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Hereditary Hemorrhagic Telangiectasia
Abstract
Hereditary hemorrhagic telangiectasia is a rare autosomal dorminant disease that features abnormal and fragile vascular dilations of terminal vessels in skin and mucous membranes, as well as arteriovenous malformations of internal organs, particularly lungs, brain, and liver. Often patients have not been diagnosed with HHT for a long time, and undiagnosed HHT patients unnecessarily develop serious complications such as severe life-threatening hemorrhage, stroke or brain abscess. Therefore, early detection and appropriate screening is very important. Early detection of HHT allows the appropriate screening for the presence of silent disease such as AVMs in the lungs, liver, or brain, and preventive treatment in the patient and their affected family members. Dentists should be familiar with HHT because the telangiectases on skin and oral mucosa are often the most dramatic and most easily identified component of HHT. Recently, we experienced a case of HHT. We present the case with a review of the literature.
... Patients with HHT have epistaxis as their main clinical manifestation, usually starting at around 10 years of age and becoming more severe with aging, occurring spontaneously or recurrently. (22) Skin telangiectasias are common and usually multiple, commonly involving the lips, tongue, palate, fingers, face, and conjunctiva. (22) Neurological symptoms such as migraine with aura, brain abscess, seizure, stroke, or transient ischemic attack have been described in these patients and may occur due to the presence of cerebrovascular abnormalities; however, most of these findings are consequences of PAVMs that allow the passage of emboli unfiltered by the pulmonary capillary network to the cerebral circulation. ...
... (22) Skin telangiectasias are common and usually multiple, commonly involving the lips, tongue, palate, fingers, face, and conjunctiva. (22) Neurological symptoms such as migraine with aura, brain abscess, seizure, stroke, or transient ischemic attack have been described in these patients and may occur due to the presence of cerebrovascular abnormalities; however, most of these findings are consequences of PAVMs that allow the passage of emboli unfiltered by the pulmonary capillary network to the cerebral circulation. (2) The clinical manifestations in the gastrointestinal (GI) tract are usually upper or lower digestive tract bleeding, which occurs owing to the presence of arteriovenous malformations, telangiectasias, or angiodysplasias that may occur in the stomach, duodenum, small intestine, or colon. ...
... (2) Among hepatic impairments, the most common are hepatic arteriovenous malformations, which manifest as high-output heart failure through the left-to-right shunt. (22) In the initial investigation of brain arteriovenous malformation, MRI should be performed. Liver malformations could be investigated at diagnosis using Doppler ultrasound, multiphase contrast CT, or contrast abdominal MRI. ...
This review aimed to provide an overview of pulmonary arteriovenous malformations, including the major clinical and radiological presentations, investigation, and treatment algorithm of the condition. The primary etiology of pulmonary arteriovenous malformations is hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber syndrome, with mutations in the ENG gene on chromosome 9 (HHT type 1) or in the ACVRL1/ALK1 complex (HHT type 2). Epistaxis should always be evaluated when repeated, when associated with anemia, and in some cases of hypoxemia. In the investigation, contrast echocardiography and chest CT are essential for evaluating this condition. Embolization is the best treatment choice, especially for correction in cases of hypoxemia or to avoid systemic infections. Finally, disease management was addressed in special conditions such as pregnancy. CT follow-up should be performed every 3-5 years, depending on the size of the afferent and efferent vessels, and antibiotic prophylactic care should always be oriented. Ultimately, knowledge of the disease by health professionals is a crucial point for the early diagnosis of these patients in clinical practice, which can potentially modify the natural course of the disease.
Keywords:
Telangiectasia, hereditary hemorrhagic; Arteriovenous malformations; Lung
... Clinical consequences are widespread telangiectasias and vascular malformations, which can cause bleeding, potentially affecting many organs of the body (2). The most common manifestation of the syndrome is epistaxis, but the associated brain and pulmonary lesions are potential sources of relevant morbidity and mortality (3,4). ...
... Bleeding starts usually before 21 years of age and become more severe in later decades. Proposed treatments include cauterization, laser ablation, estrogen therapy, septal dermatoplasty, and arterial embolization (2). ...
... PAVMs are present only in about 5 to 15% of persons with HHT (12), but drive morbidity and mortality (2). They are often multiple and usually appear in both lungs. ...
Background:
Hemorrhagic Hereditary Telangiectasia (HHT), or Rendu-Osler-Weber syndrome, is a rare genetic disorder characterized by mucocutaneous telangiectasias and visceral arteriovenous malformations.
Aim and methods:
We describe the case of a 64-year old woman in which radiology was useful to interpret an apparently unexplained constellation of symptoms.
Results:
Brain MRI showing ischemic stroke, pulmonary angiography demonstrating arteriovenous malformations, and capsule endoscopy detecting telangiectasias in the jejunum, along with a clinical history of recurrent epistaxis, allowed us to diagnose HHT.
Conclusions:
HHT is rare and difficult to diagnose. Radiology can aid the clinical suspicion. www.actabiomedica.it.
... Epistaxis, caused by nasal mucosa telangiectasia, is the most common manifestation of HHT and is often apparent by age 10. Skin involvement appears by the age of 40 as multiple telangiectasias of the lips, tongue, face, trunk, arms, and fingers ( Figure 13A-C) [56,58]. ...
... CT shows ground-glass nodules, with solid components and the architecture of the feeding artery and vein ( Figure 13D,E). An enhanced phase with thin slice thicknesses is also acquired from the upper abdomen to evaluate the presence of hepatic vascular fistulas ( Figure 13F) [58]. ...
... Epistaxis, caused by nasal mucosa telangiectasia, is the most common manifestation of HHT and is often apparent by age 10. Skin involvement appears by the age of 40 as multiple telangiectasias of the lips, tongue, face, trunk, arms, and fingers ( Figure 13A-C) [56,58]. The arteriovenous malformations in HHT are direct connections between the pulmonary artery and vein through a thin-walled aneurysm without any capillary vessels. ...
Background:
Cutaneous manifestations of systemic diseases are diverse and sometimes precede more serious diseases and symptomatology. Similarly, radiologic imaging plays a key role in early diagnosis and determination of the extent of systemic involvement. Simultaneous awareness of skin and imaging manifestations can help the radiologist to narrow down differential diagnosis even if imaging findings are nonspecific.
Aims:
To improve diagnostic accuracy and patient care, it is important that clinicians and radiologists be familiar with both cutaneous and radiologic features of various systemic disorders. This article reviews cutaneous manifestations and imaging findings of commonly encountered systemic diseases.
Conclusions:
Familiarity with the most disease-specific skin lesions help the radiologist pinpoint a specific diagnosis and consequently, in preventing unnecessary invasive workups and contributing to improved patient care.
... Hereditary hemorrhagic telangiectasia is an autosomal dominant inherited disease characterized by multisystemic vascular dysplasia (2). The main genetic mutations are in endoglin (ENG), activin receptor-like kinase1 (ACVRL1), and mothers against decapentaplegic homolog 4 (SMAD4) (3). ...
... Unfortunately, high-resolution chest tomography (HRCT) and transbronchial lung biopsy (TBLB) were not underwent. (2) The four times of pregnancies kept the pulmonary blood vessels in a state of higher circulation over an extended period of time. Although the abnormal state was not continuous, the remodeling of the pulmonary capillaries Computed tomography pulmonary angiography. ...
A young adult woman presented with exertional dyspnea and she had had recurrent epistaxis for more than 10 years. On physical examination, cyanosis was noted on the lips, and telangiectasias were seen on the oral mucosa and fingertips. Routine investigations revealed iron deficiency anemia and slightly elevated bilirubin. The result of right heart catheterization was indicative of pulmonary arterial hypertension (PAH). Pulmonary angiography showed arteriovenous malformations of the left upper pulmonary artery, and anterior cerebral artery malformation was seen in cranial computed tomographic angiogram. Genetic testing revealed that she and her three daughters carried heterozygous variant of ENG c.1195-1196del p.Arg399GlyfsTer2, which is characterized by pulmonary and cerebral arteriovenous malformations. In addition, our patient had pulmonary hypertension (PH) that is commonly associated with ACVRL1 mutations, revealing her phenotype was not consistent with isolated ENG genetic mutations. Here, we report a case with hereditary hemorrhagic telangiectasia (HHT) combined with PAH, which is associated with interesting differential diagnosis and etiological analysis. We have discussed the relationship between PH and HHT and the characteristics of PAH in HHT patients.
... A multidisciplinary focus is a vital consideration for the correct early diagnosis and treatment; and treatment is recommended to be in centers with ample experience in management of this kind of case [ 8 ,9 ]. Intervention radiologists are essential in the treatment of this kind of alteration, due to their broad experience, not only in management, but also in complex embolization, which helps to improve the prognosis and quality of life for this kind of patient [10][11][12] . ...
... In regards to treatment, endovascular therapy guided by images, such as sclerotherapy, embolization, and surgical resection, are recommended as the best option, according to the kind of patient [9][10][11][12] . In our patient, there was epistaxis and recurrent vaginal bleeding, for which she was sent to the hospital center, where she was diagnosed with Rendu-Osler-Weber syndrome. ...
Hereditary hemorrhagic telangiectasia (HHT), or Rendu-Osler-Weber disease, is a dominant autosomal disease characterized by the presence of multiple telangiectasia in skin and mucus, associated with arteriovenous malformations (AVM) of various organs, including the lungs, gastrointestinal system and brain. HHT is presented most frequently as recurrent, spontaneous epistaxis. Patients may also present digestive, pulmonary and intracranial hemorrhage, as well as secondary anemia.
This article reports the case of a female patient, 62 years old, with multiple episodes of epistaxis and vaginal bleeding, with diagnosis of complex HHT, which was managed with multiple embolizations, which improved symptoms and survival. In this kind of patient, it is possible, with timely diagnosis and treatment, to obtain a greater quality and expectation of life. Due to the fact that the severity and alterations in each patient are so variable, management should be individualized.
... Hereditary hemorrhagic telangiectasia (HHT), also called Rendu-Osler syndrome, is a rare genetic disease characterized by autosomal dominance, multisystemic vascular dysplasia, and age-related penetrance. This includes arteriovenous malformations (AVMs) in the skin, brain, lung, liver, and mucous membranes [1,2]. The current prevalence estimates for HHT are approximately 1 in 5000 worldwide [3]. ...
Hereditary hemorrhagic telangiectasia (HHT), also called Rendu–Osler syndrome, is a group of rare genetic diseases characterized by autosomal dominance, multisystemic vascular dysplasia, and age-related penetrance. This includes arteriovenous malformations (AVMs) in the skin, brain, lung, liver, and mucous membranes. The correlations between the phenotype and genotype for HHT are not clear. An HHT Chinese pedigree was recruited. Whole exome sequencing (WES) analysis, Sanger verification, and co-segregation were conducted. Western blotting was performed for monitoring ENG/VEGFα signaling. As a result, a nonsense, heterozygous variant for ENG/CD105: c.G1169A:p. Trp390Ter of the proband with hereditary hemorrhagic telangiectasia type 1 (HHT1) was identified, which co-segregated with the disease in the M666 pedigree. Western blotting found that, compared with the normal levels associated with non-carrier family members, the ENG protein levels in the proband showed approximately a one-half decrease (47.4% decrease), while levels of the VEGFα protein, in the proband, showed approximately a one-quarter decrease (25.6% decrease), implying that ENG haploinsufficiency, displayed in the carrier of this variant, may affect VEGFα expression downregulation. Pearson and Spearman correlation analyses further supported TGFβ/ENG/VEGFα signaling, implying ENG regulation in the blood vessels. Thus, next-generation sequencing including WES should provide an accurate strategy for gene diagnosis, therapy, genetic counseling, and clinical management for rare genetic diseases including that in HHT1 patients.
... The most common clinical manifestation is nose bleeds, and bleeding may also occur from the gastrointestinal tract. [16] Recurrent iron losses cause anaemia requiring iron supplementation and, in some cases, red cell transfusion. The nosebleeds may be severe, but they do not necessarily get worse with age (though, with time, more people have their first HHT nosebleed [17,18]), and a fluctuant pattern is observed [19]. ...
