Recent Advances in Basic Research for Brain Arteriovenous Malformation

Arteriovenous malformations (AVMs) are abnormal connections of vessels that shunt blood directly from arteries into veins. Rupture of brain AVMs (bAVMs) can cause life-threatening intracranial bleeding. Even though the majority of bAVM cases are sporadic without a family history, some cases are familial. Most of the familial cases of bAVMs are associated with a genetic disorder called hereditary hemorrhagic telangiectasia (HHT). The mechanism of bAVM formation is not fully understood. The most important advances in bAVM basic science research is the identification of somatic mutations of genes in RAS-MAPK pathways. However, the mechanisms by which mutations of these genes lead to AVM formation are largely unknown. In this review, we summarized the latest advance in bAVM studies and discussed some pathways that play important roles in bAVM pathogenesis. We also discussed the therapeutic implications of these pathways.

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Pathogenesis of non-hereditary brain arteriovenous malformation and therapeutic implications

Interventional Neuroradiology ◽

10.1177/1591019920901931 ◽

2020 ◽

Vol 26 (3) ◽

pp. 244-253 ◽

Cited By ~ 1

Author(s):

Takahiro Ota ◽

Masaki Komiyama

Keyword(s):

High Risk ◽

Arteriovenous Malformation ◽

Signaling Pathways ◽

Intracranial Hemorrhage ◽

Arteriovenous Malformations ◽

Genetic Factors ◽

Angiogenic Factors ◽

Brain Arteriovenous Malformation ◽

Therapeutic Implications ◽

Brain Arteriovenous Malformations

Brain arteriovenous malformations have a high risk of intracranial hemorrhage, which is a substantial cause of morbidity and mortality in patients with brain arteriovenous malformations. Although a variety of genetic factors leading to hereditary brain arteriovenous malformations have been extensively investigated, their pathogenesis is still not well elucidated, especially in sporadic brain arteriovenous malformations. The authors have reviewed the updated data of not only the genetic aspects of sporadic brain arteriovenous malformations, but also the architecture of microvasculature, the roles of the angiogenic factors, and the signaling pathways. This knowledge may allow us to infer the pathogenesis of sporadic brain arteriovenous malformations and develop pre-emptive treatments for them.

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Potential Second-Hits in Hereditary Hemorrhagic Telangiectasia

Journal of Clinical Medicine ◽

10.3390/jcm9113571 ◽

2020 ◽

Vol 9 (11) ◽

pp. 3571

Author(s):

Carmelo Bernabeu ◽

Pinar Bayrak-Toydemir ◽

Jamie McDonald ◽

Michelle Letarte

Keyword(s):

Hereditary Hemorrhagic Telangiectasia ◽

Arteriovenous Malformations ◽

Somatic Mutations ◽

Autosomal Dominant ◽

Genetic Disorder ◽

Vascular Lesions ◽

Mechanical Trauma ◽

Internal Organs ◽

Second Hit ◽

Functional Mechanisms

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disorder that presents with telangiectases in skin and mucosae, and arteriovenous malformations (AVMs) in internal organs such as lungs, liver, and brain. Mutations in ENG (endoglin), ACVRL1 (ALK1), and MADH4 (Smad4) genes account for over 95% of HHT. Localized telangiectases and AVMs are present in different organs, with frequencies which differ among affected individuals. By itself, HHT gene heterozygosity does not account for the focal nature and varying presentation of the vascular lesions leading to the hypothesis of a “second-hit” that triggers the lesions. Accumulating research has identified a variety of triggers that may synergize with HHT gene heterozygosity to generate the vascular lesions. Among the postulated second-hits are: mechanical trauma, light, inflammation, vascular injury, angiogenic stimuli, shear stress, modifier genes, and somatic mutations in the wildtype HHT gene allele. The aim of this review is to summarize these triggers, as well as the functional mechanisms involved.

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Transarterial Coil-Augmented Onyx Embolization for Brain Arteriovenous Malformation Technique and Experience in 22 Consecutive Patients

Interventional Neuroradiology ◽

10.15274/inr-2014-10012 ◽

2014 ◽

Vol 20 (1) ◽

pp. 83-90 ◽

Cited By ~ 7

Author(s):

Xu Gao ◽

Guobiao Liang ◽

Zhiqing Li ◽

Xiaogang Wang ◽

Chunyong Yu ◽

...

