Assessment and Diagnosis of Down Syndrome Regression Disorder: International Expert Consensus.

Objective: To develop standardization for nomenclature, diagnostic work up and diagnostic criteria for cases of neurocognitive regression in Down syndrome. Background: There are no consensus criteria for the evaluation or diagnosis of neurocognitive regression in persons with Down syndrome. As such, previously published data on this condition is relegated to smaller case series with heterogenous data sets. Lack of standardized assessment tools has slowed research in this clinical area. Methods: The authors performed a two-round traditional Delphi method survey of an international group of clinicians with experience in treating Down syndrome to develop a standardized approach to clinical care and research in this area. Thirty-eight potential panelists who had either previously published on neurocognitive regression in Down syndrome or were involved in national or international working groups on this condition were invited to participate. In total, 27 panelists (71%) represented nine medical specialties and six different countries reached agreement on preliminary standards in this disease area. Moderators developed a proposed nomenclature, diagnostic work up and diagnostic criteria based on previously published reports of regression in persons with Down syndrome. Results: During the first round of survey, agreement on nomenclature for the condition was reached with 78% of panelists agreeing to use the term Down Syndrome Regression Disorder (DSRD). Agreement on diagnostic work up and diagnostic criteria was not reach on the first round due to low agreement amongst panelists with regards to the need for neurodiagnostic testing. Following incorporation of panelist feedback, diagnostic criteria were agreed upon (96% agreement on neuroimaging, 100% agreement on bloodwork, 88% agreement on lumbar puncture, 100% agreement on urine studies, and 96% agreement on "other" studies) as were diagnostic criteria (96% agreement). Conclusions: The authors present international consensus agreement on the nomenclature, diagnostic work up, and diagnostic criteria for DSRD, providing an initial practical framework that can advance both research and clinical practices for this condition.

Repeat tympanostomy tubes in children with Down syndrome.

OBJECTIVES: Children with Down syndrome (DS) have a higher incidence of tympanostomy tube insertion (TTI) than children in the general population. As there were no studies investigating factors that are associated with multiple TTIs in children with DS, we sought to determine what factors increase or decrease the likelihood of repeat TTI in children with DS. METHODS: A retrospective case-control study was performed on consecutive children with DS from 2007 to 2018 with first TTI at a large tertiary children's hospital and follow-up duration at least 27 months since first TTI. RESULTS: 277 patients met the inclusion criteria. Repeat TTI rate was 61.4%. Having an indication of chronic otitis media with effusion (COME) at first TTI was an adjusted risk factor for increased rate of repeat TTI (OR: 2.01, 95%CI: 1.15-3.51, p = .014), while being older at first TTI was an adjusted protective factor for decreased rate of repeat TTI (OR: 0.84, 95%CI: 0.74-0.95, p = .004). Adenotonsillectomy at or before first TTI was not an adjusted protective factor for decreased rate of repeat TTI (OR: 0.915, 95%CI: 0.448-1.872, p = .809) and bilateral intra-operative fluid was not an adjusted risk factor for repeat TTI (OR: 1.97, 95%CI: 0.99-3.90, p = .054). CONCLUSION: Children with DS were more likely to undergo repeat TTI if they were of younger age and if the indication for surgery was COME. The repeat TTI rate for children with DS was high at 61.4%. Prospective studies are warranted to more precisely investigate factors associated with repeat TTIs in this unique patient population.

Restrictive Eating Disorders: Accelerating Treatment Outcomes in the Medical Hospital.

Pediatric patients with anorexia nervosa and atypical anorexia nervosa may present to hospitals with significant vital sign instability or serum laboratory abnormalities necessitating inpatient medical hospitalization. These patients require specialized care, numerous resources, and interdisciplinary collaboration during what can be a protracted admission. Recent evidence informs areas in which care can be accelerated, and published protocols from major children's hospitals are helpful roadmaps to creating a streamlined hospitalization. In our narrative review, we focused on 3 key areas: (1) implementation of a rapid nutritional rehabilitation program; (2) assessment and management of the refeeding syndrome; and (3) early integration of psychoeducation and therapeutic interventions during inpatient hospitalization. A practical review of the literature in these 3 areas will give concrete, actionable information to pediatric hospitalists as they care for young people with restrictive eating disorders.

