Executive and social functioning in pediatric posterior fossa tumor survivors and healthy controls.

Background: Executive and social functioning difficulty is well established in pediatric brain tumor survivors. Few studies have compared posterior fossa (PF) tumor survivors in comparison to their peers. The relationship between attention, processing speed, working memory, fatigue, and executive and social functioning was investigated to better understand the factors that impact executive and social functioning in PF tumor populations. Methods: Sixteen medulloblastomas, 9 low-grade astrocytomas (LGAs), and 17 healthy controls recruited from 4 sites completed measures of working memory and processing speed, and self-reported fatigue. One parent completed questionnaires on executive and social functioning. Results: There were no significant differences among all 3 groups on parent-reported executive and social functioning; of note, parents of LGA survivors expressed greater concerns regarding behavioral and cognitive regulation than did parents of medulloblastoma survivors and healthy controls. Parent-reported attention was related to parent-reported emotion, behavior, and cognitive regulation. Worse self-reported fatigue was associated with greater emotional dysregulation for the 2 PF tumor groups. Conclusions: Parents of PF tumor survivors described their children as performing similarly to their peers in most facets of executive and social functioning. While LGA survivors are traditionally thought to have more favorable outcomes, our finding of parent-reported executive functioning concerns to be worse for this group highlights the importance of long-term follow-up for all PF tumor survivors. Additionally, significant effects of attention on aspects of executive functioning in PF tumor survivors may inform current clinical practice and the future development of more effective interventions.

Red blood cells as glucose carriers to the human brain: Modulation of cerebral activity by erythrocyte exchange transfusion in Glut1 deficiency (G1D).

Red blood cells circulating through the brain are briefly but closely apposed to the capillary endothelium. We hypothesized that this contact provides a nearly direct pathway for metabolic substrate transfer to neural cells that complements the better characterized plasma to endothelium transfer. While brain function is considered independent of normal fluctuations in blood glucose concentration, this is not borne out by persons with glucose transporter I (GLUT1) deficiency (G1D). In them, encephalopathy is often ameliorated by meal or carbohydrate administration, and this enabled us to test our hypothesis: Since red blood cells contain glucose, and since the red cells of G1D individuals are also deficient in GLUT1, replacing them with normal donor cells via exchange transfusion could augment erythrocyte to neural cell glucose transport via mass action in the setting of unaltered erythrocyte count or plasma glucose abundance. This motivated us to perform red blood cell exchange in 3 G1D persons. There were rapid, favorable and unprecedented changes in cognitive, electroencephalographic and quality-of-life measures. The hypothesized transfer mechanism was further substantiated by in vitro measurement of direct erythrocyte to endothelial cell glucose flux. The results also indicate that the adult intellect is capable of significant enhancement without deliberate practice. ClinicalTrials.gov registration: NCT04137692 https://clinicaltrials.gov/ct2/show/NCT04137692.

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.

Comparison of neuropsychological functioning in pediatric posterior fossa tumor survivors: Medulloblastoma, low-grade astrocytoma, and healthy controls.

BACKGROUND: Neuropsychological comparison of medulloblastoma (MB) and cerebellar low-grade astrocytoma (LGA) survivors to controls can clarify treatment-related neurocognitive late effects. While both brain tumor groups undergo surgery to the posterior fossa, children with MB additionally receive craniospinal irradiation with boost and chemotherapy. This study provides an updated comparison of neuropsychological functioning in these two groups and examines effects of demographic risk factors upon outcomes. PROCEDURE: Forty-two children (16 MB, nine LGA, and 17 controls) completed measures of intellectual functioning, verbal learning/memory, visual-motor integration, and fine-motor functioning. The effects of age at diagnosis, time since diagnosis, gender, fatigue, and social status on neuropsychological functioning were examined. RESULTS: MB survivors demonstrated the worst neurocognitive late effects, but they were less severe and extensive than in prior studies. LGA survivors' mean scores were below normative expectations in working memory, processing speed, and fine-motor functioning. In this overall sample, processing speed difficulties were independent of fine-motor functioning and fatigue. Higher parental education was associated with better intellectual functioning, working memory, delayed recall, and visual-motor integration. Neuropsychological function was not associated with gender, age at diagnosis, or time since diagnosis. CONCLUSION: The results support that contemporary treatment approaches with craniospinal irradiation plus boost and chemotherapy confer the greatest risk for late effects, while surgical resection is associated with subtle but important neurocognitive difficulties. Ultimately, this study furthers our understanding of factors impacting neuropsychological function in pediatric MB and LGA survivors and contributes to empirical support for close monitoring and targeted interventions into survivorship.

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.

InterOrganizational practice committee guidance/recommendation for models of care during the novel coronavirus pandemic.

