Arteriovenous Malformations Patients Research Articles

Comparing health-related quality of life in modified Rankin Scale grades: 15D results from 323 patients with brain arteriovenous malformation and population controls

BackgroundWe wanted to understand how patients with different modified Rankin Scale (mRS) grades differ regarding their health-related quality of life (HRQoL) and how this affects the interpretation and dichotomization of the grade.MethodsIn 2016, all adult patients in our brain arteriovenous malformation (AVM) database (n = 432) were asked to fill in mailed letters including a questionnaire about self-sufficiency and lifestyle and the 15D HRQoL questionnaire. The follow-up mRS was defined in 2016 using the electronic patient registry and the questionnaire data. The 15D profiles of each mRS grade were compared to those of the general population and to each other, using ANCOVA with age and sex standardization.ResultsPatients in mRS 0 (mean 15D score = 0.954 ± 0.060) had significantly better HRQoL than the general population (mean = 0.927 ± 0.028), p < 0.0001, whereas patients in mRS 1–4 had worse HRQoL than the general population, p < 0.0001. Patients in mRS 1 (mean = 0.844 ± 0.100) and mRS 2 (mean = 0.838 ± 0.107) had a similar HRQoL. In the recently published AVM research, the most commonly used cut points for mRS dichotomization were between mRS 1 and 2 and between mRS 2 and 3.ConclusionsUsing 15D, we were able to find significant differences in the HRQoL between mRS 0 and mRS 1 AVM patients, against the recent findings on stroke patients using EQ-5D in their analyses. Although the dichotomization cut point is commonly set between mRS 1 and 2, patients in these grades had a similar HRQoL and a decreased ability to continue their premorbid lifestyle, in contrast to patients in mRS 0.

Oscillatory shear stress promotes angiogenic effects in arteriovenous malformations endothelial cells

BackgroundVascular endothelial cells (ECs) are subject to continuous shear stress due to blood circulation. Mechanical stress due to high shear flow can also cause arteriovenous malformation (AVM) when ECs respond hyper-sensitively to shear flow. This study was conducted to test the hypothesis that angiogenesis could be promoted in response to mechanical stress via regulation of pro-angiogenic factors in AVM cells.MethodsECs were extracted from the tissue samples from six AVM patients and six normal patients. Shear stress at 7 dynes/cm2 were applied for 24 h. Before and after application of shear stress to each group, RT-PCR was performed to access the expression levels of angiopoietin2(AGP2), aquaporin1(AQP1) and TGFβR1. Immunofluorescences was also performed to evaluate the level of protein expressions.ResultsIn both normal and AVM tissues, AGP2 and TGFβR1 under the shear stress showed increased expression in the ECs compared to the non-sheared samples. When AVMs and normal arterial vasculature were compared, the expression levels of both AGP2 and TGFβR1 in AVMs were higher when compared to normal arterial vasculature with or without shear stress. Immunofluorescence-based protein analysis also confirmed shear-induced AGP2 and TGFβR1 in both samples of normal and AVM patients.ConclusionsAVMs exhibited higher sensitivity to shear stress by producing higher expressions of some marked genes and proteins that regulate the endothelial functions upon exposure to shear stress. While the physiological mechanism for AVMs remain elusive, our study shows the plausibility of physical stress imposed by the shearing flow can cause the occurrence of AVMs.

Abstract MP7: Multicenter Study of Intracranial Hemorrhage and Death Risk and Predictors in the Untreated Course of Brain Arteriovenous Malformation Patients

