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BACKGROUND: This retrospective clinical study performed at a single clinical center aimed to identify the prevalence of seizures in individuals with urea cycle disorders (UCDs) with and without hyperammonemic (HA) crises. In addition, we sought to correlate the utility of biochemical markers and electroencephalography (EEG) in detecting subclinical seizures during HA. METHODS: Medical records of individuals with UCDs enrolled in Urea Cycle Disorders Consortium Longitudinal Study (UCDC-LS) (NCT00237315) at Children's National Hospital between 2006 and 2022 were reviewed for evidence of clinical and subclinical seizuress during HA crises, and initial biochemical levels concurrently. RESULTS: Eighty-five individuals with UCD were included in the analyses. Fifty-six of the 85 patients (66%) experienced HA crises, with a total of 163 HA events. Seizures are observed in 13% of HA events. Among all HA events with concomitant EEG, subclinical seizures were identified in 27% of crises of encephalopathy without clinical seizures and 53% of crises with clinical seizures. The odds of seizures increases 2.65 (95% confidence interval [CI], 1.51 to 4.66) times for every 100 µmol/L increase in ammonia and 1.14 (95% CI, 1.04 to 1.25) times for every 100 µmol/L increase in glutamine. CONCLUSIONS: This study highlights the utility of EEG monitoring during crises for patients presenting with clinical seizures or encephalopathy with HA. During HA events, measurement of initial ammonia and glutamine can help determine risk for seizures and guide EEG monitoring decisions.
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OBJECTIVE: To assess cognitive, behavioral, and adaptive functions in children and young adults with hemophilia treated according to contemporary standards of care. STUDY DESIGN: Evolving Treatment of Hemophilia's Impact on Neurodevelopment, Intelligence, and Other Cognitive Functions (eTHINK) is a US-based, prospective, cross-sectional, observational study (September 2018 through October 2019). Males (aged 1-21 years) with hemophilia A or B of any severity, with or without inhibitors, were eligible. Participants underwent neurologic examinations and age-appropriate neuropsychological assessments, including standardized tests/ratings scales of early development, cognition, emotional/behavioral adjustment, and adaptive skills. RESULTS: Five hundred and fifty-one males with hemophilia A (n = 433) or B (n = 101) were enrolled. Performance on cognitive tests was largely comparable with that of age-matched US population norms, although participants in certain age groups (4-5 and 10-21 years) performed worse on measures of attention and processing speed. Furthermore, adolescents and young adults and those with comorbid attention-deficit/hyperactivity disorder (ADHD; n = 64) reported more adaptive and executive function problems in daily life. Incidence of ADHD in adolescents (21%) was higher than expected in the general population. CONCLUSIONS: In general, males with hemophilia demonstrated age-appropriate intellectual, behavioral, and adaptive development. However, specific patient/age groups showed poorer attention performance and concerns for executive and adaptive development. This study established a normative data set for monitoring neurodevelopment in individuals with hemophilia and highlight the importance of screening and intervention for challenges with cognitive and adaptive skills in this population. CLINICAL TRIAL REGISTRATION: Evolving Treatment of Hemophilia's Impact on Neurodevelopment, Intelligence, and Other Cognitive Functions (eTHINK); NCT03660774; https://clinicaltrials.gov/ct2/show/NCT03660774.
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Hemofilia A , Humanos , Hemofilia A/complicaciones , Masculino , Adolescente , Niño , Estudios Transversales , Estudios Prospectivos , Adulto Joven , Preescolar , Lactante , Cognición , Pruebas Neuropsicológicas , Hemofilia B/complicaciones , Trastorno por Déficit de Atención con Hiperactividad , Función Ejecutiva , Adaptación PsicológicaRESUMEN
BACKGROUND: Synthetic oxytocin (sOT) is frequently administered during parturition. Studies have raised concerns that fetal exposure to sOT may be associated with altered brain development and risk of neurodevelopmental disorders. In a large and diverse sample of children with data about intrapartum sOT exposure and subsequent diagnoses of two prevalent neurodevelopmental disorders, i.e., attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), we tested the following hypotheses: (1) Intrapartum sOT exposure is associated with increased odds of child ADHD or ASD; (2) associations differ across sex; (3) associations between intrapartum sOT exposure and ADHD or ASD are accentuated in offspring of mothers with pre-pregnancy obesity. METHODS: The study sample comprised 12,503 participants from 44 cohort sites included in the Environmental Influences on Child Health Outcomes (ECHO) consortium. Mixed-effects logistic regression analyses were used to estimate the association between intrapartum sOT exposure and offspring ADHD or ASD (in separate models). Maternal obesity (pre-pregnancy BMI ≥ 30 kg/m2) and child sex were evaluated for effect modification. RESULTS: Intrapartum sOT exposure was present in 48% of participants. sOT exposure was not associated with increased odds of ASD (adjusted odds ratio [aOR] 0.86; 95% confidence interval [CI], 0.71-1.03) or ADHD (aOR 0.89; 95% CI, 0.76-1.04). Associations did not differ by child sex. Among mothers with pre-pregnancy obesity, sOT exposure was associated with lower odds of offspring ADHD (aOR 0.72; 95% CI, 0.55-0.96). No association was found among mothers without obesity (aOR 0.97; 95% CI, 0.80-1.18). CONCLUSIONS: In a large, diverse sample, we found no evidence of an association between intrapartum exposure to sOT and odds of ADHD or ASD in either male or female offspring. Contrary to our hypothesis, among mothers with pre-pregnancy obesity, sOT exposure was associated with lower odds of child ADHD diagnosis.
