Leveraging expertise and optimizing clinical research: Initial success of a pediatric epilepsy surgery collaborative.

Objective: Improve data-driven research to inform clinical decision-making with pediatric epilepsy surgery patients by expanding the Pediatric Epilepsy Research Consortium Epilepsy Surgery (PERC-Surgery) Workgroup to include neuropsychological data. This article reports on the process and initial success of this effort and characterizes the cognitive functioning of the largest multi-site pediatric epilepsy surgery cohort in the United States.

Methods: Pediatric neuropsychologists from 18 institutions completed surveys regarding neuropsychological practice and the impact of involvement in the collaborative.

Child Neurology: Reversible Dementia in an 18-Year-Old Woman Due to Undiagnosed Cobalamin-G Deficiency: A Case Report.

Cobalamin-G deficiency is an inborn error of metabolism which disrupts the biochemical utilization of vitamin B12 to covert homocysteine to methionine in the remethylation pathway. Typically, affected patients present within the first year of life with anemia, developmental delay, and metabolic crisis. Few case reports of cobalamin-G deficiency reference a later onset phenotype primarily defined by neuropsychiatric symptoms.

Ventilatory and Orthostatic Challenges Reveal Biomarkers for Neurocognition in Children and Young Adults With Congenital Central Hypoventilation Syndrome.

Background: Children and young adults with congenital central hypoventilation syndrome (CCHS) are at risk of cognitive deficits. They experience autonomic dysfunction and chemoreceptor insensitivity measured during ventilatory and orthostatic challenges, but relationships between these features are undefined.

Research Question: Can a biomarker be identified from physiologic responses to ventilatory and orthostatic challenges that is related to neurocognitive outcomes in CCHS?

Study Design And Methods: This retrospective study included 25 children and young adults with CCHS tested over an inpatient stay.

Neurocognition as a biomarker in the rare autonomic disorders of CCHS and ROHHAD.

Purpose: Congenital central hypoventilation syndrome (CCHS) and rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) are rare disorders of autonomic regulation with risk for disrupted neurocognitive development. Our aim is to summarize research on neurocognitive outcomes in these conditions, advance understanding of how to best support these individuals throughout development, and facilitate future research.

Methods: We conducted a narrative review of literature on neurocognitive outcomes in CCHS and ROHHAD, supplemented with previously unpublished data from patients with CCHS and ROHHAD at our Center for Autonomic Medicine in Pediatrics (CAMP).

Neurocognitive monitoring in congenital central hypoventilation syndrome with the NIH Toolbox®.

Congenital central hypoventilation syndrome (CCHS) is a rare neurocristopathy, caused by mutations in the paired-like homeobox gene PHOX2B, which alters control of breathing and autonomic nervous system regulation, necessitating artificial ventilation as life-support. A broad range of neurocognitive performance has been reported in CCHS, including an array of cognitive deficits. We administered the NIH Toolbox® Cognition Battery (NTCB), a novel technology comprised of seven tasks presented via an interactive computer tablet application, to a CCHS cohort and studied its convergent and divergent validity relative to traditional clinical neurocognitive measures.

Rare diseases - rare outcomes: Assessing communication abilities for the developmental and epileptic encephalopathies.

Objective: Developmental and epileptic encephalopathies (DEE) entail moderate to profound communication and other impairments that are poorly measured by typical clinical outcomes assessments (COA). We examined the potential of alternative approaches, specifically, the use of raw scores and COAs outside of their intended age ranges.

Methods: In a cross-sectional survey, 120 parents of children with Dravet Syndrome, Lennox-Gastaut syndrome, KCNQ2-DEE, KCNB1-DEE, and SCN2A-DEE (ages 1-35 years) completed the Adaptive Behavior Assessment System-3 for ages 0-5 years, modified checklist for autism (mCHAT), communication and social behavior scales (CSBS), communication matrix (CM), and several parent-reported classifiers of communication.

Evolution of physiologic and autonomic phenotype in rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation over a decade from age at diagnosis.

Unlabelled: Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare cause of syndromic obesity with risk of cardiorespiratory arrest and neural crest tumor. No ROHHAD-specific genetic test exists at present. Rapid weight gain of 20-30 pounds, typically between ages 2-7 years in an otherwise healthy child, followed by multiple endocrine abnormalities herald the ROHHAD phenotype.

Evaluation of the Aberrant Behavior Checklist for Developmental and Epileptic Encephalopathies.

Objectives: To determine the suitability of the Aberrant Behavior Checklist (ABC)-a common measure used in clinical trials for treatment of challenging behaviors of autism-as an outcome measure for pharmacological and behavioral interventions for young people with Developmental and Epileptic Encephalopathies (DEEs).