Background: Accurate and reliable models of intracranial hemorrhage (ICH) risk in the untreated course of brain arteriovenous malformation (BAVM) patients are needed to help weigh the risk-benefit of treatment. We present preliminary estimates of rates and risk factors for ICH or death in the Multicenter AVM Research Study (MARS), which is the largest individual patient data meta-analysis (IPDMA) of cohort studies of unruptured BAVM. Methods: Longitudinal data from 9 cohorts comprising 2,839 unruptured BAVM at time of diagnosis were included: UCSF (n=557), Macquarie (n=462), Kaiser Permanente Northern California (n=354), Columbia (n=335), Barrow Neurological Institute (n=324), Tiantan Hospital (n=303), Mayo Clinic-Rochester (n=244), Scottish Intracranial Vascular Malformation Study (n=194), and Toronto Western Hospital (n=66). Clinical and angiographic data were collected using standardized definitions across cohorts. Cox proportional hazards analysis of time-to-event (ICH or death) in the untreated course after diagnosis was performed, censoring at first treatment or last visit. Baseline hazard rates were stratified by cohort to account for different rates and follow-up times. Results: The combined cohort was 49% female, 72% white race, and 17% Hispanic ethnicity; mean age at diagnosis was 37±17 years and mean follow-up was 3.4±7.0 years. The most common presenting symptom was seizures (43%). Mean AVM size was 3.5±1.9 cm and 46% were Spetzler-Martin grade I-II. Overall, 123 ICH and 131 deaths occurred over 9,608 person-years (PY) for an event rate of 2.64 per 100 PY [95% CI: 2.34-2.99]. Cox regression analyses adjusting for age at diagnosis (HR=1.67 [1.54, 1.82], P&lt;0.001) identified cerebellar location (HR=1.73 [1.03-2.93], P=0.040) and exclusively deep venous drainage (HR=1.83 [1.09-3.09], P=0.022) as predictors. Conclusion: Our current model identified increasing age, exclusively deep venous drainage, and cerebellar location as risk factors for ICH or death in the untreated course of unruptured bAVM patients. Review of imaging data, multiple imputation of missing angioarchitectural data, and additional data from pending cohorts will provide greater power to search for additional risk factors in this ongoing IPDMA.

Abstract MP11: Circulating Plasma Biomarkers Associated With Brain Arteriovenous Malformations

Objective: Circulating plasma protein profiling may aid in the identification of cerebrovascular disease signatures. This study aimed to identify circulating angiogenic and inflammatory biomarkers that may serve as biomarkers to differentiate sporadic brain arteriovenous malformation (bAVM) patients from other conditions with brain AVMs, including hereditary hemorrhagic telangiectasia (HHT) patients. Methods: The Quantibody Human Angiogenesis Array 1000 (Raybiotech) is an ELISA multiplex panel that was used to assess the levels of 60 proteins related to angiogenesis and inflammation in heparin plasma samples from 13 sporadic unruptured bAVM patients (69% male, mean age 51 years) and 37 patients with HHT (40% male, mean age 47 years, n=19 (51%) with bAVM). The Quantibody Q-Analyzer tool was used to calculate biomarker concentrations based on the standard curve for each marker and log-transformed marker levels were evaluated for associations between disease states using a multivariable interval regression model adjusted for age, sex, ethnicity and collection site. Statistical significance was based on Bonferroni correction for multiple testing of 60 biomarkers (P&lt; 8.3x10 - 4 ). Results: Circulating levels of two plasma proteins differed significantly between sporadic bAVM and HHT patients: PDGF-BB (P=2.6x10 -4 , PI= 3.37, 95% CI:1.76-6.46) and CCL5 (P=6.0x10 -6 , PI=3.50, 95% CI=2.04-6.03). When considering markers with a nominal p-value of less than 0.01, MMP1 and angiostatin levels also differed between patients with sporadic bAVM and HHT. Markers with nominal p-values less than 0.05 when comparing sporadic brain AVM and HHT patients also included angiostatin, IL2, VEGF, GRO, CXCL16, ITAC, and TGFB3. Among HHT patients, the circulating levels of UPAR and IL6 were elevated in patients with documented bAVMs when considering markers with nominal p-values less than 0.05. Conclusions: This study identified differential expression of two promising plasma biomarkers that differentiate sporadic bAVMs from patients with HHT. Furthermore, this study allowed us to evaluate markers that are associated with the presence of bAVMs in HHT patients, which may offer insight into mechanisms underlying bAVM pathophysiology.

RNF213 rare variants and cerebral arteriovenous malformation in a Chinese population

ObjectiveCerebral arteriovenous malformation (AVM) is characterised by an abnormal tangle of arteries and veins, the rupture of which is a significant portion of the morbidity and mortality cases, especially in young populations. However, the exact risk factors and pathophysiologic mechanisms of AVM remain poorly understood. RNF213 variants have been identified as obvious susceptible factors of several cerebrovascular disorders, such as Moyamoya disease and intracranial aneurysms. Thus, this study aimed to determine whether there is an association between RNF213 rare variants and AVM. MethodsThe AVM group included 22 patients with AVM. The control group included 1007 samples from the GeneSky in-house database and 208 samples from the 1000 Genome Project of Chinese Han Population. Genomic DNA samples were extracted from the peripheral blood of the AVM patients, and targeted exome sequencing of RNF213 was performed to assess the existence of low-frequency or rare variants. Sanger sequencing was performed to validate the identified variants. Logistic regression analysis was performed to calculate the odds ratios (ORs) and 95 % confidence intervals (CIs) of the candidate variants and risk of AVM. Statistical analyses were performed using SPSS version 21.0. ResultsThe RNF213 c.10997T>C variant (amino acid mutation p.M3666T, NM_001256071) was observed in two AVM patients after filtration. It was significantly associated with AVM in the Chinese population (ORs, 10.30 and 25.08; 95 %; CIs, 1.38–77.10 and 4.34–144.90 compared with 1000 Genome Project of Chinese Han Population and GeneSky in-house database, respectively). ConclusionRare variants of RNF213 are associated with AVM in the Chinese population, suggesting the important role of RNF213 in AVM. Further studies are needed to verify these findings.

