaging interpreted as bleb-like or cyst-like change. Conclusions Pseudomeningoceles following ONSF may be asymptomatic or may cause symptomatic orbital mass effect and rarely visual loss, amendable to surgical excision. Post-ONSF pseudomeningoceles are identified on computed tomography or magnetic resonance imaging to occur at the locations of fenestration sites and contain cerebrospinal fluid communicating with the subdural space that may act as a "filtration" bleb in some cases. Imaging findings may represent a spectrum spanning intraorbital cerebrospinal fluid leakage, partial walling off of bleb, or fully developed cysts. Resection of optic nerve pseudomeningoceles is considered in symptomatic cysts or eyes with papilledema that fails to improve.

Background: Accurate and reliable models of intracranial hemorrhage (ICH) risk in the untreated course of brain arteriovenous malformation (BAVM) patients are needed to help weigh the risk-benefit of treatment. We present preliminary estimates of rates and risk factors for ICH or death in the Multicenter AVM Research Study (MARS), which is the largest individual patient data meta-analysis (IPDMA) of cohort studies of unruptured BAVM. Methods: Longitudinal data from 9 cohorts comprising 2,839 unruptured BAVM at time of diagnosis were included: UCSF (n=557), Macquarie (n=462), Kaiser Permanente Northern California (n=354), Columbia (n=335), Barrow Neurological Institute (n=324), Tiantan Hospital (n=303), Mayo Clinic-Rochester (n=244), Scottish Intracranial Vascular Malformation Study (n=194), and Toronto Western Hospital (n=66). Clinical and angiographic data were collected using standardized definitions across cohorts. Cox proportional hazards analysis of time-to-event (ICH or death) in the untreated course after diagnosis was performed, censoring at first treatment or last visit. Baseline hazard rates were stratified by cohort to account for different rates and follow-up times. Results: The combined cohort was 49% female, 72% white race, and 17% Hispanic ethnicity; mean age at diagnosis was 37±17 years and mean follow-up was 3.4±7.0 years. The most common presenting symptom was seizures (43%). Mean AVM size was 3.5±1.9 cm and 46% were Spetzler-Martin grade I-II. Overall, 123 ICH and 131 deaths occurred over 9,608 person-years (PY) for an event rate of 2.64 per 100 PY [95% CI: 2.34-2.99]. Cox regression analyses adjusting for age at diagnosis (HR=1.67 [1.54, 1.82], P Conclusion: Our current model identified increasing age, exclusively deep venous drainage, and cerebellar location as risk factors for ICH or death in the untreated course of unruptured bAVM patients. Review of imaging data, multiple imputation of missing angioarchitectural data, and additional data from pending cohorts will provide greater power to search for additional risk factors in this ongoing IPDMA.

Background and Purpose: Deletion of Endoglin (Eng), an arteriovenous malformation (AVM) causative gene causes AVM in the brain angiogenic region. Reduction of pericytes is correlate with brain AVM hemorrhage. The platelet-derived growth factor B and its receptor β (PDGF-B/PDGFRβ) play important roles in regulating pericyte recruitment during angiogenesis. We hypothesize that mutation of PDGFRβ causes cerebrovascular malformation and enhances bAVM severity in Eng mutant mice. Methods: Three mouse models were used: (1) Pdgfrβ F7 (F7) mice that have mutations disrupting Pdgfrβ signaling, (2) Pdgfb -icreER; Eng f /f mice that have Pdgfb promoter driving, tamoxifen (TM) inducible cre expression in ECs and an floxed Eng gene; and (3) Pdgfb -icreER; Eng f /f ;F7 +/- mice. Brain angiogenesis was induced by intra-brain injection of an adeno-associated viral vector expressing vascular endothelial growth factor (AAV-VEGF). Brain AVMs were induced in Pdgfb -icreER; Eng f /f and Pdgfb -icreER; Eng f /f ;F7 mice by TM induced EC Eng deletion and intra-brain AAV-VEGF injection. Brain AVM phenotypes were analyzed 8-weeks after model induction by latex vascular cast to detect arteriovenous shunts and macroscopic level of AVMs, immunostaining and Prussian blue staining to quantify dysplasia vessels and hemorrhage. Results: Compared to WT mice, F7 +/- and F7 +/+ mice have more dysplastic vessels and fewer vascular pericyte before and after AAV-VEGF injection. F7 +/- and F7 +/+ mice showed hemorrhage on the AAV-VEGF injection sites and AVM like vessels (a few arteriovenous shunts) in 16% F7 +/- and 66% of F7 +/+ mice. Pdgfb -icreER; Eng f /f mice showed dysplastic vessels and hemorrhage at AAV-VEGF injection sites. Compared to Pdgfb -icreER; Eng f /f mice, Pdgfb -icreER; Eng f /f ;F7 +/- had a higher penetrance of bAVM (71% vs 50%) and more dysplastic vessels. Conclusion: F7 mutation cause AVM like structure in mouse brain and exacerbates bAVM phenotype in Eng mutant mice.

