Prevalence and Predictors of Hereditary Hemorrhagic Telangiectasia and Capillary-Malformation Arteriovenous Malformation Syndrome Among Children with Neurovascular Malformations.

OBJECTIVE: To investigate the prevalence and predictors of hereditary hemorrhagic telangiectasia (HHT) and capillary-malformation arteriovenous malformation (CM-AVM) syndrome among children with no prior personal or family history of these diseases who presented with an arteriovenous shunt lesion. STUDY DESIGN: A retrospective chart review was completed on patients aged 0 through 21 years with arteriovenous shunt lesions evaluated at our Cerebrovascular Center. Diagnosis of definite or suspected HHT or CM-AVM was based on clinical features and genetic testing. Associations between final diagnosis and type and number of lesions, epistaxis, telangiectasias, CM, and pulmonary AVMs were assessed. RESULTS: Eighty-nine patients were included. Thirteen (14.6%) had definite HHT, 11 (12.4%) suspected HHT, and 4 (4.5%) definite CM-AVM. Having ≥2 episodes of epistaxis/year and ≥ 2 sites with telangiectasias were each associated with definite HHT (P < .001). Having ≥ 2 CM was associated with definite CM-AVM (P < .001). Pulmonary AVM was associated with increased odds of having definite HHT (OR = 6.3, 95% CI: 1.2-33.4). Multiple lesions (OR = 24.5, 95% CI: 4.5-134.8) and arteriovenous fistulas (OR = 6.2, 95% CI: 1.9-20.3) each increased the likelihood of having definite HHT or CM-AVM. Genetic testing was positive in 31% of patients tested. CONCLUSIONS: We recommend that children with neurovascular shunt lesions be offered genetic testing and undergo further evaluation for HHT and CM-AVM. Awareness and early diagnosis of these conditions is a critical step toward improving long-term outcomes and preventing disease-associated complications.

Comparative Study of Automated Algorithms for Brain Arteriovenous Malformation Nidus Extent Identification Using 3DRA.

PURPOSE: When performing a brain arteriovenous malformation (bAVMs) intervention, computer-assisted analysis of bAVMs can aid clinicians in planning precise therapeutic alternatives. Therefore, we aim to assess currently available methods for bAVMs nidus extent identification over 3DRA. To this end, we establish a unified framework to contrast them over the same dataset, fully automatising the workflows. MATERIALS AND METHODS: We retrospectively collected contrast-enhanced 3DRA scans of patients with bAVMs. A segmentation network was used to automatically acquire the brain vessels segmentation for each case. We applied the nidus extent identification algorithms over each of the segmentations, computing overlap measurements against manual nidus delineations. RESULTS: We evaluated the methods over a private dataset with 22 3DRA scans of individuals with bAVMs. The best-performing alternatives resulted in [Formula: see text] and [Formula: see text] dice coefficient values. CONCLUSIONS: The mathematical morphology-based approach showed higher robustness through inter-case variability. The skeleton-based approach leverages the skeleton topomorphology characteristics, while being highly sensitive to anatomical variations and the skeletonisation method employed. Overall, nidus extent identification algorithms are also limited by the quality of the raw volume, as the consequent imprecise vessel segmentation will hinder their results. Performance of the available alternatives remains subpar. This analysis allows for a better understanding of the current limitations.

Case report: A combination of nitroglycerin and adenosine proves effective in repairing a cerebral arteriovenous malformation.

Hemorrhage secondary to rupture of a brain arteriovenous malformations (AVM) is one of the initial manifestations, and the main cause of, morbidity and mortality in patients with this condition. Current treatment strategies include endovascular embolization with the goal of AVM obliteration and neurological preservation. In the transvenous endovascular embolization procedure, adenosine is the preferred agent to induce temporary hypotension and allow adequate AVM embolization. We describe the intraoperative management of an adenosine-resistant 38 year-old male who underwent a successful intracranial AVM embolization after concomitant administration of gradually increasing doses of nitroglycerin. This report suggests that nitroglycerin infusion can be combined with adenosine boluses to create a pronounced and dose-dependent hypotension in patients partially unresponsive to adenosine alone.

