Materiały źródłowe

• #1 Central nervous system vascular malformations: A clinical review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7886037/

  CNS vascular malformation is an umbrella term that encompasses a wide variety of pathologies, with a wide range of therapeutic and diagnostic importance. […] The key pathology underlying vascular malformations is impairment in integrity of capillary, venous, and arterial beds. This loss of integrity can be due to external causes such as mechanical injuries and/or defects in vascular development during angiogenesis, vessel growth, and maturation. […] Various factors such as vascular endothelial growth factors, fibroblast growth factors, platelet-derived growth factors, and angiopoietins act in concert to regulate angiogenesis. Alterations in the complex interactions between these factors can lead to the development, progression, and regression of vascular malformations. […] In addition to a faulty angiogenesis, increasing evidence indicates that inflammation plays a major role in vascular dysmorphogenesis and changes in structural and functional properties of the vessels in the central nervous system.

• #1 Potential therapeutic targets and medications for arteriovenous malformations of the central nervous system

  https://accscience.com/journal/AN/1/3/10.36922/an.v1i3.211

  Arteriovenous malformations (AVMs) of the central nervous system are high-flow arteriovenous shunts that lead to considerable risks of hemorrhagic stroke and neurological deficits in young patients. […] In recent years, the pathogenesis of AVMs has been progressively explored. The increased understanding of the mechanisms of the formation, progression, and rupture of AVMs has opened up several potential directions for AVM pharmacotherapy. […] In this review, we summarize the potential mechanisms, preliminary efficacy, and side effects of the candidate medications, including bevacizumab, minocycline or doxycycline, thalidomide, and trametinib, in the treatment of brain and spinal AVMs.

• #1 Elucidating the pathogenesis behind arteriovenous malformations of the central nervous system: a bibliometric analysis

  https://scholar.barrowneuro.org/neurosurgery/1995/

  Arteriovenous malformations (AVMs) are vascular malformations of the central nervous system (CNS) with potential for significant consequences. The exact pathophysiologic mechanism of AVM formation is not fully understood. […] While progress has been made in understanding clinical aspects and risk factors, the exact pathophysiological mechanisms and genetic basis of AVM formation remain incompletely understood. Further investigation of key genes in AVM pathogenesis can allow identification of potential therapeutic targets.

• #1 Atlas of Nervous System Vascular Malformations: A Systematic Review

  https://www.mdpi.com/2075-1729/12/8/1199

  Vascular malformations are frequent in the head and neck region, affecting the nervous system. […] They are believed to be derived from alterations in the angiogenesis process during the embryonic stage, as well as from alterations in the development of the vessels during the extrauterine life. […] The main classification system for vascular anomalies for international standardization purposes that establish clinical and histopathological criteria is the one proposed by the International Society for the Study of Vascular Anomalies (ISSVA), which was updated in 2018. […] Between 40% and 60% of vascular anomalies occur in the head and neck region, mostly affecting the nervous system. […] The way to approach these anomalies depends on the specific characteristics that they exhibit. […] The authors selected 56 articles for the analysis, with a focus on a total of five vascular malformations that belong to a simple group of anatomic classification in accordance with the 2018 ISSVA guidelines: venous malformations, arteriovenous malformations, and capillary malformations.

• #1 Arteriovenous malformation – Wikipedia

  https://en.wikipedia.org/wiki/Arteriovenous_malformation

  An arteriovenous malformation (AVM) is an abnormal connection between arteries and veins, bypassing the capillary system. Usually congenital, this vascular anomaly is widely known because of its occurrence in the central nervous system (usually as a cerebral AVM), but can appear anywhere in the body. […] AVMs can cause intense pain and lead to serious medical problems. Although AVMs are often associated with the brain and spinal cord, they can develop in other parts of the body. […] An AVM interferes with this process by forming a direct connection of the arteries and veins, bypassing the capillary bed. […] As an AVM lacks the dampening effect of capillaries on the blood flow, the AVM can get progressively larger over time as the amount of blood flowing through it increases, forcing the heart to work harder to keep up with the extra blood flow. […] The resulting tangle of blood vessels, often called a nidus (Latin for 'nest’), has no capillaries. It can be extremely fragile and prone to bleeding because of the abnormally direct connections between high-pressure arteries and low-pressure veins.

