Forty-two infants (20 males, 22 females) with classical phenylketonuria (PKU) entered a prospective, double-blind, randomized study to investigate the effects on biochemical and physiological outcomes of a phenylalanine-free infant formula containing a fat blend supplemented with the long-chain polyunsaturated fatty acids (LC-PUFA), docosahexaenoic acid (DHA, C22:6n–3), and arachidonic acid (AA, C20:4n–6). Between entry and 20 weeks (entry and 1y) of age, median DHA levels in erythrocyte membrane phospholipids decreased by 15% (22%) in the LC-PUFA supplemented group (n=21) and by 61% (64%) in the control group (p<0.001; n=18). A dietary supply of LC-PUFA in infants with PKU prevents the decline in DHA levels associated with a diet supplying minimal sources of LC-PUFA. DHA status in turn, independent of diet, may influence the maturation of the visual system in infants with PKU.

We report here on a male diagnosed with tuberous sclerosis at 6 months of age. The child was treated with vigabatrin at age 6 months after an abnormal electroencephalogram but before onset of seizures. Vigabatrin was discontinued at age 13 months to avoid possible visual field defects. At 21 months, the child developed partial seizures with secondary generalization and infantile spasms. Standardized developmental assessments were performed at 12, 18, 24, 30, and 36 months of age. Cognitive and social development were normal until age 21 months and the onset of seizures. When assessed at 24 months, the child met criteria for autism and learning disability. This case indicates that the onset of epilepsy during an early stage in brain development can be associated with autistic regression and persistent developmental disorder. The case suggests the need to consider if possible visual field defects with vigabatrin outweigh the potentially deleterious effects of uncontrolled seizures.

This study investigated the immediate effects of stimulant medication (methylphenidate) on cognitive attention processes in children with attention-deficit–hyperactivity disorder (ADHD). Thirteen males and two females (mean age 9y 5mo, SD 18.3mo) with a diagnosis of ADHD and who were to be prescribed methylphenidate were assessed twice on one day with the Test of Everyday Attention for Children, a neuropsychological battery designed to tap different aspects of cognitive attention. Between assessments, the children were administered methylphenidate (10mg). Each child had at least average intelligence (IQ 80 or over, as measured by the Wechsler Intelligence Scale for Children – III UK) and was on no other medication. A group of 16 children, who were matched for age, sex, and intelligence, also performed the cognitive tests twice on the same day to control for practice effects of testing. At the first assessment, children with ADHD demonstrated significant impairments in several aspects of cognitive attention in comparison with the control group, particularly sustained attention. After administration of methylphenidate for the children with ADHD, they showed significant improvements in their performance on measures of cognitive attention compared to controls. The immediate effects of methylphenidate and the significance of measuring cognitive aspects of attention as well as behavioural measures are discussed.

The effects of mother–infant skin-to-skin contact (Kangaroo Care; KC) on autonomic functioning, state regulation, and neurobehavioural status was examined in 70 preterm infants, half of whom received KC over 24.31 days (SD 7.24) for a total of 29.76 hours (SD 12.86). Infants were matched for sex (19 males and 16 females in each group); birthweight (KC, 1229.95g [SD 320.21]; controls, 1232.17g [SD 322.15]); gestational age (GA) (KC, 30.28 weeks [SD 2.54]; controls, 30.19 weeks [SD 2.65]); medical risk; and family demographics. Vagal tone was calculated from 10 minutes of heart rate before KC and again at 37 weeks' GA. Infant state was observed in 10-second epochs during four consecutive hours before KC and again at 37 weeks' GA. Neurobehavioural status was assessed at 37 weeks' GA with the Neonatal Behavioral Assessment Scale (NBAS). Infants receiving KC showed a more rapid maturation of vagal tone between 32 and 37 weeks' GA (p=0.029). More rapid improvement in state organization was observed in KC infants, in terms of longer periods of quiet sleep (p=0.016) and alert wakefulness (p=0.013) and shorter periods of active sleep (p=0.023). Neurodevelopmental profile was more mature for KC infants, particularly habituation (p=0.032) and orientation (p=0.007). Results underscore the role of early skin-to-skin contact in the maturation of the autonomic and circadian systems in preterm infants.

