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Background and purposeHereditary hemorrhagic telangiectasia is an autosomal dominant disease that presents in 10%-20% of patients with various brain vascular malformations. We aimed to report the radiologic features (phenotype) and the genotype-phenotype correlations of brain vascular malformations in hereditary hemorrhagic telangiectasia.Materials and methodsDemographic, clinical, genotypic, and imaging information of 75 patients with hereditary hemorrhagic telangiectasia with brain arteriovenous malformations enrolled in the Brain Vascular Malformation Consortium from 2010 to 2012 were reviewed.ResultsNonshunting, small, superficially located conglomerates of enhancing vessels without enlarged feeding arteries or draining veins called "capillary vascular malformations" were the most commonly observed lesion (46 of 75 patients; 61%), followed by shunting "nidus-type" brain AVMs that were typically located superficially with a low Spetzler-Martin Grade and a small size (32 of 75 patients; 43%). Direct high-flow fistulous arteriovenous shunts were present in 9 patients (12%). Other types of vascular malformations (dural AVF and developmental venous anomalies) were present in 1 patient each. Multiplicity of vascular malformations was seen in 33 cases (44%). No statistically significant correlation was observed between hereditary hemorrhagic telangiectasia gene mutation and lesion type or lesion multiplicity.ConclusionsDepending on their imaging features, brain vascular malformations in hereditary hemorrhagic telangiectasia can be subdivided into brain AVF, nidus-type AVM, and capillary vascular malformations, with the latter being the most common phenotype in hereditary hemorrhagic telangiectasia. No genotype-phenotype correlation was observed among patients with this condition.

OBJECTIVE: This study sought to describe a single institutions experience treating arteriovenous malformations (AVMs) of the basal ganglia, thalamus, and insula in a multimodal fashion.

Brain arteriovenous malformations (bAVM) are tangles of abnormal, dilated vessels that directly shunt blood between the arteries and veins. The pathogenesis of bAVM is currently unknown. Patients with hereditary hemorrhagic telangiectasia (HHT) have a higher prevalence of bAVM than the general population. Animal models are important tools for dissecting the disease etiopathogenesis and for testing new therapies. Here, we introduce a method that induces the bAVM phenotype through regional deletion of activin-like kinase 1 (Alk1, the causal gene for HHT2) and vascular endothelial growth factor (VEGF) stimulation. © 2014 Springer Science+Business Media New York.

Prior studies have demonstrated associations between beta-adrenergic receptor (βAR) polymorphisms and left ventricular dysfunction-an important cause of allograft nonutilization for transplantation. We hypothesized that βAR polymorphisms predispose donor hearts to LV dysfunction after brain death. A total of 1043 organ donors managed from 2001-2006 were initially studied. The following βAR single nucleotide polymorphisms were genotyped: β1AR 1165C/G (Arg389Gly), β1AR 145A/G (Ser49Gly), β2AR 46G/A (Gly16Arg) and β2AR 79C/G (Gln27Glu). In multivariable regression analyses, the β2AR46 SNP was significantly associated with LV systolic dysfunction, with each minor allele additively decreasing the odds for LV ejection fraction 10 μg/kg/min of dopamine compared to those with the CC and GG genotypes. However, no significant associations were found between βAR SNPs and cardiac dysfunction in 364 donors managed from 2007-2008, perhaps due to changes in donor management, lack of power in this validation cohort, or the absence of a true association. βAR polymorphisms may be associated with cardiac dysfunction after brain death, but these relationships require further study in independent donor cohorts.

