Neurocognitive Outcomes In Children Research Articles

Surgical outcomes in children with drug-resistant epilepsy and hippocampal sclerosis

BackgroundHippocampal sclerosis (HS) is a common surgical substrate in adult epilepsy surgery cohorts but variably reported in various pediatric cohorts. ObjectiveWe aimed to study the epilepsy phenotype, radiological and pathological variability, seizure and neurocognitive outcomes in children with drug-resistant epilepsy and hippocampal sclerosis (HS) with or without additional subtle signal changes in anterior temporal lobe who underwent surgery. MethodsThis retrospective study enrolled children with drug-resistant focal epilepsy and hippocampal sclerosis with or without additional subtle T2-Fluid Attenuated Inversion Recovery (FLAR)/Proton Density (PD) signal changes in anterior temporal lobe who underwent anterior temporal lobectomy with amygdalohippocampectomy. Their clinical, EEG, neuropsychological, radiological and pathological data were reviewed and summarized. ResultsThirty-six eligible patients were identified. The mean age at seizure onset was 3.7 years; 25% had daily seizures at time of surgery. Isolated HS was noted in 22 (61.1%) cases and additional subtle signal changes in ipsilateral temporal lobe in 14 (38.9%) cases. Compared to the normative population, the group mean performance in intellectual functioning and most auditory and visual memory tasks were significantly lower than the normative sample. The mean age at surgery was 12.3 years; 22 patients (61.1%) had left hemispheric surgeries. ILAE class 1 outcomes was seen in 28 (77.8%) patients after a mean follow up duration of 2.3 years. Hippocampal sclerosis was noted pathologically in 32 (88.9%) cases; type 2 (54.5%) was predominant subtype where further classification was possible. Additional pathological abnormalities were seen in 11 cases (30.6%); these had had similar rates of seizure freedom as compared to children with isolated hippocampal sclerosis/gliosis (63.6% vs 84%, p=0.21). Significant reliable changes were observed across auditory and visual memory tasks at an individual level post surgery. ConclusionsFavourable seizure outcomes were seen in most children with isolated radiological hippocampal sclerosis. Patients with additional pathological abnormalities had similar rates of seizure freedom as compared to children with isolated hippocampal sclerosis/gliosis.

Impact of Propofol Exposure on Neurocognitive Outcomes in Children With High-Risk B ALL: A Children's Oncology Group Study.

Many children treated for ALL develop long-term neurocognitive impairments. Increased risk of these impairments is associated with treatment and demographic factors. Exposure to anesthesia is an additional possible risk factor. This study evaluated the impact of cumulative exposure to anesthesia on neurocognitive outcomes among a multicenter cohort of children with ALL. This study was embedded in AALL1131, a Children's Oncology Group phase III trial for patients with high-risk B-ALL. In consenting patients age 6-12 years, prospective uniform assessments of neurocognitive function were performed during and at 1 year after completion of therapy. Exposure to all episodes of anesthetic agents was abstracted. Multivariable linear regression models determined associations of cumulative anesthetic agents with the primary neurocognitive outcome reaction time/processing speed (age-normed) at 1 year off therapy, adjusting for baseline neurocognitive score, age, sex, race/ethnicity, insurance status (as a proxy for socioeconomic status), and leukemia risk group. One hundred and forty-four children, 76 (52.8%) males, mean age of 9.1 (min-max, 6.0-12.0) years at diagnosis, underwent a median of 27 anesthetic episodes (min-max, 1-37). Almost all patients were exposed to propofol (140/144, 97.2%), with a mean cumulative dose of 112.3 mg/kg. One year after therapy, the proportion of children with impairment (Z-score ≤-1.5) was significantly higher compared with a normative sample. In covariate-adjusted multivariable analysis, cumulative exposure to propofol was associated with a 0.05 Z-score decrease in reaction time/processing speed per each 10 mg/kg propofol exposure (P = .03). In a multicenter and uniformly treated cohort of children with B-ALL, cumulative exposure to propofol was an independent risk factor for impairment in reaction time/processing speed 1 year after therapy. Anesthesia exposure is a modifiable risk, and opportunities to minimize propofol use should be considered.