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Trastorno por Déficit de Atención con Hiperactividad , Trastorno del Espectro Autista , Índice de Masa Corporal , Oxitocina , Efectos Tardíos de la Exposición Prenatal , Humanos , Femenino , Embarazo , Masculino , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/etiología , Niño , Trastorno del Espectro Autista/epidemiología , Trastorno del Espectro Autista/etiología , Adulto , Obesidad Materna/epidemiología , Preescolar , Estudios de Cohortes , Obesidad/epidemiologíaRESUMEN
OBJECTIVE: High demand for pediatric neuropsychological care has highlighted the time- and resource-intensive nature of traditional comprehensive evaluations. Emerging care models address these constraints by facilitating tiered neuropsychological services provided in various contexts, including multidisciplinary clinics (MDCs). We aim to demonstrate feasibility and acceptability of tiered neuropsychological care in MDCs through examples from a single institution. METHODS: A review of all current MDC practices at a tertiary pediatric care center was conducted to describe clinic workflow, services provided, and triage strategies. Pediatric neuropsychologists (n = 5) and other health care providers (n = 31) completed a survey focused on experience with neuropsychology consultation in MDCs. RESULTS: Neuropsychologists provided care in 11 MDCs, including universal monitoring with consultative interviews and questionnaires, as well as targeted screening. Neuropsychologists (89%) and other health professionals (100%) reported that tiered neuropsychological services improved patient care within MDCs. Other health professionals reported utilizing results from neuropsychology MDC care to inform their clinical approach (48-90%), referrals (58%), and treatment or surveillance decisions (55-71%). CONCLUSION: Tiered neuropsychological care in pediatric MDCs is feasible, and provider experience ratings indicate high acceptability. Practical steps for development of MDCs are provided, including identifying teams, clinic goals and outcomes, operational logistics, and billing.
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Neuropsicología , Pediatría , Humanos , Neuropsicología/normas , Pediatría/normas , Niño , Derivación y Consulta/normas , Guías de Práctica Clínica como Asunto/normas , Grupo de Atención al Paciente/normasRESUMEN
PURPOSE: Individuals with urea cycle disorders (UCDs) may develop recurrent hyperammonemia, episodic encephalopathy, and neurological sequelae which can impact Health-related Quality of Life (HRQoL). To date, there have been no systematic studies of HRQoL in people with UCDs. METHODS: We reviewed HRQoL and clinical data for 190 children and 203 adults enrolled in a multicenter UCD natural history study. Physical and psychosocial HRQoL in people with UCDs were compared to HRQoL in healthy people and people with phenylketonuria (PKU) and diabetes mellitus. We assessed relationships between HRQoL, UCD diagnosis, and disease severity. Finally, we calculated sample sizes required to detect changes in these HRQoL measures. RESULTS: Individuals with UCDs demonstrated worse physical and psychosocial HRQoL than their healthy peers and peers with PKU and diabetes. In children, HRQoL scores did not differ by diagnosis or severity. In adults, individuals with decreased severity had worse psychosocial HRQoL. Finally, we show that a large number of individuals would be required in clinical trials to detect differences in HRQoL in UCDs. CONCLUSION: Individuals with UCDs have worse HRQoL compared to healthy individuals and those with PKU and diabetes. Future work should focus on the impact of liver transplantation and other clinical variables on HRQoL in UCDs.