Background and purposeNGAVFs are rare vascular malformations usually presenting in infancy or childhood. We sought to identify clinical and angiographic predictors of clinical outcome for these lesions.Materials and methodsRetrospective review of a neurointerventional data base identified 386 pediatric patients with intracranial AVFs and AVMs, from which a cohort of 25 patients with NGAVF were selected for medical record and imaging analysis.ResultsNGAVFs constituted 7.3% of pediatric intracranial vascular lesions with a nondural arteriovenous shunt. Seven of 8 patients who presented in the first month of life had CHF and harbored large, complex fistulas with multiple sites of arteriovenous shunting. Single-hole fistulas predominated later in childhood and more frequently presented with seizures, hemorrhage, or focal neurologic deficits. More treatment procedures were performed in subjects presenting at ≤ 2 years of age compared with older children (median = 3 versus 2, P = .041), and in those harboring a multi-hole fistula versus those with a single-hole fistula (median = 3 versus 2, P = .003). Eighteen patients (72%) had complete posttreatment elimination of NGAVF shunting. Compared with patients presenting at >2 years of age, patients presenting in the first 2 years of life were more likely to have a multi-hole fistula (100% versus 25%, P = .0001) and to have a poor clinical outcome (54% versus 0%, P = .0052), defined as a pediatric mRS of ≥ 3.ConclusionsThe morbidity of NGAVF appears higher than previously reported despite a somewhat higher rate of angiographic cure. Poor clinical outcome occurred primarily in patients with multi-hole NGAVFs presenting at ≤ 2 years of age.

Bladder outlet obstruction (BOO) is common in males with benign prostate enlargement (BPE) and often presents with different lower urinary tract symptoms. Overactive bladder (OAB) has been reported to be related to BOO, although it can also be idiopathic. The storage symptoms of BOO are often similar to those of OAB. The etiology and pathophysiology of both BPE and OAB are multifactorial with metabolic syndrome known as one of the factors. As of today, transurethral prostate surgery remains the gold standard for treating BOO associated with BPE. Intradetrusor onabotulinumtoxinA (BoNT-A) injections have been shown to be effective in treating OAB. However, they are usually administered after transurethral prostate surgery. In view of the strong therapeutic effects of both surgery and injections, the feasibility of combining them in one setting to increase patient comfort, convenience, and possibly results while decreasing costs is appealing to physicians. However, patient safety and possible complications have to be considered. In this article, we review available studies of concurrent intradetrusor BoNT-A injections during transurethral prostate surgery. Although there is no definitive evidence supporting the concurrent use of intradetrusor BoNT-A during transurethral prostate surgery, there are no reports of increased complications too. Further large-scale randomized controlled trials would be necessary to validate the feasibility of combining the treatments in one setting and observe for possible complications., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Tzu Chi Medical Journal.)

Background: Ectopic kidney and median arcuate ligament syndrome are both rare conditions. The clinical presentation and diagnosis of these conditions are not well studied. There are no reports on the combination of these two rare conditions., Case Presentation: We report a 24-year-old woman with fever, dysuria, urinary frequency and left flank pain for two days. The primary diagnoses in the clinic were left acute pyelonephritis and left hydronephrosis due to throbbing pain in the left costovertebral angle and pyuria. However, further computed tomography showed right ectopic pelvic kidney, left renal pelvis dilatation without definite ureteral lesion, good bilateral renal contrast enhancement, and compression of the celiac axis due to obstruction by the median arcuate ligament. Chronic abdominal symptoms were reported by the patient after repeat history taking. The patient's condition was fully explained and discussed with her and her family, but they refused further therapy. After the acute pyelonephritis began improving, the patient was discharged for follow-up at our outpatient clinic., Conclusion: We present an extremely rare case of a combination of two rare conditions: ectopic kidney and median arcuate ligament syndrome. No study to date has reported on the relationship between the two diseases. Given the rarity of the two conditions, no evidence or even a hypothesis exists to explain the possible etiology of their combination. More reports are required to enhance the understanding of these rare conditions., (© 2023. The Author(s).)

