Evaluation of the Neurodevelopmental Outcome of Toddlers with Spinal Dysraphism after Surgical Repair Using ASQ-3™ Scores

Background: Spinal dysraphism represents a wide spectrum of congenital abnormalities of the spine. Myelomeningocele is considered the most common malformation and the most common we saw in our community, with its morbidity problems seen commonly in the postoperative period. ASQ-3TM Scores are the ages and stages questionnaire, third edition, and represent a tool to assess the development progress, especially in toddlers. Objectives: Evaluation of neurodevelopmental outcome among Sudanese toddlers with spinal dysraphism after surgical closure with or without a VP shunt using ASQ-3TM Scores. Methodology: This is a retrospective hospital-based study of 84 patients who underwent myelomeningocele repair at the National Center for Neurological Sciences (NCNS) during the period from 2017 up to 2019. Data were collected through a constructed questionnaire, including ASQ-3TM Scores. Data were processed and analyzed using the Statistical Package for Social Science (SPSS) computer program. Version 25. Results: 84 patients were included in this study;all patients were diagnosed with spinal dysraphism. Out of them, 51 (60.7%) were 2 years old, 33 (39.3%) were 3 years old, 45 (53.6%) were male, 45 (53.6%) of patients mothers attended ANC irregularly, and 54 (64.3%) their mothers didn’t receive folate supplements. 44 (52.3%) of patients underwent MMC repair only, while 40 (47.7%) underwent MMC repair and VP shunt. The commonest postoperative complication was infection, reported in 12 (14.3%) of patients, followed by VP shunt revision in 9 (10.7%) of patients. Neurological assessment showed that the majority of patients need further assessment with a professional, 57 (67.9%) of children don’t walk, run, or climb like other toddlers as their parent’s state;also, half of patients (42, 50%) had medical problems, and 27 (32.1%) of their parent’s state that they do not talk like other toddlers their age. There was a statistically significant association between post-operative complications and communication development, problem-solving development, and personal social development (P value = 0.05), and a statistically significant association was found between age at repair and neurological development (P value = 0.05). Conclusion: The majority of patients had motor deficiency (particularly gross motor) and poor personal and social skills. Age at repair and postoperative complications significantly influenced the neurological development.

Connecting neurodevelopment to neurodegeneration:a spotlight on the role of kinesin superfamily protein 2A(KIF2A)

Microtubules play a central role in cytoskeletal changes during neuronal development and maintenance.Microtubule dynamics is essential to polarity and shape transitions underlying neural cell division,differentiation,motility,and maturation.Kinesin superfamily protein 2A is a member of human kinesin 13 gene family of proteins that depolymerize and destabilize microtubules.In dividing cells,kinesin superfamily protein 2A is involved in mitotic progression,spindle assembly,and chromosome segregation.In postmitotic neurons,it is required for axon/dendrite specification and extension,neuronal migration,connectivity,and survival.Humans with kinesin superfamily protein 2A mutations suffer from a variety of malformations of cortical development,epilepsy,autism spectrum disorder,and neurodegeneration.In this review,we discuss how kinesin superfamily protein 2A regulates neuronal development and function,and how its deregulation causes neurodevelopmental and neurological disorders.

Function and dysfunction of GEMIN5:understanding a novel neurodevelopmental disorder

The recent identification of a neurodevelopmental disorder with cerebellar atrophy and motor dysfunction(NEDCAM)has resulted in an increased interest in GEMIN5,a multifunction RNA-binding protein.As the largest member of the survival motor neuron complex,GEMIN5 plays a key role in the biogenesis of small nuclear ribonucleoproteins while also exhibiting translational regulatory functions as an independent protein.Although many questions remain regarding both the pathogenesis and pathophysiology of this new disorder,considerable progress has been made in the brief time since its discovery.In this review,we examine GEMIN5 within the context of NEDCAM,focusing on the structure,function,and expression of the protein specifically in regard to the disorder itself.Additionally,we explore the current animal models of NEDCAM,as well as potential molecular pathways for treatment and future directions of study.This review provides a comprehensive overview of recent advances in our understanding of this unique member of the survival motor neuron complex.