Safety of Catheter Embolization of Pulmonary Arteriovenous Malformations-Evaluation of Possible Cerebrovascular Embolism after Catheter Embolization of Pulmonary Arteriovenous Malformations in Patients with Hereditary Hemorrhagic Telangiectasia/Osler Disease by Pre- and Post-Interventional DWI.

Background. This paper aimed to prospectively evaluate the safety of embolization therapy of pulmonary arteriovenous malformations (PAVMs) for the detection of cerebral infarctions by pre- and post-interventional MRI. Method One hundred and five patients (male/female = 44/61; mean age 48.6+/−15.8; range 5–86) with pre-diagnosed PAVMs on contrast-enhanced MRA underwent embolization therapy. The number of PAVMs treated in each patient ranged from 1–8 PAVMs. Depending on the size and localization of the feeding arteries, either Nester-Coils or Amplatzer vascular plugs were used for embolization therapy. cMRI was performed immediately before, and at the 4 h and 3-month post-embolization therapy. Detection of peri-interventional cerebral emboli was performed via T2w and DWI sequences using three different b-values, with calculation of ADC maps. Results Embolization did not show any post-/peri-interventional, newly developed ischemic lesions in the brain. Only one patient who underwent re-embolization and was previously treated with tungsten coils that corroded over time showed newly developed, small, diffuse emboli in the post-interventional DWI sequence. This patient already had several episodes of brain emboli before re-treatment due to the corroded coils, and during treatment, when passing the corroded coils, experienced additional small, clinically inconspicuous brain emboli. However, this complication was anticipated but accepted, since the vessel had to be occluded distally. Conclusion Catheter-based embolization of PAVMs is a safe method for treatment and does not result in clinically inconspicuous cerebral ischemia, which was not demonstrated previously.

Intraoperative Neuromonitoring for Cerebral Arteriovenous Malformation Embolization: A Propensity-Score Matched Retrospective Database Study.

IntroductionThe treatment of cerebral arteriovenous malformations (AVMs) may result in neurologic morbidity, particularly when an AVM is located in or adjacent to eloquent brain regions. Intraoperative neurophysiologic monitoring (IONM) may be utilized to reduce the risk of iatrogenic injury during endovascular AVM embolization; however, IONM for endovascular AVM embolization is not ubiquitously the standard of care.MethodsAdmissions for AVM embolization were assessed from the IBM MarketScan® Commercial and Medicare Supplemental databases (IBM Watson Health, Somers, NY). Inclusion criterion for patients was continuous enrollment six months before and after the index encounter. The use of IONM and presence of intracranial hemorrhage (ICH) were noted. Propensity-score matched cohorts with and without IONM were generated to minimize bias between treatment groups (adjusting for age, sex, and comorbidities).ResultsFrom 2007 to 2016, there were 16,279 patients diagnosed with cerebral AVM in the MarketScan database. Embolized patients were stratified into IONM and non-IONM cohorts; there were 357 patients in the IONM cohort and 1775 patients in the non-IONM cohort. Provider types were significantly different between cohorts (p<0.005). Unruptured AVMs were significantly more likely to be embolized with adjunctive IONM (17.7%) compared to ruptured AVMs (7.9%) (p<0.005). After balancing for baseline comorbidities, there were 266 patients in the IONM cohort, and 1347 patients in the non-IONM cohort. Among unruptured AVM patients, IONM was linked to a significantly shorter length of stay (2.72 versus 4.92 days; p<0.005), significantly lower rates of complications within 30 days of discharge (0.00% versus 1.88%; p=0.038), and significantly lower total payment ($40,179 versus $50,844; p<0.0001).ConclusionEndovascular embolization for unruptured AVMs performed with adjunctive IONM was associated with shorter length of stay, lower complication rates, and hospitalization costs.

