Relationships between hemorrhage, angioarchitectural factors and collagen of arteriovenous malformations.
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ABSTRACT:
SUBMITTER: Niu H
PROVIDER: S-EPMC5561923 | biostudies-other | 2012 Oct
REPOSITORIES: biostudies-other
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Project description:ObjectiveTo compare outcomes after intracerebral hemorrhage (ICH) from cerebral arteriovenous malformation (AVM) rupture and other causes of ICH.MethodsWe performed a retrospective population-based study using data from the Nationwide Inpatient Sample. We used standard diagnosis codes to identify ICH cases from 2002 to 2011. Our predictor variable was cerebral AVM. Our primary outcomes were inpatient mortality and home discharge. We used logistic regression to compare outcomes between patients with ICH with and without AVM while adjusting for demographics, comorbidities, and hospital characteristics. In a confirmatory analysis using a prospective cohort of patients hospitalized with ICH at our institution, we additionally adjusted for hematoma characteristics and the Glasgow Coma Scale score.ResultsAmong 619,167 ICH hospitalizations, the 4,485 patients (0.7%, 95% confidence interval [CI] 0.6-0.8) with an AVM were younger and had fewer medical comorbidities than patients without AVM. After adjustment for confounders, patients with AVM had lower odds of death (odds ratio [OR] 0.5, 95% CI 0.4-0.7) and higher odds of home discharge (OR 2.0, 95% CI 1.4-3.0) than patients without AVM. In a confirmatory analysis of 342 patients with ICH at our institution, the 34 patients (9.9%, 95% CI 7.2-13.6) with a ruptured AVM had higher odds of ambulatory independence at discharge (OR 4.4, 95% CI 1.4-13.1) compared to patients without AVM.ConclusionsPatients with ICH due to ruptured AVM have more favorable outcomes than patients with ICH from other causes.
| S-EPMC5444313 | biostudies-literature
Project description:Brain arteriovenous malformations (AVMs) are abnormal connections of arteries and veins, resulting in arteriovenous shunting of blood. Primary medical therapy is lacking; treatment options include surgery, radiosurgery, and embolization, often in combination. Judicious selection of AVM patients for treatment requires balancing risk of treatment complications against the risk of hemorrhage in the natural history course. This review focuses on the epidemiology, hemorrhage risk, and factors influencing risk of hemorrhage in the untreated natural course associated with sporadic brain AVM.
| S-EPMC4139097 | biostudies-literature
Project description:BACKGROUND AND PURPOSE:Brain arteriovenous malformation (bAVM) is an important risk factor for intracranial hemorrhage. Current treatments for bAVM are all associated with considerable risks. There is no safe method to prevent bAVM hemorrhage. Thalidomide reduces nose bleeding in patients with hereditary hemorrhagic telangiectasia, an inherited disorder characterized by vascular malformations. In this study, we tested whether thalidomide and its less toxic analog, lenalidomide, reduce bAVM hemorrhage using a mouse model. METHODS:bAVMs were induced through induction of brain focal activin-like kinase 1 (Alk1, an AVM causative gene) gene deletion and angiogenesis in adult Alk1-floxed mice. Thalidomide was injected intraperitoneally twice per week for 6 weeks, starting either 2 or 8 weeks after AVM induction. Lenalidomide was injected intraperitoneally daily starting 8 weeks after AVM induction for 6 weeks. Brain samples were collected at the end of the treatments for morphology, mRNA, and protein analyses. The influence of Alk1 downregulation on PDGFB (platelet-derived growth factor B) expression was also studied on cultured human brain microvascular endothelial cells. The effect of PDGFB in mural cell recruitment in bAVM was explored by injection of a PDGFB overexpressing lentiviral vector to the mouse brain. RESULTS:Thalidomide or lenalidomide treatment reduced the number of dysplastic vessels and hemorrhage and increased mural cell (vascular smooth muscle cells and pericytes) coverage in the bAVM lesion. Thalidomide reduced the burden of CD68+ cells and the expression of inflammatory cytokines in the bAVM lesions. PDGFB expression was reduced in ALK1-knockdown human brain microvascular endothelial cells and in mouse bAVM lesion. Thalidomide increased Pdgfb expression in bAVM lesion. Overexpression of PDGFB mimicked the effect of thalidomide. CONCLUSIONS:Thalidomide and lenalidomide improve mural cell coverage of bAVM vessels and reduce bAVM hemorrhage, which is likely through upregulation of Pdgfb expression.
