Neurodevelopmental Disorders (neurodevelopmental + disorders)

Distribution by Scientific Domains

Selected Abstracts

Gastrostomy placement in paediatric patients with neuromuscular disorders: indications and outcome

Gian Paolo Ramelli MD
Studies of children with neurodevelopmental disorders have shown that receiving nutrition through a gastrostomy can improve clinical outcomes and quality of life. However, there is little information on gastrostomy and its effect in patients with neuromuscular disorders. A retrospective casenote review of all patients with a gastrostomy, followed-up at the Hammersmith Hospital, London, was undertaken to assess the indications for, and outcomes of, gastrostomy placement. Notes for 32 patients (17 males, 15 females) were reviewed (age range 32mo,31y; median age 12y 5mo). We found three main groups of diagnoses: congenital muscular dystrophy (n=15), structural congenital myopathies (n=11), and other neuromuscular disorders (n=6). Two main patterns of feeding problems were identified before gastrostomy: swallowing difficulties, and nutrition and growth problems. The follow-up period after gastrostomy was from 12 months to 19 years (mean 5y). Weight faltering was reversed in 17 out of 22 patients, and height faltering in 9 out of 14, where data were available. Twenty-six patients had a reduced frequency of chest infections. No significant complication of gastrostomy placement was documented. Twenty-eight patients or their families were happy with the results of the gastrostomy. Gastrostomy seems to have a substantial positive impact in patients with neuromuscular disease and feeding difficulties. [source]

The clinical utility of MRI in patients with neurodevelopmental disorders of unknown origin

H. M. Engbers
Introduction:, Neuroimaging of the brain in the diagnostic work-up of patients with neurodevelopmental disorders is a matter of continuing debate. Recommendations range from performing brain imaging in all patients with neurodevelopmental disorders to performing an MRI only in those with indication on clinical examinations. Important indications for neuroimaging are head size abnormalities and focal neurological findings. Methods:, Patients with neurodevelopmental disorders of unknown origin (n = 410), referred to a specialized tertiary diagnostic center for neurodevelopmental disorders were included in a retrospective analysis. A 1-day work-up, including an MRI of the brain was performed. Studied were the: (i) yield of MRI scans of the brain and (ii) associations of specific clinical symptoms/signs with abnormal and diagnostic MRI scans. Results:, (i) In 30.7% of the 410 patients with neurodevelopmental disorders (n = 126), abnormal MRI scans were observed, leading to an etiological diagnosis in 5.4% of the patients (n = 22). (ii) Pyramidal disorders (P = 0.001), epilepsy (P = 0.04) and an abnormal head circumference (P = 0.02) were associated with an abnormal MRI scan. The presence of one of the following neurological symptoms/signs: movement disorders, pyramidal disorders, epilepsy, or an abnormal head circumference was associated with a diagnostic MRI scan (P < 0.001) (diagnostic MRI % in neurological versus no neurological symptoms/signs, 13.0% versus 1.9%). Conclusion:, Neuroimaging of the brain in a tertiary care center for patients with neurodevelopmental disorders of unknown origin is useful, especially in case of neurological symptoms/signs. [source]

Epigenetic dysregulation in cognitive disorders

Johannes Gräff
Abstract Epigenetic mechanisms are not only essential for biological functions requiring stable molecular changes such as the establishment of cell identity and tissue formation, they also constitute dynamic intracellular processes for translating environmental stimuli into modifications in gene expression. Over the past decade it has become increasingly clear that both aspects of epigenetic mechanisms play a pivotal role in complex brain functions. Evidence from patients with neurodegenerative and neurodevelopmental disorders such as Alzheimer's disease and Rett syndrome indicated that epigenetic mechanisms and chromatin remodeling need to be tightly controlled for proper cognitive functions, and their dysregulation can have devastating consequences. However, because they are dynamic, epigenetic mechanisms are also potentially reversible and may provide powerful means for pharmacological intervention. This review outlines major cognitive disorders known to be associated with epigenetic dysregulation, and discusses the potential of ,epigenetic medicine' as a promising cure. [source]

