Epigenetics enters the stage in vascular malformations.

Cerebral arteriovenous malformations represent the most common form of vascular malformations and can cause recurrent bleeding and hemorrhagic stroke. The current issue of the JCI features an article by Zhao et al. describing a mouse model of cerebral arteriovenous malformations. Endothelial cells lacking matrix Gla protein, a BMP inhibitor, underwent epigenetic changes characteristic of an endothelial-to-mesenchymal fate transition. The authors uncovered a two-step process for this transition controlled by the epigenetic regulator histone deacetylase 2 (HDAC2), which controls endothelial cell differentiation, and by enhancer of zeste homolog 1 (EZH1), which suppressed mesenchymal fate. This discovery provides a promising entry point for preventive pharmacological interventions.

Comparison of imaging modalities for the accurate delineation of arteriovenous malformations (AVM) and evaluation of setup accuracy with reference to non-invasive LINAC-based stereotactic radiosurgery (SRS).

AIMS: To compare the accuracy of nidus delineation using magnetic resonance angiography (MRA) to digital subtraction angiography (DSA) and to evaluate setup accuracy of non-invasive frame SRS treatments. SETTINGS AND DESIGN: A prospective observational study of 16 patients who underwent non-invasive frame LINAC-based SRS for brain AVMs. MATERIALS AND METHODS: The nidus was separately delineated using DSA and MRA after co-registration onto CT simulation images and compared with respect to their volume and maximum diameters. During treatment, the setup errors observed in x-, y-, and z-directions were recorded. STATISTICAL ANALYSIS: Paired t-test (to compare volume and maximum diameter). Wilcoxon signed-rank test (for setup accuracy). RESULTS: The mean volume of nidus contoured in MRA was 4.16 cc compared to 3.11 cc in DSA (P 0.297). The mean maximum diameters using MRA and DSA, respectively, in antro-posterior, cranio- caudal, and transverse diameters were 21.97 cc vs. 19.46 cc (P 0.2380), 6.59 cc vs. 9.63 cc (P 0.161), and 18.87 cc vs. 16.81 cc (P 0.178). But these modalities can potentially misinterpret the nidus volume, warranting caution for use of either modality alone. The mean translational shift observed in the x-, y-, and z-directions were 0.06 mm, 0.13 mm, and 0.13 mm, respectively, when couch was brought to neutral position after clockwise couch rotation and 0.07, 0, and 0, respectively, after counterclockwise couch rotation. CONCLUSION: This study could not demonstrate any statistically significant differences in nidus delineation between MRA and DSA. Setup accuracy achieved with non-invasive thermoplastic mask-based immobilization is within acceptable limits for SRS.

Analysis of the treatment planning metrics and their correlation with morphology of intracranial lesions in Gamma Knife stereotactic radiosurgery.

BACKGROUND: Gamma Knife Radiosurgery (GKRS) has established a role in treating various benign brain pathologies. The radiosurgery planning necessitates a proper understanding of radiation dose distribution in relation to the target lesion and surrounding eloquent area. The quality of a radiosurgery plan is determined by various planning parameters. Here, we have reviewed various GKRS planning parameters and analyzed their correlation with the morphology of treated brain lesions. METHOD: A total of 430 treatment plans (71 meningioma, 133 vestibular schwannoma/VS, 150 arteriovenous malformation/AVM, 76 pituitary adenoma/PA treated with GKRS between December 2013 and May 2023) were analyzed for target coverage (TC), conformity index (CI), homogeneity index (HI), and gradient index (GI). RESULT: The values of CIPaddick and CILomax for PA were lower and differed significantly from meningioma, VS, and AVM. The value of HI for PA was higher and differed significantly when compared with meningioma, VS, and AVM. The values of HI for AVM were also significantly higher than VS and meningioma. The mean GI was 3.02, 2.92, 3.03, and 2.88 for meningioma, VS, AVM, and PA, respectively. The value of GI for meningioma and AVM was significantly higher when compared with the values for VS and PA. The mean TC was 0.94 for meningioma, 0.96 for VS, 0.95 for AVM, and 0.90 for PA. The value TC of PA was lower and differed significantly when compared with VS, AVM, and meningioma. Lesions with a volume of ≤1 cc had poor planning metrics as the spillage of radiation may be higher. CONCLUSION: The GKRS planning parameters depend on the size, shape, nature, and location of intracranial lesions. Therefore, each treatment plan needs to be evaluated thoroughly and a long-term follow-up is needed to establish their relation with clinical outcome.