• #1 The Role and Therapeutic Implications of Inflammation in the Pathogenesis of Brain Arteriovenous Malformations

  https://www.mdpi.com/2227-9059/11/11/2876

  Brain arteriovenous malformations (bAVMs) are focal vascular lesions composed of abnormal vascular channels without an intervening capillary network. As a result, high-pressure arterial blood shunts directly into the venous outflow system. These high-flow, low-resistance shunts are composed of dilated, tortuous, and fragile vessels, which are prone to rupture. […] Critically, inflammation has been suggested to contribute to lesion progression. Here we summarize the current literature discussing the role of the immune system in bAVM pathogenesis and lesion progression, as well as the potential for targeting inflammation to prevent bAVM rupture and intracranial hemorrhage. […] Overall, this review addresses the etiology and pathogenesis of brain arteriovenous malformations from an endothelial-centric point of view, focusing on the interplay between endothelial dysfunction and immune cell dynamics and how their interplay impacts disease progression.

• #1 Central nervous system vascular malformations: A clinical review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7886037/

  The genetic basis of several CNS vascular malformations has been further explained. Certain vascular malformations classically present in an autosomal dominant fashion such as familial cases of cavernous malformation, hereditary hemorrhagic telangiectasia, and capillary malformation-arteriovenous malformation as detailed later in this article. […] Several genetic variants have been identified that can render individuals susceptible to vascular malformation formation and complications. […] These genetic variants mainly regulate blood-brain barrier integrity, transforming growth factor (TGF) signaling pathway, local inflammation response, angiogenesis, and tissue remodeling. […] Understanding the pathophysiology, natural history, and characteristics predictive of the risk of rupture are all essential for clinicians when making appropriate therapeutic decisions.

• #1 Atlas of Nervous System Vascular Malformations: A Systematic Review

  https://www.mdpi.com/2075-1729/12/8/1199

  AVMs are derived from somatic mutations of the KRAS, NRAS, HRAS, BRAF, and MAP2K1 genes. […] Regardless of the etiology of AVMs, their development coincides with errors in vascular morphogenesis in the primitive vascular plexus, involving angiogenic growth factors and their receptors, retained vascular connections, vascular changes due to inflammatory responses, and increased vascular endothelial growth factor preventing the development of capillary beds. […] The correct anatomical, morphological, and functional characterization of cerebral vascular malformations, via the various imaging studies, is highly relevant in determining a therapeutic approach, either multimodal or isolated.

• #1 Pediatric Central Nervous System Vascular Malformation : Pathological Review with Diagram

  https://www.jkns.or.kr/journal/view.php?doi=10.3340/jkns.2024.0006

  Pediatric central nervous system (CNS) vascular malformations are a group of abnormal blood vessel formations within the brain or spinal cord in children. […] The most crucial point of pediatric CNS vascular malformation is that no golden standard classifications exist. […] In addition, many genes associated with pediatric CNS vascular malformation, such as Sturge-Weber-Dimitri syndrome with guanine nucleotide-binding protein G(q) subunit alpha (GNAQ) gene mutation, and cavernous malformations with cerebral cavernous malformations 1 (CCM1), CCM2, and CCM3 gene mutation, were recently revealed. […] For proper therapeutic approaches, we must understand the lesions characterizations in anatomical, morphological, and functional views. […] The terminology of malformation has some presumptions, such as presence at birth and tendency to develop regardless of clinical onset time.

• #1 Capillary Malformation: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1084479-overview

  A somatic activating mutation encoding a p.Arg183Gln amino acid substitution in GNAQ, a q class of G-protein alpha subunits that mediates signals between G-protein-coupled receptors and their downstream effectors, has been shown to be the etiology of capillary malformations. […] This specific mutation was found in both lesional skin of nonsyndromic capillary malformations and in the lesional skin and affected brain tissue of patients with Sturge-Weber syndrome (SWS). […] An inactivating mutation of RASA1 on 5q has been detected in some kindreds with multiple, small, round-to-oval, pink capillary malformations. […] RASA1 encodes a GTPase-activating protein, which negatively regulates Ras activity. […] Use of transcutaneous videomicroscopy and handheld dermoscopy reveals two distinct patterns of vascular ectasia in capillary malformations.