Methods: We assessed score profiles on the ABC in a sample of 122 young people with DEEs, including Dravet and Lennox-Gastaut syndromes, and KCNQ2- SCN2A-, and KCNB1-associated disorders. Then we examined its internal structure using item cluster analysis.

SCN2A-Developmental and Epileptic Encephalopathies: Challenges to trial-readiness for non-seizure outcomes.

Objective: SCN2A-associated developmental and epileptic encephalopathies (DEEs) present with seizures, developmental impairments, and often both. We sought to characterize the level and pattern of development in children with SCN2A variants, and to address the sensitivity of the Vineland Adaptive Behavior Scales (VABS) in measuring changes over time in children with SCN2A-DEEs.

Methods: Clinical histories for participants with pathogenic SCN2A variants in the Simons SearchLight project were analyzed for descriptive purposes.

Nonseizure consequences of Dravet syndrome, KCNQ2-DEE, KCNB1-DEE, Lennox-Gastaut syndrome, ESES: A functional framework.

Rationale: Developmental epilepsies and encephalopathies (DEEs) are characterized by many severe developmental impairments, which are not well-described. A functional framework could facilitate understanding of their nature and severity and guide the selection instruments to measure improvements in therapeutic trials.

Methods: An online survey administered through several parent-organized foundations utilized accepted functional classifications and questionnaires derived from common instruments to determine levels of mobility, fine motor, communication, and feeding functions.

Improved neuropsychological outcomes following proton therapy relative to X-ray therapy for pediatric brain tumor patients.

Background: Survivors of pediatric brain tumors are at risk for impaired development in multiple neuropsychological domains. The purpose of this study was to compare neuropsychological outcomes of pediatric brain tumor patients who underwent X-ray radiotherapy (XRT) versus proton radiotherapy (PRT).

Methods: Pediatric patients who underwent either XRT or PRT and received posttreatment age-appropriate neuropsychological evaluation-including measures of intelligence (IQ), attention, memory, visuographic skills, academic skills, and parent-reported adaptive functioning-were identified.

Optimizing nature: Invoking the "natural" in the struggle over water fluoridation.

For the past seventy years, a host of scientific and public health bodies in the United States have strongly endorsed the practice of adding fluoride compounds to public water supplies as a prophylactic against dental caries. Throughout that period, a constant undercurrent of skepticism and outright opposition has slowed the adoption of the practice in the United States and limited its spread to just a handful of countries around the world. One of the attractions of water fluoridation is its affordability: the fluoride compounds are sourced from the phosphate and aluminum industries, for whom they would otherwise constitute an annoying toxic waste disposal problem.

Congenital central hypoventilation syndrome: Broader cognitive deficits revealed by parent controls.

Objective: To investigate neurocognitive deficits in children with Congenital Central Hypoventilation Syndrome (CCHS) by comparing them to their parents, since parents comprise a particularly suitable control group matched on disease-extrinsic factors that can influence neurocognitive functioning. We compared CCHS patients to their parents and to population norms, hypothesizing that they would obtain lower intelligence test scores than both groups. We also compared patient-parent differences against patient-normative differences, to determine whether the two analytic approaches would yield different results.

Parent-reported cognitive function is associated with leukoencephalopathy in children with brain tumors.

Purpose: Cognitive dysfunction is a major concern for children with brain tumors. A valid, user-friendly screening tool could facilitate prompt referral for comprehensive neuropsychological assessments and therefore early intervention. Applications of the pediatric perceived cognitive function item bank (pedsPCF) such as computerized adaptive testing can potentially serve as such a tool given its brevity and user-friendly nature.

Feasibility of a Mobile Cognitive Intervention in Childhood Absence Epilepsy.

Children with childhood absence epilepsy (CAE) frequently present with cognitive comorbidities and school performance concerns. The present study evaluated the feasibility of an intervention for such comorbidities using a mobile cognitive therapy application on an iPad. Eight children with CAE and school concerns aged 7-11 participated in a 4-week intervention.

Academic Underachievement in Children with Active Epilepsy.

Investigators from Lingfield, Surrey, UK; University of Gothenburg, Sweden; Great Ormond Street Hospital, London, UK, and other centers, conducted psychological assessment including measures of IQ, working memory and processing speed in 85 (74%) of 115 school aged children with active epilepsy (a seizure in the past year and/or on AEDs) from a population-based sample, without exclusion for intellectual deficiency.

Congenital Central Hypoventilation Syndrome: Neurocognition Already Reduced in Preschool-Aged Children.