Analysis of cases with maxillofacial arteriovenous malformation treated with balloon temporary block and percutaneous puncture sclerotherapy

To analysis the treatment effectiveness of maxillofacial arteriovenous malformation (AVM) by means of temporary balloon block and percutaneous puncture sclerotherapy. The treatment outcomes of 20 patients with AVM of maxillofacial deformity, aged (26.8±3.0) 18-36 years, from Dec 2012 to Dec 2019 were collected and retrospectively analyzed. All patients had been diagnosed AVM by digital substraction angiography (DSA). All the cases were treated by using balloons to temporary block responsible artery of the AVM in order to change the high-flow malformations into low-flow venous malformation. Then injection of polyethylene foam cinnamyl alcohol was conducted via percutaneous puncturing for hardening the vascular malformation. Comparing the symptoms and imaging changes before treatment with those 1-6 months after treatment according to Achauer curative effect evaluation standard. Totally 60% (12/20) of the cases were type Ⅱa AVM, and their treatments were effective. However, the treatment effects of type Ⅲb and type Ⅳ patients were relatively poor. The clinical effective rate was 85% (17/20), and the clinical curative rate was 50% (10/20). No skin necrosis, organ damage and other serious complications were observed for the 20 patients. The AVM patients with a main supply artery treated by using a balloon artery temporary block to make high flow malformations into low-flow and followed by percutaneous puncture sclerotherapy, could get good curative effect. It seemed that this approach was safe and effective.

Surgical Simulation with Three-Dimensional Fusion Images in Patients with Arteriovenous Malformation.

In arteriovenous malformation (AVM) surgery, vessel structures should be well evaluated with angiography. However, with conventional angiography, it is sometimes difficult to distinguish each feeder and its feeding territory in the nidus. In this study, we used two software systems to create three-dimensional (3D) fusion images using multiple imaging modalities and evaluated their clinical use. In the AVM patient, data were obtained from 3D rotational angiography, rotational venography, computed tomography (CT), and magnetic resonance imaging (MRI) and superimposed into 3D fusion images using imaging software (iPLAN and Avizo). Virtual surgical fields that were quite similar to the real ones were also created with these software programs. Compared with fusion images by iPLAN, those by Avizo have higher resolution and can demarcate not only each feeder but also its supplying territory in the nidus with different colors.In conclusion, 3D fusion images in AVM surgery are helpful for simulation, even though it takes time and requires special skill to create them.

A literature review of microvascular proliferation in arteriovenous malformations of skin and soft tissue

Arteriovenous malformations (AVM) are defined as being quiescent vascular masses composed of mature vessels. However, recent studies reported areas of microvascular proliferation (MVP) in AVM, indicating a process of angiogenesis. As this finding questions the previous definition, the primary objective of this review was to evaluate whether angiogenesis occurs in vascular malformations of skin and soft tissue, and second, to identify potential factors involved in MVP.Due to the multifaceted nature of this subject, a hermeneutic methodology was used to select articles that were likely to provide a deeper understanding of MVP in vascular malformations. Through citation tracking and database searching in PubMed and Web of Science, relevant articles were identified. All study designs concerning occurrence of MVP in AVM of skin and soft tissue in all age groups were included in the study. The Newcastle-Ottawa scale was used for quality assessment.16 studies were included in this review which reported occurrence of MVP areas in between the otherwise mature vessels of vascular malformations. In these studies, angiogenesis was reported only in AVM-type of vascular malformations. Increased levels of pro-angiogenic factors were also reported and proliferation was found most prominently during adolescence. Finally, several types of hormone receptors also have been described in tissues of AVM.Overall, the reviewed data support occurrence of active angiogenesis, highlighted by the presence of MVP in the arteriovenous type of vascular malformations, and a possible concurrent lesion progression towards a higher Schobinger stage of clinical severity. The relative scarcity of data at present implies that further research is required to elucidate the nature of MVP in AVM, which could have implications for developing targeted pharmacotherapy.Active angiogenesis caused by MVP in AVM patients is known to be correlating to clinical symptoms and contributing to the progression of the disease, recurrence rate, and patient's quality of life.