• #1 Arteriovenous Malformations of the Central Nervous System | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/17848

  Though the exact mechanism of AVM formation is not fully understood, they are believed to form secondary to an abnormal arrest during embryologic vascular development. Approximately 5% of AVMs are identified in patients with inherited disorders such as autosomal dominant hereditary hemorrhagic telangiectasia, also known as Osler-Weber-Rendu syndrome. […] Multiple genetic mutations have been noted in patients with sporadic AVMs, including somatic activating KRAS mutations, the stop-gain mutation in SMAD9, and an increase in Notch-3 receptor expression. Increased KRAS activity leads to increased MAPK/ERK pathway activity with downstream elevations in Notch signaling and angiogenesis factors. […] AVMs demonstrate nonphysiological hemodynamics, which affects the structure of the vessels within; they are typically high-flow, low-resistance shunts. Elevated hydrostatic pressure is a postulated contributing risk to hemorrhage. […] Arteriovenous malformations are abnormal arterial to venous structural connections without capillaries or intervening cortical tissue.

• #1

  https://journals.lww.com/idoj/fulltext/2024/15030/vascular_malformations.6.aspx

  Somatic activating mutations in TEK/TIE2 gene are responsible for up to 60% of sporadic unifocal VMs, and 20% of sporadic VMs are due to somatic mutations in the PIK3CA gene. […] The underlying pathogenesis is believed to be due to the loss of sympathetic function and subsequent unregulated blood flow in cutaneous blood vessels, leading to ectasia. […] The exact pathogenesis of GVM is not completely known yet. However, it is believed to result from abnormal proliferation and migration of glomus cells, which are specialized perivascular cells involved in thermoregulation. Mutations in novel factor glomulin (gene localized to chromosome 1p2122) are responsible for GVM. […] The underlying pathogenesis is believed to be due to abnormal function and structure of endothelial cells and blood stasis. […] There has been a growing interest in the role of RAS/RAF/MEK Kinase pathway in the pathogenesis of vascular malformations over the last decade, and trametinib, an oral inhibitor of kinase activity of MEK1 and MEK2 has shown its efficacy in vascular anomalies with mutation in RAS/RAF/MEK pathway.

• #1 The Role and Therapeutic Implications of Inflammation in the Pathogenesis of Brain Arteriovenous Malformations

  https://www.mdpi.com/2227-9059/11/11/2876

  Furthermore, transcriptomic analysis revealed an upregulation of genes characteristic of developing fetal vasculature, implying that the vessels in the nidus are either immature and/or actively remodeling. […] Gene ontology analysis of differentially expressed genes in the endothelium of the nidus highlighted angiogenic, inflammatory, and endothelial-to-mesenchymal transition pathways, while the computational prediction of ligand–receptor interactions highlighted EC–pericyte and EC–immune cell interactions associated with inflammation.

• #1 The Role and Therapeutic Implications of Inflammation in the Pathogenesis of Brain Arteriovenous Malformations

  https://www.mdpi.com/2227-9059/11/11/2876

  Notably, BBB breakdown and vascular dysfunction (e.g., cerebral hypoperfusion) can precede cognitive decline and clinical symptoms in numerous neurological pathologies, including aging, multiple sclerosis, stroke, Alzheimer’s, and epilepsy, with the disruption of vascular function in the CNS causing ion disturbance, edema, and neuroinflammation. […] These observations have prompted researchers to investigate if either BBB dysfunction contributes to, or drives, lesion rupture in bAVM rupture as well. […] Specifically, recent scRNA-sequencing studies suggest that compromised BBB function, inferred from loss of mature CNS endothelial BBB markers and increased expression of peripheral endothelial genes, could lead to an influx of inflammatory cells that may drive bAVM rupture. […] Additionally, PLVAP, a marker of fenestrated endothelium that is typically expressed by angiogenic, peripheral endothelium (e.g., outside of the mature CNS), and ANGPT2, an inducer of EC permeability, are upregulated in ECs in the nidus of bAVMs, suggesting that endothelial barrier function may be compromised in these lesions.

