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OBJECTIVE The purpose of this secondary analysis was to assess the role of hydrocephalus on neurodevelopmental outcomes in a cohort of school-age children enrolled in the Management of Myelomeningocele Study (MOMS) clinical trial. METHODS The sample analyzed in this report consisted of 150 of 183 children aged 5–10 years (mean ± SD 7 years 8 months ± 1.2) who were randomly assigned between 20 and 26 weeks of gestational age to undergo either prenatal or postnatal surgery and were enrolled in the school-age follow-up study of MOMS. These 150 children (76 prenatal and 74 postnatal) were placed into three groups: no hydrocephalus (n = 22), unshunted hydrocephalus (n = 31), and shunted hydrocephalus (n = 97). Comparisons were made on the basis of measures of adaptive behavior, intelligence, reading and math skills, verbal and nonverbal memory, fine motor dexterity, and sensorimotor skills. Parent ratings of executive functions, inattention, and hyperactivity-impulsivity were also compared. RESULTS There were no statistically significant differences in neurodevelopmental outcomes between the groups with no hydrocephalus and unshunted hydrocephalus, or between the prenatal and postnatal groups with shunted hydrocephalus, so these groups were combined (no/unshunted vs shunted hydrocephalus). The no/unshunted group showed significantly better performance (p < 0.05) than the shunted group in terms of adaptive behavior, intelligence, verbal and nonverbal memory, reading skills (but not math), fine motor dexterity, sensorimotor skills (but not visual-motor integration), and inattention (but not hyperactivity-impulsivity or executive function ratings). An assessment of the prenatal surgery group showed that the combined no/unshunted group performed better than the shunted group in terms of adaptive behavior and verbal memory skills. Both the prenatal and postnatal surgery subgroups with unshunted hydrocephalus performed as well as the group with no hydrocephalus despite significantly enlarged ventricles. CONCLUSIONS Although the primary assessment of school-age outcomes in the MOMS clinical trial did not show better adaptive behavior and cognitive skills in the prenatal group, hydrocephalus and shunting were associated with poorer neurodevelopmental outcomes (both prenatal and postnatal groups). Disease severity and dynamic changes in hydrocephalus status may be the primary factors in the need for shunting and a major determinant of adaptive behavior and cognitive outcomes after prenatal surgery.

BACKGROUND: Survival following pediatric out-of-hospital cardiac arrest (OHCA) has improved over the past 2 decades but data on survivors’ long-term outcomes are limited. We aimed to evaluate long-term outcomes in pediatric OHCA survivors more than one year after cardiac arrest. METHODS: OHCA survivors 1 or worsening from pre-arrest baseline to discharge. FINDINGS: Forty four patients were evaluable. Follow-up occurred at a median of 5.6 years [IQR 4.4, 8.9] post-arrest. Median age at arrest was 5.3 [1.3,12.6] years; median CPR duration was 5 [1.5, 7] minutes. Survivors with unfavorable outcome at discharge had worse FSS Sensory and Motor Function scores and higher rates of rehabilitation service utilization. Parents of survivors with unfavorable outcome reported greater disruption to family functioning. Healthcare utilization and educational support requirements were common among all survivors. CONCLUSIONS: Survivors of pediatric OHCA with unfavorable outcome at discharge have more impaired function multiple years post-arrest. Survivors with favorable outcome may experience impairments and significant healthcare needs not fully captured by the PCPC at hospital discharge.

BackgroundTo characterize suicidality among youth with juvenile fibromyalgia syndrome (JFMS) receiving treatment from pediatric rheumatologists at a tertiary care center in order to determine the prevalence of suicidality in JFMS and to explore risk factors for persistent suicidal ideation.MethodsWe performed a cross-sectional cohort study of children 12–17 years old with JFMS seen in a specialty pediatric rheumatology pain clinic from 7/2017–9/2019. All subjects completed patient-reported outcomes measures, complemented by retrospective chart review. Subjects who endorsed item 8 on the Children’s Depression Inventory, 2nd Edition (CDI-2) were categorized as endorsing suicidal ideation. We assessed for differences between the suicidal and non-suicidal patients using Wilcoxon-rank sum test. Logistic regression modeling was performed to identify psychosocial factors associated with suicidality.ResultsOf the 31 subjects, more than one-quarter endorsed suicidality. Nearly 90% of teens with suicidal ideation were established in outpatient counseling. In bivariate analyses, suicidality was associated with lower resilience and greater depression and anxiety (allp p = 0.06). Lower resilience was independently associated with suicidality (OR: 0.90 [95% CI: 0.82–0.98];p ConclusionsSuicidality was prevalent among youth with JFMS and persistent despite concurrent receipt of mental health services. Higher patient-level resilience was independently associated with a reduced odds of suicidality. Future work should examine the role of resilience training on reducing psychological distress and mitigating the risk of suicidality in JFMS.