Cell-free DNA as a diagnostic analyte for molecular diagnosis of vascular malformations

PurposeVascular malformations (VM) are primarily caused by somatic activating pathogenic variants in oncogenes. Targeted pharmacotherapies are emerging but require molecular diagnosis. Since variants are currently only detected in malformation tissue, patients may be ineligible for clinical trials prior to surgery. We hypothesized that cell-free DNA (cfDNA) could provide molecular diagnoses for patients with isolated VM. MethodscfDNA was isolated from plasma or cyst fluid from patients with arteriovenous malformations (AVM), venous malformations (VeM), or lymphatic malformations (LM), and assayed for known pathogenic variants using droplet digital polymerase chain reaction (ddPCR). Cyst fluid cfDNA from an independent cohort of LM patients was prospectively screened for variants using a multiplex ddPCR assay. ResultsVariants were detected in plasma cfDNA in patients with AVM (2/8) and VeM (1/3). Variants were detected in cyst fluid cfDNA (7/7) but not plasma (0/26) in LM patients. Prospective testing of cyst fluid cfDNA with multiplex ddPCR identified variants in LM patients who had never undergone surgery (4/5). ConclusionVariants were detected in plasma from AVM and VeM patients, and in cyst fluid from patients with LM. These data support investigation of cfDNA-based molecular diagnostics for VM patients, which may provide opportunities to initiate targeted pharmacotherapies without prior surgery.

Dosimetric Comparison of Robotic and Linear Accelerator Multi-Leaf Collimator-Based Stereotactic Radiosurgery for Arteriovenous Malformation.

Purpose:To investigate the dosimetric comparison of different collimators which are used in robotic radiosurgery (cyberknife-CK) and linear accelerator (LINAC) for stereotactic radiosurgery (SRS) in arteriovenous malformation (AVM).Materials and Methods:Twenty-five AVM patients were planned in CK using FIXED cone, IRIS collimator, and multi-leaf collimator (MLC) based in LINAC. Dosimetric comparison was performed using Paddick conformity index (CIPaddick) and International Commission on Radiation Units and measurements (ICRU) homogeneity index (HIICRU), gradient score (GS), normal brain dose received by 10cc (D10cc) and critical structure (brain stem, optic chiasma, optic nerves) doses. Paired sample t-test was used for statistical analysis.Results:Mean treatment volume was 3.16cc (standard deviation ± 4.91cc). No significant deviation (P =0.45, 0.237 for FIXED vs. IRIS and FIXED vs. MLC, respectively) was found in target coverage. For CIPaddick, the mean difference (MD) between FIXED- and MLC-based plans was 0.16(P = 0.001); For HIICRU, difference between FIXED and IRIS was insignificant (0.5, P = 0.823); but, when FIXED versus MLC, the deviation was 7.99% (P = 0.002). In FIXED- and MLC-based plans, significant difference was found in GS70 and GS40 (P < 0.041 and 0.005, respectively). MD between FIXED- and MLC-based plans for normal brain for 5Gy, 10Gy, 12Gy, and 20Gy were 36.08cc (P = 0.009), 7.12cc (P = 0.000), 5.84cc (P = 0.000) and 1.56cc (P = 0.000), respectively. AVM volume <0.7cc should be treated with CK FIXED and >0.7cc were treated by using FIXED or IRIS collimators. AVM volume > 1.4cc can be treated by either LINAC MLC-based SRS or CK.Conclusion:Our study shows CK collimator (IRIS and FIXED) could be able to treat brain AVMs in any size. Linac MLC-based SRS has some limitations in terms of conformity and low-dose spillage, and advantages like reduced treatment time and MU.

Improved Cerebral Arteriovenous Malformation Obliteration With 3-Dimensional Rotational Digital Subtraction Angiography for Radiosurgical Planning: A Retrospective Cohort Study.

Stereotactic radiosurgery (SRS) for cerebral arteriovenous malformations (AVMs) is well-established. Radiographic advantages exist for 3-dimensional rotational digital subtraction angiography (3DRA) over 2-dimensional digital subtraction angiography (2D DSA) in delineating AVM nidus structure for SRS treatment planning. However, currently there is limited to no data directly comparing 2D DSA versus 3DRA in terms of patient outcomes. To investigate whether the use of 3DRA over 2D DSA in radiosurgical treatment planning for AVMs associates with improved clinical outcomes. All AVM patients treated with SRS at our institution between the years 2000 and 2018 were identified. Primary outcomes were obliteration rates and time to obliteration (TTO); secondary outcomes included rates of post-SRS hemorrhage, salvage therapy, and symptomatic radionecrosis. A minimum of 12 mo of follow-up imaging/angiogram post-SRS was required, or alternatively evidence of obliteration on angiogram prior to 12 mo post-SRS. Single predictor and multivariable Cox regression and logistic regression models were constructed to test for association between radiographic, clinical, and treatment factors with outcomes. A total of 75 patients were included. Total 17 patients received 3DRA and 58 patients received 2D DSA, with a median follow-up of 3.29 yr. The 3DRA is significantly associated with improved TTO on single predictor (HR 2.87, 1.29-6.12; P=.0109) and multivariable analysis (HR 2.448, 1.076-5.750; P=.0330) and increased odds of achieving obliteration by 3 yr post-SRS on single predictor analysis (OR 6.044, 1.405-26.009; P=.0157). The 3DRA over 2D DSA in SRS treatment planning for AVMs may result in improved TTO and 3-yr obliteration rates. Further investigation and prospective study are warranted.