• #1 Genetic and epigenetic mechanisms in the development of arteriovenous malformations in the brain | Clinical Epigenetics | Full Text

  https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-016-0248-8

  Vascular malformations are developmental congenital abnormalities of the vascular system which may involve any segment of the vascular tree such as capillaries, veins, arteries, or lymphatics. […] The causative factor and pathogenic mechanisms of AVMs are unknown. Importantly, no marker proteins have been identified for AVM. […] Altered local hemodynamics in the blood vessels can affect cellular metabolism and may trigger epigenetic factors of the endothelial cell. […] We propose that AVMs result from a series of changes in the DNA methylation and histone modifications in the genes connected to vascular development. […] This review focuses on the molecular pathways of arterial and venous development and discusses the role of hemodynamic forces in the development of AVM and possible link between hemodynamic forces and epigenetic mechanisms in the pathogenesis of AVM.

• #1 Genetic and epigenetic mechanisms in the development of arteriovenous malformations in the brain | Clinical Epigenetics | Full Text

  https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-016-0248-8

  The causes for development of AVMs in the human brain are still elusive. It is widely speculated that altered hemodynamic forces at the junction of an artery and a vein might provoke the development of AVM and hemodynamic forces may be the critical epigenetic regulator in deciding the endothelial fate. […] All existing studies suggest that the abrupt changes in the hemodynamic flow in the junction of arteriovenous blood vessels might strongly influence the epigenetic mediators and eventually lead to the development of AVM. […] Thus, we speculate the presence of aberrant epigenetic landscape in AVM, particularly acquired mutations in epigenetic proteins and alterations of DNA methylations in the promoters of vascular developmental specific pathway genes.

• #1 Central Nervous System Vascular Malformations: A Patient’s Guide

  https://www.massgeneral.org/neurosurgery/treatments-and-services/vascular-malformations-patient-guide

  The purpose of this text is to provide patients who are diagnosed with central nervous system vascular malformations with some background information regarding the nature of their diagnosis and various treatments. […] There are typically four distinct types of vascular malformations which may occur throughout the central nervous system, and these will be discussed separately. […] True arteriovenous malformations (AVMs) are the most significant lesions from the clinical point of view. […] In the situation where an AVM exists, blood is shunted directly from the arterial system to the venous system. […] This elevated pressure may well contribute to hemorrhages or seizures, which occur with AVMs. […] AVMs can occur in many locations throughout the brain and spinal cord.

• #1 Brain arteriovenous malformation | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/brain-arteriovenous-malformation?lang=us

  Brain arteriovenous malformations are a type of intracranial high-flow vascular malformation composed of enlarged feeding arteries, a nidus of vessels closely associated with the brain parenchyma through which arteriovenous shunting occurs and draining veins. […] The origin of arteriovenous malformations remains uncertain, although they are thought to be multifactorial and often attributed to being congenital. Their development may involve dysregulation of vascular endothelium growth factor (VEGF) receptor-mediated endothelial proliferation and cytokine-mediated vessel remodeling. […] The nidus is fed by one or more arteries and drained by one or more veins. The feeding arteries are enlarged due to the low resistance (as blood bypasses the capillary beds) and therefore increased flow, which may lead to flow-related arterial aneurysms.

• #1 Vascular Malformations of the Central Nervous System | Thoracic Key

  https://thoracickey.com/vascular-malformations-of-the-central-nervous-system/

  The main angioarchitectural characteristic of an AVM is an area called the nidus, in which a direct shunting between arteries and veins occurs without interposed capillaries. […] The elevated intravascular flow leads to changes of the vessels. […] The presence of an intranidal aneurysm has already been described. Arteriovenous shunts can be very large, leading to the formation of large fistulas, characterized on an angiogram by an immediate injection of the venous sector. […] The fistulas are more frequent in children.