Inhibition of endothelial histone deacetylase 2 shifts endothelial-mesenchymal transitions in cerebral arteriovenous malformation models.

Cerebral arteriovenous malformations (AVMs) are the most common vascular malformations worldwide and the leading cause of hemorrhagic strokes that may result in crippling neurological deficits. Here, using recently generated mouse models, we uncovered that cerebral endothelial cells (ECs) acquired mesenchymal markers and caused vascular malformations. Interestingly, we found that limiting endothelial histone deacetylase 2 (HDAC2) prevented cerebral ECs from undergoing mesenchymal differentiation and reduced cerebral AVMs. We found that endothelial expression of HDAC2 and enhancer of zeste homolog 1 (EZH1) was altered in cerebral AVMs. These alterations changed the abundance of H4K8ac and H3K27me in the genes regulating endothelial and mesenchymal differentiation, which caused the ECs to acquire mesenchymal characteristics and form AVMs. This investigation demonstrated that the induction of HDAC2 altered specific histone modifications, which resulted in mesenchymal characteristics in the ECs and cerebral AVMs. The results provide insight into the epigenetic impact on AVMs.

Somatic BrafV600E mutation in the cerebral endothelium induces brain arteriovenous malformations.

Current treatments of brain arteriovenous malformation (BAVM) are associated with considerable risks and at times incomplete efficacy. Therefore, a clinically consistent animal model of BAVM is urgently needed to investigate its underlying biological mechanisms and develop innovative treatment strategies. Notably, existing mouse models have limited utility due to heterogenous and untypical phenotypes of AVM lesions. Here we developed a novel mouse model of sporadic BAVM that is consistent with clinical manifestations in humans. Mice with BrafV600E mutations in brain ECs developed BAVM closely resembled that of human lesions. This strategy successfully induced BAVMs in mice across different age groups and within various brain regions. Pathological features of BAVM were primarily dilated blood vessels with reduced vascular wall stability, accompanied by spontaneous hemorrhage and neuroinflammation. Single-cell sequencing revealed differentially expressed genes that were related to the cytoskeleton, cell motility, and intercellular junctions. Early administration of Dabrafenib was found to be effective in slowing the progression of BAVMs; however, its efficacy in treating established BAVM lesions remained uncertain. Taken together, our proposed approach successfully induced BAVM that closely resembled human BAVM lesions in mice, rendering the model suitable for investigating the pathogenesis of BAVM and assessing potential therapeutic strategies.

Pathologic features of brain hemorrhage after radiation treatment: case series with somatic mutation analysis.

BACKGROUND: Radiation treatment for diseases of the brain can result in hemorrhagic adverse radiation effects. The underlying pathologic substrate of brain bleeding after irradiation has not been elucidated, nor potential associations with induced somatic mutations. METHODS: We retrospectively reviewed our department's pathology database over 5 years and identified 5 biopsy specimens (4 patients) for hemorrhagic lesions after brain irradiation. Tissues with active malignancy were excluded. Samples were characterized using H&E, Perl's Prussian Blue, and Masson's Trichrome; immunostaining for B-cells (anti-CD20), T-cells (anti-CD3), endothelium (anti-CD31), macrophages (anti-CD163), α-smooth muscle actin, and TUNEL. DNA analysis was done by two panels of next-generation sequencing for somatic mutations associated with known cerebrovascular anomalies. RESULTS: One lesion involved hemorrhagic expansion among multifocal microbleeds that had developed after craniospinal irradiation for distant medulloblastoma treatment. Three bleeds arose in the bed of focally irradiated arteriovenous malformations (AVM) after confirmed obliteration. A fifth specimen involved the radiation field distinct from an irradiated AVM bed. From these, 2 patterns of hemorrhagic vascular pathology were identified: encapsulated hematomas and cavernous-like malformations. All lesions included telangiectasias with dysmorphic endothelium, consistent with primordial cavernous malformations with an associated inflammatory response. DNA analysis demonstrated genetic variants in PIK3CA and/or PTEN genes but excluded mutations in CCM genes. CONCLUSIONS: Despite pathologic heterogeneity, brain bleeding after irradiation is uniformly associated with primordial cavernous-like telangiectasias and disruption of genes implicated in dysangiogenesis but not genes implicated as causative of cerebral cavernous malformations. This may implicate a novel signaling axis as an area for future study.

