Embolization of pulmonary and systemic mycotic pseudoaneurysms in a pediatric patient.

Mycotic pseudoaneurysm is a rare complication of systemic infection in children. We report a case of a previously healthy 11-year-old female with methicillin-resistant staph aureus (MRSA) bacteremia who developed both pulmonary and systemic arterial pseudoaneurysms. These were detected on magnetic resonance (MR) and computed tomography (CT) imaging and treated with coil embolization.

Somatic activating BRAF variants cause isolated lymphatic malformations.

Somatic activating variants in PIK3CA, the gene that encodes the p110α catalytic subunit of phosphatidylinositol 3-kinase (PI3K), have been previously detected in ∼80% of lymphatic malformations (LMs).1 , 2 We report the presence of somatic activating variants in BRAF in individuals with LMs that do not possess pathogenic PIK3CA variants. The BRAF substitution p.Val600Glu (c.1799T>A), one of the most common driver mutations in cancer, was detected in multiple individuals with LMs. Histology revealed abnormal lymphatic channels with immunopositivity for BRAFV600E in endothelial cells that was otherwise indistinguishable from PIK3CA-positive LM. The finding that BRAF variants contribute to low-flow LMs increases the complexity of prior models associating low-flow vascular malformations (LM and venous malformations) with mutations in the PI3K-AKT-MTOR and high-flow vascular malformations (arteriovenous malformations) with mutations in the RAS-mitogen-activated protein kinase (MAPK) pathway.3 In addition, this work highlights the importance of genetic diagnosis prior to initiating medical therapy as more studies examine therapeutics for individuals with vascular malformations.

Migration of n-BCA glue as a complication of venous malformation treatment in children.

Preoperative n-butyl cyanoacrylate (n-BCA) embolization of venous malformations facilitates surgical resection. Although embolization is generally well-tolerated, central venous n-BCA migration can occur. The purpose of this article is to describe 3 cases of glue migration requiring glue embolectomy. Strategies for prevention and treatment of glue migration during embolization of venous malformations are reviewed.

Line days as a determinant of central line-associated bloodstream infections in pediatric patients with tunneled femoral peripherally inserted central catheters.

BACKGROUND: Ultrasound (US)-guided tunneled femoral peripherally inserted central catheters (PICCs) are a safe central venous access option in infants and neonates. Studies have shown, however, that femoral central venous access has the potential for high central line-associated bloodstream infection (CLABSI) rates with a significant increase in risk around line day 30, though no studies have evaluated these risks exclusively for tunneled femoral PICCs. OBJECTIVE: The primary purpose of this study was to evaluate the relationship between line duration and the risk of CLABSI in tunneled femoral PICCs in children. MATERIALS AND METHODS: Four hundred forty-five patients (196 females, 249 males; median age: 49.4 days; median weight: 3.7 kg) who underwent 573 tunneled femoral PICC placements or exchanges from Jan. 1, 2017, to Jan. 31, 2020, were included in the study. All tunneled femoral PICCs were placed using US technique and catheter specifications, including catheter size (French) and length (cm), were retrieved from the electronic medical record. The location of the PICC placement, the number of lumens, the laterality of placement, and the patient's age and weight were also recorded. Only non-mucosal barrier injury CLABSIs, according to the Centers for Disease Control and Prevention (CDC) definitions, were counted as CLABSI for this study. The number of central line days until a CLABSI event was analyzed with an accelerated failure time model using the exponential, Weibull, and log-normal distributions to determine the probability of a CLABSI over time, taking into consideration the recorded covariates. RESULTS: Tunneled femoral PICC placements accounted for 14,855 line days, during which 20 non-mucosal barrier injury CLABSIs (CLABSI rate of 1.35 per 1,000 line days) occurred during the study period. The highest CLABSI rate occurred in PICCs placed in the neonatal intensive care unit (NICU) at 2.01 per 1,000 line days and the lowest occurred in PICCs placed in interventional radiology at 0.26 per 1,000 line days. Overall, PICCs placed outside of interventional radiology had a CLABSI rate of 1.72 per 1,000 line days. The CLABSI rate during the first 30 days a line was in situ was lower than the rate after 30 days (0.51 per 1,000 line days vs. 3.06 per 1,000 line days, respectively). Statistical modeling and hazard estimation using the Akaike information criterion corrected for small sample size (AICc)-average of log-normal, Weibull and exponential distributions demonstrate the daily risk of CLABSI rapidly increases from day 1 to day 30, with the risk remaining high for the duration of line days. CONCLUSION: While tunneled femoral PICCs are a relatively safe and effective central venous access alternative, the rate of CLABSI appears to rapidly increase with increasing line days until around day 30 and then remains high thereafter.