• #1 Vascular malformations of central nervous system: A series from tertiary care hospital in South India – Journal of Neurosciences in Rural Practice

  https://ruralneuropractice.com/vascular-malformations-of-central-nervous-system-a-series-from-tertiary-care-hospital-in-south-india/

  Histological features are important for classifying the VMs of CNS as there are no specific clinical and radiological features. Type of VM has a bearing on management, prognosis, and risk of hemorrhage. […] The sine qua non of an AVM is the angiographic demonstration of arteriovenous shunting. […] In AVMs, the characteristic histological features are vessels of varying sizes with intervening neural parenchyma. These vessel walls show varying thickness and show muscularization, which was confirmed with the help of special stains such as MT and VVG, where MT highlights the muscle tissue and VVG highlights the elastic lamina as well as muscle tissue in the vessel wall. […] Microscopic evidence of hemorrhage was seen in 24/36 cavernomas and 6/12 AVMs, as opposed to radiologic evidence of 10 and 4, respectively. […] Repeated hemorrhages from these cavernous malformations, a sine qua non of the disease, often without clinical manifestations, suggest that this is why they are the most common VM to cause seizures and why this is the most common clinical presentation.

• #1

  https://journals.lww.com/idoj/fulltext/2024/15030/vascular_malformations.6.aspx

  Vascular malformations are intricate anomalies of the circulatory system, presenting a diverse array of clinical manifestations, and posing significant challenges in diagnosis and treatment. The pathogenesis of vascular malformations is explored through the lens of genetic and molecular mechanisms, shedding light on the pivotal role of somatic mutations and dysregulated signaling pathways. […] Port wine stain (PWS), a common congenital vascular malformation, usually affects 0.3-0.5% of all newborns. PWS is caused by abnormally dilated capillaries in the dermis, with pathogenesis involving a variety of factors, including somatic genetic mutations, abnormal vasculogenesis, and dysregulation of VEGF (vascular endothelial growth factor) signaling pathways. Recent studies have identified several genes, such as GNAQ and GNA11, which play an essential role in the development of PWS via angiopoietin-2 activation.

• #1 Capillary Malformation: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1084479-overview

  Capillary malformations and other vascular malformations are the result of abnormal morphogenesis. […] Evidence supports a neural role in both the development and progression of capillary malformations. […] Immunohistochemical studies of capillary malformations reveal a significantly decreased density of perivascular nervous tissue in lesional skin, suggesting that inadequate innervation may be in part responsible for decreased vascular tone and progressive vascular dilatation. […] The potent endothelial cell mitogen vascular endothelial growth factor (VEGF)A and its most active receptor VEGF-R2 expression are significantly increased in capillary malformation skin tissue compared with control skin. […] This may suggest that VEGF and VEGF-R could contribute to the pathogenesis of capillary malformations by inducing vessel proliferation and/or vasodilatation.

• #1 Vascular malformations of the central nervous system: a morphological overview – PubMed

  https://pubmed.ncbi.nlm.nih.gov/3550522/

  Vascular malformations of the central nervous system (C.N.S.) are classified by size, location, and morphologic type, distinguishing capillary telangiectasias, cavernous malformations, venous angiomas, arteriovenous malformations (AVMs) including varix of the great vein of Galen, and other vascular malformations (e.g. Sturge-Weber syndrome). […] The major types of cerebral vascular malformations are described with reference to their anatomical features, location, chief arterial and venous supply, and prominent complications. […] The preferential occurrence of angiomas on the dorsal surface of the cord and in the caudal regions is related to the embryologic development of spinal vasculature. […] Frequent association of spinal angiomas (20-25%) with other vascular anomalies and dysplasias emphasizes their hamartomatous nature and developmental origin.

• #1 Vascular malformations of the central nervous system: a morphological overview – PubMed

  https://pubmed.ncbi.nlm.nih.gov/3550522/

  The complications of spinal angiomas include subarachnoid hemorrhage, rare epidural hematoma, hematomyelia, compression lesions of the cord and roots, and ischemic changes causing chronic progressive radiculomyelopathy, previously referred to as Foix-Alajouanine syndrome. […] Chronic damage to the cord and spinal roots results from pressure effects, thrombosis of the abnormal vessels, disorders of venous drainage, and „steal” phenomena related to the vascular anomalies.