| S-EPMC5916043 | biostudies-literature
Project description:Objective:To assess the relationship of the grade of unruptured and untreated Brain Arteriovenous Malformations (AVMs), with the risk of subsequent stroke and death during follow-up. Methods:This prospective study was drawn from a cohort of adult patients with unruptured AVMs, who participated in the conservative treatment arm (medical management only for headache or seizures) of the randomized clinical trial of unruptured brain AVMs (ARUBA study). The grade of AVMs (Spetzler-Martin scale) was dichotomized into categories: AVMs of grades I and II were considered low grade; AVMs of grades III and IV were considered high grade. There were no grade V AVM patients in ARUBA. The primary outcome was symptomatic stroke (hemorrhagic or ischemic - documented by imaging) or death. Results:The conservative treatment group had 123 patients ("as treated" analysis). 71 (57.7%) had lesions characterized for this analysis as low-grade lesions and 52 (42.2%) as high grade. From the total of 10 (8.13%) primary outcomes, three occurred (4.22%) in low-grade AVMs and seven (13.46%) in high-grade AVMs (P = 0.0942). Interpretation:Statistical analysis of the cohort of patients with unruptured and untreated AVMs from ARUBA study showed that the graduation categories (Spetzler-Martin grades) were not associated with the outcome of subsequent stroke or death.
| S-EPMC6414495 | biostudies-literature
Project description:BackgroundBrain arteriovenous malformations (BAVMs) are a tangle of abnormal vessels directly shunting blood from the arterial to venous circulation and an important cause of intracranial hemorrhage (ICH). EphB4 is involved in arterial-venous determination during embryogenesis; altered signaling could lead to vascular instability resulting in ICH. We investigated the association of single-nucleotide polymorphisms (SNPs) and haplotypes in EPHB4 with risk of ICH at clinical presentation in patients with BAVM.Methods and resultsEight haplotype-tagging SNPs spanning approximately 29 kb were tested for association with ICH presentation in 146 white patients with BAVM (phase I: 56 ICH, 90 non-ICH) using allelic, haplotypic, and principal components analysis. Associated SNPs were then genotyped in 102 additional cases (phase II: 37 ICH, 65 non-ICH), and data were combined for multivariable logistic regression. Minor alleles of 2 SNPs were associated with reduced risk of ICH presentation (rs314313_C, P=0.005; rs314308_T, P=0.0004). Overall, haplotypes were also significantly associated with ICH presentation (chi(2)=17.24, 6 df, P=0.008); 2 haplotypes containing the rs314308 T allele (GCCTGGGT, P=0.003; GTCTGGGC, P=0.036) were associated with reduced risk. In principal components analysis, 2 components explained 91% of the variance and complemented haplotype results by implicating 4 SNPs at the 5' end, including rs314308 and rs314313. These 2 SNPs were replicated in the phase II cohort, and combined data resulted in greater significance (rs314313, P=0.0007; rs314308, P=0.00008). SNP association with ICH presentation persisted after adjusting for age, sex, BAVM size, and deep venous drainage.ConclusionsEPHB4 polymorphisms are associated with risk of ICH presentation in patients with BAVM, warranting further study.