Hereditary haemorrhagic telangiectasia (HHT) is a vascular dysplasia inherited as an autosomal dominant trait, due to a single heterozygous loss-of-function variant, usually in ACVRL1 (encoding activin receptor-like kinase 1 [ALK1]), ENG (encoding endoglin [CD105]), or SMAD4. In a consecutive single-centre series of 37 positive clinical genetic tests performed in 2021–2023, a skewed distribution pattern was noted, with 30 of 32 variants reported only once, but ACVRL1 c.1231C>T (p.Arg411Trp) identified as the disease-causal gene in five different HHT families. In the same centre’s non-overlapping 1992–2020 series where 110/134 (82.1%) HHT-causal variants were reported only once, ACVRL1 c.1231C>T (p.Arg411Trp) was identified in nine further families. In a 14-country, four-continent HHT Mutation Database where 181/250 (72.4%) HHT-causal variants were reported only once, ACVRL1 c.1231C>T (p.Arg411Trp) was reported by 12 different laboratories, the adjacent ACVRL1 c.1232G>A (p.Arg411Gln) by 14, and ACVRL1 c.1120C>T (p.Arg374Trp) by 18. Unlike the majority of HHT-causal ACVRL1 variants, these encode ALK1 protein that reaches the endothelial cell surface but fails to signal. Six variants of this type were present in the three series and were reported 6.8–25.5 (mean 8.9) times more frequently than the other ACVRL1 missense variants (all p-values < 0.0039). Noting lower rates of myocardial infarction reported in HHT, we explore potential mechanisms, including a selective paradigm relevant to ALK1′s role in the initiating event of atherosclerosis, where a plausible dominant negative effect of these specific variants can be proposed. In conclusion, there is an ~9-fold excess of kinase-inactive, cell surface-expressed ACVRL1/ALK1 pathogenic missense variants in HHT. The findings support further examination of differential clinical and cellular phenotypes by HHT causal gene molecular subtypes.
... The vast majority of HHT epistaxis patients have mutations in endorphilin (ENG) or activin receptor-like kinase 1 (ACVRL1/ ALK1), resulting in dysangiogenesis, telangiectasia on the mucosal surface, local hyperfibrinolysis in telangiectasia and arteriovenous malformation in the internal organs (Kwaan and Silverman, 1973;Watanabe et al., 1985;Shovlin, 2010). It is characterized by vascular malformations in the nasal mucosa, skin, gastrointestinal tract, brain, lungs and liver, (Guttmacher et al., 1995) and causes telangiectasia of the nasal mucosa with varying degrees of recurrent epistaxis that can occur in 95% of HHT patients, wherein the mean age of first onset is 12 years and the frequency of epistaxis is approximately 18/month (GRIGG et al., 2017). Severe recurrent epistaxis may last several hours a day, causing severe iron deficiency anemia and often transfusion dependence, and even causing social isolation, as well adversely affecting the patients' employment, travel and daily activities. ...
Objective: A meta-analysis is conducted to evaluate the effectiveness and safety of bevacizumab in hereditary hemorrhagic telangiectasia (HHT) epistaxis.
Method: Two researchers search PubMed, EMBASE and Web of Science databases from their inception until September 3th, 2023. The literature is read and screened, and valid data extracted, collated and analyzed. Its quality is then assessed using the Cochrane risk assessment scale. This study uses Endnote 9.3 software for literature management and RevMan 5.3.1 software for evaluation.
Results: A total of 7 documents met the requirements, including a total of 359 patients, and the literature quality evaluation was grade B. The Meta-analysis results showed that:Bevacizumab reduces the Epistaxis Severity Score (ESS) in patients with HHT epistaxis compared with the control [WMD = −0.22,95%CI (−0.38, −0.05), p = 0.01]. However, there is no significant effect on duration of epistaxis [WMD = −15.59, 95%CI (−70.41,39.23), p = 0.58] and number of epistaxes [WMD = −1.27,95%CI (−10.23,7.70), p = 0.78] in patients with HHT epistaxis. In terms of adverse effects, there is no significant difference between the bevacizumab group and control group [OR = 1.36, 95% CI (0.54, 3.44), p = 0.52].
Conclusion: Bevacizumab is superior to the control group in the treatment of HHT epistaxis, and adverse reactions are not further increased in the bevacizumab group than in the control group, suggesting that bevacizumab has clinical value in the treatment of HHT epistaxis.
... Up to 93% of patients suffer from mild to moderate bleeding [14,15], which interferes with their quality of life [16]. Epistaxis is due to telangiectasis of the nasal mucosa [17]. In addition to epistaxis, gastrointestinal (GI) bleeding as consequence of telangiectasias in the digestive tract is observed in up to 80% of patients with HHT especially in older age [18]. ...
Background: Hereditary Hemorrhagic Telangiectasia (HHT) is a vascular autosomically inherited rare disease. Epistaxis (nose bleeds) is the most common symptom in HHT, leading to anemia and affecting patient’s quality of life. In addition to epistaxis, gastrointestinal bleeding (GI), more often at older ages, may lead to severe anemia and need for blood transfussions. Thus, finding drugs to control both types of bleeding is a primary necessity in HHT. Methods: A cross-sectional observational study was conducted in a series of 11 HHT patients treated with low tacrolimus doses (0.5-1mg) on an off-label prescription basis. Patients showed refractory bleeding to previous treatments. Epistaxis severity score (ESS) and hemoglobin levels were parameters used to evaluate tacrolimus impact. The occurrence of side effects was also recorded. Results: Tacrolimus was well tolerated in most of the patients, except in 2 which abandoned the treatment. The remaining patients tolerated the treatment, with a general improvement in their health condition. Epistaxis was significantly reduced comparing the ESS before and after treatment. Hemoglobin levels were significantly increased overcoming the anemia in the course of the treatment. Conclusion: Tacrolimus at low doses should be considered as a promising treatment for bleeding derived of epistaxis and GI in HHT.
... Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant hereditary disorder with an estimated incidence of 1-2 cases per 10,000 individuals that results in systemic vascular dysplasia. 1,2 The genetic disorder leads to mucocutaneous telangiectasias and visceral arteriovenous malformations (AVMs), producing a phenotypically diverse clinical syndrome that ranges from recurrent epistaxis to critical solid organ bleeds. Pulmonary hypertension (PH) is a chronic, progressive condition that was initially described in patients with HHT in 1969 and is increasingly recognized as a clinical complication of the disorder, with an estimated prevalence of 8%-40%. ...
Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant hereditary disorder characterized by recurrent spontaneous epistaxis, mucocutaneous telangiectasias, and solid organ arteriovenous malformations (AVMs). Pulmonary hypertension (PH) is an increasingly recognized complication in patients with HHT, most often precipitated by high‐output heart failure in the presence of hepatic AVMs as well as pulmonary arterial hypertension in the form of a proliferative vasculopathy. The presence of PH in patients with HHT is associated with significant elevations in rates of morbidity and mortality. Additionally, there is growing recognition of a thromboembolic propensity in this population that increases the risk of chronic thromboembolic PH, posing unique clinical considerations regarding the use of anticoagulation. Patients with HHT are also at risk of PH due to disorders commonly seen in the general population, including left‐sided heart and lung disease. The etiology of PH in HHT is multifaceted and complex; the diagnostic approach and treatment strategies must consider the underlying pathophysiology of HHT. This comprehensive review summarizes current knowledge of PH in HHT, detailing the pathogenesis of known etiologies, diagnostic evaluation, and suggested treatment modalities as well as emerging therapies that may be of future interest.
... Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplasia affecting 1 in 5000 individuals and characterized by focal development of arteriovenous malformations (AVMs) in several tissues 1 . Affected organs and tissues include the liver, lungs, and brain-with up to 20% of HHT patients exhibiting cerebral vascular pathology 2 -as well as the mucosa and skin, where AVMs lead to small, enlarged, and superficial clustered vessels called telangiectasias. ...
Increased endothelial cell (EC) proliferation is a hallmark of arteriovenous malformations (AVMs) in hereditary hemorrhagic telangiectasia (HHT). The underlying mechanism and disease relevance of this abnormal cell proliferative state of the ECs remain unknown. Here, we report the identification of a CDK6-driven mechanism of cell cycle progression deregulation directly involved in EC proliferation and HHT vascular pathology. Specifically, HHT mouse liver ECs exhibited defects in their cell cycle control characterized by a G1/S checkpoint bypass and acceleration of cell cycle speed. Phosphorylated retinoblastoma (p-RB1), a marker of G1/S transition through the restriction point, significantly accumulated in ECs of HHT mouse retinal AVMs and HHT patient skin telangiectasias. Mechanistically, ALK1 loss of function increased the expression of key restriction point mediators, and treatment with palbociclib or ribociclib, two CDK4/6 inhibitors, blocked p-RB1 increase and retinal AVMs in HHT mice. Palbociclib also improved vascular pathology in the brain and slowed down endothelial cell cycle speed and EC proliferation. Specific deletion of Cdk6 in ECs was sufficient to protect HHT mice from AVM pathology. Thus, CDK6-mediated endothelial cell cycle acceleration controls EC proliferation in AVMs and is a central determinant of HHT pathogenesis. We propose that clinically approved CDK4/6 inhibitors have repurposing potential in HHT.
... Approximately 1 in 5000 to 8000 people are affected globally [1]. HHT patients can develop vascular malformations that form a direct connection between arteries and veins absent of capillaries, called telangiectasias and arteriovenous malformations (AVMs) [2,3]. Telangiectasias are superficial dilated blood vessels that form on the skin and mucocutaneous tissue [4]. ...
Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic disease characterized by aberrant angiogenesis and vascular malformations. Mutations in the transforming growth factor beta co-receptor, endoglin (ENG), account for approximately half of known HHT cases and cause abnormal angiogenic activity in endothelial cells (ECs). To date, how ENG deficiency contributes to EC dysfunction remains to be fully understood. MicroRNAs (miRNAs) regulate virtually every cellular process. We hypothesized that ENG depletion results in miRNA dysregulation that plays an important role in mediating EC dysfunction. Our goal was to test the hypothesis by identifying dysregulated miRNAs in ENG-knockdown human umbilical vein endothelial cells (HUVECs) and characterizing their potential role in EC function. We identified 32 potentially downregulated miRNAs in ENG-knockdown HUVECs with a TaqMan miRNA microarray. MiRs-139-5p and -454-3p were found to be significantly downregulated after RT-qPCR validation. While the inhibition of miR-139-5p or miR-454-3p had no effect on HUVEC viability, proliferation or apoptosis, angiogenic capacity was significantly compromised as determined by a tube formation assay. Most notably, the overexpression of miRs-139-5p and -454-3p rescued impaired tube formation in HUVECs with ENG knockdown. To our knowledge, we are the first to demonstrate miRNA alterations after the knockdown of ENG in HUVECs. Our results indicate a potential role of miRs-139-5p and -454-3p in ENG-deficiency-induced angiogenic dysfunction in ECs. Further study to examine the involvement of miRs-139-5p and -454-3p in HHT pathogenesis is warranted.
... Two of 3 dogs with definitive gastric AGD were older than 8 years. In humans, gastric and small intestinal AGD are more common than colonic AGD in young patients with a rare genetic vascular disorder called "hereditary hemorrhage telangiectasia" (HHT), also known as Osler-Weber-Rendu syndrome.44,45 No cases of suspected HHT are reported in the veterinary literature.In our study, 8/15 dogs with definitive AGD and 1/3 dogs with suspicious AGD had been treated with high doses of steroids for ≥2 weeks for a suspected IMHA. ...
Background
Angiodysplasia (AGD) is rarely diagnosed in dogs with gastrointestinal bleeding (GIB) and is reported in case reports in dogs.
Objective
Describe signalment, clinical and diagnostic features of dogs with gastrointestinal (GI) AGD diagnosed by video capsule endoscopy (VCE).
Animals
Dogs with overt or suspected GIB which underwent VCE.
Methods
Dogs for which a VCE was submitted for overt or suspected GIB from 2016 to 2021 were selected retrospectively. Medical records and full‐length VCE recordings where AGDs were initially detected, were reviewed by 2 trained internists. AGD was considered definitive if 2 readers detected it. Signalment, clinical signs, blood work, medications, concurrent diseases, findings of previous conventional endoscopy, and surgical exploration (if applicable) of dogs with AGD were recorded.
Results
Definitive AGD was diagnosed in 15 of 291 (5%) dogs (12 males, 3 females). Twelve (80%) had overt GIB, 11 (73%) had hematochezia, and 6 (40%) had microcytic and hypochromic anemia. AGD was missed by conventional endoscopy in 9/9 dogs and exploratory surgery in 3/3 dogs. Thirteen capsules were administered by mouth (1 incomplete study), and 2 via endoscopy directly into the duodenum. AGD was visualized in the stomach of 3 dogs, in the small intestine of 4, and in the colon of 13 dogs.
Conclusion and Clinical Importance
Although rare, AGD should be considered in dogs with suspected GIB after a negative conventional endoscopy or surgical exporation. Video capsuel endoscopy appears to be a sensitive test to identify AGD within the GI tract.