Keyword(s):

Arteriovenous Malformations ◽

Injection Technique ◽

Initial Experience ◽

Brain Arteriovenous Malformation ◽

Technical Feasibility ◽

Valuable Adjunct ◽

Procedural Complication ◽

Brain Avms ◽

Age Range

Onyx has been widely adopted for the treatment of arteriovenous malformations (AVMs). However, its control demands operators accumulate a considerable learning curve. We describe our initial experience using a novel injection method for the embolization of AVMs. We retrospectively reviewed the data of all 22 patients with brain AVMs (12 men, 10 women; age range, 12–68 years; mean age, 43.2 years) treated by the transarterial coil-augmented Onyx injection technique. The size of the AVMs ranged from 25 mm to 70 mm (average 35.6 mm). The technical feasibility of the procedure, procedure-related complications, angiographic results, and clinical outcome were evaluated. In every case, endovascular treatment (EVT) was completed. A total of 31 sessions were performed, with a mean injection volume of 6.1 mL (range, 1.5–16.0 mL). An average of 96.7% (range 85%-100%) estimated size reduction was achieved, and 18 AVMs could be completely excluded by EVT alone. The results remained stable on follow-up angiograms. A procedural complication occurred in one patient, with permanent mild neurologic deficit. Our preliminary series demonstrated that the coil-augmented Onyx injection technique is a valuable adjunct achieving excellent nidal penetration and improving the safety of the procedure.

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Hypoxemia without Respiratory Distress: Hereditary Hemorrhagic Telangiectasia in a Child

Journal of Pediatric Intensive Care ◽

10.1055/s-0040-1710499 ◽

2020 ◽

Author(s):

Michael D. McCann ◽

Claire Newlon ◽

Conrad Krawiec

Keyword(s):

Hereditary Hemorrhagic Telangiectasia ◽

Arteriovenous Malformations ◽

Pediatric Patients ◽

Pediatric Population ◽

Genetic Disorder ◽

Significant Morbidity ◽

Younger Patients ◽

Life Threatening ◽

Symptoms And Signs ◽

Over Time

AbstractHereditary hemorrhagic telangiectasia (HHT) is an underrecognized genetic disorder of vascular development in pediatric patients. Its presentation can range from mild cutaneous findings to life-threatening hemorrhage from arteriovenous malformations. Clinical diagnosis can be challenging in the pediatric population as disease manifestations evolve over time and may be difficult to identify in younger patients. This case highlights how nonspecific symptoms and signs in the preanesthesia period can be misleading, potentially placing a patient with unrecognized HHT at risk for significant morbidity and mortality.

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Massive haemorrhagic complications of ruptured pulmonary arteriovenous malformations: outcomes from a 12 years’ retrospective study

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01604-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xu Ma ◽

Bing Jie ◽

Dong Yu ◽

Ling-Ling Li ◽

Sen Jiang

Keyword(s):

Arteriovenous Malformations ◽

Arterial Oxygen Saturation ◽

Arterial Oxygen ◽

Hereditary Haemorrhagic Telangiectasia ◽

Pulmonary Arteriovenous Malformations ◽

Imaging Data ◽

Peripheral Lung ◽

Life Threatening ◽

The Mean

Abstract Background The life-threatening haemorrhagic complications of pulmonary arteriovenous malformations (PAVMs) are extremely rare, and only described in isolated cases. This study was designed to comprehensively investigate management of ruptured PAVMs. Methods We retrospectively assessed clinical and imaging data of ruptured PAVMs to summarize incidence, clinical characteristics, and outcomes following embolisation between January 2008 and January 2021. Results Eighteen of 406 (4.4%) patients with PAVMs developed haemorrhagic complications. Twelve of 18 patients were clinically diagnosed with hereditary haemorrhagic telangiectasia (HHT). Haemorrhagic complications occurred with no clear trigger in all cases. Eight of 18 patients (44.4%) were initially misdiagnosed or had undergone early ineffective treatment. 28 lesions were detected, with 89.3% of them located in peripheral lung. Computed tomography angiography (CTA) showed indirect signs to indicate ruptured PAVMs in all cases. Lower haemoglobin concentrations were associated with the diameter of afferent arteries in the ruptured lesions. Successful embolotherapy was achieved in all cases. After embolotherapy, arterial oxygen saturation improved and bleeding was controlled (P < 0.05). The mean follow-up time was 3.2 ± 2.5 years (range, 7 months to 10 years). Conclusions Life threatening haemorrhagic complications of PAVMs are rare, they usually occur without a trigger and can be easily misdiagnosed. HHT and larger size of afferent arteries are major risk factors of these complications. CTA is a useful tool for diagnosis and therapeutic guidance for ruptured PAVMs. Embolotherapy is an effective therapy for this life-threatening complication.