A comprehensive review on the development of sporadic cerebral arteriovenous malformations: from Padget to next-generation sequencing.

Cerebral arteriovenous malformations (AVMs) are a leading cause of intracerebral hemorrhage in both children and young adults. With the continued advancement of science and technology, the understanding of the pathophysiology behind the development of these lesions has evolved. From early theory published by Harvey Cushing and Percival Bailey in 1928, Tumors Arising from the Blood-vessels of the Brain: Angiomatous Malformations and Hemangioblastoma, which regarded AVMs as tumors arising from blood vessels, to the meticulous artistry of Dorcas Padget's embryological cataloguing of the cerebral vasculature in 1948, to the proliferative capillaropathy theory of Yasargil in 1987, to Ramey's 2014 hierarchical model of vascular development, there have been multiple hypotheses of congenital, developmental, and genetic two-hit theories in the pathogenesis of AVMs. Most recent evidence implicates somatic KRAS mutations in the cerebral endothelium, producing an important understanding of the pathogenesis of this disease, which is critical to the development of targeted therapeutics. The authors present the historical progression of their understanding of AVM pathogenesis. They focus on the foundation laid by early pioneers, discussing embryological anatomy and vasculogenesis, the prominent theories of AVM development that have emerged over time, and culminate in an overview of the most current understanding of the pathogenesis of these complex vascular lesions and the clinical implications of our scientific progress.

[Expert consensus on multidisciplinary diagnosis and treatment of brain arteriovenous malformation].

Brain arteriovenous malformation (BAVM) is a cerebral vasculature disorder caused by gene mutation. Current available treatment measures include surgical resection, interventional embolization and stereotactic radiosurgery. The three therapeutic methods have their own advantages for different vascular structures.However, due to the complex vascular architecture of the lesion and its close anatomical relationship with brain tissue, any single treatment can not safely and effectively treat all BAVM cases. Therefore, in order to better regulate and guide the clinical diagnosis and treatment of BAVM patients in China, the National Medical School for Neurological Diseases, the Professional Committee of Neurointervention of the Chinese Medical Doctor Association and the radio-neurosurgery Expert Committee of the World Chinese Neurosurgeons Association jointly discussed and formulated this expert consensus. After in-depth analysis of the evidence of evidence-based medicine at home and abroad, the expert group combined with the specific situation of China, and gave 33 recommendations on specific clinical diagnosis and treatment issues such as predictive factors of cerebral arteriovenous malformation hemorrhage, clinical risks during pregnancy, imaging diagnosis measures, and clinical treatment strategies, in order to provide guidance for the diagnosis and treatment of BAVM nationwide.

CNS resident macrophages enhance dysfunctional angiogenesis and circulating monocytes infiltration in brain arteriovenous malformation.

Myeloid immune cells are abundant in both ruptured and unruptured brain arteriovenous malformations (bAVMs). The role of central nervous system (CNS) resident and circulating monocyte-derived macrophages in bAVM pathogenesis has not been fully understood. We hypothesize that CNS resident macrophages enhance bAVM development and hemorrhage. RNA sequencing using cultured endothelial cells (ECs) and mouse bAVM samples revealed that downregulation of two bAVM causative genes, activin-like kinase 1 (ALK1) or endoglin, increased inflammation and innate immune signaling. To understand the role of CNS resident macrophages in bAVM development and hemorrhage, we administrated a colony-stimulating factor 1 receptor inhibitor to bAVM mice with brain focal Alk1 deletion. Transient depletion of CNS resident macrophages at an early stage of bAVM development mitigated the phenotype severity of bAVM, including a prolonged inhibition of angiogenesis, dysplastic vasculature formation, and infiltration of CNS resident and circulating monocyte-derived macrophages during bAVM development. Transient depletion of CNS resident macrophages increased EC tight junction protein expression, reduced the number of dysplasia vessels and severe hemorrhage in established bAVMs. Thus, EC AVM causative gene mutation can activate CNS resident macrophages promoting bAVM progression. CNS resident macrophage could be a therapeutic target to mitigate the development and severity of bAVMs.

