This prospective study determined metabolite profile in the left and right basal ganglia of children with spastic cerebral palsy (CP) compared with children without disabilities, by using proton magnetic resonance spectroscopy (1HMRS). Twenty-three patients with spastic CP (12 males, 11 females; mean age 11y 9mo [SD 4y 2mo], range 4–17y) were examined. Twenty children had spastic diplegia and three had quadriplegia. Twenty-four normally developing children (13 females, 11 males; mean age 10y 3mo [SD 4y 8mo], range 4–17y) served as a comparison group. The relative concentrations of N-acetylaspartate (NAA), choline (Cho), myo-inositol (mI), and gamma-aminobutyric acid (GABA) were measured relative to creatine (Cr) and different combinations of metabolites within 8cm3 brain voxels. Children with CP showed reduced ratios of NAA:Cr, NAA:Cho, NAA:mI, and GABA:Cr in the basal ganglia relative to a matched comparison group. Patients demonstrated a significant age-dependent increase in NAA:Cr and NAA:Cho in the basal ganglia. No sex-dependent difference was shown in children with CP nor in the comparison group for all tested metabolite ratios. Significant correlation between Apgar score and ratio of mI:Cr in the group with CP was found. None of the tested metabolite ratios were correlated with the severity scale of CP in children with CP. NAA:Cr ratios were negatively correlated with learning disability in patients with CP. Results indicate the association of the metabolite ratios in basal ganglia with learning disability.

This investigation determined the measurement properties of the Pediatric Quality of Life Inventory (PedsQL) 3.0 Cerebral Palsy (CP) Module. PedsQL 4.0 Generic Core Scales and 3.0 CP Module were administered to 245 families. Mean age of the 134 males and 107 females was 8 years 1 month (SD 4y 4mo; range 2–18y). The sample included children with hemiplegia (n=55), diplegia (n=84), and quadriplegia (n=85). Twenty eight children had a Gross Motor Function Classification System classification at Level I, 40 at Level II, 86 at Level III, 43 at Level IV, and 37 at Level V. Reliability was demonstrated for the PedsQL 4.0 (α=0.86 child, 0.89 parent) and CP Module (α=0.79 child, 0.91 parent). The PedsQL 4.0 distinguished between healthy children and children with CP. Construct validity of the CP Module was supported. Sensitivity of the PedsQL was demonstrated among children with different diagnostic categories and gross motor function.

A study of the psychosocial functioning of young adults with a history of learning disability (LD) in childhood is reported. The design was a non-clinic community follow-up investigation of a cohort of children who had received special education, the sample frame for which was a birth-period cohort survey. Participants were 149 young adults (89 males and 60 females derived from a survey of the 33800 children born in the Cambridge Health District between 1967 and 1973) at the stage of transition to adult services (age 18–22y), whose measured IQ scores in childhood were <80, and who had received special education during school years. Most of the young adults were living at home (n=108) and many were in full-time employment (independent employment n=41, sheltered employment n=20), this survey having been carried out in an area of high employment. A strong correlation was found between the child IQ score and subsequent adult Vineland Scale Score. Greater efforts should be made to detect and assess LD and its attendant problems in children in order to plan future care and transition to adulthood, especially for those with more severe disabilities.

Our aim was to study trends in the prevalence of pervasive developmental disorders (PDD) and to quantify their association with morphogenetic anomalies and with perinatal characteristics such as gestational age, birthweight, and hospitalization in a neonatal care unit. Data from a French morbidity register of childhood disabilities with the use of consistent definitions over time within the same geographical area were analyzed. The data of a total of 454 children (312 males, 142 females) with PDD, born between 1980 and 1993 and residing in Isère county, were recorded at the age of 7 years. The overall prevalence of PDD was 22.2 out of every 10000. There was a significant increase, from 14.7 to 30.8 out of every 10 000, during the period of study. Among these children with PDD, morphogenetic anomalies were observed in 12.1% (95% confidence interval [CI] 9.3–15.5), and the hospitalization rate during the neonatal period was 22% (95% CI 17.0–27.5), which is significantly higher than the observed rates in the general population. The increase in the prevalence of PDD, the association with perinatal risk factors, and the high rate of neonatal hospitalization require further studies to investigate the reasons for and mechanisms of these developmental disorders.

