High-density electroencephalography developmental neurophysiological trajectories.

Efforts to document early changes in the developing brain have resulted in the construction of increasingly accurate structural images based on magnetic resonance imaging (MRI) in newborn infants. Tractography diagrams obtained through diffusion tensor imaging have focused on white matter microstructure, with particular emphasis on neuronal connectivity at the level of fibre tract systems. Electroencephalography (EEG) provides a complementary approach with more direct access to brain electrical activity. Its temporal resolution is excellent, and its spatial resolution can be enhanced to physiologically relevant levels, through the combination of high-density recordings (e.g. by using 64 channels in newborn infants) and mathematical models (e.g. inverse modelling computation), to identify generators of different oscillation bands and synchrony patterns. The integration of functional and structural topography of the neonatal brain provides insights into typical brain organization, and the deviations seen in particular contexts, for example the effect of hypoxic-ischaemic insult in terms of damage, eventual reorganization, and functional changes. Endophenotypes can then be used for pathophysiological reasoning, management planning, and outcome measurements, and allow a longitudinal approach to individual developmental trajectories.

Phenotypic plasticity and the perception-action-cognition-environment paradigm in neurodevelopmental genetic disorders.

Careful study of the phenotype can have implications at several levels, namely clinical diagnosis, pathophysiological reasoning, management planning, and outcome measurement. Behavioural phenotypes involve cognition, communication, social skills, and motor control. They can be documented in a host of neurodevelopmental conditions and approached with the recently refined perception-action-cognition-environment (PACE) paradigm, which focuses on the neurodevelopmental processes that underlie learning and adaption to the environment through perception, action, and cognitive processing. Although this paradigm was originally developed in the context of cerebral palsy, it can be applied along developmental trajectories in several neurogenetic conditions, including Down syndrome, fragile X syndrome, Rett syndrome, Angelman syndrome, and Williams syndrome, to name but a few. It must be recognized, however, that relevant, valid tools for assessment and management strategies still need to be developed.

Prevalence of cerebral palsy and factors associated with cerebral palsy subtype: A population-based study in Belgium.

AIM: To report on the prevalence, neuroimaging patterns, and function of children with cerebral palsy (CP) in Belgium for birth years 2007-2012, and identify distinctive risk indicators and differences in outcome between CP subtypes. METHODS: Antenatal and perinatal/neonatal factors, motor and speech function, associated impairments, and neuroimaging patterns were extracted from the Belgian Cerebral Palsy Register. Prevalence was estimated per 1000 (overall, ante/perinatal, spastic, dyskinetic CP) or 10,000 (post-neonatal, ataxic CP) live births. Multinomial logistic regression analyses were performed to ascertain the effects of antenatal/perinatal/neonatal factors and neuroimaging patterns on the likelihood of dyskinetic or ataxic CP relative to spastic CP, and test the likelihood of the occurrence of impaired motor and speech function and associated impairments in dyskinetic or ataxic CP relative to spastic CP. RESULTS: In total, 1127 children with CP were identified in Belgium. The birth prevalence of overall CP was 1.48 per 1000 live births. The likelihood of dyskinetic CP increases if the child was born to a mother aged ≥35 years, mechanically ventilated, and had predominant grey matter injury, while an increased likelihood of ataxic CP is associated with ≥2 previous deliveries. Children with dyskinetic and ataxic CP are more likely to function with impairments in motor, speech, and intellectual abilities. CONCLUSION: Distinctive risk indicators and differences in outcome between CP subtypes were identified. These factors can be incorporated into clinical practice to facilitate early, accurate, and reliable classification of CP subtype, and may lead to individually tailored neonatal care and other (early) intervention options.

Multiscale entropy as a metric of brain maturation in a large cohort of typically developing children born preterm using longitudinal high-density EEG in the first two years of life.

