ISVI-IUA consensus document - diagnostic guidelines on vascular anomalies: vascular malformations and hemangiomas.

The diagnostic approach to vascular anomalies should include the distinction between vascular tumors (i.e. hemangiomas) and congential vascular malformations (CVMs). This step is based more on history and clinical examination rather than on instrumental evaluation. In children Duplex ultrasound and histology can be helpful to separate hypervasularized tumors from CVMs. Appropriate record of objective measures as size or flow volume is required in order to evaluate the progress of the pathology and/or to assess the results of adopted therapeutic interventions. The anatomic, pathological and hemodynamic characteristics, the secondary effects on the surrounding tissues and the systemic manifestations should be defined. Basic diagnostic tools are Duplex sonography followed by MRI or CT scanning. The definition of the vascular anomaly should be according to the Hamburg classification and should separate vascular tumors from vacular malformations followed by separation of high flow from low flow CVMs. Diagnostic investigations are best undertaken at centers where subsequent therapeutic interventions will be performed.

Feasibility of stereotactic MRI-based image guidance for the treatment of vascular malformations: a phantom study.

PURPOSE Treatment of vascular malformations requires the placement of a needle within vessels which may be as small as 1 mm, with the current state of the art relying exclusively on two-dimensional fluoroscopy images for guidance. We hypothesize that the combination of stereotactic image guidance with existing targeting methods will result in faster and more reproducible needle placements, as well as reduced radiationexposure, when compared to standard methods based on fluoroscopy alone. METHODS The proposed navigation approach was evaluated in a phantom experiment designed to allow direct comparison with the conventional method. An anatomical phantom of the left forearm was constructed, including an independent control mechanism to indicate the attainment of the target position. Three interventionalists (one inexperienced, two of them frequently practice the conventional fluoroscopic technique) performed 45 targeting attempts utilizing the combined and 45 targeting attempts utilizing the standard approaches. RESULTS In all 45 attempts, the users were able to reach the target when utilizing the combined approach. In two cases, targeting was stopped after 15 min without reaching the target when utilizing only the C-arm. The inexperienced user was faster when utilizing the combined approach and applied significantly less radiation than when utilizing the conventional approach. Conversely, both experienced users were faster when using the conventional approach, in one case significantly so, with no significant difference in radiation dose when compared to the combined approach. CONCLUSIONS This work presents an initial evaluation of a combined navigation fluoroscopy targeting technique in a phantom study. The results suggest that, especially for inexperienced interventionalists, navigation may help to reduce the time and the radiation dose. Future work will focus on the improvement and clinical evaluation of the proposed method.

Inherited cavernous malformations of the central nervous system: clinical and genetic features in 19 Swiss families

Cavernous malformations (CCMs) are benign, well-circumscribed, and mulberry-like vascular malformations that may be found in the central nervous system in up to 0.5% of the population. Cavernous malformations can be sporadic or inherited. The common symptoms are epilepsy, hemorrhages, focal neurological deficits, and headaches. However, CCMs are often asymptomatic. The familiar form is associated with three gene loci, namely 7q21-q22 (CCM1), 7p13-p15 (CCM2), and 3q25.2-q27 (CCM3) and is inherited as an autosomal dominant trait with incomplete penetrance. The CCM genes are identified as Krit 1 (CCM1), MGC4607 (CCM2), and PDCD10 (CCM3). Here, we present the clinical and genetic features of CCMs in 19 Swiss families. Furthermore, surgical aspects in such families are also discussed.

Cavernous malformations of the central nervous system in children: presentation, treatment and outcome of 20 cases

Cavernous malformations (CM) of the central nervous system are vascular malformations responsible for symptoms such as seizures, headache, and neurological deficits: 25% of cases already present in childhood.

Reticulate eruptions. Part 1: Vascular networks and physiology

Reticulate pattern is one of the most important dermatological signs of a pathological process involving the superficial vascular networks. Vascular malformations, such as cutis marmorata congenita telangiectasia and benign forms of livedo reticularis, and sinister conditions, such as meningococcal meningitis or Sneddon's syndrome, can all present with a reticulate pattern. The clinical presentation and morphology is determined by the nature and extent of the underlying pathology and the involvement of a particular vascular network. This review has been divided into four instalments. In the present paper, we discuss the anatomy and physiology of the complex network of vascular structures that support the function of the skin and subcutis.

