Live transplantation in children with biliary atresia and vascular anomalies

Eight of 29 infants and children undergoing orthotopic liver transplantation for extrahepatic biliary atresia had associated major vascular anomalies. A distinctive and highly unusual vascular malformation consisting of absent inferior vena cava, anomalous origin of the hepatic artery, and preduodenal portal vein was encountered in three of these children. Although at times technically difficult, single anomalies of hepatic vasculature were satisfactorily handled. In contrast, transplantation attempts were lethal in all three infants having the complex vascular malformation. The suggestion is made that this specific subgroup of patients with biliary atresia be identified in advance and that, at the moment, children with this composite anomaly are highly questionable candidates for liver transplantation. © 1974

Verrucous venous malformation

Verrucous venous malformation, also known as verrucous hemangioma, is a superficial vascular malformation with a variable degree of hyperkeratosis that is composed of capillaries and veins in the dermis and sometimes subcutaneous tissue. We describe a 53-year-old man who presented with a large hyperkeratotic plaque of the left dorsal and plantar foot. Biopsy revealed verrucous acanthosis of the epidermis and a proliferation of thin-walled vessels in the dermis. We provide a brief review of the clinical and histopathologic presentation, differential diagnosis, and management of this rare entity

Exceptional aggressiveness of cerebral cavernous malformation disease associated with PDCD10 mutations.

PurposeThe phenotypic manifestations of cerebral cavernous malformation disease caused by rare PDCD10 mutations have not been systematically examined, and a mechanistic link to Rho kinase-mediated hyperpermeability, a potential therapeutic target, has not been established.MethodsWe analyzed PDCD10 small interfering RNA-treated endothelial cells for stress fibers, Rho kinase activity, and permeability. Rho kinase activity was assessed in cerebral cavernous malformation lesions. Brain permeability and cerebral cavernous malformation lesion burden were quantified, and clinical manifestations were assessed in prospectively enrolled subjects with PDCD10 mutations.ResultsWe determined that PDCD10 protein suppresses endothelial stress fibers, Rho kinase activity, and permeability in vitro. Pdcd10 heterozygous mice have greater lesion burden than other Ccm genotypes. We demonstrated robust Rho kinase activity in murine and human cerebral cavernous malformation vasculature and increased brain vascular permeability in humans with PDCD10 mutation. Clinical phenotype is exceptionally aggressive compared with the more common KRIT1 and CCM2 familial and sporadic cerebral cavernous malformation, with greater lesion burden and more frequent hemorrhages earlier in life. We first report other phenotypic features, including scoliosis, cognitive disability, and skin lesions, unrelated to lesion burden or bleeding.ConclusionThese findings define a unique cerebral cavernous malformation disease with exceptional aggressiveness, and they inform preclinical therapeutic testing, clinical counseling, and the design of trials.Genet Med 17 3, 188-196

Familial multiple cavernous malformation syndrome : MR features in this uncommon but silent threat

Cerebral cavernous malformations (CCM) are vascular malformations in the brain and spinal cord. The familial form of cerebral cavernous malformation (FCCM) is uncommon. This autosomal dominant pathology mostly presents with seizures and focal neurological symptoms. Many persons affected by FCCM remain asymptomatic. However, acute hemorrhages may appear over time. MRI demonstrates multiple focal regions of susceptibility induced signal loss, well seen on gradient-echo sequences (GRE) or even better on susceptibility-weighted imaging (SWI). The presence of a single CCM – especially in young persons – without history of FCCM does not exclude this diagnosis. Some clinicians also advise an MRI of the spinal cord at the time of diagnosis to serve as a baseline and a control MRI of the brain every one to two years. MRI is certainly indicated in individuals with obvious new neurologic symptoms. Symptomatic siblings should also undergo an MRI of the brain to determine presence, size, and location of the lesions. Even in asymptomatic siblings, a screening MRI may be considered, as there may be an increased risk of hemorrhage, spontaneous or due to the use of certain medications; the knowledge of the presence and the type of these lesions are important. Surgical removal of a CCM may be justified to prevent a life-threatening hemorrhage. Control MRI may reveal the postoperative outcome

A Case Report and Overview of Familial Cerebral Cavernous Malformation Pathogenesis in an Adult Patient