Perinatal Morbidity, Mortality, and Neurodevelopmental Outcomes of Neonates with Fetal Growth Restriction

Objective: This study aimed to assess perinatal morbidity, mortality rates, and neurodevelopmental outcomes in the management of fetal growth restriction (FGR) at a single tertiary institute. Methods: Among 2465 deliveries between 2013 and 2019, 109 cases of FGR were reviewed retrospectively for causes, indications for pregnancy termination, perinatal death, overall neonatal outcomes, and long-term prognosis. Results: Excluding FGR due to congenital anomalies (n = 17), the mortality rate was 3.3% (3/92). One neonate delivered at 23 weeks developed cerebral palsy (1.1%). Retinopathy of prematurity occurred in four neonates (4.3%). Neurodevelopmental disorders were present in six neonates (6.5%), all of whom were delivered at 32 - 38 weeks. Significantly lower gestational age at delivery, lower birth weight, and higher umbilical artery resistance indices were observed in neonates with neurodevelopmental disorders. Conclusions: Intact survival before 27 weeks of gestation at delivery with FGR is uncommon. Neurodevelopmental disorders may still develop after delivery at 32 - 38 weeks;consideration should be given to the timing of delivery usingfetal ductus venosus Doppler waveforms measurements to reduce neurodevelopmental disorders.

Ion channels in neurodevelopment:lessons from the Integrin-KCNB1 channel complex

Ion channels modulate cellular excitability by regulating ionic fluxes across biological membranes.Pathogenic mutations in ion channel genes give rise to epileptic disorders that are among the most frequent neurological diseases affecting millions of individuals worldwide.Epilepsies are trigge red by an imbalance between excitatory and inhibitory conductances.However,pathogenic mutations in the same allele can give rise to loss-of-function and/or gain-of-function va riants,all able to trigger epilepsy.Furthermore,certain alleles are associated with brain malformations even in the absence of a clear electrical phenotype.This body of evidence argues that the underlying epileptogenic mechanisms of ion channels are more diverse than originally thought.Studies focusing on ion channels in prenatal cortical development have shed light on this apparent paradox.The picture that emerges is that ion channels play crucial roles in landmark neurodevelopmental processes,including neuronal migration,neurite outgrowth,and synapse formation.Thus,pathogenic channel mutants can not only cause epileptic disorders by alte ring excitability,but further,by inducing morphological and synaptic abnormalities that are initiated during neocortex formation and may persist into the adult brain.

Association of maternal hypertensive disorders in pregnancy with infant neurodevelopment

Inconsistent findings have been reported regarding the associations between hypertensive disorders in pregnancy (HDP) and infant neurodevelopment. Leveraging data from the Jiangsu Birth Cohort, in the present study, we re-visited such associations in one-year-old infants from 2 576 singleton pregnancies and 261 twin pregnancies. We first assessed infant neurodevelopment by the Bayley Scales of Infant and Toddler Development Screening Test (the Third Edition), and then estimated its association with maternal HDP using general linear regression models and Poisson regression models. In singleton pregnancies, compared with mothers unexposed to HDP, infants born to mothers with chronic hypertension exhibited a lower score (β, −0.67;95% confidence interval [CI], −1.19-−0.15) and a higher risk of "non-optimal" gross motor development (risk ratio [RR], 2.21;95% CI, 1.02-4.79);in twin pregnancies, infants born to mothers with HDP exhibited lower scores in cognition (β, −0.49;95% CI, −0.96-−0.01), receptive communication (β, −0.55;95% CI, −1.03-−0.06), and gross motor (β, −0.44;95% CI, −0.86-−0.03), and at a higher risk of "non-optimal" gross motor development (RR, 2.12;95% CI, 1.16-3.88). These findings indicate that infants born to mothers with HDP may have inferior neurodevelopment outcomes at the age of one year.

Network biology:A promising approach for drug target identification against neurodevelopmental disorders

Biological entities are involved in complicated and complex connections;hence,discovering biological information using network biology ideas is critical.In the past few years,network biology has emerged as an integrative and systems-level approach for understanding and interpreting these complex interactions.Biological network analysis is one method for reducing enormous data sets to clinically useful knowledge for disease diagnosis,prognosis,and treatment.The network of biological entities can help us predict drug targets for several diseases.The drug targets identified through the systems biology approach help in targeting the essential biological pathways that contribute to the progression and development of the disease.The novel strategical approach of system biologyassisted pharmacology coupled with computer-aided drug discovery(CADD)can help drugs fight multifactorial diseases efficiently.In the present review,we have summarized the role and application of network biology for not only unfolding the mechanism of complex neurodevelopmental disorders but also identifying important drug targets for diseases like ADHD,Autism,Epilepsy,and Intellectual Disability.Systems biology has emerged as a promising approach to identifying drug targets and aiming for targeted drug discovery for the precise treatment of neurodevelopmental disorders.