Neurocognitive outcome in children and adolescents following infectious encephalitis

ABSTRACT Infectious encephalitis in children is fairly uncommon, but unfavorable outcomes are seen in many survivors. The aim of this study was to prospectively describe the long-term neurocognitive consequences following infectious encephalitis in childhood. Children admitted to a primary and tertiary hospital in Sweden between 2011 and 2016 were asked to participate. Fifty-nine children were assessed at a median time of 18 months (IQR 18–20) after hospitalization. Follow-up included measures of intellectual functioning, attention, working memory, and executive functions. Caregiver ratings of executive functioning and behavioral – emotional symptoms were assessed with standardized questionnaires. Neurocognitive outcome and measures of executive functions and behavioral–emotional symptoms varied greatly among participants. Basic auditory attention, working memory, and mental processing speed were affected and significantly lower compared to a standardized mean. Other domains identified as areas of vulnerability included executive functions, sustained attention, and the exert of self-control. Behavioral–emotional symptoms were less common; however, somatic complaints and behaviors related to conduct problems were seen in about one-third of individuals. This study highlights the importance of a comprehensive neurocognitive examination to identify children with unfavorable outcomes.

47 Attention and Working Memory (WM) in Pediatric Patients Prior to Hemopoietic Stem Cell Transplant (HSCT) for Hematologic Malignancies

Objective:HSCT is increasingly used for curative therapy for patients with high risk hematologic diseases. Existing research regarding the neurocognitive impact of HSCT on pediatric patients is notably variable. One area of identified risk is attention/working memory (WM) [Perkins et al., 2007]. The current study examines the degree to which difficulties in attention/WM are present prior to HSCT, as assessed using parent-report of working memory and cognitive tests of attention span and working memory.Participants and Methods:Participants were 19 children and adolescents ages 6-17 years (M= 9.63, SD= 3.22) who were enrolled in a prospective longitudinal study monitoring neurocognitive outcomes in children undergoing HSCT. Participants were eligible for this study if they were 2-18 years old at the time of transplant and had a diagnosis that qualified for an allogenic HSCT. Participants were ineligible if they had a pre-HSCT developmental delay, were non-English speaking, and had a prior HSCT or prior CAR T-cell therapy. Participants were 53% female and 95% Caucasian. Diagnoses in the current study sample included acute lymphoblastic leukemia (n=10), acute myeloid leukemia (n=8), and myelodysplastic syndrome (n=1).Measures included were the Working Memory Index score from the Behavior Rating Inventory of Executive Function (BRIEF; Gioia et al., 2000) and the Digit Span subtest from the Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV; Wechsler, 2003) and the Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV; Wechsler, 2008).Results:Mean scores on parent-reported WM scores and cognitive measures of attention/WM fell within normal limits, including the Digit Span Total score (M = 48.42, SD= 6.33), Digit Span Forward score (M = 47.28, SD = 9.9.83), and Digit Span Backward score (M = 48.94, SD = 6.31). However, further analyses suggested that between 11-32% of patients had scores falling at least one standard deviation below the mean on these measures, with more than half of the sample (52.6%) identified with at least one measured weakness in attention and WM. The most commonly identified weakness (33.3% of patients) was Digit Span Forward. Correlations between parent-reported WM issues and cognitive measures of attention and WM were generally strong, with parent report of WM significantly correlated with the Digit Span Total score (r(18)= -0.52, p=.02) and the Digit Span Forward score (r(18) = -0.51, p=.03). No correlations were found between Digit Span Backward and other measures of attention and WM.There were no significant differences in WM scores between patients with ALL and AML. Additional analyses will examine potential contribution of medical factors (e.g., pre-HSCT treatment) to pre-HSCT performance on measures of attention and WM.Conclusions:These results suggest that, prior to undergoing HSCT, pediatric patients present with attention and WM issues. This finding has implications for research related to neurocognitive outcomes in HSCT, indicating the need to obtain pre-HSCT cognitive data in this area in order to fully understand potential change after HSCT. In addition, providers may need to consider adapting communication methods with patients during their transplant stay, given potential attention and WM issues within this population.

Adverse Childhood Experiences (ACEs) and Environmental Exposures on Neurocognitive Outcomes in Children: Empirical Evidence, Potential Mechanisms, and Implications.

The purpose of this article is to examine the current literature regarding the relationship between adverse childhood experiences (ACEs) and environmental exposures. Specifically, the paper will focus on how this relationship between ACEs and physical environmental factors impacts the neurocognitive development of children. With a comprehensive literary search focusing on ACEs, inclusive of socioeconomic status (SES), and environmental toxins common in urban environments, the paper explores how these factors contribute to cognitive outcomes that are associated with the environment and childhood nurturing. The relationship between ACEs and environmental exposures reveals adverse outcomes in children's neurocognitive development. These cognitive outcomes include learning disabilities, lowered IQ, memory and attention problems, and overall poor educational outcomes. Additionally, potential mechanisms of environmental exposures and children's neurocognitive outcomes are explored, referencing data from animal studies and evidence from brain imaging studies. This study further analyzes the current gaps in the literature, such as the lack of data focusing on exposure to environmental toxicants resulting from experiencing ACEs and discusses the research and social policy implications of ACEs and environmental exposure in the neurocognitive development of children.

