Recurrence of Pulmonary Arteriovenous Malformation after Embolization in Patients with Pulmonary Hypertension.

PURPOSE: To evaluate the correlation between pulmonary hypertension (PH) and recurrence of pulmonary arteriovenous malformation (PAVM) after embolization. MATERIALS AND METHODS: With institutional review board (IRB) approval, the records of 377 patients with PAVMs evaluated at a single hereditary hemorrhagic telangiectasia (HHT) center of excellence between January 1, 2013, and September 10, 2023, were retrospectively reviewed. PAVMs embolized during this time period were evaluated for recurrence. Patients and PAVMs not treated during this time period were excluded. Growth of previously untreated PAVMs was not considered recurrence. Patients without chest computed tomography (CT) follow-up were excluded. General demographics, HHT status as defined by genetic testing or Curacao criteria, presence of PH, history of smoking, anemia, and hepatic arteriovenous malformations (AVMs) were documented. Odds ratio (OR) was calculated and stratified analysis was performed to assay the correlation between PAVM recurrence, PH, and possible confounders. RESULTS: A total of 151 patients with PAVMs were treated during the study period, including 438 PAVMs, for which follow-up was available. This included 106 patients with definite, 31 with doubtful, and 14 with possible HHT. The presence of PH was significantly associated with PAVM recurrence both by patient (OR, 8.13; 95% CI, 3.50-19.67) and by lesion (OR, 4.07; 95% CI, 2.14-7.91). Multivariate analysis demonstrated that this correlation was independent of several variables including HHT status, smoking history, presence of hepatic AVMs, and anemia. CONCLUSIONS: There is a high correlation between PH and PAVM recurrence, suspected to be due to high pulmonary artery pressures causing recanalization. PH may suggest the need for shorter surveillance intervals.

Prenatal diagnosis of pulmonary arteriovenous malformations with a postnatal diagnosis of Osler-Weber-Rendu syndrome.

Hereditary Hemorrhagic Telangiectasia (HHT), commonly known as Osler-Weber-Rendu disease, is an autosomal dominant multisystemic vascular disease associated with approximately 70% of cases of pulmonary arteriovenous malformations (PAVMs). Prenatal cases of PAVMs typically present with pulmonary vein dilatation on ultrasonography. This study presents a prenatal diagnosis of PAVMs with enlarged right pulmonary vein, cardiomegaly, cystic-appearing areas in the right lung and subsequent confirmation of Osler-Weber-Rendu syndrome using autopsy and whole exom sequencing.

Hepatic Vascular Variants in Hereditary Haemorrhagic Telangiectasia: Imaging findings.

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterised by vascular dysplasia. Hepatic vascular malformations (VMs) range from small telangiectases to significant vascular shunting. Here we report two cases of HHT. Case 1 had diffuse ectasia of the hepatic artery along its intrahepatic and extrahepatic course with a hepatic arterial aneurysm. Case 2 presented with ileal and hepatic telangiectases. Knowledge of these vascular variants is indispensable for clinicians and radiologists in aiding diagnosis and surgical and interventional management.

Schizencephaly in Hereditary Hemorrhagic Telangiectasia.

BACKGROUND AND PURPOSE: The presence of malformations of cortical development in patients with hereditary hemorrhagic telangiectasia has been reported on previous occasions. We evaluated a sample of adults with hereditary hemorrhagic telangiectasia for the presence of malformations of cortical development, spatial coincidence of malformations of cortical development and AVMs, and the coincidence of brain and pulmonary AVMs. MATERIALS AND METHODS: A total of 141 patients 18 years of age or older who were referred to the Augusta University hereditary hemorrhagic telangiectasia clinic and underwent brain MR imaging between January 19, 2018, and December 3, 2020, were identified. MR imaging examinations were reviewed retrospectively by 2 experienced neuroradiologists, and the presence of malformations of cortical development and AVMs was confirmed by consensus. Demographic and clinical information was collected for each case, including age, sex, hereditary hemorrhagic telangiectasia status by the Curacao Criteria, mutation type, presence of malformations of cortical development, presence of brain AVMs, presence of pulmonary AVMs, and a history of seizures or learning disabilities. RESULTS: Five of 141 (3.5%) patients with hereditary hemorrhagic telangiectasia had malformations of cortical development. Two of the 5 patients with polymicrogyria also had closed-lip schizencephaly. One of the patients had a porencephalic cavity partially lined with heterotopic GM. The incidence of spatially coincident polymicrogyria and brain AVMs was 40% (2/5 cases). Of the patients with hereditary hemorrhagic telangiectasia and malformations of cortical development, 4/5 (80%) had pulmonary AVMs and 2/5 (40%) had brain AVMs. CONCLUSIONS: To our knowledge, we are the first group to report the presence of schizencephaly in patients with hereditary hemorrhagic telangiectasia. The presence of schizencephaly and porencephaly lends support to the hypothesis of regional in utero cerebral hypoxic events as the etiology of malformations of cortical development in hereditary hemorrhagic telangiectasia.