Child Neurodevelopment on Mars

This review article aims to gather differences and similarities between planet Mars and planet Earth to determine the necessities for the proper growth and development of the neonatal brain. Factors such as Environmental, Nutritional, Social, Stress, and Education are juxtaposed to understand the difference between pediatric neurodevelopment on both planets. The variation between each factor was analyzed to determine how significant the impact is on neurodevelopment for children. The factors to be discussed were generated based on extensive research on what is most important for proper early neurodevelopment. The five factors are the main categories branched out into subcategories to delve into more detail regarding neurodevelopment. Factors may vary based on the location on each planet, but the best average was cultivated to create a fair evaluation of the differences. Although each factor influences a different part of the brain, each factor (Environmental, Nutritional, Social, Stress, and Education) is equally vital for development anatomy and physiology of the brain.

Neurodevelopmental Outcomes of Extremely Premature Infants with Extremely Low and Very Low Birth Weight at Three Years of Age: A Retrospective Study

Introduction: The purpose of this retrospective study is to identify medical conditions impacting neurodevelopmental outcomes of extremely low birth weight and very low birth weight preterm infants at three years of age. Methods: Infants born in Banner Diamond Children’s University Medical Center, receiving services in the Newborn Intensive Care Unit, and attending Neonatal Developmental Follow-Up Clinic were identified. Participants received developmental assessment and follow-up from August 2012 through December 2018. Relevant clinical conditions during initial hospital stay and up to three years of age were obtained by reviewing medical and developmental records. Bayley Scales of Infant Toddler Development (Bayley III) was used to evaluate skill development at 6, 9, 12, 18, 24, 30, 36 months. Results: Data analysis did not reveal significant p-values;it did demonstrate that some predictor variables impact neurodevelopmental outcomes in cognitive, language and motor skill development. Conclusion: This retrospective study reports significant association between birth weight and low cognitive scores. Correlations were also found between gestational age and Total Language, and the longer an infant stayed in the NICU, the poorer the Total Language Scaled Scores at 8 to 12 months, 15 to 18 months, and 24 to 36 months. Birth weight was found to be the greatest predictor of poor motor scores.

Neural stem cell replacement: a possible therapy for neurodevelopmental disorders?

Neurodevelopmental disorders are characterized by an abnormal development of the central nervous system, leading to a myriad of symptoms and diseases, including intellectual disability, attention deficits, impairments in learning and memory, speech disorders and repetitive behavior （Telias and Ben-Yosef, 2014）. Common major neurodevelopmental disorders include autism and autism spectrum disorders （ASDs）, fragile X syndrome （FXS）, Down syndrome （DS）, and Rett syndrome （RTT）. They can be collectively described as disorders in which the plasticity of the brain has been severely impaired. The concept of plasticity refers to the brain＇s ability to adapt to and process new information and react accordingly, and it can be classified into three categories： a） molecular plasticity, whenever specific receptors, ion channels, enzymes,

VEGF in the nervous system: an important target for research in neurodevelopmental and regenerative medicine

Vascular endothelial growth factor（VEGF）in neurodevelopment and regeneration：VEGF is a well-known factor that promotes vascularization and angiogenesis.Besides this it participates in the pathogenesis of several diseases,such as colorectal carcinoma,lung cancer or diabetic retinopathy.Within the last decade,VEGF has been successfully integrated into the treatment of such diseases,for example as a therapy for colorectal cancer with the VEGF-receptor （VEGFR）-inhibitor axitinib.

Ultrasonic vocalizations in mice: relevance for ethologic and neurodevelopmental disorders studies

Mice use ultrasonic vocalizations(USVs)to communicate each other and to convey their emotional state.USVs have been greatly characterized in specific life phases and contexts,such as mother isolation-induced USVs for pups or female-induced USVs for male mice during courtship.USVs can be acquired by means of specific tools and later analyzed on the base of both quantitative and qualitative parameters.Indeed,different ultrasonic call categories exist and have already been defined.The understanding of different calls meaning is still missing,and it will represent an essential step forward in the field of USVs.They have long been studied in the ethological context,but recently they emerged as a precious instrument to study pathologies characterized by deficits in communication,in particular neurodevelopmental disorders(NDDs),such as autism spectrum disorders.This review covers the topics of USVs characteristics in mice,contexts for USVs emission and factors that modulate their expression.A particular focus will be devoted to mouse USVs in the context of NDDs.Indeed,several NDDs murine models exist and an intense study of USVs is currently in progress,with the aim of both performing an early diagnosis and to find a pharmacological/behavioral intervention to improve patients’quality of life.

