A Pilot Randomized Clinical Trial of Intranasal Oxytocin to Promote Weight Loss in Individuals With Hypothalamic Obesity.

Context: Hypothalamic obesity is a rare, treatment-resistant form of obesity. In preliminary studies, the hypothalamic hormone oxytocin (OXT) has shown promise as a potential weight loss therapy. Objective: To determine whether 8 weeks of intranasal OXT (vs 8 weeks of placebo) promotes weight loss in children, adolescents, and young adults with hypothalamic obesity. Methods: This randomized, double-blind, placebo-controlled, crossover pilot trial (NCT02849743), conducted at an outpatient academic medical center, included patients aged 10 to 35 years with hypothalamic obesity from hypothalamic/pituitary tumors. Participants received intranasal OXT (Syntocinon, 40 USP units/mL, 4 IU/spray) vs excipient-matched placebo, 16 to 24 IU 3 times daily at mealtimes. Weight loss attributable to OXT vs placebo and safety (adverse events) were assessed. Results: Of 13 individuals randomized (54% female, 31% pre-pubertal, median age 15.3 years, IQR 13.3-20.6), 10 completed the entire study. We observed a nonsignificant within-subject weight change of -0.6 kg (95% CI: -2.7, 1.5) attributable to OXT vs placebo. A subset (2/18 screened, 5/13 randomized) had prolonged QTc interval on electrocardiography prior to screening and/or in both treatment conditions. Overall, OXT was well-tolerated, and adverse events (epistaxis and nasal irritation, headache, nausea/vomiting, and changes in heart rate, blood pressure, and QTc interval) were similar between OXT and placebo. In exploratory analyses, benefits of OXT for anxiety and impulsivity were observed. Conclusion: In this pilot study in hypothalamic obesity, we did not detect a significant impact of intranasal OXT on body weight. OXT was well-tolerated, so future larger studies could examine different dosing, combination therapies, and potential psychosocial benefits.

Early identification of a 12-bp tandem duplication in TNFRSF11A encoding receptor activator of nuclear factor-kappa B (RANK): Clinical characterization and response to bisphosphonate therapy.

INTRODUCTION: Ultra-rare mendelian osteolytic disorders caused by different length in-frame activating duplications within exon 1 of TNFRSF11A encoding receptor activator of nuclear factor-kappa B (RANK) comprise familial expansile osteolysis (FEO), expansile skeletal hyperphosphatasia (ESH), early-onset familial Paget's disease of bone (PDB2), juvenile Paget's disease 2 (JPD2), and panostotic expansile bone disease (PEBD). FEO typically presents with childhood-onset deafness followed by resorption of permanent dentition, and then appendicular bone pain, fractures, and deformities from progressive focal expansile osteolytic lesions emerging from a background of generalized high bone turnover. An 18-bp duplication in TNFRSF11A has been reported in all kindreds with FEO, whereas a 12-bp duplication was found in the young man with PEBD complicated by a massive jaw tumor. We report the clinical course and successful treatment with bisphosphonates of a girl with the 12-bp duplication yet a skeletal phenotype seemingly milder than PEBD. CASE PRESENTATION AND DISCUSSION: This 10-year-old girl presented for dental and orthodontic treatment and was found to have progressive external tooth root resorption. Speech delay was identified at age 18 months, and audiological evaluation showed both conductive and sensorineural hearing loss subsequently treated with a cochlear implant at age 3 years. Biochemical studies indicated increased bone turnover with elevated urinary N-telopeptide levels and serum alkaline phosphatase in the upper normal range. Low lumbar spine bone mineral density (BMD) was revealed by dual-energy X-ray absorptiometry, but whole-body Technetium-99 m bone scintigraphy was normal. Genetic testing identified the identical de novo 12-bp duplication within exon 1 of TNFRSF11A harbored by the young man with PEBD and massive jaw tumor. Bisphosphonate treatment, initiated with one dose of intravenous zoledronic acid that caused prolonged hypocalcemia, then comprised weekly oral alendronate that decreased bone turnover markers and normalized her BMD. CONCLUSION: Constitutive activation of RANK signaling should be considered a possible cause in any young person with rapid bone turnover, particularly in the context of early-onset deafness and/or root resorption of permanent teeth. Early diagnosis and anti-resorptive treatment, given judiciously to avoid sudden and prolonged hypocalcemia, may prevent further skeletal disease.