Computational fluid dynamics modeling aiding surgical planning in a toddler with Parkes Weber syndrome.

Parkes Weber syndrome is a fast-flow and slow-flow vascular anomaly with limb overgrowth that can lead to congestive heart failure and limb ischemia. Current management strategies have focused on symptom management with focal embolization. A pediatric case with early onset heart failure is reported. We discuss the use of computational fluid dynamics (CFD) modeling to guide a surgical management strategy in a toddler with an MAP2K1 mutation.

Confirmatory radiographs have limited utility following ultrasound-guided tunneled femoral central venous catheter placements by interventional radiology.

BACKGROUND: Ultrasonography may reliably visualize both appropriately positioned and malpositioned femoral-approach catheter tips. Radiography may be used to confirm catheter tip position after placement, but its utility following intraprocedural ultrasound (US) catheter tip verification is unclear. OBJECTIVES: To report the utility of confirmatory radiographs after US-guided tunneled femoral central venous catheter (CVC) placements by interventional radiology in pediatric patients. MATERIALS AND METHODS: A total of 484 pediatric patients underwent bedside US-guided tunneled femoral CVC placements in an intensive care setting at a single tertiary children's hospital between Jan. 1, 2016, and April 20, 2020. Technical success, adverse events, post-procedure radiographic practices and inter-modality catheter tip concordance were recorded. All radiographs were performed within 12 h of catheter placement. RESULTS: The mean patient age was 175±508 days (range: 1 day to 19 years), including 257 (53.1%) males and 227 (46.9%) females. Of the 484 attempted placements, 472 (97.5%) were primary placements. Four hundred eighty-one (99.4%) placements were technically successful. There were three (0.6%) technical failures due to previously undiagnosed iliofemoral venous occlusive disease. Five (1.0%) adverse events occurred. Radiographs were obtained within 12 h of CVC placement in 171 (35.3%) patients, in 120 (70.2%) of whom the indication was recent catheter placement. All 171 (100%) post-placement radiographs showed catheter tip location concordance with the intra-procedural US. In one (0.2%) patient, in whom there was nonvisualization of a guidewire and clinical concern for malposition during US-guided placement, post-procedure radiographs, coupled with multiplanar venography, demonstrated inadvertent paravertebral venous plexus catheter placement. CONCLUSION: The concordance between intra-procedural US and confirmatory post-procedure radiographs of CVC placements by interventional radiology obviates the need for routine radiographs. Radiographs may be obtained in instances of proceduralist uncertainty or clinical concern.

Spinal ultrasound after failed landmarked-based lumbar puncture: a single institutional experience.

BACKGROUND: The safety and efficacy of US-guided lumbar puncture in children has been described. In the pediatric setting, children are frequently referred to interventional radiology only after a failed landmark-based attempt. Routine pre-procedure US in these children is useful to determine a safe level for subarachnoid access and to optimize success. OBJECTIVE: To determine whether pre-procedure US improves technical success and safety of US-guided lumbar puncture. MATERIALS AND METHODS: We included 47 children. Inclusion criteria were urgent US-guided lumbar puncture in pediatric patients <18 years old. Exclusion criteria were non-urgent lumbar punctures, children referred without an antecedent landmark-based attempt, lumbar punctures performed with fluoroscopic guidance, and procedures performed prior to introducing the diagnostic approach in 2017. We did not evaluate data pertaining to successful landmark-based lumbar punctures performed without subsequent need for additional attempts. We recorded technical successes, adverse events and relevant abnormalities identified on pre-procedural US. RESULTS: Thirty-six US-guided lumbar punctures were performed with 100% technical success. Eleven children referred to interventional radiology did not undergo lumbar puncture because of unfavorable US findings or interval clinical improvement obviating the need for lumbar puncture. Thirty-six children underwent US evaluation of the thecal sac prior to potential intervention. Of these 36 with pre-procedural US studies, 12 demonstrated paucity of cerebrospinal fluid and 14 demonstrated an epidural hematoma. Fifteen children who underwent lumbar puncture had a "traumatic tap," classified as a mild adverse event. No moderate or severe adverse events were recorded. CONCLUSION: Limited spinal US following failed landmark-based lumbar punctures frequently identifies procedure-related complications and can augment patient selection for future image-guided lumbar punctures.

