The purpose of the present study was to describe in greater anatomical detail the changes in brain structure that occur during maturation between childhood and adolescence. High-resolution MRI, tissue classification, and anatomical segmentation of cortical and subcortical regions were used in a sample of 35 normally developing children and adolescents between 7 and 16 years of age (mean age 11 years; 20 males, 15 females). Each cortical and subcortical measure was examined for age and sex effects on raw volumes and on the measures as proportions of total supratentorial cranial volume. Results indicate age-related increases in total supratentorial cranial volume and raw and proportional increases in total cerebral white matter. Gray-matter volume reductions were only observed once variance in total brain size was proportionally controlled. The change in total cerebral white-matter proportion was significantly greater than the change in total cerebral gray-matter proportion over this age range, suggesting that the relative gray-matter reduction is probably due to significant increases in white matter. Total raw cerebral CSF volume increases were also observed. Within the cerebrum, regional patterns varied depending on the tissue (or CSF) assessed. Only frontal and parietal cortices showed changes in gray matter, white matter, and CSF measures. Once the approximately 7% larger brain volume in males was controlled, only mesial temporal cortex, caudate, thalamus, and basomesial diencephalic structures showed sex effects with the females having greater relative volumes in these regions than the males. Overall, these results are consistent with earlier reports and describe in greater detail the regional pattern of age-related differences in gray and white matter in normally developing children and adolescents.

We conducted a double-blind placebo study to investigate the claim that hyperbaric oxygen treatment (HBO2) improves the cognitive status of children with cerebral palsy (CP). Of 111 children diagnosed with CP (aged 4 to 12 years), only 75 were suitable for neuropsychological testing, assessing attention, working memory, processing speed, and psychosocial functioning. The children received 40 sessions of HBO2 or sham treatment over a 2-month period. Children in the active treatment group were exposed for 1 hour to 100% oxygen at 1.75 atmospheres absolute (ATA), whereas those in the sham group received only air at 1.3 ATA. Children in both groups showed better self-control and significant improvements in auditory attention and visual working memory compared with the baseline. However, no statistical difference was found between the two treatments. Furthermore, the sham group improved significantly on eight dimensions of the Conners' Parent Rating Scale, whereas the active treatment group improved only on one dimension. Most of these positive changes persisted for 3 months. No improvements were observed in either group for verbal span, visual attention, or processing speed.

Understanding patterns of gyrification in neurogenetic disorders helps to uncover the neurodevelopmental etiology underlying behavioral phenotypes. This is particularly true in Williams syndrome (WS), a condition caused by de novo deletion of approximately 1 to 2Mb in the 7q11.23 region. Individuals with WS characteristically possess an unusual dissociation between deficits in visual–spatial ability and relative preservations in language, music, and social drive. A preliminary postmortem study reported anomalous gyri and sulci in individuals with WS. The present study examined gyrification patterns in 17 participants with WS (10 females, 7 males; mean age 28 years 11 months, SD 8 years 6 months) and 17 age- and sex-matched typically developing control participants (mean age 29 years 1 month, SD 8 years 1 month) using new automated techniques in MRI. Significantly increased cortical gyrification was found globally with abnormalities being more marked in the right parietal (p=0.0227), right occipital (p=0.0249), and left frontal (p=0.0086) regions. These results suggest that one or more genes in the 7q11.23 region are involved during the critical period when cortical folding occurs, and may be related to the hypothesized dorsal/ventral dissociation in this condition.