The Impact of Cumulative Anesthesia Exposure on Neurocognitive Outcomes in Children with High-Risk Precursor B Acute Lymphoblastic Leukemia: A Multicenter Children's Oncology Group Study

Background: Following contemporary therapy, a substantial proportion of children with acute lymphoblastic leukemia (ALL) have long-term neurocognitive impairments of executive function, attention, and memory. Known risk factors for these impairments include treatment with cranial radiation, exposure to intrathecal and systemic methotrexate, acute toxicities during active treatment, as well as younger age, lower socioeconomic status, and female sex. Anesthesia exposure may be an additional risk factor and importantly, one that is potentially modifiable risk factor. We evaluated the impact of cumulative anesthesia exposure on neurocognitive outcomes one-year post treatment in a multicenter cohort of children with ALL. Methods: This study an embedded aim in the Children's Oncology Group AALL1131 trial for patients ages >1 to <31 years of age with high-risk B ALL. In a subgroup of consenting patients aged 6-12 years, receiving care at 73 centers in America, Canada, New Zealand and Australia, prospective uniform assessments of neurocognitive function were performed using a validated computerized battery (Cogstate) and parent-reported executive functioning using the Behavior Rating Inventory of Executive Functioning at baseline (3 months post diagnosis), during treatment, and one year post therapy completion. All neurocognitive scores were converted to age-adjusted z-scores (expected mean=0, standard deviation =1.0), with lower scores reflecting worse performance. Exposure to all anesthetic agents was abstracted retrospectively from medical records from time of study enrollment to one year post therapy for all patients who completed treatment and the neurocognitive assessments at baseline and post therapy. For each anesthetic, data collected included the medications, dose, and route of anesthetic agents, duration of anesthesia, and the indication for anesthesia. Results: 155 children met eligibility and were included in this analysis (n=82 [59%] males, mean age 9.10 years [range 6.0-12.8]). Three patients (1.9%) received cranial radiation. The median number of anesthetic episodes per patient was 27 (range 1-37); the most common indication was lumbar puncture with or without the administration of intrathecal therapy (median 24, range 0-32). Though multiple anesthetic agents were utilized, almost all patients were exposed to propofol (151/155, 97%). The mean cumulative dose of propofol for exposed patients was 109.6 mg/kg. At one year post therapy, the proportion of children with impairment (age-adjusted scores ≥ 1.5 standard deviations below the mean) was significantly higher compared to a standardized population in multiple domains including reaction time, sustained attention, working memory and executive function. In multivariable analysis accounting for baseline neurocognitive score, age, sex, race/ethnicity, socioeconomic status and leukemia risk group, cumulative exposure to propofol was associated with poorer reaction time/processing speed (decrease of 0.05 Z-score per 10 mg/kg propofol exposure, 95th CI 0.003, 0.09; p=0.035) and impaired executive function (decrease of 0.23 Z-score per 10 mg/kg propofol exposure, 95th CI 0.003-0.46; p=0.048). Conclusion: In a multicenter cohort of children treated for high-risk ALL and with variable anesthesia exposure, cumulative anesthesia exposure, as reflected by propofol total dosing (mg/kg) was an independent risk factor for impairments in neurocognitive function measured by both performance based and parent report one year post therapy. Anesthesia exposure is a modifiable risk and opportunities to minimize use, when feasible, in this group of patients should be systematically pursued.

Association between Day-to-Day Pulsatility Index Change and Neurocognitive Outcomes in Pediatric Traumatic Brain Injury.