Background: Congenital Central Hypoventilation Syndrome (CCHS) is a rare neurocristopathy characterized by severe hypoventilation and autonomic dysregulation, with typical presentation in the neonatal period, and deficient cognitive skills in school-aged patients. We hypothesized that younger (preschool) children with CCHS would also show neurocognitive delay and that CCHS-related physiologic factors would impact neurocognitive test results.

Methods: We studied developmental (Bayley) test results collected during routine clinical care in 31 children (mean age 25.

A simple behavioral-developmental checklist versus formal screening for children in an epilepsy center.

We compare a 7-item checklist for developmental and behavioral concerns to formal screening with the Ages & Stages Questionnaires, Third Edition (ASQ-3) in children aged 1-5.5years old seen in a tertiary epilepsy care setting. The checklist was derived from a 35-item parent questionnaire used as a routine component of pediatric neuropsychology evaluations at our center.

Validation of the Neuro-QoL measurement system in children with epilepsy.

Objective: Children with epilepsy often face complex psychosocial consequences that are not fully captured by existing patient-reported outcome (PRO) measures. The Neurology Quality of Life Measurement System "Neuro-QoL" was developed to provide a set of common PRO measures that address issues important to people with neurologic disorders. This paper reports Neuro-QoL (anxiety, depression, interaction with peers, fatigue, pain, cognitive function, stigma, and upper and lower extremity functions) validation in children with epilepsy.

Cognitive Performance Scores for the Pediatric Automated Neuropsychological Assessment Metrics in Childhood-Onset Systemic Lupus Erythematosus.

Objective: To develop and initially validate a global cognitive performance score (CPS) for the Pediatric Automated Neuropsychological Assessment Metrics (PedANAM) to serve as a screening tool of cognition in childhood lupus.

Methods: Patients (n = 166) completed the 9 subtests of the PedANAM battery, each of which provides 3 principal performance parameters (accuracy, mean reaction time for correct responses, and throughput). Cognitive ability was measured by formal neurocognitive testing or estimated by the Pediatric Perceived Cognitive Function Questionnaire-43 to determine the presence or absence of neurocognitive dysfunction (NCD).

Blood-based candidate biomarkers of the presence of neuropsychiatric systemic lupus erythematosus in children.

Objective: To examine select brain-reactive proteins for their usefulness to serve as blood-based biomarkers in the screening for neurocognitive deficits in childhood-onset systemic lupus erythematosus (cSLE-NCD).

Methods: Patients withcSLE (n=40) were studied longitudinally (month 1; month 18): working memory, psychomotor speed and visuoconstructional ability were assessed using formal neurocognitive testing to determine the presence of cSLE-NCD. Patients also completed the computerised Paediatric Automated Neuropsychological Assessment Metrics.

The Postconcussion Symptom Scale: utility of a three-factor structure.

Purpose: This study aimed to determine the factor structure of a 19-item Postconcussion Symptom Scale and to examine associations between factor scores and sex, previous history of concussion, and length of time since injury.

Methods: This is a retrospective medical record review of pediatric patients with concussion seen in a sports medicine clinic from April 2008 to September 2012. We performed an exploratory factor analysis (EFA) followed by a confirmatory factor analysis (CFA).

Longitudinal study of cognitive and academic outcomes after pediatric liver transplantation.

Objective: To determine the evolution of cognitive and academic deficits and risk factors in children after liver transplantation.

Study Design: Patients ≥2 years after liver transplantation were recruited through Studies of Pediatric Liver Transplantation. Participants age 5-6 years at Time 1 completed the Wechsler Preschool and Primary Scale of Intelligence, 3rd edition, Wide Range Achievement Test, 4th edition, and Behavior Rating Inventory of Executive Function (BRIEF).

Regional brain volumes and cognition in childhood epilepsy: does size really matter?

Purpose: Recent studies have correlated neurocognitive function and regional brain volumes in children with epilepsy. We tested whether brain volume differences between children with and without epilepsy explained differences in neurocognitive function.

Methods: The study sample included 108 individuals with uncomplicated non-syndromic epilepsy (NSE) and 36 healthy age- and gender-matched controls.

Value of questionnaire-based screening as a proxy for neurocognitive testing in childhood-onset systemic lupus erythematosus.

Objective: To investigate the utility of questionnaire-based assessment of cognitive function and behavioral/emotional symptoms to screen for neurocognitive dysfunction in childhood-onset systemic lupus erythematosus (cSLE).

Methods: Forty children with cSLE and 24 healthy controls ages 10–16 years were enrolled. Formal neurocognitive testing (FNCT) was done to determine cognitive performance in 4 key areas that appear to be sensitive to the adverse effects of cSLE: attention, working memory, psychomotor speed, and visuoconstructional ability.