Late Diagnosis of Congenital Toxoplasmosis with Macrocephaly in Dizygotic Twins after Incidental Detection of Leukocoria: A Case Report.

Untreated congenital toxoplasmosis remains an important cause of neurologic and ocular disease worldwide. However, congenitally infected infants may not have signs and symptoms their physicians recognize, leading to delayed diagnosis and missed opportunities for treatment. We describe a pair of twins diagnosed with congenital toxoplasmosis at 11 months of age following incidental detection of leukocoria in one twin.

Job-Readiness After Pediatric Neuroradiology Training: Defining Trainee Needs.

RATIONALE AND OBJECTIVES: To describe and analyze the pediatric neuroradiology implicit curriculum for general-pediatric and neuro-pediatric radiology fellowship training in order to define specific trainee needs and inform an explicit pediatric neuroradiology curriculum. MATERIALS AND METHODS: A focus group of pediatric radiologists, pediatric neuroradiologists and fellows was conducted to create a needs assessment questionnaire that focused on training experience, current job, and a list of essential competency items. The questionnaire was distributed to 175 members of the Society for Pediatric Radiology. Data were derived from categorical and continuous survey variables. Using an inductive approach, we analyzed and systematically inspected the data to derive themes regarding trainee needs and how they might inform an explicit curriculum. RESULTS: Fifty-seven pediatric radiologists (response rate of 33%) responded to the survey. Sixty-three percent of respondents were fellowship trained in general pediatric radiology, 21% in pediatric neuroradiology, and 16% in both. In their current jobs, 75% of respondents were responsible for interpreting some pediatric neuroradiology. 50% or greater reported limited or no fellowship instruction in five areas of imaging interpretation: fetal neuroimaging; ear and/or nose and/or throat imaging; head and neck imaging; neuroembryology; neuro-spectroscopy and four areas of technical skills and/or image quality: reducing imaging time; choice of contrast agents; sedation; understanding clinical management pathways. CONCLUSION: Trainees endorse inadequate training in certain aspects of imaging interpretation and technical skills which are known to remain a significant and vital aspect of pediatric neuroradiology practice, revealing an opportunity to emphasize these aspects in an explicit curriculum and dedicate educational resources towards this cause.

Correction to: Venous pathologies in paediatric neuroradiology: from foetal to adolescent life.

The original version of this article unfortunately contained a referencing omission. Figure 11 is reused from the original publication of Figure 10 of Gunny and Lin [1].

Venous pathologies in paediatric neuroradiology: from foetal to adolescent life.

The interpretation of cerebral venous pathologies in paediatric practice is challenging as there are several normal anatomical variants, and the pathologies are diverse, involving the venous system through direct and indirect mechanisms. This paper aims to provide a comprehensive review of these entities, as their awareness can avoid potential diagnostic pitfalls. We also propose a practical classification system of paediatric cerebral venous pathologies, which will enable more accurate reporting of the neuroimaging findings, as relevant to the underlying pathogenesis of these conditions. The proposed classification system comprises of the following main groups: arterio-venous shunting-related disorders, primary venous malformations and veno-occlusive disorders. A multimodal imaging approach has been included in the relevant subsections, with a brief overview of the modality-specific pitfalls that can also limit interpretation of the neuroimaging. The article also summarises the current literature and international practices in terms of management options and outcomes in specific disease entities.

Imaging of Pediatric Hearing Loss.

Temporal bone high-resolution computed tomography (HRCT) and magnetic resonance (MR) imaging are valuable tools in the evaluation of pediatric hearing loss. Computed tomography is important in the evaluation of pediatric conductive hearing loss and is the imaging modality of choice for evaluation of osseous abnormalities. MR imaging is the modality of choice for evaluation of sensorineural hearing loss. A broad spectrum of imaging findings can be seen with hearing loss in children. HRCT and MR imaging provide complementary information and are often used in conjunction in the preoperative evaluation of pediatric candidates for cochlear implantation.

Predictors of pediatric blunt cerebrovascular injury.