Neurodevelopmental Timing of Ethanol Exposure May Contribute to Observed Heterogeneity of Behavioral Deficits in a Mouse Model of Fetal Alcohol Spectrum Disorder (FASD)

Maternal drinking during pregnancy can result in a wide spectrum of cognitive and behavioral abnormalities termed fetal alcohol spectrum disorders (FASD). The heterogeneity observed in FASD-related phenotypes can be attributed to a number of environmental and genetic factors;however, ethanol dose and timing of exposure may have significant influences. Here, we report the behavioral effects of acute, binge-like ethanol exposure at three neurodevelopmental times corresponding to the first, second, and third trimester of human development in C57BL/6J mice. Results show that developmental ethanol exposure consistently delays the development of basic motor skill reflexes and coordination as well as impairs spatial learning and memory. Observed changes in activity and anxiety-related behaviors, however, appear to be dependent on timing of alcohol exposure. The variability in behaviors between different treatment models suggests that these may be useful in evaluating the mechanisms disrupted by ethanol at specific neurodevelopmental times. The results provide further evidence that, regardless of developmental stage, the developing brain is acutely sensitive to alcohol exposure.

Okur-Chung neurodevelopmental综合征1例并文献复习

Okur-Chung neurodevelopmental综合征的发生与CSNK2A1基因突变有关,患儿以特殊面容和多系统受累为主要表现。本文通过文献复习Okur-Chung neurodevelopmental综合征,提高临床对本病的认识和诊断。此外,Okur-Chung neurodevelopmental综合征由于缺乏确切的临床诊断标准,确诊仍有赖于基因突变分析。

Neurodevelopmental outcome in congenital diaphragmatic hernia: Evaluation, predictors and outcome

To review the reported neurodevelopmental outcome of congenital diaphragmatic hernia(CDH) survivors, identify important predictors of developmental disabilities, and describe the pathophysiological mechanisms contributing to adverse outcome. A Medline search was performed for English-language articles cross-referencing CDH with pertinent search terms. Retrospective, prospective, and longitudinal follow-up studies were examined. The reference lists of identified articles were also searched. Neurodevelopmental dysfunction has been recognized as one of most common and potentially most disabling outcome of CDH. Intelligence appears to be in the low normal to mildly delayed range. Neuromotor dysfunction is common during early childhood. Behavioral problems, hearing impairment, and quality of life related issues are frequently encountered in older children and adolescence. Disease severity correlates with the degree of neurological dysfunction. Neurodevelopmental follow-up in CDH children should become standard of care to identify those who would benefit from early intervention services and improve neurological outcomes.

Preterm nutrition and neurodevelopmental outcomes

Survival of preterm infants has been steadily improving in recent years because of many recent advances in perinatal and neonatal medicine.Despite these advances,the growth of survivors does not reach the ideal target level of the normal fetus of the same gestational age.Postnatal weight gain is often not achieved because extrauterine growth has higher energy requirements than intrauterine growth,due to the intensive care environment,illness and inadequate nutrition.Although many other factors influence infant brain development,including family socioeconomic and educational background,the role of nutrition is considerable and fortunately,amenable to intervention.In the preterm neonate,the brain is the most metabolically demanding organ,consuming the largest proportions of energy and nutrient intake for its function and programmed growth and maturation.Weight gain,linear and head circumference growth are all markers of nutritional status and are independently associated with long-term neurodevelopment.Brain development is not only the result of nutrients intake,but in addition,of the interaction with growth factors which depend on adequate nutrient supply and overall health status.This explains why conditions such as sepsis,necrotizing enterocolitis and chronic lung disease alter the distribution and accretion of nutrients thereby suppressing growth factor synthesis.In this review,we will focus on the direct role of nutrition on neurodevelopment,emphasizing why it should be started without delay.The nutritional requirements of the preterm infant will be discussed,followed by the effects of general nutritional interventions and specific nutrients,as well as the role of nutritional supplements on neurodevelopment.The primordial role of human breast milk,breast milk fortifiers and human milk oligosaccharides will be discussed in detail.We will also examine the role of nutrition in preventing neonatal complications which can affect neurodevelopment in their own right.