Objectives: The aim is to evaluate the safety and efficacy of retrograde ureteral catheterization under local anesthesia in patients with urinary tract infections complicated by hydronephrosis caused by ureteral stone obstruction., Materials and Methods: From October 2020 to September 2021, a retrospective analysis of patients' medical records was performed. Records of past history, physical examination, laboratory tests, and imaging investigations were reviewed. Retrograde ureteric stent (RUS) was performed under local anesthesia using cystoscopes and guided by portable fluoroscopy. Real-time fluoroscopy was used to verify the double-J stent position and confirm a smooth process. The postoperative recovery and length of admission were also recorded., Results: A total of 14 patients with ureteral stone obstruction with infective hydronephrosis received 15 total emergency RUS procedures (one bilateral). Intraoperative findings, operation times, and infection signs were recorded and analyzed. All patients met systemic infection criteria, with a mean body temperature of 38.7°C ± 1.7°C. Leukocytosis was noted in 8 (57.1%) patients. Elevated C-reactive protein (8.5 ± 6.3 mg/L) and procalcitonin (24.1 ± 22.0 ng/mL) were found in 13 (92.9%) and 9 (64.3%) patients, respectively. Mean stone size was 8.5 ± 6.3 mm, mostly localized to the upper ureter (upper: 12; middle: 0; lower: 3). Mean operation time was 14.1 ± 4.3 min. After emergency drainage, all patients improved and were discharged after infection was controlled. The average length of admission was 6.2 ± 2.2 days., Conclusion: RUS under local anesthesia is safe and effective for treating infective hydronephrosis due to ureteral stone obstruction. A randomized controlled trial with a large sample remains necessary to validate these findings., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Tzu Chi Medical Journal.)

This study examined the interval between stone management and emergency percutaneous nephrostomy drainage in patients with infection and hydronephrosis secondary to ureteral calculi. A retrospective chart review was conducted for 88 patients treated for 94 stones enrolled in this study from 2005 to 2020. The mean age was 60.7 ± 15.2 years (range: 2-87 years). The average stone size was 1.51 ± 0.8 cm (range: 0.4-4 cm). The most common location was the upper ureter (n = 71, 75.5%), followed by the lower (n = 17, 18.1%) and middle (n = 6, 6.4%) ureter. The mean interval between percutaneous nephrostomy drainage and secondary stone management was 8.17 ± 11.6 days (range: 1-76 days). Most patients underwent operations within 1 week (n = 72, 81.8%). Abnormal white blood cell counts were found in most patients (58, 65.9%). Tachycardia was detected in 40 (45.5%) patients. Only 11 (12.5%) patients had fever upon emergency department arrival. Severe shock was reported in 6 (6.8%) patients. More than half of all patients (45, 51.1%) experienced acute kidney injury, and 37 (42%) patients had elevated C-reactive protein levels. Most patients (69, 73.4%) received ureteroscopic lithotripsy as stone management. Mean arterial pressure (MAP) was the only significant parameter (p = 0.016) affecting the operation interval, with MAP < 60 mmHg associated with longer operation intervals (16.2 days). The timing of stone surgery depends on clinician discretion and patient recovery., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Brain arteriovenous malformation (bAVM), characterized by tangled dysplastic vessels, is an important cause of intracranial hemorrhage in young adults, and its pathogenesis and progression are not fully understood. Patients with haploinsufficiency of transforming growth factor-β (TGF-β) receptors, activin receptor-like kinase 1 (ALK1) or endoglin (ENG) have a higher incidence of bAVM than the general population. However, bAVM does not develop effectively in mice with the same haploinsufficiency. The expression of integrin β8 subunit (ITGB8), another member in the TGF-β superfamily, is reduced in sporadic human bAVM. Brain angiogenic stimulation results at the capillary level of vascular malformation in adult Alk1 haploinsufficient (Alk1 +/- ) mice. We hypothesized that deletion of Itgb8 enhances bAVM development in adult Alk1 +/- mice. An adenoviral vector expressing Cre recombinase (Ad-Cre) was co-injected with an adeno-associated viral vector expressing vascular endothelial growth factor (AAV-VEGF) into the brain of Alk1 +/- ;Itgb8-floxed mice to induce focal Itgb8 gene deletion and angiogenesis. We showed that compared with Alk +/- mice (4.75 ± 1.38/mm 2 ), the Alk1 +/- ;Itgb8-deficient mice had more dysplastic vessels in the angiogenic foci (7.14 ± 0.68/mm 2 , P = 0.003). More severe hemorrhage was associated with dysplastic vessels in the brain of Itgb8-deleted Alk1 +/- , as evidenced by larger Prussian blue-positive areas (1278 ± 373 pixels/mm 2 vs. Alk1 +/-  : 320 ± 104 pixels/mm 2 ; P = 0.028). These data indicate that both Itgb8 and Alk1 are important in maintaining normal cerebral angiogenesis in response to VEGF. Itgb8 deficiency enhances the formation of dysplastic vessels and hemorrhage in Alk1 +/- mice., Competing Interests: The authors declare that they have no conflict of interest.