Neurovascular Manifestations in Pediatric Patients With Hereditary Haemorrhagic Telangiectasia.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a multiorgan vascular dysplasia with limited data regarding its neurovascular manifestations and genotype-phenotype correlation in children. The objective of this study was to describe the neurovascular findings in a large cohort of children with HHT and correlate between phenotype and genotype. METHODS: This retrospective study was conducted on 221 children (<18 years) with a definite or possible diagnosis of HHT based on Curacao criteria, or with positive genetics for the mutated genes of ENG, ACVRL-1, and SMAD-4, who also underwent brain MRI and/or conventional angiography. Demographic and clinical information, imaging findings, and follow up information were gathered. RESULTS: Two hundred twenty-one children with HHT (70.6% genetically confirmed, and 99.5% positive family history) were included, with a median age of 7 years (interquartile range: 3 to 11 years) and 58.8% male predominance. Neurovascular lesions were found in 64 of 221 (28.9%), with 3.1% prevalence of intracranial hemorrhage. The most commonly observed vascular malformations were developmental venous anomalies (48.5%) and brain arteriovenous malformations (AVMs) (31.2%), followed by capillary malformations (14.1%). Multiple AVMs were seen in 10.0% of the cohort. We found no instances of de novo AVM (1281.8 patient-years).A significantly higher proportion of patients with ENG mutations (19.7%) had brain AVM than those with ACVRL-1 (4.9%) and SMAD-4 (0%) mutations (P < 0.01). There was no significant difference in the hemorrhagic risk of shunting lesions associated with ENG (35.3%) or ACVRL-1 (33.3%) positivity (P = 0.9). CONCLUSIONS: We describe the neurovascular imaging and genetic findings from a large pediatric cohort of HHT, to enhance clinical awareness and guide management of patients with HHT.

Prevalence of and Factors Associated with Arterial Aneurysms in Patients with Hereditary Hemorrhagic Telangiectasia: 17-Year Retrospective Series of 418 Patients.

PURPOSE: To estimate the prevalence of and identify characteristics associated with the presence of aneurysms in a cohort of patients with hereditary hemorrhagic telangiectasia (HHT). MATERIALS AND METHODS: In the study institution's HHT database, 418 patients with a definite HHT diagnosis were identified based on the clinical Curaçao criteria and/or an HHT-associated genetic mutation. Regression modeling was used to evaluate the association between arterial aneurysms and older age, male sex, smoking, alcohol consumption, hypertension, hyperlipidemia, genetic mutations, the presence of arteriovenous malformations (AVMs) unrelated to the aneurysms, and HHT-related genetic mutations. RESULTS: Forty-three (10.3%) patients had at least 1 aneurysm. Sixteen (3.8%) patients had multiple aneurysms. Of the variables analyzed, older age (odds ratio [OR] = 1.02; 95% confidence interval [CI]: 1.0-1.1), the presence of anatomically and flow-unrelated AVMs (OR = 3.2; 95% CI: 1.3-8.0), and the presence of activin A receptor type II-like 1 (ACVRL1) mutation (OR = 4.0; 95% CI: 1.5-10) were associated with the presence of at least 1 aneurysm. CONCLUSIONS: In this cohort of patients with HHT, the prevalence of intracranial and visceral arterial aneurysms was estimated to be 10.3%. Older age, the presence of unrelated AVMs, and the presence of the ACVRL1 mutation were associated with the presence of arterial aneurysms. Further study is required to assess the clinical importance and risk of rupture of aneurysms in patients with HHT.

First Time Wheezing in a 2-Year-Old.

Pediatric patients with respiratory signs and symptoms who are found to be wheezing present a diagnostic dilemma to pediatricians. The majority of these cases are diagnosed as some degree of reactive airway disease, either as viral bronchiolitis or asthma. In this scenario, a patient with wheezing was initially given 2 courses of appropriate antibiotics on the basis of the duration and concurrence of other symptoms. However, he was subsequently referred to a pediatric pulmonologist for further workup after failure to improve and persistent oxygen saturations in the low-to-mid 90s. More extensive testing was completed by the pediatric pulmonologist, in addition to a short hospital admission. A rigid bronchoscopy was eventually completed, which revealed small pieces of partially digested material. Although his persistent cough resolved, his saturations continued to be suboptimal. A chest computed tomography scan with contrast was then completed, which eventually led to his diagnosis and appropriate treatment and resolution of his symptoms.