... Osler-Weber-Rendu syndrome, which is also known as hereditary hemorrhagic telangiectasia, is an autosomal dominant disorder characterized by mucocutaneous telangiectasia and arteriovenous malformations. The frequency is estimated to be 1 in 2000-40,000 [1]. ...
Background:
Osler-Weber-Rendu syndrome is characterized by mucocutaneous telangiectasia and arteriovenous malformations in organs. Anesthesia for patients with Osler-Weber-Rendu syndrome is challenging due to complications and physiological changes.
Case presentation:
The case was a 49-year-old female with Osler-Weber-Rendu syndrome, multiple pulmonary arteriovenous malformations and pheochromocytoma who presented for femoral bone head fracture with metastatic adenocarcinoma. The patient was scheduled to undergo bone tumor resection and artificial bone replacement, being positioned laterally with a planned operation duration of 5 h. Anesthesia was managed with spinal and epidural anesthesia, combined with sedation by sevoflurane using a supraglottic airway (SGA) device under spontaneous breathing. Her intraoperative and postoperative courses were uneventful.
Conclusion:
Neuraxial anesthesia combined with general anesthesia using an SGA device to maintain spontaneous ventilation in order to minimize the risk of rupture of pulmonary arteriovenous malformations could be an option.
... HHT, also known as Rendu-Osler-Weber disease, is an inherited (autosomal dominant) vascular dysplasia with prevalence of 1 in 5000-8000 [6,7]. It is characterized by recurrent epistaxis, muco-cutaneous telangiectasia, gastrointestinal bleeding, and multiple arteriovenous circulatory malformations in the lung, brain, and liver [3,4]. ...
Patient: Male, 37-year-old
Final Diagnosis: Brain abscesses • hereditary haemorrhagic telangiectasia • pulmonary arteriovenous malformations
Symptoms: Tonic-clonic seizures
Clinical Procedure: Embolization
Specialty: General and Internal Medicine
Objective
Rare disease
Background
Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant genetic disease associated with arteriovenous malformations involving diverse organs. Neurological complications from brain abscesses (BA) secondary to pulmonary arteriovenous malformations (PAVMs) is a serious and recognized, albeit infrequent, medical problem. We report the case of a 37-year-old man with familial HHT and PAVMs who presented with seizures as a manifestation of BA.
Case Report
A 37-year-old man was admitted for first tonic-clonic seizures. He had a history of recurrent epistaxis and recurrent gastrointestinal bleeds treated with fulguration and oral iron therapy. A diagnosis of HHT was made because the patient met 3 of 4 Curaçao criteria. Physical examination revealed hypoxemia without dyspnea. A chest X-ray detected nodular pulmonary lesions in both lower lobes. Cranial computed tomography (CT) revealed 3 space-occupying lesions. Antiepileptics and dexamethasone were started. Cranial magnetic resonance and positron emission tomography suggested that lesions were BA. Thoracoabdominal CT with contrast revealed several bilateral PAVMs. Blood cultures were repeatedly negative. With the presumptive diagnosis of septic-embolic BA, empirical antibiotic therapy was started for 8 weeks. Neurological symptoms resolved and malformations >2 cm were selectively embolized. A genetic study revealed exon5 mutations in the ENG gene.
Conclusions
This report highlights the association between PAVMs in a patient with HHT and development of BA. Clinicians should be aware of this association so that diagnosis and treatment can be provided as fast as possible to ensure the best outcome for the patient. Embolization was performed as preventive treatment, and a genetic study was conducted as it is potentially useful for primary prevention in the patient’s offspring.
... It has an estimated prevalence of 1-2 cases per 10,000 in the Japanese population [2]. In patients with this condition, the post-capillary venules are dilated and fuse with arterioles, bypassing the capillary network, resulting in arterio-venous communication and telangiectasia [3]. Telangiectasia with Osler disease is a rare systemic fibrovascular dysplasia that bears-as basic defect-an alteration in the elastic and muscle layers of the vessel walls, making them more vulnerable to spontaneous rupture and injury [4]. ...
Background
Rendu–Osler–Weber disease (Osler disease) is a genetic disease with an autosomal dominant inheritance pattern. It is characterized by widespread telangiectasia in multiple organs. Liver involvement of FNH is relatively common, but liver cancer is very rare, and there are few reports on hepatectomy or postoperative complications. We report a very rare case in which hepatectomy was performed for a patient with Osler disease.
Case presentation
The patient was a 39-year-old man with Osler disease who had been previously diagnosed with multiple FNH and who had been followed for 8 years. During follow-up, the diameter of an S6 lesion gradually increased from 30 to 50 mm; no other lesions increased in size. We decided to perform partial liver resection as total biopsy for the growing tumor, due to the possibility that the growing tumor lesion included malignant components. The pathological examination revealed no obvious malignancy, which was finally diagnosed FNH. The postoperative course was uneventful and he was discharged on the 14th day after surgery. In the second month after discharge, he was transferred to our hospital with sudden abdominal pain in the right hypochondrium with severe tenderness. CT showed extravasation of contrast medium from the hepatic dissection surface in S6, and the hematoma extended to the pelvic floor. Emergency IVR was performed and revealed leakage of the contrast medium from the A6 branch. We embolized the A6 with Lipiodol. After embolization, there were no major problems, and the patient was discharged on the 9th day after the treatment.
Conclusions
Postoperative hemorrhage often occurs within 24 h after surgery, and 2 months after surgery is considered to be the late stage of the wound healing process, and postoperative hemorrhage at this timepoint is considered rare. This unexpected delayed postoperative hemorrhage may have been related to the etiology and pathology of Osler disease, nevertheless, case reports of hepatectomy for patients with Osler disease are limited. We, therefore, report the present case with a review of the relevant literature.
... Loss of function mutations in ALK1 and ENG cause hereditary hemorrhagic telangiectasia (HHT), a genetic bleeding disorder characterized by EC proliferation and migration defects that leads to the development of systemic vascular lesions [53][54][55][56] . VE-cadherin's role in AJ disassembly and angiogenesis could be relevant to HHT pathology 57 . ...
Classical cadherins, including vascular endothelial (VE)-cadherin, are targeted by matrix metalloproteinases (MMPs) and γ-secretase during adherens junction (AJ) disassembly, a mechanism that might have relevance for endothelial cell (EC) integrity and vascular homeostasis. Here, we show that oxidative stress triggered by H2O2 exposure induced efficient VE-cadherin proteolysis by MMPs and γ-secretase in human umbilical endothelial cells (HUVECs). The cytoplasmic domain of VE-cadherin produced by γ-secretase, VE-Cad/CTF2—a fragment that has eluded identification so far—could readily be detected after H2O2 treatment. VE-Cad/CTF2, released into the cytosol, was tightly regulated by proteasomal degradation and was sequentially produced from an ADAM10/17-generated C-terminal fragment, VE-Cad/CTF1. Interestingly, BMP9 and BMP10, two circulating ligands critically involved in vascular maintenance, significantly reduced VE-Cad/CTF2 levels during H2O2 challenge, as well as mitigated H2O2-mediated actin cytoskeleton disassembly during VE-cadherin processing. Notably, BMP9/10 pretreatments efficiently reduced apoptosis induced by H2O2, favoring endothelial cell recovery. Thus, oxidative stress is a trigger of MMP- and γ-secretase-mediated endoproteolysis of VE-cadherin and AJ disassembly from the cytoskeleton in ECs, a mechanism that is negatively controlled by the EC quiescence factors, BMP9 and BMP10.
... Loss of function mutations in ALK1 and ENG cause hereditary hemorrhagic telangiectasia (HHT), a genetic bleeding disorder characterized by EC proliferation and migration defects that leads to the development of systemic vascular lesions [53][54][55][56] . VE-cadherin's role in AJ disassembly and angiogenesis could be relevant to HHT pathology 57 . ...
Classical cadherins, including vascular endothelial (VE)-cadherin, are targeted by matrix metalloproteinases (MMPs) and γ-secretase during adherens junction (AJ) disassembly, a mechanism that might have relevance for endothelial cell (EC) integrity and vascular homeostasis. Here, we show that oxidative stress triggered by H2O2 exposure induced efficient VE-cadherin proteolysis by MMPs and γ-secretase in human umbilical endothelial cells (HUVECs). The cytoplasmic domain of VE-cadherin produced by γ-secretase, VE-Cad/CTF2 - a fragment that has eluded identification so far - could readily be detected after H2O2 treatment. VE-Cad/CTF2, released into the cytosol, was tightly regulated by proteasomal degradation and was sequentially produced from an ADAM10/17-generated C-terminal fragment, VE-Cad/CTF1. Interestingly, BMP9 and BMP10, two circulating ligands critically involved in vascular maintenance, significantly reduced VE-Cad/CTF2 levels during H2O2 challenge, as well as mitigated H2O2- mediated actin cytoskeleton disassembly during VE-cadherin processing. Notably, BMP9/10 pretreatments efficiently reduced apoptosis induced by H2O2, favoring endothelial cell recovery. Thus, oxidative stress is a trigger of MMP- and γ-secretase-mediated endoproteolysis of VE-cadherin and AJ disassembly from the cytoskeleton in ECs, a mechanism that is negatively controlled by the EC quiescence factors, BMP9 and BMP10.
... Hereditary hemorrhagic telangiectasia (HHT) is a genetic vascular disorder characterized by the presence of arteriovenous malformation (AVM) in multiple organs [1][2][3]. AVMs are direct shunts between arteries and veins without intervening capillary beds. AVMs are prone to rupture which cause gushing bleeding. ...
Hereditary hemorrhagic telangiectasia (HHT) is a genetic vascular disorder characterized by the presence of arteriovenous malformation (AVM) in multiple organs. HHT is caused by mutations in genes encoding major constituents for transforming growth factor-β (TGF-β) family signaling: endoglin (ENG), activin receptor-like kinase 1 (ALK1), and SMAD4. The identity of physiological ligands for this ENG-ALK1 signaling pertinent to AVM formation has yet to be clearly determined. To investigate whether bone morphogenetic protein 9 (BMP9), BMP10, or both are physiological ligands of ENG-ALK1 signaling involved in arteriovenous network formation, we generated a novel Bmp10 conditional knockout mouse strain. We examined whether global Bmp10-inducible knockout (iKO) mice develop AVMs at neonatal and adult stages in comparison with control, Bmp9-KO, and Bmp9/10-double KO (dKO) mice. Bmp10-iKO and Bmp9/10-dKO mice showed AVMs in developing retina, postnatal brain, and adult wounded skin, while Bmp9-KO did not display any noticeable vascular defects. Bmp10 deficiency resulted in increased proliferation and size of endothelial cells in AVM vessels. The impaired neurovascular integrity in the brain and retina of Bmp10-iKO and Bmp9/10-dKO mice was detected. Bmp9/10-dKO mice exhibited the lethality and vascular malformation similar to Bmp10-iKO mice, but their phenotypes were more pronounced. Administration of BMP10 protein, but not BMP9 protein, prevented retinal AVM in Bmp9/10-dKO and endothelial-specific Eng-iKO mice. These data indicate that BMP10 is indispensable for the development of a proper arteriovenous network, whereas BMP9 has limited compensatory functions for the loss of BMP10. We suggest that BMP10 is the most relevant physiological ligand of the ENG-ALK1 signaling pathway pertinent to HHT pathogenesis.
... However, the most important ones for which clinicians should screen their patients are in the brain, lungs, GI tract, and liver. [49]. ...
In this overview of vascular changes of the liver, variations in the liver vessels are discussed, in addition to congenital malformations such as Abernethy malformation, patent ductus venosus Arantii and hereditary hemorrhagic telangiectasia (OslerWeber-Rendu disease). Particular attention is paid to focal liver lesions, especially focal nodular hyperplasia (FNH), but also other solid tumours that develop as a result of altered liver vascularisation. The article focuses on the ultrasonic appearances and changes of the liver, depicted in B-mode sonography, Doppler studies and in contrast-enhanced ultrasonography (CEUS). The clinical manifestations of these conditions associated with other organ systems are also highlighted.
... Early electron microscopy assessment of dermal telangiectases in HHT reported a notable leukocyte presence, primarily lymphocytes, pointing to an inflammatory component of these lesions (103). However, this observation does not inform whether lymphocytes have a causal vascular injury effect, or whether they represent a later adaptive immune response to a pre-existing vascular lesion. ...