Transgenic and knock-out mouse pups: the growing need for behavioral analysis

I. Branchi
Few laboratories working with transgenic and knock-out mice analyze the neurobehavioral consequences of genetic manipulation in early ontogeny. However, the study of behavioral endpoints during the early postnatal period in genetically modified mice is important not only to assess possible developmental abnormalities, but also to better understand and disentangle the effects of genetic manipulations in adulthood. We propose that the assessment of neurobehavioral development represents an appropriate strategy to identify possible compensatory and/or unexpected effects. Nowadays, a large number of experimental protocols that take into account the practical constraints imposed by the peculiar physiological and behavioral responses of an immature subject are available to assess the neurobehavioral profile of developing mice. While this knowledge should be applied to the field of transgenic and knock-out mice in general, it should be recommended, in particular, for the study of mouse models of neurodevelopmental disorders. [source]

Porphyrinuria in childhood autistic disorder is not associated with urinary creatinine deficiency

Robert Nataf
Abstract Background: Urinary metabolite measurements are often normalized to levels of the ubiquitous metabolite creatinine (CRT) to take account of variations in fluid export. Following CRT normalization, excesses of porphyrins and isoprostanes have been reported in the urines of children with neurodevelopmental disorders. It was suggested (Whiteley et al., 2006, Pediatr. Int. 2006; 48: 292,297) that urinary CRT levels may be depressed in children with autism spectrum disorders. This prompted re-evaluation of CRT levels in such children. Methods: First matinal urinary CRT levels were compared between subjects in different diagnostic categories including autistic disorder, pervasive developmental disorder not otherwise specified (PDD-NOS) and hyperactivity, before and after correction for age and gender. A larger reference group, consisting of subjects with unrelated disorders and Asperger disorder, with no reported porphyrin excess, was also compared to the group with autistic disorder, both for CRT and for porphyrin (coproporphyrin, COPRO) excess. Results: No significant difference in CRT was observed between any of the categories analyzed, also when corrected for age and gender. In contrast, urinary COPRO levels were significantly higher in autistic disorder versus reference groups, either when expressed as absolute values (independent of CRT levels) or when normalized to CRT. Conclusions: These data do not support a systematic reduction in urinary CRT levels in subjects with autism spectrum disorders including autistic disorder and PDD-NOS. Urinary COPRO excess in autistic disorder was not associated with or consequent upon urinary CRT deficiency. Differences between affected and control subjects in age and sampling time, as reported by Whiteley et al., may underlie the apparent CRT reduction. [source]

School neuropsychology consultation in neurodevelopmental disorders,

Scott L. Decker
The role of school psychologists with training in neuropsychology is examined within the context of multitiered models of service delivery and educational reform policies. An expanded role is suggested that builds on expertise in the assessment of neurodevelopmental disorders and extends to broader tiers through consultation practice. Changes in federal legislation to allow more flexible approaches toward assessment are viewed as a catalyst toward the integration of neuropsychological practice in school-based practice. As a set of priorities, recommendations are made for reforming assessment practice in schools, linking neuropsychological test results to academic treatment outcomes, and developing consultation practice with parents and teachers for early identification purposes and to integrate school-based services with community mental health services. © 2008 Wiley Periodicals, Inc. [source]

Sleep problems, sleepiness and daytime behavior in preschool-age children

Beth Goodlin-Jones
Background:, Sleep problems are a common complaint of parents of preschool children. Children with neurodevelopmental disorders have even more disrupted sleep than typically developing children. Although disrupted nighttime sleep has been reported to affect daytime behavior, the pathway from sleep disruption to sleep problems, to impairments in daytime performance or behavior is not clear. This multi-method, preliminary study assessed this path in 68 children with autism, matched to 57 children with developmental delay without autism and 69 children developing typically. Methods:, Actigraphy, structured questionnaires, laboratory assessments, and parent reports were obtained in 194 children. Results:, Controlling for diagnosis and developmental age of the child, nighttime sleep problems determined by parent reports were significantly associated with decrements in daytime behavior, also measured by parent report instruments. However, actigraph-defined sleep problems and objective measures of daytime sleepiness were not associated with decrements in daytime performance. Conclusions:, Parent report measures substantiate relationships between disrupted sleep patterns and waking behavior. Further understanding of the pathway from sleep disorders to daytime sleepiness and decrements in waking performance, however, may require more rigorous methods of assessment such as polysomnography and the multiple sleep latency test. [source]

Research Review: Crossing syndrome boundaries in the search for brain endophenotypes

