Cases Of Brain Arteriovenous Malformations Research Articles

Case Series: Gamma Knife Radiosurgery in Brain Arteriovenous, Is It Good Enough?

Highlight: Brain AVMs are a special concern due to their inherent high risk of bleeding. Gamma Knife radiosurgery (GKRS), as one of the modality treatments, is intended to induce progressive occlusion of an AVM by using high-dose targeted radiation The result of Gamma Knife radiosurgery (GKRS) can be full obliteration, with complications because adverse radiation effects. ABSTRACT Introduction: Brain arteriovenous malformations (AVMs) are relatively uncommon. Gamma Knife radiosurgery (GKRS) is one of the AVM’s therapeutic interventions, with both advantages and disadvantages. Here, we report the results of two cases of brain AVM after GKRS. Cases: Case 1: Non-contrast head MRI imaging of a 45-year-old man with persistent left-sided headaches revealed a 1.4 x 2.5 x 2.28 cm AVM nidus in the left parasagittal frontal lobe. After a single GKRS with a 25-Gy marginal dose, the MRI contrast showed complete obliteration, with persistent perifocal edema and headache. Case 2: A 25-year-old woman with a history of generalized seizures. The angiograms revealed an AVM nidus with a diameter of 32.58 mm on her right posterior frontal lobe. After a single GKRS with a 22-Gy marginal dose, the MRI contrast showed full obliteration with large edema. The patient had presented with hemiparesis. Conclusion: In these cases, the results after GKRS were full obliteration with complications of edema, headache, and hemiparesis. We also found that complications appear to be associated with adverse radiation effects.

Real-Time MRI Monitoring of Liquid Embolic Agent (Onyx) Injection in a Swine Arteriovenous Malformation Model.

The paradigm is gradually shifting, with radiosurgery and endovascular embolization being increasingly chosen over surgical resection in the selected cases of brain arteriovenous malformations. Routinely used X-ray monitoring of liquid embolic infusion has very good spatial and temporal resolution but is not without significant drawbacks regarding poor visualization of the complex AVM angioarchitecture, especially after many embolizations in the past and therefore limiting the technical ability of the embocure-total occlusion of the feeding arteries, nidus, and draining veins. The purpose of this study was to evaluate the use of real-time MRI guidance in endovascular embolization with Onyx (instead of X-ray) in a single swine rete mirabile (RM) AVM model in order to provide the scaffolding for the real-time MRI guidance method. Onyx propagation was observed in real-time dynamic GE-EPI scan with initial ipsilateral RM filling followed by main cerebral arterial branch distribution. The relatively bright signal within RM and the brain prior to Onyx injection provided a good background for the dark, low signal of the embolic agent spreading in rete mirabile and brain arteries. X-ray picture confirmed Onyx cast distribution at the end of the procedure. In this initial experience, real-time MRI seems to be a promising method that may significantly improve liquid embolic agent infusion monitoring in the future, although requiring further development before clinical use.

KRAS G12D or G12V Mutation in Human Brain Arteriovenous Malformations

Brain arteriovenous malformations (BAVMs) are vascular malformations composed of tangles of abnormally developed vasculature without capillaries. Abnormal shunting of arteries and veins is formed, resulting in high-pressure vascular channels, which potentially lead to rupture. BAVMs are generally considered a congenital disorder. But clinical evidence regarding involution, regrowth, and de novo formation argue against the static condition of this disease. Recently, the presence of the somatic activating KRAS mutations in more than half of BAVM cases was reported, suggesting the role of KRAS function in the pathogenesis. KRAS mutation in codon35 (G→A, G12D; G→T, G12V) was examined by a digital polymerase chain reaction analysis using genome purified from paraffin-embedded slides of human BAVMs. We also examined protein expression of KRAS G12D in lesions to corroborate results from digital polymerase chain reaction analysis. We detected codon35 G→A mutation in 15 (39.5%) among 38 samples and codon35 G→T mutation in 10 (27.0%) among 37 samples we could assess mutations. There were no samples positive for both codon35 G→A and G→T mutation. The ratio of codon35 G→A mutation ranged from 0.60% to 12.28% and that of G→T was from 1.20% to 8.99%. We next examined protein expression of KRAS G12D in BAVM lesions in immunohistochemistry. A KRAS G12D mutant was detected mainly in endothelial cells of dilated vessels in lesions. KRAS mutations in codon35 were detected in about two thirds of specimens examined. KRAS function may actively contribute to the pathobiology of BAVM and can become a therapeutic target.