Objective.We aimed to analyze whether complexity of brain electrical activity (EEG) measured by multiscale entropy (MSE) increases with brain maturation during the first two years of life. We also aimed to investigate whether this complexity shows regional differences across the brain, and whether changes in complexity are influenced by extrauterine life experience duration.Approach.We measured MSE of EEG signals recorded longitudinally using a high-density setup (64 or 128 electrodes) in 84 typically developing infants born preterm (<32 weeks' gestation) from term age to two years. We analyzed the complexity index and maximum value of MSE over increasing age, across brain regions, and in function of extrauterine life duration, and used correlation matrices as a metric of functional connectivity of the cerebral cortex.Main results.We found an increase of strong inter-channel correlation of MSE (R > 0.8) with increasing age. Regional analysis showed significantly increased MSE between 3 and 24 months of corrected age in the posterior and middle regions with respect to the anterior region. We found a weak relationship (adjusted R2= 0.135) between MSE and extrauterine life duration.Significance.These findings suggest that brain functional connectivity increases with maturation during the first two years of life. EEG complexity shows regional differences with earlier maturation of the visual cortex and brain regions involved in joint attention than of regions involved in cognitive analysis, abstract thought, and social behavior regulation. Finally, our MSE analysis suggested only a weak influence of early extrauterine life experiences (prior to term age) on EEG complexity.

A multidisciplinary approach and consensus statement to establish standards of care for Angelman syndrome.

BACKGROUND: Angelman syndrome (AS) is a rare neurogenetic disorder present in approximately 1/12,000 individuals and characterized by developmental delay, cognitive impairment, motor dysfunction, seizures, gastrointestinal concerns, and abnormal electroencephalographic background. AS is caused by absent expression of the paternally imprinted gene UBE3A in the central nervous system. Disparities in the management of AS are a major problem in preparing for precision therapies and occur even in patients with access to experts and recognized clinics. AS patients receive care based on collective provider experience due to limited evidence-based literature. We present a consensus statement and comprehensive literature review that proposes a standard of care practices for the management of AS at a critical time when therapeutics to alter the natural history of the disease are on the horizon. METHODS: We compiled the key recognized clinical features of AS based on consensus from a team of specialists managing patients with AS. Working groups were established to address each focus area with committees comprised of providers who manage >5 individuals. Committees developed management guidelines for their area of expertise. These were compiled into a final document to provide a framework for standardizing management. Evidence from the medical literature was also comprehensively reviewed. RESULTS: Areas covered by working groups in the consensus document include genetics, developmental medicine, psychology, general health concerns, neurology (including movement disorders), sleep, psychiatry, orthopedics, ophthalmology, communication, early intervention and therapies, and caregiver health. Working groups created frameworks, including flowcharts and tables, to help with quick access for providers. Data from the literature were incorporated to ensure providers had review of experiential versus evidence-based care guidelines. CONCLUSION: Standards of care in the management of AS are keys to ensure optimal care at a critical time when new disease-modifying therapies are emerging. This document is a framework for providers of all familiarity levels.

Nocturnal Transcutaneous Blood Gas Measurements in a Pediatric Neurologic Population: A Quality Assessment.

Objective: To assess the quality of SpO2 and PCO2 recordings via transcutaneous monitoring in children with neurological conditions.Methods: Overnight transcutaneous SpO2 and PCO2 were analyzed. The presence of drift and drift correction was noted, and the rate of disrupted recordings scored (0: absence, 1; presence). The quality of recordings was also scored (0, 1, 2 for poor, medium, and high).Results: A total of 228 recordings from 64 children aged 9.7 ± 6 years were analyzed of which 42 used positive pressure respiratory support. The mean quality of the recordings was scored as 1.27 (0-2). PCO2 drift, drift correction, and disrupted recordings were present in 25%, 58%, and 26% of recordings, respectively. Satisfactory clinical decisions were taken in 91% of cases.Conclusion: The quality of transcutaneous sensor recordings was acceptable and clinical findings were deemed as satisfactory in the large majority of cases. Correction of PCO2 drift was challenging.

Are there distinctive sleep problems in Angelman syndrome?