Systemic and CNS manifestations of inherited cerebrovascular malformations.

Cerebrovascular malformations occur in both sporadic and inherited patterns. This paper reviews imaging and clinical features of cerebrovascular malformations with a genetic basis. Genetic diseases such as familial cerebral cavernous malformations and hereditary hemorrhagic telangiectasia often have manifestations in bone, skin, eyes, and visceral organs, which should be recognized. Genetic and molecular mechanisms underlying the inherited disorders are becoming better understood, and treatments are likely to follow. An interaction between the intestinal microbiome and formation of cerebral cavernous malformations has emerged, with possible treatment implications. Two-hit mechanisms are involved in these disorders, and additional triggering mechanisms are part of the development of malformations. Hereditary hemorrhagic telangiectasia encompasses a variety of vascular malformations, with widely varying risks, and a more recently recognized association with cortical malformations. Somatic mutations are implicated in the genesis of some sporadic malformations, which means that discoveries related to inherited disorders may aid treatment of sporadic cases. This paper summarizes the current state of knowledge of these conditions, salient features regarding mechanisms of development, and treatment prospects.

Vascular anomalies associated with hepatic shunting.

Congenital vascular anomalies affecting the liver have been described in the scientific literature for decades. Understanding these malformations begins with knowledge of hepatic vascular embryology. Surgeons have applied numerous classification systems to describe both intrahepatic and extrahepatic shunts, which can confuse the reader and clinician. In our experience, focusing on one classification system for extrahepatic shunts and one for intrahepatic shunts is better. Today many patients with these shunts carry good long-term prognosis thanks to advances in imaging to better detect shunts earlier and classify them. Timely intervention by skilled radiologists and surgeons have also limited complications arising from dynamic shunts and can avoid a liver transplant. Congenital hepatic shunts are not the only vascular condition affecting the liver. Hereditary hemorrhagic telangiectasia, also known as Osler Weber Rendu syndrome, particularly type 2, may have varying severity of hepatic involvement which warrants longitudinal care from an experienced hepatologist. Lastly, congenital hemangiomas, often first identified on the skin and oral mucosa, also can affect the liver. While most will resolve in infancy and childhood, the pediatric hepatologist must understand how and when to treat persistent lesions and their complications. This article serves as a concise reference to help clinicians better care for patients with these rare conditions.

Homozygous GDF2-Related Hereditary Hemorrhagic Telangiectasia in a Chinese Family.

Hereditary hemorrhagic telangiectasia (HHT) can be clinically diagnosed, but children often lack characteristic features. We report a family with homozygous growth differentiation factor 2 (GDF2)-related HHT diagnosed by genetic testing. A boy aged 5 years and 2 months presented with isolated hypoxemia. He was the product of a consanguineous marriage; his parents were second cousins. Physical examination revealed cyanosis of nail beds and clubbed fingers. Pulse oxygen saturation was 84% to 89%. Lung function, contrast-enhanced lung computed tomography, and noncontrast echocardiography were normal. A pulmonary perfusion scan revealed radioactivity in the brain and bilateral kidney, suggesting the existence of a intrapulmonary shunt. Whole-exome sequencing revealed a homozygous variant [c.1060_1062delinsAG (p.Tyr354ArgfsTer15)] in GDF2, which was found to be inherited from his heterozygous parents. At the age of 8 years, he developed epistaxis, and an angiogram revealed diffuse pulmonary arteriovenous malformations. At the age of 9 years, he was treated with sirolimus, and his condition improved significantly. However, his now 7-year-old sister with the same homozygous variant currently has no symptoms. Physical examinations revealed 1 pinpoint-sized telangiectasia on the chest of his mother and a vascular lesion on the forehead of his sister. Additionally, the patient's father and great-uncle had a history of mild to moderate epistaxis. Mutation in GDF2 is a rare cause of HHT. Ours is the first report of homozygous GDF2-related HHT; in addition, this variant has not been reported previously. In our report, we also confirm variable expressivity, even with the same pathogenic variant in GDF2-related HHT.

[Rendu-Osler disease and recurrent thromboembolic venous disease]. / Maladie de Rendu-Osler et maladie veineuse thromboembolique récidivante.

