Massive Release of CD9+ Microvesicles in Human Immunodeficiency Virus Infection, Regardless of Virologic Control.

BACKGROUND: The role of extracellular vesicles (EVs) in human immunodeficiency virus (HIV) pathogenesis is unknown. We examine the cellular origin of plasma microvesicles (MVs), a type of ectocytosis-derived EV, the presence of mitochondria in MVs, and their relationship to circulating cell-free mitochondrial deoxyribonucleic acid (ccf-mtDNA) in HIV-infected patients and controls. METHODS: Five participant groups were defined: 30 antiretroviral therapy (ART)-naive; 30 ART-treated with nondetectable viremia; 30 elite controllers; 30 viremic controllers; and 30 HIV-uninfected controls. Microvesicles were quantified and characterized from plasma samples by flow cytometry. MitoTrackerDeepRed identified MVs containing mitochondria and ccf-mtDNA was quantified by real-time polymerase chain reaction. RESULTS: Microvesicle numbers were expanded at least 10-fold in all HIV-infected groups compared with controls. More than 79% were platelet-derived MVs. Proportions of MVs containing mitochondria (22.3% vs 41.6%) and MV mitochondrial density (706 vs 1346) were significantly lower among HIV-infected subjects than controls, lowest levels for those on ART. Microvesicle numbers correlated with ccf-mtDNA levels that were higher among HIV-infected patients. CONCLUSIONS: A massive release of platelet-derived MVs occurs during HIV infection. Some MVs contain mitochondria, but their proportion and mitochondrial densities were lower in HIV infection than in controls. Platelet-derived MVs may be biomarkers of platelet activation, possibly reflecting pathogenesis even in absence of HIV replication.

Inconsistency in classifying vascular anomalies: What's in a name?

BACKGROUND: Vascular anomalies are a heterogeneous group of disorders seen in children and adults. A standard nomenclature for classification has been offered by the International Society for the Study of Vascular Anomalies. Its application is important for communication among the multiple specialties involved in the care of patients and for planning treatment, as well as for research and billing. We hypothesized that terminology still is not uniformly applied, and that this could have an impact on treatment. METHODS: We retrospectively reviewed the medical records of patients with nonbrain lesions from our institutional vascular anomalies database seen during 2010-2016 for whom at least one clinic visit, radiologic imaging report, and pathology report were available to compare diagnoses among and within disciplines, and treatment recommendations. Diagnoses and referral patterns by community healthcare providers were also reviewed. RESULTS: Of 400 patients seen during the targeted time interval, 35 had clinical, imaging, and pathology reports. Agreement in terminology from initial clinic notes with imaging and pathology reports was noted in only three cases (9%). "Hemangioma" was often misused; "lymphangioma" and "cystic hygroma" persist as diagnostic labels. Community healthcare providers referred vascular malformations with a diagnosis of "mass" or "hemangioma" in 17 of 18 cases where that information was available. Incomplete or mislabeling of vascular anomalies sometimes delayed referrals to appropriate clinics, though it did not have a major impact on treatment. CONCLUSIONS: An understanding of vascular anomalies as tumors or malformations is not uniform. Ongoing education will be needed to promote consensus terminology and facilitate referrals.

Characterization of chronic HCV infection in Northwest Spain: Impact of the treatment strategic plan of the Spanish National Health Service on HCV cure.

The aim of the study was to characterize HCV infection in Northwest Spain and assess the impact of the Spanish Strategic Plan to cure HCV infection. Overall, 387 patients were included (60.9% HIV/HCV coinfected and 28.2% cirrhotic). Of these, 72.9% of patients that were recognized as priority for HCV treatment according to the Spanish Strategic Plan (≥F2, transplant or extrahepatic manifestations), initiated treatment during 2015. Globally, SVR12 was achieved in 96.5% of patients. The implementation of the Spanish Strategic Plan has been critical to advance in HCV cure, but 27.1% of priority patients still remain awaiting HCV treatment initiation.

Imaging spectrum of CNS vasculitis.