ImportanceNeurodevelopmental disabilities are commonly associated with congenital heart disease (CHD), but medical and sociodemographic factors explain only one-third of the variance in outcomes.ObjectiveTo examine whether potentially damaging de novo variants (dDNVs) in genes not previously linked to neurodevelopmental disability are associated with neurologic outcomes in CHD and, post hoc, whether some dDNVs or rare putative loss-of-function variants (pLOFs) in specific gene categories are associated with outcomes.Design, Setting, and ParticipantsThis cross-sectional study was conducted from September 2017 to June 2020 in 8 US centers. Inclusion criteria were CHD, age 8 years or older, and available exome sequencing data. Individuals with pathogenic gene variants in known CHD- or neurodevelopment-related genes were excluded. Cases and controls were frequency-matched for CHD class, age group, and sex.ExposuresHeterozygous for (cases) or lacking (controls) dDNVs in genes not previously associated with neurodevelopmental disability. Participants were separately stratified as heterozygous or not heterozygous for dDNVs and/or pLOFs in 4 gene categories: chromatin modifying, constrained, high level of brain expression, and neurodevelopmental risk.Main Outcomes and MeasuresMain outcomes were neurodevelopmental assessments of academic achievement, intelligence, fine motor skills, executive function, attention, memory, social cognition, language, adaptive functioning, and anxiety and depression, as well as 7 structural, diffusion, and functional brain magnetic resonance imaging metrics.ResultsThe study cohort included 221 participants in the post hoc analysis and 219 in the case-control analysis (109 cases [49.8%] and 110 controls [50.2%]). Of those 219 participants (median age, 15.0 years [IQR, 10.0-21.2 years]), 120 (54.8%) were male. Cases and controls had similar primary outcomes (reading composite, spelling, and math computation on the Wide Range Achievement Test, Fourth Edition) and secondary outcomes. dDNVs and/or pLOFs in chromatin-modifying genes were associated with lower mean (SD) verbal comprehension index scores (91.4 [20.4] vs 103.4 [17.8]; P = .01), Social Responsiveness Scale, Second Edition, scores (57.3 [17.2] vs 49.4 [11.2]; P = .03), and Wechsler Adult Intelligence Scale, Fourth Edition, working memory scores (73.8 [16.4] vs 97.2 [15.7]; P = .03), as well as higher likelihood of autism spectrum disorder (28.6% vs 5.2%; P = .01). dDNVs and/or pLOFs in constrained genes were associated with lower mean (SD) scores on the Wide Range Assessment of Memory and Learning, Second Edition (immediate story memory: 9.7 [3.7] vs 10.7 [3.0]; P = .03; immediate picture memory: 7.8 [3.1] vs 9.0 [2.9]; P = .008). Adults with dDNVs and/or pLOFs in genes with a high level of brain expression had greater Conners adult attention-deficit hyperactivity disorder rating scale scores (mean [SD], 55.5 [15.4] vs 46.6 [12.3]; P = .007).Conclusions and RelevanceThe study findings suggest neurodevelopmental outcomes are not associated with dDNVs as a group but may be worse in individuals with dDNVs and/or pLOFs in some gene sets, such as chromatin-modifying genes. Future studies should confirm the importance of specific gene variants to brain function and structure.