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Multidisciplinary Approach to Suspected Sudden Death Caused by Arteriovenous Malformation Rupture: A Case Report

Medicina ◽

10.3390/medicina57070644 ◽

2021 ◽

Vol 57 (7) ◽

pp. 644

Author(s):

Federico Giuseppe Patanè ◽

Massimiliano Esposito ◽

Andrea Giovanni Musumeci ◽

Monica Palermo ◽

Marco Torrisi ◽

...

Keyword(s):

Arteriovenous Malformation ◽

Cause Of Death ◽

Venous Malformation ◽

Healthy Woman ◽

Unexpected Death ◽

Medical Problems ◽

Variable Diameter ◽

Life Threatening ◽

Brain Avms ◽

The Brain

Arteriovenous malformations (AVMs) are rare congenital conditions with a prevalence of less than 1% and are mostly asymptomatic. However, these malformations can suddenly cause intense pain or bleeding, leading to life-threatening medical problems. This report presents a case of an unexpected death in a 37-year-old previously healthy woman due to an intra-cerebellum arteriovenous malformation rupture identified during autopsy. While infective processes where preliminarily excluded, a Post Mortem Computed Tomography (PMCT) identified a tetra ventricular hemorrhage and intra-cerebellum hemorrhage. Toxicological examination was negative for most substances of abuse. During autopsy an intense hemorrhagic infiltrate in the subarachnoid space was observed. After formalin fixation of the brain the cerebellum showed hemorrhagic infarction on fourth ventricle sides, as well as several small reddish infarctions across the entire cerebellum parenchyma. Histological examination of the brain and cerebellum showed a suffusion of erythrocytes in the sub-arachnoid region. Evidence of an arterio-venous malformation, with several intertwine vessels of variable diameter, surrounded by hemorrhagic evidence. The autopsy played a crucial role in identifying the location and the possibly affected vessel, as well as defining the cause of death. It is necessary to have a greater number of autopsies to make an epidemiological contribution. Furthermore, it is crucial to create a multicenter data network with other authors from other departments to improve information about epidemiological, clinical, diagnostic and therapeutic data. Most brain AVMs as cause of death are often undiscovered.

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Hereditary haemorrhagic telangiectasia: A case report

SAGE Open Medical Case Reports ◽

10.1177/2050313x211003076 ◽

2021 ◽

Vol 9 ◽

pp. 2050313X2110030

Author(s):

Asfandyar Mufti ◽

Muskaan Sachdeva ◽

Khalad Maliyar ◽

Marissa Joseph

Keyword(s):

Arteriovenous Malformations ◽

Genetic Disorder ◽

Clinical Manifestations ◽

Hereditary Haemorrhagic Telangiectasia ◽

Lower Lip ◽

Recurrent Epistaxis ◽

Receptor Like Kinase ◽

History Of ◽

The Right ◽

Symptoms And Signs

Background: Hereditary haemorrhagic telangiectasia is an autosomal dominant genetic disorder characterized by abnormalities in blood vessel formation. The clinical manifestations of patients affected with hereditary haemorrhagic telangiectasia include mucocutaneous telangiectasias and visceral arteriovenous malformations. Case Summary: We report the case of a 30-year-old female diagnosed with hereditary haemorrhagic telangiectasia presenting with the classic triad of recurrent epistaxis, mucocutaneous telangiectasias and family history of hereditary haemorrhagic telangiectasia with activin receptor-like kinase 1 mutation. Upon skin examination, she was noted to have telangiectasias under left naris, inner lower lip and surface of the tongue, and a vascular malformation on the right forearm. Conclusion: Although the skin involvement and epistaxis may be mild symptoms and signs of hereditary haemorrhagic telangiectasia, timely recognition of these can ensure vigilant monitoring of potential severe complications from cerebral and pulmonary visceral arteriovenous malformations.

