Effects of sleep disturbance on neuropsychological functioning in patients with pediatric brain tumor.

PURPOSE: While the effects of sleep on cognition in typically developing children are well established, there is a paucity of research in patients with pediatric brain tumor (PBT), despite their increased risk for sleep-related disturbances. The aim of this retrospective study was to examine the impact of sleep factors on patient-reported outcome (PRO) measures, including adaptive and executive functioning within this population. METHODS: 133 patients with PBT (52% male) ages 5-23 (x̄ = 12.8 years; SD = 4.5 years) underwent neuropsychological evaluation, including assessment of adaptive and executive functioning. Subjective sleep concerns, nocturnal sleep duration, and daytime sleep behavior were also collected and compared to age-based guidelines. RESULTS: Nearly 30% of patients endorsed subjective sleep concerns, while the sample as a whole reported reduced nocturnal sleep duration (approximately one hour below age-based recommendations). Despite the expectation for monophasic sleep by age five, nearly half of the sample reported consistent daytime napping. Inadequate sleep predicted decreased adaptive functioning, F(1, 56) = 4.23, p = .022 (R2 = .07), as well as increased symptoms of executive dysfunction, F(1, 108) = 3.51, p = .003 (R2 = .03). CONCLUSION: Patients with PBT demonstrate several aspects of abnormal sleep, which are associated with poorer long-term PROs. Further exploration of diagnostic, treatment-related, and demographic variables will be needed to better understand these relationships among patients with PBT in order to inform appropriate interventions.

Efficacy of early treatment in patients with cobalamin C disease identified by newborn screening: a 16-year experience.

PURPOSE: Despite implementation of newborn screening (NBS), outcomes in cobalamin C disease (cblC) remain poor. Therapy with hydroxycobalamin and betaine is widely used, but dietary recommendations vary among metabolic centers. We present a longitudinal analysis of the relationship between metabolic control, diet, and outcomes in a cohort of cblC patients. METHODS: We completed a retrospective analysis of 12 patients with cblC referred for abnormal NBS results and followed in our center between 1999 and 2015. RESULTS: Of the patients, 87.5% had intellectual disability and 75% had retinopathy; 16.7% had one episode of mild acidosis. However, no patients manifested major metabolic decompensation. Developmental outcomes correlated more closely with initial metabolic abnormalities than with long-term metabolic control. Increased intake of medical foods resulted in better control but also perturbations in the ratios of essential amino acids and lower z-scores for head circumference. We found no relationship between diet and cognitive outcomes. CONCLUSIONS: Although dietary therapy for cblC patients improves metabolic control, few patients experience metabolic decompensation regardless of diet. Increased incomplete protein intake is not correlated with improvements in outcomes. Overall, outcomes are poor despite early initiation of therapy and regardless of the dietary strategy used.Genet Med advance online publication 02 February 2017.

Assessing learning and memory among patients with pediatric brain tumor (PBT): a comparison of measures.

Patients with pediatric brain tumor (PBT) can have memory deficits due to tumor location, medical complications, and treatment. The main objective of this study was to investigate whether the California Verbal Learning Test-Children's Version (CVLT-C; 1994) and briefer Child and Adolescent Memory Profile (ChAMP; 2015) similarly identify such deficits. Seventy-five patients with PBT ages 8-16 (x‾ = 13.1 years, SD = 2.1) were administered the ChAMP or CVLT-C. Rote verbal learning, long-term retrieval, and recognition were analyzed using standardized z-scores. Analyses of differences between measures did not reach statistical significance. Both measures indicated significant downward shifts across free retrieval trials from normative means, with scores approximately 1/3 (ChAMP) to 1/2 (CVLT-C) SD below means across learning and long-term retrieval trials. Scores on recognition trials did not differ significantly from the normative mean. Post-hoc analyses using a subset of the sample who received cranial irradiation (n = 45) similarly found no significant differences between memory measures. Additional post-hoc examination of proportion of participants falling within or below the "below average" range (≤8th percentile) revealed comparable performance between the two measures, whereas the proportion of participants falling at or below 1.5 SDs below the mean on retrieval trials was lower using ChAMP Lists as compared to the CVLT-C. Given the ChAMP is less demanding in terms of time and effort and utilizes more updated and representative normative data, this study supports the ChAMP as a useful tool to evaluate learning and memory within this population.