Endoglin (ENG) is expressed on the surface of endothelial cells (ECs) where it efficiently binds circulating BMP9 and BMP10 ligands to initiate activin A receptor like type 1 (ALK1) protein signalling to protect the vascular architecture. Patients heterozygous for ENG or ALK1 mutations develop the vascular disorder known as hereditary haemorrhagic telangiectasia (HHT). Many patients with this disorder suffer from anaemia, and are also at increased risk of stroke and high output heart failure. Recent work using animal models of HHT has revealed new insights into cellular and molecular mechanisms causing this disease. Loss of the ENG (HHT1) or ALK1 (HHT2) gene in ECs leads to aberrant arteriovenous connections or malformations (AVMs) in developing blood vessels. Similar phenotypes develop following combined EC specific loss of SMAD1 and 5, or EC loss of SMAD4. Taken together these data point to the essential role of the BMP9/10-ENG-ALK1-SMAD1/5-SMAD4 pathway in protecting the vasculature from AVMs. Altered directional migration of ECs in response to shear stress and increased EC proliferation are now recognised as critical factors driving AVM formation. Disruption of the ENG/ALK1 signalling pathway also affects EC responses to vascular endothelial growth factor (VEGF) and crosstalk between ECs and vascular smooth muscle cells. It is striking that the vascular lesions in HHT are both localised and tissue specific. Increasing evidence points to the importance of a second genetic hit to generate biallelic mutations, and the sporadic nature of such somatic mutations would explain the localised formation of vascular lesions. In addition, different pro-angiogenic drivers of AVM formation are likely to be at play during the patient’s life course. For example, inflammation is a key driver of vessel remodelling in postnatal life, and may turn out to be an important driver of HHT disease. The current wealth of preclinical models of HHT has led to increased understanding of AVM development and revealed new therapeutic approaches to treat AVMs, and form the topic of this review.
... Most symptomatic patients present with abdominal pain, discomfort in the right upper abdomen, and nausea. Very few have palpable masses (21)(22)(23)(24)(25)(26). Liver enzyme values are abnormal in the serum of 10% to 14% of patients (27).Abdominal ultrasound, CT, and magnetic resonance imaging (MRI) with radioactive labels may reveal star scars (28).MRI has higher sensitivity and specificity for diagnosis of FNH than CT and abdominal ultrasound, especially magnetic resonance cholangiopancreatography (29,30). ...
Focal nodular hyperplasia (FNH) of the liver is a benign lesion characterized by hypertrophic nodules with central star-shaped fibrous scars. The etiology and pathogenesis of FNH are not completely understood. A 43-year-old man was hospitalized because of acute abdominal pain. Emergency computed tomography(CT) showed hepatic tumor rupture and bleeding. The patient's condition improved following arteriographic embolization to stop bleeding. Laparotomy confirmed spontaneous rupture and hemorrhage of focal hyperplasia and the patient remains asymptomatic after an uneventful recovery. FNH with spontaneous rupture and bleeding is extremely rare. Currently, there is no unified management standard for FNH and most previous studies recommend observation and follow-up. We recommend consideration of surgical treatment of cases with spontaneous rupture and bleeding.
... Most symptomatic patients present with abdominal pain, discomfort in the right upper abdomen, and nausea. Very few have palpable masses (21)(22)(23)(24)(25)(26). Liver enzyme values are abnormal in the serum of 10% to 14% of patients (27).Abdominal ultrasound, CT, and magnetic resonance imaging (MRI) with radioactive labels may reveal star scars (28).MRI has higher sensitivity and specificity for diagnosis of FNH than CT and abdominal ultrasound, especially magnetic resonance cholangiopancreatography (29,30). ...
Focal nodular hyperplasia (FNH) of the liver is a benign lesion characterized by hypertrophic nodules with central star-shaped fibrous scars. The etiology and pathogenesis of FNH are not completely understood. A 43-year-old man was hospitalized because of acute abdominal pain. Emergency computed tomography(CT) showed hepatic tumor rupture and bleeding. The patient’s condition improved following arteriographic embolization to stop bleeding. Laparotomy confirmed spontaneous rupture and hemorrhage of focal hyperplasia and the patient remains asymptomatic after an uneventful recovery. FNH with spontaneous rupture and bleeding is extremely rare. Currently, there is no unified management standard for FNH and most previous studies recommend observation and follow-up. We recommend consideration of surgical treatment of cases with spontaneous rupture and bleeding.
... The disease of HHT is characterized by vascular lesions, including arteriovenous malformations (AVMs) and telangiectasia (3). The recognized manifestations of HHT are all due to abnormalities of the vascular structure (4). They can occur anywhere in the body, such as in the central nervous system, lungs, liver, or spine. ...
Zusammenfassung
Vaskuläre Anomalien im Kopf-Hals-Bereich sind meist seltene Erkrankungen und stellen diagnostisch und therapeutisch eine besondere Herausforderung dar. Sie werden eingeteilt in vaskuläre Tumore und vaskuläre Malformationen. Bei den Tumoren unterscheidet man benigne Tumore, wie z. B. das infantile Hämangiom. von seltenen malignen Tumoren, wie z. B. dem Angiosarkom. Die vaskulären Malformationen werden eingeteilt in einfache Malformationen, gemischte Malformationen, Anomalien großer Gefäße und Anomalien im Rahmen von Syndromen. Die Behandlung erfolgt interdisziplinär und es stehen verschiedene Modalitäten zur Verfügung. Hierzu gehören klinische Beobachtung, Sklerotherapie, Embolisation, ablative und koagulierende Verfahren, chirurgische Resektion und medikamentöse Systemtherapie. Die Therapie ist herausfordernd, da bei vaskulären Anomalien im Kopf-Hals-Bereich praktisch immer Funktion und Ästhetik betroffen sind. Ein besseres Verständnis der genetischen und molekularbiologischen Grundlagen vaskulärer Anomalien führte in jüngster Zeit zur klinischen Erforschung zielgerichteter medikamentöser Therapien. Dieser Artikel bietet eine aktuelle Übersicht über die Diagnostik, Klink und Therapie vaskulärer Anomalien im Kopf-Hals-Bereich.
Arteriovenous Malformation (AVM) is a sporadic vascular disease caused by the aberrant direct connection between arterioles and veins, resulting in disorganized blood shunting and oxygen level disparities. Previous research has elucidated some of the genetic underpinnings of AVM and related vascular anomalies. Despite its significant prevalence, current therapeutic approaches remain largely conservative, underscoring the need for a deeper understanding of AVM pathogenesis. This study focuses on the GPRASP1 gene, which encodes the G-protein coupled receptor-associated sorting protein 1 (GASP-1), a molecule implicated in vascular development. Utilizing western blotting and cellular assays, we explored the role of GPRASP1 in angiogenesis, neoplastic formation, and other mechanical aspects of AVM. Our findings suggested that mutations in the GPRASP1 gene may contribute to elevated levels of angiogenic factors and altered cellular functions related to angiogenesis, such as enhanced proliferative and migratory capabilities. This research lays the groundwork for identifying novel therapeutic targets in the management of AVM and offers insights into precision medicine approaches.
Arteriovenous malformations (AVMs) are congenital vascular lesions that may appear throughout the central nervous system. They consist of direct connections between arteries and veins, without an intervening capillary bed. They are believed to be about one-tenth as common as intracranial aneurysms. Spinal AVMs are discussed in Chap. 20. Vein of Galen malformations and pial arteriovenous fistulas are separate entities and are discussed in the Appendix to this chapter.
Background:
It is unclear whether hereditary hemorrhagic telangiectasia (HHT) patients can tolerate antithrombotic therapies (AT) including antiplatelet (AP) and/or anticoagulant (AC) agents.
Objectives:
Primary endpoint was tolerance to AT in HHT. Secondary endpoints were to identify factors associated with major bleeding events (MBE) and premature discontinuation of AT.
Methods:
Retrospective multicenter study in French national HHT Registry patients exposed to AT.
Results:
We included 126 patients with 180 courses of AT. Median follow-up was 24 [11-52] months. Mean age was 65.6 ± 13.1 years. The first 3 months of AT exposure had an increased risk of hospitalization for hemorrhage (p < 0.001) and transfusions (p < 0.001). MBE (n = 63) occurred more frequently in the first 3 months of AT exposure (p < 0.001). Premature discontinuation of AT occurred in 61 cases. Rate of premature discontinuation was 29 % under both AP and AT therapy but significantly higher under dual AP therapy (n = 4/7, 57 % p = 0.008). Risk factors for MBE were: age ≥ 60 years (HR 2.34 [1.12;4.87], p = 0.023), prior hospitalization in the 3 months before starting AT for hemorrhage (HR 3.59 [1.93;6.66], p < 0.001) or transfusion (HR 3.15 [1.61;6.18], p = 0.001), previous history of gastro-intestinal bleeding (HR 2.71 [1.57;4.65], p < 0.001) or MBE (HR 4.62 [2.68;7.98], p < 0.001). Frequency of MBE did not differ between groups except for a higher risk in the dual AP group (HR 3.92 [1.37;11.22], p = 0.011).
Conclusion:
Tolerance of AC or AP therapy was similar in HHT population but not dual AP therapy. We identified risk factors for MBE occurrence or premature discontinuation under AT.
Hereditary haemorrhagic telangiectasia (HHT) can result in challenging anaemia and thrombosis phenotypes. Clinical presentations of HHT vary for relatives with identical casual mutations, suggesting other factors may modify severity. To examine objectively, we developed unsupervised machine learning algorithms to test whether haematological data at presentation could be categorised into sub‐groupings and fitted to known biological factors. With ethical approval, we examined 10 complete blood count (CBC) variables, four iron index variables, four coagulation variables and eight iron/coagulation indices combined from 336 genotyped HHT patients (40% male, 60% female, 86.5% not using iron supplementation) at a single centre. T‐SNE unsupervised, dimension reduction, machine learning algorithms assigned each high‐dimensional datapoint to a location in a two‐dimensional plane. k‐Means clustering algorithms grouped into profiles, enabling visualisation and inter‐profile comparisons of patients’ clinical and genetic features. The unsupervised machine learning algorithms using t‐SNE and k‐Means identified two distinct CBC profiles, two iron profiles, four clotting profiles and three combined profiles. Validating the methodology, profiles for CBC or iron indices fitted expected patterns for haemorrhage. Distinct coagulation profiles displayed no association with age, sex, C‐reactive protein, pulmonary arteriovenous malformations (AVMs), ENG / ACVRL1 genotype or epistaxis severity. The most distinct profiles were from t‐SNE/k‐Means analyses of combined iron‐coagulation indices and mapped to three risk states – for venous thromboembolism in HHT; for ischaemic stroke attributed to paradoxical emboli through pulmonary AVMs in HHT; and for cerebral abscess attributed to odontogenic bacteremias in immunocompetent HHT patients with right‐to‐left shunting through pulmonary AVMs. In conclusion, unsupervised machine learning algorithms categorise HHT haematological indices into distinct, clinically relevant profiles which are independent of age, sex or HHT genotype. Further evaluation may inform prophylaxis and management for HHT patients’ haemorrhagic and thrombotic phenotypes.
Hereditary hemorrhagic Telangiectasia (HHT) is a rare genetic disease caused by mutations affecting components of Bone Morphogenetic Protein and Transforming Growth Factor-β (BMP/TGF-β) signaling in endothelial cells. This disorder is characterized by arterio-venous malformations which are prone to rupture and the ensuing hemorrhages are responsible for iron deficiency anemia. Along with Activin receptor-like kinase ALK1, mutations in ENDOGLIN are associated with the vast majority of HHT cases. In this report, we characterized zebrafish endoglin locus and demonstrated that it produces two phylogenetically conserved protein isoforms using a distinctive alternative splicing mechanism. Functional analysis of a Crispr/Cas9 zebrafish endoglin mutant revealed that Endoglin deficiency is lethal during the course from juvenile stage to adulthood. Endoglin deficient zebrafish develop cardiomegaly resulting in heart failure and hypochromic anemia which both stem from chronic hypoxia. Furthermore, endoglin mutant zebrafish display structural alterations of the developing gills and underlying vascular network that coincide with hypoxia. Finally, phenylhydrazine treatment demonstrated that lowering hematocrit/blood viscosity alleviates heart failure and enhances survival of Endoglin deficient fish.