Long-term outcomes of the ketogenic diet in the treatment of epilepsy have not previously been reported. A retrospective chart review of children treated with the ketogenic diet for more than 6 years at the Johns Hopkins Hospital was performed. The response was documented at clinic visits and by telephone contacts; laboratory studies were obtained approximately every 6 to 12 months. Satisfaction and tolerability were assessed by means of a brief parental telephone questionnaire. In all, 28 patients (15 males, 13 females), currently aged 7 to 23 years, were identified. The median baseline seizure frequency per week at diet onset was 630 (range 1–1400). Diet duration ranged from 6 to 12 years; 19 remain on the diet currently. After 6 years or more, 24 children experienced a more than 90% decrease in seizures, and 22 parents reported satisfaction with the diet's efficacy. Ten children were at less than the 10th centile for height at diet initiation; this number increased to 23 at the most recent follow-up (p=0.001). Kidney stones occurred in seven children and skeletal fractures in six. After 6 years or more the mean cholesterol level was 201mg/dl, high-density lipoprotein was 54mg/dl, low-density lipoprotein was 129mg/dl, and triglycerides were 97mg/dl. Efficacy and overall tolerability for children are maintained after prolonged use of the ketogenic diet. However, side effects, such as slowed growth, kidney stones, and fractures, should be monitored closely.

The purpose of the study was to determine the prevalence of ‘soft’ motor deficits in school-aged children with either developmental language disorder (DLD), autism (with high IQ [HiAD] or low IQ [LoAD]), or low IQ without autism (LoIQ), and to evaluate the utility of a refined neurological examination to discriminate between these groups. A total of 242 children (74% male), aged 7 or 9 years, were evaluated as part of a longitudinal, multi-institutional study, with a standardized neurological examination that included Denckla's Physical and Neurological Examination for Soft Signs. Most of the scores separated children into two groups defined by nonverbal IQ, with the DLD and HiAD groups performing better than the LoAD and LoIQ groups. Exceptions included motor impersistence and stereotypies, which were more likely in the autistic groups. The neurologists' summary clinical impressions indicated better sensory/motor skills, oromotor skills, and praxis in the HiAD than in the DLD children. Inability/unwillingness to perform tasks was much more frequent in LoAD than LoIQ children.

This paper examines ethnic differences in the attainment of developmental milestones during infancy and possible explanations for observed differences are investigated. Data from the first survey of the Millennium Cohort Study (n=15 994; 8212 males, 7782 females; mean age 9.2mo [SD 0.5]) were examined. We found that Black Caribbean (odds ratio [OR]=0.23, 95% confidence interval [CI]=0.11–0.48), Black African (OR 0.31, 95% CI 0.18–0.55), and Indian (OR 0.55, 95% CI 0.33–0.93) infants were less likely to show delay in the attainment of gross motor milestones compared with White infants after adjustment for a range of explanatory variables. Pakistani and Bangladeshi infants were more likely to have delays in fine motor development (OR 1.69, 95% CI 1.21–2.35 and OR 2.17, 95% CI 1.17–4.02 respectively) and communicative gestures (OR 4.19, 95% CI 1.47–11.94 and OR 7.64, 95% CI 3.96–14.76 respectively), but these differences were explained by socioeconomic factors and markers of cultural tradition. In conclusion, unexplained ethnic differences were seen in the attainment of gross motor milestones, with Indian, Black Caribbean, and Black African children less likely to be delayed (in adjusted models). Increased likelihood of fine motor and communicative gesture delays among Pakistani and Bangladeshi infants, that disappear when socioeconomic factors are taken into account, point to the need to address deprivation among these groups to reduce the likelihood of developmental delay and possible longer term behavioural and cognitive problems and consequent opportunities throughout life.

We present a prospective study at school age of neuropsychiatric and neurodevelopmental outcome of language delay suspected at child health screening around 30 months of age. In a community sample, 25 children (21 males, 4 females) screening positive and 80 children (38 males, 42 females) screening negative for speech and language problems at age 30 months were examined in detail for language disorders at age 6 years. The screen-positive children were then followed for another year and underwent in-depth neuropsychiatric examination by assessors blind to the results of previous testing. Detailed follow-up results at age 7 years were available for 21 children. Thirteen of these 21 children (62%) had a major neuropsychiatric diagnosis (autism, atypical autism, Asperger's syndrome, attention-deficit–hyperactivity disorder [ADHD]), or combinations of these. Two further children (10%) had borderline IQ with no other major diagnosis. We conclude that children in the general population who screen positive for speech and language problems before age 3 years appear to be at very high risk of autism spectrum disorders or ADHD, or both, at 7 years of age. Remaining language problems at age 6 years strongly predict the presence of neuropsychiatric or neurodevelopmental disorders at age 7 years.

