Parent ratings of executive functioning in pediatric survivors of medulloblastoma and pilocytic astrocytoma.

The present study compared parent-rated executive functioning in pediatric medulloblastoma (MB) and pilocytic astrocytoma (PA) survivors. Although standard care for both includes surgical resection, children with MB additionally receive chemotherapy and craniospinal irradiation. Given well-documented neurocognitive late effects associated with the latter, we anticipated poor parent-reported executive functioning in MB survivors. Parents/guardians of 36 MB survivors and 20 PA survivors completed the Behavior Rating Inventory of Executive Functioning (BRIEF). PA survivors were younger at diagnosis (t[51.97] = 3.07, p < .001, d = 0.86) and demonstrated higher IQ (t[54] = -3.51, p < .001, d = 0.95). However, relative to the MB group, the PA group was rated as having significantly more problems on all BRIEF scales (all p ≤ .05; d = 0.30 - 1.10), except the Shift scale. Additionally, all mean BRIEF scores for MB survivors were within normal limits, whereas for PA survivors, all mean BRIEF scores except for Organization of Materials were significantly discrepant from normative means. Overall, PA survivors were rated as demonstrating poorer executive function than MB survivors. Five theories are discussed as possible explanations for these surprising findings: two related to group differences, two related to potential sources of parental bias, and one related to the nature of questionnaire-based assessment. All these theories represent directions for future research. Parent questionnaires such as the BRIEF may have real-world implications for pediatric brain tumor survivors. Future research should explore factors affecting parent ratings of executive functioning in these populations, along with comparison to performance-based measures.

Sleep Disturbance and Its Association With Sluggish Cognitive Tempo and Attention in Pediatric Brain Tumor Survivors.

Background: Pediatric brain tumor (PBT) survivors are at risk for developing sleep disturbances. While in other pediatric populations sleep disturbance has been associated with worse cognitive functioning, it is unclear to what extent this relationship generalizes to PBT survivors. The aim of the current study was to assess the relationship between sleep disturbance and aspects of cognition, including sluggish cognitive tempo (SCT) as well as attention and working memory. Materials and Methods: Eighty-three PBT survivors 6-18 years of age who were at least 3 months post-treatment were included in the present cross-sectional study. Level of sleep disturbance was measured as a composite score reflecting various sleep problems as rated by caregivers. Cognitive measures included caregiver-ratings of sluggish cognitive tempo and attention problems, as well as performance-based cognitive measures assessing attention and executive functioning. Hierarchical regression analysis was used to assess associations between sleep and cognition. Results: Of all caregivers, 32.5% reported one or more sleep disturbances as "very/often true" and over 68% of caregivers rated at least one sleep-related item as "somewhat true." Of all cognitive variables, scores were most frequently impaired for SCT (30%). A higher level of sleep disturbance was associated with worse SCT and parent-rated attention problems. Associations between sleep and performance-based cognitive measures assessing attention and working memory were not statistically significant. Conclusion: Findings of the current study highlight the importance of further investigation into the relationship between sleep and cognition in PBT survivors, which may assist efforts to maximize cognitive outcome and health-related quality of life in PBT survivors. The current study additionally suggests further investigation of SCT in this population is warranted, as it may be more sensitive to detecting possible associations with sleep disturbance relative to discrete measures that assess cognitive performance under ideal circumstances.

Prevalence of Sleep Disturbances in Pediatric Cancer Patients and Their Diagnosis and Management.

Sleep disturbances represent an understudied yet common source of distress among pediatric cancer patients and survivors, with deleterious effects on quality of life. Sleep issues stem from multiple risk factors, yet individual contributors are difficult to isolate, consequently impeding the identification of targets for intervention. In many pediatric cancer patients, disrupted sleep and its negative impact on quality of life continue into adulthood and may affect various functional domains. This literature review highlights the types and prevalence of sleep disturbances in pediatric cancer patients during active treatment and through survivorship. Potential etiological and risk factors for disturbed sleep are summarized, including the effects of cancer and its treatment, psychosocial and family factors, as well as individual-patient aspects, such as genetics, mood and coping skills. While existing assessment and management strategies are reviewed, the literature is incomplete, and significant gaps emerge in our understanding of sleep disturbances in pediatric cancer patients and survivors. The review concludes with recommendations of areas where further research is needed. The aims of this review include increasing clinicians' awareness of sleep disturbances as a significant source of poor quality of life in pediatric cancer patients and survivors and directing researchers to gaps in our understanding of sleep disturbances in pediatric cancer patients and survivors.