BACKGROUND: Hyperinsulinism (HI) is the most common cause of persistent hypoglycemia in neonates, infants and children. Persistent hypoglycemia due to HI in the neonatal period and infancy has detrimental effects on the developing brain, leading to permanent brain damage. As such, neonatal hypoglycemia due to HI may be one of the most readily preventable causes of neurodevelopmental impairment. While monogenic forms of HI are rare with an estimated incidence in the US of 1:50,000 live births, perinatal stress-induced HI (PSIHI) is common and affects up to 50% of at-risk neonates, with an estimated incidence of 1:12,000 live births. There is a paucity of high quality evidence investigating neurodevelopmental outcomes in PSIHI. Methods: Subjects with HI and history of perinatal stress diagnosed between 2013 - 2018 and with demonstrated cure by fasting test by 2 years were included. Exclusion criteria included patients born prior to 32 wks gestation, congenital or syndromic HI and other diagnoses known to impact development. Medical records were reviewed and families were interviewed and asked to complete questionnaires for three validated neurodevelopmental assessments: ABAS-3, BRIEF-P, and CBCL (1.5–5). Results: Medical records of 98 eligible subjects were reviewed to date (74% males), 37% were born between 32–37 wks (mean gestational age 37.2 wks). Mean birth weight was 2.53kg. Median age of hypoglycemia presentation was 0 days, as 67% of subjects presented on day of life 0. Median age at HI diagnosis was 12 days, and the median length of time from first episode of hypoglycemia to definitive treatment was 14 days. Mean maximum glucose infusion rate was 12 mg/kg/min. 81% of subjects were successfully treated with diazoxide. Median time to demonstrated resolution of disease was 210 days. Parent interviews were completed for 33 subjects to date. Developmental concerns were reported by 52% of parents, and 41% reported pediatrician concerns. A diagnosis of speech delay was reported by 45% of parents, and 24% reported concerns for a learning disability. Behavioral concerns were reported by 45%, with 21% reporting diagnoses or specific concerns for ADHD and 12% reported diagnoses or strong concerns for autism. Neurodevelopmental assessments were completed in 15 subjects to date. The proportion of study subjects who scored more than 1 SD and 2 SDs outside the normal range on any of the major assessment scales was 33% and 6%, respectively (vs 15.8% and 2.2% in the general population for any individual scale). Conclusion: Children with PSIHI are predominantly male and most are born at term. While the majority of infants presented with hypoglycemia in the first day of life, diagnosis occurred most often 12 days later, with definitive treatment achieved after two weeks of life. Patients with PSIHI are at high risk of neurodevelopmental deficits, and are more likely to perform below average on developmental testing.

BACKGROUND AND OBJECTIVES: The Management of Myelomeningocele Study (MOMS), a randomized trial of prenatal versus postnatal repair for myelomeningocele, found that prenatal surgery resulted in reduced hindbrain herniation and need for shunt diversion at 12 months of age and better motor function at 30 months. In this study, we compared adaptive behavior and other outcomes at school age (5.9–10.3 years) between prenatal versus postnatal surgery groups. METHODS: Follow-up cohort study of 161 children enrolled in MOMS. Assessments included neuropsychological and physical evaluations. Children were evaluated at a MOMS center or at a home visit by trained blinded examiners. RESULTS: The Vineland composite score was not different between surgery groups (89.0 ± 9.6 in the prenatal group versus 87.5 ± 12.0 in the postnatal group; P = .35). Children in the prenatal group walked without orthotics or assistive devices more often (29% vs 11%; P = .06), had higher mean percentage scores on the Functional Rehabilitation Evaluation of Sensori-Neurologic Outcomes (92 ± 9 vs 85 ± 18; P < .001), lower rates of hindbrain herniation (60% vs 87%; P < .001), had fewer shunts placed for hydrocephalus (49% vs 85%; P < .001) and, among those with shunts, fewer shunt revisions (47% vs 70%; P = .02) than those in the postnatal group. Parents of children repaired prenatally reported higher mean quality of life z scores (0.15 ± 0.67 vs 0.11 ± 0.73; P = .008) and lower mean family impact scores (32.5 ± 7.8 vs 37.0 ± 8.9; P = .002). CONCLUSIONS: There was no significant difference between surgery groups in overall adaptive behavior. Long-term benefits of prenatal surgery included improved mobility and independent functioning and fewer surgeries for shunt placement and revision, with no strong evidence of improved cognitive functioning.