Neuropsychological surveillance model for survivors of pediatric cancer: A descriptive report of methodology and feasibility.

Objective: Neuropsychological late effects of pediatric cancer may not become apparent for years after therapy; therefore, serial monitoring is necessary for detecting changes to ensure timely intervention. Unfortunately, lack of access to neuropsychologists, increased patient volume, insurance authorization and reimbursement issues, time required for neuropsychological evaluation, and practice effects related to repeat testing present many challenges to provision of neuropsychological care for survivors of childhood cancer. Models involving surveillance and monitoring have been proposed, though minimal data exist related to the implementation and feasibility of such models. Method: In this descriptive feasibility study, the Neuropsychology Consult Clinic (NCC) at Children's Hospital Los Angeles is presented, outlining a methodology and algorithm for neuropsychological surveillance of survivors of non-CNS pediatric cancer and an account of the first three years of clinic implementation. Participants included 215 survivors (x̅ age = 5.6 years), including 75.3% Latinx patients. Results: The overall clinic implementation was found to be feasible, with approximately 75% of patients "passing" the screening and 25% "failing" the screening. Clinical judgment only conflicted with the algorithm 8.6% of the time. However, several limitations to feasibility were noted, including validity concerns and ability/time to complete parent-reported outcomes using Spanish forms, as well as access to bilingual examiners. Conclusions: These preliminary data support the feasibility of the NCC model with limitations as outlined above. This is the first phase in a multiphase plan to develop an appropriate screening clinic for survivors of pediatric cancer, with the next phase focusing on sensitivity/specificity of measures.

Neuropsychological outcomes on Head Start III: a prospective, multi-institutional clinical trial for young children diagnosed with malignant brain tumors.

BACKGROUND: Current pediatric brain tumor treatment focuses on titrating toxicity based on risk factors while simultaneously improving survivorship. The Head Start (HS) protocols I to IV (1991-present) use high-dose chemotherapy (HDCTx) with an aim of reducing or eliminating cranial irradiation in very young children, the most vulnerable to its effects. METHODS: We examined estimated Full Scale IQ, overall Adaptive Functioning, Working Memory, Processing Speed, and Verbal and Nonverbal Memory outcome data for 43 HS III patients diagnosed between ages 2 months and 7 years from 15 institutions in the United States and Canada. RESULTS: At a mean of 5.12 years postdiagnosis, the HS III patients performed within the average to low-average ranges across these variables; however, individual variability was noted with scores ranging from superior to impaired, and the sample as a whole performed lower than age expectations. Performance did not significantly differ by sex or ethnicity, diagnosis, or for those treated with an intravenous methotrexate dose of 400 mg/kg vs 270 mg/kg. Additionally, performance did not significantly differ by age at diagnosis or length of follow-up. CONCLUSIONS: The results, indicating overall average to low-average neurocognitive functioning, are encouraging, though significant individual variability was noted. Those who were younger at diagnosis, received more intensive methotrexate, and were further out from treatment were not at significantly increased risk of cognitive decline within our sample, suggesting a strategy of using HDCTx and autologous hematopoietic progenitor cell rescue to reduce or eliminate irradiation may allow for continued CNS development in young children treated for a brain tumor.

Excellent outcome of young children with nodular desmoplastic medulloblastoma treated on "Head Start" III: a multi-institutional, prospective clinical trial.

