Neurological and Cognitive Performance After Childhood Encephalitis.
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ABSTRACT:
SUBMITTER: Poyhonen H
PROVIDER: S-EPMC8055844 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Neurological soft signs (NSSs), minor neurological abnormalities, have been implicated as risk factors for poor cognitive performance in small-scale studies. Here we investigate the associations between NSSs and multiple domains of cognitive performance in a large, population-based cohort and evaluate sex differences in these associations. We analyzed data from 35,710 seven-year-old children in the Collaborative Perinatal Project to study the association between the number of NSSs and cognitive test scores using multiple linear regression models adjusting for risk factors for brain injury and aberrant neurodevelopment. NSSs were associated with lower scores on all domains of cognitive performance. Each additional soft sign was associated with lower full-scale IQ (b = -4.83, 95% CI [-5.06, -4.60]), performance IQ (b = -4.28, 95% CI [-4.54, -4.02]), and verbal IQ scores (b = -4.53, 95% CI [-4.76, -4.30]), as well as arithmetic (b = -4.06, 95% CI [-4.26, -3.85]), spelling (b = -3.53, 95% CI [-3.75, -3.30]), and reading (b = -4.00, 95% CI [-4.26, -3.75]) scores on the Wide Range Achievement Test (WRAT). Only one sex difference was observed: The association between NSS and the WRAT spelling test was somewhat stronger in girls (b = -4.01, 95% CI [-4.26, -3.36]) than in boys (b = -3.53, 95% CI [-3.75, -3.30]). There is an association between NSSs and poor cognitive performance that is not attributable to established risk factors for brain injury and aberrant neurodevelopment. Further research is needed to investigate the mechanisms underlying this association and to determine if interventions targeting NSS in children might have beneficial effects on neurocognitive development. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
| S-EPMC6202138 | biostudies-literature
Project description:OBJECTIVE:Childhood trauma is common and associated with both worse cognitive performance and disruption to the hypothalamic-pituitary-adrenal axis in younger adults. The extent to which these associations persist into older adulthood remains unknown. The aim of this study was to investigate self-reported childhood trauma in relation to cognitive performance, and the extent to which cortisol explained this association, in 2 independent samples of older adults. METHODS:In this cross-sectional study, participants in the discovery sample (N = 76) consisted of older adults with a DSM-IV diagnosis of generalized anxiety disorder (N = 57) and age-equated psychiatrically healthy comparison subjects (N = 19) who were referred largely through primary care clinics between 2004-2006. The replication sample (N = 48) consisted of older adults with DSM-IV anxiety or depressive disorders recruited between 2012-2013. Participants were administered the Early Trauma Inventory Self-Report-Short Form and a neuropsychological assessment (primary outcome). RESULTS:Across both samples, childhood trauma was significantly associated with worse performance on measures of processing speed, attention, and executive functioning. The effect of trauma exposure was stronger when general, physical, and sexual traumatic events were examined specifically (all P < .05). Childhood trauma was not associated with cortisol levels, and cortisol did not explain the association between trauma and cognitive functioning. CONCLUSIONS:Self-reported traumatic events experienced in childhood are associated with poorer cognitive performance in anxious and depressed older adults. Findings demonstrate a deleterious impact of childhood trauma on brain health in old age.