BACKGROUND/PURPOSE: Blunt cerebrovascular injury (BCVI) is clinically challenging because these injuries are hard to detect and can have serious neurological consequences, and optimal screening criteria have not been established for children. This study aims to determine risk factors for BCVI in pediatric patients and to evaluate screening practices in a single institutional series. METHODS: A retrospective review of all pediatric blunt trauma patients evaluated over a 10-year period was performed. Demographic, clinical, and radiographic data were reviewed, including the presence of adult risk factors for BCVI. Logistic regression analyses were performed with statistical significance established at p<0.05. RESULTS: Of the 11,596 patients evaluated during the study period, 1018 (8.8%) had at least one adult risk factor for BCVI, but only 62 (6.1% of those with risk factors) underwent angiographic evaluation. Overall, 11 BCVIs were observed, resulting in an incidence of 0.095%. All 11 patients with BCVI had at least one risk factor. Multivariate logistic regression analysis identified cervical spine fracture (OR 36.88 [8.36, 169.95]), GCS score ≤ 8 (OR 16.42 [2.16, 102.33]), male gender (OR 10.52 [1.33, 363.30]), Le Fort II or III facial fracture (OR 63.71 [2.16, 1124.68]), and ISS (unit OR 1.10 [1.04, 1.17]) as independent risk factors for BCVI. CONCLUSION: Adult screening criteria for BCVI appear appropriate for pediatric patients, but most at-risk children are not being screened. LEVEL OF EVIDENCE: Level III (retrospective case-control study).

Brain Tumors in the Neonate.

Brain tumors can develop in the prenatal and neonatal time periods. Neuroimaging studies are crucial for the early detection of prenatal and neonatal brain tumors. Imaging allows for characterization of morphology, as well as the detection of hydrocephalus, local invasion, and distant spread. The imaging features of the more common neonatal brain tumors, including teratomas, choroid plexus tumors, ATRTs, and neoplasm mimics are described.

The Implications of Brain MRI in Autism Spectrum Disorder.

Our objective was to describe the types of providers who refer children with autism spectrum disorder (ASD) for brain magnetic resonance imaging (MRI), the referral reason, and MRI results. The most common referral reasons were autism spectrum disorder with seizures (33.7%), autism spectrum disorder alone (26.3%), and autism spectrum disorder with abnormal neurologic examination or preexisting finding (24%). Neurology (62.5%), general pediatric (22.3%), and developmental/behavioral practitioners (8.9%) referred the most patients. The prevalence of definite pathology was highest in children referred for autism spectrum disorder with abnormal neurologic examination/preexisting finding (26.2%, 95% CI: 16.8%-36%), headaches (25.7%, 95% CI: 11.2%-40.2%), or seizures (22%, 95% CI: 14.6%-29.5%), and was lowest in children referred for autism spectrum disorder alone (6.5%, 95% CI: 1.5%-11.6%). We concluded that there is a low prevalence of definite pathology in children with autism spectrum disorder undergoing brain MRI. In children with abnormal neurologic examination or preexisting finding, seizures, or headaches, one may consider performing brain MRI given the higher prevalence of pathology.

Imaging of Abusive Trauma.

"Shaken baby syndrome" is a term often used by the physicians and public to describe abusive trauma inflicted on infants and young children. Advances in the understanding of the mechanisms and the associated clinical spectrum of injury has lead us to modify our terminology and address it as "abusive trauma" (AT). Pediatric abusive head trauma is defined as an injury to the skull or intracranial contents of an infant or a young child (< 5 y age) due to inflicted blunt impact and/or violent shaking. This chapter focuses on the imaging aspects of childhood abusive trauma along with a brief description of the mechanism and pathophysiology of abusive injury. The diagnosis of AT is not always obvious, and abusive injuries in many infants may remain unrecognized. Pediatricians should be cognizant of AT since pediatricians play a crucial role in the diagnosis, management and prevention of AT.

Early Head CT Findings Are Associated With Outcomes After Pediatric Out-of-Hospital Cardiac Arrest.