Yonata Levy
The inherent imprecision of behavioral phenotyping is the single most important factor contributing to the failure to discover the biological factors that are involved in psychiatric and neurodevelopmental disorders (e.g., Bearden & Freimer, 2006). In this review article we argue that in addition to an appreciation of the inherent complexity at the biological level, a rather urgent task facing behavioral scientists involves a reconsideration of the role that clinical syndromes play in psychological theorizing, as well as in research into the biological basis of cognition and personality. Syndrome heterogeneity, cross-syndrome similarities and syndrome comorbidities question the relevance of syndromes to biological research. It is suggested that the search for brain endophenotypes, intermediate between genes and behavior, should be based on cross-syndrome, trait classification. Cohort selection should rest on behavioral homogeneity, enabling, when necessary, syndrome heterogeneity. [source]

The future of psychotherapy for mentally ill children and adolescents

John S. March
Objective:, Given striking advances in translational developmental neuroscience and its convergence with developmental psychopathology and developmental epidemiology, it is now clear that mental illnesses are best thought of as neurodevelopmental disorders. This simple fact has enormous implications for the nature and organization of psychotherapy for mentally ill children, adolescents and adults. Method:, This article reviews the ,trajectory' of psychosocial interventions in pediatric psychiatry, and makes some general predictions about where this field is heading over the next several decades. Results:, Driven largely by scientific advances in molecular, cellular and systems neuroscience, psychotherapy in the future will focus less on personal narratives and more on the developing brain. In place of disorders as intervention targets, modularized psychosocial treatment components derived from current cognitive-behavior therapies will target corresponding central nervous system (CNS) information processes and their functional behavioral consequences. Either preventive or rehabilitative, the goal of psychotherapy will be to promote development along typical developmental trajectories. In place of guilds, psychotherapy will be organized professionally much as physical therapy is organized today. As with other forms of increasingly personalized health care, internet-based delivery of psychotherapy will become commonplace. Conclusion:, Informed by the new field of translational developmental neuroscience, psychotherapy in the future will take aim at the developing brain in a service delivery model that closely resembles the place and role of psychosocial interventions in the rest of medicine. Getting there will be, as they say, interesting. [source]

Antenatal maternal stress and long-term effects on child neurodevelopment: how and why?

Nicole M. Talge
We review a significant body of evidence from independent prospective studies that if a mother is stressed while pregnant, her child is substantially more likely to have emotional or cognitive problems, including an increased risk of attentional deficit/hyperactivity, anxiety, and language delay. These findings are independent of effects due to maternal postnatal depression and anxiety. We still do not know what forms of anxiety or stress are most detrimental, but research suggests that the relationship with the partner can be important in this respect. The magnitude of these effects is clinically significant, as the attributable load of emotional/behavioral problems due to antenatal stress and/or anxiety is approximately 15%. Animal models suggest that activity of the stress-responsive hypothalamic-pituitary-adrenal (HPA) axis and its hormonal end-product cortisol are involved in these effects in both mother and offspring. The fetal environment can be altered if stress in the mother changes her hormonal profile, and in humans, there is a strong correlation between maternal and fetal cortisol levels. However, many problems remain in understanding the mechanisms involved in this interaction. For example, maternal cortisol responses to stress decline over the course of pregnancy, and earlier in pregnancy, the link between maternal and fetal cortisol is less robust. It is possible that the effects of maternal anxiety and stress on the developing fetus and child are moderated by other factors such as a maternal diet (e.g., protein load). It is suggested that extra vigilance or anxiety, readily distracted attention, or a hyper-responsive HPA axis may have been adaptive in a stressful environment during evolution, but exists today at the cost of vulnerability to neurodevelopmental disorders. [source]

Practitioner Review: Short-term and working memory impairments in neurodevelopmental disorders: diagnosis and remedial support

Susan E. Gathercole
Background:, This article provides an introduction to current models of working and short-term memory, their links with learning, and diagnosis of impairments. The memory impairments associated with a range of neurodevelopmental disorders (Down's syndrome, Williams syndrome, Specific Language Impairment, and attentional deficits) are discussed. Methods:, Methods of alleviating the adverse consequences of working and short-term memory impairments for learning are identified. Conclusion:, Impairments of short-term and working memory are associated with learning difficulties that can be substantial, and that can be minimised by appropriate methods of remedial support. [source]

Annotation: Deconstructing the attention deficit in fragile X syndrome: a developmental neuropsychological approach