Effect of Cobalt-60 Treatment Dose Rate on Arteriovenous Malformation Obliteration After Stereotactic Radiosurgery With Gamma Knife.

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) marginal dose is associated with successful obliteration of cerebral arteriovenous malformations (AVM). SRS dose rate-how old the cobalt-60 sources are-is known to influence outcomes for some neurological conditions and benign tumors. The objective of this study was to determine the association between cobalt-60 treatment dose rate and cerebral AVM obliteration in patients treated with SRS. METHODS: We performed a retrospective cohort study of 361 patients undergoing 411 AVM-directed SRS treatments between 2005 and 2019 at a single institution. Lesion characteristics, SRS details, obliteration dates, and post-treatment toxicities were recorded. Univariate and multivariate regression analyses of AVM outcomes regarding SRS dose rate (range 1.3-3.7 Gy, mean = 2.4 Gy, median = 2.5 Gy) were performed. RESULTS: At 10 years post-SRS, 68% of AVMs were obliterated on follow-up imaging. Dose rates >2.9 Gy/min were found to be significantly associated with AVM obliteration compared with those <2.1 Gy/min ( P = .034). AVM size, biologically effective dose, and SRS marginal dose were also associated with obliteration, with obliteration more likely for smaller lesions, higher biologically effective dose, and higher marginal dose. Higher dose rates were not associated with the development of post-SRS radiological or symptomatic edema, although larger AVM volume was associated with both types of edema. CONCLUSION: Patients with cerebral AVMs treated with higher SRS dose rates (from newer cobalt-60 sources) experience higher incidences of obliteration without a significant change in the risk of post-treatment edema.

Evolution of clinical and translational advances in the management of pediatric arteriovenous malformations.

Arteriovenous malformations (AVMs) represent one of the most challenging diagnoses in pediatric neurosurgery. Until recently, the majority of AVMs was only identified after hemorrhage and primarily treated with surgery. However, recent advances in a wide range of fields-imaging, surgery, interventional radiology, radiation therapy, and molecular biology-have profoundly advanced the understanding and therapy of these complex lesions. Here we review the progress made in pediatric AVMs with a specific focus on innovations relevant to clinical care.

Arterial Spin-Labeling MR Imaging for the Differential Diagnosis of Venous-Predominant AVMs and Developmental Venous Anomalies.

BACKGROUND AND PURPOSE: Venous-predominant AVMs are almost identical in appearance to developmental venous anomalies on conventional MR imaging. Herein, we compared and analyzed arterial spin-labeling findings in patients with developmental venous anomalies or venous-predominant AVMs, using DSA as the criterion standard. MATERIALS AND METHODS: We retrospectively collected patients with either DVAs or venous-predominant AVMs, each available on both DSA and arterial spin-labeling images. Arterial spin-labeling imaging was visually assessed for the presence of hyperintense signal. CBF measured at the most representative section was normalized to the contralateral gray matter. The temporal phase of developmental venous anomalies or venous-predominant AVMs was measured on DSA as a delay between the first appearance of the intracranial artery and the lesion. Correlation between the normalized CBF and the temporal phase was evaluated. RESULTS: Analysis of 15 lesions (13 patients) resulted in categorization into 3 groups: typical venous-predominant AVMs (temporal phase, <2 seconds), intermediate group (temporal phase between 2.5 and 5 seconds), and classic developmental venous anomalies (temporal phase, >10 seconds). Arterial spin-labeling signal was markedly increased in the typical venous-predominant AVM group, while there was no discernible signal in the classic developmental venous anomaly group. In the intermediate group, however, 3 of 6 lesions showed mildly increased arterial spin-labeling signal. The normalized CBF on arterial spin-labeling and the temporal phase on DSA were moderately negatively correlated: r(13) = 0.66, P = .008. CONCLUSIONS: Arterial spin-labeling may predict the presence and amount of arteriovenous shunting in venous-predominant AVMs, and using arterial spin-labeling enables confirmation of typical venous-predominant AVMs without DSA. However, lesions with an intermediate amount of shunting suggest a spectrum of vascular malformations ranging from purely vein-draining developmental venous anomalies to venous-predominant AVMs with overt arteriovenous shunting.