Traumatic brain injury (TBI) remains a significant cause of morbidity and mortality in children despite advances in prevention and mitigation strategies. Transcranial Doppler (TCD) ultrasound measures cerebral arterial circulation and allows for the calculation of pulsatility indices (PIs), which provides an assessment of cerebral blood flow changes. Yet, the use of PIs in children with TBI is not well understood. In this study, we defined the day-to-day (DTD) PI change of the anterior cerebral circulation and describe its relationship with injury characteristics and neurocognitive outcomes in children with TBI. A prospective observational parent study of 42 children, 2 months to 15 years of age, with mild or moderate-severe TBI who had serial TCDs provided data for this analysis. Both the mean and variation of DTD PI change were evaluated in the context of injury severity, injury sidedness, and neurocognitive outcome. In those with a unilateral injury, a larger mean DTD PI change in both the injured and uninjured side was found in those with a worse Glasgow Outcome Scale-Extended Pediatrics score at discharge. A larger variation in PI was associated with a worse neurocognitive outcome, irrespective of injury severity. Therefore, the mean and variation of DTD PI change may serve as a potential cerebral vascular biomarker of ongoing secondary injury. The use of PI measurements in the monitoring of children with TBI may provide clinicians with new diagnostic and prognostic insights to inform therapeutic interventions and recovery strategies. However, a larger prospective study is needed to confirm these findings and elucidate potential mechanistic links between DTD PI and clinical outcome measures. To our knowledge, this study is the first of its kind to evaluate the use of PI changes in cerebral vasculature in pediatric TBI patients admitted to the hospital.

Neurocognitive functioning in children with sickle cell anemia and history of abnormal transcranial doppler ultrasonography.

Transcranial doppler (TCD) ultrasonography can be used to identify stroke risk in children with sickle cell anemia. Previous studies have reported mixed findings on neurocognitive outcomes in children with elevated TCD. This study examined associations between TCD velocity and neurocognitive outcomes in children and adolescents without prior history of stroke. Participants were selected from the Sickle Cell Clinical Research Intervention Program cohort. The highest recorded mean maximum TCD velocity was selected for analysis, along with participant's most recent data from serial neurocognitive surveillance. A total of 200 children with sickle cell anemia completed neurocognitive testing (109 males, 91 females; mean age 12.7 years [SD=3.56]). Most participants were prescribed hydroxyurea (72%) at the time of neurocognitive testing and nearly 16% had a history of chronic transfusions prior to neurocognitive evaluation. Mean age at time of highest TCD value was 6.6 years (SD=2.5) and 13.5% of screenings were abnormal (≥200cm/s). Mean interval between TCD and most recent neurocognitive evaluation was 6.1 years (±3.5). There were no significant differences in the interval between TCD and neurocognitive testing across normal, conditional, and abnormal groups. Maximum TCD velocity was not significantly associated with neurocognitive outcomes in multivariate models. History of elevated TCD in the absence of overt stroke should not be considered a risk factor for poor neurocognitive outcomes in children and adolescents with sickle cell anemia on modern disease-modifying therapy.

Multidisciplinary early intervention in Down syndrome: a retrospective study.

Scientific community agrees on the importance of early, global multidisciplinary family-based care in the neuropsychological development of children with disabilities, including those with Down Syndrome (DS). This study aim to assess whether a structured, multidisciplinary early intervention carried out at the outpatient service of Stella Maris I.R.C.C.S. can lead to better outcomes in children with DS, in development and cognitive functioning, compared to conventional care provided by the local health centres (ASL). We included in the study 20 children with DS. The experimental group received early treatment (0-36 months), while the control group only underwent cognitive assessments. In order to examine the outcome of long-term cognitive functioning, our study evaluated assessments of the children at 5 years of age, by administering the WPPSI-III scale. In our result we can confirm the typical profile of children with Down Syndrome described in the literature. Comparing the results obtained in both groups, we see that the mean scores obtained by the experimental group, in all three of the quotients examined, are higher than the mean scores obtained by the control group. This study makes it clear that early, structured, multidisciplinary interventions play a fundamental role in modifying neurocognitive outcomes in children with Down Syndrome. The results of this study thus confirm the usefulness of the outpatient service in the early management of individuals with DS, following a multidisciplinary, structured pathway focused on the child and his/her family.

Neurocognitive deficits in survivors of childhood acute myeloid leukemia

BackgroundAlthough treatment of acute myeloid leukemia (AML) contains neurotoxic agents, studies investigating neurocognitive outcomes in children with AML are sparse. We evaluated late cognitive effects in children treated with a high-dose cytarabine based regimen, focusing on general intellectual ability and specific neurocognitive domains.MethodsWe evaluated 12 survivors of childhood AML who were treated between 2006 and 2016 and completed the Wechsler Intelligence Scales. One-sample t-tests were used to compare full-scale intelligence quotient (FSIQ) and primary index scores to norms. The overall effect of index scores and subtests was examined with one-way ANOVA. Univariate analyses and multiple regression models examined demographic and clinical characteristics associated with FSIQ.ResultsParticipants who underwent the Wechsler Intelligence Scale for Children demonstrated impairment on working memory index and participants who underwent the Wechsler Adult Intelligence Scale showed low score in the subtests that reflect working memory, whereas they exhibited no statistical differences versus the population means for FSIQ. There were no significant differences in the overall effect of index scores and subtests. On univariate analysis, FSIQ were related to time since diagnosis and age at assessment, and both were significant predictors of FSIQ on multiple linear regression.ConclusionsSurvivors of childhood AML exhibited impairment of working memory, even if their FSIQ was within the normal range. Difficulties in specific cognitive domains are associated with reduced quality of life. It is important to identify survivors who are at risk and provide tailored interventions.

