Dysmature superficial white matter microstructure in developmental focal epilepsy

Benign epilepsy with centrotemporal spikes is a common childhood epilepsy syndrome that predominantly affects boys, characterized by self-limited focal seizures arising from the perirolandic cortex and fine motor abnormalities. Concurrent with the age-specific presentation of this syndrome, the brain undergoes a developmentally choreographed sequence of white matter microstructural changes, including maturation of association u-fibres abutting the cortex. These short fibres mediate local cortico-cortical communication and provide an age-sensitive structural substrate that could support a focal disease process. To test this hypothesis, we evaluated the microstructural properties of superficial white matter in regions corresponding to u-fibres underlying the perirolandic seizure onset zone in children with this epilepsy syndrome compared with healthy controls. To verify the spatial specificity of these features, we characterized global superficial and deep white matter properties. We further evaluated the characteristics of the perirolandic white matter in relation to performance on a fine motor task, gender and abnormalities observed on EEG. Children with benign epilepsy with centrotemporal spikes (n = 20) and healthy controls (n = 14) underwent multimodal testing with high-resolution MRI including diffusion tensor imaging sequences, sleep EEG recordings and fine motor assessment. We compared white matter microstructural characteristics (axial, radial and mean diffusivity, and fractional anisotropy) between groups in each region. We found distinct abnormalities corresponding to the perirolandic u-fibre region, with increased axial, radial and mean diffusivity and fractional anisotropy values in children with epilepsy (P = 0.039, P = 0.035, P = 0.042 and P = 0.017, respectively). Increased fractional anisotropy in this region, consistent with decreased integrity of crossing sensorimotor u-fibres, correlated with inferior fine motor performance (P = 0.029). There were gender-specific differences in white matter microstructure in the perirolandic region; males and females with epilepsy and healthy males had higher diffusion and fractional anisotropy values than healthy females (P ≤ 0.035 for all measures), suggesting that typical patterns of white matter development disproportionately predispose boys to this developmental epilepsy syndrome. Perirolandic white matter microstructure showed no relationship to epilepsy duration, duration seizure free, or epileptiform burden. There were no group differences in diffusivity or fractional anisotropy in superficial white matter outside of the perirolandic region. Children with epilepsy had increased radial diffusivity (P = 0.022) and decreased fractional anisotropy (P = 0.027) in deep white matter, consistent with a global delay in white matter maturation. These data provide evidence that atypical maturation of white matter microstructure is a basic feature in benign epilepsy with centrotemporal spikes and may contribute to the epilepsy, male predisposition and clinical comorbidities observed in this disorder.K23 NS092923 - NINDS NIH HHSPublished versio

Reduced Hippocampal Volumes in Children with History of Hypoxic Ischemic Encephalopathy after Therapeutic Hypothermia

Hypoxic ischemic encephalopathy (HIE) remains a significant cause of disability despite treatment with therapeutic hypothermia (TH). Many survive with more subtle deficits that affect daily functioning and school performance. We have previously shown an early indication of hippocampal changes in infants with HIE despite TH. The aim of this study was to evaluate the hippocampal volume via MRI and memory function at 5 years of age. A cohort of children followed from birth returned for a 5-year follow-up (n = 10 HIE treated with TH, n = 8 healthy controls). The children underwent brain MRI and neurodevelopmental testing to assess their brain volume, general development, and memory function. Children with HIE had smaller hippocampal volumes than the controls despite no differences in the total brain volume (p = 0.02). Children with HIE generally scored within the average range on developmental testing. Though there was no difference in the memory scores between these groups, there was a positive within-group correlation between the hippocampal volume and memory scores in children with HIE (sentence recall r = 0.66, p = 0.038). There was no relationship between newborn memory function and 5-year hippocampal size. Children with HIE treated with TH experienced significant and lasting changes to the hippocampus despite improvements in survival and severe disability. Future studies should target diminishing injury to the hippocampus to improve overall outcomes

Neurobehavioral outcomes of neonatal asymptomatic congenital cytomegalovirus infection at 12-months