Background: The pathogenesis of sporadic brain arteriovenous malformations (BAVMs) remains unknown, but studies suggest a genetic component. We estimated the heritability of sporadic BAVM and performed a genome-wide association study (GWAS) to investigate association of common single nucleotide polymorphisms (SNPs) with risk of sporadic BAVM in the international, multicentre Genetics of Arteriovenous Malformation (GEN-AVM) consortium., Methods: The Caucasian discovery cohort included 515 BAVM cases and 1191 controls genotyped using Affymetrix genome-wide SNP arrays. Genotype data were imputed to 1000 Genomes Project data, and well-imputed SNPs (>0.01 minor allele frequency) were analysed for association with BAVM. 57 top BAVM-associated SNPs (51 SNPs with p<10(-05) or p<10(-04) in candidate pathway genes, and 6 candidate BAVM SNPs) were tested in a replication cohort including 608 BAVM cases and 744 controls., Results: The estimated heritability of BAVM was 17.6% (SE 8.9%, age and sex-adjusted p=0.015). None of the SNPs were significantly associated with BAVM in the replication cohort after correction for multiple testing. 6 SNPs had a nominal p<0.1 in the replication cohort and map to introns in EGFEM1P, SP4 and CDKAL1 or near JAG1 and BNC2. Of the 6 candidate SNPs, 2 in ACVRL1 and MMP3 had a nominal p<0.05 in the replication cohort., Conclusions: We performed the first GWAS of sporadic BAVM in the largest BAVM cohort assembled to date. No GWAS SNPs were replicated, suggesting that common SNPs do not contribute strongly to BAVM susceptibility. However, heritability estimates suggest a modest but significant genetic contribution., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Brain arteriovenous malformations (bAVMs) are vascular lesions that can cause significant morbidity and mortality, particularly when they bleed, i.e., rupture. Determining the risk of rupture for bAVMs is a crucial task to determine the most appropriate approach to patients with bAVM. Furthermore, patients who present with a hemorrhagic event also have a higher risk of subsequent hemorrhage. Determination of the hemorrhage risk and management strategy for incidentally discovered bAVMs still remains a controversial subject. In recent years, we have identified silent intralesional microhemorrhages (SIMs) as a possible risk factor for subsequent hemorrhage in patients with bAVMs. The principal aim of this study was to determine critical histological features that can be correlated with preoperative radioimaging findings, and allow better identification of patients with greater risk of adverse outcome. Here we provide a detailed descriptive analysis of the morphometric assessment of bAVMs in order to provide reproducible methodology that will aid in correlating preoperative radioimaging findings with histological features that may be significantly associated with increased risk of hemorrhage/rupture.

