Embolization of brain arteriovenous malformations with squid co-polymer embolic material:Initial experience

Objective:To analyze the safety and effectiveness of the ethylene-vinyl alcohol copolymer(EVOH)liquid embolic agent Squid(Emboflu,Switzerland)for the treatment of brain arteriovenous malformations.Materials and procedures:Between April 2015 and July 2017,46 embolization treatments for brain arteriovenous malformations(BAVM)were performed in 25 patients using two Squid formulations(18 and 12).Six female and 19 male patients with a mean age of 34 years(range,9–62 years)were included.A total of 46 procedures were performed.The BAVMs were classified as Spetzler-Martin gradeⅡin 4 procedures,Ⅲin 27 procedures,and 1V in 15 procedures.Among the 25 patients,15 presented with hemorrhage,5 with seizures,and 5 with headache and neurology.The BAVMs were located in the temporal lobe in 5 patients,parietal lobe in 7 patients,frontal lobe in 3 patients,posterior fossa in 6 patients,basal ganglia in 3 patients,and parasagittal lobe in 1 patient.Results:The obliteration rate of the BAVMs ranged from 10%to 100%,with a mean of 33%.Most patients underwent their first or second embolization procedure.Four patients(8%)developed intracranial bleeding post procedure,with one death(2%).One patient(2%)experienced a seizure during the procedure;however,no intracranial bleeding was observed.Seven patients(15%)experienced perforations during catheter manipulation.One case(2%)of fractured catheter was recorded,but no significant complications were observed.The average volume of copolymer injected was 0.6 ml per nidus.Thirteen procedures used the Squid-12 formulation,29 procedures used the Squid-18 formulation,and 3 procedures used a combination of Squid-12 and-18 formulations.Conclusion:Squid is a safe and effective embolic agent for treating BAVMs.

Delayed versus immediate intervention of ruptured brain arteriovenous malformations:A case report

BACKGROUND Brain arteriovenous malformations(bAVMs)remains one of the most prevalent causes of intracranial hemorrhage and stroke-like syndromes in the young adult population.Although it has been agreed upon that definitive treatment using either single or multi-modal approach is warranted for successful bAVM management,much debate still revolves regarding the optimal timing of definitive treatment.CASE SUMMARY In this report,we present a case of delayed,definitive endovascular treatment for ruptured bAVM in a 21-year-old female,3 mo post-ictus.The bAVM,with a left pericallosal feeding artery and cortical draining veins,was successfully obliterated through embolization using the Onyx 18.On follow-up the patient has recommenced her daily activities and experiences only mild occasional headaches with mild motor deficits.The report leads to our review on an important issue regarding the optimal timing of ruptured bAVM definitive management and bring forward the current evidence available on delayed vs immediate definitive bAVM intervention.We also highlight current issues that need to be addressed for clearer guidelines on definitive therapy initiation.CONCLUSION Current treatment paradigms of ruptured bAVM remains elusive,with substantial heterogeneity in the current literature.A consensus on the definition of“acute”vs“delayed”,management goal,follow-up length and outcome parameters are required to support formation of a clear paradigm.

Understanding the role of miRNAs in the pathogenesis of brain arteriovenous malformations

Brain arteriovenous malformations(AVMs)are abnormal vessels that are prone to rupture,ausing life threatening intracerebral hemorrhage(ICH).Understanding the moleaular basis of pathogenesis,timely diagnosis,and treatment of brain AVMs are some of the urgent problems in neur osur gery.MiaoRNAs(miRNAs)are small endogenous RNAs that regulate gene-epression psttranscriptionally.MiRNAs are involved in almost all biological procsss,induding cell proliferation,apoptosis,and cell differentiation.Recent studies have shown that miRNAs an be involved in brain AVMs formation and rupture.There are also extracellular forms of miRNAs.Circulating miRNAs have been detected in the blood circulation and other body fluids.Owing to their stability and resistance to endogenous RNase activity,circulating miRNAs have been proposed as diagnostic and prognostic biomarkers for various diseases,such as tumors,cardiovascular and autoimmune diseases.In this review,we summarized the role of some miRNAs in brain AVMs pathogenesis and discussed their potential cdinical appliation as non-invasive biomarkers.