BACKGROUND: "Head Start" III, was a prospective clinical trial using intensive induction followed by myeloablative chemotherapy and autologous hematopoietic cell rescue (AuHCR) to either avoid or reduce the dose/volume of irradiation in young children with medulloblastoma. METHODS: Following surgery, patients received 5 cycles of induction followed by myeloablative chemotherapy using carboplatin, thiotepa, and etoposide with AuHCR. Irradiation was reserved for children >6 years old at diagnosis or with residual tumor post-induction. RESULTS: Between 2003 and 2009, 92 children <10 years old with medulloblastoma were enrolled. Five-year event-free survival (EFS) and overall survival (OS) rates (±SE) were 46 ±â€…5% and 62 ±â€…5% for all patients, 61 ±â€…8% and 77 ±â€…7% for localized medulloblastoma, and 35 ±â€…7% and 52 ±â€…7% for disseminated patients. Nodular/desmoplastic (ND) medulloblastoma patients had 5-year EFS and OS (±SE) rates of 89 ±â€…6% and 89 ±â€…6% compared with 26 ±â€…6% and 53 ±â€…7% for classic and 38 ±â€…13% and 46 ±â€…14% for large-cell/anaplastic (LCA) medulloblastoma, respectively. In multivariate Cox regression analysis, histology was the only significant independent predictor of EFS after adjusting for stage, extent of resection, regimen, age, and sex (P <0.0001). Five-year irradiation-free EFS was 78 ±â€…8% for ND and 21 ±â€…5% for classic/LCA medulloblastoma patients. Myelosuppression was the most common toxicity, with 2 toxic deaths. Twenty-four survivors completed neurocognitive evaluation at a mean of 4.9 years post-diagnosis. IQ and memory scores were within average range overall, whereas processing speed and adaptive functioning were low-average. CONCLUSION: We report excellent survival and preservation of mean IQ and memory for young children with ND medulloblastoma using high-dose chemotherapy, with most patients surviving without irradiation.

Neuropsychological implications of Cobalamin C (CblC) disease in Hispanic children detected through newborn screening.

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.

A neurodevelopmental approach to understanding memory processes among intellectually gifted youth with attention-deficit hyperactivity disorder.

Intellectual giftedness is associated with strong strategic verbal memory while attention-deficit hyperactivity disorder (ADHD) is associated with strategic verbal memory deficits; however, no previous research has explored how this contradiction manifests in gifted populations with diagnoses of ADHD. The purpose of this study was to explore strategic verbal memory processes among intellectually gifted youth with and without ADHD to provide clarification regarding this specific aspect of neuropsychological functioning within this population. One hundred twenty-five youth completed neuropsychological evaluations including the Wechsler Intelligence Scale for Children-Fourth Edition and California Verbal Learning Test-Children's Version (CVLT-C). Results revealed significant differences between groups, with intellectually gifted youth with ADHD achieving lower T scores on CVLT-C Trials 1 through 5 compared with intellectually gifted youth without ADHD, and intellectually gifted youth with ADHD achieving higher T scores than youth of average intellectual abilities with ADHD. Additionally, repeated-measures analysis of variance revealed a main effect improvement among gifted youth with ADHD in short-delay recall when provided with organizational cues. Findings revealed new evidence about the role of twice exceptionality (specifically intellectual giftedness and ADHD) in strategic verbal memory and have important implications for parents, educators, psychologists and neuropsychologists, and other mental health professionals working with this population.

Intellectual ability as a predictor of performance on the Wisconsin Card-Sorting Test.

The purpose of this study was to explore the relationship between intelligence and executive functioning in youth. More specifically, the authors hypothesized that there would be a positive correlation between scores on the Wechsler Intelligence Scale for Children-Fourth Edition General Ability Index (GAI) and understanding of sorting principles as measured by percent conceptual-level responses on the Wisconsin Card-Sorting Test (WCST). One hundred eighty-five children and adolescents completed neuropsychological evaluations. Results revealed a curvilinear regression with bright youth (GAI = 115-129) and gifted youth (GAI ≥130) performing better than average youth (GAI = 90-114) and no difference in performance between bright and gifted youth. Additionally, post-hoc analyses revealed intelligence in children 5 to 8 years of age and 12 to 16 years of age did not significantly predict percent conceptual-level responses, while intelligence predicted more than 19% of the variance in percent conceptual-level responses for children ages 9 to 11 years old. Findings revealed new evidence about the role of intellectual ability in executive functioning among different age ranges and have important implications for psychologists, caregivers, educators, and other professionals working with this population.