Angelman syndrome is a neurogenetic condition characterized by developmental delay, absence of speech, motor impairment, epilepsy and a peculiar behavioral phenotype that includes sleep problems. It is caused by lack of expression of the UBE3A gene on the maternal chromosome 15q11-q13. Although part of the diagnostic description, 'sleep problems' are not well characterized. A pattern emerges from the available reports. It includes reduced total sleep time, increased sleep onset latency, disrupted sleep architecture with frequent nocturnal awakenings, reduced rapid eye movement (REM) sleep and periodic leg movements. Poor sleep does not significantly interfere with daytime alertness and sleep problems commonly diminish by late childhood, with continuing improvement through adolescence and adulthood. Sleep problems in Angelman syndrome reflect abnormal neurodevelopmental functioning presumably involving dysregulation of GABA-mediated inhibitory influences in thalamocortical interactions. Management may be difficult, particularly in young children; it primarily involves behavioral approaches, though pharmacological treatment may be required. The relationship between sleep and seizure disorder, and between sleep and learning raises critical questions, but more studies are needed to address these relationships adequately.

Metachromatic leukodystrophy without arylsulfatase A deficiency: a new case of saposin-B deficiency.

Metachromatic leukodystrophy (MLD) is an autosomal recessive neurodegenerative lysosomal disease characterized by accumulation of sulfatides, extensive white matter damage and loss of both cognitive and motor functions. In vivo, the catabolism of sulfatide requires both the enzyme arylsulfatase A and a specific sphingolipid activator protein, saposin-B, encoded by the PSAP gene. Arylsulfatase A activity is deficient in the classical forms of MLD, but exceedingly rare cases of MLD are due to saposin-B deficiency. We report here a detailed clinical, radiological and histological description of a new case in a 2-year-old Italian girl, who presented as a late infantile case of MLD with normal arylsulfatase A activity, urinary excretion of sulfatides and mutations in the PSAP gene.

Epilepsy in Angelman syndrome.

Angelman syndrome is a neurogenetic disorder caused by lack of UBE3A gene expression from the maternally inherited chromosome 15 due to various 15q11-q13 abnormalities. In addition to severe developmental delay, virtual absence of speech, motor impairment, a behavioural phenotype that includes happy demeanor, and distinctive rhythmic electroencephalographic features, over 90% of patients have epilepsy. Many different seizure types may occur, atypical absences and myoclonic seizures being particularly prevalent. Non-convulsive status epilepticus is common, sometimes in the context of the epileptic syndrome referred to as myoclonic status in non-progressive encephalopathies. Epilepsy predominates in childhood, but may persist or reappear in adulthood. Management is difficult in a proportion of patients. It might be improved by better understanding of pathophysiology. Current hypotheses involve abnormal inhibitory transmission due to impaired regulation of GABAA receptors related to functional absence of UBE3A and abnormal hippocampal CaMKII activity.

Multicentre prospective randomised single-blind controlled study protocol of the effect of an additional parent-administered sensorimotor stimulation on neurological development of preterm infants: Primebrain.

INTRODUCTION: Preterm and very low birthweight infants are at increased risk for neurodevelopmental disorders, including cerebral palsy, sensory impairment and intellectual disability. Several early intervention approaches have been designed in the hope of optimising neurological development in this context. It seems important that the intervention takes into account parental mental health, focuses on parent-child interactions and lasts sufficiently long. This study aims to evaluate the effects of a stimulation programme administered by parents until 6 months post-term on motor and neurophysiological development of infants born preterm. METHODS AND ANALYSIS: Participants will be infants born <32 weeks' gestation and/or with a birth weight <1500 g recruited prospectively from two tertiary neonatal intensive care units. They will be randomly assigned to receive nationally recommended follow-up only (control group) or also a stimulation programme between 37 weeks' gestation and 6 months' corrected age. Perinatal, clinical neurodevelopmental, socio-demographic and neuroimaging (ultrasonography or MRI) data will be collected. Bayley Scales of Infant Development will be used up to 24 months' corrected age and Parental Stress Index at 6, 12, 18 and 24 months' corrected age. High-density (64 or 128 electrodes) EEG, visual, somatosensory and long latency auditory evoked potentials will be recorded at term age, 3, 6, 12, 18 and 24 months' corrected age. They will be analysed for spatiotemporal frequency bands contents and source localisation. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committees of the Hôpital Universitaire des Enfants Reine Fabiola and CHU Saint-Pierre. Results dissemination will be made for stakeholders and families, reports will be written for parents, healthcare providers and policymakers, and scientific papers will be published. TRIAL REGISTRATION NUMBER: NCT02159534; Pre-results.