K.M. Cornish
Background:, Fragile X syndrome is one of the world's leading hereditary causes of developmental delay in males. The past decade has witnessed an explosion of research that has begun to unravel the condition at its various levels: from the genetic and brain levels to the cognitive level, and then to the environmental and behavioural levels. Our aim in this review is to attempt to integrate some of the extensive body of knowledge to move the research a step closer to understanding how the dynamics of atypical development can influence the specific cognitive and behavioural end-states frequently observed in children and adolescents with fragile X syndrome. Methods:, We conducted a review of the current neuropsychological and neuropsychiatric approaches that have attempted to delineate the pattern of ,spared' and ,impaired' functions associated with the phenotype. Results:, The profile of findings suggests that fragile X syndrome should not be viewed merely as a catalogue of spared and impaired cognitive functions or modules. Instead, there appears to be a process of almost gradual modularisation whereby cognitive mechanisms become domain specific as a function of development itself (Karmiloff-Smith, 1992). The results of a decade of intense research point towards an early weakness in one or more components of executive control rather than single, static higher-level deficits (e.g., spatial cognition, speech processing). This weakness affects both the development of more complex functions and current performance. Conclusions:, The prevailing tendency to interpret developmental disorders in terms of fixed damage to distinct modular functions needs to be reconsidered. We offer this review as an example of an alternative approach, attempting to identify an initial deficit and its consequences for the course of development. Through better definition of the cognitive and behavioural phenotype, in combination with current progress in brain imaging techniques and molecular studies, the next decade should continue to hold exciting promise for fragile X syndrome and other neurodevelopmental disorders. [source]

A comprehensive volumetric analysis of the cerebellum in children and adolescents with autism spectrum disorder

Julia A. Scott
Abstract Magnetic resonance imaging (MRI) and postmortem neuropathological studies have implicated the cerebellum in the pathophysiology of autism. Controversy remains, however, concerning the nature and the consistency of cerebellar alterations. MRI studies of the cross-sectional area of the vermis have found both decreases and no difference in autism groups. Volumetric analysis of the vermis, which is less prone to "plane of section artifacts" may provide a more reliable assessment of size differences but few such studies exist in the literature. Here we present the results of a volumetric analysis of the structure of the whole cerebellum and its components in children and adolescents with autism spectrum disorders. Structural MRI's were acquired from 62 male participants (7.5 to 18.5 years-old) who met criteria for the following age-matched diagnostic groups: low functioning autism, high functioning autism (HFA), Asperger syndrome, and typically developing children. When compared to controls, the midsagittal area of the vermis, or of subgroups of lobules, was not reduced in any of the autism groups. However, we did find that total vermis volume was decreased in the combined autism group. When examined separately, the vermis of only the HFA group was significantly reduced compared to typically developing controls. Neither IQ nor age predicted the size of the vermis within the autism groups. There were no differences in the volume of individual vermal lobules or cerebellar hemispheres. These findings are discussed in relation to the pathology of autism and to the fairly common alterations of vermal morphology in various neurodevelopmental disorders. [source]

Gene expression profiling differentiates autism case,controls and phenotypic variants of autism spectrum disorders: evidence for circadian rhythm dysfunction in severe autism

Valerie W. Hu
Abstract Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by delayed/abnormal language development, deficits in social interaction, repetitive behaviors and restricted interests. The heterogeneity in clinical presentation of ASD, likely due to different etiologies, complicates genetic/biological analyses of these disorders. DNA microarray analyses were conducted on 116 lymphoblastoid cell lines (LCL) from individuals with idiopathic autism who are divided into three phenotypic subgroups according to severity scores from the commonly used Autism Diagnostic Interview-Revised questionnaire and age-matched, nonautistic controls. Statistical analyses of gene expression data from control LCL against that of LCL from ASD probands identify genes for which expression levels are either quantitatively or qualitatively associated with phenotypic severity. Comparison of the significant differentially expressed genes from each subgroup relative to the control group reveals differentially expressed genes unique to each subgroup as well as genes in common across subgroups. Among the findings unique to the most severely affected ASD group are 15 genes that regulate circadian rhythm, which has been shown to have multiple effects on neurological as well as metabolic functions commonly dysregulated in autism. Among the genes common to all three subgroups of ASD are 20 novel genes mostly in putative noncoding regions, which appear to associate with androgen sensitivity and which may underlie the strong 4:1 bias toward affected males. [source]

Mental health services for people with intellectual disability: challenges to care delivery