Uncommon clinical problems can present serious challenges in any medical specialty, particularly in those areas providing acute care. Bringing together all uncommon problems relevant to the treatment of seriously ill patients in a quick one-stop reference, this book is an easy-to-use and practical reference for the clinician at any level faced with an uncommon acute medical problem at the bedside. Using a popular A-Z format, over 1000 entries reflect the current breadth of the specialty's extension to hospital-wide issues of acute care. Each topic contains both essential diagnostic and treatment information and discusses the implications for intensive care management. Extensive cross-referencing throughout aids rapid access to key information and the use of cartoons enhances learning. The book offers a source of reference for the many issues so often overlooked in major textbooks, which can be difficult not only to locate elsewhere but also for experienced clinicians to remember in detail. An invaluable resource within a single volume for intensivists, anaesthetists, emergency specialists, and a wide range of other healthcare professionals.
Purpose:
To compare post-embolotherapy follow-up graded transthoracic contrast echocardiography (TTCE) and high-resolution chest CT (HRCT) and to evaluate the use of graded TTCE in the early post-embolization period.
Methods:
Thirty-five patients (6M;29F, mean age 56y, range 27-78y) presenting for post-embolotherapy follow-up between 2017-2021 with concurrent HRCT and graded TTCE were analyzed retrospectively. Untreated PAVMs with a feeding artery > 2 mm were considered treatable.
Results:
Ninety-four percent of patients (33/35) did not have treatable PAVMs on HRCT. TTCE was negative (grade 0) in 34% of patients (n=12). Of patients with a positive TTCE (23/35, 66%), 83% had a grade 1 shunt, 13% a grade 2 shunt, and 4% a grade 3 shunt. No patients with a grade 0 or 1 shunt had a treatable PAVM on HRCT. Of the two patients with PAVMs requiring treatment, one had a grade 2 shunt, and one had a grade 3 shunt. TTCE grade was significantly associated with the presence of a treatable PAVM on HRCT (P<0.01).
Conclusion:
Graded TTCE predicts the need for repeat embolotherapy and does so reliably in the early post-embolotherapy period. This suggests that graded TTCE can be utilized in the post-embolotherapy period for surveillance, which has the potential to lead to a decrease in cumulative radiation in this patient population.
Hereditary hemorrhagic telangiectasia (HHT) also known as Osler-Weber-Rendu disease is a rare autosomal dominant, multi-organ disorder that leads to formation of abnormal vascular connections resulting in devastating and life-threatening complications. Due to its multisystem character, wide range of clinical manifestations and variable expressivity, HHT remains a diagnostic challenge and requires close cooperation of specialists from various medical fields. Interventional radiology plays a key role in the management of this disease, helping maintain the health of HHT patients and minimize the risk of fatal complications. The aim of this article is to review clinical manifestations, diagnostic guidelines and criteria of HHT as well as to present the means of endovascular therapy in the management of HHT patients.
Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu disease, is a rare disorder with a case prevalence as high as one in 5000, causing arteriovenous malformations in multiple organ systems. HHT is familial with autosomal dominant inheritance, with genetic testing allowing confirmation of the diagnosis in asymptomatic kindreds. Common clinical manifestations are epistaxis and intestinal lesions causing anemia and requiring transfusions. Pulmonary vascular malformations predispose to ischemic stroke and brain abscess and may cause dyspnea and cardiac failure. Brain vascular malformations can cause hemorrhagic stroke and seizures. Rarely, liver arteriovenous malformations can cause hepatic failure. A form of HHT can cause juvenile polyposis syndrome and colon cancer. Specialists in multiple fields may be called to care for one or more aspects of HHT, but few are familiar with evidence-based guidelines for HHT management or see a sufficient number of patients to gain experience with the unique characteristics of the disease. Primary care physicians and specialists are often unaware of the important manifestations of HHT in multiple systems and the thresholds for their screening and appropriate management. To improve familiarity, experience, and coordinated multisystem care for patients with HHT, the Cure HHT Foundation, which advocates for patients and families with this disease, has accredited 29 centers in North America with designated specialists for the evaluation and care of patients with HHT. Team assembly and current screening and management protocols are described as a model for evidence-based, multidisciplinary care in this disease.
Hereditary Haemorrhagic Telangiectasia (HHT) causes arteriovenous malformations (AVMs) in multiple organs to cause bleeding, neurological and other complications. HHT is caused by mutations in the BMP co-receptor endoglin. We characterised a range of vascular phenotypes in embryonic and adult endoglin mutant zebrafish and the effect of inhibiting different pathways downstream of VEGF signalling.
Adult endoglin mutant zebrafish developed skin AVMs, retinal vascular abnormalities, and cardiac enlargement. Embryonic endoglin mutants develop an enlarged basilar artery (similar to the previously described enlarged aorta and cardinal vein) and larger numbers of endothelial membrane cysts (kugeln) on cerebral vessels. VEGF inhibition prevented these embryonic phenotypes, leading us to investigate specific VEGF-signalling pathways. Inhibiting TOR or MEK pathways prevented abnormal trunk and cerebral vasculature phenotypes, while inhibiting NOS or MAPK pathways had no effect. Combined subtherapeutic TOR and MEK inhibition prevented vascular abnormalities, confirming synergy between these pathways in HHT.
These results indicate the HHT-like phenotype in zebrafish endoglin mutants can be mitigated through modulation of VEGF signalling. Combined low dose MEK and TOR pathway inhibition may represent a novel therapeutic strategy in HHT.
Epistaxis is a common disease, most of which is naturally improved without treatment. However, some patients experience recurrent epistaxis despite having received various treatments. In such cases, the control of epistaxis may require a more invasive technique, such as embolization or surgical ligation of the main feeding arteries of the nasal cavity. However, the nasal septum receives blood supply from various branches of blood vessels, so these vascular controls can be inappropriate. In this case report, we applied septodermoplasty - a surgical technique mostly aimed for the treatment of intractable epistaxis from hereditary hemorrhagic telangiectasia (HHT) - to treat patients suffering recurrent epistaxis from the nasal septum. Although the two patients we treated were non-HHT, our application of this surgical technique turned out to be successful. Here, we suggest expanding the indication of septodermoplasty to non-HHT patients presenting with recurrent and difficult-to-treat epistaxis.
La coagulación intravascular diseminada (CID) es una entidad clínica frecuente que se presenta como fenómeno secundario a diversas enfermedades entre las cuales se destacan las infecciones graves, las neoplasias y las catástrofes obstétricas. Se caracteriza por una activación difusa y simultánea de los sistemas endógenos de la coagulación y la fibrinólisis. El depósito de pequeños trombos en la circulación conduce finalmente a disfunción orgánica múltiple y en algunos casos a la muerte. Las manifestaciones clínicas pueden incluir fenómenos trombóticos y hemorrágicos. Se ha propuesto un puntaje de fácil aplicación para simplificar el diagnóstico de la entidad. El tratamiento incluye el control específico de la causa subyacente que favorece la aparición de la CID, el soporte con hemoderivados en pacientes con manifestaciones de sangrado y la anticoagulación terapéutica en pacientes con trombosis mayores. El desarrollo de CID es un factor pronóstico adverso que aumenta significativamente la tasa de mortalidad. En este artículo de revisión se incluyen los siguientes aspectos de la CID: historia, epidemiología, clasificación, entidades asociadas, fisiopatología, clínica, diagnóstico, tratamiento y pronóstico.
Objectives:
Hereditary hemorrhagic telangiectasia (HHT) is a rare disorder encompassing facial and oral telangiectasias and visceral vascular malformations (VMs). Pulmonary VMs can lead to paradoxical embolism of thrombi or bacteria, e.g., due to dental procedures. Early detection can reduce morbidity and mortality and is recommended. However, diagnosis is often delayed for decades. Our study is assessing the feasibility and effect of a nationwide awareness campaign for early diagnosis of HHT addressing all dentists in Germany.
Methods:
In 2018, one article and two reminders about HHT were published in a nationwide awareness campaign. As a proxy for the effectiveness of the campaign, researchers measured the number of first-time inquiries from patients and physicians about HHT documented by the German HHT self-help group from September 2016 until September 2019.
Results:
A total of 411 first contacts with the German self-help group were documented, mainly via Internet platforms (Internet forum (n = 130) and Facebook® (n = 189)). For 9% of those patients (n = 36/411), the physician or dentist (physician: (n = 31/36, 86%; dentist: n = 5/36, 14%) informed patients about the disease HHT and the self-help group. Before publishing the first article about HHT, no dentist referred patients to the German self-help group; afterwards, 5 patients received information about HHT from their dentist and contacted the patient organization for the first time. After each publication in June, September, and December 2018, the number of new contacts increased. Contacts via phone and e-mail had the highest relative increase.
Conclusions:
The repeated call for dental screening for HHT in Germany led to increased awareness of this rare disease; more patients with possible HHT received information about the condition. The authors conclude that targeted campaigns may contribute to a shorter diagnostic latency resulting in increased quality of life and life expectancy in HHT. This trial is registered with CT03549949.
Background
Transcatheter embolization is a commonly used minimally invasive technique in the treatment of pulmonary arteriovenous malformation (PAVM) with a high probability of post-operative recurrence, and some recurrent cases of PAVM cannot be treated via pulmonary arterial re-embolization. Here, we report the first case, to our knowledge, a 55-year-old female undergoing percutaneous direct puncture embolization for recurrent PAVM with good short-term efficacy.
Case Presentation
The patient was a 55-year-old female presenting to the emergency department of our hospital with acute exacerbation of chest tightness and shortness of breath for 2 hours. The patient was diagnosed with PAVM and undergone embolization half a year ago. DSA-guided embolization was performed through percutaneous puncture approach. After embolization with four spring coils, the blood flow to the PAVMs was stopped and the surgery completed. The patient reported improvement of chest tightness and shortness of breath and was discharged from the hospital 3 days later.
Conclusion
Our case was unique as a portion of the PAVMs was closely attached to the chest wall and PVP was slightly increased, which made percutaneous puncture embolization possible. Our case can be helpful in the treatment of recurrent PAVM in patients who cannot undergo re-embolization through pulmonary artery.
This report summarizes an adolescent diagnosed with HHT after presenting with a cerebral abscess due to undiagnosed PAVMs. The importance of this report is several‐fold. First, it reviews the diagnosis and management of PAVMs, and subsequent follow‐up for PAVMs for children with HHT. Second, it underscores that cerebral abscess, a rare but severe complication, could be the initial manifestation of HHT This article is protected by copyright. All rights reserved.
Cerebrovascular malformations comprise abnormal development of cerebral vasculature. They can result in hemorrhagic stroke due to rupture of lesions as well as seizures and neurological defects. The most common forms of cerebrovascular malformations are brain arteriovenous malformations (bAVMs) and cerebral cavernous malformations (CCMs). They occur in both sporadic and inherited forms. Rapidly evolving molecular genetic methodologies have helped to identify causative or associated genes involved in genesis of bAVMs and CCMs. In this review, we highlight the current knowledge regarding the genetic basis of these malformations.
The circulatory system connects all organ systems to sustain life using a complex network of arteries, veins, and lymphatics. These three vessel types can be distinguished by structural differences attributable to their corresponding biological function; in addition, the molecular determinants that specify each vessel type during embryogenesis persist throughout adulthood as specific markers of vascular identity. Ephrin-B2, Ephrin type B receptor 4 (Eph-B4), and Vascular Endothelial Growth Factor Receptor (VEGFR-3) are determinants of vascular identity, arising early during embryonic development and serve as molecular signatures of arteries, veins, or lymphatics, respectively. However, the expression of these markers can be altered in pathological conditions such as vascular malformations and vascular tumors, resulting in mutation or absence of critical molecular markers; for example, capillary malformations of arterial–venous malformations can result from loss-of-function mutations in Eph-B4, and Kaposi sarcoma is characterized by phenotypic switch in veins from Eph-B4 to ephrin-B2 expression. Interestingly, vascular surgery in adult patients shows a plasticity of vascular identity. Vein graft adaptation to the arterial environment results in the loss of venous identity, with loss of Eph-B4 expression; arteriovenous fistula maturation is characterized by gain of arterial identity resulting in dual arterial–venous identity, with expression of Eph-B4, Delta-like-4, ephrin-B2, and Neuropilin . These data show the complexity of vascular identity and suggest that these markers of identity may have function in adults with potential for translational applications.
The theory of organizational path dependence helps us to understand why organizational change is sometimes extremely difficult, if not impossible. Although recent conceptualizations of path dependence allow for strategic agency, the theory is still underspecified regarding how to break an organizational path. In an attempt to develop the theory in this regard, we make use of a case in the sphere of global health with an undisputed life-saving impact. More precisely, we trace a significant improvement in the field of pediatric cancer care back to path-breaking organizational change: the successful introduction of multi¬center cooperation within a health-care system that is arguably locked-into a centralization path. Drawing on longitudinal research conducted within Russian hospitals, we conclude that path-breaking change is an intricate process based upon distinct activities, and supported by mechanisms, directed towards the creation of a new organizational path.