Cerebral vasculitis is characterized by inflammation of the walls of blood vessels and may affect vessels of any size. The pathogenesis of vasculitis remains poorly understood. Vasculitis may affect large vessels (Takayasu arteritis, giant cell arteritis), medium-sized vessels (Kawasaki disease, polyarteritis nodosa), small vessels (immunoglobulin A vasculitis, microscopic polyangiitis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis), or variable-sized vessels (Behçet disease, Cogan syndrome). Primary angiitis of the central nervous system (CNS) is an idiopathic disorder with no evidence of generalized inflammation that may simulate reversible cerebral vasoconstriction syndromes. Vasculitis may be secondary to systemic disease, infection, malignancy, drug use, or radiation therapy. Imaging findings vary from small ischemic changes to frank infarction, hemorrhage, and white matter edema and may show contrast material enhancement. The cerebral arteries may demonstrate a beaded appearance with variable degrees of stenosis, occlusion, and contrast enhancement of the vessel wall. Correlation of imaging findings with clinical presentation and laboratory test results helps establish the diagnosis of CNS vasculitis.

Giant dural venous sinus ectasia in neonates.

In this report, the authors describe 4 recent cases of posterior giant dural venous sinus ectasia in neonates diagnosed during pregnancy and encountered at 3 different institutions. Posterior giant venous sinus ectasia was diagnosed in 4 patients using antenatal ultrasonography and confirmed in 2 patients using prenatal MR imaging and in 3 patients using postnatal MR angiography. In 2 children angiography was performed at the age of 6 months. The pregnancy was terminated in 1 case, and the fetus underwent an autopsy. The 3 children who were born presented with various degree of cardiac insufficiency and were admitted to the intensive care unit after birth. Signs of increased intracranial pressure were present immediately after birth, including a bulging fontanel. No endovascular treatment was used in these cases. Surgery was performed in 2 cases as an attempt to alleviate increased intracranial pressure symptoms, without any real benefit. A slow venous flow in the ectasia was shown by ultrasonography in the case in which the pregnancy was terminated. Angiography or MR angiography did not show an obvious arteriovenous malformation in any of the cases, but an arteriovenous fistula secondary or contributing to the formation of the venous ectasia is one of the physiopathological hypotheses of the cause of this condition. Interestingly, spontaneous progressive thrombosis and regression of the intravascular component of the venous sinus ectasia was observed in all cases. The clinical outcome was acceptable in 1 child (who had a moderate handicap after the surgery) and good for the other 2 children (who had normal neurological development). Stratified thrombi of different ages are found in these giant venous ectasias and develop within the leaves of the dura close to the confluence of the major posterior venous sinuses. Therefore, it appears that the formation of a progressive thrombosis represents the normal evolution of these giant dural venous sinus ectasias, which explains the favorable outcome in some cases without specific surgical treatment, except for resuscitation techniques.

Imaging in spinal vascular disease.

Spinal vascular diseases are rare and constitute only 1% to 2% of all vascular neurologic pathologies. In this article, the following vascular pathologies of the spine are described: spinal arterial infarcts, spinal cavernomas, and arteriovenous malformations (including perimedullary fistulae and glomerular arterivenous malformations), and spinal dural arteriovenous fistulae. This article gives an overview about their imaging features on MRI, MR angiography, and digital subtraction angiography. Clinical differential diagnoses, the neurologic symptomatology, and the potential therapeutic approaches of these diseases, which might vary depending on the underlying pathologic condition, are given.

A report of two cases with dolichosegmental intracranial arteries as a new feature of PHACES syndrome.

BACKGROUND: We describe two previously unreported cases with complete or incomplete expression of PHACES syndrome, a rare congenital syndromal pediatric disorder, which is characterized by posterior cranial fossa malformations, large facial hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, abnormalities of the eye, sternal and supraabdominal raphe defects. CASE REPORTS: These two children exhibited a feature not reviewed extensively in the literature, namely, segmental elongation and dilatation of intracranial arteries associated with intracranial occlusive arterial disease, predominantly on the anterior division of the internal carotid artery (ICA) and on the P2 segment of the posterior cerebral artery. This dolichoectasia was found at the distal cervical internal carotid artery, the intradural segment of the ICA before the division, the trigeminal artery, and the posterior division of the ICA. We presume that the different forms of arterial involvement in PHACES syndrome (arterial stenoses, segmental agenesis of vessels, and the dolichoectasia described in this study) constitute a spectrum of angiogenetic dysfunctions related to an embryonic event involving several cephalic neural crest segments of the dorsal aorta.

