Congenital Vascular Lesions Research Articles

Peculiar Characteristics of Arteriovenous Malformations Arising in the Galenic Region.

Arteriovenous malformations (AVM) are congenital vascular lesions fed by arterial feeders originating from branches of the internal carotid artery (ICA) or vertebrobasilar artery. We experienced unique AVMs arising in the midline Galenic region, receiving blood supply from the ICA/vertebral artery systems and the external carotid artery system. We retrospectively reviewed data on eight patients who had an AVM arising in the Galenic region and were treated in the University of Tokyo Hospital between 1990 and 2019. The median age at diagnosis was 62 years. Three cases (38%) presented with obstructive hydrocephalus due to aqueduct obstruction caused by an engorged vein of Galen. In all cases, feeders from dural arteries were present and the vein of Galen was the primary drainer. All patients underwent stereotactic radiosurgery. Five patients were followed for > two years; nidus obliteration was confirmed in one, and > 75% shrinkage was confirmed in three, while one patient died due to hemorrhage. Altogether, AVMs arising in the Galenic region are rare and exhibit several peculiar characteristics including the presence of dural feeders, an older age at presentation and presentation with obstructive hydrocephalus.

Comprehensive analysis of dysregulated exosomal long non-coding RNA networks associated with arteriovenous malformations.

Arteriovenous malformations (AVMs) are congenital vascular lesions with a high tendency for aggravation and recurrence after treatment, and their genesis remains enigmatic. In this study, we investigated exosomal long non-coding RNA (lncRNA) and mRNA expression and constructed a competitive endogenous RNA regulatory network in AVMs. Ethics approval was provided, and informed written consent was given prior to the inclusion of all participants. Blood samples were obtained from patients with AVMs and healthy controls at Shanghai Ninth People's Hospital, China, from May to November 2018, and total exosomes were isolated and validated. Differentially expressed exosomal lncRNAs and mRNAs were detected by RNA-seq, analysed by bioinformatic methods and validated by qRT-PCR. A competitive endogenous RNA regulatory network was constructed. The characteristics of the captured extracellular vesicles conformed to the features of exosomes. A total of 117 dysregulated exosomal lncRNAs and 1159 dysregulated exosomal mRNAs were identified in AVMs. qRT-PCR demonstrated that the exosomal lncRNAs MIR4435-1HG, LINC00657, LOC101927854 and SEPT5-GP1BB were upregulated in AVM exosomes. The Gene Ontology (GO) terms haemopoiesis and negative regulation of neuron projection development were significantly enriched in relation to dysregulated exosomal cis lncRNAs. A total of 199 GO terms and 80 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were enriched for the dysregulated exosomal mRNAs. In the exosomal lncRNA-miRNA-mRNA-related ceRNA regulatory network, the top 3 significant modules involved 31 dysregulated exosomal lncRNAs and 114 dysregulated exosomal mRNAs, which were enriched in the Rap 1, Ras, MAPK signalling pathways and platelet activation KEGG pathway. This study comprehensively identified dysregulated exosomal lncRNAs and mRNAs in AVMs, demonstrated the involvement of dysregulated lncRNA and mRNA patterns in AVMs and constructed an exosomal competitive endogenous RNA regulatory network.

Effectiveness of sirolimus in the treatment of complex lymphatic malformations: Single center report of 56 cases

BackgroundLymphatic malformations are common congenital vascular lesions. Neither surgical resection nor other surgical treatments have been found to be effective for invasive cases. Recent research has suggested that sirolimus is effective in treating complex lymphatic malformations (LMs). We aimed to evaluate the effectiveness and safety of oral sirolimus for children living with LMs in our hospital. MethodsFifty-six cases of complex LMs treated with sirolimus were collected from Shanghai Children's Medical Centre between June 2016 and March 2019. All cases were confirmed either by pathology (44) or enhanced MRI (12). Following informed consent, sirolimus 0.8 mg/m2 bid was administered orally to participants and maintained at a trough concentration of 10–15 ng/ml. Children's ages at diagnosis were neonate to 16 years (mean 44.3 months). All children were followed up for 5 to 30 months, with a mean of 16.8 months. ResultsDuring the follow-up period, blood, liver and kidney function as well as disseminated intravascular coagulation was regularly reviewed in all 56 children. Enhanced MRI was regularly performed to evaluate therapeutic effects. Total effective rate (complete response or partial response) of LMs was 89.3% (50/56). No serious adverse reactions were found. ConclusionThis study suggests that sirolimus is effective and tolerable for decreasing lesions in children with complex LMs, leading to fewer and more tolerable side effects. There is no need to pursue an excision rate to reduce unnecessary operative complications since adjuvant sirolimus therapy modifies the complex LMs clinical appearance and alleviates their symptoms. Type of studyClinical research. Level of evidenceLevel IV.