Educational Pain Points for Pediatric Brain Tumor Survivors: Review of Risks and Remedies.

Evolving treatment paradigms have led to increased survival rates for children diagnosed with a brain tumor, and this has increasingly shifted clinical and research focus to morbidity and quality of life among survivors. Among unfavorable outcomes, survivors of pediatric brain tumors are at risk for academic failure and low educational attainment, which may then contribute to lower health related quality of life, lower income and vocational status, and a greater likelihood of dependence on others in adulthood. Several specific risk factors for lower educational performance and attainment have been investigated. These are typically examined in isolation from one another which clouds understanding of the full range and potential interplay of contributors to educational difficulties. This review integrates and summarizes what is known about the direct and indirect barriers to educational success and performance (i.e., educational pain points) to enhance clinician knowledge of factors to consider when working with pediatric brain tumor survivors. Specific barriers to educational success include neurocognitive difficulties, school absences, psychosocial challenges, challenges to knowledge and communication, and physical and sensory difficulties. Finally, we discuss the current state of educational interventions and supports and offer recommendations for future research to improve educational outcomes for pediatric brain tumor survivors.

Non-pharmacological sleep interventions for pediatric cancer patients and survivors: a systematic review protocol.

BACKGROUND: Sleep disturbances constitute a common complication in pediatric cancer patients and survivors and are frequently severe enough to warrant treatment. Suboptimal sleep has been associated with decreased emotional well-being and cognitive functioning and increased behavioral problems. Standardized guidelines for non-pharmacological sleep interventions for adults with cancer exist, but no standard of care intervention or standard guidelines are available to guide such intervention in pediatric cancer patients and survivors. Therefore, effective behavioral interventions for improving sleep quality need to be identified. The objective of the review is to evaluate the effect of non-pharmacological sleep interventions on sleep quality in pediatric cancer patients and survivors. METHODS: The review will consider studies that include children and adolescents between 0 and 18 years diagnosed with cancer or who have a history of cancer who have non-respiratory sleep disturbance. We will include experimental and quasi-experimental studies evaluating non-pharmacological interventions such as psychological interventions, technical/device interventions, interventions targeting physical activity, and complementary and alternative medicine interventions (e.g., yoga, massage, music). Interventions involving medications, ingestible supplements, products purported to work through absorption, and medical devices will be excluded. Primary outcome will be sleep quality as measured by methods including retrospective ratings, daily sleep diary, and validated questionnaires. Secondary outcomes will include total sleep time, sleep onset latency, wake after sleep onset, daytime sleepiness, and daytime sleep duration (naps) as measured by retrospective ratings, daily sleep diary, validated questionnaires, and/or actigraphy. Databases will include MEDLINE (Ovid), EMBASE (Ovid), Cochrane Library, CINAHL (Ebsco), and PsycINFO (Ovid) and will be queried from database inception to present. Two reviewers will independently screen all citations, full-text articles, and extract data. The study methodological quality will be assessed using Joanna Briggs Institute (JBI) critical appraisal tools. Data will be extracted and findings pooled and synthesized using a meta-aggregation approach via the JBI System for the Unified Management, Assessment, and Review of Information (SUMARI). If feasible, we will conduct random effects meta-analysis. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., methodological quality, study design, outcome measures). DISCUSSION: This systematic review will synthesize and consolidate evidence on existing non-pharmacological interventions to improve sleep in pediatric cancer patients and survivors. Findings may help inform practitioners working with pediatric cancer patients and survivors experiencing sleep disturbances and is intended to identify gaps and opportunities to improve methodical quality of further non-pharmacological sleep intervention research in this population toward developing an eventual standard of care. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020200397 .

Neurocognitive Effects and Necrosis in Childhood Cancer Survivors Treated With Radiation Therapy: A PENTEC Comprehensive Review.