STUDY OBJECTIVES: Depressive symptoms following adenotonsillectomy (AT) relative to controls were examined in children with obstructive sleep apnea syndrome (OSAS). METHODS: The Childhood Adenotonsillectomy Trial (CHAT) multisite study examined the impact of AT in 453 children aged 5 to 9.9 years with polysomnographic evidence of OSAS without prolonged desaturation, randomized to early adenotonsillectomy (eAT) or watchful waiting with supportive care (WWSC). One hundred seventy-six children (eAT n = 83; WWSC n = 93) with complete evaluations for depressive symptomatology between baseline and after a 7-month intervention period were included in this secondary analysis. RESULTS: Exact binomial test assessed proportion of depressive symptomatology relative to norms, while effects of AT and OSAS resolution were assessed through linear quantile mixed-models. Treatment group assignment did not significantly impact depression symptoms, although self-reported depression symptoms improved over time (p < 0.001). Resolution of OSAS symptoms demonstrated a small interaction effect in an unexpected direction, with more improvement in parent ratings of anxious/depressed symptoms for children without resolution (p = 0.030). Black children reported more severe depressive symptoms (p = 0.026) and parents of overweight/obese children reported more withdrawn/depressed symptoms (p = 0.004). Desaturation nadir during sleep was associated with self-report depressed (r = −0.17, p = 0.028), parent-reported anxious/depressed (r = −0.15, p = 0.049), and withdrawn/depressed (r = −0.24, p = 0.002) symptoms. CONCLUSIONS: Increased risk for depressed and withdrawn/depressed symptoms was detected among children with OSAS, and different demographic variables contributed to risk in self-reported and parent-reported depression symptoms. Arterial oxygen desaturation nadir during sleep was strongly associated with depressed symptoms. However, despite improvements in child-reported depressed symptoms over time, changes were unrelated to either treatment group or OSAS resolution status. TRIALS REGISTRATION: Childhood Adenotonsillectomy Study for Children with OSAS (CHAT), https://clinicaltrials.gov/show/NCT00560859, NCT00560859.

Objectives The childhood obstructive sleep apnea syndrome (OSAS) is associated with behavioral abnormalities. Studies on the effects of OSAS treatment on behavior are conflicting, with few studies using a randomized design. Further, studies may be confounded by the inclusion of behavioral outcome measures directly related to sleep. The objective of this study was to determine the effect of adenotonsillectomy on behavior in children with OSAS. We hypothesized that surgery would improve behavioral ratings, even when sleep symptom items were excluded from the analysis. Methods This was a secondary analysis of Child Behavior Checklist (CBCL) data, with and without exclusion of sleep-specific items, from the Childhood Adenotonsillectomy Trial (CHAT). CBCL was completed by caregivers of 380 children (7.0+1.4 [range 5-9] years) with OSAS randomized to early adenotonsillectomy (eAT) versus 7 months of watchful waiting with supportive care (WWSC). Results There was a high prevalence of behavioral problems at baseline; 16.6% of children had a Total Problems score in the clinically abnormal range. At follow-up, there were significant improvements in Total Problems (p < .001), Internalizing Behaviors (p = .04), Somatic Complaints (p = .01), and Thought Problems (p = .01) in eAT vs. WWSC participants. When specific sleep-related question items were removed from the analysis, eAT showed an overall improvement in Total (p = .02) and Other (p = .01) problems. Black children had less improvement in behavior following eAT than white children, but this difference attenuated when sleep-related items were excluded. Conclusions This large, randomized trial showed that adenotonsillectomy for OSAS improved parent-rated behavioral problems, even when sleep-specific behavioral issues were excluded from the analysis.

Cobalamin C (CblC) disease is the most common inborn error of cobalamin metabolism and recent data has indicated a higher prevalence among children of Hispanic heritage in particular. The purpose of this study was to (a) describe the neuropsychological characteristics of a pilot sample of Hispanic children with CblC disease and (b) explore potential differences in outcome based on underlying genetic mutation(s) and biochemical levels. Six Hispanic children (ages 2-10) diagnosed with CblC disease through newborn screening (NBS) underwent neuropsychological evaluation with a bilingual examiner. Biochemical levels and underlying mutation(s) were obtained through medical records. The overall sample performed below normative expectations across neuropsychological domains, including general cognition, adaptive functioning, language ability, and visual-motor integration. Underlying mutations and associative clinical phenotypes were found to significantly predict general cognitive abilities, while plasma methionine and Hcy at the time of diagnosis were significantly correlated with language outcomes. Despite limited sample size, results indicate that Hispanic children with CblC disease detected through NBS and treated early experience neuropsychological deficits even when treated with current standard treatments. However, consistent with prior research in non-Hispanic children with CblC disease, underlying mutations and early biochemical levels may predict better outcomes in this population as well.