• #1 Arteriovenous malformation – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/arteriovenous-malformation/symptoms-causes/syc-20350544

  An arteriovenous malformation happens when arteries and veins connect in an irregular way. Experts don’t understand why this happens. Certain genetic changes might play a role, but most types are not usually passed down in families. […] The most common complications of an arteriovenous malformation are bleeding and seizures. Bleeding can cause brain damage and may cause death if you don’t get treated.

• #1 Central nervous system vascular malformations | Beacon Health System

  https://www.beaconhealthsystem.org/library/diseases-and-conditions/central-nervous-system-vascular-malformations?content_id=CON-20301691

  Central nervous system vascular malformations are rare issues with the blood vessels in the brain or spinal cord and their coverings, called membranes. […] The cause of central nervous system vascular malformations is unclear. Some are present at birth, called congenital. Others come later. […] Some genetic conditions can increase the risk of having vascular malformation. Injury to the central nervous system might be another cause. […] Central nervous system vascular malformations can damage the brain or spinal cord. Damage can come from bleeding, called hemorrhage, into nearby tissues. Vascular malformations also can block oxygen flow to tissues and put pressure on parts of the brain or spinal cord. […] Once bleeding occurs, there’s a greater risk of having another bleed. For someone who has a vascular malformation, being pregnant might increase the risk of bleeding.

• #1 The Role and Therapeutic Implications of Inflammation in the Pathogenesis of Brain Arteriovenous Malformations

  https://www.mdpi.com/2227-9059/11/11/2876

  The treatment of symptomatic bAVMs, whether as a part of a complex inherited genetic syndrome (such as HHT), or as an isolated sporadic lesion initiated by a somatic variant within the endothelium (e.g., KRAS gain of function), represents an incredible challenge for neurosurgical teams, due to the fragility of intracranial vessels and the associated risk of stroke and hemorrhage. […] The decision for intervention is patient-specific and depends on bAVM eloquence, size, location, vascular anatomy, and complexity, as well as hemorrhage history. […] Currently no FDA-approved drug therapies exist for treating bAVM, although efforts are focused on the use of FDA-approved MEK1/2 inhibitors, as the MAPK kinase cascade (RAF-MEK-ERK) is an obligate target of KRAS in the endothelium. […] With limited treatment option for these patients, there is an urgent need to identify novel therapeutic targets based on our current understanding of bAVM pathogenesis. Since the single greatest risk bAVM patients face is the possibility of lesion rupture and intracerebral hemorrhage, identifying factors that promote or prevent rupture is critical for understanding lesion progression and identifying novel potential therapies that may reduce the risk of intracranial hemorrhage. Inflammation, in particular, proves an important target for drug research based on both the “second hit” model and its overall association with intracranial hemorrhage in both bAVMs and other cerebrovascular conditions.

• #2 Central nervous system vascular malformations – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/central-nervous-system-vascular-malformations/symptoms-causes/syc-20356113

  Central nervous system vascular malformations are rare issues with the blood vessels in the brain or spinal cord and their coverings, called membranes. […] The cause of central nervous system vascular malformations is unclear. Some are present at birth, called congenital. Others come later. […] Some genetic conditions can increase the risk of having vascular malformation. Injury to the central nervous system might be another cause. […] Central nervous system vascular malformations can damage the brain or spinal cord. Damage can come from bleeding, called hemorrhage, into nearby tissues. Vascular malformations also can block oxygen flow to tissues and put pressure on parts of the brain or spinal cord.

• #2 Vascular Malformations of the Central Nervous System | Thoracic Key

  https://thoracickey.com/vascular-malformations-of-the-central-nervous-system/

  The certain pathogenesis of AVMs is not clear. They are considered to be congenital malformations. […] The causes of an aberrant vasculo-angiogenesis leading to AVMs are unknown. Many factors are probably involved; among them, some endothelial growth factors (VEGFR1-VEGFR2) and their binding receptors (FLt-1; FLk-1) have been identified as important for the normal development of cerebral vessels. […] When considering the embryological development of the cerebral arteries and veins, some authors (Mullan et al. 1996a, b) have suggested that AVMs could already be present before the third month of gestation. […] These observations raise doubts about the congenital nature of cerebral AVMs, which at least in some cases seem to be acquired lesions caused by different nonspecific insults on the brain.