In the development of a new diagnostic motor performance test to spare more children from painful muscle biopsy, seven functional items were used to measure muscle strength and muscle endurance in a prospective study on new patients. Over a 2-year period, 22 patients (12 males, 10 females; mean age 8y 1mo [SD 2y 6mo], range 4–11y) were recruited for the study. They had all been referred with suspected myopathy. The motor performance test was administered before muscle biopsy. Validity of the seven items was assessed using logistic regression analysis and receiver operating characteristic (ROC) analysis. Two items were withdrawn from the test because they were not suitable for children aged 4 to 5 years. The five remaining items were: Heels, Circuit, Stairs, Jump, and Gowers. A full logistic regression model including these five items was fitted to the total population of 90 patients suspected of having myopathy (from this study and our previous study) to make the best prediction of whether myopathy was present. The ROC area under the curve of the diagnostic prediction model was 0.92 (95% confidence interval [CI] 0.87–0.98) and 0.89 (95% CI 0.87–0.92) after bootstrap correction. This indicated the high diagnostic power that can be expected for future, similar patients. This non-invasive and child-friendly motor performance test can improve diagnostic procedure and, therefore, spare more children from unnecessary muscle biopsy.

A neurodevelopmental model for understanding the spectrum of developmental disabilities postulates that developmental delay, dissociation, and deviance reflect underlying central nervous system dysfunction. In this study, we determined the occurrence of the dissociated and developmentally deviant behavioral profile of attention-deficit–hyperactivity disorder (ADHD) among children with and without developmental cognitive delays (borderline-to-mild intellectual disability) in a population-based birth cohort (n=5718). Among the 70 children identified to have borderline-to-mild intellectual disability, 30% (n=21; 7 females, 14 males) met research criteria for ADHD, compared to only 6.4% of children without intellectual disability (n=358; 88 females, 270 males). The odds ratio for comorbid ADHD for children with versus without borderline-to-mild intellectual disability was 6.3 (95% confidence interval: 3.7–10.6; p<0.001). These data illustrate that developmental dissociation and/or deviance, as represented by ADHD, are more likely to occur in the context of developmental delay, represented by borderline-to-mild intellectual disability.

The rate of autism spectrum disorders (ASDs) and brain abnormalities was analyzed in 31 individuals (15 males, 16 females; age range 1mo to 31y, mean age 8y 11mo) with CHARGE association, as part of a multidisciplinary study. A meticulous neuropsychiatric examination was performed, including standardized autism diagnostic interviews. Judgement regarding ASDs was impossible in three infants and three patients who were deaf and blind. Five individuals met diagnostic criteria for autism, five for an autistic-like condition, and seven for autistic traits. Brain abnormalities were indicated in almost three-quarters of examined individuals, and midline abnormalities of the forebrain in one-third. Awareness of the coexistence of CHARGE and ASDs is important in habilitation care in CHARGE. Moreover, the results indicate that a subgroup of ASDs may be associated with errors in early embryonic brain development.

We compared the effect of sex and attention-deficit–hyperactivity disorder (ADHD) subtyping in groups of females and males. One hundred and one females with ADHD (mean age 10y 4mo [SD 2y 8mo]; range 5y–18y) were classified according to subtype by Diagnostic and Statistical Manual of Mental Disorders (4th edn) criteria (inattentive [ADHD-I]; combined [ADHD-C]) and balanced by subtype to 101 males (mean age 10y 5mo [SD 2y 9mo]; range 5y 4mo–17y 6mo). All children underwent IQ and reading assessment, and 109 underwent the continuous performance task (Test Of Variables of Attention [TOVA]). Parents completed the Conners' Abbreviated Rating Scale (ABRS), the Child Behavior Checklist (CBCL), learning disability questionnaires, and reported use and efficacy of methylphenidate. Teachers completed the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) rating scale. Sex differences were found only on the CBCL; females were more impaired on the attention (p<0.001) and somatization (p=0.028) subscales but not for IQ, other questionnaires, TOVA scores, methylphenidate treatment, or demographics. Females with ADHD-C, but not males, had significantly higher T-scores than females with ADHD-I on social, attention, delinquent, and aggressive behaviours. Regardless of sex, children with ADHD-C had higher scores on all CBCL subscales (p=0.047), ABRS (p<0.001), and SKAMP (p=0.03) than children with ADHD-I. The results support the supposition that ADHD in females is the same disorder as in males. ADHD subtyping was the important determinant of ADHD core symptoms; females with ADHD were found to have significant risk of psychopathology.