Embolization of brain arteriovenous malformations with ethylene vinyl alcohol copolymer： technical aspects

Background Endovascular therapy plays an important role in the treatment of brain arteriovenous malformations （BAVMs）. Ethylene vinyl alcohol copolymer （Onyx） is a novel liquid embolic material. This study aimed to summarize our experience of using Onyx for embolization of BAVMs with the focus on embolization technique. Methods From September 2003 to November 2007, 115 patients （43 women and 72 men, with a mean age of 29 years） with BAVMs were endovascularly treated with Onyx in our department. The following features of all AVMs were evaluated prior to treatment： type of nidus and shunt, draining veins, and feeding arteries. A total of 196 endovascular procedures were performed. Results The course of endovascular treatment was completed in 88 patients. Additional sessions were planned in 27 patients. Of the 88 patients, total occlusion was obtained in 23 patients （26.1%）, near-total （〉80% of the original volume） occlusion was obtained in 35 patients （39.8%） and partial occlusion （〈80% of the original volume） was obtained in 30 patients （34.1%） using embolization as the sole therapeutic technique. Mean volume reduction was 72% （range 30%-100%） in 115 patients. Thirty four patients （38.6%, 34/88） underwent radiosurgical treatment. Additional embolization sessions were planned in 27 patients. Complications occurred in 19 patients （16.5%, 19/115）, leading to death in one patient （mortality 0.9%） and permanent disabling in 3 patients （morbidity 2.6%）. Conclusions Onyx was shown to be feasible and safe for embolization of BAVMs. Proper use of the Onyx injection technique largely improved the endovascular treatment of BAVMs. Large AVMs can be adequately reduced in size through the use of additional treatment.

Distinctive distribution of lymphocytes in unruptured and previously untreated brain arteriovenous malformation

Aim:To test the hypothesis that lymphocyte infiltration in brain arteriovenous malformation(bAVM)is not associated with iron deposition(indicator of micro-hemorrhage).Methods:Sections of unruptured,previously untreated bAVM specimens(n=19)were stained immunohistochemically for T-lymphocytes(CD3+),B-lymphocytes(CD20+),plasma cells(CD138+)and macrophages(CD68+).Iron deposition was assessed by hematoxylin and eosin and Prussian blue stains.Superficial temporal arteries(STA)were used as control.Results:Both T-lymphocytes and macrophages were present in unruptured,previously untreated bAVM specimens,whereas few B cells and plasma cells were detected.Iron deposition was detected in 8 specimens(42%;95%confidence intervals=20-67%).The samples with iron deposition tended to have more macrophages than those without(666±313 vs.478±174 cells/mm2;P=0.11).T-cells were clustered on the luminal side of the endothelial surface,on the vessel-wall,and in the perivascular regions.There was no correlation between T-lymphocyte load and iron deposition(P=0.88).No macrophages and lymphocytes were detected in STA controls.Conclusion:T-lymphocytes were present in bAVM specimens.Unlike macrophages,the load and location of T-lymphocytes were not associated with iron deposition,suggesting the possibility of an independent cell-mediated immunological mechanism in bAVM pathogenesis.

Application of Principle Component Analysis and Logistic Regression in Analyzing miRNA Markers of Brain Arteriovenous Malformation

Brain arteriovenous malformation(BAVM) is frequently described as vascular malformation. Although computer tomography(CT), magnetic resonance imaging(MRI) and angiography can clearly detect lesions, there are no diagnostic biological markers of BAVM available. Current study demonstrated that micro RNA(mi RNA)showed a feasible marker for vascular disease. To find key correlations between these mi RNAs and the onset of BAVM, we carried out chip analysis of serum mi RNAs by identifying 18 potential markers of BAVM. We then constructed a principle component analysis and logistic regression(PCA-LR) model to analyze the 18 mi RNAs collected from 77 patients. Another 9 independent samples were used to test the resulting model. The results showed that mi RNAs hsa-mir-126-3p and hsa-mir-140 are important protective factors, while hsa-mir-338 is a dominating risk factor, all of which have stronger correlation with BAVM than others. We also compared the testing results using PCA-LR model with those using LR model. The comparison revealed that PCA-LR model is better in predicting the disease.

Human brain arteriovenous malformation:an analysis of differential expressed genes

Background:Much still remains unknown about the pathogenesis of brain arteriovenous malformations (AVMs).Previous studies have revealed the abnormal expression of various angiogenesis-related genes in AVMs.To further understand this disease,we sought to identify genes differently expressed in AVMs by means of the gene microarray technique.Methods:Nine AVMs specimen and nine samples of normal vessels are collected.Total RNA isolated from these specimen is hybridized with Oligonucleotide array and gene analysis was conducted.Analyzing data with the help of significance analysis of microarrays (SAM) and a free web-based molecular annotation system 3.0 (MAS 3.0).Results:The SAM method identify 37 gene significantly up-regulated and 10 genes down-regulated in AVMs.Conclusions:Among those genes,VACN,SPARK and ARHGAP18 seem to play a facilitating role during the genesis of AVMs.Multiple pathways,as MAPK pathway,may also be involved.