High Grade Incidental Brain Arteriovenous Malformation

Brain arteriovenous malformations (BAVM) are congenital vascular lesions consisting of direct arterial to venous connection without a capillary network. They occur in 0.1% of the population, most commonly in the supratentorial region. Aneurysm, intracranial hemorrhage and stroke are the major complications. We present 2 cases two cases of high grade incidental BAVM. A thorough evaluation of the lesion and the risks of surgical intervention determine the appropriate management.

Genome-wide association study of sporadic brain arteriovenous malformations

BackgroundThe 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)...

Common variants on 9p21.3 are associated with brain arteriovenous malformations with accompanying arterial aneurysms

ObjectiveTo 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...

A Genome-Wide Investigation of Copy Number Variation in Patients with Sporadic Brain Arteriovenous Malformation

BackgroundBrain arteriovenous malformations (BAVM) are clusters of abnormal blood vessels, with shunting of blood from the arterial to venous circulation and a high risk of rupture and intracranial hemorrhage. Most BAVMs are sporadic, but also occur in patients with Hereditary Hemorrhagic Telangiectasia, a Mendelian disorder caused by mutations in genes in the transforming growth factor beta (TGFβ) signaling pathway.MethodsTo investigate whether copy number variations (CNVs) contribute to risk of sporadic BAVM, we performed a genome-wide association study in 371 sporadic BAVM cases and 563 healthy controls, all Caucasian. Cases and controls were genotyped using the Affymetrix 6.0 array. CNVs were called using the PennCNV and Birdsuite algorithms and analyzed via segment-based and gene-based approaches. Common and rare CNVs were evaluated for association with BAVM.ResultsA CNV region on 1p36.13, containing the neuroblastoma breakpoint family, member 1 gene (NBPF1), was significantly enriched with duplications in BAVM cases compared to controls (P = 2.2×10−9); NBPF1 was also significantly associated with BAVM in gene-based analysis using both PennCNV and Birdsuite. We experimentally validated the 1p36.13 duplication; however, the association did not replicate in an independent cohort of 184 sporadic BAVM cases and 182 controls (OR = 0.81, P = 0.8). Rare CNV analysis did not identify genes significantly associated with BAVM.ConclusionWe did not identify common CNVs associated with sporadic BAVM that replicated in an independent cohort. Replication in larger cohorts is required to elucidate the possible role of common or rare CNVs in BAVM pathogenesis.

Abstract TMP30: Genetic Variants on 9p21.3 are Associated with Brain Arteriovenous Malformations with Associated Arterial Aneurysms

Background: The 9p21.3 locus is associated with risk of coronary artery disease and intracranial and abdominal aortic aneurysms (rs10757278). We investigated whether previously reported 9p21.3 SNPs are associated with risk of brain arteriovenous malformations (BAVM), which often have accompanying flow-related arterial aneurysms. Methods: Genotypes for 6 SNPs, including rs10757278, were imputed using 1000 Genomes Phase 1 CEU data (R2>0.9). We tested for association using logistic regression of imputed dosages adjusting for age, sex and top 3 components of ancestry in 338 BAVM cases vs. 504 controls. Of these, 205 cases had aneurysm data available for subgroup analysis: (a) 74 BAVM+(with) aneurysm cases vs. 504 controls, and (b) 131 BAVM-(without) aneurysm cases vs. 504 controls. Results: rs10757278-G was marginally associated with increased risk of BAVM (OR=1.23, 95% CI=0.99-1.53, P=0.064). Compared to controls, the association was stronger in BAVM+aneurysm (OR=1.52, 95% CI=1.03-2.22, P=0.032) than in BAVM-aneurysm cases (OR=0.98, 95% CI=0.72-1.34, P=0.91). Similar effects were observed for other SNPs in linkage disequilibrium (r2>0.8) with rs10757278 (Table). Conclusion: Common 9p21.3 variants showed similar effect sizes as previously reported for aneurysmal disease. The SNP association with BAVM appears to be explained by known association with aneurysms, suggesting that BAVM associated aneurysms share similar vascular pathology mechanisms.