Arteriovenous malformations (AVMs) are highly complex vascular lesions characterized by abnormal connections between arteries and an intervening nidus. Definitive and safe treatment of AVMs may require the combination of multiple treatment modalities to address the various complex features of the AVM.1 Endovascular embolization can be used as an adjuvant to surgery in order to control deep feeders, reduce flow, and address high-risk features such as aneurysms. In addition, by progressively reducing the AVM flow, staged embolization can lead to normalization of peri-AVM hemodynamics and therefore may decrease the risk of postresection hemorrhage.2,3 In this operative video, we present a case of a 41-yr-old female who presented with progressively worsening left-sided hemiparesis. Magnetic resonance imaging (MRI) and angiography revealed a complex right fronto-parietal AVM with significant associated edema, likely due to the vascular steal phenomenon. The area of edema, which included the motor cortex, was thought to be at high risk for postoperative hemorrhage from normal perfusion pressure breakthrough. We therefore decided to proceed with staged presurgical embolization to gradually normalize the perilesional hemodynamics, and therefore possibly reduce the risk of postoperative morbidity. The patient underwent 3 embolization sessions at 6-wk intervals. An MRI after the last embolization showed near-complete resolution of the fluid-attenuated inversion-recovery (FLAIR) signal around the AVM. Microsurgical resection was performed on the day after the last embolization. The patient tolerated the procedure well and was discharged at her neurological baseline with mild contralateral hemiparesis, which has continued to improve at follow-up. Postoperative angiography showed complete resection of the AVM. The patient consented to the procedure as shown in this operative video and gave informed written consent for use of her images in publication.

Arteriovenous malformation (AVM) is an abnormal vascular formation where the artery and vein are connected directly to each other without capillary connections. Although it is common in the head and neck region, AVMs located in the parotid gland are quite rare. A 12-year-old female patient presented to our clinic with a mass in her left cheek area. As a result of physical examinations and tests, she was diagnosed with an AVM limited to the left parotid gland superficial lobe. Clinical follow-up was performed for AVM which has no sign except for prominence with Valsalva and surface temperature increase. The case was presented with a literature review.

Introduction: 3D printed human vascular in vitro models of aneurysms and acute stroke have been utilized for training, simulation and device development. However, there are no realistic in vitro arteriovenous malformation (AVM) models. Current experimental models analyzing the efficacy of embolic materials or flow conditions are limited by their simplistic design, lacking complex AVM nidus anatomic features. The purpose of this study is to develop a new in vitro AVM model for embolic material testing and flow analysis. Methods: 3D images of the AVM nidus were extracted from 3D rotational angiography from a patient. Artificial feeders and drainers were added to the nidus and an inner vascular mold was printed using a 3D printer. The inner mold was coated with polydimethylsiloxanes. The inner plastic mold was removed by acetone, leaving a hollow AVM model. ONYX injection and 4DFlow MRI (Phase Contrast MRA) were performed using the AVM models. In addition, computational fluid dynamics (CFD) analysis was performed to compare flow rate with 4DFlow MRI. Results: An in vitro AVM model with realistic representation of nidus vasculature and complexity was successfully created. Liquid onyx injection performed in the in vitro model successfully replicated real-life treatment conditions. The model effectively simulated plug and push technique before penetration of the ONYX into the AVM nidus. 4DFlow MRI flow rates were similar to the CFD analysis. Conclusions: An in vitro AVM model using 3D printing technology was successfully created. The model demonstrated realistic pliability during ONYX injection. This in vitro AVM model may represent a useful tool for training and development of new materials, and have potential of highly-resolved flow quantifications.

