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.

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 5 272); 146 children demonstrated deficits at baseline and were randomly assigned to lovastatin (n 5 74; 40 mg/d) or placebo (n 5 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: 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.

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.

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.

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 PARTICIPANTSUnsponsored, 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 MEASURESFirst, 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 RELEVANCETriheptanoin 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.

Children with cancer and their families experience shifts in spiritual wellness from diagnosis through treatment and survivorship or bereavement. An interdisciplinary team conducted a systematic review of quantitative and qualitative research on spiritual assessments, interventions, and outcomes in childhood cancer following PRISMA guidelines using a PROSPERO registered protocol. Thirty‐nine well‐designed studies were included in the final analysis. The findings from this systematic review indicate the need for early spiritual assessment with offering of continued support for the spiritual functioning of children with cancer and their families as a standard of care.

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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. Fluidattenuated 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, HLVItotal 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.