Cerebral Arteriovenous Malformations in Pediatric Patients with Hereditary Hemorrhagic Telangiectasia: Re-evaluating Appearance, Bleeding Risk, and Treatment Necessity in a Selective Meta-analysis

2020 ◽  
Vol 18 (06) ◽  
pp. 279-285
Author(s):  
Oliver Mueller ◽  
Ekkehard Kasper ◽  
Freya Droege ◽  
Sophia Goericke ◽  
Klaus-Peter Stein ◽  
...  
Keyword(s):  
Hereditary Hemorrhagic Telangiectasia ◽  
Arteriovenous Malformations ◽  
Pediatric Patients ◽  
Vascular Malformations ◽  
Meta Analysis ◽  
Treatment Algorithm ◽  
Rare Event ◽  
Bleeding Risk ◽  
Disease Diagnosis ◽  
Capillary Telangiectasia

AbstractPediatric patients suffering from cerebral nidal arteriovenous malformations are a unique population due to the rare occurrence of the disease. Diagnosis of hereditary hemorrhagic telangiectasia (HHT) in children is a rare event and mainly restricted to coincidental detection from screening of possibly afflicted family members. In patients with HHT, it is well known that the incidence of cerebral vascular malformations (CVMs) is higher than expected when compared with the nonafflicted population. Even though CVMs comprise a variety of different distinct anatomical and radiographic entities (e.g., capillary telangiectasia, nidal arteriovenous malformation [AVM], cavernous malformation, dural or pial as well as mixed fistula, and vein of Galen malformation), they are mostly summarized and analyzed all in one category due to the low number of individual cases identified in single centers. Nevertheless, the best treatment algorithm will likely vary significantly between different CVMs as does the clinical presentation and the natural course of the CVM. It is therefore the objective of this article to focus on nidal AVMs in pediatric patients suffering from HHT. To this end, we performed a systematic selective literature research to estimate incidence, clinical and radiological appearance, as well as classification according to established grading system, and to evaluate the necessity of treatment of these lesions in light of their respective outcomes. Our line of arguments explains why we recommend to follow these lesions expectantly and suggest to keep pediatric patients under surveillance with sequential scans until they reach adulthood.

Cerebral vascular malformations in hereditary hemorrhagic telangiectasia

2014 ◽  
Vol 120 (1) ◽  
pp. 87-92 ◽  
Author(s):  
M. Neil Woodall ◽  
Melissa McGettigan ◽  
Ramon Figueroa ◽  
James R. Gossage ◽  
Cargill H. Alleyne
Keyword(s):  
Hereditary Hemorrhagic Telangiectasia ◽  
Arteriovenous Malformations ◽  
Vascular Malformations ◽  
Cerebral Aneurysms ◽  
Developmental Venous Anomalies ◽  
Capillary Telangiectasia ◽  
The Brain ◽  
Single Modality ◽  
Cerebral Vascular Malformations ◽  
Cerebral Vascular

Object Hereditary hemorrhagic telangiectasia (HHT) is a hereditary disorder characterized by mucocutaneous telangiectasias, frequent nosebleeds, and visceral arteriovenous malformations (AVMs). Few reports have outlined the prevalence of the various cerebral vascular malformations found in patients with HHT. The authors set out to define the prevalence of cerebral vascular malformations in a population of HHT patients who underwent imaging with 3-T imaging (MRI/MR angiography [MRA]) of the brain. Methods A retrospective review of prospectively collected data was carried out using a database of 372 HHT patients who were seen and examined at the Georgia Regents University HHT Center and screened with 3-T MRI/MRA. Data were tabulated for numbers and types of vascular malformations in this population. Results Arteriovenous malformations were identified in 7.7%, developmental venous anomalies in 4.3%, and cerebral aneurysms in 2.4% of HHT patients. The HHT AVMs tended to be supratentorial, small, and cortical in this series, findings consistent with other recent studies in the literature. An arteriovenous fistula, cavernous malformation, and capillary telangiectasia were identified in 0.5%, 1%, and 1.9% of HHT patients, respectively. Conclusions Few studies have investigated the prevalence of the various vascular malformations found in HHT patients screened with 3-T MRI/MRA of the brain. Hereditary hemorrhagic telangiectasia AVMs are more likely to be multiple and have a tendency toward small size and cortical location. As such, they are often treated using a single-modality therapy.