Eddie Chaplin
Accessible summary ,,This paper looks at how care is given to people with intellectual disability who have mental health problems. ,,The paper looks at care since Valuing People came out in 2001. ,,It shows there are not enough services for people with intellectual disability who have mental health problems. ,,It shows there are not enough services for people who have autism and mental health problems. ,,Lots of people feel that mainstream mental health services are not good enough for people with intellectual disability. Lots of people feel mainstream services could be better. ,,The paper looks at how people can get help and support in their local area and not having to move away to get help. ,,The paper looks at what services might be needed in the future. What can be done to make services better? ,,The people who pay for services are called commissioners. They should think about how they can make local services better for with intellectual disability and mental health problems. ,,Commissioners should work more together with those who support people with intellectual disability to improve services. ,,People with intellectual disability should be happy with the services they have in their local places. ,,Services need to remember that people change as they get older. ,,Services need to remember that what people want. This can change when they get older. Summary The commissioning and provision of mental health services for people with intellectual disability is often complex and characterised by different service delivery models. This paper looks at the current situation 7 years after the White Paper, Valuing People (From words into action: London learning disabilities strategic framework, Department of Health, London), within the context of the National Service Framework for Mental Health (Establishing responsible commissioner; draft guidance. HSC draft, Department of Health, London). It sets out to illustrate problems faced in providing local services in the United Kingdom for those with intellectual disability and other neurodevelopmental disorders. This paper proposes new ways of working and introduces the concept of a neurodevelopmental model designed to address gaps and inequalities within services by offering solutions that embrace joint working. [source]

Schools: Central to Providing Comprehensive CAMH Services in the Future?

Gill Salmon
It is now widely agreed that meeting the mental health needs of children and young people is a task only possible if all children's services work together. Recent epidemiological data indicate that schools are a key entry point to mental health services for children and young people, and have an important role in the assessment and management of children with neurodevelopmental disorders. This paper explores the rationale for collaborative working between health and educational professionals, examines some examples of good practice, explores factors contributing to their success or failure and considers future developments. [source]

An Eye for Detail: An Event-Related Potential Study of the Rapid Processing of Fearful Facial Expressions in Children

Petra H. J. M. Vlamings
There is converging evidence for the presence of a fast subcortical face-processing route that operates on global face characteristics in the mature brain. Until now, little has been known about the development of such a route, which is surprising given suggestions that this fast subcortical face-processing route might be affected in neurodevelopmental disorders such as autism. To address this, early visual event-related potentials to pictures of fearful and neutral faces containing detailed or global information in 3- to 4-year-old (n = 20), 5- to 6-year-old (n = 25), and 7- to 8-year-old (n = 25) children were compared. In children, emotional processing was driven by detailed information. Developmental effects are discussed in terms of maturation of the fast subcortical face-processing route as well as an increase in experience with facial expressions with age. [source]

Autism spectrum disorders: clinical and research frontiers

Richard Reading
Autism spectrum disorders: clinical and research frontiers . CaronnaE. B., MilunskyJ. M. & Tager-FlusbergH. ( 2008 ) Archives of Disease in Childhood , 93 , 518 , 523 . DOI: 10.1136/adc.2006.115337 . Autism spectrum disorders (ASD) are common neurodevelopmental disorders that occur along a broad continuum of severity with impairments in social interactions, communication and behaviour. This review highlights recent advances in autism research that shed light on the causes of the disorder and that have implications for clinical practice. It focuses on (1) the rising prevalence of ASD with attention given to recent epidemiological studies, (2) important genetic discoveries that may affect clinical evaluation of children with ASD, (3) active areas of research in cognitive neuroscience that seek to explain the underlying mechanisms of a complex disorder and (4) important studies on clinical populations with implications for screening and early identification of infants and toddlers with ASD. [source]

Development of cortical GABAergic circuits and its implications for neurodevelopmental disorders

G Di Cristo
GABAergic interneurons powerfully control the function of cortical networks. In addition, they strongly regulate cortical development by modulating several cellular processes such as neuronal proliferation, migration, differentiation and connectivity. Not surprisingly, aberrant development of GABAergic circuits has been implicated in many neurodevelopmental disorders including schizophrenia, autism and Tourette's syndrome. Unfortunately, efforts directed towards the comprehension of the mechanisms regulating GABAergic circuits formation and function have been impaired by the strikingly heterogeneity, both at the morphological and functional level, of GABAergic interneurons. Recent technical advances, including the improvement of interneurons-specific labelling techniques, have started to reveal the basic principles underlying this process. This review summarizes recent findings on the mechanisms underlying the construction of GABAergic circuits in the cortex, with a particular focus on potential implications for brain diseases with neurodevelopmental origin. [source]