Introduction: Microglia are closely communicating with endothelial cells and involved in cerebrovascular disease. In brain arteriovenous malformation (bAVM), microglia are highly detected in the vascular walls and brain parenchyma, however, the role of microglia in bAVM are not clear. Meanwhile, soluble endoglin (sENG) has been involved in inflammation and endothelial dysfunction in bAVM. Therefore, we hypothesized that microglia mediate sENG-induced endothelial dysfunction in bAVM. Methods: sENG was subcutaneously injected to mice with VEGF overexpression in the brain. After latex casting to visualize brain vasculature, dysplastic capillaries were measured by Zen software. Microglia was detected by iba-1 staining. In in vitro , sENG or vehicle was treated in BV2 microglial cell line and the cultured media from BV2 (BV2-CM) were transferred to primary mouse brain endothelial cell (EC). We determined the expression of inflammatory/angiogenic factors in the BV2 and EC, and tested the tube formation in the EC. Results: The sENG with VEGF induced dysplastic/enlarged capillaries in the mouse brain (8567 μm 2 ± 2797 vs 2584 μm 2 ± 763, p in vitro study, sENG increased inflammatory cytokines (TNF-α and IL-6) and angiogenic mediators (MMP-9 and VEGF-A) in BV2 cells. The sENG-treated BV2-CM significantly increased angiogenic factors (Notch-1 and TGF-β) but decreased an anti-angiogenic factor (IL-17RD), and it was accompanied with increased pERK1/2 in EC. In addition, we observed that tube formation is significantly increased in EC treated with sENG-treated BV2-CM. Conclusion: The study shows that sENG-stimulated microglia released inflammatory and angiogenic factors and it regulates endothelial functions. It suggests that microglia may contribute to sENG-induced dysplastic capillary via regulating inflammatory and angiogenic factors.

Introduction: Cerebral arteriovenous malformation (AVM) is an intracranial pial vascular lesion which is treated with microsurgery, endovascular treatment or stereotactic radiosurgery (SRS). We introduce the long-term clinical results of linear accelerator (LINAC) stereotactic radiosurgery for cerebral AVM which is treated in single institution for 18 years period. Methods: Retrospective chart review was held in cerebral AVM patients treated with Novalis (BrainLAB AG, Heimstetten, Germany) stereotactic radiotherapy from 2001 to 2018. Clinical results such as obliteration rate, hemorrhage rate after SRS, and radiosurgery related adverse event was analyzed. Furthermore, predictors for obliteration and symptomatic radiosurgery induced adverse event was analyzed with multivariate logistic regression test. Results: Among 117 patients with cerebral AVMs treated with LINAC-based SRS, 72 were included in study. Total obliteration rate was 80.6% (58/72) for mean 57.0±48.3 months follow up period. Post-SRS hemorrhage and mortality rate was 6.9% (4/72) and 1.4% (1/72), respectively. Mean radiation dose and volume was 22.8Gy and 3.7cc, respectively. Independent predictive factors for nidus obliteration was: (1) radiation dose (OR 1.43, 95% CI 1.04-2.08, p=0.0374), (2) Ruptured AVM (OR 12.18, 95% CI 2.38-86.47, p=0.0054), (3) Virginia AVM score (OR 0.21, 95% CI 0.07-0.53, p=0.0028), and (4) follow up period months (OR 1.03, 95% CI 1.01-1.06, p=0.0261). Independent risk factors for symptomatic radiosurgery related adverse event was radiation volume (OR 1.61, 95% CI 1.09-2.65, p=0.0326). Conclusion: LINAC-based SRS is effective and relatively safe method for treatment of cerebral AVMs. Independent predictive factors for obliteration was high radiation dosage, ruptured status, low Virginia AVM score, and long follow up period. High radiation volume was related to symptomatic radiation induced adverse event.

