Arteriovenous Malformations Patients Research Articles

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.

4D Digital Subtraction Angiography for the Temporal Flow Visualization of Intracranial Aneurysms and Vascular Malformations

PurposeTo assess the benefit and radiation dose of four-dimensional (4D) digital subtraction angiography (DSA) - a time resolved three-dimensional (3D) DSA application - to evaluate the flow and architecture of aneurysms and vascular malformations. MethodsAll patients with cerebrovascular disease were considered who underwent 4D-DSA at our institution between January 2015 and February 2016. For the aneurysm patients, we evaluated the image quality in terms of the visualization of contrast flow in the aneurysm on a 3-point scale (excellent, fair and poor). Interrater agreement between two raters was estimated using Cohen's Kappa statistics. For the shunt disease patients, the additional information obtained from the 4D-DSA was described for each disease. The median radiation dose and volume of contrast medium required for the acquisitions were estimated. ResultsA total of 173 patients underwent 4D-DSA; 126 intracranial aneurysms, 10 arteriovenous malformations (AVM), 15 dural arteriovenous fistula (dAVF) and 22 other diseases. For aneurysm patients, excellent and fair visualization of the intra-aneurysmal flow was observed in 27.7%, 72.3%, and excellent (κ = 0.9) agreement between the raters was found. For AVM and dAVF patients, 4D-DSA clarified the complex vasculature by viewing the discrete time phase of contrast filling. Median radiation dose for intracranial lesions was 79.6 mGy for 6s 4D-DSA, and 175 mGy for 12s 4D-DSA. The median amount of contrast medium used was 18.0 ml for 6s 4D-DSA and 21.0 ml for 12s 4D-DSA. Conclusions4D-DSA provided additional information regarding intra-aneurysmal flow and contributed to detect different component of nidus or shunt points.

The transvenous retrograde pressure cooker technique for the curative embolization of high-grade brain arteriovenous malformations

BackgroundTransvenous embolization of brain arteriovenous malformations (AVMs) can be curative. We aimed to evaluate the cure rate and safety of the transvenous retrograde pressure cooker technique (RPCT) using coils and...

IntuitivePlan inverse planning performance evaluation for Gamma Knife radiosurgery of AVMs.

PurposeTo compare planning indices achieved using manual and inverse planning approaches for Gamma Knife radiosurgery of arterio‐venous malformations (AVMs).Methods and materialsFor a series of consecutive AVM patients, treatment plans were manually created by expert planners using Leksell GammaPlan (LGP). Patients were re‐planned using a new commercially released inverse planning system, IntuitivePlan. Plan quality metrics were calculated for both groups of plans and compared.ResultsOverall, IntuitivePlan created treatment plans of similar quality to expert planners. For some plan quality metrics statistically significant higher scores were achieved for the inversely generated plans (Coverage 96.8% vs 96.3%, P = 0.027; PCI 0.855 vs 0.824, P = 0.042), but others did not show statistically significant differences (Selectivity 0.884 vs 0.856, P = 0.071; GI 2.85 vs 2.76, P = 0.096; Efficiency Index 47.0% vs 48.1%, P = 0.242; Normal Brain V12(cc) 5.81 vs 5.79, P = 0.497). Automatic inverse planning demonstrated significantly shorter planning times over manual planning (3.79 vs 11.58 min, P < 10−6) and greater numbers of isocentres (40.4 vs 10.8, P < 10−6), with an associated cost of longer treatment times (57.97 vs 49.52 min, P = 0.009). When planning and treatment time were combined, there was no significant difference in the overall time between the two methods (61.76 vs 61.10, P = 0.433).ConclusionsIntuitivePlan can offer savings on the labor of treatment planning. In many cases, it achieves higher quality indices than those achieved by an “expert planner”.

Somatic Gain of KRAS Function in the Endothelium Is Sufficient to Cause Vascular Malformations That Require MEK but Not PI3K Signaling.