Theoretical Study on Pressure Damage Based on Clinical Purpura during the Laser Irradiation of Port Wine Stains with Real Complex Vessels

Port wine stains (PWSs) are congenital dermal vascular lesions composed of a hyperdilated vasculature. Purpura represented by local hemorrhage from water vaporization in blood during laser therapy of PWS is typically considered a clinical feedback, but with a low cure rate. In this study, light propagation and heat deposition in skin and PWSs is simulated by a tetrahedron-based Monte Carlo method fitted to curved bio-tissues. A curvature-corrected pressure damage model was established to accurately evaluate the relationship between purpura-bleeding area (rate) and laser therapy strategy for real complex vessels. Results showed that the standard deviation of Gaussian curvature of the vessel wall has negative relation with the fluence threshold of vessel rupture, but has positive relation with the effective laser fluence of vessel damage. This finding indicated the probable reason for the poor treatment of PWS, that is, considering purpura formation as a treatment end point (TEP) only leads to partial removal of vascular lesions. Instead, appropriate purpura area ratio with marked effects or rehabilitation should be adopted as TEP. The quantitative correlation between the fluence of a pulsed dye laser and the characteristics of vascular lesions can provide personalized and precise guidance for clinical treatments.

Successful treatment of pathologic femoral shaft fracture associated with large arteriovenous malformations using a 3-dimensional external fixator and teriparatide: a case report

BackgroundArteriovenous malformations (AVMs) are rare congenital vascular lesions associated with early quiescence, late expansion, and, ultimately, infiltration and destruction of local soft tissue and bone. The extremities are a common location. Incidence of bony involvement by AVM has been reported as high as 31%. However, there are few reports on management of pathologic fracture associated with AVM. Teriparatide is a recombinant parathyroid hormone (PTH) analogue consisting of the 1–34 fragment of PTH. Recently, some reports have shown the ability of teriparatide to improve fracture healing. Here, we present a case of pathologic femoral shaft fracture associated with large AVMs that was treated successfully by external fixation and teriparatide.Case presentationA 68-year-old Japanese woman, previously diagnosed as having large AVMs, sustained a right femoral shaft fracture due to a fall. At the time of admission, she presented with massive swelling and venous varicosities of the right thigh. Plain radiography of the right thigh revealed femoral shaft fracture with bony erosion and calcification of soft tissue. We planned closed reduction and intramedullary nailing with a unilateral external fixator following embolization of the feeding artery. However, closed reduction using the fracture table was difficult. When we attempted open reduction, massive bleeding (1000 mL) after incision of subcutaneous tissue occurred. Finally, we carefully applied a Taylor Spatial Frame. Fracture displacement was corrected successfully and bony union was obtained with administration of teriparatide 15 months after the initial surgery. The patient is able to walk using 1 cane.ConclusionWe present the first report of pathologic fracture associated with large AVMs that achieved bony union using a 3-dimensional external fixator and teriparatide.

Vascular changes of the head and neck

Many types of vascular changes on the face can be treated after proper diagnosis in such a way as to take into account the behavior of the aesthetic appearance. There are many different congenital vascular lesions in the skin, but they are mainly vascular malformations and hemangiomas. The paper presents the characteristics of changes and therapeutic options.

P.116 Orbital lymphaticovenous malformation with intradural extension: a rare case

Orbital lymphaticovenous malformations (LVM) are congenital vascular lesions that are typically infiltrative in nature. There have been reports of orbital LVMs extending intracranially through orbital fissures, but there have been no reports of intradural extension that we are aware of. We present the case of an otherwise healthy 25-year-old female with an orbital LVM extending intradurally. Imaging revealed an intraorbital lesion extending through a bony defect in the medial orbital roof to the orbitofrontal cortex. A modified orbitozygomatic approach was used to obliterate this lesion. A durotomy was created to examine the intradural extension of the lesion, which appeared as a lobulated red vascular structure emanating from the dura along the roof of the orbit. This was gradually and comprehensively bipolar coagulated and subsequently obliterated. Neurosurgical and ophthalmological collaboration was used in the surgical management of this case. In summary, we report the first case of an orbital LVM extending intradurally, and provide pre and post-operative imaging as well as images captured through the intraoperative microscope. Through this case we highlight the importance of an interdisciplinary approach when managing orbital LVMs, as both ophthalmological and neurosurgical expertise were critical in the success of the surgery.