scholarly journals Diagnostic yield of capsule endoscopy for small bowel arteriovenous malformations in patients with hereditary hemorrhagic telangiectasia: a systematic review and meta-analysis

2019 ◽  
Vol 07 (02) ◽  
pp. E282-E289 ◽  
Author(s):  
Kevin Singh ◽  
Ayla Zubair ◽  
Andrew Prindle ◽  
Ahmed Nadeem ◽  
Gulam Khan
Keyword(s):  
Systematic Review ◽  
Small Bowel ◽  
Capsule Endoscopy ◽  
Hereditary Hemorrhagic Telangiectasia ◽  
Arteriovenous Malformations ◽  
Diagnostic Yield ◽  
Meta Analysis ◽  
Bleeding Risk ◽  
Diagnostic Modality ◽  
Non Invasive

Abstract Background and study aims Small bowel arteriovenous malformations (AVMs) pose a bleeding risk and have traditionally been diagnosed by invasive enteroscopic procedures in patients with hereditary hemorrhagic telangiectasia (HHT). Capsule endoscopy (CE) is emerging as a safe and non-invasive alternative for small intestinal evaluation, but its diagnostic yield and utility in diagnosing small bowel AVMs in HHT patients are understudied. The aim of this study was to meta-analyze the utility of CE for diagnosing AVMs in HHT patients. Methods A meta-analysis and systematic review of the literature on CE in HHT patients identified in the PubMed, EMBASE, Scopus, and Cochrane databases from inception to March 2018 were conducted. Summary effects were estimated using a random effects model. Results After applying exclusion criteria, five studies (n = 124 patients) were eligible for meta-analysis. The pooled diagnostic yield for visualization of small bowel AVMs by CE was 77.0 % (95 % CI 65.8 – 85.4 %, P < 0.001). Conclusions CE has a good diagnostic yield for small bowel AVMs in HHT. It can be regarded as a sufficient, noninvasive diagnostic modality for identifying small bowel AVMs in HHT patients.

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

2017 ◽  
Vol 127 (2) ◽  
pp. 302-310 ◽  
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.

Return of the lesion: a meta-analysis of 1134 angiographically cured pediatric arteriovenous malformations

2021 ◽  
pp. 1-8
Author(s):  
David C. Lauzier ◽  
Ananth K. Vellimana ◽  
Arindam R. Chatterjee ◽  
Joshua W. Osbun ◽  
Christopher J. Moran ◽  
...  
Keyword(s):  
Arteriovenous Malformations ◽  
Pediatric Patients ◽  
Web Of Science ◽  
Meta Analysis ◽  
Study Cohort ◽  
Fisher Exact Test ◽  
Exact Test ◽  
Risk Of Rupture ◽  
Brain Avms ◽  
Prospective Database

OBJECTIVE Brain arteriovenous malformations (AVMs) carry a risk of rupture and subsequent morbidity or mortality unless fully treated. AVMs in pediatric patients are known to occasionally recur after obliteration. The objective of this study was to characterize the risk of AVM recurrence following angiographically confirmed obliteration in children. METHODS Consecutive pediatric AVMs treated at a single center were identified from a prospective database. Patients with angiographically confirmed AVM obliteration following treatment were included in this study. Associations between AVM recurrence and patient or procedural factors were characterized using the two-tailed Fisher exact test or Mann-Whitney U-test. A literature search was conducted using PubMed, Scopus, Embase, and the Clarivate Web of Science with defined search criteria, and eligible studies were included alongside this study cohort in a meta-analysis. Rates of AVM recurrence following obliteration were pooled across studies with a random-effects model and reported with 95% confidence intervals (CIs). RESULTS Recurrence after angiographic confirmation of AVM obliteration was observed in 10.4% (7/67) of pediatric AVMs treated at the authors’ center. Patients with recurrent AVMs were significantly younger than those without recurrence (p = 0.002). In the meta-analysis, which included 1134 patients across 24 studies, the rate of recurrence was 4.8% (95% CI 3.0%–6.7%). The rate of AVM recurrence following radiosurgery was 0.7% (95% CI 0%–1.6%), which was significantly lower than the 8.5% rate (95% CI 5.0%–12.0%) following microsurgery. CONCLUSIONS Recurrence of obliterated brain AVMs is common in children. Recurrence is more common in young children and following microsurgery.