The relation between spasticity and strength in individuals with cerebral palsy (CP) has not been extensively researched. Knee and ankle spasticity and strength were quantified in a retrospective analysis of 60 individuals with spastic diplegic CP (mean age 12 years, range 3 to 38) and a group of 50 individuals without disabilities (WD group; mean age 12 years, range 4 to 36). Spasticity was measured using a KinCom dynamometer that stretched the passive knee flexors or ankle plantarflexors at different speeds and recorded the amount of resistive torques. For the strength tests, the participant performed a maximum contraction of the knee flexors/extensors and ankle plantarflexors/dorsiflexors throughout their range of motion at a speed of 10°/s on the dynamometer. Pearson's correlation coefficient was used to determine if a relation existed between spasticity and strength within the same muscle group and in opposing muscle groups at the knee and ankle joints. A t-test was performed to determine if greater spasticity and less strength existed at the ankles compared with the knees in those with CP. Results show that there was no relation between spasticity and strength either within the same muscle group or at opposing muscle groups at the knee and ankle joints in persons with CP. Individuals with spastic diplegic CP were more involved (greater spasticity, less strength) distally at the ankles compared with the knees. The findings conflict with the literature, which contains several assumptions, one of which is that a spastic muscle is a strong muscle and that spasticity causes weakness in the opposing muscle group. We found no relation between spasticity and strength in individuals with CP. Our findings support the literature, which states that individuals with spastic diplegic CP are more involved distally compared with proximally in the lower extremities.

Ultrasound images were obtained of the medial gastrocnemius at different ankle joint positions with the knee extended. Fascicle length and deep fascicle angle were measured in five normally developing adults (mean age 33 years, age range 24 to 36 years) and in five normally developing children (mean age 7.8 years, age range 7 to 11 years), and in seven children with spastic diplegia (mean age 10 years, age range 6 to 13 years). These architectural variables were similar in the groups of normally developing adults and children. Importantly, no statistical difference could be found between the normally developing children and those with diplegia for fascicle length. Deep fascicle angles were reduced significantly in the clinical group at a particular ankle joint angle but not at the resting angles. The difference in deep fascicle angles is explained as a function of resting muscle length and is not attributed any clinical importance. Our results do not explain the structural origin of muscle contracture explicitly. However, they do indicate that most of the fixed shortness in the medial gastrocnemii of ambulant children with spastic diplegia is not due to reduced muscle fibre length. We suggest that muscle contracture may be better explained in terms of shortness of the aponeuroses of pennate muscles, such as the medial gastrocnemius, through reduced muscle fibre diameter.

One hundred and twenty-nine children, 2 to 8 years old, with idiopathic autistic spectrum disorder diagnosed by standard instruments (Childhood Austim Ratings Scale and Autism Diagnostic Observation Schedule) were treated with fluoxetine (0.15 to 0.5mg/kg) for 5 to 76 months (mean 32 to 36 months), with discontinuation trials. Response criteria are described. Family histories were obtained using the family history method in repeated interviews. Fluoxetine response, family history of major affective disorder, and unusual intellectual achievement, pretreatment language, and hyperlexia were used to define a coherent subgroup of autistic spectrum disorder. Statistical analyses were post hoc. Of the children, 22 (17%) had an excellent response, 67 (52%) good, and 40 (31%) fair/poor. Treatment age did not correlate with response. Fluoxetine response correlated robustly with familial major affective disorder and unusual intellectual achievement, and with hyperlexia in the child. Family history of bipolar disorder and of unusual intellectual achievement correlated strongly. Five children developed bipolar disorder during follow-up. Fluoxetine response, family history of major affective disorder (especially bipolar), unusual achievement, and hyperlexia in the children appear to define a homogeneous autistic subgroup. Bipolar disorder, unusual intellectual achievement, and autistic spectrum disorders cluster strongly in families and may share genetic determinants.

This study was designed to test the hypothesis that systemic hypotension during the first postnatal week increases the risk of ultrasonographic echolucency in the white matter of preterm infants ([les ]28 weeks' gestation) while adjusting for confounders. From a study base of 1607 very-low-birthweight neonates (500 to 1500g), a subsample of 243 preterm infants (122 females; [les ]28 weeks' gestation) was selected for echolucency and data collection prospectively for the entire first postnatal week. Data analyses were performed separately for the first 24 hours of life, for the interval from the end of the first 24 hours to the end of the fourth postnatal day, and for days 5, 6, and 7. Systemic hypotension was defined as the mean arterial blood pressure in the lowest quartile for the infant's week of gestational age. Protocol cranial ultrasounds were those obtained closest to days 1, 7, and 21. A committee of sonologists classified the infants as having either echolucency (echolucency group) or not (control group). Systemic hypotension during the first week of life appeared to be associated with echolucency in univariable analyses but the association did not persist after adjustment for potential confounders. Detailed summaries of 13 previous studies, the majority of which did not show an association between systemic hypotension and white-matter damage, are presented. In sum, these results do not support the hypothesis that systemic hypotension contributes to echolucency among preterm infants.