Recognition of emotional facial expressions in attention-deficit hyperactivity disorder.

In ADHD, impaired interpersonal relationships have been documented. They have been hypothesized to be secondary to impairment of receptive nonverbal language. Recognition of emotional facial expressions is an important aspect of receptive nonverbal language, and it has been demonstrated to be central to organization of emotional and social behavior. This study investigated the identification of facial expression of four emotions (joy, anger, disgust, and sadness) in a group of 30 children aged 7-12 years who met the DSM-IV criteria for ADHD disorder of the predominantly hyperactive-impulsive type and have no comorbid mental retardation, specific learning difficulties, developmental coordination disorder, pervasive developmental disorders, conduct disorder, bipolar disorder, or substance abuse, and in 30 matched unimpaired control children. The test used includes 16 validated photographs depicting these emotions in varying intensities constructed by morphing. Children with ADHD exhibited a general deficit in decoding emotional facial expressions, with specific deficit in identifying anger and sadness. Self-rating of the task difficulty revealed lack of awareness of decoding errors in the ADHD group as compared with control subjects. Within the ADHD group, there was a significant correlation between interpersonal problems and emotional facial expression decoding impairment, which was more marked for anger expressions. These results suggest suboptimal nonverbal decoding abilities in ADHD that may have important implications for therapy.

Pediatric SUNCT Syndrome.

This report describes a 5-year-old male with sudden unilateral headache attacks (2-50 seconds) accompanied by conjunctival injection, lacrimation, and nasal congestion. The episodes occurred without a precipitating factor, never during sleep. Brain imaging was normal. The attacks resolved spontaneously within 5 months. This headache syndrome (short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing) was previously described in two other children aged 10 and 11.

Motor strategies in standing up in children with hemiplegia.

In spastic hemiplegia, the organization of whole body movements is impaired by deficient postural control. We studied segmental motor patterns involved in standing up from supine position in 15 children with spastic hemiplegic cerebral palsy and 14 unimpaired children using a visual analysis scale previously validated for developmental research. This approach examines specific movement patterns in upper limbs, axis, and lower limbs. We found that children with hemiplegia use movement patterns described in normal children but with reduced interindividual variability and a significant preponderance of asymmetric patterns. One previously undescribed stereotyped lower limb pattern was observed in two children with spastic hemiplegia. Emergence of these patterns is consistent with the referent body image theory. This approach can systematically characterize the limited repertoire of movement in patients with disorders of movement and posture and therefore contribute to a better understanding of motor control. The approach may guide management proposals with particular reference to variability and symmetry and might be used as a follow-up tool.

Effect of ankle-foot orthoses on trunk sway and lower limb intersegmental coordination in children with bilateral cerebral palsy.

INTRODUCTION: Ankle-foot orthoses may significantly improve lower limb kinematics in the gait of children with cerebral palsy. Here we aimed to analyze the effect of ankle-foot orthoses on trunk postural control and lower limb intersegmental coordination in children with mild spastic diplegia (GMFCS I or II). METHODS: We recorded tridimensional trunk kinematics and thigh, shank, and foot elevation angles in 20 4-12 year-old children born preterm with spastic diplegia and 20 typically developing children while walking either barefoot or with ankle-foot orthoses. RESULTS: We found significantly greater trunk excursions in children with cerebral palsy compared to typically developing children in both conditions. When wearing ankle-foot orthoses cerebral palsy children showed increased trunk frontal angular velocity. No significant changes in trunk displacement and angular velocity were recorded in the sagittal plane in either group. Typically developing children wearing orthoses showed increased trunk frontal displacement. Wearing orthoses induced significant changes in shank and foot elevation in both groups. CONCLUSION: Ankle-foot orthoses affect postural control and intersegmental coordination in children with cerebral palsy. This should be taken into account when planning therapeutic management.