Vascular endothelial cell-specific phosphotyrosine phosphatase (VE-PTP) activity is required for blood vessel development

VE-PTP, a receptor-type phosphotyrosine phosphatase, associates with the tyrosine kinase receptor Tie-2 and VE-cadherin and enhances the adhesive function of the latter. Here, VE-PTP was found to be restricted to endothelial cells, with a preference for arterial endothelium. Mutant mice expressing a truncated, secreted form of VE-PTP lacking the cytoplasmic and transmembrane domains and the most membrane-proximal extracellular fibronectin type III repeat, showed severe vascular malformations causing lethality at 10 days of gestation. Although blood vessels were initially formed, the intraembryonic vascular system soon deteriorated. Blood vessels in the yolk sac developed into dramatically enlarged cavities. In explant cultures of mutant allantoides, endothelial cells were found next to vessel structures growing as cell layers. No signs for enhanced endothelial apoptosis or proliferation were observed. Thus, the activity of VE-PTP is not required for the initial formation of blood vessels, yet it is essential for their maintenance and remodeling.

Functional interaction of vascular endothelial-protein-tyrosine phosphatase with the angiopoietin receptor Tie-2

During development of the vertebrate vascular system essential signals are transduced via protein-tyrosine phosphorylation. Null-mutations of receptor-tyrosine kinase (RTK) genes expressed in endothelial cells (ECs) display early lethal vascular phenotypes. We aimed to identify endothelial protein-tyrosine phosphatases (PTPs), which should have similar importance in EC-biology. A murine receptor-type PTP was identified by a degenerated PCR cloning approach from endothelial cells (VE-PTP). By in situ hybridization this phosphatase was found to be specifically expressed in vascular ECs throughout mouse development. In experiments using GST-fusion proteins, as well as in transient transfections, trapping mutants of VE-PTP co-precipitated with the Angiopoietin receptor Tie-2, but not with the Vascular Endothelial Growth Factor receptor 2 (VEGFR-2/Flk-1). In addition, VE-PTP dephosphorylates Tie-2 but not VEGFR-2. We conclude that VE-PTP is a Tie-2 specific phosphatase expressed in ECs, and VE-PTP phosphatase activity serves to specifically modulate Angiopoietin/Tie-2 function. Based on its potential role as a regulator of blood vessel morphogenesis and maintainance, VE-PTP is a candidate gene for inherited vascular malformations similar to the Tie-2 gene.

Vascular birthmarks

Vascular birthmarks can be classified into hemangioma and vascular malformations. Hemangioma are frequent tumours of early infancy demonstrating endothelial hyperplasia, a history of rapid neonatal growth and slow involution during later childhood. Treatment of hemangioma is dependent of stage and type of the lesion. Given the current availability of drugs, lasers, and other techniques to treat hemangioma safely, philosophy of "benign neglect" should not be considered anymore. Vascular malformations show a normal endothelial turnover, being present at birth and growing commensurately with the child. Exact diagnosis by employing modern diagnostic means,which are able to differentiate low-flow from high flow lesions is important for further therapeutic management. Beside conservative treatment strategies, use of laser, sclerotherapy, interventional embolization and surgical treatment are possible management options. Patients should receive multidisciplinary care in qualified vascular centres.

Percutaneous embolization of arteriovenous malformations at the plantar aspect of the foot

Peripheral arteriovenous malformations (AVM) remain most challenging among various congenital vascular malformations to be treated. Here we present three illustrative patients with Yakes type IIIb and type IV AVM at the plantar aspect of the foot who were successfully treated by minimally invasive embolization. The value of the Yakes AVM classification system to guide the therapeutic decision making by directing specific therapeutic procedures to specific AVM types defined by their angioarchitecture is demonstrated. Direct percutaneous AVM puncture with coiling of aneurysmal outflow vein and subsequent ethanol embolization is shown. Finally, the report illustrates that several AVM types can coexist.