Corpus Callosum Diffusion Anisotropy and Hemispheric Lateralization of Language in Patients with Brain Arteriovenous Malformations.

Background: The corpus callosum (CC) plays a key role in mediating interhemispheric connectivity and developing functional hemispheric asymmetries. The purpose of this study was to investigate the changes in CC microstructure accompanying interhemispheric language reorganization in patients with brain arteriovenous malformations (AVMs). Methods: Forty-one patients with an unruptured AVM located in anatomically defined language areas underwent functional magnetic resonance imaging and diffusion tensor imaging. Hemispheric dominance in Broca's area (BA) and Wernicke's area (WA) was assessed separately. Right-sided or bilateral language dominance was classified as atypical lateralization. The CC was segmented into five subregions, and the mean fractional anisotropy (FA) was extracted. The relationship between callosal FA and language lateralization patterns was statistically analyzed. Results: We observed atypical language lateralization in 16 (39.0%) patients. Patients with atypical lateralization exhibited significantly higher mean FA values in the total CC (p = 0.002) and the anterior (p = 0.047), midanterior (p = 0.001), and midposterior (p = 0.043) subregions. Significant interaction effects of BA and WA lateralization were found for FA values in the total CC (p = 0.005) and the midanterior subregion (p = 0.004). Conclusions: These results indicate that AVM patients with atypical language lateralization exhibit higher callosal FA values, reflecting greater interhemispheric connectivity. Our findings contribute additional insights into the understanding of functional and structural plasticity of the human brain under pathological states. Impact statement Brain arteriovenous malformations (AVMs) are congenital lesions that frequently lead to interhemispheric language reorganization. In this study, by combining diffusion tensor imaging and functional magnetic resonance imaging, we investigated the relationship between callosal fractional anisotropy (FA) and language reorganization in patients with AVMs. We found that callosal FA was significantly higher in patients with atypical language lateralization, especially in those with crossed lateralization of Broca's and Wernicke's areas. This study demonstrated the remodeling of the corpus callosum microstructure accompanying language reorganization in AVM patients, providing insights into the structural and functional plasticity of the human brain associated with congenital cerebrovascular disease.

Semiautomatic cerebrovascular territory mapping based on dynamic ASL MR angiography without vessel-encoded labeling.

Characterizing vessel territories can provide crucial information for evaluation of cerebrovascular disorders. In this study, we present a novel postprocessing pipeline for vascular territorial imaging of cerebral arteries based on a noncontrast enhanced time-resolved 4D magnetic resonance angiography (MRA). Eight healthy participants, 1 Moyamoya patient, and 1 arteriovenous malformations patient were recruited. Territorial segmentation and relative blood flow rate calculations of cerebral arteries including left and right middle cerebral arteries and left and right posterior cerebral arteries were carried out based on the 4D MRA-derived arterial arrival time maps of intracranial vessels. Among healthy young subjects, the average relative blood flow rate values corresponding to left and right middle cerebral arteries and left and right posterior cerebral arteries were 35.9 ± 5.9%, 32.9 ± 7.5%, 15.4 ± 3.8%, and 15.9 ± 2.5%, respectively. Excellent agreement was observed between relative blood flow rate values obtained from the proposed 4D MRA-based method and reference 2D phase contrast MRI. Abnormal cerebral circulations were visualized and quantified on both patients using the developed technique. The vascular territorial imaging technique developed in this study allowed for the generation of territorial maps with user-defined level of details within a clinically feasible scan time, and as such may provide useful information to assess cerebral circulation balance in different pathologies.