We previously identified somatic activating mutations in the KRAS (Kirsten rat sarcoma viral oncogene homologue) gene in the endothelium of the majority of human sporadic brain arteriovenous malformations; a disorder characterized by direct connections between arteries and veins. However, whether this genetic abnormality alone is sufficient for lesion formation, as well as how active KRAS signaling contributes to arteriovenous malformations, remains unknown. To establish the first in vivo models of somatic KRAS gain of function in the endothelium in both mice and zebrafish to directly observe the phenotypic consequences of constitutive KRAS activity at a cellular level in vivo, and to test potential therapeutic interventions for arteriovenous malformations. Using both postnatal and adult mice, as well as embryonic zebrafish, we demonstrate that endothelial-specific gain of function mutations in Kras (G12D or G12V) are sufficient to induce brain arteriovenous malformations. Active KRAS signaling leads to altered endothelial cell morphogenesis and increased cell size, ectopic sprouting, expanded vessel lumen diameter, and direct connections between arteries and veins. Furthermore, we show that these lesions are not associated with altered endothelial growth dynamics or a lack of proper arteriovenous identity but instead seem to feature exuberant angiogenic signaling. Finally, we demonstrate that KRAS-dependent arteriovenous malformations in zebrafish are refractory to inhibition of the downstream effector PI3K but instead require active MEK (mitogen-activated protein kinase kinase 1) signaling. We demonstrate that active KRAS expression in the endothelium is sufficient for brain arteriovenous malformations, even in the setting of uninjured adult vasculature. Furthermore, the finding that KRAS-dependent lesions are reversible in zebrafish suggests that MEK inhibition may represent a promising therapeutic treatment for arteriovenous malformation patients. Graphical Abstract: A graphical abstract is available for this article.

Late recovery of stereotactic radiosurgery induced perilesional edema of an arteriovenous malformation after bevacizumab treatment

Purpose: Today, stereotactic surgery (SRS) is among the treatment options for many intracranial lesions including vascular pathologies. One of the most common late complications of SRS is perilesional edema which can be treated with steroids. In addition to steroids, some new medical therapies are being investigated and one of the promising one is Bevacizumab; a monoclonal antibody against vascular endothelial growth factor (VEGF). In the cases of steroid resistant perilesional edemas, however bevacizumab has a late term effect resolution of symptoms and radiological improvement can be seen as late as more than 1,5 years after its initiation. Materials and Methods We present a 41-year old male patient who was admitted to our clinic with epileptic seizures, headaches and hemiparesis 14 months after SRS treatment for a left fronto-parietal Spetzler-Martin Grade III arteriovenous malformation (AVM). On his first-year follow-up perilesional edema was observed for which the patient received steroid treatment, but the patient did not show any benefit from it. In the cases of steroid resistant perilesional edemas, bevacizumab can be used for reducing symptoms and even radiological perilesional edema as well. Results In our case, we have seen the effect of bevacizumab for symptomatic perilesional edema in a AVM patient after SRS treatment after radiological / neurological recovery. Our patient's headaches decreased rapidly after 2 days after treatment and was able to mobilize himself after 2 months but total resolution of symptoms and radiological findings observed after 1,5 years. Conclusions The duration and optimum dose of bevacizumab therapy needed to further investigation. Our study showed that bevacizumab was a long-term and effective treatment option for the cases with peritumoral edema resistant to glucocorticoid treatment, where the patient had conditions such as severe headache and neurological deficits.

Predictive factors of epilepsy in arteriovenous malformation

ObjectiveStructural epilepsy related to cerebral arteriovenous malformation (AVM) suggests different epileptogenic mechanisms. The aim of our study was to determine factors associated with epilepsy into a retrospective cohort of AVM patients. Patients and methodsRuptured and unruptured AVM data retrieved from a prospective single center registry (2009–2016) were retrospectively assessed. Demographic, clinical and radiological features were identified in AVM patients with or without epilepsy according to the International League Against Epilepsy classification. ResultsEpilepsy concerned 22 out of 80 consecutive patients with AVM (27.5%). Univariate analysis comparing both groups revealed a significant association of different variables with the structural epilepsy: young age (P=0.02), large nidus size (P=0.02), venous dilation (P=0.02), posterior cerebral artery (PCA) feeder (P<0.001) and Spetzler-Martin grade (P=0.02). Based on multivariate analysis, only the PCA feeder was identified (OR=5.2 [95% CI 1.1–24,5], P=0.04). ConclusionPCA feeder for cerebral AVM was significantly associated with structural epilepsy. The hypothesis of a vascular steal phenomenon to the detriment of internal temporal lobe vascularization could be related to the development of epilepsy.