PURPOSE: A PENTEC review of childhood cancer survivors who received brain radiation therapy (RT) was performed to develop models that aid in developing dose constraints for RT-associated central nervous system (CNS) morbidities. METHODS AND MATERIALS: A comprehensive literature search, through the PENTEC initiative, was performed to identify published data pertaining to 6 specific CNS toxicities in children treated with brain RT. Treatment and outcome data on survivors were extracted and used to generate normal tissue complication probability (NTCP) models. RESULTS: The search identified investigations pertaining to 2 of the 6 predefined CNS outcomes: neurocognition and brain necrosis. For neurocognition, models for 2 post-RT outcomes were developed to (1) calculate the risk for a below-average intelligence quotient (IQ) (IQ <85) and (2) estimate the expected IQ value. The models suggest that there is a 5% risk of a subsequent IQ <85 when 10%, 20%, 50%, or 100% of the brain is irradiated to 35.7, 29.1, 22.2, or 18.1 Gy, respectively (all at 2 Gy/fraction and without methotrexate). Methotrexate (MTX) increased the risk for an IQ <85 similar to a generalized uniform brain dose of 5.9 Gy. The model for predicting expected IQ also includes the effect of dose, age, and MTX. Each of these factors has an independent, but probably cumulative effect on IQ. The necrosis model estimates a 5% risk of necrosis for children after 58.9 Gy or 59.9 Gy (2 Gy/fraction) to any part of the brain if delivered as primary RT or reirradiation, respectively. CONCLUSIONS: This PENTEC comprehensive review establishes objective relationships between patient age, RT dose, RT volume, and MTX to subsequent risks of neurocognitive injury and necrosis. A lack of consistent RT data and outcome reporting in the published literature hindered investigation of the other predefined CNS morbidity endpoints.

Risk Factors for Bullying Victimization in Children with Neurofibromatosis Type 1 (NF1).

Neurofibromatosis type 1 (NF1) is an autosomal disorder associated with numerous physical stigmata. Children with NF1 are at known risk for attention-deficit/hyperactivity disorder (ADHD), academic struggles, and significant social difficulties and adverse social outcomes, including bullying victimization. The primary aim of this study was to identify risk factors associated with bullying victimization in children with NF1 to better inform clinicians regarding targets for prevention and clinical intervention. Children and a parent completed questionnaires assessing the bully victim status, and parents completed a measure of ADHD symptoms. Analyses were completed separately for parent-reported victimization of the child and the child's self-report of victimization. According to the parent report, results suggest ADHD symptoms are a significant risk factor for these children being a target of bullying. Findings for academic disability were not conclusive, nor were findings related to having a parent with NF1. Findings indicate the need for further research into possible risk factors for social victimization in children with NF1. Results provide preliminary evidence that may guide clinicians working with children with NF1 and their parents in identifying higher-risk profiles that may warrant earlier and more intensive intervention to mitigate later risk for bullying victimization.

Auditory attention late effects in pediatric acute lymphoblastic leukemia.

This study sought to characterize auditory attention functioning among pediatric Acute Lymphoblastic Leukemia (ALL) survivors treated on a chemotherapy-only protocol, given previous literature suggesting late impact on sustained visual attention. We hypothesized similar deficits would be observed in auditory attention relative to previous literature indicating weakness with aspect of visual attention in this population. Survivors (n = 107, 53 females, M = 12.80 years) completed the Conners Continuous Auditory Test of Attention (CATA). Parents completed the Behavior Assessment System for Children, Second Edition and reported educational performance and services via structured questionnaire. Results indicated several CATA indices associated with sustained auditory attention were significantly worse than normative data, though group means were average. Reflecting individual variability in performance, 50% of the sample performed worse than one standard deviation from the mean on at least one CATA variable. Parent report of attention did not differ from normative means for the sample. Parent-report data indicated that 60% of the sample utilized academic support services, with a large proportion of survivors having utilized special education services. Poorer performance with sustained auditory attention was associated with poor academic outcomes. Greater methotrexate exposure and younger age at diagnosis were risk factors for inattentiveness. No gender differences were identified on direct assessment of auditory attention or parent report of attention, though male gender was associated with poorer educational performance. Findings suggest that auditory attention is an at-risk cognitive domain following treatment for pediatric ALL, and that an association exists between auditory attention and school performance in this population.

Rate and frequency of bullying victimization in school-age children with neurofibromatosis type 1 (NF1).