OBJECTIVE: Research reveals mixed evidence for the effects of adenotonsillectomy (AT) on cognitive tests in children with obstructive sleep apnea syndrome (OSAS). The primary aim of the study was to investigate effects of AT on cognitive test scores in the randomized Childhood Adenotonsillectomy Trial. METHODS: Children ages 5 to 9 years with OSAS without prolonged oxyhemoglobin desaturation were randomly assigned to watchful waiting with supportive care (n = 227) or early AT (eAT, n = 226). Neuropsychological tests were administered before the intervention and 7 months after the intervention. Mixed model analysis compared the groups on changes in test scores across follow-up, and regression analysis examined associations of these changes in the eAT group with changes in sleep measures. RESULTS: Mean test scores were within the average range for both groups. Scores improved significantly (P < .05) more across follow-up for the eAT group than for the watchful waiting group. These differences were found only on measures of nonverbal reasoning, fine motor skills, and selective attention and had small effects sizes (Cohen’s d, 0.20–0.24). As additional evidence for AT-related effects on scores, gains in test scores for the eAT group were associated with improvements in sleep measures. CONCLUSIONS: Small and selective effects of AT were observed on cognitive tests in children with OSAS without prolonged desaturation. Relative to evidence from Childhood Adenotonsillectomy Trial for larger effects of surgery on sleep, behavior, and quality of life, AT may have limited benefits in reversing any cognitive effects of OSAS, or these benefits may require more extended follow-up to become manifest.

Newborn screening for galactosemia has shown a high prevalence of partial galactose uridyl transferase deficiencies such as Duarte (DG) galactosemia. Study objective: To determine whether (a) there is any clinical impact of DG galactosemia on development (b) there is a relationship between outcome and biochemical parameters in patients who receive no treatment. Study population: Twenty-eight children with DG galactosemia. Group-I—17 children had a lactose restricted diet in the first year of life. Group-II—11 children had a regular diet since birth. Methods: Developmental, physical, and ophthalmologic assessments were completed on both DG groups. RBC gal-1-p and urine galactitol were monitored during the follow-up visits in every child with DG galactosemia. Gal-1-p, urine galactitol, liver function tests, and FSH were tested at the time of study visit. Results: The groups had statistically significant differences on RBC gal-1-p and urine galactitol at the 2 week, 1 month, 6 month, and 1 year time points. There was no statistical difference of gal-1-p or urine galactitol in group-I and -II at the time of study. The groups had statistically significant differences on adaptive scores, but not on language or IQ. None of the DG subjects had abnormal liver function at the time of diagnosis or the study visit. The FSH levels were normal. There were no statistically significant relationships between the first year metabolic values and developmental outcomes. Conclusions: The data presented here indicate that clinical and developmental outcomes in DG galactosemics are good regardless of any diet changes.