Health care transition for individuals with Down syndrome: A needs assessment.

Transition to adulthood is a multifaceted process that requires integration of numerous domains within a young person's life, including their health care. For children with special health care needs, the transition process can be markedly more difficult to navigate. This is especially true for children with Down syndrome (DS) who receive fewer transition planning services. The aim of this needs assessment was to identify current trends, potential gaps, and areas for targeted intervention within the current transition landscape for individuals with DS. We utilized DS-Connect, a National Institutes of Health (NIH) funded family/self-advocate survey repository, as a platform to recruit respondents to the "Transition to Adulthood" survey. Sixty-five respondents (64 parents and 1 caregiver) completed the survey. Responses indicated that 42% of respondents reported comfort in the transition process, but 5% or less reported completing one of the core transition outcomes: transition readiness assessment, portable medical summary, or written transition plan. These findings translated across other domains of respondents' lives. While many individuals with DS and their caregivers are aware of the transition process, there appears to be a disconnect between the introduction of transition concepts and an actualization of transition outcomes necessary for success.

Subglottic hemangioma: Understanding the association with facial segmental hemangioma in a beard distribution.

OBJECTIVE: A subglottic hemangioma (SGH) is a benign tumor of infancy that can cause severe obstruction of the airway. Infantile hemangiomas, in general, are the most common head and neck tumor in children, affecting 4-5% of the pediatric population. This retrospective cohort study characterizes subglottic infantile hemangiomas at a single vascular anomaly center over a 5-year period (2013-2017) during the era of propranolol treatment. METHODS: Queried the Vascular Anomaly Database at Children's Hospital of Pittsburgh for all infantile hemangioma(s) and then identified case of subglottic hemangiomas. Characterized key features of presentation, natural history and management for subglottic hemangiomas. A secondary differentiation focused on differences between subglottic hemangiomas associated with Beard Distribution (BD) vs not (NBD). RESULTS: Analysis of 761 cases of infantile hemangiomas demonstrated only 13 patients with subglottic hemangiomas (1.7%). Of those 13 patients, only 4 patients (30%) had BD while 2 patients (15%) had other cutaneous hemangiomas and 7 patients (55%) had no cutaneous hemangiomas. Secondarily, a total of 31 case of beard distribution cutaneous hemangiomas with 11 patients having oropharyngeal involvement (35%) but only 4 patients with subglottic hemangiomas (13%). Interestingly, 2 of the 4 BD patients had treatment failure on propranolol and required second line treatment with steroids or surgical excision while only 1 of 9 NBD patients failed propranolol treatment. As well the same 2 BD patients which failed propranolol also had PHACES syndrome. CONCLUSION: Subglottic hemangiomas are a rare presentation of infantile hemangiomas but with significant morbidity. While the classic teaching that a segmental beard distribution hemangioma raises concern for a subglottic hemangioma, this cohort indicates subglottic hemangiomas occur in a NBD presentation (1.3%), and demonstrated only an approximate 10% incidence rate with a beard distribution. But more importantly, this study raises the question that beard distribution in setting of PHACES syndrome may herald a more recalcitrant and complicated natural history for a subglottic hemangioma. This is of significant concern as risk for CVA in setting of PHACES is highest with use of steroid treatment. None of our patients had high risk extra or intra cranial vascular arterial anomalies and no CVA were noted.

What might parents read: Sorting webs of online information on vascular anomalies.