The autistic spectrum/pervasive developmental disorders (termed autism here) are neurobehavioral conditions which are characterized by severe qualitative impairments in social reciprocity and communication, associated with stereotypical behaviors and interests. Autism is frequently combined with other symptoms of neurological dysfunction, including abnormal electroencephalograms (EEGs) and clinical seizures in at least 50% of affected individuals. A subgroup of children who develop the impairments of autism after initially normal development (termed ‘autistic regression’) is of particular interest. These children have an increased incidence of abnormal EEGs similar to those found in individuals with Landau–Kleffner syndrome (LKS) (acquired epileptiform aphasia). Recognition of overlapping clinical and electrophysiological features in these two conditions has led to speculation that there may be a pathophysiological relationship between them. This commentary will discuss the diagnosis and treatment of autistic regression (AR) and LKS, to provide a clinical perspective on their sometimes confusing relationships.

This study compares bone mass in a national sample of girls with Rett syndrome (RS) with a sample of control children. The Australian RS Database was the source of cases for this population-based study. Hand radiographs were available from 101 of 137 subjects (74% of the known Australian population of girls with RS aged [les ]20 years). Control radiographs matched for age, sex, and laterality were obtained from hospital radiology departments. A measure of cortical thickness was made from the difference between the outer diameter and the medullary space in the second metacarpal bone. A mean z-score value for cortical thickness and percentage cortical area for each individual was calculated. The mean cortical thickness (z score) for girls with RS was −1.94 compared with −0.38 for control children (P<0.001). In girls with RS, the mean cortical thickness decreased with age (P<0.001). In girls who were taking epilepsy medication it was −2.21 compared with −1.23 in those not taking epilepsy medication (P<0.001). There was no evidence of a beneficial effect of increased calcium intake on cortical thickness. A similar pattern was obtained when percentage cortical area was estimated. In multivariate analysis, increasing age and use of anticonvulsant medication were associated with decreased cortical thickness and only use of anticonvulsant medication with decreased percentage cortical area. Fractures had occurred in one-third of cases and it was estimated that just over 40% of girls would sustain a fracture by the age of 15 years. Girls with RS may be at increased risk of fractures and their bone quality compromised as determined by cortical thickness and percentage cortical area measurements from the second metacarpal.

Effects of perinatal exposure to polychlorinated biphenyls (PCBs) on auditory P300 latencies and amplitudes were evaluated in children from a Rotterdam cohort. From this cohort of healthy, term babies, the 26 lowest and 26 highest prenatally PCB-exposed children from the breastfed and the formula-fed groups (n=104) were invited for P300 assessment when they were 9 years of age. For P300 assessment an auditory simple odd-ball paradigm was used. In the 83 participating children, 60 assessments (32 males, 28 females) satisfied the measurement criteria and were included in the data analyses. After adjusting for confounding variables, children with high prenatal exposure were found to have longer P300 latencies than children with low prenatal exposure. Lactational exposure to PCBs through breastfeeding milk was not related to P300 latencies. P300 latencies were shorter in children breast-fed for at least 16 weeks than in children breastfed for 6 to 16 weeks and formula-fed children. P300 amplitudes were not related to perinatal PCB exposure nor breastfeeding. Results of this exploratory study suggest that prenatal exposure to environmental levels of PCBs and related compounds delays mechanisms in the central nervous system that evaluate and process relevant stimuli, whereas breastfeeding accelerates these mechanisms.