Brain Arteriovenous Malformations: Impact of Neurologic Status, Bleeding, and Type of Treatment on Final Outcome

Well-designed studies assessing the treatment outcome of brain arteriovenous malformations (AVMs) are infrequent and have not consistently included all of the available treatment modalities, making their results not completely generalizable. Moreover, the predictors of poor outcome are not well defined. We performed an observational retrospective study of AVM patients. We included patients with clinical, radiologic, and outcome data, with a minimum follow-up of 1 year. Neurologic outcome was documented using the modified Rankin Scale (mRS) at the AVM diagnosis and 30 days after the treatment. There were 117 patients, with equal male/female proportion. The mean follow-up time was 51 months. Treatment distribution in the Spetzler-Martin grades I-III was as follows: 52 (54.6%) surgery, 31 (32.35%) radiosurgery, 2 (0.02%) embolization, and 11 (12%) conservative follow-up. Treatment distribution in Spetzler-Martin grades IV and V was as follows: 4 (20%) surgery, 7 (35%) radiosurgery, and 10 (45%) conservative follow-up. Poor neurologic outcome (mRS ≥ 3) was significantly associated with poor clinical status at diagnosis (Glasgow Coma Scale [GCS] score< 14; odds ratio [OR]: 0.20; 95% confidence interval [CI]: 0.001-0.396; p = 0.010). The rupture of the AVM was associated with poor neurologic outcome. The Lawton-Young Supplementary scale (LYSS) proved to be the most effective in predicting poor outcome. The existence of seizures, treatment-related complications, and conservative treatment was associated with the worsening of the mRS score, whereas the existence of hemorrhage was associated with the likelihood of disability. Our results suggest that poor neurologic status at diagnosis, AVM rupture, and conservative treatment were associated with worse outcome. Hemorrhage as initial presentation is related to disability, not with mRS worsening. The LYSS appeared to be the best method to predict outcome.

Cigarette Smoking Is More Prevalent in Patients With Brain Arteriovenous Malformations Compared to General Population: A Cross-Sectional Population-Based Study.

Research on the prevalence of smokers in patients with brain arteriovenous malformation (AVM) remains nonexistent, even though smoking is a well-known risk factor for intracranial aneurysms. To examine the prevalence and smoking habits of AVM patients. Data on smoking habits were collected with a quality-of-life questionnaire mailed in 2016 to all patients in our large AVM database. These smoking data were supplemented with registry data derived from medical records. The prevalence of smokers was compared to that of the general population, derived from statistics of National Institute for Health and Welfare. Logit transformation of proportions and Students t distribution were used to calculate the 95% CIs for prevalence estimates. Of the 384 patients aged over 18 yr on admission, 277 (72.1%) returned the questionnaires in 2016. When compared to age, sex, and admission year matched general population, the proportion of smokers in AVM patients was 48% (CI=41%-55%) and 19% (CI=16%-21%) in the general population. The difference increased in older age groups; in those aged 65 to 77 yr, the percentage of smokers reached 73% (CI=46%-90%), while the corresponding percentage in the general population was 7% (CI=5%-9%). We observed considerably higher rates of smoking among AVM patients when compared to age, sex, and admission year matched general population. Our results suggest that in the development of AVMs, the role played by nicotine and other substances in tobacco smoke should be examined. Cigarette smoking could potentially be a common cerebrovascular risk factor.

Single-Stage Combined Embolization and Resection for Spetzler-Martin Grade III/IV/V Arteriovenous Malformations: A Single-Center Experience and Literature Review.

Background and Purpose: This study sought to identify the efficacy and intraoperative operational details of single-stage combined embolization and microsurgery strategy for Spetzler-Martin (SM) grade III/IV/V arteriovenous malformations (AVMs).Methods: The authors retrospectively reviewed consecutive SM grade III/IV/V AVMs who underwent hybrid procedures and surgical resection alone procedures from January 2016 to February 2018. Outcomes [modified Rankin Scale (mRS)] were compared between hybrid group and surgical resection alone group in ruptured or unruptured subgroup. Factors associated with long-term disability were assessed using multivariable logistic regression analyses.Results: A total of 100 AVM patients (47 corrected using hybrid procedures whereas 53 by surgical resection alone) were evaluated. After a mean follow-up of 2.3 ± 0.6 years, we found no difference in long-term prognosis and incidences of disability rates between these two strategies. However, the hybrid strategy offers significant advantage in accelerating the resection process [ruptured (P = 0.000); unruptured (P = 0.002)]. In the analysis of risk factors, excessive embolization (Grade C, 60–100%) was significantly associated with long-term disability in the hybrid cohorts (P = 0.041; odds ratio, 24.000; 95% CI, 1.140–505.194), and involvement of deep perforating arteries was the significant predictor of long-term disability in the surgical resection alone cohort (P = 0.025; odds ratio, 15.389; 95% CI, 1.412–167.66). In the subgroup analysis of the hybrid cohort, moderate embolization (Grade B, 30–60%) was recommended because of the low risk ratio of major intraoperative bleeding (P = 0.033).Conclusions: Single-stage combined embolization and resection is an efficient strategy for the treatment of SM grade III/IV/V AVMs. Although the long-term outcomes were similar to surgical resection alone, the hybrid strategy had obvious advantages of shorter resection. In the hybrid technique, moderate embolization was recommended, and excessive embolization might be detrimental to the subsequent microsurgical resection.Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT04136860.