Hereditary hemorrhagic telangiectasia (HHT) is characterized by vascular malformations (VMs) and caused by mutations in TGFβ/BMP9 pathway genes, most commonly ENG or ACVRL1. Patients with HHT have diverse manifestations related to skin and mucosal telangiectases and organ VMs, including arteriovenous malformations (AVM). The clinical heterogeneity of HHT suggests a role for genetic modifiers. We hypothesized that the ACVRL1 c.314-35A>G and ENG c.207G>A polymorphisms, previously associated with sporadic brain AVM, are associated with organ VM in HHT. We genotyped these variants in 716 patients with HHT and evaluated association of genotype with presence of any organ VM, and specifically with brain VM, liver VM and pulmonary AVM, by multivariate logistic regression analyses stratified by HHT mutation. Among all patients with HHT, neither polymorphism was significantly associated with presence of any organ VM; ACVRL1 c.314-35A>G showed a trend toward association with pulmonary AVM (OR = 1.48, P = 0.062). ACVRL1 c.314-35A>G was significantly associated with any VM among patients with HHT with ENG (OR = 2.66, P = 0.022), but not ACVRL1 (OR = 0.79, P = 0.52) mutations. ACVRL1 c.314-35A>G was also associated with pulmonary AVM and liver VM among ENG mutation heterozygotes. There were no significant associations between ENG c.207G>A and any VM phenotype. These results suggest that common polymorphisms in HHT genes other than the mutated gene modulate phenotype severity of HHT disease, specifically presence of organ VM., (© 2015 Wiley Periodicals, Inc.)

Background and Purpose: Hereditary hemorrhagic telangiectasia (HHT) is a systemic disease characterized by mucocutaneous telangiectasias, epistaxis, and arteriovenous malformations (AVMs). Intracranial hemorrhage (ICH) rates in this population are not well described. We report ICH rates and characteristics in HHT patients with brain AVMs (HHT-BAVMs)., Methods: We studied the first 153 HHT-BAVM patients with follow-up data enrolled in the Brain Vascular Malformation Consortium HHT Project. We estimated ICH rates after BAVM diagnosis., Results: The majority of patients were women (58%) and white (98%). The mean age at BAVM diagnosis was 31±19 years (range, 0-70), with 61% of cases diagnosed on asymptomatic screening. Overall, 14% presented with ICH; among symptomatic cases, 37% presented ruptured. During 493 patient-years of follow-up, 5 ICH events occurred yielding a rate of 1.02% per year (95% confidence interval, 0.42-2.44%). ICH-free survival differed significantly by ICH presentation (P=0.003); ruptured cases had a higher ICH rate (10.07%; 95% confidence interval, 3.25-31.21%) than unruptured cases (0.43%; 95% confidence interval, 0.11-1.73%)., Conclusions: Patients with HHT-BAVM who present with hemorrhage are at a higher risk for rehemorrhage compared with patients with BAVM detected presymptomatically., (© 2015 American Heart Association, Inc.)

Object: Resection is an appealing therapy for brain arteriovenous malformations (AVMs) because of its high cure rate, low complication rate, and immediacy, and has become the first-line therapy for many AVMs. To clarify safety, efficacy, and outcomes associated with AVM resection in the aftermath of A Randomized Trial of Unruptured Brain AVMs (ARUBA), the authors reviewed their experience with low-grade AVMs-the most favorable AVMs for surgery and the ones most likely to have been selected for treatment outside of ARUBA's randomization process., Methods: A prospective AVM registry was searched to identify patients with Spetzler-Martin Grade I and II AVMs treated using resection during a 16-year period., Results: Of the 232 surgical patients included, 120 (52%) presented with hemorrhage, 33% had Spetzler-Martin Grade I, and 67% had Grade II AVMs. Overall, 99 patients (43%) underwent preoperative embolization, with unruptured AVMs embolized more often than ruptured AVMs. AVM resection was accomplished in all patients and confirmed angiographically in 218 patients (94%). There were no deaths among patients with unruptured AVMs. Good outcomes (modified Rankin Scale [mRS] score 0-1) were found in 78% of patients, with 97% improved or unchanged from their preoperative mRS scores. Patients with unruptured AVMs had better functional outcomes (91% good outcome vs 65% in the ruptured group, p = 0.0008), while relative outcomes were equivalent (98% improved/unchanged in patients with ruptured AVMs vs 96% in patients with unruptured AVMs)., Conclusions: Surgery should be regarded as the "gold standard" therapy for the majority of low-grade AVMs, utilizing conservative embolization as a preoperative adjunct. High surgical cure rates and excellent functional outcomes in patients with both ruptured and unruptured AVMs support a dominant surgical posture for low-grade AVMS, with radiosurgery reserved for risky AVMs in deep, inaccessible, and highly eloquent locations. Despite the technological advances in endovascular and radiosurgical therapy, surgery still offers the best cure rate, lowest risk profile, and greatest protection against hemorrhage for low-grade AVMs. ARUBA results are influenced by a low randomization rate, bias toward nonsurgical therapies, a shortage of surgical expertise, a lower rate of complete AVM obliteration, a higher rate of delayed hemorrhage, and short study duration. Another randomized trial is needed to reestablish the role of surgery in unruptured AVM management.