Spinal arteriovenous shunts presenting before 2 years of age: analysis of 13 cases.

BACKGROUND AND PURPOSE: A minority of patients with spinal arteriovenous malformations (SAVM) are symptomatic as neonates or infants. We analyzed the clinical and anatomic factors associated with this early presentation, and reviewed our experience in treating patients with these lesions. METHODS: A retrospective review of clinical records and imaging studies was performed for patients with SAVM who presented at less than 2 years of age and who were examined by the diagnostic and interventional neuroradiology service at our institution. Clinical, imaging and treatment data had been entered prospectively into a department database. RESULTS: Thirteen patients were identified that had SAVMs that were either diagnosed or that became symptomatic before 2 years of age (nine boys, four girls). These represented 13% of the SAVM seen during the same period of time. The mean age at presentation was 6.9+/-6.4 months. Of the 13 patients, 11 had neurologic symptoms attributable to the spinal lesion. The presentation was nonhemorrhagic in ten patients and associated with hemorrhage in three. Ten lesions were fistulas [spinal cord arteriovenous fistulas (SCAVFs)] (77%); two were of the nidus type of malformation. There were syndromic associations in eight patients: hereditary hemorrhagic telangectasia (HHT) in six patients, all but one of these lesions were intradural high-flow perimedullary SCAVFs (46% of overall SAVM and 56% of SCAVF), and spinal arteriovenous metameric syndrome in two patients. One patient had Hirschprung's anomaly. Eight patients underwent endovascular treatment alone, one had surgery and embolization, and four were not treated. In all patients undergoing embolization, n-butyl cyanoacrylate liquid adhesive was used. Of those patients who underwent endovascular treatment, the lesion was completely obliterated in 7 and a 90% reduction in nidal size was achieved in the remaining 2. There was one treatment complication (infection) which resolved with medical therapy. No procedure-related permanent morbidity or mortality was seen. Follow-up data were available (mean 31.4 months) in ten patients (nine treated). All treated patients were either stable or improved, with none showing further deterioration following treatment. CONCLUSION: Factors associated with early presentation in neonates and infants with spinal arteriovenous shunts include the presence of high-flow, solitary fistulas and HHT. Specifically, the presence of SCAVF in a child less than 2 years of age is highly suggestive of HHT. Despite the aggressive nature of these lesions, many are amenable to endovascular treatment, and this is associated with a favorable posttreatment course in most cases.

Spinal cord intradural arteriovenous fistulae: anatomic, clinical, and therapeutic considerations in a series of 32 consecutive patients seen between 1981 and 2000 with emphasis on endovascular therapy.

OBJECTIVE: To review our series of intradural spinal cord arteriovenous fistulas (SCAVFs), analyzing symptoms and related angioarchitecture, and to study the morphological and clinical results of embolization. METHODS: Thirty-two SCAVFs (in 22 adults and 10 children) were treated between 1981 and 2000. These lesions were classified as microarteriovenous fistulas (mAVFs) or macroarteriovenous fistulas (MAVFs) according to shunt morphology. Location, architecture, presenting symptoms, and age group were detailed. The selection of patients for endovascular versus surgical treatments was analyzed, as were the anatomic and clinical results obtained by embolization with n-butylcyanoacrylate. Clinical status was evaluated according to the Karnofsky Performance Scale score. RESULTS: Ten SCAVFs were found in the pediatric population (four mAVFs and six MAVFs). All four mAVFs presented with acute symptoms. Three mAVFs (two cervical and one thoracic) presented hematomyelia; in one patient with a thoracic AVF, subarachnoid hemorrhage was suspected. All six MAVFs were located in the thoracolumbar cord (five associated with hereditary hemorrhagic telangiectasias). Four of the six MAVFs presented with hemorrhage. In the adult population, there were 21 mAVFS (95%) and one MAVF (5%). Only two mAVFs were found in the cervical cord, all other shunts affecting the thoracolumbar region. Hemorrhage was present in 6 of the 22 cases seen in adults (27%). The symptoms of SCAVFs did not differ from those found in spinal cord arteriovenous shunts of nidus type. Pial venous reflux and congestion were the most frequently encountered features in both the adult and pediatric groups. Arterial aneurysms (different from false aneurysms) were not found in association with hemorrhagic presentation of SCAVFs. Mean follow-up in our series was 3.3 years. Of the MAVFs, 86% were embolized, with 67% cured. The others had more than 75% occlusion. All patients followed up improved significantly. Of the mAVFs, 48% were treated endovascularly. Successful embolization was performed in 75% of patients. One patient was not embolized because of vasospasm, whereas 67% percent of mAVFs were completely occluded, 22% were more than 90% occluded, and 11% were 75% occluded. Complementary surgery was deemed unnecessary. All patients with mAVFs improved significantly at follow-up. Transient complications occurred in 22% of all patients, with no permanent morbidity or mortality. No patient bled or rebled after embolization. Thirty-six percent of mAVFs were operated on because of anticipated technical difficulties for endovascular approach or distal localization of the shunt. CONCLUSION: Endovascular treatment of SCAVFs stabilizes, normalizes, or improves neurological symptoms in all patients at long-term follow-up, with no bleeds or rebleeds. Embolization of SCAVFs with glue is a safe treatment that compares favorably with other approaches and significantly improves the poor natural history of the disease.

