Brain Abscess: A Need to Screen for Pulmonary Arteriovenous Malformations

Gargiulo, Mauro; Lepore, Vito; Pasculli, Giuseppe; Gennaro, Leonardo Di; Logroscino, Giancarlo; Carella, A.; White, Robert I.; Sabbá, Carlo

doi:10.1159/000081053

Cited by 18 publications

(13 citation statements)

References 18 publications

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“…None of the HHT2 patients with large PAVMs had experienced neurological sequelae, but neurological complications secondary to PAVMs have been reported in HHT2 patients in literature, though to a lesser extent than that observed in HHT1 [19,24]. As neurological complications mainly occur in PAVMs with a feeding artery > 3 mm [22,25], few HHT2 patients are expected to suffer from brain involvement secondary to PAVMs. It is noteworthy that 6/12 HHT1 patients with PAVM‐related neurological complications were younger than 45 years; moreover, 11 HHT1 and only two HHT2 patients with large PAVMs were observed at an age < 45 years, suggesting that not only large PAVMs are more frequent in HHT1, but they are also rare in young HHT2 patients.…”

Section: Discussionmentioning

confidence: 99%

Hereditary hemorrhagic telangiectasia: clinical features in ENG and ALK1 mutation carriers

Sabbá

Pasculli

Suppressa

et al. 2007

Journal of Thrombosis and Haemostasis

165

128

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To cite this article: Sabbà C, Pasculli G, Lenato GM, Suppressa P, Lastella P, Memeo M, Dicuonzo F, Guanti G. Hereditary hemorrhagic telangiectasia: clinical features in ENG and ALK1 mutation carriers. J Thromb Haemost 2007; 5: 1149-57.Summary. Background: Hereditary hemorrhagic telangiectasia (HHT) is a genetic disorder characterized by epistaxis, mucocutaneous telangiectases and visceral arteriovenous malformations (AVMs), particularly in the brain (CAVMs), lungs (PAVMs), liver (HAVMs) and gastrointestinal tract (GI). The identification of a mutated ENG (HHT1) or ALK-1 (HHT2) gene now enables a genotype-phenotype correlation. Objective: To determine the incidence of visceral localizations and evaluate phenotypic differences between ENG and ALK1 mutation carriers. Methods: A total of 135 consecutive adult patients were subjected to mutational screening in ENG and ALK1 genes and instrumental tests to detect AVMs, such as chest-abdomen multislice computed tomography (MDCT), brain magnetic resonance imaging and magnetic resonance angiography (MRI/MRA), upper endoscopy, were offered to all patients, independent of presence of clinical symptoms. The 122 patients with identified mutations were enrolled in the study and genotype-phenotype correlations were established. Results: PAVMs and CAVMs were significantly more frequent in HHT1 (75% vs. 44%, P < 0.0005; 20% vs. 0%, P < 0.002, respectively) and HAVMs in HHT2 (60% vs. 84%, P < 0.01). No age difference was found for PAVMs whereas HAVMs were significantly higher in older patients in both HHT1 and HHT2. Neurological manifestations secondary to CAVMs/PAVMs were found only in HHT1 patients, whereas severe liver involvement was detected only in HHT2. Respiratory symptoms were mainly detected in HHT1. Conclusions: Our study evidences a higher visceral involvement in HHT1 and HHT2 compared with previous reports. HHT1 is more frequently associated with congenital AVM malformations, such as CAVMs and PAVMs whereas HHT2 predominantly involves the liver. The ENG gene should be first targeted for mutational screening in the presence of large PAVM in patients < 45 years.

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Section: Discussionmentioning

confidence: 99%

Hereditary hemorrhagic telangiectasia: clinical features in ENG and ALK1 mutation carriers

Sabbá

Pasculli

Suppressa

et al. 2007

Journal of Thrombosis and Haemostasis

165

128

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“…We consider that the risk is mostly influenced by the severity of the right-to-left shunting. The presence of PAVMs may not be recognized at the time of the brain abscess [18, 85, 86], which may develop in patients with diagnosed but untreated PAVMs [18]. Cerebral abscesses in HHT are frequently due to multiple anaerobic organisms [83] and predominate in supratentorial areas of the brain [80].…”