Children and adolescents with the genetic, tumor predisposition syndrome neurofibromatosis type I (NF1) have varying degrees of physical stigmata characteristic of the disease and experience high rates of social difficulties. The present study was the first to formally examine the rate (i.e., percentage of participants) and frequency of bullying victimization in a school-age sample of individuals with NF1. Bullying is defined as harmful behavior that is intentional, repeated, and involves a power imbalance between perpetrators and targets. Given that physical stigmata are characteristic of NF1 to varying degrees, it was hypothesized that bullying experiences would be common in school-age children with NF1. The present study also examined factors including age, gender, and health care provider ratings of severity of physical stigmata on self-reported rates of bullying victimization. Eighty-one school-age children with NF1 and a parent completed established bullying questionnaires. Results showed about 62% of the sample reported being bullied at least once in the last year, with 24.7% reporting being bullied daily. Boys reported significantly greater frequencies of bullying than did girls. Unique differences of gender and level of physical stigmata emerged, such that girls with low stigmata burden experienced significantly higher rates of bullying than girls with high stigmata burden. No differences in frequencies of bullying between low stigmata boys and high stigmata boys were found. The present study suggests that rates of bullying in NF1 are very high, which may be undervalued among adults and medical professionals, given the lack of research on bullying toward youth with NF1. School psychologists are uniquely positioned to implement programs and interventions to address the high rate of bullying toward the school-age NF1 population. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Neurocognitive and Psychosocial Outcomes in Pediatric Brain Tumor Survivors.

The late neurocognitive and psychosocial effects of treatment for pediatric brain tumor (PBT) represent important areas of clinical focus and ongoing research. Neurocognitive sequelae and associated problems with learning and socioemotional development negatively impact PBT survivors' overall health-related quality of life, educational attainment and employment rates. Multiple factors including tumor features and associated complications, treatment methods, individual protective and vulnerability factors and accessibility of environmental supports contribute to the neurocognitive and psychosocial outcomes in PBT survivors. Declines in overall measured intelligence are common and may persist years after treatment. Core deficits in attention, processing speed and working memory are postulated to underlie problems with overall intellectual development, academic achievement and career attainment. Additionally, psychological problems after PBT can include depression, anxiety and psychosocial adjustment issues. Several intervention paradigms are briefly described, though to date research on innovative, specific and effective interventions for neurocognitive late effects is still in its early stages. This article reviews the existing research for understanding PBT late effects and highlights the need for innovative research to enhance neurocognitive and psychosocial outcomes in PBT survivors.

Impact of attention on social functioning in pediatric medulloblastoma survivors.

BACKGROUND: Parent-reported attention problems have been associated with social functioning in a broad sample of pediatric cancer survivors. OBJECTIVE: The present study focused on a more homogeneous sample (pediatric medulloblastoma survivors), with the novel inclusion of self-reported attention ratings. PARTICIPANTS/METHODS: Thirty-three pediatric medulloblastoma survivors, ages 7-18 years, completed a brief IQ measure and self-report of attentional and social functioning. Parents rated patients' attentional and social functioning. RESULTS: Mean attention ratings were average based on both parent- and self-report, though parent ratings were significantly discrepant from normative means. No significant demographic or treatment-related predictors of self-reported attention problems were identified, whereas female gender was associated with greater parent-reported attention problems. Canonical correlation analysis revealed a significant association between parent-reported attention difficulties and social functioning in pediatric medulloblastoma survivors, but there was no association between self-reported attention problems and measures of social functioning. CONCLUSIONS: Consistent with existing literature in broader samples of pediatric cancer survivors, the present study further affirms attention deficits as an underlying contributor to social deficits in pediatric medulloblastoma survivors while also finding little relationship between self-reports of attention and social performance. Notably, present findings provide additional support suggesting that attention functioning is a more significant contributor to social outcomes for pediatric medulloblastoma survivors than the level of cognitive ability.

Elevated cranial ultrasound resistive indices are associated with improved neurodevelopmental outcomes one year after pediatric cardiac surgery: A single center pilot study.