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Diabetes Mellitus , Hiperamonemia , Trasplante de Hígado , Fenilcetonurias , Trastornos Innatos del Ciclo de la Urea , Niño , Humanos , Adulto , Calidad de Vida , Trastornos Innatos del Ciclo de la Urea/diagnóstico , Hiperamonemia/diagnóstico , Fenilcetonurias/complicaciones , Estudios Multicéntricos como AsuntoRESUMEN
PURPOSE: We evaluate singular and combined effects of prenatal maternal depression and stress on early childhood neurobehavioral outcomes among 536 mother-child pairs. METHODS: First, we used multivariable linear regression to investigate associations of women's Edinburgh Postnatal Depression Scale (EPDS) score and Perceived Stress Scale (PSS) score, separately, with offspring Child Behavior Checklist score. Next, to assess the combined effect of EPDS and PSS, we dichotomized each score at the fourth versus first to third quartiles and created a four-level variable comprising combinations of high and low depression and stress. Across all models, we accounted for household chaos, hubbub, and order scale (CHAOS) score, an indicator of the household environment associated with offspring behavioral outcomes. RESULTS: Each one-unit increment in maternal EPDS and PSS scores corresponded with 0.75 (95% CI: 0.53, 0.96) and 0.72 (95% CI: 0.48, 0.95) units higher offspring total problems T-score, respectively. Children of women with high EPDS and PSS had highest T-scores for total problems. All associations remained materially unchanged after adjustment for CHAOS score. CONCLUSIONS: Prenatal maternal depression and stress is associated with worse neurobehavioral outcomes among offspring, with the most unfavorable outcomes among children whose mothers had high scores for both EPDS and PSS.
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Madres , Estrés Psicológico , Embarazo , Femenino , Preescolar , Humanos , Madres/psicología , Escalas de Valoración PsiquiátricaRESUMEN
OBJECTIVE: Improve data-driven research to inform clinical decision-making with pediatric epilepsy surgery patients by expanding the Pediatric Epilepsy Research Consortium Epilepsy Surgery (PERC-Surgery) Workgroup to include neuropsychological data. This article reports on the process and initial success of this effort and characterizes the cognitive functioning of the largest multi-site pediatric epilepsy surgery cohort in the United States. METHODS: Pediatric neuropsychologists from 18 institutions completed surveys regarding neuropsychological practice and the impact of involvement in the collaborative. Neuropsychological data were entered through an online database. Descriptive analyses examined the survey responses and cognitive functioning of the cohort. Statistical analyses examined which patients were evaluated and if composite scores differed by domain, demographics, measures used, or epilepsy characteristics. RESULTS: Positive impact of participation was evident by attendance, survey responses, and the neuropsychological data entry of 534 presurgical epilepsy patients. This cohort, ages 6 months to 21 years, were majority White and non-Hispanic, and more likely to have private insurance. Mean intelligence quotient (IQ) scores were below to low average, with weaknesses in working memory and processing speed. Full-scale IQ (FSIQ) was lowest for patients with younger age at seizure onset, daily seizures, and magnetic resonance imaging (MRI) abnormalities. SIGNIFICANCE: We established a collaborative network and fundamental infrastructure to address questions outlined by the Epilepsy Research Benchmarks. There is a wide range in the age and IQ of patients considered for pediatric epilepsy surgery, yet it appears that social determinants of health impact access to care. Consistent with other national cohorts, this US cohort has a downward shift in IQ associated with seizure severity.
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Epilepsia , Humanos , Niño , Epilepsia/complicaciones , Convulsiones/complicaciones , Pruebas de Inteligencia , Cognición , Imagen por Resonancia Magnética , Pruebas Neuropsicológicas , Resultado del TratamientoRESUMEN
BACKGROUND: Prenatal exposure to cannabis may influence childhood cognition and behavior, but the epidemiologic evidence is mixed. Even less is known about the potential impact of secondhand exposure to cannabis during early childhood. OBJECTIVE: This study sought to assess whether prenatal and/or postnatal exposure to cannabis was associated with childhood cognition and behavior. STUDY DESIGN: This sub-study included a convenience sample of 81 mother-child pairs from a Colorado-based cohort. Seven common cannabinoids (including delta 9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD)) and their metabolites were measured in maternal urine collected mid-gestation and child urine collected at age 5 years. Prenatal and postnatal exposure to cannabis was dichotomized as exposed (detection of any cannabinoid) and not exposed. Generalized linear models examined the associations between prenatal or postnatal exposure to cannabis with the NIH Toolbox and Child Behavior Checklist T-scores at age 5 years. RESULTS: In this study, 7% (n = 6) of the children had prenatal exposure to cannabis and 12% (n = 10) had postnatal exposure to cannabis, with two children experiencing this exposure at both time points. The most common cannabinoid detected in pregnancy was Δ9-THC, whereas the most common cannabinoid detected in childhood was CBD. Postnatal exposure to cannabis was associated with more aggressive behavior (ß: 3.2; 95% CI: 0.5, 5.9), attention deficit/hyperactivity problems (ß: 8.0; 95% CI: 2.2, 13.7), and oppositional/defiant behaviors (ß: 3.2; 95% CI: 0.2, 6.3), as well as less cognitive flexibility (ß: -15.6; 95% CI: -30.0, -1.2) and weaker receptive language (ß: -9.7; 95% CI: -19.2, -0.3). By contrast, prenatal exposure to cannabis was associated with fewer internalizing behaviors (mean difference: -10.2; 95% CI: -20.3, -0.2) and fewer somatic complaints (mean difference: -5.2, 95% CI: -9.8, -0.6). CONCLUSIONS: Our study suggests that postnatal exposure to cannabis is associated with more behavioral and cognitive problems among 5-year-old children, independent of prenatal and postnatal exposure to tobacco. The potential risks of cannabis use (including smoking and vaping) during pregnancy and around young children should be more widely communicated to parents.