Combined surgical treatment of the cerebral arteriovenous malformations in patients with the torpid course of the disease

Objective – to optimize the results of surgical treatment of the cerebral arteriovenous malformations (AVM) with a torpid clinical course of the disease.Materials and methods. The results of combined surgical treatment of cerebral AVMs of 36 patients without a history of AVM rupture were analyzed (this variant of clinical course was defined as «torpid»). Patients were treated in the departments of vascular neurosurgery at the Romodanov Neurosurgery Institute NAMS of Ukraine during the period from 2010 till September 2019. Among the patients there were 18 (50 %) men and 18 (50 %) women. The average age of patients was 28.1 years (10–47 years). Clinical, neurological, laboratory, instrumental, functional and morphological methods of examination were used as well as neuroimaging evaluation and follow-up investigation.Results. The «torpid» course of disease in patients with AVM was presented as heterogeneous epileptiform manifestations in 24 (66.7 %) cases. One (2.8 %) patient had seizure that were combined with internal hydrocephalus, 9 (25 %) patients had different severity cephalalgic syndrome (according to the International classification of headache – 3β). Progressive neurological deficit was detected in 2 (5.55 %) patients. The distribution of AVMs according Spetzler–Martin scale (1986) was as follows: grade I – in 2 (5.55 %) patients, grade II – in 10 (27.8 %), grade III – in 13 (36.1 %), grade IV – in 9 (25.0 %), grade V – in 2 (5.55 %). In most cases (94.44 %), AVMs were supratentorial, and in 2 (5.55 %) cases they were subtentorial. The average AVM size in the largest dimension was 3.7 cm (2.8–6.7 cm). Intranidal aneurysms in the AVM structure were diagnosed in 8 (22.2 %) patients, fistulas – in 7 (19.4 %) cases. In all cases, at the first stage, endovascular embolization (EE) of AVM was performed. All 36 patients underwent 64 endovascular procedures. Curative treatment after 1 stage was performed in 16 (44.4 %) patients, after 2 stages – in 13 (36.1%), after 3 stage – in 6 (16.66 %), and after 4 stage in 1 (2.77 %) patient. In 36 (56.25 %) cases, embolization was performed with Onyx composition (eV3), in 24 (37.5 %) – with n-butylcyanoacrylate, and in 3 (4.7 %) – with their combination. In 1 (1.56 %) patient, the fistula was excluded from the blood flow using detached balloon-catheter. Embolization was supplemented with radiosurgical treatment (RST) in 30 (83.3 %) cases, microsurgical removal – in 2 (5.55 %), radiotherapy – in 2 (5.55 %) patients. In 1 (2.77 %) case EE was combined with shunting procedure and RST. One (2.77 %) patient after EE with RST suffered hemorrhagic stroke with intracerebral hematoma formation. An operation was performed for hematoma removal and partially functioning AVM resection. In 7 (10.9 %) cases after EE of AVM, patients developed motor deficits. At the time of discharge, they regressed completely in 6 patients, and partially in 1 patient. In (1.5 %) case homonymous hemianopsia had occurred. After RST, total obliteration of AVM was achieved in 17 (58.6 %) patients, in 5 (17.2 %) – subtotal (repeated RST was recommended). In 7 (24.1 %) cases, positive signs of AVM obliteration was noted, and the timing of radiation exposure did not reach the recommended ones. In 2 (3.1 %) patients after microsurgical resection, the AVM was removed completely, which was confirmed by cerebral angiography. After radiotherapy, decreasing of the AVM size and a positive neurological dynamics were noted. There were no fatal outcomes. According to the modified Rankine scale, patients were distribution to group 0 (33 (91.7 %)) and group I (3 (8.3 %)).Conclusions. The obtained data indicate the promising result of combined surgical treatment of cerebral AVM with a torpid type of clinical manifestations. The leading technique in the applied staged combined surgical treatment of AVM was EE. Its successful use is due to the effectiveness of its impact on all components of the «complex» AVM.