| S-EPMC6959209 | biostudies-literature
Project description:AimTo investigate the severity of acute phase magnetic resonance imaging (MRI) findings and severity of acute illness as risk factors for disability after recovery from encephalitis.MethodChildren with encephalitis (n = 98; median age 6 years 10 months, interquartile range 3 years-11 years 6 months; 59 males, 39 females) treated in Turku University Hospital during the years 1995 to 2016 were identified in this retrospective cohort study. The acute phase (<2 months of symptom onset) brain MRIs were re-evaluated and classified based on the severity of neuroimaging finding by a neuroradiologist. Neurological outcome at discharge, at short-term (<3 months from discharge) follow-up, and at long-term (>1 year from discharge) follow-up was assessed from medical records using the Glasgow Outcome Scale.ResultsLong-term recovery was poor in 24 of 82 (29%) children with follow-up data. Two children died, eight had severe disability, and 14 had moderate disability. Acute phase MRI was available for re-evaluation from 74 of 82 patients with follow-up data. The increasing severity of MRI findings was associated with need for ventilator therapy and with poor recovery.InterpretationThe risk for poor recovery in paediatric encephalitis is high, and it is associated with the severity of MRI findings.What this paper addsPoor long-term recovery was found in 29% of children with encephalitis. Severe disability measured by Glasgow Outcome Scale was found in 8%. The most severe neuroimaging findings were a risk factor for severe acute illness and poor long-term recovery.
| S-EPMC9545686 | biostudies-literature
Project description:ImportanceInequities in social environments are likely associated with a large portion of racial disparities in childhood cognitive performance. Identification of the specific exposures associated with cognitive development is needed to inform prevention efforts.ObjectiveTo identify modifiable factors associated with childhood cognitive performance.Design, setting, and participantsThis longitudinal pregnancy cohort study included 1503 mother-child dyads who were enrolled in the University of Tennessee Health Science Center-Conditions Affecting Neurodevelopment and Learning in Early Life study between December 1, 2006, and July 31, 2011, and assessed annually until the children were aged 4 to 6 years. The analytic sample comprised 1055 mother-child dyads. A total of 155 prenatal, perinatal, and postnatal exposures were included to evaluate environment-wide associations. Participants comprised a community-based sample of pregnant women who were recruited between 16 weeks and 28 weeks of gestation from 4 hospitals in Shelby County, Tennessee. Women with high-risk pregnancies were excluded. Data were analyzed from June 1, 2018, to April 15, 2019.ExposuresIndividual and neighborhood socioeconomic position, family structure, maternal mental health, nutrition, delivery complications, birth outcomes, and parenting behaviors.Main outcomes and measuresChild's full-scale IQ measured by the Stanford-Binet Intelligence Scales, Fifth Edition, at age 4 to 6 years.ResultsOf 1055 children included in the analytic sample, 532 (50.4%) were female. Among mothers, the mean (SD) age was 26.0 (5.6) years; 676 mothers (64.1%) were Black, and 623 mothers (59.0%) had an educational level of high school or less. Twenty-four factors were retained in the least absolute shrinkage and selection operator regression analysis and full models adjusted for potential confounding. Associations were noted between child cognitive performance and parental education and breastfeeding; for each increase of 1.0 SD in exposure, positive associations were found with cognitive growth fostering from observed parent-child interactions (β = 1.12; 95% CI, 0.24-2.00) and maternal reading ability (β = 1.42; 95% CI, 0.16-2.68), and negative associations were found with parenting stress (β = -1.04; 95% CI, -1.86 to -0.21). A moderate increase in these beneficial exposures was associated with a notable improvement in estimated cognitive test scores using marginal means (0.5% of an SD). Black children experienced fewer beneficial cognitive performance exposures; in a model including all 24 exposures and covariates, no racial disparity was observed in cognitive performance (95% CIs for race included the null).Conclusions and relevanceThe prospective analysis identified multiple beneficial and modifiable cognitive performance exposures that were associated with mean differences in cognitive performance by race. The findings from this observational study may help guide experimental studies focused on reducing racial disparities in childhood cognitive performance.