Abstract 17: Microglial Specific Aryl Hydrocarbon Receptor Activation Via Gut-derived Microbial Indole-metabolites Improves Outcomes After Neonatal-HIE

Introduction: Neonatal Hypoxic Ischemic Encephalopathy (nHIE) is a major cause of mortality and morbidity in infants, occurring in 1.5/1000 live births. Inflammation persists years after injury and detrimentally affects neurocognitive outcomes in children. Recent evidence shows that neuroinflammation and gut injury alters microbial populations in the gut (gut dysbiosis) and reduces the level of bacteria capable of producing beneficial, anti-inflammatory tryptophan (Trp) metabolites. Metabolites are detected by microglia (MG) with the aryl hydrocarbon receptor (AHR). Ligand specific AHR activation can influence MG behavior after CNS injury, potentially modifying recovery. We hypothesize that nHIE leads to chronic gut dysbiosis and reduced microbial-derived Trp metabolites, which exacerbates MG-induced CNS damage. We also hypothesize that Trp-derivatives bind MG AHR to reduce inflammation and improve neurological outcomes in males and females. Methods: We used a modified Rice Vannucci Model on PND9 C57BL/6J mice to investigate the role of MG AHR as a mediator of gut microbiome-brain communication after nHIE and demonstrated direct microbial metabolite modulation of MG using in vitro cell culture assays. Results: We found an increase in AHR and CD45 expression in MG 24hrs after nHIE (p=0.0169 and p=0.0047 respectively, n=5). RT-qPCR of SIM-A9 MG cells showed that pretreatment with indole-acetic-acid (IAA) followed by LPS injury produced significantly more Il10 than cells pretreated with AHR agonist FICZ, suggesting Trp-derivatives activate an anti-inflammatory response (p=0.013, n=8). IAA mildly reduced Il1β , Il6 , and Tnfα after LPS administration. 16S rRNA sequencing, behavior and metabolomics analysis of acute (24hrs) and chronic (7wks) cohorts showed detriments in behavioral tasks and dysbiotic changes after nHIE. Conclusion: nHIE results in increased AHR expression in MG, gut dysbiosis, and alterations in microbial-Trp metabolites in males and females. In vitro assays demonstrated that absence of Trp metabolites result in greater inflammatory activity of MG after injury via the AHR pathway, supporting our hypothesis that reduction of microbial-derived Trp metabolites after nHIE worsens MG-induced CNS damage.

Investigation of possible associations of the BDNF, SNAP-25 and SYN III genes with the neurocognitive measures: BDNF and SNAP-25 genes might be involved in attention domain, SYN III gene in executive function

Objectives Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous disorder and Sluggish Cognitive Tempo (SCT) might be a second inattention disorder that might be even affected by different attention pathways. SCT is characterized by daydreaming, mental confusion, staring blankly and hypoactivity. In the present study, we evaluated 5 common variants (rs6265, rs3746544, rs1051312, rs133946 and rs133945) located in 3 candidate genes (BDNF, SNAP25 and SYN III) that are known to take part in synaptic plasticity and neurotransmitter transmission. Methods We tested the effects of these variants on neuropsychological findings assessed by a computer-based neuropsychological test battery in children with inattention symptoms (SCT and/or ADHD). Results BDNF (rs6265), SNAP25 (rs3746544 and rs1051312) and SYN III (rs133946 and rs133945) polymorphisms were associated with variable cognitive measures. BDNF gene (rs6265) polymorphism Met allele carriers and SNAP25 gene (rs3746544) T allele carriers had an association with the attention domain. SNAP25 gene (rs1051312) C allele carriers were only associated with reaction time scores. Cognitive flexibility, which is one of the key components of executive function evaluation and shifting attention test scores were associated with BDNF (rs6265) Met allele and SYN III (rs133946) gene G allele. SYN III (rs133945) gene C allele carriers had an association with verbal memory correct hit scores. Conclusions As a conclusion, BDNF, SNAP25 and SYN III genes were associated with specific neurocognitive outcomes in children with inattention symptoms. It is important to note that exploring genotyping effects on neurocognitive functions instead of a heterogeneous psychiatric diagnosis can improve our understanding of psychopathologies.