Longitudinal Assessment of Curaçao Criteria in Children with Hereditary Hemorrhagic Telangiectasia.

OBJECTIVE: To assess the utility of the Curaçao criteria by age over time in children with hereditary hemorrhagic telangiectasia (HHT). STUDY DESIGN: This was a single-center, retrospective analysis of patients attending the HHT clinic at the Hospital for Sick Children (Toronto, Canada) between 2000 and 2019. The evaluation of the Curaçao criteria was completed during initial and follow-up visits. Screening for pulmonary and brain arteriovenous malformations was completed at 5 yearly intervals. RESULTS: A total of 116 patients with genetic confirmation of HHT were included in the analysis. At initial screening at a median (IQR) age of 8.4 (2.8, 12.9) years, 41% met criteria for a definite clinical diagnosis (≥3 criteria). In children <6 years at presentation, only 23% fulfilled at least 3 criteria initially. In longitudinal follow-up, 63% reached a definite clinical diagnosis, with a median (IQR) follow-up duration of 5.2 (3.2, 7.9) years (P = .005). Specifically, more patients met the epistaxis and telangiectasia criteria at last visit compared with initial (79% vs 60%; P = .006; 47% vs 30%; P = .02) but not for the arteriovenous malformation criterion (59% vs 57%; P = .65). CONCLUSIONS: In the pediatric population, most patients do not meet definite clinical criteria of HHT at initial presentation. Although the number of diagnostic criteria met increased over time, mainly due to new onset of epistaxis and telangiectasia, accuracy remained low during follow-up visits. Relying solely on clinical criteria may lead to underdiagnosis of HHT in children.

Posterior-Transcallosal Approach to a Choroidal Fissure Arteriovenous Malformation: Video of Adapting a "Bridging Vein Free" Corridor to This Complex Region.

Choroidal fissure arteriovenous malformations (ChFis-AVMs) are uncommon and challenging to treat due to their deep location and pattern of supply.1 The choroidal fissure lies between the thalamus and fornix, from the foramen of Monroe to the inferior choroidal point.2 AVMs in this location receive their supply from the anterior, lateral posterior choroidal artery and medial posterior choroidal arteries and drain to the deep venous system.3 The anterior-transcallosal corridor to the ChFis is favored due to the ease in opening the taenia fornicis from the foramen Monroe, and it increases in length for lesions located more posteriorly.4-7 We present a case of a posterior ChFis-AVM. The patient, a previously healthy woman in her 20s, presented with a sudden severe headache. She was diagnosed with intraventricular hemorrhage. This was managed conservatively with subsequent magnetic resonance imaging and digital subtraction angiography revealing a ChFis-AVM at the body of the left lateral ventricle, between the fornix and superior layer of the tela choroidae. It received its supply from the left lateral posterior choroidal artery and medial posterior choroidal artery and drained directly into the internal cerebral vein, classified as Spetzler-Martin grade II.8 A posterior-transcallosal approach to the ChFis was chosen to reduce the working distance and afford a wider corridor by avoiding cortical bridging veins (Video 1). Complete resection of the AVM was achieved with no additional morbidity. Microsurgery in experienced hands offers the best chance of cure for AVMs.9 In this case we demonstrate how to adapt the transcallosal corridor to the choroidal fissures for safe AVM surgery in this complex location.

Importance of Arachnoid Dissection in Arteriovenous Malformation Microsurgery: A Technical Note.