Section: Clinical Manifestations and Complications Of Pavmsmentioning

confidence: 99%

Pulmonary Vascular Manifestations of Hereditary Hemorrhagic Telangiectasia (Rendu-Osler Disease)

et al. 2007

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Hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler-Weber disease is a genetic disorder with autosomal dominance and variable penetrance, characterized by epistaxis, telangiectasia and visceral manifestations of the disease. The estimated minimal prevalence is 1/10,000 inhabitants. The diagnosis is established on clinical criteria, and may be further confirmed by the identification of causative mutations in either the ENG or the ACVRL1 gene coding for endoglin and ALK1, respectively. Pulmonary vascular manifestations of HHT include pulmonary arteriovenous malforma- tions (PAVMs; especially in patients with ENG mutations) and less frequently pulmonary hypertension (especially in patients with ACVRL1 mutations). In 15–33% of patients with HHT, PAVMs consist of abnormal communications between pulmonary arteries and pulmonary veins, causing right-to-left shunting, and thus, frequently hypoxemia and dyspnea on exertion, although PAVMs may remain asymptomatic and frequently undiagnosed unless complications occur. PAVMs result in severe and frequent complications often at a young age, which may reveal the diagnosis, e.g. transient ischemic attack and cerebral stroke (10–19% of patients), systemic severe infections and abscesses (including cerebral abscess in 5–19% of patients), and rarely massive hemoptysis or hemothorax. Infections in HHT are related to the right-to-left shunting that bypasses the pulmonary capillaries and facilitates the passage of septic or aseptic emboli into the systemic and especially cerebral circulation, and potentially to minor defects in innate immunity. Treatment of PAVMs based on transcatheter coil vaso-occlusion of the feeding artery significantly decreases right-to-left shunting, hypoxemia and dyspnea on exertion, and reduces the risk of systemic complications. Long-term follow-up is warranted after transcatheter vaso-occlusion of PAVMs due to frequent recanalization of treated PAVMs and development or growth of untreated PAVMs. Patients with HHT should be informed of the risk of PAVM and potentially severe complications occurring in heretofore asymptomatic subjects. All adult patients with HHT should be proposed systematic screening for PAVM, by contrast echocardiography (preceded by anteroposterior chest radiograph) or computed tomography of the chest. Pulmonary hypertension is rare in HHT, and may be due either to systemic arteriovenous shunting in the liver increasing cardiac output or be clinically and histologically indistinguishable from idiopathic pulmonary arterial hypertension. Pulmonary hypertension is detected by systematic examination of right cardiac cavities and tricuspid regurgitation flow at echocardiography, and the diagnosis is established by right heart catheterization.

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“…Clinically, an association between HHT and infectious diseases has been reported. Numerous cases indicated that particularly patients with HHT and pulmonary vascular malformations (PAVMs) or prolonged nasal packings for epistaxis are more susceptible to infections, cerebral abscesses, or septic thrombi [7][8][9][10][11]. A few studies reported life-threatening extracerebral severe infections, including osteoarthritis, septicemia, and spondylodiscitis, typically due to Staphylococcus aureus infection [12,13].…”

Section: Introductionmentioning

confidence: 99%

Impaired Release of Neutrophil Extracellular Traps and Anemia-Associated T Cell Deficiency in Hereditary Hemorrhagic Telangiectasia

Droege

Pylaeva

Siakaeva

et al. 2020

JCM

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Hereditary hemorrhagic telangiectasia (HHT) is characterized by mucocutaneous telangiectases and visceral vascular malformations. Individuals suffering from HHT have a significantly increased risk of bacterial infections, but the mechanisms involved in this are not clear. White blood cell subpopulations were estimated with flow cytometry in 79 patients with HHT and 45 healthy individuals, and association with clinicopathological status was assessed. A prominent decrease in absolute numbers of T cells in HHT was revealed (0.7 (0.5–1.1) vs. 1.3 (0.8–1.6), 106/mL, p < 0.05), and in multivariate regression analysis, hemoglobin level was associated with lymphopenia (OR = 0.625, 95% CI: 0.417–0.937, p < 0.05). Although no changes in absolute numbers of neutrophils and monocytes were observed, we revealed a significant impairment of neutrophil antibacterial functions in HHT (n = 9), compared to healthy individuals (n = 7), in vitro. The release of neutrophil extracellular traps (NETs) against Pseudomonas aeruginosa MOI10 was significantly suppressed in HHT (mean area per cell, mm2: 76 (70–92) vs. 121 (97–128), p < 0.05), due to impaired filamentous actin organization (% of positive cells: 69 (59–77) vs. 92 (88–94), p < 0.05). To conclude, this study reveals the categories of patients with HHT that are prone to immunosuppression and require careful monitoring, and suggests a potential therapeutic strategy based on the functional activation of neutrophils.

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Brain Abscess: A Need to Screen for Pulmonary Arteriovenous Malformations

Cited by 18 publications

References 18 publications

Hereditary hemorrhagic telangiectasia: clinical features in ENG and ALK1 mutation carriers

Hereditary hemorrhagic telangiectasia: clinical features in ENG and ALK1 mutation carriers

Pulmonary Vascular Manifestations of Hereditary Hemorrhagic Telangiectasia (Rendu-Osler Disease)

Impaired Release of Neutrophil Extracellular Traps and Anemia-Associated T Cell Deficiency in Hereditary Hemorrhagic Telangiectasia

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