Key biomarkers in cerebral arteriovenous malformations: Updated review.

The formation of vascular networks consisting of arteries, capillaries, and veins is vital in embryogenesis. It is also crucial in adulthood for the formation of a functional vasculature. Cerebral arteriovenous malformations (CAVMs) are linked with a remarkable risk of intracerebral hemorrhage because arterial blood is directly shunted into the veins before the arterial blood pressure is dissipated. The underlying mechanisms responsible for arteriovenous malformation (AVM) growth, progression, and rupture are not fully known, yet the critical role of inflammation in AVM pathogenesis has been noted. The proinflammatory cytokines are upregulated in CAVM, which stimulates overexpression of cell adhesion molecules in endothelial cells (ECs), leading to improved leukocyte recruitment. It is well-known that metalloproteinase-9 secretion by leukocytes disrupts CAVM walls resulting in rupture. Moreover, inflammation alters the angioarchitecture of CAVMs by upregulating angiogenic factors impacting the apoptosis, migration, and proliferation of ECs. A better understanding of the molecular signature of CAVM might allow us to identify biomarkers predicting this complication, acting as a goal for further investigations that may be potentially targeted in gene therapy. The present review is focused on the numerous studies conducted on the molecular signature of CAVM and the associated hemorrhage. The association of numerous molecular signatures with a higher risk of CAVM rupture is shown through inducing proinflammatory mediators, as well as growth factors signaling, Ras-mitogen-activated protein kinase-extracellular signal-regulated kinase, and NOTCH pathways, which are accompanied by cellular level inflammation and endothelial alterations resulting in vascular wall instability. According to the studies, it is assumed that matrix metalloproteinase, interleukin-6, and vascular endothelial growth factor are the biomarkers most associated with CAVM and the rate of hemorrhage, as well as diagnostic methods, with respect to enhancing the patient-specific risk estimation and improving treatment choices.

Radiological Parameters for Gamma Knife Radiosurgery.

Accurate lesion targeting is the essence of stereotactic radiosurgery. With the currently available imaging modalities, scanning has become quick and robust providing a high degree of spatial resolution resulting in optimal contrast between normal and abnormal tissues. Magnetic resonance imaging (MRI) forms the backbone of Leksell radiosurgery. It produces images with excellent soft tissue details highlighting the target and surrounding "at-risk" structures conspicuously. However, one must be aware of the MRI distortions that may arise during treatment. Computed tomography (CT) has quick acquisition times giving excellent bony information but inferior soft tissue details. To avail benefits of both these modalities and overcome their individual fallacies and shortcomings, they are often co-registered/fused for stereotactic guidance. Vascular lesions like an arteriovenous malformation (AVM) are best planned with cerebral digital subtraction angiography (DSA) in conjunction with MRI. In specific cases, specialized imaging methods like magnetic resonance (MR) spectroscopy, positron emission tomography (PET), magneto-encephalography (MEG), etc., may be added to the treatment planning for stereotactic radiosurgery (SRS).

You Take the Low Road: Differential Outcomes After Tangential and Transcortical Approaches to Medial Temporal Brain Arteriovenous Malformations.