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Cannabidiol , Cannabinoides , Cannabis , Alucinógenos , Efectos Tardíos de la Exposición Prenatal , Femenino , Embarazo , Humanos , Preescolar , Efectos Tardíos de la Exposición Prenatal/epidemiología , Efectos Tardíos de la Exposición Prenatal/psicología , CogniciónRESUMEN
Aims/hypotheses: People with type 1 (T1D) or type 2 diabetes (T2D) who also have diabetes complications can have pronounced cognitive deficits. It remains unknown, however, whether and how multiple diabetes complications co-occur with cognitive dysfunction, particularly in youth-onset diabetes. Methods: Using data from the SEARCH for Diabetes in Youth study cohort, a prospective longitudinal cohort, we examined clustering of complications and their underlying clinical factors with performance on cognitive tests in young adults with youth-onset T1D or T2D. Cognition was assessed via the NIH Toolbox Cognition Battery. The main cognitive variables were age-corrected scores for composite fluid cognition and associated cognitive subdomains. Diabetes complications included retinopathy, microalbuminuria, and peripheral neuropathy (PN). Lipids, systolic blood pressure (SBP), hemoglobin A1c, and other clinical factors were included in the analyses. Clustering was applied separately to each group (T1D=646; T2D=165). A three-cluster(C) solution was identified for each diabetes type. Mean values and frequencies of all factors were compared between resulting clusters. Results: The average age-corrected score for composite fluid cognition differed significantly across clusters for each group (p<0.001). People with T1D and the lowest average fluid cognition scores had the highest frequency of self-reporting at least one episode of hypoglycemia in the year preceding cognitive testing and the highest prevalence of PN. Persons with T2D and the lowest average fluid cognition scores had the highest SBP, the highest central systolic and diastolic blood pressures, and highest prevalence of PN. Conclusions/interpretations: These findings highlight shared (PN) and unique factors (hypoglycemia in T1D; SBP in T2D) that could be targeted to potentially mitigate cognitive issues in young people with youth-onset diabetes.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/psicología , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/psicología , Masculino , Femenino , Adulto Joven , Adolescente , Estudios Longitudinales , Adulto , Estudios Prospectivos , Cognición/fisiología , Complicaciones de la Diabetes/epidemiología , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/etiología , Neuropatías Diabéticas/epidemiología , Neuropatías Diabéticas/etiologíaRESUMEN
Objective: We evaluated the association of household food insecurity (FI) with cognition in youth and young adults with type 1 diabetes (T1D) or type 2 diabetes (T2D). Design: In this cross-sectional study, age-adjusted scores for composite Fluid Cognition, and sub-domain scores for Receptive Language and Inhibitory Control and Attention, were modeled stratified by diabetes-type using linear regression, with FI in the past year as the predictor, controlling for covariates. Tests for processing speed, inhibitory control/attention, working memory, episodic memory, and cognitive flexibility were administered to measure composite Fluid Cognition score. The NIHT-CB Picture Vocabulary Test was used to assess Crystallized Cognition score and rapid identification of congruent versus noncongruent items were used to assess Inhibitory Control and Attention score. Setting: The SEARCH for Diabetes in Youth study, representative of 5 U.S. states. Participants: Included 1574 youth and young adults with T1D or T2D, mean age of 21 years, mean diabetes duration of 11 years, 51% non-Hispanic white, and 47% had higher HbA1c levels (>9% HbA1c). Results: Approximately 18% of the 1,240 participants with T1D and 31% of the 334 with T2D experienced FI. The food-insecure group with T1D had a lower composite Fluid Cognition score (ß= -2.5, 95% confidence interval (CI)= -4.8, -0.1) and a lower Crystallized Cognition score (ß= -3.4, CI= -5.6, -1.3) than food-secure peers. Findings were attenuated to non-significance after adjustment for demographics. Among T2D participants, no associations were observed. In participants with T1D effect modification by glycemic levels were found in the association between FI and composite Fluid Cognition score but adjustment for socioeconomic characteristics attenuated the interaction (p=0.0531). Conclusions: Food-insecure youth and young adults with T1D or T2D did not have different cognition compared to those who were food-secure after adjustment for confounders. Longitudinal research is needed to further understand relations amongst these factors.