Intracranial arteriovenous malformations (AVMs) are congenital anomalies where arteries and veins connect without a capillary bed. AVMs are the leading cause of nontraumatic intracerebral hemorrhages in people younger than 35 years old.1 The leptomeninges (arachnoid and pia) form from the meninx primitiva.2,3 Endothelial channels produce a vascular plexus in the meninx connected by primitive arachnoid. Remodeling of the plexus in response to changing metabolic demands results in a recognizable pattern of arteries and veins.2,3 Defects at the level of capillaries during arteriovenous specification are most likely responsible for arteriovenous fistula formation.4-6 Interplay between the congenital dysfunction and flow-related maturation in adulthood, when vasculogenesis has stopped, produces the AVM.6,7 The relationship between the primitive arachnoid and aberrant AVM vessels is preserved and forms the basis of microsurgical disconnection discussed in Video 1. Several authors have described dissecting these natural planes to delineate the abnormal AVM vessels, relax the brain, and avoid morbidity during AVM surgery.8-10 We recommend sharp arachnoid dissection with a scalpel or microscissors, occasionally helped by blunt dissection with patties or bipolar forceps. We present a 2-dimensional video of the microsurgical resection of a right parietal AVM. The patient, a healthy 30-year-old female, presented with intermittent headaches and mild impairment of arithmetic and visuospatial ability. Magnetic resonance imaging and digital subtraction angiography showed a compact 3.5-cm supramarginal gyrus AVM supplied by the middle cerebral artery, with superficial drainage. Complete microsurgical resection was performed without morbidity. We demonstrate the principles of arachnoid dissection requisite to disentanglement of the nidus and safe resection of the AVM.

Impact of ARUBA trial on trends and outcomes in symptomatic non-ruptured brain AVMs: A national sample analysis.

INTRODUCTION: The real-world evolution of management and outcomes of patients with unruptured brain arteriovenous malformations (AVMs) has not been well-delineated following the ARUBA trial findings of no general advantage of initial interventional (surgical/endovascular/radiotherapy) vs. initial conservative medical therapy. METHODS: We analyzed the National Inpatient Sample from 2009-2018, capturing 20% of all admissions in the U.S. Validated ICD-9 and -10 codes defined brain AVMs, comorbidities, and the use of interventional modalities. Analyses were performed by year and for the dichotomized periods of pre-ARUBA (2009-2013) vs. post-ARUBA (2014-2018). RESULTS: Among the national projected 88,037 AVM admissions, 72,812 (82.7%) were unruptured AVMs and 15,225 (17.3%) were ruptured AVMs. Among uAVMs, 51.4% admitted pre-ARUBA and 48.6% in post-ARUBA period. The post-ARUBA patients were mildly older (median age 53.3 vs. 51.8 (p = 0.001) and had more comorbidities including hypertension, diabetes, obesity, renal impairment, and smoking. Before the first platform report of ARUBA (2009-2012), rates of use of interventional treatments during uAVM admissions trended up from 31.8% to 35.4%. Thereafter, they declined significantly to 26.4% in 2018 (p = 0.02). The decline was driven by a reduction in the frequency of endovascular treatment from 18.8% to 13.9% and inpatient stereotactic radiosurgery from 0.5% to 0.1%. No change occurred in the frequency of microsurgery or combined endovascular and surgical approaches. Adjusted multivariable model of uAVMs showed increased odds of discharge to a long-term inpatient facility or in-hospital death [OR 1.14 (1.02-1.28), p = 0.020] in post-ARUBA. A significantly increased proportion of ruptured AVMs from 17.0% to 23.3% was observed consistently in post-ARUBA. CONCLUSION: Nationwide practice in the management of unruptured AVMs changed substantially with the publication of the ARUBA trial in a durable and increasing manner. Fewer admissions with the interventional treatment of unruptured AVMs occurred, and a corresponding increase in admission for ruptured AVMs transpired, as expected with a strategy of watchful waiting and treatment only after an index bleeding event. Further studies are needed to determine whether these trends can be considered to be ARUBA trial effect or are merely coincidental.

Microsurgical Treatment for Arteriovenous Malformation in Eloquent Area: A 2-Dimensional Surgical Video and Step-by-Step Practical Guide.