Transforaminal intrathecal delivery of nusinersen for older children and adults with spinal muscular atrophy and complex spinal anatomy: an analysis of 200 consecutive injections.

BACKGROUND: Nusinersen is the only approved treatment for all spinal muscular atrophy (SMA) subtypes and is delivered intrathecally. Distorted spinal anatomy and instrumentation preclude standard approaches for intrathecal access, necessitating alternative techniques for delivery. The purpose of this study is to report technical success and adverse events of transforaminal intrathecal delivery of nusinersen. METHODS: 28 patients, mean age 24.1±9.8 years (range 10.0-51.0 years), with intermediate or late onset SMA, underwent a combined 200 transforaminal nusinersen injections. All patients had osseous fusion or spinal instrumentation precluding standard posterior access routes. Patients who underwent nusinersen injections using a technique other than transforaminal lumbar puncture (n=113) were excluded. Technical success, adverse events (AEs) and radiation exposure were recorded. RESULTS: 200 (100%) procedures were technically successful; 6 (3%) required a second level of attempt for access. 187 (93.5%) interventions were completed using cone beam computed tomography (CBCT) with two-axis fluoroscopic navigational overlay. 13 (6.5%) procedures were performed with fluoroscopic-guidance only at subsequent sessions. There were 8 (4.0%) mild AEs and 2 (0.5%) severe AEs; one patient received antibiotics for possible traversal of the large bowel but did not develop meningitis, and one patient developed aseptic meningitis. Mean air kerma was 74.5±161.3 mGy (range 5.2-1693.0 mGy). CONCLUSION: Transforaminal intrathecal delivery of nusinersen is feasible and safe for gaining access in patients with distorted spinal anatomy. The use of CBCT delineates anatomy and optimizes needle trajectory during the initial encounter, and may be used selectively for subsequent procedures.

Combined endolymphatic and surgical treatment of a leaking central conducting lymphatic malformation in a neonate.

Lymphatic malformations are congenital alterations of normal embryonic lymphatic development. We present a case of a premature 7-week-old male with a large central conducting lymphatic malformation and significant abdominal chylorrhea. He was successfully treated with combined endolymphatic and surgical approaches. To the authors' knowledge, this is the first case to be described.

Initial experience with the Ellipsys Vascular Access System for percutaneous arteriovenous fistula creation in adolescents: A case report.

This retrospective, single center, case report describes the first use of the Ellipsys Vascular Access System for percutaneous arteriovenous fistula (pAVF) creation in children. Two adolescent (<20 year of age) patients (18 and 19-year-old females), one of whom was developmentally delayed, were not considered candidates for traditional surgical arteriovenous fistula creation. pAVF creation was successful in both patients using the Ellipsys device and physiologic maturation of the fistula was achieved within 8 weeks of creation with subsequent 2 needle cannulation. No complications or adverse events were encountered. pAVF creation with the Ellipsys device can be safely performed in adolescents. Further studies will be needed to validate the expanded use of these devices in children.

Ultrasound Evaluation of Pediatric Slow-Flow Vascular Malformations: Practical Diagnostic Reporting to Guide Interventional Management.

OBJECTIVE. This article reviews the ultrasound characteristics of pediatric slow-flow vascular malformations and underscores findings that significantly impact diagnosis and treatment. Key imaging features are discussed including lesion size, malformation location, morphology, and mimics. CONCLUSION. Ultrasound findings affect the management of slow-flow vascular malformations and should be emphasized in lesion diagnosis. Superficial, focal lesions with well-defined margins are ideal for ultrasound evaluation.