Orbital Lymphaticovenous Malformation with Intradural Extension: Rare Case

Orbital lymphaticovenous malformations (LVMs) are congenital vascular lesions that are typically infiltrative in nature. There have been reports of orbital LVMs extending intracranially through orbital fissures, but there have been no reports of intradural extension. We report the first case of orbital LVM extending intradurally through a bony defect in the medial orbital roof. A modified orbitozygomatic approach was used to successfully obliterate this lesion. Neurosurgical and ophthalmologic collaboration was used in the surgical management of this case. This case highlights the importance of an interdisciplinary approach when managing infiltrative orbital LVMs, as both ophthalmologic and neurosurgical expertise were critical in the success of the surgery.

Current status, pitfalls and future directions in the diagnosis and therapy of lymphatic malformation.

Lymphatic malformations are complex congenital vascular lesions composed of dilated, abnormal lymphatic channels of varying size that can result in significant esthetic and physical impairment due to relentless growth. Lymphatic malformations comprised of micro-lymphatic channels (microcystic) integrate and infiltrate normal soft tissue, leading to a locally invasive mass. Ultrasonography and magnetic resonance imaging assist in the diagnosis but are unable to detect microvasculature present in microcystic lymphatic malformations. In this review, we examine existing tools and elaborate on alternative diagnostic methods in assessing lymphatic malformations. In particular, photoacoustics, low-toxicity nanoparticles and optical clearing can overcome existing challenges in the examination of lymphatic channels in vivo. In combination with photothermal scanning and flow cytometry, Photoacoustic techniques may provide a versatile tool for lymphatic-related clinical applications, potentially leading to a single diagnostic and therapeutic platform to overcome limitations in current imaging techniques and permit targeted theranostics of microcystic lymphatic malformations.

Congenital capillary proliferation of the kidney: a distinctive renal vascular lesion of childhood

Renal vascular lesions (RVL) are rare, and their morphological spectrum remains largely unknown, particularly in children. In this study, we characterize the clinicopathological features of RVL in a cohort of 12 children. Seven lesions were classified as previously recognized entities: vascular malformations (4), papillary endothelial hyperplasia (2), and pyogenic granuloma (lobular capillary hemangioma; 1). An eighth lesion showed nonspecific findings, which were interpreted as reactive during our review. The remaining 4 cases presented either prenatally, at birth, or shortly after birth and were morphologically similar. These were characterized by a peculiar pattern of capillary proliferation with entrapment of native renal structures, variable amounts of extramedullary hematopoiesis and reactive lymphocytes, foci of infarction and hemorrhage, and the presence of feeding and draining vessels at their periphery. To our knowledge, this represents a previously undescribed congenital vascular lesion involving the kidney, which we have descriptively and provisionally termed congenital capillary proliferation of the kidney (CCPK). While it is unclear whether CCPK represents a malformation or neoplastic proliferation, it shows overlapping features with congenital hemangioma of the liver (solitary congenital hepatic hemangioma) and congenital nonprogressive hemangioma (CNH) of the skin and soft tissue, suggesting a possible common pathogenesis among these 3 entities.

High Grade Incidental Brain Arteriovenous Malformation

Brain arteriovenous malformations (BAVM) are congenital vascular lesions consisting of direct arterial to venous connection without a capillary network. They occur in 0.1% of the population, most commonly in the supratentorial region. Aneurysm, intracranial hemorrhage and stroke are the major complications. We present 2 cases two cases of high grade incidental BAVM. A thorough evaluation of the lesion and the risks of surgical intervention determine the appropriate management.

Genetic and epigenetic mechanisms in the development of arteriovenous malformations in the brain.

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. Arteriovenous malformations (AVMs) are congenital vascular lesions, initially described as “erectile tumors,” characterized by atypical aggregation of dilated arteries and veins. They may occur in any part of the body, including the brain, heart, liver, and skin. Severe clinical manifestations occur only in the brain. There is absence of normal vascular structure at the subarteriolar level and dearth of capillary bed resulting in aberrant arteriovenous shunting. The causative factor and pathogenic mechanisms of AVMs are unknown. Importantly, no marker proteins have been identified for AVM. AVM is a high flow vascular malformation and is considered to develop because of variability in the hemodynamic forces of blood flow. Altered local hemodynamics in the blood vessels can affect cellular metabolism and may trigger epigenetic factors of the endothelial cell. The genes that are recognized to be associated with AVM might be modulated by various epigenetic factors. We propose that AVMs result from a series of changes in the DNA methylation and histone modifications in the genes connected to vascular development. Aberrant epigenetic modifications in the genome of endothelial cells may drive the artery or vein to an aberrant phenotype. 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.