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Cognición , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Inseguridad Alimentaria , Humanos , Femenino , Masculino , Adolescente , Estudios Transversales , Diabetes Mellitus Tipo 1/psicología , Diabetes Mellitus Tipo 1/epidemiología , Adulto Joven , Cognición/fisiología , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/psicología , Adulto , Niño , Composición FamiliarRESUMEN
Objective: To capture multidimensional maternal psychosocial stress using responses from the Edinburgh Postnatal Depression Scale (EPDS) and Cohen's Perceived Stress Scale (PSS) administered during pregnancy, and to identify sociodemographic, biological, and health behavioral correlates of the stress domains. Methods: Using data from 1,079 pregnant women, we implemented principal component analysis on EPDS and PSS responses and retained factors based on the Scree plot and Eigenvalues >1. We then used linear regression to identify perinatal correlates of each domain. Results: We identified three stress domains: "Feeling Overwhelmed," "Anhedonia," and "Lack of Control," which accounted for 10.6% of variance in questionnaire responses. In multivariable analyses, household income ≤$70,000 (ß = 0.21 confidence interval [95% CI: 0.05-0.39]), primiparity (0.36 [0.02-0.71]), inadequate (0.21 [0.04-0.39]) or excessive gestational weight gain (0.27 [0.11-0.42]), and Healthy Eating Index (HEI) score ≤57 (0.14 [0.00-0.28]) were associated with Feeling Overwhelmed. Older age (0.02 [0.00-0.03] per 1-year), Hispanic ethnicity (0.19 [0.00-0.38]), and HEI score ≤57 (0.15 [0.02-0.28]) were associated with Anhedonia. Non-Hispanic Black race/ethnicity (0.37 [0.10-0.63]), not having graduated from college (0.16 [-0.02 to 0.35]), having a partner born outside the United States (0.17 [-0.02 to 0.37]), household size of ≥5 persons (0.21 [-0.02 to 0.37]), receiving public assistance (0.18 [-0.02 to 0.37]), and prenatal smoking (0.32 [0.05-0.59]) were associated with Lack of Control. Conclusions: Three domains of maternal psychosocial stress during pregnancy (Feeling Overwhelmed, Anhedonia, and Lack of Control) were differentially related to sociodemographic, biological, and health behavioral characteristics that may be targets for interventions to ameliorate stress in pregnant women. Clinical Trial Registry: : The Healthy Start study is registered as an observational study at clinicaltrials.gov (NCT #002273297).
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OBJECTIVE: Developmental and epileptic encephalopathies (DEE) entail moderate to profound communication and other impairments that are poorly measured by typical clinical outcomes assessments (COA). We examined the potential of alternative approaches, specifically, the use of raw scores and COAs outside of their intended age ranges. METHODS: In a cross-sectional survey, 120 parents of children with Dravet Syndrome, Lennox-Gastaut syndrome, KCNQ2-DEE, KCNB1-DEE, and SCN2A-DEE (ages 1-35â¯years) completed the Adaptive Behavior Assessment System-3 for ages 0-5â¯years, modified checklist for autism (mCHAT), communication and social behavior scales (CSBS), communication matrix (CM), and several parent-reported classifiers of communication. Adaptive Behavior Assessment System communication and social raw scores were the primary and adjunctive outcomes. Floor and ceiling effects, dispersion and convergence with related measures were assessed with appropriate parametric and nonparametric statistical techniques. RESULTS: Median chronological age (CA) was 8.7â¯years (Interquartile range (IQR): 5.3-13.5). Adaptive Behavior Assessment Systemcommunication and social age equivalents were 12.5â¯months (IQR 7.5-28) and 16.5â¯months (IQR 9-31). Most raw scores corresponded to standardized scores indicating performance <3 standard deviations below the general population mean. Adaptive Behavior Assessment System raw scores demonstrated minimal floor and ceiling effects (<1-2.5%). In linear regression models, scores correlated with age under 6â¯years (communication, pâ¯=â¯0.001; social, pâ¯=â¯0.003) but significantly flattened out thereafter. Scores varied substantially by DEE group (both pâ¯<â¯0.001) and decreased with higher convulsive seizure frequency (communication, pâ¯=â¯0.01, social, pâ¯=â¯0.02). There was good convergence with mCHAT, CSBS, and CM scores (all râ¯>â¯0.8). SIGNIFICANCE: Raw scores and out-of-range COAs may provide measures that are sensitive at the very limited levels of functioning typical of profoundly impaired, older patients with DEEs. To ensure that targeted trial outcomes are responsive to meaningful change, development of these approaches will be essential to clinical trial readiness for novel therapies for rare DEEs.