The aim of this study was to investigate the reliability and sensitivity of the Wartenberg pendulum test for quantification of muscle tone in young children with spastic diplegia undergoing selective dorsal rhizotomy (SDR). Fourteen non-disabled children (mean age of 5.5 years, age range 2.3 to 8.8 years, one female and one male in each year) were tested twice. Twenty children with spastic diplegia (12 males, eight females; mean age of 4.3 years, age range 2.5 to 6.3 years) consecutively selected for SDR, were assessed before and 6 months after SDR. Parameters of the pendulum test: R2, R1, maximal velocity, and swing time were correlated with clinical assessments for spasticity (modified Ashworth scale, quadriceps reflex) and measurements of gross motor function: the Gross Motor Function Classification System and the Gross Motor Function Measure. The Wartenberg pendulum test was found to be an objective and sensitive method for quantifying spasticity in knee extensor muscles in children as young as 2.5 years old. The method was responsive to changes after SDR. The only correlation with clinical measurements of spasticity was between the R2 ratio and the quadriceps reflex. Swing time was the most reliable and sensitive variable; it showed a weak correlation with measurements for gross motor function.

Preterm birth can affect many neurological functions and is known to affect vision when damage to the visual cortex or optic radiations occurs. However, it is not known whether extreme preterm birth affects visual development, either favorably or unfavorably. Additional time in an extrauterine environment could conceivably allow the acceleration of visual abilities as a result of additional experience. Although recent studies suggest that even apparently healthy preterm infants may suffer some degree of loss of neurological function. In this paper we describe what is known about visual development in preterm infants, and we make the case that additional studies are needed to clarify the impact of preterm birth on vision. Because the visual system now lends itself to quantitative studies of function, it could offer researchers and clinicians a method of detecting subtle effects of preterm birth on neurological development and function.

Executive functions (EFs), seizure-related factors, and school performance were studied in a population-based sample of children with epilepsy (n=117; 71 males, 46 females; mean age 10y 5mo [SD 2y]; range 6y–12y 11mo) and a comparison group (n=124; 71 males, 53 females; mean age 10y 1mo [SD 2y 1mo]; range 6y–12y 11mo). EF, cognitive function, depression, socioeconomic status, and school performance were examined. Patients with epilepsy performed significantly lower than the comparison group on all EF measures except incidental memory. Intellectual dysfunction and depression accounted for 43% of EF problems. All epilepsy syndrome groups (except Rolandic epilepsy) were associated with decreased EF in addition to early epilepsy onset, high seizure frequency, and polytherapy. Patients had more school performance problems than comparison children which were attributed partly to EF difficulties. All aspects of EF were affected in children with epilepsy and all epilepsy syndrome groups, except Rolandic epilepsy, influenced EF negatively. EF problems contributed to patients' school difficulties beyond intellectual dysfunction.

Dilated cardiomyopathy, hypertrophic cardiomyopathy, and cardiac rhythm disturbances are important features of certain neuromuscular disorders in children, adolescents, and young adults. This article summarizes the cardiac features seen in patients with Duchenne muscular dystrophy, Becker muscular dystrophy, myotonic dystrophy, Friedreich's ataxia, and Emery-Dreifuss muscular dystrophy. The optimal management of these cardiac features remains contentious, but increasingly these patients are referred for routine cardiological assessment in the absence of symptoms. This article examines the value of routine screening and drug interventions for cardiac complications in asymptomatic and symptomatic individuals with neuromuscular disorders. We recommend a pragmatic approach, actively looking for cardiac conditions which will benefit from early intervention, but avoiding routine screening for asymptomatic conditions in which there is no evidence of benefit from early intervention.

The goal was to compare children with hemiplegia with those with diplegia within Gross Motor Functional Classification System (GMFCS) levels using multiple validated outcome tools. Specifically, we proposed that children with hemiplegia would have better gait and gross motor function within levels while upper extremity function would be poorer. Data were collected on 422 ambulatory children with cerebral palsy: 261 with diplegia and 161 with hemiplegia, across seven centers. Those with hemiplegia in each level performed significantly and consistently better on gait or lower extremity function and poorer on upper extremity and school function than those with diplegia. In GMFCS Level II, the group with hemiplegia walked faster (p=0.017), scored 6.6 points higher on Dimension E of the Gross Motor Function Measure (p=0.017), 6.7 points lower on Upper Extremity subscale of the Pediatric Outcomes Data Collection Instrument, and 9.1 points lower on WeeFIM self-care (p=0.002). Basing motor prognosis on GMFCS level alone may underestimate lower extremity skills of children with hemiplegia, and overestimate those of children with diplegia.