Polymorphisms in ACVRL1 and Endoglin Genes are Not Associated with Sporadic and HHT-Related Brain AVMs in Dutch Patients

We aimed to replicate the association of the IVS3-35A>G polymorphism in the activin receptor-like kinase (ACVRL) 1 gene and the 207G>A polymorphism in the endoglin (ENG) gene with sporadic brain arteriovenous malformations (BAVM) in Dutch BAVM patients. In addition, we assessed whether these polymorphisms contribute to the risk of BAVM in patients with hereditary haemorrhagic telangiectasia type 1 (HHT1). We genotyped 143 Dutch sporadic BAVM patients and 360 healthy volunteers for four variants in the ACVRL1 gene including IVS3-35A>G and two variants in the ENG gene including 207G>A. Differences in allele and genotype frequencies between sporadic BAVM patients and controls and their combined effect were analysed with a likelihood ratio test. Furthermore, we compared the allele and genotype frequencies between 24 HHT1 patients with a BAVM with those of a relative with HHT1 without a BAVM in a matched pair analysis using Wilcoxon signed rank test. No significant differences in allele frequency were found between sporadic BAVM cases and controls or between HHT1 patients with and without BAVM for any of the polymorphisms or the combination of ACVRL1 and ENG polymorphisms. Meta-analysis of the current and the two previous studies for the ACVRL1 IVS3-35A polymorphism showed a persisting association between the ACVRL1 IVS3-35A polymorphism and risk of sporadic BAVM (odds ratio, 1.86; 95% CI: 1.32-2.61, p<0.001). We did not replicate the previously found association between a polymorphism in ACVRL1 IVS3-35A>G and BAVM in Dutch patients. However, meta-analysis did not rule out a possible effect.

Angiopoietin-Like 4 (ANGPTL4) Gene Polymorphisms and Risk of Brain Arteriovenous Malformations

Background: Brain arteriovenous malformations (BAVM) are high-flow vascular lesions prone to intracranial hemorrhage (ICH). Abnormal angiogenesis is a key characteristic of BAVM tissue. Angiopoietin-like 4 (ANGPTL4), a secreted glycoprotein, is thought to be involved in angiogenesis and required for proper postnatal blood vessel partitioning. We investigated whether common single nucleotide polymorphisms (SNPs) in ANGPTL4 were associated with risk of BAVM or ICH. Methods and Results: We conducted a case-control study of 216 Caucasian BAVM cases and 246 healthy controls, and a secondary case-only analysis, comparing 83 ruptured (ICH) with 133 unruptured BAVM cases at presentation. Four tagSNPs in ANGPTL4 captured variation over a 10-kb region (rs2278236, rs1044250, rs11672433, and rs1808536) and were tested for association with BAVM or ICH. The minor allele (A) of rs11672433 (exon 6, Pro389Pro) was associated with an increased risk of BAVM (p = 0.006), which persisted after adjusting for multiple comparisons (p = 0.03). After adjustments for age and sex, carriers of the minor allele (A) remained at higher risk for BAVM compared to noncarriers (odds ratio, OR = 1.56; 95% confidence interval, CI = 1.01–2.41; p = 0.046) and risk of BAVM was increased with increasing copy of the minor A allele (OR = 1.49, 95% CI = 1.03–2.15; p_trend = 0.03). Five common haplotypes (frequency >1%) were inferred; overall haplotype distribution differed between BAVM cases and controls (χ² = 12.2, d.f. = 4, p = 0.02). Neither SNPs (p > 0.05) nor haplotype distribution (χ² = 1.1, d.f. = 4, p = 0.89) were associated with risk of ICH among BAVM cases. Conclusion: A synonymous SNP in ANGPTL4 and haplotypes carrying it are associated with risk of BAVM but not with ICH presentation in BAVM cases.