OBJECTIVE We present a case of a 39 year-old woman who presented with a solitary cavernous malformation hemorrhage without any other lesions, and subsequently presented several months later with a new hemorrhage from a de novo lesion. We discuss mechanisms of paradominant inheritance and haploinsufficiency to describe phenotype expression of familial cavernous malformations. CASE DESCRIPTION The patient presented with unremitting headaches, who had a known history of a solitary cerebral cavernous malformation (CCM) for which she underwent resection several months prior with no evidence of any other CCM lesions seen on post-operative MRI. She has no history of whole brain radiation, family history of cavernous malformations, or prior head trauma. During this hospital visit, she was found to have develop two new lesions in the left fronto-parietal lobe and cerebellum. She was treated with surgical resection of the left frontoparietal lesion, and recovered fully. It is of interest that a patient approaching her fourth decade of life would start to develop formation of multiple de novo cavernous malformations, especially with an absent family history. Paradominant Inheritance and haploinsufficiency are two proposed models of inheritance that can be related to this patient’s disease progression. CONCLUSION The case illustrates an atypical clinical course of a patient with familia

High-Flow Vascular Malformations in Children.

Children can have a variety of intracranial vascular anomalies ranging from small and incidental with no clinical consequences to complex lesions that can cause substantial neurologic deficits, heart failure, or profoundly affect development. In contrast to high-flow lesions with direct arterial-to-venous shunts, low-flow lesions such as cavernous malformations are associated with a lower likelihood of substantial hemorrhage, and a more benign course. Management of vascular anomalies in children has to incorporate an understanding of how treatment strategies may affect the normal development of the central nervous system. In this review, we discuss the etiologies, epidemiology, natural history, and genetic risk factors of three high-flow vascular malformations seen in children: brain arteriovenous malformations, intracranial dural arteriovenous fistulas, and vein of Galen malformations

The roles of endoglin gene in cerebrovascular diseases.

Endoglin (ENG, also known as CD105) is a transforming growth factor β (TGFβ) associated receptor and is required for both vasculogenesis and angiogenesis. Angiogenesis is important in the development of cerebral vasculature and in the pathogenesis of cerebral vascular diseases. ENG is an essential component of the endothelial nitric oxide synthase activation complex. Animal studies showed that ENG deficiency impairs stroke recovery. ENG deficiency also impairs the regulation of vascular tone, which contributes to the pathogenesis of brain arteriovenous malformation (bAVM) and vasospasm. In human, functional haploinsufficiency of ENG gene causes type I hereditary hemorrhagic telangiectasia (HHT1), an autosomal dominant disorder. Compared to normal population, HHT1 patients have a higher prevalence of AVM in multiple organs including the brain. Vessels in bAVM are fragile and tend to rupture, causing hemorrhagic stroke. High prevalence of pulmonary AVM in HHT1 patients are associated with a higher incidence of paradoxical embolism in the cerebral circulation causing ischemic brain injury. Therefore, HHT1 patients are at risk for both hemorrhagic and ischemic stroke. This review summarizes the possible mechanism of ENG in the pathogenesis of cerebrovascular diseases in experimental animal models and in patients

Arterial dysgenesis and limb defects : Clinical and experimental examples

Acknowledgements This article is dedicated to Dr David S. Packard Jr. With thanks to Dr John DeSesso, Dr Lewis B. Holmes, Dr Mark Levinsohn, Dr David S. Packard Jr, Prof Lewis Wolpert for discussions on vascular disruption, particularly arterial dysgenesis and limb defects. We apologise to the many authors whose work we were unable to cite due to space limitations. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Peer reviewedPostprin

Arterial anatomy and arteriographic diagnosis of arteriogenic impotence

One hundred twenty-six bilateral selective arteriographic examinations of the iliopudendal vascular tree were performed after comprehensive multidisciplinary evaluation in patients with chronic erectile dysfunction. Best imaging results were obtained by performing the arteriography under epidural anesthesia after intracavernous injection of a vasoactive drug combination. The arteriography is mandatory prior to revascularization procedures. It is further indicated in primary erectile dysfunction and posttraumatic erectile failure. The importance of cavernosography and selective arteriography in primary erectile dysfunction is stressed. Increasing knowledge about the influence of vasoactive drugs on penile hemodynamics has led to its application in diagnosis and therapy of erectile dysfunction. Pharmacocovernosography, Doppler-ultrasound of penile arteries after intracavernous injection of a vasoactive drug combination, and pharmacoarteriography are refined techniques to prove a vascular etiology of erectile dysfunction. The results of the morphologic studies of the vascular system are correlated with functional testing of erectile capacity by intracavernous application of a papaverinephentolamine drug combination