Introduction: Liquid embolic material (LEM) plays an essential role in the treatment of hemorrhagic stroke caused by arteriovenous malformation or dural arteriovenous fistula. However, currently available non-adhesive LEMs has the problem of catheter entrapment, and also known to have a cytotoxic effect due to the organic solvents such as Dimethyl Sulfoxide (DMSO). The New Generation Liquid Embolic Material (NGLEM) is a clear liquid that immediately forms a solid hydrogel cast upon exposure to Ca2+ in the bloodstream, and organic solvents are not required (Figure1). The performance of this new liquid embolic material was evaluated using an in vivo experimental model using rabbit. Methods: Under general anesthesia, a renal artery of New Zealand rabbit (4.5-5.0kg) was catheterized under fluoroscopy using a microcatheter, and NGLEM was injected into the artery. Following factors were assessed; 1) the amount of LEM required for the complete occlusion, 2) injection speed, 3) duration of the injection, 4) radiopacity during the deployment and 5) incidence of catheter entrapment after the injection. Results: Five renal arteries in five rabbits were treated, and all arteries were completely occluded without technical complication. The injected materials immediately formed LEM cast in all vessels followed by the reflux over the microcatheter. All catheters were withdrawn without any sign of catheter entrapment. The NGLEM mixed with both iodine-based (3 animals) and tantalum based (2 animals) contrasts medium showed sufficient radiopacity under fluoroscopy. With the injection speed of 0.02ml/sec, the average volume required was 0.68ml. Average time for the complete occlusion was 237 seconds. No increased thrombogenicity or vasospasm near the treated lesion was observed during the procedure. Conclusions: NGLEM, which is a DMSO free, non-adhesive bio-polymer may be used as an embolic material for the treatment of hemorrhagic stroke caused by cerebrovascular diseases.

Background: Hereditary Hemorrhagic Telangiectasia type 2 (HHT2) is an inherited genetic disorder characterized by vascular malformations and hemorrhage. HHT2 results from ACVRL1 haploinsufficiency, the remaining wild-type allele being unable to contribute sufficient protein to sustain endothelial cell function. Blood vessels function normally but are prone to respond to angiogenic stimuli, leading to the development of telangiectasic lesions that can bleed. How ACVRL1 haploinsufficiency leads to pathological angiogenesis is unknown. Methods: We took advantage of Acvrl1 +/− mutant mice that exhibit HHT2 vascular lesions and focused on the neonatal retina and the airway system after Mycoplasma pulmonis infection, as physiological and pathological models of angiogenesis, respectively. We elucidated underlying disease mechanisms in vitro by generating Acvrl1 +/− mouse embryonic stem cell lines that underwent sprouting angiogenesis and performed genetic complementation experiments. Finally, HHT2 plasma samples and skin biopsies were analyzed to determine whether the mechanisms evident in mice are conserved in humans. Results: Acvrl1 +/− retinas at postnatal day 7 showed excessive angiogenesis and numerous endothelial “tip cells” at the vascular front that displayed migratory defects. Vascular endothelial growth factor receptor 1 (VEGFR1; Flt-1) levels were reduced in Acvrl1 +/− mice and HHT2 patients, suggesting similar mechanisms in humans. In sprouting angiogenesis, VEGFR1 is expressed in stalk cells to inhibit VEGFR2 (Flk-1, KDR) signaling and thus limit tip cell formation. Soluble VEGFR1 (sVEGFR1) is also secreted, creating a VEGF gradient that promotes orientated sprout migration. Acvrl1 +/− embryonic stem cell lines recapitulated the vascular anomalies in Acvrl1 +/− (HHT2) mice. Genetic insertion of either the membrane or soluble form of VEGFR1 into the ROSA26 locus of Acvrl1 +/− embryonic stem cell lines prevented the vascular anomalies, suggesting that high VEGFR2 activity in Acvrl1 +/− endothelial cells induces HHT2 vascular anomalies. To confirm our hypothesis, Acvrl1 +/− mice were infected by Mycoplasma pulmonis to induce sustained airway inflammation. Infected Acvrl1 +/− tracheas showed excessive angiogenesis with the formation of multiple telangiectases, vascular defects that were prevented by VEGFR2 blocking antibodies. Conclusions: Our findings demonstrate a key role of VEGFR1 in HHT2 pathogenesis and provide mechanisms explaining why HHT2 blood vessels respond abnormally to angiogenic signals. This supports the case for using anti-VEGF therapy in HHT2.