Cerebral arteriovenous malformations (AVMs) are dynamic neurovascular disorders that occur mainly in young adults, presenting an annual risk of rupture of 2% - 4% per year.1 They can be asymptomatic, representing an incidental radiologic finding, or present with neurologic deficits according to their brain location, size, and presence or absence of bleeding.2,3 AVMs located in eloquent areas4 represent a great challenge for neurosurgeons, sometimes directed to alternatives therapies (e.g., embolization, radiotherapy) due to the difficulty in planning and surgical technique. Despite the complexity, we consider that there is benefit to removing these lesions; this can be done safely, as with the adequate microsurgical strategy and neuroanatomic knowledge. In Video 1, we show the case of a 55-year-old male patient with an AVM positioned over the right central sulcus. He presented with intermittent left-hand paresthesia followed by an episode of involuntary movements in the left arm without loss of consciousness and with spontaneous resolution. Angiography showed an AVM feed by branches of the middle cerebral artery and multiple venous drainage for the Trolard complex and superficial middle cerebral vein, with a 4-cm nidus, making it grade III in the Spetzler-Martin classification.4 The patient underwent surgery with total resection of the lesion without any complication or new neurologic deficits.

Nasal Endoscopy in the Clinical Diagnosis of Hereditary Hemorrhagic Telangiectasia.

OBJECTIVES: To evaluate the role of nasal endoscopy for early clinical diagnosis of hereditary hemorrhagic telangiectasia (HHT) in children and to investigate the characteristics of epistaxis and mucocutaneous telangiectases in our pediatric population. STUDY DESIGN: From May 2016 to December 2019, a cross-sectional observational study was conducted, recruiting children aged 2-18 years with a parent affected by HHT. To identify the Curaçao criteria, all children underwent collection of clinical history, mucocutaneous examination, and nasal endoscopy. The clinical data were then compared with the genetic data acquired subsequently. RESULTS: Seventy children (median age, 10.8 years) were included. All underwent nasal endoscopy without complications. Forty-six children were positive by genetic testing; of these, 26 % had skin and oral telangiectases and 91 % had nasal telangiectases. The diagnostic sensitivity of the Curaçao criteria increased from 28 % (95 % CI, 16%-43 %) to 85 % (95 % CI, 71%-94 %; P < .0001) when the nasal telangiectases were included. CONCLUSIONS: The magnified and complete endoscopic view of the nasal cavities proved useful in increasing the diagnostic sensitivity of the Curaçao criteria. Such an examination turned out to be feasible and safe. For this reason, we believe that nasal endoscopy should be included in the diagnostic assessment of pediatric patients with suspected HHT.

Interhemispheric Contralateral Transfalcine Approach for Subparacentral Arteriovenous Malformation: 3-Dimensional Operative Video.

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.

Microsurgical Resection of a Left Supramarginal Gyrus AVM Causing Radionecrosis.

Late radiation necrosis is a rare entity presenting in 2.2% to 9% of radiation-treated arteriovenous malformations (AVMs). It occurs by a mean of 3 years following treatment. There are few reports in the literature of radionecrosis and solid lesions treated with surgery.1-4 To the authors' knowledge, this case has the longest interval between radiosurgery and the presentation of cerebral necrosis. In this surgical video, we present the case of a 51-year-old female with a left supramarginal gyrus AVM that received radiosurgery with gamma knife; after 20 years, she began having seizures and aphasia. The magnetic resonance imaging scan revealed a lesion simulating an intra-axial tumor causing important edema and mass effect. Medical treatment was given including high-dose steroids without success, therefore microsurgery was performed. The surgery was presented in a step-by-step basis and correlation was performed with the involved adjacent anatomy, to illustrate the anatomy of the approach and surgical landmarks. The patient's symptoms resolved completely, and the postoperative magnetic resonance imaging scan showed complete resection and resolution of the edema. The histopathological findings were consistent with a radionecrosis and AVM. The patient signed the Institutional Consent Form, which states that she accepts the procedure and allows the use of her images and videos for any type of medical publications in conferences and/or scientific articles.

Multimodal cerebral arteriovenous malformation treatment: a 12-year experience and comparison of key outcomes to ARUBA.