To study the coordination of respiration and swallow rhythms we assessed feeding episodes in 20 preterm infants (gestational age range at birth 26–33wks; postmenstrual age [PMA] range when studied 32–40wks) and 16 term infants studied on days 1 to 4 (PMA range 37–41wks) and at 1 month (PMA range 41–45wks). A pharyngeal pressure transducer documented swallows and a thoracoabdominal strain gauge recorded respiratory efforts. Coefficients of variation (COVs) of breath–breath (BR–BR) and swallow–breath (SW–BR) intervals during swallow runs, percentage of apneic swallows (at least three swallows without interposed breaths), and phase of respiration relative to swallowing efforts were analyzed. Percentage of apneic swallows decreased with increasing PMA (16.6% [SE 4.7] in preterm infants [les ]35wks' PMA; 6.6% [SE 1.6] in preterms >35wks; 1.5% [SE 0.4] in term infants; p<0.001). Term infants had significantly lower BR–BR COV (0.405 [SE 0.016]) than preterm infants (0.641 [SE 0.052] at >35wks' PMA; 0.693 [SE 0.059] at [les ]35wks' PMA). Phase relation between swallowing and respiration stabilized with increasing PMA, with decreased apnea, and a significant increase in percentage of swallows occurring at end-inspiration. These data indicate that unlike the stabilization of suck and suck–swallow rhythms, which occur before about 36 weeks' PMA, improvement in coordination of respiration and swallow begins later. Coordination of swallow–respiration and suck–swallow rhythms may be predictive of feeding, respiratory, and neurodevelopmental abnormalities.

This study aimed at investigating the possible dissociation between visual–object and visual–spatial working memory (WM) in individuals with Williams syndrome (WS) and Down syndrome (DS). Four study groups were included: WS group (10 males, 5 females) with a mean chronological age (CA) of 19 years 8 months (SD 6y 1mo) and a mean mental age (MA)of 6 years 11 months (SD 1y 5mo); WS comparison group (7 males, 8 females) comprised of typically developing children with a mean CA of 6 years 10 months (SD 10mo) and a mean MA of 6 years 11 months (SD 8mo)matched as a group with the participants with WS on the basis of mental age; DS group (11 males, 7 females) with a mean CA of 15 years 10 months (SD 5y 8mo) and a mean MA of 5 years 2 months (SD 8mo); and DS comparison group (10 males, 8 females) with a mean CA of 5 years and 1 month (SD 7mo)and a mean MA of 5 years 2 months (SD 8mo) selected to match the DS group on the basis of mental age. They were all administered tests that explored visual perception (Visual Perception Test – Subtest 4 and Line Orientation tests), visual imagery (imaging the colour of objects and the tail length of well-known animals), spatial imagery (mental rotation of visually presented or verbally evoked objects), and WM for visual–object and visual–spatial information. Individuals with WS exhibited specific difficulties in the visual–spatial, but not the visual–object, WM task. Instead, people with DS showed reduced performance in both tests. However, whereas the observed deficit in individuals with DS persisted when perceptual abilities were taken into account, the deficit in individuals with DS was compensated when their scores were adjusted for performance on perceptual tasks. These results support the hypothesis of a dissociation within the sketch-pad slave system in the WM model and reinforce the view of intellectual disability as a non-unitary condition.

In this investigation of 45 children born to mothers with hypertension in pregnancy, our objective was to examine the role of a fetal risk factor (suboptimal intrauterine growth [SOIUG]) in determining developmental outcome. There were two groups of children: Group 1 (n=26; 10 males, 16 females; mean testing age 56.77 mo [SD 13.03], range 41–82 mo; mean gestational age 32.96 wks [SD 2.24], range 27–38 wks; mean birthweight 1984.42g [SD 563], range 1046–3515g) without, and Group 2 (n=19; 6 males, 13 females; mean testing age 57.63 mo [SD 14.86], range 40–84 mo; mean gestational age 34.21 wks [SD 2.10], range 29–39 wks, mean birthweight 1572g [SD 365], range 855–2690g) with SOIUG. We found that SOIUG was associated with a significant reduction in cognitive and motor skills (p<0.05). Visuospatial (p<0.01) as well as motor skills (p<0.001) were linearly associated with the extent of intrauterine growth deficit when the latter was treated as a continuous variable. To conclude, an increase in intrauterine growth deficit is accompanied by a proportionate decline in quality of developmental outcome in children born to mothers with hypertension in pregnancy.