scholarly journals A Meta-Analysis Evaluating the Incidence of Bleeding Events With Intravenous Defibrotide Treatment Outside the Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome Setting

2020 ◽  
Vol 26 ◽  
pp. 107602962093520
Author(s):  
William Tappe ◽  
Saurabh Aggarwal ◽  
Ozlem Topaloglu ◽  
Massimo Iacobelli
Keyword(s):  
Pediatric Patients ◽  
Hematopoietic Cell Transplantation ◽  
Meta Analysis ◽  
Bleeding Risk ◽  
The United States ◽  
Occlusive Disease ◽  
Sinusoidal Obstruction Syndrome ◽  
The European Union ◽  
Bleeding Events ◽  
Prescribing Information

Defibrotide is approved to treat hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) with renal/pulmonary dysfunction following hematopoietic cell transplantation (HCT) in adult and pediatric patients in the United States, and to treat severe hepatic VOD/SOS post-HCT in adult and pediatric patients aged >1 month in the European Union. The defibrotide prescribing information warns that defibrotide may increase bleeding risk in VOD/SOS patients. To broaden our understanding of the incidence of bleeding with defibrotide, we performed a meta-analysis of the published literature of defibrotide use outside of the post-HCT VOD/SOS setting. Of 1857 records identified, 125 reported on defibrotide; 23 contained data on bleeding events. The estimated overall incidence of bleeding events was 1% (95% confidence interval [CI]: 0%-2%) and 8% (95% CI: 3%-14%) in studies using intravenous defibrotide and studies with controls, respectively. The risk ratio for bleeding events with intravenous defibrotide versus controls was 0.36 (95% CI: 0.24-0.52; P < .00001) among studies with data on intravenous defibrotide and controls. This meta-analysis of defibrotide use outside of the post-HCT VOD/SOS setting suggests that the incidence of bleeding with defibrotide is lower than controls.

scholarly journals High output cardiac failure in 3 patients with hereditary hemorrhagic telangiectasia and hepatic vascular malformations, evaluation of treatment

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Lilian B. Olsen ◽  
Anette D. Kjeldsen ◽  
Mikael K. Poulsen ◽  
Jens Kjeldsen ◽  
Annette D. Fialla
Keyword(s):  
Liver Transplantation ◽  
Orthotopic Liver Transplantation ◽  
Cardiac Failure ◽  
Hereditary Hemorrhagic Telangiectasia ◽  
Arteriovenous Malformations ◽  
Vascular Malformations ◽  
Symptom Relief ◽  
Case Series ◽  
Hospital Treatment ◽  
High Output

Abstract Background This report addresses how patients with hereditary hemorrhagic telangiectasia (HHT) and high output cardiac failure (HOCF) due to hepatic vascular malformations, should be evaluated and could be treated. HHT is a genetic disorder, leading to vascular abnormalities with potentially serious clinical implications. In the liver, arteriovenous malformations occur in more than 70% of patients, but only about 8% present clinical symptoms such as HOCF with pulmonary hypertension and less commonly portal hypertension, biliary ischemia and hepatic encephalopathy. Results Three female patients with HHT type 2 and HOCF caused by severe arteriovenous malformations in the liver are presented in this case series. The patients were seen at the HHT-Centre at Odense University Hospital. Treatment with either orthotopic liver transplantation (one patient) or bevacizumab (two patients) was initiated. All patients experienced marked symptom relief and objective improvement. New York Heart Association—class were improved, ascites, peripheral edema and hence diuretic treatment was markedly reduced or discontinued in all three patients. Bevacizumab also resulted in notable effects on epistaxis and anemia. Conclusion Our findings substantiate the importance of identification of symptomatic arteriovenous malformations in the liver in patients with HHT. Bevacizumab may possibly, as suggested in this case series and supported by previous case studies, postpone the time to orthotopic liver transplantation or even make it unnecessary. Bevacizumab represents a promising new treatment option, which should be investigated further in clinical trials.