OBJECTIVE: To determine if a non-invasive, repeatable test can be used to predict neurodevelopmental outcomes in patients with congenital heart disease. METHODS: This was a prospective study of pediatric patients less than two months of age undergoing congenital heart surgery at the Children's Health Children's Medical Center at Dallas. Multichannel near-infrared spectroscopy (NIRS) was utilized during the surgery, and ultrasound (US) resistive indices (RI) of the major cranial vessels were obtained prior to surgery, immediately post-operatively, and prior to discharge. Pearson's correlation, Fischer exact t test, and Fischer r to z transformation were used where appropriate. RESULTS: A total of 16 patients were enrolled. All had US data. Of the sixteen patients, two died prior to the neurodevelopmental testing, six did not return for the neurodevelopmental testing, and eight patients completed the neurodevelopmental testing. There were no significant correlations between the prior to surgery and prior to discharge US RI and neurodevelopmental outcomes. The immediate post-operative US RI demonstrated a strong positive correlation with standardized neurodevelopmental outcome measures. We were able to demonstrate qualitative differences using multichannel NIRS during surgery, but experienced significant technical difficulties implementing consistent monitoring. CONCLUSIONS: A higher resistive index in the major cerebral blood vessels following cardiac surgery in the neonatal period is associated with improved neurological outcomes one year after surgery. Obtaining an ultrasound with resistive indices of the major cerebral vessels prior to and after surgery may yield information that is predictive of neurodevelopmental outcomes.

Randomized placebo-controlled study of lovastatin in children with neurofibromatosis type 1.

OBJECTIVE: To assess the efficacy of lovastatin on visuospatial learning and attention for treating cognitive and behavioral deficits in children with neurofibromatosis type 1 (NF1). METHODS: A multicenter, international, randomized, double-blind, placebo-controlled trial was conducted between July 2009 and May 2014 as part of the NF Clinical Trials Consortium. Children with NF1 aged 8-15 years were screened for visuospatial learning or attention deficits (n = 272); 146 children demonstrated deficits at baseline and were randomly assigned to lovastatin (n = 74; 40 mg/d) or placebo (n = 70). Treatment was administered once daily for 16 weeks. Primary outcomes were total errors on the Cambridge Neuropsychological Test Automated Battery Paired Associate Learning task (visuospatial learning) and the Score subtest from the Test of Everyday Attention for Children (sustained attention). Secondary outcomes measured executive function, attention, visuospatial skills, behavior, and quality of life. Primary analyses were performed on the intention-to-treat population. RESULTS: Lovastatin had no significant effect on primary outcomes after 16 weeks of treatment: visuospatial learning (Cohen d = -0.15, 95% confidence interval -0.47 to 0.18) or sustained attention (Cohen d = 0.19, 95% confidence interval -0.14 to 0.53). Lovastatin was well tolerated, with no increase in reported adverse events compared to placebo. CONCLUSIONS: Lovastatin administered once daily for 16 weeks did not improve visuospatial learning or attention in children with NF1 and is not recommended for amelioration of cognitive deficits in this population. CLINICALTRIALSGOV IDENTIFIER: This study was registered at ClinicalTrials.gov (NCT00853580) and Australian New Zealand Clinical Trials Registry (ACTRN12607000560493). CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for children with NF1, lovastatin does not improve visuospatial learning or attention deficits.

Effect of motivation on academic fluency performance in survivors of pediatric medulloblastoma.

It has been proposed previously that extrinsic motivation may enable survivors of childhood medulloblastoma to significantly improve aspects of neurocognitive performance. In healthy populations, enhanced motivation has been shown to promote academic fluency, a domain likely more relevant to the educational outcomes of pediatric medulloblastoma survivors than academic skill development. The present study investigates the effect of enhanced extrinsic motivation on fluent (i.e., accurate and efficient) academic performance in pediatric medulloblastoma survivors. Participants were 36 children, ages 7-18, who had completed treatment for medulloblastoma. Participants completed a neuropsychological battery that included administration of equivalent tasks on Forms A and B of the Woodcock-Johnson III Tests of Achievement. Half were randomly assigned to an incentive condition prior to the administration of Form B. Provision of a performance-based incentive resulted in statistically significant improvement, but not normalization of function, in performance on measures of academic fluency. No demographic, treatment-related, academic, neuropsychological, or self-perception variables predicted response to incentive. Findings suggest that academic performance of survivors may significantly improve under highly motivating conditions. In addition to implications for educational services, this finding raises the novel possibility that decreased motivation represents an inherent neuropsychological deficit in this population and provides a rationale for further investigation of factors affecting individual differences in motivational processes. Further, by examining effort in a context where effort is not inherently suspect, present findings also significantly contribute to the debate regarding the effects of effort and motivation on neuropsychological performance.