Research progress on the influence of opioids on fetal neurodevelopment during pregnancy

Women usually suffer from chronic pain due to pregnancy or have an increased level of chronic pain.In view of the definite curative effect of opioids on chronic pain and opioid use disorders,opioids have attracted much attention in the treatment of bone,joint,neuropathic and other chronic pain and opioid use disorders in pregnant women.Considering that the unreasonable use of opioids by pregnant women will lead to risks such as drug accumulation and increased neural sensitivity in the fetus,the correct and reasonable use of opioids is the key to the treatment.In recent years,it has been found that opioids can cross the blood fetal barrier into the fetal circulation,and damage fetal nerve development to varying degrees.However,the studies on the typical diseases such as neonatal neural tube defects and neonatal abstinence syndrome are not comprehensive.Therefore,this article has clarified the unreasonable use of opioids during pregnancy and its effect on fetal nerve development,and put forward relevant measures in order to provide reference for clinicians/pharmacists in obstetrics and gynecology.

Classification,prevalence and integrated care for neurodevelopmental and child mental health disorders:A brief overview for paediatricians

‘Neurodevelopmental disorders’comprise a group of congenital or acquired longterm conditions that are attributed to disturbance of the brain and or neuromuscular system and create functional limitations,including autism spectrum disorder,attention deficit/hyperactivity disorder,tic disorder/Tourette’s syndrome,developmental language disorders and intellectual disability.Cerebral palsy and epilepsy are often associated with these conditions within the broader framework of paediatric neurodisability.Co-occurrence with each other and with other mental health disorders including anxiety and mood disorders and behavioural disturbance is often the norm.Together these are referred to as neurodevelopmental,emotional,behavioural,and intellectual disorders(NDEBIDs)in this paper.Varying prevalence rates for NDEBID have been reported in developed countries,up to 15%,based on varying methodologies and definitions.NDEBIDs are commonly managed by either child health paediatricians or child/adolescent mental health(CAMH)professionals,working within multidisciplinary teams alongside social care,education,allied healthcare practitioners and voluntary sector.Fragmented services are common problems for children and young people with multi-morbidity,and often complicated by subthreshold diagnoses.Despite repeated reviews,limited consensus among clinicians about classification of the various NDEBIDs may hamper service improvement based upon research.The recently developed“Mental,Behavioural and Neurodevelopmental disorder”chapter of the International Classification of Diseases-11 offers a way forward.In this narrative review we search the extant literature and discussed a brief overview of the aetiology and prevalence of NDEBID,enumerate common problems associated with current classification systems and provide recommendations for a more integrated approach to the nosology and clinical care of these related conditions.

Postnatal therapeutic approaches in genetic neurodevelopmental disorders

Genetic neurodevelopmental disorders are characterized by abnormal neurophysiological and behavioral phenotypes,affecting individuals worldwide.While the subject has been heavily researched,current treatment options relate mostly to alleviating symptoms,rather than targeting the altered genome itself.In this review,we address the neurogenetic basis of neurodevelopmental disorders,genetic tools that are enabling precision research of these disorders in animal models,and postnatal gene-therapy approaches for neurodevelopmental disorders derived from preclinical studies in the laboratory.

Neurodevelopmental in Relation to Breastfeeding–Experiences among Hungarian Preterm Infants at 12 Months of Corrected Age:Empirical Study

Preterm and low birth weight infants are at higher risk of neurodevelopmental outcomes;breastfeeding offers sev-eral beneficial aspects for them.This study aimed to describe the average neurodevelopmental outcomes of pre-term infants and examine the associations between neurodevelopment and breastfeeding among Hungarian preterm infants at 12 months of corrected age.154 preterm infants with low birth weight(<2500 g)and their mothers were participated in this study.Bayley-III Screening Test(Bayley Scales of Infant and Toddler Develop-ment Screening Test,Third Edition)was administered to measure the cognitive,language and motor skills of infants;breastfeeding data was obtained through parental anamnesis.To analyze data,independent sample t-test or the Welch t-test,Mann-Whitney tests,Chi-square tests of independence and Spearman’s rank correlation test were used to.Concerning the risk of developmental delay,Receptive and Expressive language and Fine motor subscales were the lowest.Examination of the associations between breastfeeding and neurodevelopmental per-formance identified significantly higher cognitive(U=2047.5;P=0.023)andfine motor(U=2096.0;P=0.037)skills in infants who were breastfed.We found significant positive correlations between the duration of breastfeeding and cognitive,expressive language andfine motor skills.The study draws the attention to the importance of breastfeeding and early screening.Further research is required to examine the casual relationship between neurodevelopmental outcomes and breastfeeding.