scholarly journals Spontaneous intracranial hemorrhage in children – ruptured lobar arteriovenous malformations: report of two cases

2015 ◽  
Vol 22 (1) ◽  
pp. 86-93
Author(s):  
A. Tascu ◽  
C. Pascal ◽  
S.M. Florea ◽  
St.M. Iencean
Keyword(s):  
Intracranial Hemorrhage ◽  
Arteriovenous Malformations ◽  
Vascular Malformations ◽  
Pediatric Population ◽  
Bleeding Risk ◽  
Neurological Status ◽  
Recurrent Bleeding ◽  
Surgical Interventions ◽  
Spontaneous Intracranial Hemorrhage ◽  
Angiographic Examination

Abstract Brain arteriovenous malformations (AVMs) are lesions thought to be primarily congenital in origin, consisting of fistulous connections of abnormal arteries and veins, without normal intervening capillary beds and no cerebral parenchyma between vessels. In the pediatric population, AVMs represent the most common cause of spontaneous intracranial hemorrhage (ICH), with a high recurrent bleeding risk. The aim of this paper is to report 2 cases of ruptured lobar AVMs in children, presenting with spontaneous ICH. Due to the patients’ neurological status, the only imaging examination performed preoperatively was a CT scan, showing intraparenchymal hemorrhage. Thus, there was no MRI/angiographic examination to prove the existence of a brain AVM prior to the surgical interventions. Also, the cerebral angiography performed after the surgery showed, in both patients, no signs of residual vascular malformations. Therefore, the diagnosis of AVM was certified by macroscopic and microscopic pathological findings, with no brain imaging suggestive of a vascular malformation.

scholarly journals Defective flow-migration coupling causes arteriovenous malformations in hereditary hemorrhagic telangiectasia

2021 ◽  
Author(s):  
Hyojin Park ◽  
Jessica Furtado ◽  
Mathilde Poulet ◽  
Minhwan Chung ◽  
Sanguk Yun ◽  
...  
Keyword(s):  
Blood Flow ◽  
Endothelial Cell ◽  
Hereditary Hemorrhagic Telangiectasia ◽  
Arteriovenous Malformations ◽  
Nuclear Translocation ◽  
Vascular Malformations ◽  
Critical Role ◽  
Cell Polarization ◽  
Endothelial Cell Migration ◽  
Cardiovascular Development

Background: Activin receptor-like kinase 1 (ACVRL1, hereafter ALK1) is an endothelial transmembrane serine threonine kinase receptor for BMP family ligands that plays a critical role in cardiovascular development and pathology. Loss-of-function mutations in the ALK1 gene cause type 2 hereditary hemorrhagic telangiectasia (HHT), a devastating disorder that leads to arteriovenous malformations (AVMs). Here we show that ALK1 controls endothelial cell polarization against the direction of blood flow and flow-induced endothelial migration from veins through capillaries into arterioles. Methods: Using Cre lines that recombine in different subsets of arterial, capillary-venous or endothelial tip cells, we showed that capillary-venous Alk1 deletion was sufficient to induce AVM formation in the postnatal retina. Results: ALK1 deletion impaired capillary-venous endothelial cell polarization against the direction of blood flow in vivo and in vitro. Mechanistically, ALK1 deficient cells exhibited increased integrin signaling interaction with VEGFR2, which enhanced downstream YAP/TAZ nuclear translocation. Pharmacological inhibition of integrin or YAP/TAZ signaling rescued flow migration coupling and prevented vascular malformations in Alk1 deficient mice. Conclusions: Our study reveals ALK1 as an essential driver of flow-induced endothelial cell migration and identifies loss of flow-migration coupling as a driver of AVM formation in HHT disease. Integrin-YAP/TAZ signaling blockers are new potential targets to prevent vascular malformations in HHT patients.

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