Relationships Between Regional Cerebral Blood Flow and Neurocognitive Outcomes in Children and Adolescents With Congenital Heart Disease

To identify regional cerebral blood flow (rCBF) alterations in children and adolescents with congenital heart disease (CHD) in relation to neurocognitive outcomes using a nonbiased data-driven approach. This is a prospective, observational study of children and adolescents with CHD without brain injury and healthy controls using pseudo-continuous arterial spin labeling (pCASL) MRI. Quantitative rCBF was compared between participants with CHD and healthy controls using a voxelwise data-driven method. Mediation analysis was then performed on a voxelwise basis, with the grouping variable as the independent variable, neurocognitive outcomes (from the NIH Toolbox Cognitive Battery) as the dependent variables, and rCBF as the mediator. After motion correction, a total of 80 studies were analyzable (27 for patients with CHD, 53 for controls). We found steeper age-related decline in rCBF among those with CHD compared to normal controls in the insula/ventromedial prefrontal regions (salience network) and the dorsal anterior cingulate and precuneus/posterior cingulate (default mode network), and posterior parietal/dorsolateral prefrontal (central executive network) (FWE-corrected P< 0.05). The reduced rCBF in the default mode/salience network was found to mediate poorer performance on an index of crystallized cognition from the NIH Toolbox Cognitive Battery in those with CHD compared to controls. In contrast, reduced rCBF in the central executive network/salience network mediated reduced deficits in fluid cognition among patients with CHD compared to controls. Regional cerebral blood flow alterations mediate domain-specific differences in cognitive performance in children and adolescents with CHD compared to healthy controls, independent of injury, and are likely related to brain and cognitive reserve mechanisms. Further research is needed to evaluate the potential of interventions in CHD targeting regional cerebral blood flow across lifespan.

Differential At-Risk Pediatric Outcomes of Parental Sensitivity Based on Hearing Status.

Purpose The aim of this study was to investigate the role of parental sensitivity in language and neurocognitive outcomes in children who are deaf and/or hard of hearing (DHH). Method Sixty-two parent-child dyads of children with normal hearing (NH) and 64 of children who are DHH (3-8 years) completed parent and child measures of inhibitory control/executive functioning and child measures of sentence comprehension and vocabulary. The dyads also participated in a video-recorded, free-play interaction that was coded for parental sensitivity. Results There was no evidence of associations between parental sensitivity and inhibitory control or receptive language in children with NH. In contrast, parental sensitivity was related to children's inhibitory control and all language measures in children who are DHH. Moreover, inhibitory control significantly mediated the association between parental sensitivity and child language on the Clinical Evaluation of Language Fundamentals-Fifth Edition Following Directions subscale (6-8 years)/Clinical Evaluation of Language Fundamentals Preschool-Second Edition Concepts and Following Directions subscale (3-5 years). Follow-up analyses comparing subgroups of children who used hearing aids (n = 29) or cochlear implants (CIs; n = 35) revealed similar correlational trends, with the exception that parental sensitivity showed little relation to inhibitory control in the group of CI users. Conclusions Parental sensitivity is associated with at-risk language outcomes and disturbances in inhibitory control in young children who are DHH. Compared to children with NH, children who are DHH may be more sensitive to parental behaviors and their effects on emerging inhibitory control and spoken language. Specifically, inhibitory control, when scaffolded by positive parental behaviors, may be critically important for robust language development in children who are DHH.

Neuroprotection: further evidence for the early and universal use of hydroxyurea in children with sickle cell disease.