Managing systemic venous occlusions in children.

Pediatric venous disease is increasing in incidence in both inpatient and outpatient populations. The widespread use of central venous access devices as well as the rising incidence of thromboembolic events in pediatrics is leading to more systemic venous occlusions in both the central and peripheral veins. This review focuses on the etiology, presentation, workup, and general technical considerations of recanalization as well as procedural complications related to pediatric systemic venous occlusive disease. The potential role for pediatric interventional radiology guided treatments will be discussed in detail.

Hepatopulmonary Syndrome in an Adolescent With Insidious Hypoxia and Small Intrahepatic Portal Venous Shunts: Posttransplant Benefit From Sildenafil.

We report a patient without known preexisting liver disease who presented with hepatopulmonary syndrome (HPS) due to aberrant intrahepatic portal venous development leading to portosystemic shunting. Liver transplantation resulted in resolution of portal hypertension and HPS and sildenafil was safely tolerated in the treatment of persistent fatigue and hypoxemia. Twelve months later, patient has normal allograft function and has returned to normal activity.

Intrahepatic veno-venous collateralization and misrepresentative hepatic venous pressure gradients in children.

BACKGROUND: Accurate and reproducible means of measuring the portosystemic gradient are essential for risk stratification and treatment of portal hypertension. OBJECTIVE: To report the reliability of hepatic venous pressure gradients in children with intrahepatic veno-venous collateralization. MATERIALS AND METHODS: Between January 2012 and December 2019 (96 months), 39 patients with native livers underwent wedge hepatic venography and hepatic venous pressure gradient measurements at a tertiary pediatric center. All archived images were reviewed for balloon isolation of the hepatic vein and hepatic vein-to-hepatic vein (HV-HV) collaterals. HV-HV collaterals were categorized as present on the basis of non-catheterized segmental venous opacification despite appropriate balloon isolation. Hepatic venous pressure gradient was defined as the difference of wedge and free hepatic venous pressures. Wedge portosystemic gradient was defined as the difference between wedge hepatic venous pressure and right atrial (RA) pressures. For patients subsequently undergoing portal venous catheterization, portosystemic gradient was defined as the difference between main portal vein and RA pressures. RESULTS: Thirteen of 39 (33.3%) patients demonstrated HV-HV collaterals on wedge hepatic venography. The mean hepatic venous pressure gradient was 5.2±3.8 mmHg (range: 0-15 mmHg). The mean hepatic venous pressure gradient was 3.6±2.6 mmHg (range: 0-9 mmHg) in the presence of HV-HV collaterals and 5.9±4.2 mmHg (range: 1-15 mmHg) in the absence of HV-HV collaterals (P=0.043). Twelve (30.8%) patients were found to have varices: 10 gastroesophageal, 1 rectal and 1 stomal. The mean hepatic venous pressure gradient in patients with varices was 5.4±47 mmHg (range: 0-15 mmHg). For patients with varices, mean hepatic venous pressure gradient was 3.0±2.7 mmHg (range: 0-9 mmHg) in the presence of HV-HV collaterals and 10.3±4.1 mmHg (range: 5-15 mmHg) in the absence of HV-HV collaterals (P=0.004). Four (10.3%) patients had extrahepatic portal vein occlusion: 3 with cavernous transformation and 1 with type Ib Abernethy malformation. All patients with extrahepatic portal vein occlusion demonstrated HV-HV collaterals compared with 8 of 35 (22.9%) patients without extrahepatic portal vein occlusion (P=0.002). Four of 39 (10.3%) patients underwent direct portal pressure measurements: 3 via transhepatic and 1 via trans-splenic portal access. All had demonstrated HV-HV collaterals on wedged imaging. One had extrahepatic portal vein occlusion. The mean time between wedge portosystemic gradient and portosystemic gradient measurement was 3.75 days (range: 0-8 days). The mean wedge portosystemic gradient was 4.5±3.1 mmHg (range: 2-9 mmHg) and the mean portosystemic gradient was 14.5±3.7 mmHg (range: 12-20 mmHg) (P=0.006). CONCLUSION: HV-HV collateralization is frequently observed in children undergoing wedged portal venography and leads to misrepresentative hepatic venous pressure gradients. All patients undergoing hepatic venous pressure gradient measurement should have wedged venography to identify HV-HV collaterals and to qualify measured pressures. Additional techniques to obtain representative pressures in the presence of HV-HV collaterals warrant further investigation.