INTRODUCTION: The internet is increasingly a source of healthcare information utilized by parents, especially in rarer pathologies such as vascular malformations. The quality, validity and thoroughness of these websites is variable and unregulated. The goal of this study was to evaluate the quality and understandability of websites related to vascular malformations. METHODS: The terms "hemangioma", "vascular malformation", and "vascular anomalies" were searched in Google. The first 30 websites meeting inclusion and exclusion criteria were evaluated. Quality and readability were assessed using the DISCERN criteria and the Flesh-Kincaid Reading Grade Level (FKGL), respectively. Date of last update, HONcode accreditation, and the website category were recorded. RESULTS: Most websites were owned by academic institutions (n = 19, 63.3%). The mean DISCERN score for all websites was 2.97, or a partially valid source of information on a 1-5 scale. The average reading level estimated by FKGL was grade 12; only one website was scored at less than a grade 9 level. Two websites were HONcode accredited. Of the 18 sites giving an explicit date of last update, 12 (67.7%) had been updated in the previous 12 months. CONCLUSIONS: Websites relating information about vascular anomalies may not be understandable to the general public, including parents. Health care providers should be cognizant of the quality and availability of such information as it may impact parent perspectives and bias toward treatment options.

PHACE syndrome is associated with intracranial cavernous malformations.

INTRODUCTION: PHACE syndrome is a neurocutaneous disorder involving large facial hemangiomas in association with posterior fossa abnormalities, cerebral arterial anomalies, cardiac defects, and eye abnormalities. A recent consensus statement has delineated criteria necessary for the diagnosis of PHACE syndrome. Extracutaneous manifestations of PHACE syndrome predominately affect the cerebrovascular system. To date, there are no reports of cerebral cavernous malformations (CCMs) in children with PHACE syndrome. METHODS: We reviewed the charts of children admitted to the Children''s Hospital of Pittsburgh who met criteria for PHACE syndrome, and evaluated neuroimaging for cerebrovascular abnormalities, including the finding of CCMs. RESULTS: Six children met criteria for PHACE syndrome at our institution over a 10-year period. All children were female. All children had cerebrovascular abnormalities sufficient to meet major criteria for diagnosis. Four children (66.7 %) were found incidentally to have CCMs; all lesions measured less than 5 mm at the time of diagnosis and were asymptomatic. CONCLUSION: At present, CCMs are not listed among the diagnostic criteria for PHACE syndrome, and they have not previously been reported in association with PHACE syndrome. Hypoxic injury in utero may be the common denominator in the pathogenesis of many of the abnormalities already accepted in the criteria for PHACE syndrome and the formation of CCMs. In the setting of PHACE syndrome, we encourage clinicians to evaluate children for CCMs, which are readily apparent on the already-recommended screening MRIs.

Role of oxidative stress in intermittent hypoxia-induced immediate early gene activation in rat PC12 cells.

Intermittent hypoxia (IH) occurs in many pathophysiological conditions. The molecular mechanisms associated with IH, however, have received little attention. Previous studies have reported that the c-fos gene via formation of activator protein-1 (AP-1) transcription factor contributes to adaptive responses to continuous hypoxia. In the present study, using a cell culture model we examined whether IH activates c-fos and AP-1 and if so, by what mechanisms. Experiments were performed on rat phaeochromocytoma cells exposed to 21% O(2) (normoxia) or 60 and 120 cycles of IH, each cycle consisting 15 s of hypoxia followed by 4 min of normoxia. IH resulted in a significant elevation of c-fos mRNA as well as transcriptional activation. IH was more potent and induced a longer lasting activation of c-fos than comparable cumulative duration of continuous hypoxia. IH increased AP-1 activity and tyrosine hydroxylase (TH) mRNA, an AP-1-regulated downstream gene, and these effects were prevented by antisense c-fos. Superoxide dismutase mimetic, a potent scavenger of superoxide anions, prevented IH-induced c-fos, AP-1 and TH activations. IH increased superoxide anion levels in mitochondria as evidenced by decreased aconitase enzyme activity and increased levels of hydrogen peroxide, a stable dismutated product of superoxide anions. Complex I of the mitochondrial electron transport chain was markedly inhibited in IH exposed cells. Pharmacological inhibitors of complex I mimicked the effects of IH during normoxia and occluded the effects of IH on c-fos activation, suggesting the involvement of the mitochondrial electron transport chain in the generation of superoxide anions during IH. These results suggest IH-induced c-fos-mediated transcriptional activation involves oxidative stress.