The neuroanatomic and neurophysiological complications of sickle cell disease (SCD) are well described and include overt stroke and silent cerebral infarctions, which disproportionately affect areas of the brain involved in executive functioning and attention.1, 2 However, even individuals with SCD without evidence of neuroanatomical changes on imaging score significantly lower on measures of full-scale intelligence (FSIQ) than community-matched peers.3 These changes begin early, often within the first decade of life, and affect academic achievement and later job attainment.4, 5 Nevertheless, to say that the disease itself is the only contributor to neurocognition would be to oversimply a complex process; other biological and socio-environmental factors, including parental education, household income and family cohesion, also play a major role.6, 7 In this issue, Heitzer et al.,8 expand on the work published last year by Partanen et al.,9 specifically describing the results of a cross-sectional analysis of the neurocognitive function of children and young adults aged 8–25 years with all SCD genotypes, treated with and without hydroxyurea. In those with the higher risk genotypes, HbSS and HbSβ0-thalassemia, patients treated with hydroxyurea achieved higher scores on measures of verbal comprehension, perceptual reasoning and FSIQ. In addition, importantly, the age at starting hydroxyurea was significantly associated with FSIQ, with those starting earlier in childhood having improved neurocognitive performance compared to those who began later or not at all. While it is encouraging that the authors determined a significant difference in neurocognitive functioning between treated and untreated children, the average age at starting hydroxyurea in this study was 8 years for those with the HbSS and HbSβ0-thalassemia genotypes; data from the BABY HUG trial showed that neurocognitive decline begins within the first year of life for children with SCD,10 who score significantly lower on measures of kindergarten readiness than matched peers.11 Even as early as primary school, grade repetition rates as high as 20% are seen, significantly higher than regional and national trends.12, 13 The growing body of literature to demonstrate that hydroxyurea can attenuate the progressive neurocognitive decline seen in children with SCD provides further evidence for its universal prescription for all children with HbSS and HbSβ0-thalassemia within the first year of life, regardless of apparent disease severity.14 It is also important to note that another significant contributor to FSIQ (the largest contributor at 6% to the variance in FSIQ seen in those with the HbSS and HbSβ0-thalassemia genotypes) was the social vulnerability index. This finding supports earlier work showing the critical role that parental education and household income play in neurocognitive outcomes in children with SCD.6 Further, it also highlights how individuals with SCD are disproportionately affected by social determinants of health;15 indeed, over 75% of their cohort fell into the highest overall vulnerability ranking, which is consistent with other published cohorts.13 As the authors state, a major limitation of this work is its cross-sectional nature; the recent encouraging data from these small cross-sectional studies lend support to the need for a long-term, longitudinal assessment of neurocognition in individuals with SCD treated with hydroxyurea from early childhood. Definitive evidence for a neuroprotective effect elicited by hydroxyurea should further convince providers to expand their use of this disease-modifying therapy to all children with the more severe genotypes of SCD.

The Impact of Traumatic Brain Injury on Neurocognitive Outcomes in Children: a Systematic Review and Meta-Analysis

ObjectiveTo assess the burden of paediatric traumatic brain injury (TBI) on neurocognition via a systematic review and meta-analysis.MethodsStudies that compared neurocognitive outcomes of paediatric patients with TBI and controls were...

Spike-Wave Index Assessment and Electro-Clinical Correlation in Patients with Encephalopathy Associated with Epileptic State During Slow Sleep (ESES / CSWS); Single-Center Experience

PurposeThis study aimed to describe the electroclinical spectrum and neurocognitive outcome in children with epileptic encephalopathy with status epilepticus during sleep (ESES) according to the EEG patterns. MethodsRecords of 48 (19 males, 29 females) patients with ESES/CSWS syndrome were retrospectively evaluated for data on sleep and awake EEGs, psychometric tests, and brain MRI. Patients with a spike-wave index (SWI) of at least 50 % in the NREM sleep EEG were included in the study. Electrophysiologic findings were separated into two groups based on SWI: SWI>85-100 % (typical ESES) and SWI < 85 % (atypical ESES). The neurocognitive prognosis was also evaluated in two groups; favorable and unfavorable. ResultsThe median age at the onset of ESES was 6 years and 5 months and ranged from 3 to 13 years. The median duration of follow-up after the ESES diagnosis was 57 months (range 24–150 months). Etiology was evaluated in three groups: symptomatic/structural, idiopathic, and unknown (cryptogenic). Twenty-seven (56.25 %) patients had atypical ESES patterns and 21 patients (43.75 %) had typical ESES patterns. Twenty-eight patients (58.3 %) had cognitive deterioration. Long term neurocognitive outcome was unfavorable in half of the patients. Symptomatic/structural etiology was more common in patients with unfavorable (p < 0.001) outcomes. The median age at the diagnosis of ESES (p < 0.001) was significantly earlier in the patients with unfavorable neurocognitive outcomes. The longer duration of ESES(p < 0.001), and the longer time between the onset of epilepsy and ESES (p = 0.039) was significantly associated with unfavorable outcomes. We found that patients with typical ESES had a higher risk for poor neurocognitive outcomes than patients with atypical ESES (OR: 31.096 [1.565–617.696]). ConclusionThe long-term outcome of ESES is exceedingly variable. An unfavorable neurocognitive outcome seems to be related to ESES with a long-duration and early-onset epileptic activity, SWI ≥ 85 %, and etiology.

Long-Term Neurocognitive Outcomes in Sagittal Synostosis: The Impact of Reoperation.