Pediatric Hepatobiliary Interventions in the Setting of Intrahepatic Vascular Malformations, Portal Hypertension, and Liver Transplant.

Within the broad spectrum of pediatric hepatobiliary disorders, hepatic vascular malformations, portal hypertension, and hepatic transplant interventions pose numerous challenges. The role of interventional radiology within each of these conditions is discussed herein, beginning with endovascular management of high flow hepatic vascular malformations. Next, while becoming less common in adult populations, surgical portoportal and portosystemic shunts remain prevalent in many pediatric centers. Shunt anatomy is reviewed along with endovascular management techniques for shunt dysfunction. Next, the growing experience with pediatric transjugular intrahepatic portosystemic shunt placement is reviewed along with tips for success in pediatric patients. Finally, pediatric hepatic transplant interventions are discussed with technical notes pertinent to split liver anatomy.

Genotype correlates with clinical severity in PIK3CA-associated lymphatic malformations.

Lymphatic malformations (LMs) are congenital, nonneoplastic vascular malformations associated with postzygotic activating PIK3CA mutations. The mutation spectrum within LMs is narrow, with the majority having 1 of 3 hotspot mutations. Despite this relative genetic homogeneity, clinical presentations differ dramatically. We used molecular inversion probes and droplet digital polymerase chain reaction to perform deep, targeted sequencing of PIK3CA in 271 affected and unaffected tissue samples from 81 individuals with isolated LMs and retrospectively collected clinical data. Pathogenic PIK3CA mutations were identified in affected LM tissue in 64 individuals (79%) with isolated LMs, with variant allele fractions (VAFs) ranging from 0.1% to 13%. Initial analyses revealed no correlation between VAF and phenotype variables. Recognizing that different mutations activate PI3K to varying degrees, we developed a metric, the genotype-adjusted VAF (GVAF), to account for differences in mutation strength, and found significantly higher GVAFs in LMs with more severe clinical characteristics including orofacial location or microcystic structure. In addition to providing insight into LM pathogenesis, we believe GVAF may have broad applicability for genotype-phenotype analyses in mosaic disorders.

Endovascular treatment of surgical mesoportal and portosystemic shunt dysfunction in pediatric patients.

BACKGROUND: Published data describing the endovascular treatment of dysfunctional mesoportal and portosystemic shunts in the pediatric population are limited. OBJECTIVE: We sought to describe the treatment and follow-up of such shunts managed by interventional radiology at a single pediatric hospital. We hypothesized that stenotic and occluded pediatric portosystemic and mesoportal shunts can be maintained patent by interventional radiology in the moderate term. MATERIALS AND METHODS: We conducted a single-center retrospective study at a tertiary pediatric hospital. We included children with surgical mesoportal (meso-Rex) or portosystemic (mesocaval, splenorenal or splenocaval) shunts treated with attempted angioplasty or stenting from 2010 to 2018. Technical success was defined as catheterization and intervention upon the shunt with venographic evidence of flow improvement. The primary outcome variables were shunt patency at 1 month, 6 months, 12 months and 24 months post-procedure and freedom from reintervention. RESULTS: Twenty pediatric patients (11 boys, 9 girls; mean age 8.25 years, range 1.3-17 years) met inclusion criteria. Fifty-two interventions (primary and reintervention) on 13 splenorenal, 3 meso-Rex, 2 mesocaval and 2 splenocaval shunts were performed because of evidence of shunt failure, including gastrointestinal bleeding, hypersplenism, or radiographic evidence of a flow defect. The 11 stenotic shunts were treated with 100% technical success, while the remaining 9 occluded shunts were treated with 66.7% technical success. The mean number of reinterventions was 1.9 (standard deviation [SD] = 3.1) per child, which did not differ between stenotic and occluded shunts (P=0.24). Primary patency at 1-month, 6-month, 12-month and 24-months follow-up visits was 17/17 (100%), 10/16 (62.5%), 7/15 (46.7%) and 4/10 (40%), respectively. However, 100% of shunts were either primary patent or primary-assisted patent by endovascular reintervention. There were no cases of shunt occlusion following initial technical success. Finally, the median freedom from reintervention duration was 387 days (SD=821 days). CONCLUSION: Dysfunctional portosystemic surgical shunts are effectively managed by endovascular methods. While many shunts require reintervention, combined primary patency and assisted primary patency rates are excellent.