Previous reports indicated an association between hemorrhagic presentation and flow-related aneurysms in arteriovenous malformation (AVM) patients. However, it remains unclear whether these flow-related aneurysms result in the hemorrhage of AVM.To characterize this hemorrhage risk using our institutional experience over 25 yr.We retrospectively reviewed records of patients at our institution diagnosed with AVM from 1990 to 2015. Patients without associated aneurysms (AVM only) and those with flow-related aneurysms (AVM-FA) were compared. Those with intranidal or unrelated aneurysms were excluded. Annual risk of AVM-related hemorrhage was calculated using the birth-to-treatment approach and compared using Poisson rate ratio test.Among 526 patients, there were 457 AVM only patients and 69 with flow-related aneurysms. AVM-FA patients were older (P = .005). AVMs with flow-related aneurysms were more likely located in the cerebellar vermis and hemispheres (P = .023 and .001, respectively). Presence of flow-related aneurysms increased the risk of presentation with subarachnoid hemorrhage (P .001). Interestingly, no significant differences in presenting hemorrhage due to AVM rupture were found (P .356). The majority of aneurysms were untreated (69.5%), and only 8 (9.8%) had ruptured presentation. At follow-up (mean = 5.3 yr), patients with flow-related aneurysms were less likely to develop seizures (P = .004). The annual risk of AVM hemorrhage was 1.33% and 1.05% for AVM only patients and AVM-FA patients, respectively (P = .248).Despite increased risk of subarachnoid hemorrhage at presentation, there was no increased likelihood of rupture in AVMs with flow-related aneurysms. More studies are warranted, as clarifying the competing risks of AVM vs aneurysm rupture may be critical in determining optimal treatment strategy.

Background and Purpose— Brain arteriovenous malformation (bAVM) is an important risk factor for intracranial hemorrhage. Current treatments for bAVM are all associated with considerable risks. There is no safe method to prevent bAVM hemorrhage. Thalidomide reduces nose bleeding in patients with hereditary hemorrhagic telangiectasia, an inherited disorder characterized by vascular malformations. In this study, we tested whether thalidomide and its less toxic analog, lenalidomide, reduce bAVM hemorrhage using a mouse model. Methods— bAVMs were induced through induction of brain focal activin-like kinase 1 ( Alk1 , an AVM causative gene) gene deletion and angiogenesis in adult Alk1 -floxed mice. Thalidomide was injected intraperitoneally twice per week for 6 weeks, starting either 2 or 8 weeks after AVM induction. Lenalidomide was injected intraperitoneally daily starting 8 weeks after AVM induction for 6 weeks. Brain samples were collected at the end of the treatments for morphology, mRNA, and protein analyses. The influence of Alk1 downregulation on PDGFB (platelet-derived growth factor B) expression was also studied on cultured human brain microvascular endothelial cells. The effect of PDGFB in mural cell recruitment in bAVM was explored by injection of a PDGFB overexpressing lentiviral vector to the mouse brain. Results— Thalidomide or lenalidomide treatment reduced the number of dysplastic vessels and hemorrhage and increased mural cell (vascular smooth muscle cells and pericytes) coverage in the bAVM lesion. Thalidomide reduced the burden of CD68 + cells and the expression of inflammatory cytokines in the bAVM lesions. PDGFB expression was reduced in ALK1-knockdown human brain microvascular endothelial cells and in mouse bAVM lesion. Thalidomide increased Pdgfb expression in bAVM lesion. Overexpression of PDGFB mimicked the effect of thalidomide. Conclusions— Thalidomide and lenalidomide improve mural cell coverage of bAVM vessels and reduce bAVM hemorrhage, which is likely through upregulation of Pdgfb expression.