The objective of this study was to develop a method to use digital signal processing (DSP) technology to describe quantitatively and statistically swallow-associated sounds in preterm infants and to use this method to analyze changes as infants mature. Twelve recordings of accelerometric and physiological data on bottle-feeding preterm infants between 32 and 39 weeks' postmenstrual age (PMA) were analyzed. Cervical auscultation was performed using an accelerometer attached over the larynx. Acoustic data were recorded and graphically displayed using DSP software. Initial discrete sounds (IDSs) were identified and used to construct an average waveform from which a ‘variance index’ (VI) was calculated for each infant. The shape of the IDS waveforms became progressively more uniform with advancing PMA, as indicated by a significant inverse correlation between VI and PMA (r=0.739; p=0.006). DSP technology facilitated the development of a new method to quantitatively analyze feeding in preterm infants. This method provides an elegant tool to track maturation of infant feeding and assessing feeding readiness. This technique makes the interpretation of cervical auscultation data less subjective by replacing the verbal description of the sounds of feeding with quantitative numeric values. It is anticipated that this method can be automated to facilitate further the analysis of cervical accelerometry data.

Several studies have tried to establish the prevalence of visual–perceptual impairment in children with physical disabilities, particularly in those with cerebral palsy (CP), but failed to take into account the selective impairment of non-verbal intelligence that is frequent in these children. This has resulted in the confounding of visual–perceptual and non-verbal intelligence impairment. In the present study we aimed to determine how widespread visual–perceptual impairment is in children with CP by evaluating perceptual ability together with the performance level on non-verbal intelligence subtests. All children (n=96; 44 females, 52 males) who attended an institute for children with physical disabilities were included (age ranged from 4 years 11 months to 21 years 5 months) who had a non-verbal mental age between 3 and 7 years; Total IQ was <85 in 91% of participants. They were given a grating acuity task and the visual–perceptual battery L94, comprising six visual object recognition and two visuoconstruction tasks. Relative to their performance level on non-verbal intelligence subtests, 37.5% of the children were impaired on at least one task, and 18.7% on two or more tasks. No child was impaired on the visuoconstruction tasks. Visual–perceptual impairment was highest among six children with brain malformation (67%), followed by spastic CP (40%), and brain damage acquired after the first year of life (38%). There was no difference in visual–perceptual impairment between the subtypes of spastic CP. Results are not secondary to visual acuity deficits, as only one L94 task was significantly correlated with acuity impairment. We conclude that visual–perceptual impairment is frequent in children with physical disabilities, and not restricted to children with CP of hypoxic–ischaemic origin.

The aim of the study was to determine whether learning and memory are compromised in school children with recently diagnosed idiopathic and/or cryptogenic epilepsy and to study relationships between learning and memory and psychosocial and epilepsy variables. Word span and learning of locations were assessed within 48 hours after diagnosis of epilepsy and three and 12 months later, in 69 school children with epilepsy (aged 9.1 years, SD 2.7; 33 males, 36 females) and 66 classmates. Results showed that patients and controls performed similarly in registration, recall, and retention. Patients recalled slightly less than controls when probed under conditions of increased demand on working memory. Maladaptive reactions of parents and children to the onset of epilepsy and not reaching 6-months of seizure remission contributed to poor performance. Individually, those patients who required special assistance at school, under-performed occasionally in one or the other component of memory. Although the proportion of under-performers was stable over time, the children composing the group did change. It was concluded that school children with new onset idiopathic or cryptogenic epilepsy are inordinately vulnerable when processing memory tasks. The vulnerability is neither persistent nor memory-specific.