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Encefalopatías , Síndrome de Lennox-Gastaut , Adolescente , Adulto , Niño , Preescolar , Comunicación , Estudios Transversales , Humanos , Lactante , Recién Nacido , Enfermedades Raras , Adulto JovenRESUMEN
OBJECTIVE: To evaluate the feasibility of administering caregiver-report neuropsychological screening measures in pediatric multidisciplinary clinics (MDCs) and investigate predictive utility for cognitive and academic difficulties on follow-up testing. METHOD: The Pediatric Perceived Cognitive Functioning (Peds PCF) and Colorado Learning Difficulties Questionnaire (CLDQ) were administered to caregivers of youth with history of brain tumor (BT), non-central nervous system (CNS) cancer, or Fontan circulation as part of routine neuropsychological consultation in MDCs from 2017 to 2019. We examined cross-sectional differences on screening measures, and relationships between screening and intellectual and academic test performance in a subset who presented for follow-up neuropsychological evaluation. Receiver operating characteristic (ROC) curve analysis was used to identify suggested cut scores on screening measures for predicting who would most benefit from further evaluation. RESULTS: Screening was completed with 192 families. Children with history of non-CNS cancer (n = 29) had fewer parent-reported cognitive and academic concerns compared with either BT (n = 88) or Fontan (n = 75) groups. Peds PCF and CLDQ scores were related to intellectual and academic test performance in the group presenting for neuropsychological evaluation (n = 68). ROC curve analysis identified cut scores across screening measures with maximal sensitivity and specificity for detecting neuropsychological difficulties. CONCLUSIONS: It is feasible to utilize parent rating measures during neuropsychological consultation in pediatric MDCs. The Peds PCF and CLDQ demonstrated sensitivity to intellectual and academic difficulties in children with significant medical histories. Screening may be a helpful tool for pediatric neuropsychologists and other professionals during MDC consultation to inform clinical management.
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Neoplasias Encefálicas , Tamizaje Masivo , Adolescente , Niño , Estudios Transversales , Humanos , Pruebas Neuropsicológicas , Encuestas y CuestionariosRESUMEN
OBJECTIVE: Poor cognition has been observed in children and adolescents with youth-onset type 1 (T1D) and type 2 diabetes (T2D) compared with control subjects without diabetes. Differences in cognition between youth-onset T1D and T2D, however, are not known. Thus, using data from SEARCH for Diabetes in Youth, a multicenter, observational cohort study, we tested the association between diabetes type and cognitive function in adolescents and young adults with T1D (n = 1,095) or T2D (n = 285). RESEARCH DESIGN AND METHODS: Cognition was assessed via the National Institutes of Health Toolbox Cognition Battery, and age-corrected composite Fluid Cognition scores were used as the primary outcome. Confounder-adjusted linear regression models were run. Model 1 included diabetes type and clinical site. Model 2 additionally included sex, race/ethnicity, waist-to-height ratio, diabetes duration, depressive symptoms, glycemic control, any hypoglycemic episode in the past year, parental education, and household income. Model 3 additionally included the Picture Vocabulary score, a measure of receptive language and crystallized cognition. RESULTS: Having T2D was significantly associated with lower fluid cognitive scores before adjustment for confounders (model 1; P < 0.001). This association was attenuated to nonsignificance with the addition of a priori confounders (model 2; P = 0.06) and Picture Vocabulary scores (model 3; P = 0.49). Receptive language, waist-to-height ratio, and depressive symptoms remained significant in the final model (P < 0.01 for all, respectively). CONCLUSIONS: These data suggest that while youth with T2D have worse fluid cognition than youth with T1D, these differences are accounted for by differences in crystallized cognition (receptive language), central adiposity, and mental health. These potentially modifiable factors are also independently associated with fluid cognitive health, regardless of diabetes type. Future studies of cognitive health in people with youth-onset diabetes should focus on investigating these significant factors.
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Diabetes Mellitus Tipo 2 , Adolescente , Niño , Cognición , Estudios de Cohortes , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Humanos , Obesidad , Padres , Adulto JovenRESUMEN
OBJECTIVES: To determine the suitability of the Aberrant Behavior Checklist (ABC)-a common measure used in clinical trials for treatment of challenging behaviors of autism-as an outcome measure for pharmacological and behavioral interventions for young people with Developmental and Epileptic Encephalopathies (DEEs). METHODS: We assessed score profiles on the ABC in a sample of 122 young people with DEEs, including Dravet and Lennox-Gastaut syndromes, and KCNQ2- SCN2A-, and KCNB1-associated disorders. Then we examined its internal structure using item cluster analysis. We used both unrestricted item cluster analysis to determine the number of item clusters that maximize reliability and restricted analyses in which we pre-specified models with 5-, 6-, and 7-clusters, to examine consistency with previous factor analytic studies. We also conducted validity analysis on the various scoring methods with age, sex, and autism spectrum screening measure scores. RESULTS: Unrestricted item cluster analysis suggested that three clusters maximized reliability of ABC scores. These broadly represented other-directed behaviors (i.e., "externalizing"), self-directed behaviors (i.e., "internalizing"), and inappropriate speech. Restricted models separated item clusters for stereotypy from other self-directed problem behaviors, and self-injurious behaviors from the other externalizing behaviors. Validity analysis also supported these structures. Overall, all scores were low, and less than 20% of DEE participants had symptoms severe enough to qualify for most randomized trials of behavioral therapies. SIGNIFICANCE: These results are broadly consistent with the extant ABC scoring algorithms. They suggest a high internal consistency reliability, which may support the use of the ABC in future clinical trials in patients with DEEs who exhibit the behaviors assessed by the ABC. Alternatively, concerns about overall low scores raise cautions about using the ABC as a measure of behavior in unselected populations with DEE.