OBJECTIVE: Curative treatment of unruptured brain arteriovenous malformations (AVMs) remains controversial after the only randomized controlled trial, A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA), was halted prematurely because interim analysis revealed superiority of the medical management group. In contrast, meta-analyses of retrospective cohorts suggest that intervention is much safer than was found in ARUBA. METHODS: The authors retrospectively analyzed 318 consecutive adult patients with brain AVMs treated at their institution with embolization, surgery, and/or proton beam radiosurgery. Analysis was performed in 142 ARUBA-eligible patients (baseline modified Rankin Scale [mRS] score 0-1, no history of hemorrhage), and results were compared to primary and secondary outcomes from ARUBA, as well as to natural history cohorts. RESULTS: The annualized stroke rate (hemorrhagic or ischemic) in this cohort was 1.8%, 4.9% in the first 12 months and 0.8% after the first 12 months, which was lower than in natural history studies and the ARUBA medical management arm (p = 0.001). The primary ARUBA endpoint of symptomatic stroke was reached in 13 patients (9.2%), which compares favorably to the ARUBA intervention arm (39.6%, p = 0.0001) and is similar to the ARUBA medical management arm (9.2%, p = 1.0). The secondary ARUBA endpoint (mRS score ≥ 2 at 5 years of follow-up) was reached in 14.3% of patients, compared to 40.5% in the ARUBA intervention arm (p = 0.002) and 16.7% in the ARUBA medical management arm (p = 0.6). CONCLUSIONS: This multimodal approach to the selection and treatment of patients with brain AVMs yields good clinical outcomes with key safety endpoints (stroke, death, and mRS score 0-1) better than the ARUBA intervention arm and similar to the ARUBA medical arm at 5 years of follow-up. Results compare favorably to natural history cohorts at longer follow-up times. This suggests that tertiary care centers with integrated programs, expertise in patient selection, and individualized treatment approaches may allow for better clinical outcomes than reported in ARUBA. It supports current registry studies and merits consideration of future randomized controlled trials in patients with brain AVMs.

Intraoperative Ultrasound Navigation with Doppler Function to Guide Arteriovenous Malformation Resection: 3-Dimensional Operative Video.

Intraoperative ultrasound navigation was initially introduced in the neurosurgical field for brain tumor surgery and was then extended to arteriovenous malformation surgery with good success. This tool provides real-time intraoperative images.1 Moreover, Doppler ultrasound permits early identification of feeding arteries and supplies the surgeon with a global impression of the flow dynamics.2 A further use of doppler is to check for residual nidus. Other advantages are the capacity to identify intracerebral hemorrhage.2 In this video, we demonstrate the case of a 15-yr-old patient who presented intracranial hemorrhage. Magnetic resonance imaging revealed the presence of left frontoparietal hematoma associated with an image suggestive of cerebral arteriovenous malformation (AVM). Arteriography confirmed the diagnosis of AVM fed by branches of the anterior cerebral and superficial drainage for the superior sagittal sinus. The patient was placed in dorsal decubitus with his head turned to the right and a left parietal-frontal craniotomy was performed. After the dura mater was opened, cortical mapping was performed to locate the motor and sensory cortex. After the mapping, ultrasound with doppler was performed to locate the AVM and the hematoma and determine its relation to the motor and sensory cortex. At the end of the surgery, doppler ultrasound was used again to ensure complete resection of the AVM. Intraoperative Ultrasound navigation with doppler is an inexpensive technology that can be used in the treatment of AVMs, especially in the subcortex, as it assists in locating the nidus and confirms its complete resection.

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?

BACKGROUND: The optimal management of unruptured brain arteriovenous malformations (AVMs) is controversial after the ARUBA trial. OBJECTIVE: To confirm or repudiate the ARUBA conclusion that "medical management only is superior to medical management with interventional therapy for unruptured brain arteriovenous malformations." METHODS: 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. RESULTS: 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. CONCLUSION: The ARUBA trial conclusion that medical management is superior to medical management with interventional therapy for all unruptured AVMs could be repudiated.

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.