Acquired Port-wine Stain in an Adult Male: First Reported Case from India with Review of Literature.

Port-wine stains (PWSs) are congenital vascular lesions caused by progressive ectasia of blood vessels located in the vascular plexus of the dermis. Acquired PWSs develop later in life but are identical in morphology and histology to the congenital PWSs. Less than 75 cases of acquired PWSs have been reported in the published literature, of which there has not been a single report from India so far. Various factors have been proposed for its pathogenesis like trauma, actinic exposure, drugs, tumors, and herpes zoster infection. We report an acquired port-wine stain in a 41-year-old male. The causative factors, treatment, and previous reports of this uncommon entity have also been reviewed.

Surgical treatment and outcome of cerebral cavernomas – a 10 years’ experience

Abstract Cavernous malformations (cavernomas) are congenital low flow angiographic occult vascular lesions with a high tencency to bleeding. The prevalence of cerebral cavernous vascular malformations is estimated to be 0.4% to 0.9%.2,7 CMs in deep locations, including the brainstem, thalamus, and basal ganglia, account for 9% to 35% of all malformations in the brain. We performed a retrospective 10 years study on 130 operated cerebral cavernomas and discussed the clinical status at presentation, the choice and timing of the surgical approach and the short and longterm follow up. The 130 operated cases were divided into a supratentorial 102 (78.46%) group and an infratantorial group 28 (21.53%). The average age at presentation was 43,62 years old (17-76) and there was no sex predominance, male/female = 1,44 (77/53). Only in 14 cases (10.76%) we could find multiple cavernomas which had relatives with multiple cavrnomas, but the familial inheritance was not studied, and only the symptomatic lesion was resected. We divided the outcome results reporting for agroup with superficial respectively profound lesions. The long term follow up for the patients in the profound lesions group showed that 31/37 (83,78%) of patients had a mRS between 0 and 2, and the rest had a poor long term outcome. After surgery there was no clinical deterioration in the superficial lesions group and 22 patients from those who presented in mRS 2 showed neurological improvement on long term follow up, meaning that 82,79% of patients had a 0 or 1 mRS. Microsurgery is the treatment of choice in symptomatic brain cavernomas, total resection being the only curative treatment, capable to prevent further bleeding and to offer an efficient control of seizures.

Intraventricular hemorrhage secondary to AVM of the septum pellucidum

AbstractArteriovenous malformations (AVMs) of the brain include congenital vascular lesions that represent about 2% of all hemorrhagic strokes. Despite the relative rarity of the disease (with a detection rate estimated at approximately 1/100.000 person-years), AVMs represent a significant neurological problem. Affected patients are mostly young and healthy. AVMs located in the medial region of the cerebral hemisphere and the limbic system comprise a special group with difficult access and consequent difficulties of resection. Furthermore, there is a high incidence of intracranial hemorrhage resulting from a complex venous drainage, sometimes directed to the superficial veins, but mostly to the deep venous system. The present case report illustrates a patient with an AVM centered on the septum pellucidum, whose initial clinical resulted from an intra-ventricular hemorrhage.

Vein of Galen malformation: What to do when vascular access is not feasible?

Abstract Background: The vein of Galen aneurysmal malformation (GVAM) is a rare congenital vascular lesion, with high morbidity and mortality without treatment, endovascular management is the best alternative available today. Aim: The purpose of this work is to report the case of a female patient with imaginological and angiographical diagnosis of GVAM, which was difficult for endovascular managent alone, due to this was decided an alternative endovascular direct access guided by stereotactic assistance. Case report: We report the case of an infant with imaging and angiographic diagnosis of GVAM, with absence of the vein access through classical embolization could be done, complicating and making difficult for endovascular management alone, hence was decided an alternative endovascular direct access guided by stereotactic assistance, ensuring total embolization of the lesion with coils. The patient progressed satisfactorily. Discussion: VGAM generally represents only 1% or less of total cerebral vascular malformations, but in pediatrics may be as high as 30%. The malformation is occupying the subarachnoid space of the velum interpositum and the quadrigeminal cistern. It is characterized by the presence of the vein embryonic precursor of the vein of Galen, and abnormal arterial shunts from arteries normally developed but extremely dilated. Mortality rate is high in these patients without treatment, developing hydrocephalus and cerebral complications related to the occupying mass that could drive to epilepsy, serious cognitive sequelae, intracerebral emorrhage and death within the possibilities. Heart failure is often a common complication. To our knowledge this is the first report of the use of stereotactic assistance in the endovascular therapeutic management of VGAM. Conclusions: In cases where clasical venous access cannot be achieved as in the case we report, further technical assistance can be obtained with stereotactic guidance, making easier the procedure, remembering that without therapy, VGAM result in lifethreatening hydrocephalus and/or intracranial hemorrhage, rapidly driving to death.