To study the behavioral style or temperament of 45 boys, aged 47 to 88 months, with full-mutation fragile X syndrome (FXS), 102 parent ratings on the Behavioral Style Questionnaire (McDevitt and Carey 1978) were recorded. These ratings were analysed with a variety of statistical techniques. Considerable variability was evident in temperament profiles; consequently, a characteristic profile was not identified for FXS. Boys with FXS differed significantly from the reference sample on five of nine temperament dimensions. They were more active and less intense, approachable, adaptable, and persistent. No significant differences were found in distractibility, rhythmicity, mood, or sensory threshold. Only 16 of the 45 boys in the sample could be classified as easy, difficult, or slow to warm up. There was no link between severity of developmental disability and temperament ratings. This supports the theory that intelligence and temperament are separate constructs. Scores on temperament dimensions were stable over time. Our results suggest that many of the behaviors observed in boys with FXS may be related to temperament. Consequently, parent counseling and environmental modifications should be considered as first line treatment. The question of whether the behavior problems observed in boys with FXS are innate or whether they result from poorness of fit between child and environment is an important issue that needs further study.

This paper examines the perceptions of mainstreaming among six young people (mean age, 15.5 years; range 13 to 18 years) with physical disabilities, their parents, and seven teaching staff of one ‘designated’ school in the United Kingdom. The study used semistructured interviews to allow the participants to talk about their experiences of mainstreaming in their own words. The results were then analysed and formed the basis for a multiperspective case study. The analysis revealed that the processes involved that exclude the child with a physical disability from mainstream school life are highlighted. They appear to be subtle and also specific to individual children and families.

The effects of congenital, unilateral, focal brain lesions on early linguistic development and hemispheric lateralization for language were investigated longitudinally in 24 preschool children with hemiplegia(14 males, 10 females), 12 with left hemisphere damage (LHD) and 12 with right hemisphere damage (RHD). A comprehensive linguistic assessment was performed at 2 and 3 years of life; cerebral lateralization for language was measured by the Fused Dichotic Words Listening Test. An early left-side specificity for language was indicated by the presence of lexical and grammatical delay in most children with LHD. In the dichotic listening test all 12 children with LHD showed a shift of language lateralization from the left to the right hemisphere. Atypical lateralization coefficients (lambda), i.e. values falling more than two standard deviations from the mean of a normative sample, were associated with a delay in lexical and grammatical development, especially after LHD. In addition, cortical–subcortical–periventricular lesions rather than solely periventricular damage, and larger lesions rather than small, were associated with the most atypical lateralization coefficients, irrespective of lesion side. Results of this study suggest that language and lateralization data are closely related and that reallocation of language functions in alternative regions of the brain has a cost in terms of a slow rate of language acquisition.

Hip adductor spasticity and strength in participants with cerebral palsy (CP) were quantified before and after selective dorsal rhizotomy (SDR) and intensive physical therapy. Twenty-four participants with cerebral palsy (CP group) and 35 non-disabled participants (ND controls) were tested with a dynamometer (CP group: mean age 8 years 5 months, 13 males, 11 females; ND group: mean age 8 years 6 months, 19 males, 16 females). According to the Gross Motor Function Classification System (GMFCS), of the 24 participants with CP, eight were at level I, six were at level II, and 10 participants were at level III. For the spasticity measure, the dynamometer quantified the resistive torque of the hip adductors during passive abduction at 4 speeds. The adductor strength test recorded a maximum concentric contraction. CP group spasticity was significantly reduced following SDR and adductor strength was significantly increased after surgery. Both pre- and postoperative values remained significantly less than the ND controls. Spasticity results agreed with previous studies indicating a reduction. Strength results conflicted with previous literature subjectively reporting a decrease following SDR. However, results agreed with previous objective investigations examining knee and ankle strength, suggesting strength did not decrease following SDR.