Predicting Outcome after Pediatric Traumatic Brain Injury by Early Magnetic Resonance Imaging Lesion Location and Volume.

Brain lesions after traumatic brain injury (TBI) are heterogeneous, rendering outcome prognostication difficult. The aim of this study is to investigate whether early magnetic resonance imaging (MRI) of lesion location and lesion volume within discrete brain anatomical zones can accurately predict long-term neurological outcome in children post-TBI. Fluid-attenuated inversion recovery (FLAIR) MRI hyperintense lesions in 63 children obtained 6.2±5.6 days postinjury were correlated with the Glasgow Outcome Scale Extended-Pediatrics (GOS-E Peds) score at 13.5±8.6 months. FLAIR lesion volume was expressed as hyperintensity lesion volume index (HLVI)=(hyperintensity lesion volume / whole brain volume)×100 measured within three brain zones: zone A (cortical structures); zone B (basal ganglia, corpus callosum, internal capsule, and thalamus); and zone C (brainstem). HLVI-total and HLVI-zone C predicted good and poor outcome groups (p<0.05). GOS-E Peds correlated with HLVI-total (r=0.39; p=0.002) and HLVI in all three zones: zone A (r=0.31; p<0.02); zone B (r=0.35; p=0.004); and zone C (r=0.37; p=0.003). In adolescents ages 13-17 years, HLVI-total correlated best with outcome (r=0.5; p=0.007), whereas in younger children under the age of 13, HLVI-zone B correlated best (r=0.52; p=0.001). Compared to patients with lesions in zone A alone or in zones A and B, patients with lesions in all three zones had a significantly higher odds ratio (4.38; 95% confidence interval, 1.19-16.0) for developing an unfavorable outcome.

School Competence and Fluent Academic Performance: Informing Assessment of Educational Outcomes in Survivors of Pediatric Medulloblastoma.

Academic difficulties are widely acknowledged but not adequately studied in survivors of pediatric medulloblastoma. Although most survivors require special education services and are significantly less likely than healthy peers to finish high school, measured academic skills are typically average. This study sought to identify potential factors associated with academic difficulties in this population and focused on school competence and fluent academic performance. Thirty-six patients (ages 7-18 years old) were recruited through the Departments of Neurosurgery and Neuro-Oncology at Children's Medical Center Dallas and Cook Children's Medical Center in Fort Worth, TX. Participants completed a neuropsychological screening battery including selected Woodcock-Johnson III Tests of Achievement subtests. Parents completed the Child Behavior Checklist. School competence was significantly correlated with measured academic skills and fluency. Basic academic skill development was broadly average, in contrast to significantly worse fluent academic performance. School competence may have utility as a measure estimating levels of educational success in this population. Additionally, academic difficulties experienced by childhood medulloblastoma survivors may be better captured by measuring deficits in fluent academic performance rather than skills. Identification of these potential factors associated with educational outcomes of pediatric medulloblastoma survivors has significant implications for research, clinical assessment, and academic services/interventions.

Triheptanoin for glucose transporter type I deficiency (G1D): modulation of human ictogenesis, cerebral metabolic rate, and cognitive indices by a food supplement.