BACKGROUND For sustainability of arteriovenous malformation (AVM) surgery, results from early career cerebrovascular neurosurgeons (ECCNs) must be acceptably safe. OBJECTIVE To determine whether ECCNs performance of Spetzler-Ponce Class A AVM (SPC A) resection can be acceptably safe. METHODS ECCNs completing a cerebrovascular fellowship (2004-2015) with the last author were included. Inclusion of the ECCN cases occurred if they: had a prospective database of all AVM cases since commencing independent practice; were the primary surgeon on SPC A; and had made the significant management decisions. All SPC A surgical cases from the beginning of the ECCN's independent surgical practice to a maximum of 8 yr were included. An adverse outcome was considered a complication of surgery leading to a new permanent neurological deficit with a last modified Rankin Scale score >1. A cumulative summation (Cusum) plot examined the performance of each surgery. The highest acceptable level of adverse outcomes for the Cusum was 3.3%, derived from the upper 95% confidence interval of the last author's reported series. RESULTS Six ECCNs contributed 110 cases for analysis. The median number of SPC A cases operated by each ECCN was 16.5 (range 4-40). Preoperative embolization was performed in 5 (4.5%). The incidence of adverse outcomes was 1.8% (95% confidence interval

Purpose Dilated superior ophthalmic vein (SOV) is an uncommon radiographic finding. The authors review the presentation, etiology, radiography, and visual implications of 113 patients with dilated SOV. Methods An observational case series and multicenter retrospective chart review were conducted. There were 113 patients with a dilated SOV. Outcome measures included patient demographics, clinical features, radiographic findings, diagnosis, and treatment, and treatment outcomes were assessed. Results Cases included 75 women (66%) and 38 men (34%) with a mean age of 49 ± 24 years (range, 0.4-90 years). Diagnoses fell under 6 categories: vascular malformation (n = 92, 81%), venous thrombosis (n = 11, 10%), inflammatory (n = 6, 5%), traumatic hemorrhage (n = 2, 2%), lymphoproliferative (n = 1, 1%), and infectious (n = 1, 1%). Imaging modalities utilized included MRI (n = 98, 87%), digital subtraction angiography (n = 77, 68%), CT (n = 29, 26%), and ultrasonography (n = 4, 4%). Disease status at last follow up included no evidence of disease (n = 57, 50%), alive with persistent disease (n = 53, 47%), and expired from disease (n = 3, 3%). Treatment and management was tailored to the underlying disease process with a mean follow up of 18 months (range, 1 day to 180 months). Visual impairment observed at presentation and last follow up across all cases was 26% and 22%, respectively. Conclusion Dilated SOV is a rare radiographic finding resulting from a wide spectrum of etiologies with clinical implications ranging from benign to sight- and life-threatening. Dilated SOV is most often found with dural-cavernous fistula or carotid-cavernous fistula, orbital or facial arteriovenous malformation, and venous thrombosis. Recognition of this finding and management of the underlying condition is critical.