Embolization of spinal cord arteriovenous shunts: morphological and clinical follow-up and results--review of 69 consecutive cases.

OBJECTIVE: We sought to analyze the results of embolization in patients with intradural spinal cord arteriovenous shunts. METHODS: The clinical and radiological files of 69 of a population of 155 patients treated with embolization between 1981 and 1999 were reviewed retrospectively. The patients' clinical status was evaluated according to Karnofsky Performance Scale score. Twenty-one (14%) of 155 patients were treated surgically because they were thought to be poor candidates for embolization. Twenty-four (15%) of 155 patients were considered untreatable with surgery or embolization; in these patients, follow-up was proposed, but only 8 of them were followed appropriately and remained stable after the first consultation. Forty-one (26%) of 155 patients consulted our group, but no follow-up could be obtained. In 69 (45%) of 155 patients, comprising 20 children and 49 adults, endovascular treatment was performed with the patients under general anesthesia and without provocative tests, mainly with acrylic glue, in 99% of these patients. RESULTS: The mean number of diagnostic and therapeutic sessions was 3.5 per patient, and the mean number of pure therapeutic sessions was 1.5 per patient. Follow-up ranged between 6 months and 18 years (mean, 5.6 yr). In 16% of patients, anatomic obliteration of spinal cord arteriovenous shunts was obtained. Embolization reduced more than 50% of the spinal cord arteriovenous shunts in 86% of cases. No recanalization was noted on follow-up angiograms. Good clinical outcomes were obtained in 83% of the patients: 15% of them were asymptomatic, 43% were improved, and 25% were stable. In 4% of patients, embolization failed to stabilize the disease. Transient deficits were seen after embolization in 14% of the patients, and permanent severe complications occurred in 4% of the patients (Karnofsky Performance Scale score

Manifestaciones oftalmológicas de las facomatosis en niños / Ophthalmologic features of the phakomatoses in children

Las facomatosis son un grupo de enfermedades que afectan piel, sistema nervioso central, vasos sanguíneos y globo ocular. La mayoría de ellas se presentan desde la niñez. Para su diagnóstico es necesario un grupo multidisciplinario, incluyendo al oftalmólogo pediatra. En este estudio retrospectivo se encontraron las manifestaciones oculares más frecuentes que se observan en cada entidad. En la neurofibromatosis tipo 1, los nódulos de Lisch se observaron en 74 por ciento de los casos y neorofibroma plexiforme del párpado en 10 por ciento. En la esclerosis tuberosa el dato más frecuente fue la hipopigmentación de iris en el 10 por ciento de los pacientes. El glaucoma estuvo presente en 60 por ciento de los casos con síndrome de Sturge Weber. Por último en la ataxia telangiectasia el signo ocular relevante para el diagnóstico fue la telangiectasia conjuntival en 85 por ciento de los pacientes. No se registro ningún paciente con síndrome de von Hippel Lindau ni síndrome de Wyburn Mason