IMPORTANCE: Disorders of brain metabolism are multiform in their mechanisms and manifestations, many of which remain insufficiently understood and are thus similarly treated. Glucose transporter type I deficiency (G1D) is commonly associated with seizures and with electrographic spike-waves. The G1D syndrome has long been attributed to energy (ie, adenosine triphosphate synthetic) failure such as that consequent to tricarboxylic acid (TCA) cycle intermediate depletion. Indeed, glucose and other substrates generate TCAs via anaplerosis. However, TCAs are preserved in murine G1D, rendering energy-failure inferences premature and suggesting a different hypothesis, also grounded on our work, that consumption of alternate TCA precursors is stimulated and may be detrimental. Second, common ketogenic diets lead to a therapeutically counterintuitive reduction in blood glucose available to the G1D brain and prove ineffective in one-third of patients. OBJECTIVE: To identify the most helpful outcomes for treatment evaluation and to uphold (rather than diminish) blood glucose concentration and stimulate the TCA cycle, including anaplerosis, in G1D using the medium-chain, food-grade triglyceride triheptanoin. DESIGN, SETTING, AND PARTICIPANTS: Unsponsored, open-label cases series conducted in an academic setting. Fourteen children and adults with G1D who were not receiving a ketogenic diet were selected on a first-come, first-enrolled basis. INTERVENTION: Supplementation of the regular diet with food-grade triheptanoin. MAIN OUTCOMES AND MEASURES: First, we show that, regardless of electroencephalographic spike-waves, most seizures are rarely visible, such that perceptions by patients or others are inadequate for treatment evaluation. Thus, we used quantitative electroencephalographic, neuropsychological, blood analytical, and magnetic resonance imaging cerebral metabolic rate measurements. RESULTS: One participant (7%) did not manifest spike-waves; however, spike-waves promptly decreased by 70% (P = .001) in the other participants after consumption of triheptanoin. In addition, the neuropsychological performance and cerebral metabolic rate increased in most patients. Eleven patients (78%) had no adverse effects after prolonged use of triheptanoin. Three patients (21%) experienced gastrointestinal symptoms, and 1 (7%) discontinued the use of triheptanoin. CONCLUSIONS AND RELEVANCE: Triheptanoin can favorably influence cardinal aspects of neural function in G1D. In addition, our outcome measures constitute an important framework for the evaluation of therapies for encephalopathies associated with impaired intermediary metabolism.

Complicated subdural empyema in an adolescent.

Little is known regarding typical neuropsychological outcomes of intracranial empyema, a rare complication of sinusitis marked by accumulation of purulent material adjacent to the brain. A 15-year-old, right-handed male presented with a 3-day history of congestion, lethargy, fever, headache, dizziness, unequal pupil dilation, and right-sided facial droop. Computed tomography revealed right-sided subdural empyema causing subfalcine, central, foraminal uncal, and tonsillar herniation. Postoperative inpatient neuropsychological consultation was requested 17 days postsurgery due to language deficits. Through comparison of neuropsychological and radiological findings, this case of subdural empyema demonstrates the anatomical and functional impact of mass effect on the brainstem and the vasculature of the contralateral hemisphere. Deficits were observed in expressive language, processing speed, and fine motor functioning, all of which lingered 6 months postacute. This case study reviews the pathophysiology of subdural empyema and illustrates its potential neuropsychological impact to inform clinicians encountering this rare condition.

Attention training for school-aged children with ADHD: results of an open trial.

OBJECTIVE: The article discusses a feasibility study conducted to examine whether Pay Attention!, an intervention training sustained, selective, alternating, and divided attention, could be utilized in a clinical setting with children diagnosed with ADHD, and whether children who received the intervention made attention and executive functioning gains. METHOD: After a diagnostic and baseline evaluation, 23 school-aged children with ADHD participate in up to 16 sessions of Pay Attention! and the outcomes are evaluated. RESULTS: Results show the intervention is feasible to administer and acceptable to participants. Parents and clinicians rate fewer ADHD symptoms following the intervention and report improvements in executive function. Child performance on neuropsychological tests showed improvements in fluid reasoning and cognitive flexibility and working memory. CONCLUSION: The findings suggest that a randomized clinical trial of Pay Attention! is warranted to investigate its viability as a treatment for attention and executive functioning deficits in ADHD.

Executive functioning in children and adolescents with Major Depressive Disorder.

The present investigation examined neurocognitive functioning, focusing on executive functioning (EF), in 39 children and adolescents with Major Depressive Disorder (MDD) and 24 healthy control subjects all ages 8 to 17 years. The Wechsler Intelligence Scale for Children-Third Edition along with several measures of executive functioning including the Wisconsin Card Sorting Task, Trail Making Test, Controlled Oral Word Association Test, and the Stroop Color Word Test were administered. The neurocognitive profiles for the group of depressed children and adolescents were grossly intact as most scores on intellectual and EF measures fell within the average range and did not differ from the comparison group. Mental processing speed was decreased in the MDD versus normal control group and 27% of the depressed group performed below average on the Trail Making Test. This investigation provided a good base from which to compare future literature on EF in outpatients with early-onset MDD.