Myelomeningocele (MMC) represents the first nonlethal anomaly to be treated by prenatal intervention. Case series and a prospective, randomized study show that fetal surgery for MMC before 26 weeks' gestation may preserve neurological function. Long-term follow-up is a fundamental component to evaluate the overall efficacy of any new medical or surgical procedure. To further delineate the long-term impact of fMMC surgery, we continued to follow children treated in our institution before the Management of Myelomeningocele Study trial by the means of parental questionnaires to assess changes in functional, developmental, and cognitive status as these unique patients grow older.The objective of the study was to evaluate the long-term neurological outcome, executive functioning (EF), and behavioral adaptive skills (BAS) following fetal myelomeningocele (fMMC) surgery.Prior to the Management of Myelomeningocele Study trial, 54 patients underwent fMMC surgery at our institution. Parents of 42 children (78%) participated in structured questionnaires focusing on neurofunctional outcome. EF and BAS were measured by the Behavior Rating Inventory of Executive Function (BRIEF) and the Adaptive Behavioral Assessment System II. The BRIEF is organized into 3 primary indices including the following: Global Executive Composite, Metacognition Index, and Behavioral Regulation Index. The Adaptive Behavioral Assessment System II results in a general adaptive composite score. Based on SD intervals, EF and BAS were categorized as being average, borderline, or impaired.At a median follow-up age of 10 years (range, 8-14 years), 33 (79%) are community ambulators, 3 (9%) are household ambulators, and 6 (14%) are wheelchair dependent. Preschool ambulation was predictive of long-term ambulation (P.01), whereas the need for tethered cord surgery was associated with persistent deterioration of ambulatory status (P = .007). Normal bladder function was found in 26%. Although the majority scored within the average range for the Behavioral Regulation Index, Metacognition Index, and Global Executive Composite indices, significantly more children who had fMMC surgery had deficits in EF in all 3 BRIEF indices compared with the population norms. The general adaptive composite scores were also more likely to fall below average following fMMC surgery. Normal early neurodevelopmental outcomes were predictive of normal EF and BAS (P.01). Need for shunting was associated with a significant impairment of BAS (P = .02).The present study suggests that fMMC surgery improves long-term functional outcome. The majority of fMMC children can successfully complete everyday tasks at home and at school. Abnormalities of BAS appear to be more common than impairments in EF and therefore offer an area for early screening and interventional therapy for these at-risk children. Non-shunted fMMC children with normal early neurodevelopmental outcome are less likely to experience problems with EF and BAS. fMMC surgery improves long-term ambulatory status. Symptomatic spinal cord tethering with or without intradural inclusion cyst is associated with functional loss. More than expected fMMC children are continent, but bowel and bladder control continue to be an ongoing challenge for the fMMC children.

Each year, over 500,000 adenotonsillectomies (AT), mostly for the treatment of pediatric obstructive sleep apnea (OSA) are performed in the US in children under 15 years of age. No definitive study, however, has been yet conducted that has rigorously evaluated the effectiveness of AT for not only improving sleep disordered breathing, but also for improving clinically relevant outcomes, such as neurocognitive function, behavior, and quality of life. The Childhood Adenotonsillectomy Trial (CHAT) was designed to assess neuropsychological and health outcomes in children randomized to receive early AT (eAT) as compared to Watchful Waiting with Supportive Care (WWSC). Important secondary goals of the study are to evaluate outcomes in subgroups defined by obesity and race. This paper addresses key elements in the design and implementation of a controlled trial for a widely used "standard practice" surgical intervention in a pediatric population, that include establishment of standardized data collection procedures across sites for a wide variety of data types, establishment of equipoise, and approaches for minimizing unblinding of selected key personnel. The study framework that was established should provide a useful template for other pediatric controlled studies or other studies that evaluate surgical interventions.

Background: Duarte galactosemia (DG) is frequently detected in newborn-screening programs. DG patients do not manifest the symptoms of classic galactosemia, but whether they require dietary galactose restriction is controversial. We sought to assess the relationships of selected galactose metabolites (plasma galactose, plasma galactitol, erythrocyte (RBC) galactitol, RBC galactonate, and urine galactitol and galactonate) to RBC galactose 1-phosphate (Gal-1-P), dietary galactose intake, and neurodevelopmental/clinical outcomes in DG children. Methods: We studied 30 children 1–6 years of age who had DG galactosemia and were on a regular diet. All participants underwent a physical and ophthalmologic examination and a neurodevelopmental assessment. RBC galactitol, RBC galactonate, RBC Gal-1-P, plasma galactose, plasma galactonate, and urine galactitol and galactonate concentrations were measured. Results: RBC galactitol and galactonate concentrations were about 2 and 6 times higher, respectively, than control values. Plasma galactose and galactitol concentrations were also about twice the control values. The mean values for RBC Gal-1-P and urine galactitol were within the reference interval. We found a relationship between plasma and urine galactitol concentrations but no relationship between RBC galactose metabolites and urine galactitol. There was a significant relationship between galactose intake and RBC galactose metabolites, especially RBC galactitol (P < 0.0005) and RBC galactonate (P < 0.0005). Galactose intake was not related to the urine galactitol, plasma galactose, or plasma galactitol concentration. RBC galactitol, RBC galactonate, plasma galactose, plasma galactitol, and urine galactonate concentrations showed no relationship with clinical or developmental outcomes. Conclusions: DG children on a regular diet have RBC Gal-1-P concentrations within the reference interval but increased concentrations of other galactose metabolites, including RBC galactitol and RBC galactonate. These increased concentrations correlate with galactose intake and neither cause any developmental or clinical pathology during early childhood nor oblige a lactose-restricted diet.