Abstract Background Congenital cytomegalovirus (cCMV) is the most common congenital viral infection in the United States. Symptomatic infections can cause severe hearing loss and neurological disability, although ~ 90% of cCMV infections are asymptomatic at birth. Despite its prevalence, the long-term neurobehavioral risks of asymptomatic cCMV infections are not fully understood. The objective of this work was to evaluate for potential long-term neurobehavioral sequelae in infants with asymptomatic cCMV. Methods Infants with cCMV were identified from a universal newborn cCMV screening study in a metropolitan area in the midwestern United States. Asymptomatic infants with cCMV were enrolled in a longitudinal neurodevelopmental study (N = 29). Age- and sex-matched healthy control infants (N = 193) were identified from the Baby Connectome Project (BCP), a longitudinal study of brain and behavioral development. The BCP sample supplemented an additional group of healthy control infants (N = 30), recruited from the same participant registry as the BCP specifically for comparison with infants with asymptomatic cCMV. Neurobehavioral assessments and parent questionnaires, including the Mullen Scales of Early Learning, the Repetitive Behavior Scales for Early Childhood (RBS-EC), and the Infant Toddler Social Emotional Assessment (ITSEA) were administered at 12 months of age. Neurobehavioral scores were compared between infants with asymptomatic cCMV and all identified healthy control infants. Results Infants with asymptomatic cCMV performed equivalently compared to healthy control infants on the neurobehavioral measures tested at 12 months of age. Conclusions These results indicate that at 12 months of age, infants with asymptomatic cCMV are not statistically different from controls in a number of neurobehavioral domains. Although follow-up is ongoing, these observations provide reassurance about neurobehavioral outcomes for infants with asymptomatic cCMV and inform the ongoing discussion around universal screening. Additional follow-up will be necessary to understand the longer-term outcomes of these children

Additional file 1 of Neurobehavioral outcomes of neonatal asymptomatic congenital cytomegalovirus infection at 12-months

Additional file 1: Figure S1. On a sensitivity analysis excluding infants (N = 6) with mild symptoms, consistent with the full analyses, asymptomatic cCMV infants again performed equivalently or better on all measures. Of the participants excluded in this analysis, one was the only asymptomatic cCMV infant who fell “Below Average” on the Mullen composite score, and another had the highest (> 30) RBS-EC composite endorsed scale

The global dietary database 2017: data availability and gaps on 54 major foods, beverages and nutrients among 5.6 million children and adults from 1,220 surveys worldwide

Background We aimed to systematically identify, standardise and disseminate individual-level dietary intake surveys from up to 207 countries for 54 foods, beverages and nutrients, including subnational intakes by age, sex, education and urban/rural residence, from 1980 to 2015. Methods Between 2008–2011 and 2014–2020, the Global Dietary Database (GDD) project systematically searched for surveys assessing individual-level intake worldwide. We prioritised nationally or subnationally representative surveys using 24-hour recalls, Food-Frequency Questionnaires or short standardised questionnaires. Data were retrieved from websites or corresponding members as individual-level food group microdata or aggregate stratum-level data. Standardisation included quality assessment; data cleaning; categorising of foods and nutrients and their units; aggregation by demographic strata and energy adjustment. Results We standardised and incorporated 1220 surveys into the final GDD 2017 database, together represented 188 countries and 99.0% of the world’s population in 2015. 72.1% were nationally, 17.0% subnationally, and 10.9% community-level representative. 41.2% used Food-Frequency Questionnaires; 23.4%, 24-hour recalls; 15.8%, Demographic Health Survey questionnaires; 13.1%, biomarkers and 6.4%, household surveys. 73.9% of surveys included data on children; 52.2%, by urban and rural residence; and 30.2%, by education. Most surveys were in high-income countries, followed by sub-Saharan Africa and Asia. Most commonly ascertained foods were fruits (N=803 surveys), non-starchy vegetables (N=787) and sugar-sweetened beverages (N=440); and nutrients, sodium (N=343), energy (N=256), calcium (N=224) and fibre (N=200). Least available data were on iodine, vitamin A, plant protein, selenium, added sugar and animal protein. Conclusions This systematic search, retrieval and standardised effort provides the most comprehensive empirical evidence on dietary intakes across and within countries worldwide