Human endoglin is a dimeric protein that binds transforming growth factor-beta (TGF-beta). A porcine cDNA clone for endoglin was obtained from a porcine uterus cDNA library. The deduced sequence of the primary translated product of endoglin consists of 643 amino acids with a high sequence identity (96%) to human endoglin in the transmembrane and intracellular domains, but with a lower sequence similarity (66%) in the extracellular domain. In contrast to human endoglin, porcine endoglin has no Arg-Gly-Asp tripeptide in its sequence. Antibodies, raised against a peptide corresponding to the intracellular domain of porcine endoglin, immunoprecipitated an 84-kDa protein under reducing condition and a 130-kDa protein under nonreducing condition in porcine aortic endothelial cells. Porcine endoglin bound TGF-beta1 and -beta3 efficiently, but TGF-beta2 less efficiently. Endoglin was found to be coimmunoprecipitated with TGF-beta receptors type I and/or II by the endoglin antibodies or by TGF-beta receptor II antibodies in the presence of ligand. Thus, endoglin and TGF-beta receptors I and/or II most likely formed a heteromeric receptor complex. Endoglin was phosphorylated on serine residue(s), which did not change after stimulation by TGF-beta1. These results revealed that endoglin is a phosphorylated protein which forms a heteromeric complex with signaling receptors for TGF-beta.
Endoglin, a dimeric membrane glycoprotein expressed at high levels on human vascular endothelial cells, shares regions of sequence identity with beta-glycan, a major binding protein for transforming growth factor-beta (TGF-beta) that co-exists with TGF-beta receptors I and II in a variety of cell lines but is low or absent in endothelial cells. We have examined whether endoglin also binds TGF-beta and demonstrate here that the major TGF-beta1-binding protein co-existing with TGF-beta receptors I and II on human umbilical vein endothelial cells is endoglin, as determined by specific immunoprecipitation of endoglin affinity-labeled with I-125-TGF-beta. Furthermore, endoglin ectopically expressed in COS cells binds TGF-beta1. Competition affinity-labeling experiments showed that endoglin binds TGF-beta1 (K(D) approximately 50 pM) and TGF-beta3 with high affinity but fails to bind TGF-beta2. This difference in affinity of endoglin for the TGF-beta isoforms is in contrast to beta-glycan which recognizes all three isoforms. TGF-beta however is binding with high affinity to only a small fraction of the available endoglin molecules, suggesting that some rate-limiting event is required to sustain TGF-beta binding to endoglin.
The occurrence of significant pulmonary hemorrhage associated with pulmonary arteriovenous malformations (PAVMs) and hereditary hemorrhagic telangiectasia (HHT) and the incidence of PAVMs in family members of patients with PAVMs and HHT are poorly defined. We reviewed our experience in 143 patients with PAVMs and HHT. Eleven (8 percent) of the 143 patients with HHT and PAVMs had a history of either massive hemoptysis or of hemothorax which required hospitalization. One patient died directly related to the pulmonary hemorrhage. There were four men and seven women. Three of the seven women experienced pulmonary hemorrhage during pregnancy. Seven of the 11 families participated in screening for PAVMs. Thirty-six (80 percent) of the 45 screened family members were found to have HHT. Thirteen (36 percent) of the 36 family members with HHT were proven to have PAVMs by pulmonary angiography. Pulmonary hemorrhage due to spontaneous rupture of the PAVM is a potentially life-threatening complication that should be treated aggressively with transcatheter embolotherapy. It occurs more frequently than previously recognized in patients with PAVMs and HHT. In addition, because of the increased incidence of PAVMs in family members of patients with HHT and PAVM, screening of family members with HHT is recommended especially in women of childbearing age.
Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by multisystemic vascular dysplasia and recurrent haemorrhage. Linkage for some families has been established to chromosome 9q33-q34. In the present study, endoglin, a transforming growth factor beta (TGF-beta) binding protein, was analysed as a candidate gene for the disorder based on chromosomal location, expression pattern and function. We have identified mutations in three affected individuals: a C to G substitution converting a tyrosine to a termination codon, a 39 base pair deletion and a 2 basepair deletion which creates a premature termination codon. We have identified endoglin as the HHT gene mapping to 9q3 and have established HHT as the first human disease defined by a mutation in a member of the TGF-beta receptor complex.
Endoglin, a dimeric membrane glycoprotein expressed at high levels on human vascular endothelial cells, shares regions of sequence identity with betaglycan, a major binding protein for transforming growth factor-beta (TGF-beta) that co-exists with TGF-beta receptors I and II in a variety of cell lines but is low or absent in endothelial cells. We have examined whether endoglin also binds TGF-beta and demonstrate here that the major TGF-beta 1-binding protein co-existing with TGF-beta receptors I and II on human umbilical vein endothelial cells is endoglin, as determined by specific immunoprecipitation of endoglin affinity-labeled with 125I-TGF-beta. Furthermore, endoglin ectopically expressed in COS cells binds TGF-beta 1. Competition affinity-labeling experiments showed that endoglin binds TGF-beta 1 (KD approximately 50 pM) and TGF-beta 3 with high affinity but fails to bind TGF-beta 2. This difference in affinity of endoglin for the TGF-beta isoforms is in contrast to beta-glycan which recognizes all three isoforms. TGF-beta however is binding with high affinity to only a small fraction of the available endoglin molecules, suggesting that some rate-limiting event is required to sustain TGF-beta binding to endoglin.
We studied 10 cutaneous telangiectatic lesions of hereditary hemorrhagic telangiectasia (HHT), ranging in size from pinpoint to 2 mm, by light and electron microscopy. Four representative lesions were reconstructed by computer from serial 1- or 2-mm plastic embedded sections. The earliest clinically detectable lesion of HHT is a focal dilatation of postcapillary venules, which continue to enlarge and eventually connect with dilated arterioles through capillaries. As the vascular lesion increases in size, the capillary segments disappear and a direct arterio-venous communication is formed. This entire sequence of morphologic events is associated with a perivascular mononuclear cell infiltrate in which the majority of cells are lymphocytes and the minority are monocytes/macrophages by ultrastructure. Comparison of these findings with the telangiectatic mats of scleroderma and cherry angiomas revealed that the former, previously shown to be composed of dilated postcapillary venules, are also associated with perivascular infiltrates, but the latter, which are produced by capillary loop aneurysms, are not.
The effect of Yag laser photocoagulation on the course of bleeding of gastrointestinal vascular malformations was studied in 59 patients, with a total of 482 lesions. The lesions were located in the upper gastrointestinal tract alone in 25 patients, in the lower tract alone in 31 patients and in both the lower and the upper gastrointestinal tract in three patients. In the month before laser therapy the number of bleeding episodes averaged 1.09 +/- 0.6 (SD) per patient (n = 57) and the transfusion requirements 2.4 +/- 2.6 red blood cells units per patient, while in the month after treatment the bleeding incidence averaged 0.16 +/- 0.5 and the transfusion requirements 0.21 +/- 0.8 (both p less than 0.001). Long term results were analysed considering for each patient an equally long pretreatment and follow up period. After a mean follow up period of 11.5 months (1-48 months), 17 of the 57 patients available for follow up rebled. The reduction of the bleeding rate was statistically significant at one, six, 12, and 18 months of follow up, while transfusion rate was significantly decreased at one, six, and 12 months. The results were disappointing in patients with Osler-Weber-Rendu (n = 4) and in patients with angiomas associated with Von Willebrand's disease (n = 3), who all rebled. In angiodysplasia the treatment was successful in 82% of the 49 patients. The more numerous the lesions, the less effective the reduction in bleeding rate by laser treatment was. Histological studies showed that the haemostatic effect of Yag laser photocoagulation was obtained by destruction of the lesion. Rebleeding was due to lesions missed at the first treatment, incompletely treated lesions and recurrence of new lesions. In two patients a free caecal perforation necessitated a right hemicolectomy. In both patients numerous or very large lesions had been treated in the caecum.
Sixty-four patients with symptomatic hereditary hemorrhagic telangiectasia were retrospectively studied in order to determine the true incidence of clinical manifestations in this disease. This select group had a significantly higher incidence of gastrointestinal hemorrhage and pulmonary arteriovenous fistula formation than has been previously reported. Data are presented regarding the course and severity of nasal and gastrointestinal hemorrhage, the use of endoscopy for diagnosis, the incidence of associated neurological, cardiac, and hepatic disease, and mortality.
Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant disorder with unknown pathophysiology that is characterised by arteriovenous lesions and recurrent haemorrhage in virtually every organ. Linkage of HHT to markers on chromosome 9q has recently been reported. In this study we report confirmation of this localisation in three unrelated families of Dutch origin. A fourth unrelated HHT family, in which considerably fewer pulmonary arteriovenous malformations (PAVM) were present, yielded evidence for non-linkage to this region. We conclude that HHT is a genetically heterogeneous disorder and our results indicate that the presence of PAVM may be more common in patients with a chromosome 9 linked form of HHT than in patients with the non-linked form.
Hereditary haemorrhagic telangiectasia (HHT) or Osler-Weber-Rendu syndrome is an autosomal dominant vascular dysplasia characterised by recurrent haemorrhage. Our initial linkage studies found an HHT gene to be localised to 9q3 in two large kindreds. In the present study, we examine an additional five unrelated HHT families. Linkage analysis in this region resulted in a peak multipoint location score of 13.03, 10 cM proximal of D9S60. We found significant evidence for heterogeneity of HHT. Multipoint analysis supports the family specific two point studies with odds of 3,000,000:1 showing linkage and heterogeneity over linkage and homogeneity. Four of the seven families give a posterior probability of > 99% of being of the linked type, and three families appear unlinked to this region of 9q, and by multipoint analysis completely exclude the candidate region for HHT. Two new crossovers in affected persons in one of the linked families further define the proximal border of the candidate region on 9q3. A possible correlation in clinical phenotype between the 9q3 linked families and unlinked families is described. Although six of the seven families clearly meet the clinical criteria for HHT diagnosis, a significant absence of pulmonary arteriovenous malformations is seen in all three 9q3 unlinked families. Genetic heterogeneity of HHT and its potential correlation with a clinical phenotype may have a significant impact on the clinical management and treatment of HHT patients.
Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder that is characterized by frequent nosebleeds, mucocutaneous telangiectases and vascular malformations that cause recurrent haemorrhage and arteriovenous shunting. Linkage analyses in one kindred identified an HHT locus on the long arm of chromosome 9 (maximum multipoint lod score = 6.20 between D9S60 and D9S61). Analyses in two other unrelated HHT families demonstrated that the disease in one was not linked to the locus on chromosome 9q3. We conclude that HHT is a genetically heterogeneous disorder. Based on its map location (9q3) and expression in vascular tissues, type V collagen is a possible candidate gene for HHT.
Hereditary hemorrhagic telangiectasia is a familial disease characterized by the presence of telangiectasia of the skin and mucous membranes. It is indicated clinically by recurrent bleeding, most commonly epistaxis. Involvement of multiple systems occurs, and vascular lesions have been recognized in the lips, oral cavity, respiratory tract, alimentary tract, urinary tract, liver, spleen, eye, brain, meninges, spinal cord, and bone. The incidence of gastrointestinal hemorrhage is significant and has proved to be a difficult diagnostic and therapeutic problem. We report here the vascular abnormalities and hemodynamic alterations that have been found in an investigation of gastrointestinal bleeding in patients with hereditary hemorrhagic telangiectasia (Table I). There are many reports in the literature describing telangiectasia and phlebectasia of various abdominal organs. These lesions have been recognized at the time of gastroscopy and sigmoidoscopy and at surgery and autopsy. We have been able to find o...
Plauchu Henri y Bideau Alain. — Epidemiologie de la concentracion geografica de una enfermedad hereditaria rara y constitucion de un registre de poblacion. Los autores presentan los resultados de un estudio realizado a partir del hallazgo de una concentracion geografica de una enfermedad hereditaria rara (la genopatia de Rendu- Osier) en los montes de Jura del departamento de Ain. Se trata de un estudio doble : constitucion de un banco de datos en torno a las cuatro aldeas que constituyen el foco de la enfermedad y enseguida el estudio de la difusion espacial del gene a partir de ese foco. La constitucion del registro de enfermedades amplia el enfoque puramente epidemiolo- gico y permite el estudio de numerosos aspectos comunes de los datos demograficos y geneticos recolectados en las cuatro aldeas bajo observacion. El aspecto original del estudio epide- miologico esta caracterizado por la metodologia empleada y especialmente por la encuesta postal que se efectuo para incluir en forma exhaustiva todos los casos pertinentes.