We have previously reported that significant hyperopia at 9 months predicts mild deficits on visuocognitive and visuomotor measures between 2 years and 5 years 6 months. Here we compare the motor skills of children who had been hyperopic in infancy (hyperopic group) with those who had been emmetropic (control group), using the Movement Assessment Battery for Children (Movement ABC). Children were tested at 3 years 6 months (hyperopic group: 47 males, 63 females, mean age 3y 7mo, SD1.6mo; control group: 61 males, 70 females, mean age 3y 7mo, SD1.2mo) and at 5 years 6 months (hyperopic group: 43 males, 56 females, mean age 5y 4mo, SD1.7mo; control group: 51 males, 62 females, mean age 5y 3mo, SD1.6mo). The hyperopic group performed significantly worse at both ages, overall and on at least one test from each category of motor skill (manual dexterity, balance, and ball skills). Distributions of scores showed that these differences were not due to poor performance by a minority but to a widespread mild deficit in the hyperopic group. This study also provides the first normative data on the Movement ABC for children below 4 years of age, and shows that it provides a useful measure of motor development at this young age.

Bone-mineral content (BMC; g) and density (BMD; g/cm2) were measured by dual energy X-ray absorptiometry in the proximal femur, femoral neck, and total body of nutritionally adequate children (n=17; 11 girls, six boys; aged 7.6 to 13.8 years) with spastic cerebral palsy (CP). Bone-mineral-free lean tissue (BMFL; g) and fat mass (FM; g) were obtained from total body scans. Chronological and developmental age-based z scores for the children with CP were derived from a pediatric database (n=894). Children with CP had BMC z scores from –1.8 (total body) to –3.2 (femoral neck) SDs below the normative sample. Non-independent ambulators had lower z scores for total body BMD, femoral neck BMD, and BMC than independent ambulators. The BMFL z score of individuals with CP was 2 SDs below that of the reference group and higher in the independent ambulators than in the non-independent ambulators, whereas FM deviated little. These findings suggest that non-nutritional factors, such as ambulation, account for the low BMC, BMD, and BMFL tissue observed in this population.

The aim of this study was to determine the incidence of respiratory depression following the use of diazepam in children presenting with seizures. All children presenting with seizures to a children's A & E department over a period of 9 months were studied prospectively. Respiratory depression was defined as a fall in respiratory rate or oxygen saturation, or apnoea resulting in ventilation or resuscitation with bag-and-mask oxygen. There were 130 patient episodes involving 97 children who received treatment for their seizures before admission and/or in the A & E department. Administration of diazepam resulted in 122 patient episodes. The route of administration was rectal in 91 episodes, intravenous in 12 episodes, and both rectal and intravenous in 19 episodes. Eleven children had respiratory depression in relation to diazepam administration. Eight of these children required ventilation. The overall incidence of respiratory depression following the use of diazepam was 9%. The incidence of respiratory depression following diazepam given intravenously or rectally is high. The use of diazepam as first-line therapy for children with acute seizures needs to be reviewed.

A review of the measures relating to the monitoring of disease progression in Duchenne muscular dystrophy was undertaken as part of the work of the North Star Clinical Network for Paediatric Neuromuscular Disease Management developing a standardized assessment protocol for ambulant children in the UK. This article outlines the process of identifying possible measures. Detailed consideration has been given to key measures of muscle strength and function. As well as the usual assessment of the validity and reliability of the measures, three key characteristics were identified as necessary to the assessment of scales used in health care: (1) the type of scale used; (2) the clinical significance of the attribute being measured; and (3) the mathematical properties of the data provided. Consideration of such aspects in the early stage of a study facilitates the choice of measures, and the analysis and interpretation of data in the longer term.