Objective: The Inter Organizational Practice Committee (IOPC) convened a workgroup to develop guidance on models to provide neuropsychological (NP) care during the COVID-19 pandemic while minimizing risks of novel coronavirus transmission as lockdown orders are lifted and ambulatory clinical services resume.Method: A collaborative panel of experts from major professional organizations developed provisional guidance for models of neuropsychological practice during the pandemic. The stakeholders included the American Academy of Clinical Neuropsychology/American Board of Clinical Neuropsychology, the National Academy of Neuropsychology, Society of Clinical neuropsychology (Division 40) of the American Psychological Association, the American Board of Professional Neuropsychology, and the American Psychological Association Services, Inc.Results: This guidance reviews the risks and benefits of conducting NP exams in several ways, including standard in-person, mitigated in-person, in-clinic teleneuropsychology (TeleNP), and in-home TeleNP. Strategies are provided for selecting the most appropriate model for a given patient, taking into account four levels of patient risk stratification, level of community risk and the concept of stepped models of care. Links are provided to governmental agency and professional organization resources as well as an outline and discussion of essential infection mitigation processes based on commonalities across recommendations from diverse federal, state, local, and professional organization recommendations.Conclusion: This document provides recommendations and guidance with analysis of the risks relative to the benefits of various models of neuropsychological care during the COVID-19 pandemic. These recommendations may be revised as circumstances evolve, with updates posted continuously on the IOPC website (https://iopc.online/).

Inter Organizational Practice Committee Guidance/Recommendation for Models of Care During the Novel Coronavirus Pandemic.

OBJECTIVE: The Inter Organizational Practice Committee (IOPC) convened a workgroup to develop guidance on models to provide neuropsychological (NP) care during the COVID-19 pandemic while minimizing risks of novel coronavirus transmission as lockdown orders are lifted and ambulatory clinical services resume. METHOD: A collaborative panel of experts from major professional organizations developed provisional guidance for models of neuropsychological practice during the pandemic. The stakeholders included the American Academy of Clinical Neuropsychology/American Board of Clinical Neuropsychology, the National Academy of Neuropsychology, Society of Clinical neuropsychology (Division 40) of the American Psychological Association, the American Board of Professional Neuropsychology, and the American Psychological Association Services, Inc. RESULTS: This guidance reviews the risks and benefits of conducting NP exams in several ways, including standard in-person, mitigated in-person, in-clinic teleneuropsychology (TeleNP), and in-home TeleNP. Strategies are provided for selecting the most appropriate model for a given patient, taking into account four levels of patient risk stratification, level of community risk, and the concept of stepped models of care. Links are provided to governmental agency and professional organization resources as well as an outline and discussion of essential infection mitigation processes based on commonalities across recommendations from diverse federal, state, local, and professional organization recommendations. CONCLUSION: This document provides recommendations and guidance with analysis of the risks relative to the benefits of various models of NP care during the COVID-19 pandemic. These recommendations may be revised as circumstances evolve, with updates posted continuously on the IOPC website (https://iopc.online/).

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).

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.

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.

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.

Fatigue, emotional functioning, and executive dysfunction in pediatric multiple sclerosis.

OBJECTIVE: Fatigue, depression, anxiety, and executive dysfunction are associated with multiple sclerosis (MS) in adults. Existing research suggests similar problems in pediatric MS, but relationships between these variables have not been investigated. This study investigates the associations between executive functioning and fatigue, emotional functioning, age of onset, and disease duration in pediatric MS. METHODS: Twenty-six MS or Clinically Isolated Syndrome (CIS) patients, ages 7 to 18, were evaluated through a multidisciplinary demyelinating diseases clinic. Participants completed neuropsychological screening including Verbal Fluency, Digit Span, and Trail-Making Test. Parents completed rating forms of behavioral, emotional, and executive functioning. Patients and parents completed questionnaires related to the patient's quality of life and fatigue. Pearson's correlation coefficients were calculated to investigate relationships between fatigue, emotional functioning, and executive functioning, as well as to examine correlations between parent and child reports of fatigue. RESULTS: Rates of parent-reported anxiety, depression, fatigue, and executive dysfunction varied widely. Means were below average on the Trail-Making Test and average on Verbal Fluency and Digit Span, though scores varied widely. Various fatigue and emotional functioning indices-but not age of onset or disease duration-significantly correlated with various performance-based measures of executive functioning. CONCLUSION: Results indicate pediatric MS is associated with some degree of fatigue, emotional difficulties, and executive dysfunction, the latter of which is associated with the two former. Notably, age of onset and disease duration did not significantly correlate with executive functioning. Results advance understanding of psychological and clinical variables related to neurocognitive outcomes in pediatric MS.

Cognitive functioning in pediatric transverse myelitis.

BACKGROUND: Transverse myelitis (TM) is an inflammatory disease of the spinal cord. In pediatric TM patients, cognitive and psychological problems have been described only anecdotally. OBJECTIVES: Study aims include describing cognitive dysfunction among a cohort of pediatric TM patients as well as qualitatively exploring the impact of depression, medication, and fatigue on cognitive functioning. METHODS: Twenty-four consecutive TM patients referred to a pediatric demyelinating diseases clinic completed neuropsychological screening. Means, standard deviations (SD), and percentages of patients performing at or below 1.0, 1.5, and 2.0 SD from the mean on tests administered are presented. RESULTS: Means were generally average across domains; however, scores ranged widely across subjects within each domain. The highest rate of deficits was observed in fine-motor speed/dexterity. Slightly higher frequencies of impairment were observed in attention and memory as compared to processing speed and verbal fluency. Results did not suggest a clear association between cognitive problems and depression or medication use but did suggest that fatigue may impact cognitive functioning. CONCLUSIONS: This study is the first to document cognitive deficits in pediatric TM and raises questions regarding our understanding of the central nervous system (CNS) injury associated with TM. Findings warrant further exploration of neuropsychological outcomes in TM to inform appropriate intervention.

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.