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Project description:Mutations in either the mitochondrial or nuclear genomes are associated with a diverse group of human disorders characterized by impaired mitochondrial respiration. Within this group, an increasing number of mutations have been identified in nuclear genes involved in mitochondrial RNA biology. The TEFM gene codes for the mitochondrial transcription elongation factor responsible for enhancing the processivity of mitochondrial RNA polymerase, POLRMT. Here, we report for the first time that TEFM variants are associated with mitochondrial respiratory chain deficiency and a wide range of clinical presentations including neonatal lactic acidosis, epileptic encephalopathy, developmental delay, intellectual disability or mitochondrial myopathy with a treatable neuromuscular transmission defect. Mechanistically, we show that muscle samples and primary fibroblasts from the affected individuals have reduced levels of promoter distal mitochondrial RNA transcripts, consistent with decreased processivity of POLRMT when TEFM is dysfunctional. We provide further evidence for the pathogenicity of these variants by investigating mitochondrial transcription and proteomic changes in patient cells and muscle and by studying TEFM activity in an in vitro system. Finally, tefm knock-down in zebrafish embryos resulted in neuromuscular junction abnormalities and abnormal mitochondrial function, strengthening the genotype-phenotype correlation. In conclusion, our study highlights that TEFM regulates mitochondrial transcription elongation in human tissues and its defect results in variable, tissue specific neurological and neuromuscular symptoms.
2022-11-07 | PXD030427 | Pride
Project description:OBJECTIVE:To evaluate the hypothesis that metabolic measures (fasting glucose, insulin, and Homeostatic Model of Assessment for Insulin Resistance [HOMA-IR] levels) are inversely associated with performance on cognitive tasks using data from young (4- to 6-year-old), typically developing, healthy children. STUDY DESIGN:Data were obtained from children participating in the Healthy Start study, a pre-birth cohort in Colorado. HOMA-IR, glucose, and insulin values were centered and scaled using the study sample means and SD. Thus, they are reported in number of SD units from the mean. Fully corrected T scores for inhibitory control (Flanker task), cognitive flexibility (Dimensional Change Card Sort test), and receptive language (Picture Vocabulary test) were obtained via the National Institutes of Health Toolbox cognition battery. RESULTS:Children included in this analysis (n = 137) were 4.6 years old, on average. Per 1-SD unit, fasting glucose (B = -2.0, 95% CI -3.5, -0.5), insulin (B = -1.7, 95% CI -3.0, -0.4), and HOMA-IR values (B = -1.8, 95% CI -3.1, -0.5) were each significantly and inversely associated with inhibitory control (P < .05 for all, respectively). Fasting glucose levels were also inversely associated with cognitive flexibility (B = -2.0, 95% CI -3.7, -0.2, P = .03). CONCLUSIONS:Our data suggest that metabolic health may impact fluid cognitive function in healthy, young children.
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Project description:Altered mental status is a major criterion for a diagnosis of encephalitis to be made with alteration in behavior, a key manifestation of altered mental status. We reviewed all evaluated cases identified by the Australian Childhood Encephalitis study between May 2013 and June 2018, to review the frequency and features of altered behavior (ALB). ALB was reported in >72% of cases of childhood encephalitis in all three major etiologic groups (infectious, immune-mediated, and unknown). The duration of ALB was >7 days in a minority, but significantly more frequent in immune-mediated compared with infectious encephalitis (27 and 10%, respectively, p < 0.01). ALB was most frequently characterized as irritability/agitation (47%), which predominated in children aged <1 year, and among the leading infectious causes in this age group (enterovirus, parechovirus, and bacterial meningoencephalitis). ALB in the form of disorientation/confusion (25%) was most prominent in those aged >1 year and most frequent in immune-mediated encephalitis. Hallucinations, paranoia, and aggression were all infrequent; suicidality/self-harm was not observed. ALB was reported in 20 of 21 cases of anti-N-methyl-d-aspartate receptor (anti-NMDAr), 19% for >7 days, and disorientation/confusion was the most frequent feature. Only one case was reported as presenting with "psychosis" and was diagnosed with anti-NMDAr encephalitis. Clinician-reported ALB is frequent but most often non-specific in childhood encephalitis. A longer duration of ALB is associated with an immune-mediated cause. More specific psychiatric symptoms (hallucinations, paranoia) are very infrequent. ALB is a hallmark of anti-NMDAr encephalitis, but psychosis is uncommon in contrast to the disorder in adults.
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