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Trastorno Autístico , Síndrome de Lennox-Gastaut , Conducta Autodestructiva , Adolescente , Lista de Verificación , Humanos , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVE: SCN2A-associated developmental and epileptic encephalopathies (DEEs) present with seizures, developmental impairments, and often both. We sought to characterize the level and pattern of development in children with SCN2A variants, and to address the sensitivity of the Vineland Adaptive Behavior Scales (VABS) in measuring changes over time in children with SCN2A-DEEs. METHODS: Clinical histories for participants with pathogenic SCN2A variants in the Simons SearchLight project were analyzed for descriptive purposes. VABS scores obtained at study entry and yearly thereafter were analyzed for floor and ceiling effects, change with age, and association with epilepsy through use of regression and longitudinal regression methods. RESULTS: Sixty-four participants (50 with epilepsy, 30 [47%] female, median age 49 months, interquartile range [IQR] 28 to 101) were included. Histories of birth complications (N = 34, 54%), neonatal neurological signs (N = 45, 74%), and other neurological symptoms (N = 31, 48%) were common and similar in epilepsy and nonepilepsy subgroups. Mean standardized VABS scores (Composite 53.5; Motor, 55.8, Communication, 54.1, Socialization, 59.4, and Daily living skills, 55.1) reflected performance ~3 standard deviations below the normative test average. In longitudinal regression analyses, standardized scores decreased between 1.3 and 2.8 points per year, suggesting regression of abilities. Raw score analyses, however, revealed several subdomains with substantial floor effects (eg, community use); other raw scores increased with increasing age. Participants with epilepsy scored 0.6 to 1 SD lower than those without epilepsy (all P's < .05). SIGNIFICANCE: The VABS, as standardly administered, has shortcomings for addressing growth or regression in individuals with SCN2A-DEEs. Some subdomain raw scores reflected substantial floor effects. Raw scores increased so slowly over time that standardized scores declined. Alternative measures sensitive to incremental meaningful change are required if outcomes such as adaptive behavior are to be primary outcomes in short-term clinical trials.
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Adaptación Psicológica , Encefalopatías/fisiopatología , Síndromes Epilépticos/fisiopatología , Canal de Sodio Activado por Voltaje NAV1.2/genética , Trastornos del Neurodesarrollo/fisiopatología , Adolescente , Encefalopatías/genética , Niño , Preescolar , Ensayos Clínicos como Asunto , Comunicación , Síndromes Epilépticos/genética , Femenino , Humanos , Lactante , Desarrollo del Lenguaje , Masculino , Destreza Motora , Trastornos del Neurodesarrollo/genética , Adulto JovenRESUMEN
RATIONALE: Developmental epilepsies and encephalopathies (DEEs) are characterized by many severe developmental impairments, which are not well-described. A functional framework could facilitate understanding of their nature and severity and guide the selection instruments to measure improvements in therapeutic trials. METHODS: An online survey administered through several parent-organized foundations utilized accepted functional classifications and questionnaires derived from common instruments to determine levels of mobility, fine motor, communication, and feeding functions. Statistical analyses focused on overall levels of function and across-group comparisons adjusted for age. RESULTS: From 6/2018 to 2/2020, 252 parents provided information for one or more functional domains. Median age was 7.2â¯years (interquartile range (IQR): 3.9 to 11.8), and 128 (51%) were females. DEE groups were Dravet syndrome (Nâ¯=â¯72), KCNQ2-DEE (Nâ¯=â¯80), KCNB1-DEE, (Nâ¯=â¯33), Lennox-Gastaut syndrome (LGS; Nâ¯=â¯26), electrographic status epilepticus in sleep (ESES; Nâ¯=â¯15), and others (Nâ¯=â¯26). Overall, functional hand grasp was absent in 48 (20%). Of children ≥2â¯years old, 60/214 (28%) could not walk independently, 85 (40%) were dependent on someone else for feeding, and 153 (73%) did not effectively communicate with unfamiliar people. Impairments entailing absence or near absence of independent function (profound impairment) were observed in 0, 1, 2, 3, and 4 domains for 58 (25%), 78 (34%), 40 (17%), 33 (14%), and 22 (10%) children, respectively. After adjustment for age, impairment levels varied substantially across DEE group for mobility (pâ¯<â¯0.0001), feeding (pâ¯<â¯0.0001), communication (pâ¯<â¯0.0001), hand grasp (pâ¯<â¯0.0001), and number of profoundly impaired domains (pâ¯<â¯0.0001). Three or four profoundly affected domains were reported in 44% of KCNQ2-DEE participants, followed by LGS (29%), KCNB1-DEE (27%), ESES (7%), and Dravet syndrome (6%). CONCLUSIONS: Many children with DEEs experience severe functional impairments, and few children have typical function. As precision therapies will emphasize nonseizures consequences of DEEs, understanding the nature of abilities and impairments will be critical to selecting appropriate outcome measures in therapeutic trials.