| S-EPMC2939745 | biostudies-literature
Project description:ImportanceThe dilemma between natural rupture risk and adverse outcomes of intervention is of major concern for patients with unruptured arteriovenous malformations (AVMs). The existing risk score for AVM rupture includes factors that are controversial and lacks prospective validation.ObjectiveTo develop and robustly validate a reliable scoring system to predict the rupture risk of AVMs.Design, setting, and participantsThis prognostic study developed a prediction model derived from a single-center cohort (derivation cohort) and validated in a multicenter external cohort (multicenter external validation cohort) and a cohort of patients receiving conservative treatment management (conservative treatment validation cohort). Patients were recruited from a nationwide multicenter prospective collaboration registry in China. A total of 4135 patients were enrolled in the registry between August 1, 2011, and September 1, 2021. Of those, 3962 patients were included in the study (3585 in the derivation cohort and 377 in the multicenter external validation cohort); 1028 patients from the derivation cohort who had time-to-event data and prerupture imaging results were included in the conservative treatment validation cohort. Data were analyzed from March 10 to June 21, 2022.Main outcomes and measuresA scoring system was developed based on risk factors identified from a literature review and a robust selection process. Patients were stratified into different risk groups based on scores to calculate hemorrhage-free probability in future years, and Kaplan-Meier curves were plotted to visualize risk stratification. Receiver operating characteristic curves were used to assess the discrimination of models. Univariable analyses (logistic regression analysis for descriptive data and Cox regression analysis for survival data) were used to compare baseline information and assess bias.ResultsAmong 3962 patients (2311 men [58.3%]; median [IQR] age, 26.1 [14.6-35.5] years), 3585 patients (2100 men [58.6%]; median [IQR] age, 25.9 [14.6-35.0] years) were included in the derivation cohort, and 377 patients (211 men [56.0%]; median [IQR] age, 26.4 [14.5-39.2] years) were included in the multicenter external validation cohort. Thirty-six hemorrhages occurred over a median (IQR) follow-up of 4.2 (0.3-6.0) years among 1028 patients in the conservative treatment validation cohort. Four risk factors were used to develop the scoring system: ventricular system involvement, venous aneurysm, deep location, and exclusively deep drainage (VALE). The VALE scoring system performed well in all 3 cohorts, with areas under the receiver operating characteristic curve of 0.77 (95% CI, 0.75-0.78) in the derivation cohort, 0.85 (95% CI, 0.81-0.89) in the multicenter external validation cohort, and 0.73 (95% CI, 0.65-0.81) in the conservative treatment validation cohort. The 10-year hemorrhage-free rate was 95.5% (95% CI, 87.1%-100%) in the low-risk group, 92.8% (95% CI, 88.8%-97.0%) in the moderate-risk group, and 75.8% (95% CI, 65.1%-88.3%) in the high-risk group; the model discrimination was significant when comparing these rates between the high-risk group and the low- and moderate-risk groups (P < .001 for both comparisons).Conclusions and relevanceIn this prognostic study, the VALE scoring system was developed to distinguish rupture risk among patients with AVMs. The stratification of unruptured AVMs may enable patients with low risk of rupture to avoid unnecessary interventions. These findings suggest that the scoring system is a reliable and applicable tool that can be used to facilitate patient and physician decision-making and reduce unnecessary interventions or unexpected AVM ruptures.
| S-EPMC9978947 | biostudies-literature
Project description:BackgroundKnowledge about the natural course of brain arteriovenous malformations (AVMs) have increased during the past 20 years, as has the number of AVMs treated, especially larger ones. It is thus timely to again analyze the risk for hemorrhage after Gamma Knife Surgery (GKS).ObjectiveTo confirm or contradict conclusions drawn 20 years ago regarding factors that affect the risk for post-GKS hemorrhage.MethodsThe outcome after GKS was studied in 5037 AVM patients followed for up to 2 years. The relation between post-treatment hemorrhage rate and a number of patient, AVM, and treatment parameters was analyzed. The results were also compared with the results from our earlier study.ResultsThe annual post-treatment hemorrhage rate was 2.4% the first 2 years after GKS. Large size, low treatment dose, and old age were independent risk factors for AVM hemorrhage. After having compensated for the factors above, peripheral AVM location and female sex, at least during their child bearing ages, were factors associated with a lower post-GKS hemorrhage rate.ConclusionLarge AVMs (>5 cm 3 ) treated with low doses (≤16 Gy) had higher and small AVMs treated with high doses a lower risk for hemorrhage as compared with untreated AVMs. This was detectable within the first 6 months after GKS. No difference in hemorrhage rate could be detected for the other AVMs. Based on our findings, it is advisable to prescribe >16 Gy to larger AVMs, assuming that the risk for radiation-induced complications can be kept at an acceptable level.