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Endovascular transvenous cure for ruptured brain arteriovenous malformations in complex cases with high Spetzler-Martin grades

Journal of Neurosurgery ◽

10.3171/2014.9.jns141714 ◽

2015 ◽

Vol 122 (5) ◽

pp. 1229-1238 ◽

Cited By ~ 42

Author(s):

Christina Iosif ◽

Georges A. C. Mendes ◽

Suzana Saleme ◽

Sanita Ponomarjova ◽

Eduardo Pedrolo Silveira ◽

...

Keyword(s):

Arteriovenous Malformations ◽

Clinical Status ◽

Surgical Techniques ◽

Venous Drainage ◽

Endovascular Embolization ◽

Modified Rankin Scale ◽

Transvenous Embolization ◽

Scale Scores ◽

Therapeutic Decision Making ◽

Brain Avms

OBJECT Ruptured cerebral arteriovenous malformations (AVMs) with deep localization and high Spetzler-Martin grades are associated with considerable challenges regarding nidus eradication treatment. The authors report their experience with curative endovascular transvenous embolization in a series of patients harboring “untreatable” lesions. METHODS Between January 2008 and June 2013, a transvenous endovascular embolization protocol was implemented at the authors' institution for consecutive patients with ruptured brain AVMs that were considered incurable by classic endovascular and surgical techniques. Therapeutic decision making was based on Spetzler-Martin grades, AVM location, type of venous drainage, and angioarchitectural evaluation. Complete exclusion of the nidus was the objective of treatment. RESULTS Twenty patients (10 male and 10 female, mean age 36.7 ± 17.7 years) were included. Initial Spetzler-Martin grades were III–V for 90.0% of the patients. The lesions were deeply seated in 80% and in eloquent locations in 90% of cases. The preprocedural modified Rankin Scale score was 0–2 for 12 of the 20 patients (60.0%), 3 for 2 patients (10.0%), and 4 for 6 patients (30.0%). The postprocedural clinical status was unchanged for all patients. The procedure was technically feasible in all cases. Procedure-related mortality was 0%. Ninety percent of the patients were independent in their everyday lives (modified Rankin Scale Scores 0–2) at the 6-month follow-up. In all cases but one (95%) the embolization was curative, confirmed by selective DSA at 6 months and 18 months postintervention. CONCLUSIONS Single-session endovascular transvenous embolization seems to be a safe and effective curative treatment for patients harboring complex brain AVMs with high Spetzler-Martin grade.

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The 2011 National Science Foundation Political Science Awards

Political Science and Politics ◽

10.1017/s1049096511001892 ◽

2012 ◽

Vol 45 (01) ◽

pp. 124-126

Keyword(s):

Political Science ◽

National Science Foundation ◽

Research Training ◽

Basic Research ◽

Science Research ◽

Fiscal Year ◽

The Political ◽

Science Program ◽

Political Processes ◽

National Science

The Political Science Program at the National Science Foundation (NSF) announces it awards for basic research support and dissertation improvement grants for fiscal year 2011. The Program funded 25 new projects and 44 doctoral dissertation improvement proposals. The Political Science Program spent $5,234,470 on these research, training and workshop projects and $483,822 on dissertation training grants for political science students. The program holds two grant competitions annually —Regular Research, August and January 15; Dissertation Improvement, September 16 and January 15— and constitutes a major source of political science research funding as part of fulfilling NSF's mission to encourage theoretically focused empirical investigations aimed at improving the explanation of fundamental social and political processes and structures.

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

Journal of Neurosurgery ◽

10.3171/2016.7.jns16847 ◽

2017 ◽

Vol 127 (2) ◽

pp. 302-310 ◽

Cited By ~ 20

Author(s):

Waleed Brinjikji ◽

Vivek N. Iyer ◽

Christopher P. Wood ◽

Giuseppe Lanzino

Keyword(s):

Systematic Review ◽

Hereditary Hemorrhagic Telangiectasia ◽

Arteriovenous Malformations ◽

Clinical Presentation ◽

Meta Analysis ◽

Prevalence Rates ◽

Brain Avm ◽

Martin Grade ◽

Cerebral Avms ◽

Brain Avms

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

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