Meningocerebral angiodysplasia with metanephric induction failure: Broadening the spectrum of an emerging maldevelopmental syndrome

The uncommon simultaneous occurrence of an exuberant, angioma-like proliferation of superficial cerebral microvessels along with absence of the kidneys has been proposed to constitute a syndromic complex for which the term "meningocerebral angiodysplasia (or angiomatosis) with renal agenesis" (MCA-RA) is being descriptively used. We observed this constellation in one of a pair of dichorionic male twins following postpartal death in the 38th week of pregnancy. General autopsy revealed rudimentary metanephric anlagen made up of few residual glomeruli, cysts lined by flattened tubular epithelium, and islands of cartilage - corresponding to renal aplastic dysplasia. Largely inconspicuous with respect to its gyral pattern, as well as the configuration of the ventricular system, the brain microscopically showed extensive replacement of the cortex by a lattice of proliferating capillaries with necrosis of the intervening parenchyma. Minute foci of calcified necrosis were scattered in the deep subcortical white matter as well, while the ventricular ependyma and the subventricular germ cell layer remained remarkably intact. The cerebellum and brain stem appeared unaffected as well. Karyotyping of skin fibroblasts indicated a normal chromosome set of 46XY without gross structural anomalies. We interpret these findings as ones apt to being reasonably accommodated within the spectrum of MCA-RA. Although exceedingly rare, accurate identification of individual cases of MCA-RA is relevant both to differential diagnosis from its prognostically different look-alike "proliferative vasculopathy and hydranencephaly-hydrocephaly" (PVHH), and to refine the nosology of unconventional pediatric vascular malformations, for which the rather nonspecific label "angiodysgenetic necrotizing encephalopathy" is still commonly used.

Consensus Document of the International Union of Angiology (IUA)-2013. Current concept on the management of arterio-venous management

Arterio-venous malformations (AVMs) are congenital vascular malformations (CVMs) that result from birth defects involving the vessels of both arterial and venous origins, resulting in direct communications between the different size vessels or a meshwork of primitive reticular networks of dysplastic minute vessels which have failed to mature to become 'capillary' vessels termed "nidus". These lesions are defined by shunting of high velocity, low resistance flow from the arterial vasculature into the venous system in a variety of fistulous conditions. A systematic classification system developed by various groups of experts (Hamburg classification, ISSVA classification, Schobinger classification, angiographic classification of AVMs,) has resulted in a better understanding of the biology and natural history of these lesions and improved management of CVMs and AVMs. The Hamburg classification, based on the embryological differentiation between extratruncular and truncular type of lesions, allows the determination of the potential of progression and recurrence of these lesions. The majority of all AVMs are extra-truncular lesions with persistent proliferative potential, whereas truncular AVM lesions are exceedingly rare. Regardless of the type, AV shunting may ultimately result in significant anatomical, pathophysiological and hemodynamic consequences. Therefore, despite their relative rarity (10-20% of all CVMs), AVMs remain the most challenging and potentially limb or life-threatening form of vascular anomalies. The initial diagnosis and assessment may be facilitated by non- to minimally invasive investigations such as duplex ultrasound, magnetic resonance imaging (MRI), MR angiography (MRA), computerized tomography (CT) and CT angiography (CTA). Arteriography remains the diagnostic gold standard, and is required for planning subsequent treatment. A multidisciplinary team approach should be utilized to integrate surgical and non-surgical interventions for optimum care. Currently available treatments are associated with significant risk of complications and morbidity. However, an early aggressive approach to elimiate the nidus (if present) may be undertaken if the benefits exceed the risks. Trans-arterial coil embolization or ligation of feeding arteries where the nidus is left intact, are incorrect approaches and may result in proliferation of the lesion. Furthermore, such procedures would prevent future endovascular access to the lesions via the arterial route. Surgically inaccessible, infiltrating, extra-truncular AVMs can be treated with endovascular therapy as an independent modality. Among various embolo-sclerotherapy agents, ethanol sclerotherapy produces the best long term outcomes with minimum recurrence. However, this procedure requires extensive training and sufficient experience to minimize complications and associated morbidity. For the surgically accessible lesions, surgical resection may be the treatment of choice with a chance of optimal control. Preoperative sclerotherapy or embolization may supplement the subsequent surgical excision by reducing the morbidity (e.g. operative bleeding) and defining the lesion borders. Such a combined approach may provide an excellent potential for a curative result. Conclusion. AVMs are high flow congenital vascular malformations that may occur in any part of the body. The clinical presentation depends on the extent and size of the lesion and can range from an asymptomatic birthmark to congestive heart failure. Detailed investigations including duplex ultrasound, MRI/MRA and CT/CTA are required to develop an appropriate treatment plan. Appropriate management is best achieved via a multi-disciplinary approach and interventions should be undertaken by appropriately trained physicians.