Rendu-Osler-Weber syndrome is a rare systemic fibrovascular dysplasia, recognized by mucocutaneous telangiectasias, arteriovenous malformations, epistaxis and family history. Venous thromboembolic disease is a poor prognostic factor in this disease given the risk of increased bleeding caused by anticoagulant therapy. We report a new case of a 56-year-old patient with Osler disease who developed recurrent thromboembolic venous disease when anticoagulants were discontinued. According to a review of the literature, this association does not appear to be fortuitous and is a factor of disease severity.

[An Unusual Hemisphere Syndrome]. / Ein nicht alltägliches Hemisyndrom.

An Unusual Hemisphere Syndrome Abstract. A patient with known hereditary hemorrhagic telangiectasia presents with transient right arm weakness and dizziness. A transient ischemic attack is diagnosed on clinical and risk factors. In the course of the disease, the patient suffers a convulsive event and fever occurs twice without a clear focus on the infection. The initial skull MRI shows a centroparietal lesion on the left with signs of accompanying edema. Due to this unusual concomitant edema, a neoplastic event must also be considered for differential diagnosis. However, the further examinations show no evidence of neoplasia, but the course MRI of the skull shows the image of septic embolisms with a brain abscess. After neurosurgical remediation and appropriate antibiotic treatment, the clinical course is pleasing. The cause of the septic embolisms was a pulmonary arteriovenous malformation due to hereditary hemorrhagic telangiectasia, which could be coiled without complications.

Recurrence of Hereditary Hemorrhagic Telangiectasia After Liver Transplantation: Clinical Implications and Physiopathological Insights.

Liver transplantation (LT) has been proposed as a curative treatment in hereditary hemorrhagic telangiectasia (HHT) with severe hepatic involvement. We provide a long-term evaluation of graft status after LT for HHT, with a focus on the risk of recurrence. The present study included all patients prospectively followed up after LT for HHT in the Lyon Liver Transplant Unit from 1993 to 2010, with a survival of more than 1 year. Protocol clinical, radiological, and histological examinations were performed at regular intervals. Fourteen patients were included (13 women and one man). Median age at LT was 52.5 years (range: 33.1-66.7). In eight patients (seven female), disease recurrence was diagnosed by abnormal radiological features, suggestive of microcirculatory disturbances. Typical vascular lesions, including telangiectasia, were demonstrated by liver biopsy in five of these patients. The median interval between LT and diagnosis of recurrence was 127 months (range: 74-184). The risk of recurrence increased over time; estimated cumulative risk was 47.9% at 15 years. Liver tissue analysis found the coexistence of an angiogenic process combined with endothelial microchimerism, as shown by the presence of vascular lining cells of recipient origin. Conclusion: The present data show that disease recurrence occurs, usually after a long delay, in a significant number of patients treated by LT for liver complications of HHT. This strongly supports the necessity of a lifelong follow-up and suggests that therapeutic strategy needs discussion and evaluation, especially of the role of potential adjuvant treatments to LT, such as antiangiogenic medications, when recurrent disease appears.

De Novo Vascular Lesions After Liver Transplant in a Case With Hereditary Hemorrhagic Telangiectasia and Fibropolycystic Liver Disease: Long-Term Follow-Up With Magnetic Resonance Imaging and Magnetic Resonance Angiography.

We report a case of a 62-year-old woman who received a liver transplant 19 years previously for end-stage liver disease due to hereditary hemorrhagic telangiectasia and fibropolycystic liver disease. During long-term follow-up 8 years after the liver transplant, de novo vascular lesions were detected with magnetic resonance imaging and magnetic resonance angiography. Hepatic vascular lesions had slowly progressed, despite no symptoms. To our knowledge, there are few reports in the English literature of de novo vascular lesions after liver transplant in patients with hepatic telangiectasias.

Liver involvement in hereditary hemorrhagic telangiectasia.

Liver vascular malformations (VMs) in hereditary hemorrhagic telangiectasia (HHT) are typically diffuse and can evolve from small telangiectasias to large arteriovenous malformations, with various stages of severity. Doppler US is the ideal first-line investigation for the assessment of liver VMs in HHT due to its safety, tolerability, low costs, and accuracy for the detection of liver VMs. The caliber, course, and flow characteristics in the hepatic artery, portal vein, and hepatic vein as determined by Doppler US, together with parenchymal abnormalities, support the diagnosis of liver VMs in HHT and their severity staging. When Doppler US expertise is lacking or an assessment of HHT patients with symptoms/signs suggestive of complicated liver VMs is required, particularly if OLT is considered, multiphase CT or MRI is suitable to investigate symptomatic liver VMs. Liver biopsy is neither necessary for the diagnosis of hepatic VMs related to HHT nor should be considered in HHT patients with liver mass/es suggestive of focal nodular hyperplasia.