Relationships between early motor development and language and reading skills were studied in 154 children, of whom 75 had familial risk of dyslexia (37 females, 38 males; at-risk group) and 79 constituted a control group (32 females, 47 males). Motor development was assessed by a structured parental questionnaire during the child's first year of life. Vocabulary and inflectional morphology skills were used as early indicators of language skills at 3 years 6 months and 5 years or 5 years 6 months of age, and reading speed was used as a later indicator of reading skills at 7 years of age. The same subgroups as in our earlier study (in which the cluster analysis was described) were used in this study. The three subgroups of the control group were ‘fast motor development’, ‘slow fine motor development’, and ‘slow gross motor development’, and the two subgroups of the at-risk group were ‘slow motor development’ and ‘fast motor development’. A significant difference was found between the development of expressive language skills. Children with familial risk of dyslexia and slow motor development had a smaller vocabulary with poorer inflectional skills than the other children. They were also slower in their reading speed at the end of the first grade at the age of 7 years. Two different associations are discussed, namely the connection between early motor development and language development, and the connection between early motor development and reading speed.

The aim of this retrospective study was to describe signs, symptoms, and clinical outcomes of individuals undergoing intrathecal baclofen (ITB) therapy who experienced pump-related Gram-negative infections including meningitis. Participants included 12 individuals (nine males, three females) aged 10 to 32 years (mean 17y 9mo), nine of whom had quadriplegic CP. A total of 571 baclofen pump surgeries were performed with 45 total infections. Of the 45 infections, 12 were by Gram-negative organisms, two resulting in meningitis. Ten of 12 Gram-negative infections (21 site encounters) occurred within 60 days of surgery. Eleven of 12 pumps were explanted. By site encounters, Pseudomonas aeruginosa accounted for eight Gram-negative infections, Escherichia coli for five, Proteus for three, Enterobacter cloacae for two, and Klebsiella, Enterobacter aerogenes, and Enterobacter vulnaris for one each. Two individuals with Gram-negative meningitis were admitted 72 to 96 hours after hospital discharge following pump replacement. Both patients had rapid deterioration requiring transfer to the pediatric intensive care unit, and developed coagulopathy and decrease in responsiveness. Both have improved and have elected not to replace the ITB pump. In Gram-negative infections in ITB therapy, the progression of signs and symptoms can be swift and devastating. Identification of the infectious agent in such cases is imperative; these infections can quickly become life threatening.

We previously suggested that antenatal pestivirus infection might play a role in the pathogenesis of perinatal brain white matter damage (WMD) in preterm infants. We have now examined 22 brains from stillborns and deceased newborns (both preterm and term) for the presence of bovine virus diarrhoea virus (BVDV) antigen. The brains of five females and five males with WMD (median gestational age 36.5wks), and nine female and three male controls (median gestational age 36.5wks) were used in the study. No BVDV antigen was detected in any of the 22 brains. We conclude that brain infection with BVDV is unlikely to play a role in WMD pathogenesis among preterm or term newborns. Further research is needed to test the hypothesis that intrauterine exposure to pestivirus antigen elicits a fetal inflammatory response which then contributes to WMD.

Palatal tremor (PT) is a rhythmic movement of the soft palate that often causes an ear click. PT can be symptomatic (SPT) or essential (EPT). The symptomatic form usually occurs in adults and the essential form mainly occurs in children. Several different treatments for EPT in children appear in the literature with variable reported efficacy. This report details four paediatric patients with EPT (three males, one female; mean age 6y 4mo [SD 6mo]; age at onset 6–7y) treated with piracetam (2-oxo-1-pyrrolidine acetamide). Piracetam was used to treat EPT because of its antimyoclonic properties. All children showed a good response to doses of 100 to 300mg/kg/day. EPT relapsed on withdrawal of piracetam and remitted on reintroduction. Piracetam's effect on EPT was sustained. It is concluded that piracetam is an effective drug for the treatment of EPT in children.

According to previous case reports, some congenital abnormalities (CAs) of the brain, such as microcephaly, are a result of intrauterine herpes simplex virus infection. A population-based case–control study was conducted to determine the risk of neural tube defects (NTDs) after maternal herpes labialis infection during pregnancy. Data were taken from the Hungarian Case–Control Surveillance of Congenital Abnormalities from 1980 to 1996, which included 1202 children with NTDs and 21641 comparison children with CAs other than NTDs. The adjusted relative risks (odds ratio [OR]) for NTDs associated with maternal herpes labialis in the first trimester of pregnancy was OR 1.19 (95% confidence interval [CI] 0.68–2.06), and in the entire pregnancy was OR 0.94 (95% CI 0.61–1.44). Self-reported maternal herpes labialis during pregnancy was not associated with a substantially increased risk of NTDs in infants.