[Acute headache in a case of cerebral cavernomas]

We report a case of a 52-year-old female patient with known cerebral cavernomas and acute headache. A cranial CT scan excluded an intracranial bleeding. Cavernomas are rare vascular malformations of the venous blood system (synon. cavernous angiomas) with a slow blood flow. Clinical manifestation is presented between an age of 30-50 years with mostly unspecific neurological symptoms like headache, nausea, vomiting and dizziness, but also epileptic seizures and bleedings may occur. In general, therapy is symptomatic. In cases of seizures, however, anticonvulsive treatment is indicated. Operation can be discussed for peripheral localized cavernomas with bleeding or for refractory seizures. If antiplatelet or anticoagulation therapy is necessary due to other diseases (coronary heart disease, atrial fibrillation, thrombosis, pulmonary embolism), cerebral cavernomas are not considered as an absolute contraindication. The risk for an ischemic stroke under atrial fibrillation (5-20%), for example, is higher than the risk for bleeding of a cerebral cavernoma under anticoagulation therapy.

3D Ultrasound imaging--a useful non-invasive tool to detect AV fistulas in transplanted kidneys

BACKGROUND: A precise, non-invasive, non-toxic, repeatable, convenient and inexpensive follow-up of renal transplants, especially following biopsies, is in the interest of nephrologists. Formerly, the rate of biopsies leading to AV fistulas had been underestimated. Imaging procedures suited to a detailed judgement of these vascular malformations are to be assessed. METHODS: Three-dimensional (3D) reconstruction techniques of ultrasound flow-directed and non-flow-directed energy mode pictures were compared with a standard procedure, gadolinium-enhanced nuclear magnetic resonance imaging angiography (MRA) using the phase contrast technique. RESULTS: Using B-mode and conventional duplex information, AV fistulas were localized in the upper pole of the kidney transplant of the index patient. The 3D reconstruction provided information about the exact localization and orientation of the fistula in relation to other vascular structures, and the flow along the fistula. The MRA provided localization and orientation information, but less functional information. Flow-directed and non-flow-directed energy mode pictures could be reconstructed to provide 3D information about vascular malformations in transplanted kidneys. CONCLUSION: In transplanted kidneys, 3D-ultrasound angiography may be equally as effective as MRA in localizing and identifying AV malformations. Advantages of the ultrasound method are that it is cheaper, non-toxic, non-invasive, more widely availability and that it even provides more functional information. Future prospective studies will be necessary to evaluate the two techniques further.

Microsurgical treatment of perimedullary spinal arteriovenous fistulas

Objective: Perimedullary arteriovenous fistulas (PMAVF) are exceptional spinal vascular malformations and their best therapeutic management remains controversial. Here the authors present their experience with PMAVF to characterize the clinical, neuroimaging and treatment data of patients operated on PMAVF and to analyse both incidence of complications and resurgery in the microsurgical therapy of PMAVF. Method: Fifteen patients (13 men, 2 women, mean age 51 years) with PMAVF identified by selective spinal angiography were microsurgically treated at our institution between 1992 and 2006. The presenting symptoms (duration 3 months to 5 years) were consistent with progressive myelopathy (13) or included isolated pain syndrome (2). Lumbar PMAVF location (6) was predominant followed by the sacral (5) and thoracic (4) site including 6 PMAVF of the filum terminale and 2 PMAVF associated with a glomerular AVM and dural arteriovenous fistula, respectively. Microsurgical PMAVF obliteration and postoperative angiography were routinely performed. All patients were available for follow-up evaluation within 6 months postoperatively. Results: Surgery with complete (12) or almost complete (3) PMAVF occlusion resulted in neurological improvement (10) or stabilization (1), 4 patients deteriorated postoperatively. Whereas no complications occured, a second operation because of residual or recanalized PMAVF was indicated in one case each. Two associated dual spinal vascular malformations could be observed and subsequently obliterated. Conclusions: Microsurgical occlusion of PMAVF appears to be a secure and adequate therapeutic option that prevents progressive neurological deterioration and results in good outcome in the majority of patients. Complications associated with surgery, recurrences and reoperations are infrequent. Therefore, in the authors experience microsurgery is the preferred therapy to treat PMAVF. Despite the rarity of PMAVF the possibility of the coincidence of associated second vascular malformations should be considered.