Embolization of Residual Fistula Following Stereotactic Radiosurgery in Cerebral Arteriovenous Malformations

Treatment of brain arteriovenous malformations (BAVMs) often requires a multitechnique approach. We present 2 cases of BAVM, in which initial stereotactic radiosurgery (SRS) was successful in obliterating a significant volume of the nidus. At follow-up angiography, residual fistulas were identified and selectively embolized; this procedure cured the lesions. Many series describe initial embolization to reduce the nidal volume followed by SRS to the remnant. The described cases highlight the value of primary radiosurgery followed by selective fistula embolization.

Brain Arteriovenous Malformations

Although intracranial hemorrhages,1 interest in brain arteriovenous malformations (BAVMs) is expanding from its origins as a neuropathologic curiosity to the treatment-oriented specialties of neurological surgery, interventional neuroradiology, radiosurgery/therapy, and clinical neurology, and is even emerging as a subject in neuroepidemiology. Recent insights from uncontrolled series: argue for some genetic derangements in the origin of some of the lesions2,3; have revised some issues of pathophysiology4–7; track the risk of hemorrhage over time8; suggest the risk for hemorrhage can be predicted by vascular factors discoverable by noninvasive or minimally invasive imaging9,10; indicate many initial hemorrhage syndromes are mild,11 more so than that caused by non-BAVM parenchymal or aneurysmal subarachnoid hemorrhages12; have reassessed the outcomes from intervention in a variety of forms after initial hemorrhage13–15; raise questions concerning the safety and …

Long-Term Hemorrhage Risk in Children Versus Adults With Brain Arteriovenous Malformations

Children with brain arteriovenous malformations (BAVMs) are said to be at higher risk for intracranial hemorrhage (ICH) than adults. Although this notion affects treatment decisions, the evidence to support this claim is limited. To compare the risk of ICH in children versus adults with BAVM, we studied all cases of BAVM evaluated at the University of California, San Francisco (January 2000 to December 2004; n=400) and Kaiser Permanente Northern California (January 1993 to December 2004; n=819). In Kaplan-Meier survival analyses, the index date was the date of initial BAVM detection; cases were censored at time of subsequent ICH (the primary outcome, defined as ICH after initial presentation), first BAVM treatment, or loss to follow-up. Cox proportional hazards models included childhood presentation (<20 years old), hemorrhagic presentation, and other potential confounders. Our study included 996 person-years of follow-up in the childhood presentation group and 3260 in the adult presentation group. In the unadjusted survival analysis, the subsequent ICH rates were similar for the 2 age groups (average annual rate 2.0% for children; 2.2% for adults; P=0.82 by log-rank test). BAVMs in childhood were more likely to present initially with ICH (P<0.001). After adjustment for presentation in the multivariate model, subsequent ICH rates were lower in children (hazard ratio, 0.10; 95% CI, 0.01 to 0.86; P=0.036). Children with BAVMs do not appear to be at increased risk for a subsequent ICH compared with adults, and may even be relatively protected. Confounding by hemorrhagic presentation should be considered in any study comparing BAVM hemorrhage rates in children versus adults.

Endovascular Treatment of Brain Arteriovenous Malformations

In spite of major advances in the endovascular tools and a better understanding of the disease, the treatment of brain arteriovenous malformations remains difficult. Many aspects of the disease are still unpredictable, and the therapeutic approach frequently depends on the experience and skill of the teams involved. Different approaches - neuro/radiosurgical or endovascular, are possible. A consensus on the best treatment has not yet been reached and to date a combined treatment is probably the best possible choice for the majority of the patients, avoiding overestimation of a single technique. We report our experience in the endovascular treatment of 44 consecutive cases of brain arteriovenous malformations.