Asunto(s)
Discapacidades del Desarrollo/genética , Epilepsias Mioclónicas/genética , Canal de Potasio KCNQ2/genética , Síndrome de Lennox-Gastaut/genética , Canales de Potasio Shab/genética , Estado Epiléptico/genética , Adolescente , Niño , Preescolar , Estudios Transversales , Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/fisiopatología , Electroencefalografía/métodos , Epilepsias Mioclónicas/diagnóstico , Epilepsias Mioclónicas/fisiopatología , Femenino , Humanos , Lactante , Síndrome de Lennox-Gastaut/diagnóstico , Síndrome de Lennox-Gastaut/fisiopatología , Masculino , Sueño/fisiología , Estado Epiléptico/diagnóstico , Estado Epiléptico/fisiopatología , Encuestas y CuestionariosRESUMEN
OBJECTIVE: The impact of in utero exposure to maternal overweight and obesity on offspring metabolic health is well documented. Neurodevelopmental outcomes among these children are, however, less well studied. To address this gap, the current study investigated brain function among 4- to 6-year-old children exposed to maternal overweight or obesity during gestation compared with that of children born to mothers with healthy BMI in pregnancy. METHODS: Resting-state functional magnetic resonance imaging was used to study neuronal activity and connectivity during a passive viewing task (movie) among 101 typically developing children enrolled in the Healthy Start study, a longitudinal prebirth cohort in Colorado. RESULTS: Forty-nine children (48%) were exposed to maternal overweight or obesity in utero (mean age = 5 years, SD = 0.9). Children born to mothers with overweight or obesity demonstrated hyperactivity in the left posterior cingulate cortex and hypoactivity in the dorsal anterior cingulate and the supplementary motor area (P < 0.05 for all). Children born to mothers with overweight or obesity also showed ubiquitously weaker brain connectivity (P < 0.05 for all). CONCLUSIONS: These novel results suggest altered brain function among children exposed to maternal overweight and obesity in utero.
Asunto(s)
Encéfalo/patología , Ganancia de Peso Gestacional/genética , Imagen por Resonancia Magnética/métodos , Obesidad/complicaciones , Sobrepeso/complicaciones , Adulto , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Masculino , Herencia Materna , EmbarazoRESUMEN
OBJECTIVE: To explore the associations between prenatal exposure to tobacco and neurocognitive development, in the absence of prematurity or low birth weight. STUDY DESIGN: We followed mother-child pairs within Healthy Start through 6 years of age. Children were born at ≥37 weeks of gestation with a birth weight of ≥2500 g. Parents completed the Third Edition Ages and Stages Questionnaire (n = 246) and children completed a subset of the National Institutes of Health Toolbox Cognition Battery (n = 200). The Ages and Stages Questionnaire domains were dichotomized as fail/monitor and pass. Maternal urinary cotinine was measured at approximately 27 weeks of gestation. Separate logistic regression models estimated associations between prenatal exposure to tobacco (cotinine below vs above the limit of detection) and the Ages and Stages Questionnaire domains. Separate linear regression models estimated associations between prenatal exposure to tobacco and fully corrected T-scores for inhibitory control, cognitive flexibility, and receptive language, as assessed by the National Institutes of Health Toolbox. A priori covariates included sex, maternal age, maternal education, daily caloric intake during pregnancy, race/ethnicity, household income, maternal psychiatric disorders, and, in secondary models, postnatal exposure to tobacco. RESULTS: Compared with unexposed offspring, exposed offspring were more likely to receive a fail/monitor score for fine motor skills (OR, 3.9; 95% CI, 1.5-10.3) and decreased inhibitory control (B: -3.0; 95% CI, -6.1 to -0.7). After adjusting for postnatal exposure, only the association with fine motor skills persisted. CONCLUSIONS: Prenatal and postnatal exposures to tobacco may influence neurocognitive development, in the absence of preterm delivery or low birth weight. Increased developmental screening may be warranted for exposed children.