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder with unknown pathophysiology that is characterized by arteriovenous lesions and recurrent hemorrhage in virtually every organ. The prevalence of HHT ranges between 1-2 per 100,000 and 1 per 10,000 with almost complete penetrance by the age of 40 years. The mode of inheritance is autosomal dominant. Linkage of HHT to markers on chromosome 9q has recently been reported. In this study we present confirmation of this localization in three unrelated families of Dutch origin. A fourth family yielded evidence for non-linkage to this region. Heterogeneity analysis was performed and clearly demonstrated that HHT is a genetically heterogeneous disorder. We have rigorously investigated all patients in our four families by chest radiography, measurement of arterial oxygenation iv-DSA of the pulmonary circulation and iv-DSA of the cerebral circulation. In the family that is not linked to chromosome 9, considerably less pulmonary arteriovenous malformations (PAVM) were present. We conclude that HHT is a genetically heterogeneous disorder and our results indicate that the presence of PAVM may be more common in patients with a chromosome 9-linked form of HHT than in patients with the non-linked form. Linkage of HHT with a locus on chromosome 9q34 locus has now been reported in three independent studies. However, two studies report genetic heterogeneity. This will limit the applicability of linked DNA markers in small families for presymptomatic testing. Only extended pedigrees will be informative enough to determine whether or not the chromosome 9 locus is responsible for disease onset in the patient. The eventual isolation of the gene responsible for HHT on chromosome 9 will help to gain insight into the processes that take place in the development and remodelling of the vascular system.
Hereditary hemorrhagic telangiectasia (HHT) is a disease that varies from being asymptomatic to causing life-threatening hemorrhage. The most common manifestation is epistaxis for which there is an array of therapeutic options, ranging from nasal packing to pedicled myocutaneous flaps. This article discusses therapeutic options and emphasizes the neodymium:yttrium-aluminum-garnet (Nd:YAG) laser for photocoagulation of nasal hemorrhagic telangiectasias. This laser was chosen because of its deep tissue penetration and excellent hemostatic properties. The laser procedure can be done on an ambulatory basis, with local anesthesia, and can be repeated indefinitely. The role of the Nd:YAG laser in this disease is strictly palliative; however, with proper patient selection and repetitive applications, it can provide substantial long-term improvement in symptoms. Our experience has been with 41 patients having 85 total treatments with a mean follow-up period of 3.5 years.
We have treated 21 patients (13 female, 8 male) with pulmonary arteriovenous malformations (PAVMs). Mean age at diagnosis was 37.5 years (range, 15 to 72 years). Presenting symptoms included dyspnea on exertion (67%), hereditary hemorrhagic telangiectasia (57%), and major neurologic events (33%). In our early experience, 8 patients had no specific treatment; their case histories illustrate the major neurologic complications of untreated PAVMs. Nine patients (8 primarily, 1 after recurrence) underwent conservative surgical excision; 4 had lobectomy, and 5 had segmentectomy or subsegmental excision. One patient underwent staged bilateral thoracotomies for multiple bilateral lesions. The arterial oxygen tension was found to increase after excision of large or solitary PAVMs. All surgically treated patients were relieved of dyspnea, and none had postoperative recurrence of PAVMs or neurologic complications related to PAVMs. Five patients underwent balloon occlusion of PAVMs. Two patients chose to have solitary PAVMs occluded rather than undergo thoracotomy. One underwent surgical excision 5 years later, and the other required repeat balloon embolization 4 years later when recanalization of the PAVMs was documented. Three patients with numerous PAVMs received palliation with multiple balloon embolizations. The high incidence of associated major neurologic complications mandates aggressive treatment of PAVMs whenever feasible. Conservative surgical resection remains the treatment of choice. Balloon cmbolization offers an alternative therapy for patients who are poor surgical risks or those whose lesions are too numerous to resect.
Hereditary haemorrhagic teleangiectasia (Rendu-Osler-Weber disease) is an inborn error of vascular structure with multiple manifestations. Its incidence is about 1-2:100 000 in the European population. The incidence of telangiectases and/or fistula formation was estimated to be 1 in 10 carriers of the Osler trait. The findings in the family reported herewith suggest a much higher incidence if angiography is more frequently performed. Apart from the skin and mucous membrane, teleangiectases and/or arteriovenous fistulas may be present in the lungs, intestinal tract, spleen, kidney, brain, and bones. The liver apparently is more involved than was orginally suspected. The vascular derangement includes teleangiectases, arteriovenous fistulas, and connective tissue formation with fibrosis and atypical cirrhosis. In intestinal bleeding laser coagulation seems to be very efficient. The pathogenesis of teleangiectases is not known but involves several factors such as special formation of venules, capillaries and arterioles, abnormal perivascular connective tissue and endothelial cells.
Two cases of hereditary hemorrhagic telangiectasia (HHT) with neurological involvement are presented. One patient had multiple vascular malformations including telangiectasias of the brain, medulla, and spinal cord and a berry aneurysm of the internal carotid artery; she also had a large cerebellar abscess, presumably reflecting the presence of a pulmonary arteriovenous fistula. The second patient had an idiopathic subarachnoid hemorrhage.
In more than 200 reported patients with HHT involving the nervous system, 61% had lesions secondary to a pulmonary arteriovenous fistula (cerebral hypoxemia, paradoxical and septic emboli, and brain abscess). The findings emphasize the need for early surgical correction of such fistulas. In 36% of the patients with neurological involvement and HHT, vascular malformations of the brain and spinal cord were documented, and in 3%, portal-systemic encephalopathy was noted. Multiple lesions were frequent.
HHT should be considered a generalized vascular dysplasia (universal or systemic angiomatosis), and not simply a benign mucocutaneous disease.
The several neurologic manifestations of hereditary hemorrhagic telangiectasia (HHT) may be caused by complications of pulmonary arteriovenous fistulae or associated central nervous system vascular malformations. The presence of skin and mucosal telangiectases should alert the clinician to the possibility of the disorder and in turn of its potential for associated neurologic disease, including cerebral hemorrhage and abscess. This report describes two cases and demonstrates that the clinical spectrum of HHT should be enlarged to include its admittedly rare, but serious, neurologic aspects.
Data from 98 patients with hereditary haemorrhagic telangiectasia (HHT) are presented. All were symptomatic by 40 years of age and 62% by 16 years. Nose bleeding was the first symptom of disease in 90% of cases with mucocutaneous telangiectases appearing 5 to 20 years later. Complications of HHT are discussed and an age of onset curve given.
A total of 109 single or multiple pulmonary arteriovenous malformations (PAVMs) were evaluated with computed tomography (CT) of the chest in 40 patients separated into three groups to study the usefulness of CT (a) in the diagnosis and pretherapeutic management of PAVMs by comparison with selective pulmonary angiography of each lung (group 1: 20 patients), (b) in the follow-up of patients who received treatment (group 2: 27 patients), and (c) as an isolated diagnostic procedure in elderly patients (n = 3) or family members with Osler-Weber-Rendu disease (n = 8) (group 3: 11 patients). Follow-up ranged from several weeks to 10 years (mean follow-up, 4 years). In group 1, conventional and dynamic CT enabled identification of 107 PAVMs (98.2%) (vs 65 PAVMs [59.6%] identified with angiography), with confident segmental location in 56 of 65 PAVMs (86%) and reliable analysis of angioarchitecture in 17 PAVMs (26%) (vs 39 PAVMs [60%] analyzed with angiography). In group 2, progressive aneurysmal retraction was associated with successful occlusion. In group 3, CT enabled noninvasive evaluation of patients unable to undergo treatment and detection of PAVMS in family members.
The purpose of this retrospective study is to document the natural history of epistaxis in patients with hereditary hemorrhagic telangiectasia. A telephone questionnaire was administered to 73 patients who had been previously screened for pulmonary arteriovenous malformations (PAVMs). The incidence of epistaxis in this population was 93%, with a mean onset age of epistaxis of 12 years, a mean frequency of bleeding of 18 episodes per month, and a mean duration of bleeding of 7.5 minutes. More than 90% of patients experienced the onset of epistaxis before the age of 21 and symptoms were progressive with age. There were no differences in the age of onset, frequency of epistaxis, or duration of epistaxis between patients with PAVMs versus those without PAVMs. Although the natural history of epistaxis does not predict the presence or absence of pulmonary arteriovenous malformations, epistaxis is an early marker of the disease, hereditary hemorrhagic telangiectasia, and might guide screening for pulmonary and cerebral arteriovenous malformations in children of affected parents.
10 patients with frequent and severe bleeding from gastrointestinal vascular malformations took part in a double-blind, placebo-controlled, cross-over trial of a daily dose of 0.05 mg ethinyloestradiol plus 1 mg norethisterone given by mouth. Each arm of the trial lasted 6 months. Oestrogen-progesterone significantly decreased the transfusion need from 10.9 to 1.1 units packed cells (p less than 0.003). While on oestrogen-progesterone 2 of 9 patients required transfusions (mean 1.1 units packed cells per patient over 6 months), whereas all patients had to be transfused while on placebo (mean 10.9 units per patient over 6 months; p = 0.002 for number of patients). No significant excess of side-effects was noted with the active agents. The findings indicate that oestrogen-progesterone is an effective treatment for severely bleeding gastrointestinal vascular malformations.
From our series of 203 patients with cerebral vascular lesions, 18 (9%) could be included in the multiple arteriovenous malformation category. There were five patients with Rendu-Osler-Weber, one with Wyburn-Mason syndromes and two with concurrent arteriovenous malformations. The remaining ten patients (4%) had multiple brain arteriovenous malformations. Careful angiography with magnification is necessary to try to diagnose multiple brain AVMs, since these sometimes become apparent only after embolization of a larger dominant AVM. The incidence of multiple brain arteriovenous malformations is likely to have been underestimated due to the failure to recognize micro-arteriovenous malformations associated with larger arteriovenous malformations.
Although hereditary hemorrhagic telangiectasia is a cause of blood tears from the conjunctival telangiectasias, visual loss from intraocular vascular malformations is a rare complication. We examined 20 patients with hereditary hemorrhagic telangiectasia to determine the prevalence of ocular abnormalities in this disease. Seven patients (35%) had conjunctival telangiectasias and two (10%) had retinal vascular malformations.
We report the results of a comprehensive and systematic clinical study of 324 patients with hereditary hemorrhagic telangiectasia, selected from a total of 1,270 cases recruited by epidemiological survey. In 94% of the cases, familial occurrence suggested autosomal dominant inheritance; maximum penetrance for at least one manifestation was 97%. Epistaxis was reported by 96% of the patients and, in more than 50%, developed before age 20. Heavy and frequent bleeding occurred mainly in middle-aged patients. Telangiectasia was documented in 74% of cases, half of whom were younger than 30 years. The frequency of involvement of the hands and wrists was 41%, and for the face, 33%. Visceral involvement was present in 25% of patients, with affected lungs and CNS in the young and gastrointestinal tract and liver in older patients. Symptomatic urinary tract involvement was seen in only two/324 patients. Involvement of other internal sites was not observed.
Over a 10-year period, 276 pulmonary arteriovenous malformations (PAVMs) were occluded with balloon embolotherapy in 76 patients, 67 (88%) of whom had hereditary hemorrhagic telangiectasia. Eleven patients (14%) were discovered by means of family screening with measurement of arterial blood gases and chest radiography. Epistaxis, dyspnea, hemoptysis, and hemothorax occurred in 79%, 71%, 13%, and 9% of patients, respectively. Clinical histories of strokes and transient ischemic attacks were present in 18% and 37% of patients, respectively. Computed tomographic scans of 59 patients showed stroke in 36%. Sixty-five percent of PAVMs were located in the lower lobes, which correlated with the finding of more pronounced hypoxemia in the upright position. After embolotherapy, symptomatic hypoxemia was corrected, and serial values have remained constant for 5 years. Complications were minimal, and no patient required surgery. Balloon embolotherapy is effective long-term therapy for PAVMs, and family screening should be pursued because of the possibility of a higher frequency of paradoxical embolization (stroke) than previously recognized.