The understanding of the pathophysiology of brain arteriovenous malformations and arteriovenous fistulas has improved thanks to animal models. A rat model creating an artificial fistula between the common carotid artery (CCA) and the external jugular vein (EJV) has been widely described and proved technically feasible. This construct provokes a consistent cerebral venous hypertension (CVH), and therefore has helped studying the contribution of venous hypertension to formation, clinical symptoms, and prognosis of brain AVMs and dural AVFs. Equivalent mice models have been only scarcely described and have shown trouble with stenosis of the fistula. An established murine model would allow the study of not only pathophysiology but also potential genetic therapies for these cerebrovascular diseases. We present a model of arteriovenous fistula that produces a durable intracranial venous hypertension in the mouse. Microsurgical anastomosis of the murine CCA and EJV can be difficult due to diminutive anatomy and frequently result in a non-patent fistula. In this step-by-step protocol we address all the important challenges encountered during this procedure. Avoiding excessive retraction of the vein during the exposure, using 11-0 sutures instead of 10-0, and making a carefully planned end-to-side anastomosis are some of the critical steps. Although this method requires advanced microsurgical skills and a longer learning curve that the equivalent in the rat, it can be consistently developed. This novel model has been designed to integrate transgenic mouse techniques with a previously well-established experimental system that has proved useful to study brain AVMs and dural AVFs. By opening the possibility of using transgenic mice, a broader spectrum of valid models can be achieved and genetic treatments can also be tested. The experimental construct could also be further adapted to the study of other cerebrovascular diseases related with venous hypertension such as migraine, transient global amnesia, transient monocular blindness, etc.

Objective: To investigate whether previously reported 9p21.3 single nucleotide polymorphisms (SNPs) are associated with risk of brain arteriovenous malformations (BAVM), which often have accompanying arterial aneurysms. Common variants in the 9p21.3 locus have been reported to be associated with multiple cardiovascular phenotypes, including coronary artery disease and intracranial aneurysms (rs10757278 and rs1333040)., Methods: We used data from 338 BAVM cases participating in the University of California, San Francisco (UCSF)-Kaiser Brain AVM Study Project and 504 healthy controls to evaluate genotypes for seven common SNPs (minor allele frequency>0.05) that were imputed using 1000 Genomes Phase 1 European data (R(2)>0.87). Association with BAVM was tested using logistic regression adjusting for age, sex and the top three principal components of ancestry. Subgroup analysis included 205 BAVM cases with aneurysm data: 74 BAVM with aneurysm versus 504 controls and 131 BAVM without aneurysm versus 504 controls., Results: We observed suggestive association with BAVM and rs10757278-G (OR=1.23, 95% CI 0.99 to 1.53, p=0.064) and rs1333040-T (OR=1.27, 95% CI 1.01 to 1.58, p=0.04). For rs10757278-G, the association was stronger in BAVM cases with aneurysm (OR=1.52, 95% CI 1.03 to 2.22, p=0.032) than in BAVM without aneurysm (OR=0.98, 95% CI 0.72 to 1.34, p=0.91). Similar patterns of effects were observed for rs1333040 and for other SNPs in linkage disequilibrium (r(2)>0.8) with rs10757278., Conclusions: Common 9p21.3 variants showed similar effect sizes for association with BAVM as previously reported for aneurysmal disease. The association with BAVM appears to be explained by known associations with aneurysms, suggesting that BAVM-associated aneurysms share similar vascular pathology mechanisms with other aneurysm types., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)