Scalp arteriovenous malformations (AVMs) are rare entities that may present as large, tortuous vascular lesions with resultant craniofacial deformity. Radiologic findings include feeding arteries and veins associated with dilated tortuous vessels. Intracranial extension is rare. A 5-year-old African American male presented with an occipital mass presumed to be a dermoid cyst on referral. Further workup revealed the presence of a scalp AVM that demonstrated extension into the left sigmoid sinus. Radiologic and intraoperative images are presented. Literature search revealed only 4 patients with scalp AVM extending intracranially into the sagittal sinus, 2 of which were managed with coagulation and division of the feeding vessels and the other 2 underwent preoperative embolization. Our patient is the 1st to be reported to have sigmoid sinus extension. Scalp AVMs with intracranial extension are rare, and require further preoperative workup. Following ultrasound evaluation, computed tomography angiography, magnetic resonance angiography, magnetic resonance imaging, or cerebral angiography can be considered. Treatment entails resection, but preoperative embolization is increasingly used, mirroring patients without intracranial extension. Further studies are needed to evaluate the efficacy and risk profile of these treatments.

Neurovascular procedures along the interhemispheric fissure harbor unique features differentiating them from those arteriovenous malformations (AVMs) located at the lateral surface of the brain.1-4 The aim of this 3-dimensional operative video is to present a microsurgical resection of an AVM in a subparacentral location, operated through an interhemispheric contralateral transfalcine approach.1,3,5 This is a case of a 29-yr-old female, with headaches and history of seizures. The patient presented an interhemispheric bleeding 6 mo before the surgery. The magnetic resonance imaging (MRI) showed a vascular lesion located on the medial surface of the right hemisphere at the confluence between the cingulate sulcus and its ascending sulcus. In the cerebral angiography, a right medial AVM was observed, receiving afference from the right anterior cerebral artery and draining to the superior longitudinal sinus. The patient signed an informed consent for the procedure and agreed with the use of her images and surgical video for research and academic purposes. The patient was in a supine position, and a left interhemispheric contralateral transfalcine approach was performed,1-3 a circumferential dissection of the nidus, and, finally, the AVM was resected in one piece. The patient evolved without neurological deficits after the surgery. The postoperative MRI and angiography showed a complete resection of the AVM. In the case presented, to avoid exposing the drainage vein first and to use the gravity of the exposure, the contralateral transfalcine interhemispheric approach was used,1,2 which finally accomplished the proposed objectives.

A 67-year-old man complained of red and bulging eyes for 3 months. He was diagnosed with laryngeal cancer and his bilateral internal jugular vein (IJV) was resected during the surgery. Ophthalmic examination revealed corkscrew-shaped arterialized conjunctival veins and severe bilateral papilledema. Magnetic resonance angiography revealed malformation vessels near the right sigmoid sinus (Figure). Cerebral digital subtraction angiography revealed an occipital dural arteriovenous malformation (AVM) near the right sigmoid sinus and venous drainage of the brain with a retrograde direction to cavernous sinus, superior/inferior ophthalmic vein, and finally external jugular vein, due to the resection of IJV (Video 1). After the embolization, most of the abnormal flow disappeared (Video 2), with partially improved papilledema on late follow-up. There is a very high probability that the formation of dural AVM is a complication of the neck dissection.

Tentorial margin arteriovenous malformations (AVMs) at the cerebello-mesencephalic fissure are deep lesions, which can be safely resected via a lateral supracerebellar infratentorial approach. This video illustrates the case of a patient who presented with hemorrhage from a tentorial AVM. He was managed in the hybrid neurovascular operating room with Onyx (Medtronic) embolization of a superior cerebellar artery feeder followed by resection of the AVM, which included cerebellar relaxation from lumbar cerebrospinal fluid (CSF) drainage and lateral positioning. Wide cisternal arachnoid dissection at the quadrigeminal cistern allowed for a straight trajectory to the AVM without fixed retraction. Intraoperative transradial angiography confirmed complete AVM exclusion. This video was deemed Institutional Review Board (IRB) exempt by the University of Pennsylvania IRB as it is considered a case report, which does not require IRB approval or patient consent. The patient consented to the procedure.