Ninety-three consecutive patients with transfusion-dependent gastrointestinal bleeding from vascular malformations (VMs) underwent systematic assessment in our gastrointestinal laser suite with extended upper gastrointestinal endoscopy and colonoscopy. Of these patients, 83 had angiodysplasia and 10 had the Osler-Weber-Rendu (OWR) syndrome. The median age in each of these groups was 70 and 63 years, respectively. Cardiovascular disease, especially valvular disease, was common. A poor correlation existed between the results of endoscopically identified VMs and visceral angiography in patients with angiodysplasia. A combination of upper and lower gastrointestinal VMs was found in 11% of patients with angiodysplasia and 60% of those with the OWR syndrome. All identified VMs were completely obliterated by photocoagulation with use of a neodymium:yttrium-aluminum-garnet (Nd:YAG) laser. Bleeding was successfully controlled in 9 patients with the OWR syndrome and in 72 patients with angiodysplasia (range of follow-up, 1 to 39 months). In 243 laser treatments, 3 perforations and 5 episodes of delayed bleeding occurred. This experience demonstrates that extended upper endoscopy is useful in identifying VMs and that gastrointestinal bleeding from VMs can be safely and successfully controlled with use of endoscopic Nd:YAG laser therapy.
Gastrointestinal bleeding is the most frequent form of bleeding after epistaxis in patients with hereditary hemorrhagic telangiectasia. As a part of an epidemiologic study, gastrointestinal telangiectases could be endoscopically demonstrated in 28 patients with hereditary hemorrhagic telangiectasia, most frequently in the upper gastrointestinal tract and predominantly in the stomach and the duodenum. The typical endoscopic finding was nodular angiomas that did not differ, with regard to form and size, from external telangiectases. However, in 15 patients some of the gastrointestinal telangiectases were surrounded by an anemic halo. A significant difference was found in the age at onset of epistaxis (median 11 yr) and of gastrointestinal bleeding (median 55.5 yr). There was no intrafamilial or interfamilial variation as to heredity and clinical manifestations. The blood group distribution in patients with hereditary hemorrhagic telangiectasia and gastrointestinal telangiectases did not differ from that of other patients with hereditary hemorrhagic telangiectasia, whereas there was a significantly higher frequency of blood group O among patients with hereditary hemorrhagic telangiectasia than among the background population.
Four of five patients with asymptomatic small or moderate-size pulmonary arteriovenous malformation (PAVM) presented with a paradoxical embolus and stroke. In these patients chest radiographic findings were subtle and arterial hypoxemia provided the real clue to diagnosis. Computed tomography (CT) and cerebral arteriography confirmed embolic occlusion in four of five patients. Careful family screening including posteroanterior (PA) and lateral chest radiographs and arterial oxygen determinations in sitting or standing positions are recommended for early detection of asymptomatic patients with PAVM. Early therapeutic intervention (with balloon embolotherapy) is recommended to avoid paradoxical embolization.
The operation of septal dermoplasty, first described in 1958 and designed for patients with severe epistaxis caused by hereditary hemorrhagic telangiectasia, is used currently for that condition and for several others. This discussion reviews the rationale of the operation and its indications, describes the exact technique, and presents results from experience in 160 cases.
Over a 20 yr period (Jan. 1, 1952, through Dec. 31, 1972) 63 cases of pulmonary arteriovenous fistula were seen at the Mayo Clinic. Angiography permitted classification of these cases into two groups: pulmonary arteriovenous fistula with pulmonary arterial blood supply (60 cases), and pulmonary arteriovenous fistula with systemic blood supply (3 cases). Of these 63 cases, 36 were treated surgically; in 23, hereditary telangiectasia was an associated finding. The indications for surgery include the occurrence of one or more pulmonary arteriovenous fistulas that cause symptoms or show roentgenographic enlargement, the association of a single fistula with hereditary telangiectasia, and the presence of pulmonary arteriovenous fistulas with systemic arterial blood supply. Among the remaining 27 cases were 15 with associated Rendu Osler Weber syndrome. Fistulas were single in 41 cases and multiple in 22, including 5 cases of bilateral fistulas. Among the total of 63 cases, there were 6 deaths; A were due to cerebrovascular accidents, in patients who had been symptomatic and had manifested cyanosis and polycythemia. Review of these cases indicates that in patients with pulmonary arteriovenous fistulas and hereditary telangiectasia there is an increased incidence of multiplicity in fistulas, an increased rate of fistula growth, and an increased frequency of complications.
The clinical courses of 31 episodes of brain abscess and one episode of meningitis occurring in patients with hereditary hemorrhagic telangiectasia are reviewed. Pulmonary arteriovenous malformations were demonstrable in all but two patients and presumably permitted septic microemboli to evade the normal pulmonary capillary filter and lodge in the brain. Obtundation, headache, visual disturbances, hemiplegia, and seizures were the most common presenting features. Cyanosis, clubbing, polycythemia, and hypoxemia were routinely encountered, but leukocytosis and fever were present in a minority of cases, and all blood cultures were sterile. Anaerobic and microaerophilic streptococci were the commonest pathogens found in the brain abscesses. Thirteen patients died, and patients without abscess drainage or with delayed diagnosis had a higher mortality rate. A brain abscess may develop in approximately 1 percent of patients with hereditary hemorrhagic telangiectasia, and awareness of this risk should lead to early investigation of any patient with hereditary hemorrhagic telangiectasia who has neurologic symptoms.
Recurrent epistaxis is usually the main symptom found in patients with hereditary hemorrhagic telangiectasia (HHT)—Osler Rendu Weber syndrome. Therapies have included intranasal cautery, septal dermoplasty, intra-arterial embolization, and arterial ligation. These procedures have met with limited success. Laser photocoagulation has achieved early success in the gastrointestinal (GI) telangiectatic lesions.
In this report, cutaneous and intranasal lesions of eight HHT patients have been treated with laser photocoagulation using a flexible fiber delivery system connected to 3 W argon and 55 W neodymium:yttrium-aluminum-garnet (Nd:YAG) laser sources. The patients noted a great reduction in the frequency and severity of epistaxis, reduction in the need for blood transfusion, and reduction in iron therapy necessary to maintain adequate hemoglobin levels. Previously, five of these patients were considered treatment failures after extensive surgical therapy. No serious complications have been encountered.
Laser photocoagulation of HHT patients appears to be a promising therapeutic advance. The progressive nature of HHT necessitates close follow-up and retreatment of new lesions as they appear.
Otitis media continues to be one of the most common diagnoses made in the offices of family physicians, pediatricians, and otolaryngologists. The emergence of ampicillin resistant Hemophilus influenzae as an important etiologic agent for otitis media has altered the selection of a therapeutic antimicrobial drug. This article reviews the role of the penicillins, cephalosporins, and sulfonamides in the treatment of otitis media. Amoxicillin continues to be the drug chosen for the uncultured otitis media. Backup drugs for use in unresponsive cases include trimethoprim-sulfamethoxazole, erythromycin-sulfisoxazole, and cefaclor. The cost of the drug should be a factor in the selection when efficacy is equal.
The effect of estrogen treatment in 31 patients with hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease was evaluated in a randomized double-blind trial. After a 3-month control period there was a 3-month treatment period during which 17 patients were treated with peroral estrogen (estradiol valerate), 4 mg dialy, and 14 with placebo. The results showed no significant reduction in the frequency of bleeding or its intensity. The hemoglobin values remained unchanged in the estrogen group compared with the previous control period as well as with the placebo group. The only demonstrable effect of estrogen treatment was a significant fall in transferrin.
Within a 25 year period, 118 patients with a definitive diagnosis of familial hemorrhagic telangiectasia were treated for recurrent epistaxis. Twenty-eight patients had dermoplasty but 67 patients received large dose estrogen therapy using ethinyl estradiol. The latter regime proved successful in every patient and the side effects and possible disadvantages of this treatment are considered in detail.
Hereditary haemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease is an autosomal dominant vascular disorder which associates epistaxis, mucocutaneous and visceral telangiectases, and recurrent haemorrhage with chronic anaemia and visceral shuntings. Recently, the tumour growth factor (TGF)-beta binding protein endoglin localized to 9q33-34 was identified as responsible for HHT in several large kindreds with pulmonary arteriovenous malformations (PAVMs). Additional linkage studies demonstrated that HHT is a genetically heterogeneous disorder with families unlinked to this region of 9q. In the families in which HHT was not linked to chromosome 9, less PAVMs were present. Furthermore, in one of these families, HHT was found linked to 3p22, where the TGF-beta II receptor is located. In this linkage study, we have analysed DNA from two families, in which HHT was unlinked to chromosome 9q and 3p, and PAVMs were absent, with a series of genetic markers on the centromeric region of chromosome 12. Using two-point linkage analysis, a significant lod score of Zmax = 7.86 at theta = 0.05 was obtained with the D12S85 microsatellite marker.
A locus causing hereditary haemorrhagic telangiectasia (HHT) has recently been mapped to 9q34 in four families and designated HHT1. In this paper, the results of a linkage study showing genetic heterogeneity in four families in whom HHT is segregating are reported. All the previously reported 9q34 linked families contain at least one affected member with a symptomatic pulmonary arteriovenous malformation. We postulate that clinical heterogeneity may also be a feature of HHT with a significantly higher predisposition to symptomatic PAVMs associated with the HHT1 linked families.
Ninety-seven patients were referred to the Toronto Hospital (Western Division) between January 1984 and January 1992 for selective angiographic embolization (108 embolizations, including repeat procedures) to control intractable or recurrent severe epistaxis. Eighty-one patients (comprising 94 embolizations) were referred on an emergent basis because of failure of conventional conservative therapy, consisting of anterior and posterior packing. The remaining 16 patients (14 embolizations) were referred electively for recurrent epistaxis. A retrospective review of these cases was performed, with long-term telephone follow-up achieved in over 95% of cases. Embolization safely controlled active hemorrhage in 88% of the emergent cases. The success rate increased to 90% when two cases in which the source of epistaxis was found to be from the internal carotid artery were excluded (because these vessels could not be safely embolized). Of the patients whose epistaxis was initially controlled by embolization, 82% had no further nosebleeds (follow-up time ranged from 2 to 82 months; average, 26.8 months). More than half of the long-term failures were seen in patients with Osler-Weber-Rendu disease. Overall, the mortality rate was 0% and the long-term morbidity rate was 2% (one cerebral vascular accident and one case of skin slough in the territory of the superficial temporal artery.
To evaluate spin-echo (SE) and cine gradient-echo (GRE) magnetic resonance (MR) imaging with velocity mapping for detecting late complications of the Mustard operation.
Twenty-one patients were studied with MR imaging 1-22 years after undergoing the Mustard operation. Twenty were also studied with transthoracic echocardiography, 18 with angiocardiography, and five with transesophageal echocardiography.
MR imaging showed no venoatrial obstruction in nine patients. This result was confirmed with angiocardiography in seven cases and postmortem examination in one case. In one case, MR imaging demonstrated a leak at the baffle suture line. Of 12 cases with venoatrial obstruction at MR imaging, nine were confirmed with angiocardiography or surgery. There were two false-positive MR studies and one case in which no conclusion was reached.
With addition of cine GRE sequences and velocity mapping to SE sequences, MR imaging is a useful noninvasive method of investigating late complications of the Mustard operation.
Hereditary haemorrhagic telangiectasia (HHT), or Osler-Weber-Rendu disease, is an autosomal dominant vascular dysplasia of unknown pathogenesis leading to 'widespread' dermal, mucosal and visceral telangiectases and recurrent haemorrhage. We have mapped the HHT gene, by linkage analysis, to markers on 9q33-34 in two large multi-generation families. Haplotype analysis and mapping of recombination breakpoints gives a 4 cM interval between D9S61 and D9S63 as the most likely location of the gene. The closest marker, D9S65, is estimated to be within 1 cM of the gene and shows a combined lod score of 11.41. Two potential candidate genes, COL5A1 and ZNF79, are also located within 9q33-34. These results provide a starting point for the eventual cloning of the HHT gene.
To determine the clinical utility of three-dimensional (3D) helical computed tomography (CT) in pretherapy evaluation of the angioarchitecture of pulmonary arteriovenous malformations (PAVMs).
Thirty-seven PAVMs were prospectively evaluated with both helical CT and pulmonary angiography. Single-threshold shaded-surface displays were obtained with 2- or 5-mm section thickness, a pitch of 1, and a 360 degrees linear interpolation algorithm but without injection of contrast medium.
A reliable analysis of the angioarchitecture of 28 PAVMs (76%)--25 simple and three complex--was provided by 3D reconstructions; combined interpretation of 3D images and transverse sections led to accurate evaluation of 35 PAVMs (95%). Positioning of the target anatomy in the reconstructed volume, threshold value, number of stacked sections, and section thickness influenced the diagnostic information.
Unenhanced 3D helical CT appears to be a reliable noninvasive tool for pretherapy evaluation of PAVMs.