OBJECTIVES: Head CT after out-of-hospital cardiac arrest is often obtained to evaluate intracranial pathology. Among children admitted to the PICU following pediatric out-of-hospital cardiac arrest, we hypothesized that loss of gray-white matter differentiation and basilar cistern and sulcal effacement are associated with mortality and unfavorable neurologic outcome. DESIGN: Retrospective, cohort study. SETTING: Single, tertiary-care center PICU. PATIENTS: Seventy-eight patients less than 18 years old who survived out-of-hospital cardiac arrest to PICU admission and had a head CT within 24 hours of return of spontaneous circulation were evaluated from July 2005 through May 2012. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Median time to head CT from return of spontaneous circulation was 3.3 hours (1.0, 6.0). Median patient age was 2.3 years (0.4, 9.5). Thirty-nine patients (50%) survived, of whom 29 (74%) had favorable neurologic outcome. Nonsurvivors were more likely than survivors to have 1) loss of gray-white matter differentiation (Hounsfield unit ratios, 0.96 [0.88, 1.07] vs 1.1 [1.07, 1.2]; p < 0.001), 2) basilar cistern effacement (93% vs 7%; p = 0.001; positive predictive value, 94%; negative predictive value, 59%), and 3) sulcal effacement (100% vs 0%; p ≤ 0.001; positive predictive value, 100%; negative predictive value, 68%). All patients with poor gray-white matter differentiation or sulcal effacement had unfavorable neurologic outcomes. Only one patient with basilar cistern effacement had favorable outcome. CONCLUSIONS: Loss of gray-white matter differentiation and basilar cistern effacement and sulcal effacement are associated with poor outcome after pediatric out-of-hospital cardiac arrest. Select patients may have favorable outcomes despite these findings.

Adverse Fat Depots and Marrow Adiposity Are Associated With Skeletal Deficits and Insulin Resistance in Long-Term Survivors of Pediatric Hematopoietic Stem Cell Transplantation.

Allogeneic hematopoietic stem-cell transplantation (alloHSCT) survivors treated with total body irradiation (TBI) exhibit bone deficits and excess adiposity, potentially related to altered mesenchymal stem cell differentiation into osteoblasts or adipocytes. We examined associations among fat distribution, bone microarchitecture, and insulin resistance in alloHSCT survivors after TBI. This was a cross-sectional observational study of 25 alloHSCT survivors (aged 12 to 25 years) a median of 9.7 (4.3 to 19.3) years after alloHSCT compared to 25 age-, race-, and sex-matched healthy controls. Vertebral MR spectroscopic imaging and tibia micro-MRI were used to quantify marrow adipose tissue (MAT) and trabecular microarchitecture. Additional measures included DXA whole-body fat mass (WB-FM), leg lean mass (Leg-LM), trunk visceral adipose tissue (VAT), and CT calf muscle density. Insulin resistance in alloHSCT survivors was estimated by HOMA-IR. AlloHSCT survivors had lower Leg-LM (p < 0.001) and greater VAT (p < 0.01), MAT (p < 0.001), and fat infiltration of muscle (p = 0.04) independent of WB-FM, versus matched controls; BMI did not differ. Survivors had lower bone volume fraction and abnormal microarchitecture including greater erosion and more rod-like structure versus controls (all p = 0.04); 14 had vertebral deformities and two had compression fractures. Greater WB-FM, VAT, MAT, and muscle fat infiltration were associated with abnormal trabecular microarchitecture (p < 0.04 for all). AlloHSCT HOMA-IR was elevated, associated with younger age at transplantation (p < 0.01), and positively correlated with WB-FM and VAT (both p < 0.01). In conclusion, the markedly increased marrow adiposity, abnormal bone microarchitecture, and abnormal fat distribution highlight the risks of long-term treatment-related morbidity and mortality in alloHSCT recipients after TBI. Trabecular deterioration was associated with marrow and visceral adiposity. Furthermore, long-term survivors demonstrated sarcopenic obesity, insulin resistance, and vertebral deformities. Future studies are needed to identify strategies to prevent and treat metabolic and skeletal complications in this growing population of childhood alloHSCT survivors.

Magnetic resonance imaging of the pediatric neck: an overview.

Evaluation of neck lesions in the pediatric population can be a diagnostic challenge, for which magnetic resonance (MR) imaging is extremely valuable. This article provides an overview of the value and utility of MR imaging in the evaluation of pediatric neck lesions, addressing what the referring clinician requires from the radiologist. Concise descriptions and illustrations of MR imaging findings of commonly encountered pathologic entities in the pediatric neck, including abnormalities of the branchial apparatus, thyroglossal duct anomalies, and neoplastic processes, are given. An approach to establishing a differential diagnosis is provided, and critical points of information are summarized.

Fetal MRI: head and neck.

Abnormalities of the fetal head and neck may be seen in isolation or in association with central nervous system abnormalities, chromosomal abnormalities, and syndromes. Magnetic resonance imaging (MRI) plays an important role in detecting associated abnormalities of the brain as well as in evaluating for airway obstruction that may impact prenatal management and delivery planning. This article provides an overview of the common indications for MRI of the fetal head and neck, including abnormalities of the fetal skull and face, masses of the face and neck, and fetal goiter.