An update on the use of an arterial closure device following femoral arterial puncture in children.

BACKGROUND: The use of arterial closure devices in achieving femoral hemostasis has been well documented in adults but insufficiently studied in the pediatric population. An earlier study from our institution of 40 Angio-Seal devices in 38 patients concluded that the arterial closure device is safe in children with only a single minor complication. Ongoing experience with this device at our institution, however, suggests a higher rate of complication. OBJECTIVE: To retrospectively evaluate the safety and efficacy of the Angio-Seal in a pediatric population. MATERIALS AND METHODS: A retrospective analysis reviewed all cases in which the Angio-Seal was deployed from June 2011 to September 2017. Peri-procedural documentation was reviewed for pre-procedure labs, clinical effectiveness in achieving hemostasis and complications related to the use of this device. Logistic regression analysis was also used to evaluate the relationship between patient demographic, vessel size and indication for angiography, and the presence or absence of complications. RESULTS: During the study period, 48 additional Angio-Seal devices were deployed in 41 consecutive patients. Five patients were excluded for being older than 18 years. The mean age of the patients was 13.3 years (range: 4-18 years) with 18 patients female. The mean common femoral artery diameter was 5.98 mm in short axis diameter (range: 4-9 mm). Complications were present in 6/43 cases (14%) including 3 minor and 3 major complications that included additional procedures. No significant relationship was identified between vessel size, age and the indication for angiography, and the rate of complication on logistic regression analysis. CONCLUSION: While percutaneous arterial closure devices can be efficacious for achieving hemostasis, our experience demonstrates a higher rate of complications in children, contrary to a previous report. The deployment of such devices should be performed with prejudice in this population.

Homozygous Mutations in CSF1R Cause a Pediatric-Onset Leukoencephalopathy and Can Result in Congenital Absence of Microglia.

Microglia are CNS-resident macrophages that scavenge debris and regulate immune responses. Proliferation and development of macrophages, including microglia, requires Colony Stimulating Factor 1 Receptor (CSF1R), a gene previously associated with a dominant adult-onset neurological condition (adult-onset leukoencephalopathy with axonal spheroids and pigmented glia). Here, we report two unrelated individuals with homozygous CSF1R mutations whose presentation was distinct from ALSP. Post-mortem examination of an individual with a homozygous splice mutation (c.1754-1G>C) demonstrated several structural brain anomalies, including agenesis of corpus callosum. Immunostaining demonstrated almost complete absence of microglia within this brain, suggesting that it developed in the absence of microglia. The second individual had a homozygous missense mutation (c.1929C>A [p.His643Gln]) and presented with developmental delay and epilepsy in childhood. We analyzed a zebrafish model (csf1rDM) lacking Csf1r function and found that their brains also lacked microglia and had reduced levels of CUX1, a neuronal transcription factor. CUX1+ neurons were also reduced in sections of homozygous CSF1R mutant human brain, identifying an evolutionarily conserved role for CSF1R signaling in production or maintenance of CUX1+ neurons. Since a large fraction of CUX1+ neurons project callosal axons, we speculate that microglia deficiency may contribute to agenesis of the corpus callosum via reduction in CUX1+ neurons. Our results suggest that CSF1R is required for human brain development and establish the csf1rDM fish as a model for microgliopathies. In addition, our results exemplify an under-recognized form of phenotypic expansion, in which genes associated with well-recognized, dominant conditions produce different phenotypes when biallelically mutated.