OBJECTIVE: Microsurgical resection of medial temporal brain arteriovenous malformations (AVMs) is typically conducted through 2 approaches: the orbitozygomatic-tangential and subtemporal-transcortical. Relative indications and outcomes for these techniques have not been formally compared. METHODS: The cerebrovascular database of a quaternary center was reviewed for patients with medial temporal AVMs treated between January 1, 1997, and July 31, 2021. Demographic characteristics, lesion characteristics, surgical approaches, and outcomes were retrospectively analyzed and compared. Postoperative outcome testing was performed using the Montreal Cognitive Assessment and Global Quality of Life Scale. RESULTS: Fifty-nine patients were assessed. Mean (standard deviation) age was 31 (18) years; 30 (51%) patients were male. Of the AVMs, 29 (49%) were left-sided and 30 (51%) were right-sided. The tangential approach was selected in 20 (34%) cases, whereas the transcortical technique was preferred in 39 (66%). Improved modified Rankin Scale status was significantly associated with the tangential resection technique both in the early postoperative period (P = 0.02) and at last follow-up (P = 0.01). Differences between the tangential and transcortical approaches were not significant with respect to new postoperative deficits (5/20 [25%] vs. 12/39 [31%], P = 0.87) or the presence of residual AVM on follow-up angiography (1/20 [6%] vs. 5/39 [14%], P = 0.65). CONCLUSIONS: The orbitozygomatic-tangential strategy was associated with favorable functional and quality-of-life outcomes after medial temporal AVM resection. These benefits are likely to be attributable to minimization of temporal retraction, avoidance of brain transgression, and avoidance of traction on the vein of Labbé, rendering the orbitozygomatic-tangential approach the preferred option for cases that are anatomically amenable to either strategy.

The micro-pathological characteristics in cerebral arteriovenous malformations(cAVMs).

BACKGROUND: Rupture and hemorrhage is the most serious complication of cerebral arteriovenous malformation(cAVMs), and have a significant impact on quality of life. OBJECTIVES: We investigated the hematoxylin and eosin staining and ultrastructural features of cAVMs and characterized the abnormal vascular structure of cAVMs. METHODS: Light and electron microscopy were performed on a series of pathological specimens obtained from 12 patients with cAVMs who underwent surgical resection for the first time without radiosurgery or embolization therapy. RESULTS: In tunica intima, we found that the vascular endothelial cells of cAVMs were damaged, and the lysis of the cell body occurred in multiple regions. In tunica media, the arrangement of the elastic layer was disordered, and the thickness was uneven. Part of the structure of the elastic lamina was missing. The part of tunica adventitia was fractured and discontinuous. In addition, we also observed the phenomenon that different blood vessels share the same vascular wall. Macrophage phagocytosis and lymphocyte infiltration in the adventitial region of ruptured cAVMs. Abnormal lipid deposition in vascular endothelial cells and smooth muscle cells. CONCLUSIONS: The structural incompleteness of cAVMs may be an important cause of hemorrhage.

New approaches for brain arteriovenous malformations-related epilepsy.

BACKGROUND: The purpose of this review is to present the current literature and to highlight the most recent findings in brain arteriovenous malformations (bAVM)-related epilepsy research. METHODS: We searched Medline, PubMed, Biblioinserm, Cochrane Central to study the latest research reports about the different factors that could be responsible for the genesis of bAVM-related epilepsy. We analyzed if epileptogenesis has any characteristics traits and its relation with the vascular malformation. The results of different treatments on epilepsy were considered. Typical errors that may lead towards incorrect or worse management of the seizures for these patients were also examined. RESULTS: The development of bAVM results from multifactorial etiologies and bAVM-related epileptogenesis is likely specific for this pathology. Different types of evidence demonstrate a bidirectional relationship between bAVM and epilepsy. Currently, there is not enough published data to determine what may be the right management for these patients. CONCLUSIONS: A better understanding of epileptogenesis in conjunction with knowledge of the complex alterations of structures and functions following bAVM-related seizures is necessary. Identification of biomarkers that can identify subgroups most likely to benefit from a specific intervention are needed to help guide clinical management. A new concept for the treatment of epilepsy related to an unruptured bAVM that cannot be treated invasively is proposed as well as new therapeutic perspectives. The next necessary step will be to propose additional algorithms to improve the development of future trials.

Segmentation techniques of brain arteriovenous malformations for 3D visualization: a systematic review.