Altered Brain Structural Networks in Patients with Brain Arteriovenous Malformations Located in Broca's Area.

Focal brain lesions, such as stroke and tumors, can lead to remote structural alterations across the whole-brain networks. Brain arteriovenous malformations (AVMs), usually presumed to be congenital, often result in tissue degeneration and functional displacement of the perifocal areas, but it remains unclear whether AVMs may produce long-range effects upon the whole-brain white matter organization. In this study, we used diffusion tensor imaging and graph theory methods to investigate the alterations of brain structural networks in 14 patients with AVMs in the presumed Broca's area, compared to 27 normal controls. Weighted brain structural networks were constructed based on deterministic tractography. We compared the topological properties and network connectivity between patients and normal controls. Functional magnetic resonance imaging revealed contralateral reorganization of Broca's area in five (35.7%) patients. Compared to normal controls, the patients exhibited preserved small-worldness of brain structural networks. However, AVM patients exhibited significantly decreased global efficiency (p = 0.004) and clustering coefficient (p = 0.014), along with decreased corresponding nodal properties in some remote brain regions (p < 0.05, family-wise error corrected). Furthermore, structural connectivity was reduced in the right perisylvian regions but enhanced in the perifocal areas (p < 0.05). The vulnerability of the left supramarginal gyrus was significantly increased (p = 0.039, corrected), and the bilateral putamina were added as hubs in the AVM patients. These alterations provide evidence for the long-range effects of AVMs on brain white matter networks. Our preliminary findings contribute extra insights into the understanding of brain plasticity and pathological state in patients with AVMs.

Automated Deep Learning-Based Image Segmentation for the Correction of Normal Brain Dose-Volume Parameters in Brain SRS for Cerebral AVMs

Brain radiation necrosis (RN) is a dose-limiting toxicity of stereotactic radiosurgery (SRS) for cerebral arteriovenous malformations (AVMs). Prior studies show a significant relationship between the probability of RN and the volume of brain receiving high doses, in particular, the volume receiving at least 12Gy (V12). However, due to the prohibitive time cost of manually segmenting brain from other intracranial tissues, prior studies have treated all intracranial tissues homogenously as brain. Large AVMs can cause significant anatomical distortions, with dilated ventricles, draining veins, and embolized nidus elements potentially displacing brain tissue from the high dose volume. We hypothesized that there would be a significant difference between estimated V12 for all intracranial tissues (V12ic) and V12 for brain parenchyma specifically (V12brain) in AVM cases. To assess the difference between V12ic and V12brain (ΔV12), we used a convolutional neural network (CNN) to auto-segment magnetic resonance images (MRIs) from SRS-treated patients into vascular structures, CSF, and brain tissue, fusing the segmented images with treatment plans to calculate V12ic and V12brain. SRS plans from 8 AVM patients who underwent single stage SRS and 4 who underwent multistage SRS were included. For multistage SRS plans, each stage was treated as an independent plan, for a total of 16 analyzed treatment plans. A previously trained CNN was used to automatically segment multiparametric pre-treatment MRIs into arteries, veins, CSF, embolized vessels, and brain parenchyma. Segmentation labels were converted into contours and registered to treatment plans. Dose-volume histograms were generated, from which V12ic and V12brain for all intracranial tissue and brain parenchyma, respectively, were analyzed. We assessed the relationship between ΔV12 (V12ic - V12brain) and target volume using linear regression. Median target volume was 1.75cc (range [0.22-9.95cc]). Median V12ic was 8.31cc (range [2.1-21.4cc]) while median V12brain was 4.0cc (range [1.3-13.3cc]). Median ΔV12 was 3.7cc (range [0.46-9.4cc]). There was a significant linear relationship between target volume and ΔV12 (Pearson r2 = 0.57, p < 0.01), with larger targets associated with a greater ΔV12. Anatomical distortions produced by an AVM nidus can produce a significant difference between V12ic and V12brain, an effect that is more pronounced for larger lesions. Further studies are needed to directly assess the relationship between V12brain and likelihood of post-SRS RN; however, estimating dose to brain tissue specifically may help identify patients who can safely receive dose-escalated therapy as well as patients who require a more conservative approach. CNN-based automated segmentation provides a means of overcoming the previously prohibitive time cost of performing such an analysis.