Adenotonsillectomy is commonly performed in children with the obstructive sleep apnea syndrome, yet its usefulness in reducing symptoms and improving cognition, behavior, quality of life, and polysomnographic findings has not been rigorously evaluated. We hypothesized that, in children with the obstructive sleep apnea syndrome without prolonged oxyhemoglobin desaturation, early adenotonsillectomy, as compared with watchful waiting with supportive care, would result in improved outcomes.We randomly assigned 464 children, 5 to 9 years of age, with the obstructive sleep apnea syndrome to early adenotonsillectomy or a strategy of watchful waiting. Polysomnographic, cognitive, behavioral, and health outcomes were assessed at baseline and at 7 months.The average baseline value for the primary outcome, the attention and executive-function score on the Developmental Neuropsychological Assessment (with scores ranging from 50 to 150 and higher scores indicating better functioning), was close to the population mean of 100, and the change from baseline to follow-up did not differ significantly according to study group (mean [±SD] improvement, 7.1±13.9 in the early-adenotonsillectomy group and 5.1±13.4 in the watchful-waiting group; P=0.16). In contrast, there were significantly greater improvements in behavioral, quality-of-life, and polysomnographic findings and significantly greater reduction in symptoms in the early-adenotonsillectomy group than in the watchful-waiting group. Normalization of polysomnographic findings was observed in a larger proportion of children in the early-adenotonsillectomy group than in the watchful-waiting group (79% vs. 46%).As compared with a strategy of watchful waiting, surgical treatment for the obstructive sleep apnea syndrome in school-age children did not significantly improve attention or executive function as measured by neuropsychological testing but did reduce symptoms and improve secondary outcomes of behavior, quality of life, and polysomnographic findings, thus providing evidence of beneficial effects of early adenotonsillectomy. (Funded by the National Institutes of Health; CHAT ClinicalTrials.gov number, NCT00560859.).

Background and PurposezzPET scanning with fluorodeoxyglucose (FDG-PET) is a non-in-vasive method that measures regional glucose metabolic rate. Phenylalanine (Phe) and its me-tabolites appear to impair several aspects of brain energy metabolism. 1) To evaluate brain glu-cose metabolism with FDG-PET imaging in phenylketonuria (PKU) patients before and 4 months after sapropterin therapy; 2) to evaluate neurodevelopmental changes, blood Phe levels and di-etary Phe tolerance before and after sapropterin therapy; 3) to generate pilot data to assess the feasibility of evaluating brain glucose metabolism with FDG-PET imaging and to explore po-tential trends resulting from the administration of sapropterin therapy.MethodszzWe enrolled 5 subjects, ranged in age from 22 years to 51 years, with PKU. Subjects underwent FDG-PET brain imaging, blood tests for Phe and tyrosine levels, and neurocognitive evaluations before and 4 months after sapropterin therapy (20 mg/kg/day). All subjects’ Phe and tyrosine levels were monitored once a week during the study. Subjects kept 3 day diet records that allow calculation of Phe intake.ResultszzNone of the subjects responded to sapropterin therapy based on 30% decrease in blood Phe level. The data show that glucose metabolism appeared depressed in the cerebellum and left parietal cortex while it was increased in the frontal and anterior cingulate cortices in all five subjects. In response to sapropterin therapy, relative glucose metabolism showed significant increases in left Broca’s and right superior lateral temporal cortices. Interestingly, there was cor-responding enhanced performance in a phonemic fluency test performed during pre- and post-neurocognitive evaluation. ConclusionszzFurther studies with a larger sample size are needed to confirm the above changes in both sapropterin non-responsive and responsive PKU patients. J Clin Neurol 2013;9:151-156Key Wordszzphenylketonuria, sapropterin, fluorodeoxyglucose positron emission tomography.