BACKGROUND: Visualization, analysis and characterization of the angioarchitecture of a brain arteriovenous malformation (bAVM) present crucial steps for understanding and management of these complex lesions. Three-dimensional (3D) segmentation and 3D visualization of bAVMs play hereby a significant role. We performed a systematic review regarding currently available 3D segmentation and visualization techniques for bAVMs. METHODS: PubMed, Embase and Google Scholar were searched to identify studies reporting 3D segmentation techniques applied to bAVM characterization. Category of input scan, segmentation (automatic, semiautomatic, manual), time needed for segmentation and 3D visualization techniques were noted. RESULTS: Thirty-three studies were included. Thirteen (39%) used MRI as baseline imaging modality, 9 used DSA (27%), and 7 used CT (21%). Segmentation through automatic algorithms was used in 20 (61%), semiautomatic segmentation in 6 (18%), and manual segmentation in 7 (21%) studies. Median automatic segmentation time was 10 min (IQR 33), semiautomatic 25 min (IQR 73). Manual segmentation time was reported in only one study, with the mean of 5-10 min. Thirty-two (97%) studies used screens to visualize the 3D segmentations outcomes and 1 (3%) study utilized a heads-up display (HUD). Integration with mixed reality was used in 4 studies (12%). CONCLUSIONS: A golden standard for 3D visualization of bAVMs does not exist. This review describes a tendency over time to base segmentation on algorithms trained with machine learning. Unsupervised fuzzy-based algorithms thereby stand out as potential preferred strategy. Continued efforts will be necessary to improve algorithms, integrate complete hemodynamic assessment and find innovative tools for tridimensional visualization.

Whole-Exome Sequencing Reveals Pathogenic SIRT1 Variant in Brain Arteriovenous Malformation: A Case Report.

Arteriovenous malformations of the brain (bAVMs) are plexuses of pathological arteries and veins that lack a normal capillary system between them. Intracranial hemorrhage (hemorrhagic stroke) is the most frequent clinical manifestation of AVM, leading to lethal outcomes that are especially high among children and young people. Recently, high-throughput genome sequencing methods have made a notable contribution to the research progress in this subject. In particular, whole-exome sequencing (WES) methods allow the identification of novel mutations. However, the genetic mechanism causing AVM is still unclear. Therefore, the aim of this study was to investigate the potential genetic mechanism underlying AVM. We analyzed the WES data of blood and tissue samples of a 30-year-old Central Asian male diagnosed with AVM. We identified 54 polymorphisms in 43 genes. After in-silica overrepresentation enrichment analysis of the polymorphisms, the SIRT1 gene variant (g.67884831C>T) indicated a possible molecular mechanism of bAVM. Further studies are required to evaluate the functional impact of SIRT1 g.67884831C>T, which may warrant further replication and biological investigations related to sporadic bAVM.

Giant intracranial arteriovenous malformation as a possibility of epileptic seizures in a case of drowning.

A male in his late 50s had been complaining of headaches and dizziness for 25 years. He also had episodes of losing consciousness, but had not sought treatment because of financial hardship. He was found in the ocean. Autopsy revealed foamy liquid leaking from his nose and mouth, and pleural effusions. The trachea and bronchi contained the same foamy liquid. The lungs were swollen and edematous, and leaked a large amount of foamy liquid. His cause of death was diagnosed as drowning. In the brain, the veins on the frontal lobe and the temporal pole, each on the right cerebral hemisphere, were dilated. A vascular lesion measuring 5 × 5 × 8 cm was found on the bottom of the right frontal lobe, and was located between the right middle cerebral artery and those veins. This vascular lesion extended to the brain parenchyma, and the basal ganglia of the right cerebrum was displaced outward and upward. The vascular lesions in the brain showed blood vessels of various sizes and shapes, and some of the vessel walls were thickened. The vascular lesion on the right frontal lobe was diagnosed as an arteriovenous malformation (AVM). According to the police investigation, the harbor where his body was found was a place he often came for fishing and walking. The possibility of suicide cannot be ruled out. Moreover, it was considered that his AVM might have rendered him unconscious, causing him to fall into the ocean.