Microsurgical treatment for arteriovenous malformation of the corpus callosum and choroidal fissure.

The management of arteriovenous malformations (AVMs) of the corpus callosum and choroidal fissure is challenging because they commonly receive arterial feeders from the anterior and posterior circulation, and drain to deep veins. In this video the authors present the case of a 20-year-old man who presented with acute onset of headache, loss of consciousness, and nuchal rigidity. Computed tomography, MRI, and cerebral angiography performed in tandem revealed a ruptured, large, Grade IV AVM of the corpus callosum and choroidal fissure with two groups of arterial feeders: one from the pericallosal artery and the other from the medial and lateral posterior choroidal arteries. The treatment strategy included two stages. The first stage involved preoperative embolization of the arterial feeders from the posterior circulation, which promoted reduction of the nidus flow of the AVM. The second involved a microsurgical resection, using the interhemispheric approach, with the patient in the prone position, which allowed accessing the anterior circulation feeders and the complete resection of the AVM, without associated morbidity. The video can be found here: https://youtu.be/5wcYKhcJtls .

Responses to ARUBA: a systematic review and critical analysis for the design of future arteriovenous malformation trials.

OBJECTIVE The ARUBA study (A Randomized Trial of Unruptured Brain Arteriovenous Malformations [AVMs]) on unruptured brain AVMs has been the object of comments and editorials. In the present study the authors aim to systematically review critiques, discuss design issues, and propose a framework for future trials. METHODS The authors performed a systematic review of the French and English literature on the ARUBA study published between January 2006 and February 2015. The electronic search, including the Cochrane Library, MEDLINE (PubMed and Ovid), CINAHL, and EMBASE databases, was complemented by hand searching and cross-referencing. The comments were categorized as items related to the design, the conduct, and the analysis and interpretation of the trial. RESULTS Thirty-one articles or letters were identified. The pragmatic design, with heterogeneity of patients and lack of standardization of the treatment arm, were frequently stated concerns. The choice of outcome measures was repeatedly criticized. During the trial, low enrollment rates, selection bias, and premature interruption of enrollment were frequent comments. The short follow-up period, the lack of subgroup analyses, the lack of details on the results of the various treatments, and a contentious interpretation of results were noted at the analysis stage. A fundamental problem was the primary hypothesis testing conservative management. The authors believe that other trials are needed. Future trials could be pragmatic, test interventions stratified at the time of randomization, and look for long-term, hard clinical outcomes in a large number of patients. CONCLUSIONS In the authors' view, the ARUBA trial is a turning point in the history of brain AVM management; future trials should aim at integrating trial methodology and clinical care in the presence of uncertainty.

Treatment and outcomes of ARUBA-eligible patients with unruptured brain arteriovenous malformations at a single institution.

OBJECT: Management of unruptured arteriovenous malformations (AVMs) is controversial. In the first randomized trial of unruptured AVMs (A Randomized Trial of Unruptured Brain Arteriovenous Malformations [ARUBA]), medically managed patients had a significantly lower risk of death or stroke and had better outcomes. The University of California, San Francisco (UCSF) was one of the participating ARUBA sites. While 473 patients were screened for eligibility, only 4 patients were enrolled in ARUBA. The purpose of this study is to report the treatment and outcomes of all ARUBA-eligible patients at UCSF. METHODS: The authors compared the treatment and outcomes of ARUBA-eligible patients using prospectively collected data from the UCSF brain AVM registry. Similar to ARUBA, they compared the rate of stroke or death in observed and treated patients and used the modified Rankin Scale to grade outcomes. RESULTS: Of 74 patients, 61 received an intervention and 13 were observed. Most treated patients had resection with or without preoperative embolization (43 [70.5%] of 61 patients). One of the 13 observed patients died after AVM hemorrhage. Nine of the 61 treated patients had a stroke or died. There was no significant difference in the rate of stroke or death (HR 1.34, 95% CI 0.12-14.53, p = 0.81) or clinical impairment (Fisher's exact test, p > 0.99) between observed and treated patients. CONCLUSIONS: The risk of stroke or death and degree of clinical impairment among treated patients was lower than reported in ARUBA. The authors found no significant difference in outcomes between observed and treated ARUBA-eligible patients at UCSF. Results in ARUBA-eligible patients managed outside that trial led to an entirely different conclusion about AVM intervention, due to the primary role of surgery, judicious surgical selection with established outcome predictors, and technical expertise developed at high-volume AVM centers.