The ARUBA Trial: How Should We Manage Brain AVMs?

Brain arteriovenous malformations (bAVMs) are abnormal shunts that bypass the capillary bed and directly divert blood from the arterial to the venous circulation, without exchanging nutrients or dissipating the arterial blood pressure. They are thought to be congenital vascular lesions that occur during the late stages of fetal development, however the exact pathogenesis has not been elucidated yet.1 History of hemorrhage, small AVM size, high arterial feeding blood pressure, and deep venous drainage are the main risk factors that increase the likelihood of AVM rupture. According to the American Stroke Association, 1 in 200-500 people have an AVM, while 25% of AVM patients experience seizures and 50% of patients suffer intracranial hemorrhage (ICH) at some point in their lives.2 Also, 5-15% of AVM patients experience severe headaches because of the increased intracranial pressure and a similar percentage of patients exhibit neurological deficits.1 With the advent of noninvasive imaging, AVMs are being detected at an early, unruptured stage, but the optimal course of action for preventing future complications still remains uncertain. The ARUBA trial strove to determine whether medical management or interventional therapy has a better long-term outcome for patients with unruptured AVMs. While it provides important data, limitations in its study design raise doubts concerning the generalizability of its findings.

Treatment of port-wine stains with flash lamp pumped pulsed dye laser on Indian skin: a six year study.

Context:Port-wine stain (PWS) is one of the commonly encountered congenital cutaneous vascular lesions, with an equal sex distribution. Pulsed dye lasers (PDL) have revolutionized the treatment of both congential and acquired cutaneous vascular lesions. The pulsed dye lasers owing to its superior efficacy and safety profile have become the gold standard for the management of port-wine stains.Aims:To evaluate the efficacy and side effects of pulsed dye laser for the management of Port-wine stain on Indian skin.Materials and Methods:Seventy five patients of Fitzpatrick skin types IV&V with PWS underwent multiple treatments with PDL (V beam-Candela) over a period of six years at monthly intervals. Laser parameters were wavelength 595nm, spot sizes 7-10mm, fluence 6-12 j/cm2, pulse duration 0.45-10ms, along with cryogen cooling. Serial photographs were taken before and after every session. Clinical improvement scores of comparable photographs using a quartile grading (o=<20%, 1=21-40%, 2=41-60%, 3=61-80%, 4=>80%) were judged independently by two dermatologists after the series of treatment. Minimum number of treatments was 6 and maximum 17. They were followed up at six monthly intervals to observe re darkening of PWS.Results:No patient showed total clearance.Grade3 improvement was observed in 70 % of children and 50% of adults after 8-10 sessions. Children showed better and faster response than adults. Thirty percent of patients developed post inflammatory hyper pigmentation which resolved over a period of six to eight weeks. Two patients had superficial scarring due to stacking of pulses. None of the patients showed re darkening of PWS till now.Conclusion:Pulsed dye laser is an effective and safe treatment for port-wine stain in Indian skin.

Psychological Impact of Cutaneous Congenital Vascular Lesions

Vascular lesions are abnormalities of vascular elements that appear at birth or in infancy. Cutaneous congenital vascular lesions are the most common pediatric birthmarks and can be divided into two different categories: hemangiomas and vascular malformations. Hemangiomas tend to involute, as the child grows older while other vascular malformations tend to persist. Congenital vascular lesions are found most commonly on the head and neck and can be isolated or part of a congenital syndrome such as Klippel-Trenaunay syndrome, Sturge-Weber syndrome and others. Vascular lesions, especially on exposed sites, can cause significant psychological distress for patients and family members.

Lasers for cutaneous congenital vascular lesions: a comprehensive overview and update

The use of laser to treat cutaneous lesions began with Dr. Leon Goldman and his coworkers in 1963. Ten years later, these authors described promising effects on angiomas using the continuous-wave neodymium:yttrium-aluminum-garnet laser. In 1983, Anderson et al. proposed the photothermolysis theory. The selective destruction of vascular lesions is based on this principle, and it is still a guide for treatment of vascular lesions. Over the past 25years, laser treatment of cutaneous vascular lesions has progressed significantly. Vascular lasers such as argon, tunable dye, krypton, and copper vapor were used in the past and were associated not only with risk of scarring but also hyper- and hypopigmentation. Since then, new devices were developed in order to minimize these side effects. This article presents an overview and update of the current available treatment of cutaneous vascular lesions and covers future directions for vascular laser technology.