• #2 Central Nervous System Vascular Malformations: A Patient’s Guide

  https://www.massgeneral.org/neurosurgery/treatments-and-services/vascular-malformations-patient-guide

  The purpose of this text is to provide patients who are diagnosed with central nervous system vascular malformations with some background information regarding the nature of their diagnosis and various treatments. […] There are typically four distinct types of vascular malformations which may occur throughout the central nervous system, and these will be discussed separately. […] True arteriovenous malformations (AVMs) are the most significant lesions from the clinical point of view. […] In the situation where an AVM exists, blood is shunted directly from the arterial system to the venous system. […] This elevated pressure may well contribute to hemorrhages or seizures, which occur with AVMs. […] AVMs can occur in many locations throughout the brain and spinal cord.

• #2 Arteriovenous Malformations of the Central Nervous System | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/17848

  Though the exact mechanism of AVM formation is not fully understood, they are believed to form secondary to an abnormal arrest during embryologic vascular development. Approximately 5% of AVMs are identified in patients with inherited disorders such as autosomal dominant hereditary hemorrhagic telangiectasia, also known as Osler-Weber-Rendu syndrome. […] Multiple genetic mutations have been noted in patients with sporadic AVMs, including somatic activating KRAS mutations, the stop-gain mutation in SMAD9, and an increase in Notch-3 receptor expression. Increased KRAS activity leads to increased MAPK/ERK pathway activity with downstream elevations in Notch signaling and angiogenesis factors. […] AVMs demonstrate nonphysiological hemodynamics, which affects the structure of the vessels within; they are typically high-flow, low-resistance shunts. Elevated hydrostatic pressure is a postulated contributing risk to hemorrhage. […] Arteriovenous malformations are abnormal arterial to venous structural connections without capillaries or intervening cortical tissue.

• #2 Ongoing Lab Projects < Jenny Zhou Lab

  https://medicine.yale.edu/lab/jenny-zhou/projects/

  Cerebral cavernous malformations (CCMs) are common vascular malformations with a prevalence of 0.4-0.8% that affect the vasculature of central nervous system in the human population where they result in increased risk for stroke, seizures and focal neurological deficits. […] I expand my current study of CCM3 to explore the hypothesis that loss of CCM3 in endothelial cells (EC) and pericytes (PC) alters signaling critical for EC-PC interactions, contributing to vascular disassembly and capillary dilation within the neurovascular unit, leading to CCM (Nat Med, 2016; Arterioscler Thromb Vasc Biol, 2020; Nat Commun, 2021). […] Furthermore, CCM3 deletion augments the VEGFR3-ERK1/2 signaling in lymphatic endothelial cells that drives lymphatic hyperplasia and malformation and warrant further investigation on the potential clinical relevance of lymphatic dysfunction in patients with CCM (Arterioscler Thromb Vasc Biol, 2021).

• #2 Pediatric Central Nervous System Vascular Malformation : Pathological Review with Diagram

  https://www.jkns.or.kr/journal/view.php?doi=10.3340/jkns.2024.0006

  Pediatric central nervous system (CNS) vascular malformations are a group of abnormal blood vessel formations within the brain or spinal cord in children. […] The most crucial point of pediatric CNS vascular malformation is that no golden standard classifications exist. […] In addition, many genes associated with pediatric CNS vascular malformation, such as Sturge-Weber-Dimitri syndrome with guanine nucleotide-binding protein G(q) subunit alpha (GNAQ) gene mutation, and cavernous malformations with cerebral cavernous malformations 1 (CCM1), CCM2, and CCM3 gene mutation, were recently revealed. […] For proper therapeutic approaches, we must understand the lesions characterizations in anatomical, morphological, and functional views. […] The terminology of malformation has some presumptions, such as presence at birth and tendency to develop regardless of clinical onset time.

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