Resección quirúrgica de malformación arteriovenosa de alto flujo en ángulo nasogeniano con embolización preoperatoria: reporte de un caso / Surgical resection of high-flow arteriovenous malformation of the nasogenian sulcus with preoperatory embolization: a case report

El 50% de las malformaciones arteriovenosas (MAVs) de alto flujo se ubican en la región craneofacial y pueden producir sangrado con riesgo vital sin diagnóstico y tratamiento adecuado. La resonancia magnética (RM) es útil en el diagnóstico diferencial de las lesiones vasculares, siendo el gold standard la angiografía selectiva. Dado que las MAVs de alto flujo no involucionan espontáneamente, el tratamiento usualmente consiste en embolización con posterior resección quirúrgica. Se presenta un paciente de sexo masculino de 20 años que consulta por aumento de volumen nasogeniano derecho, progresivo, violáceo, blando y pulsátil. Se objetiva mediante RM una zona de vasos serpentiginosos, que se extiende desde el subcutáneo hasta la pared anterior del maxilar. La angiografía cerebral confirma MAV de alto flujo e informa mapeo vascular. Se decide embolización prequirúrgica superselectiva con posterior resección tumoral mediante acceso transvestibular.

The 50 % of arteriovenous malformations (AVMs) of high flow are located in the craniofacial region and can cause life-threatening bleeding without a diagnosis and appropriate treatment. Magnetic resonance imaging is useful in the differential diagnosis of vascular lesions, being the gold standard selective angiography. Since high-flowA VMs do not regress spontaneously, treatment usually involves surgical resection with subsequent embolization. We present a 20 years male patient consulting with a purple, progressive, soft, pulsating enlargement of right-side nasogenian region. Magnetic resonance imaging shows serpiginous vessels, extending from the subcutaneous to the anterior wall of the maxillary. Cerebral angiography confirms high flowAVM and shows vascular mapping. It was decided superselective preoperative embolization with subsequent tumor by transvestibular access.

Síndrome de malformaciones capilares-malformaciones arteriovenosas (CM-AVM) / -Capillary malformation syndrome arteriovenous malformation (CM-AVM)

El síndrome de malformaciones capilares-malformaciones arteriovenosas (CM-AVM) es una entidad descripta recientemente, que se caracteriza por la asociación de malformaciones capilares con malformaciones arteriales o fístulas arteriovenosas. Es de herencia autosómica dominante y se produce por mutaciones en el gen RASA1. Las malformaciones capilares en este síndrome presentan ciertas características particulares por lo que son llamadas atípicas. Algunas son congénitas y otras aparecen en forma progresiva. Presentan tamaño variable (desde lesiones puntiformes hasta de varios cm de diámetro), son rosadas o amarronadas, tienen aumento de temperatura local y están rodeadas por un halo pálido. En ocasiones comprometen mucosa oral. Es importante que el dermatólogo sea capaz de reconocer este síndrome, ya que en ocasiones puede asociarse con compromiso interno.

Capillary malformation-arteriovenous malformation is a recently described disorder, characterized by the association of capillary malformations with arterial malformation or arteriovenous fistulae. It is an autosomal dominant disease caused by mutations in RASA1. Capillary malformations in this syndrome are called atypical because they share some particular characteristics. Some are congenital and others appear progressively. They varied in size (from pinpoint lesions to several centimeters of diameter), are pink or brown, sometimes warmer than normal skin and are surrounded by a pale halo. Oral mucosa can be affected. It is important for the dermatologist to recognize this syndrome, taking in account that it can be associated to internal compromise.