| S-EPMC9632947 | biostudies-literature
Project description:Abnormalities in arterial versus venous endothelial cell identity and dysregulation of angiogenesis are deemed important in the pathophysiology of brain arteriovenous malformations (AVMs). The Sonic hedgehog (Shh) pathway is crucial for both angiogenesis and arterial versus venous differentiation of endothelial cells, through its dual role on the vascular endothelial growth factor/Notch signaling and the nuclear orphan receptor COUP-TFII. In this study, we show that Shh, Gli1 (the main transcription factor of the Shh pathway), and COUP-TFII (a target of the non-canonical Shh pathway) are aberrantly expressed in human brain AVMs. We also show that implantation of pellets containing Shh in the cornea of Efnb2/LacZ mice induces growth of distinct arteries and veins, interconnected by complex sets of arteriovenous shunts, without an interposed capillary bed, as seen in AVMs. We also demonstrate that injection in the rat brain of a plasmid containing the human Shh gene induces the growth of tangles of tortuous and dilated vessels, in part positive and in part negative for the arterial marker αSMA, with direct connections between αSMA-positive and -negative vessels. In summary, we show that the Shh pathway is active in human brain AVMs and that Shh-induced angiogenesis has characteristics reminiscent of those seen in AVMs in humans.
| S-EPMC8369994 | biostudies-literature
Project description:Cowden syndrome (OMIM No 158350) is a pleomorphic, autosomal dominant syndrome characterised by hamartomas in tissues derived from the endoderm, mesoderm, and ectoderm. It is caused by germline mutations in the PTEN gene and is allelic to the Bannayan-Riley-Ruvalcaba and Lhermitte-Duclos syndromes. The three syndromes are defined on clinical grounds but there is overlap in their definitions. The clinical features include trichilemmomas, verrucose lesions of the skin, macrocephaly, intellectual disability, cerebellar gangliocytoma, thyroid adenomas, fibroadenomas of the breast, and hamartomatous colonic polyps. Cutaneous haemangiomas are occasionally noted. Malignancies often arise in the affected tissues. Visceral arteriovenous malformations are a recognised component of the Bannayan-Riley-Ruvalcaba syndrome but have been reported rarely in Cowden syndrome. A family is described with a clinical diagnosis of Cowden syndrome, a familial frameshift mutation in the PTEN gene, and large visceral arteriovenous malformations. The association of these pleomorphic syndromes with arteriovenous malformations can be explained by the putative role of the PTEN gene in suppressing angiogenesis. Recognition of arteriovenous malformations as a clinical feature of Cowden syndrome has implications for the clinical management of patients with this disorder.
| S-EPMC1736111 | biostudies-literature
Project description:Brain arteriovenous malformations (bAVMs) represent a high risk of intracranial hemorrhages, which are substantial causes of morbidity and mortality of bAVMs, especially in children and young adults. Although a variety of factors leading to hemorrhages of bAVMs are investigated extensively, their pathogenesis is still not well elucidated. The author has reviewed the updated data of genetic aspects of bAVMs, especially focusing on clinical and experimental knowledge from hereditary hemorrhagic telangiectasia, which is the representative genetic disease presenting with bAVMs caused by loss-of-function in one of the two genes: endoglin and activin receptor-like kinase 1. This knowledge may allow us to infer the pathogensis of sporadic bAVMs and in the development of new medical therapies for them.
| S-EPMC4908075 | biostudies-literature