Optimal age at surgery in nonsyndromic sagittal craniosynostosis continues to be debated. Previous reports suggest that earlier age at whole vault cranioplasty more frequently requires reoperation. It is unknown, however, whether reoperation affects neurocognitive outcome. This study examined the impact of reoperation on neurocognitive outcome in children with nonsyndromic sagittal craniosynostosis using comprehensive neurocognitive testing. Forty-seven school-age children (age 5-16 years) with nonsyndromic sagittal craniosynostosis who underwent whole-vault cranioplasty were included in this analysis. Participants were administered a battery of standardized neuropsychological testing to measure neurocognitive outcomes. Thirteen of the 47 participants underwent reoperation (27.7%); 11 out of the 13 reoperations were minor revisions while 2 reoperations were cranioplasties. Reoperation rate was not statistically different between patients who had earlier surgery (at age ≤6 months) versus later surgery (at age >6 months) (P > 0.05). Nonreoperated patients who had only one later-in-life surgery did not perform statistically better than reoperated patients on any outcome measure of neurocognitive function, including IQ, academic achievement, visuomotor integration, executive function, and behavior. Comparing reoperated earlier surgery patients with nonreoperated later surgery patients, reoperated earlier surgery patients had higher full-scale and verbal IQ (P < 0.05), scored higher on word reading, reading comprehension, spelling, numerical operations, and visuomotor integration (P < 0.05), and had fewer indicators of suspected learning disabilities (P < 0.01) compared to nonreoperated later surgery patients. Reoperation rate after whole vault cranioplasty was 27.7%, with few cases of repeat cranioplasty (4.2% of all patients). Reoperation was not associated with worse neurocognitive outcome. Reoperated earlier surgery patients in fact performed better in IQ, academic achievement and visuomotor integration when compared to nonreoperated later surgery patients.

Early-childhood cytomegalovirus infection and children's neurocognitive development.

Despite a clear association seen in congenitally infected children, the effect of postnatal cytomegalovirus (CMV) infection during early childhood on cognitive development has not yet been determined. CMV-infection status was obtained based on serological measurements when children were 7 years old. Using population-based longitudinal data, we employed multivariate Poisson regression with a robust variance estimator to characterize the relationship between childhood CMV infection and adverse neurocognitive outcomes in children. Suboptimal neurocognitive outcomes were compared between CMV-positive and CMV-negative children using various cognitive assessments from 8 to 15 years of age. Children were evaluated on the cognitive domains of language, reading, memory and general intelligence, with a suboptimal score being >2 standard deviations lower than the mean score. Approximate Bayes factor (ABF) analysis was used to determine the level of evidence for the observed associations. With adjustment for potential confounders, we observed that early-childhood CMV infection was associated with suboptimal total intelligence quotient (IQ) at 8 years of age [incidence-rate ratio (IRR) = 2.50, 95% confidence interval (CI) 1.35-4.62, ABF = 0.08], but not with suboptimal total IQ at 15 years of age (IRR = 0.97, 95% CI 0.43-2.19, ABF = 1.68). Suboptimal attentional control at 8 years (IRR = 1.74, 95% CI 1.13-2.68, ABF = 0.18) and reading comprehension at 9 years (IRR = 1.93, 95% CI 1.12-3.33, ABF = 0.24) were also associated with CMV infection. ABF analysis provided strong evidence for the association between CMV infection and total IQ at 8 years, and only anecdotal evidence for attentional control at 8 years and reading comprehension at 9 years. All other cognitive measures assessed were not associated with CMV infection. In this large-scale prospective cohort, we observed some evidence for adverse neurocognitive effects of postnatal CMV infection on general intelligence during early childhood, although not with lasting effect. If confirmed, these results could support the implementation of preventative measures to combat postnatal CMV infection.

Neurocognitive Outcomes in Children with Brain Tumors.

Brain tumors are the most common solid tumor in childhood, and although survival outcomes continue to improve, survival is frequently offset by devastating late effects from tumor and treatment. The long-term effects of brain tumors and the therapy necessary to treat them range from sensory and neuroendocrine abnormalities to neurocognitive deficits leading to inferior quality of life. The multifactorial neurocognitive injury is one of the most broadly impacting and challenging late effects to predict and subsequently treat. Certain treatment modalities, such as intrathecal methotrexate and radiation, have been shown to be associated with poor neurocognition; however, long-term outcomes remain highly variable. There are efforts underway to investigate how to better predict, identify, and manage such neurocognitive injury in survivors of pediatric brain tumors. Herein, we focus on the current knowledge of neurocognitive outcomes and potential treatment strategies for this high-risk group.