This study is a comparative analysis and meta-analysis of three randomized clinical trials. Children with spastic diplegia received either ‘selective’ dorsal rhizotomy (SDR) plus physiotherapy (SDR+PT) or PT without SDR (PT-only). Common outcome measures were used for spasticity (Ashworth scale) and function (Gross Motor Function Measure [GMFM]). Baseline and 9- to 12-month outcome data were pooled (n=90). At baseline, 82 children were under 8 years old and 65 had Gross Motor Function Classification System level II or III disability. Pooled Ashworth data analysis confirmed a reduction of spasticity with SDR+PT (mean change score difference –1.2; Wilcoxon p<0.001). Pooled GMFM data revealed greater functional improvement with SDR+PT (difference in change score +4.0, p=0.008). Multivariate analysis in the SDR+PT group revealed a direct relationship between percentage of dorsal root tissue transected and functional improvement. SDR+PT is efficacious in reducing spasticity in children with spastic diplegia and has a small positive effect on gross motor function.

This study aimed to evaluate functional effects of Bobath therapy in children with cerebral palsy (CP). Fifteen children with a diagnosis of CP were recruited (9 males, 6 females; mean age 7 years 4 months, SD 2 years 8 months; age range 2 to 12 years). Types of motor disorder were as follows: spastic quadriplegia (n=9); spastic diplegia (n=4); athetoid quadriplegia (n=1), and ataxia (n=1). Participants were distributed across the following Gross Motor Function Classification levels: level I, n=1; level II, n=4; level III, n=5; level IV, n=4; and level V, n=1. Children awaiting orthopaedic intervention were excluded. A repeated measures design was used with participants tested with the Gross Motor Function Measure (GMFM) and Pediatric Evaluation of Disability Inventory (PEDI) at 6-weekly intervals (baseline, before and after Bobath therapy, and follow-up). As the data were of ordinal type, non-parametric statistics were used, i.e. Wilcoxon's test. Participants showed a significant improvement in scores in the following areas following Bobath therapy compared with the periods before and after Bobath therapy: GMFM total score (p=0.009); GMFM goal total (p=0.001); PEDI self care skills (p=0.036); and PEDI caregiver assistance total score (p=0.012). This demonstrates that in this population, gains were made in motor function and self care following a course of Bobath therapy.

The aims of this study were to determine the types of chronic-stage EEG abnormalities that exist and to clarify their relation to neurodevelopmental outcome in preterm infants. We evaluated 183 preterm infants with gestational ages of less than 33 weeks (mean age 29.2 weeks) and weighing less than 2000g (mean weight 1275g). The first EEG was performed within 72 hours of life; thereafter, EEG was performed once every 1 to 4 weeks until the infant reached a post-conceptional age of 40 to 42 weeks. Two kinds of EEG abnormalities, acute- and chronic-stage abnormalities, were evaluated and we assessed mainly the latter. Chronic-stage EEG abnormalities were divided into two patterns: disorganized and dysmature. Periventricular leukomalacia (PVL) and intraventricular haemorrhage (IVH) were diagnosed on the basis of ultrasound findings. Psychomotor development was examined every 3 months after discharge until at least 18 months of the infants' corrected age. Disorganized and dysmature patterns were observed in 52 and 28 infants respectively. Among the 52 infants with disorganized patterns, PVL was observed in 31 and IVH in seven infants. Thirty-nine infants had cerebral palsy (CP). Twenty-six achieved normal cognitive development. Of the 28 infants with dysmature patterns, PVL was seen in one and IVH in 11 infants. CP was seen in five infants. Only eight infants achieved normal cognitive development. Gestational age and birthweight were significantly lower in infants with dysmature patterns than in those with disorganized ones. Results indicate that types of chronic-stage EEG abnormalities are related to types of neurological sequelae and are useful for assessing the mode of brain injury in preterm infants.

In a population-based follow-up study (the Stockholm Neonatal Project), 182 children with a birthweight of 1500g or less (very-low birthweight: VLBW) and a control group of 125 children born healthy at term were examined with the Wechsler Preschool and Primary Scale of Intelligence–Revised (WPPSI–R) and a neuropsychological test battery (Nepsy) at 5½ years of age. The WPPSI–R results of the VLBW children fell well within the normal range: WPPSI–R full-scale IQ 95.7, verbal subscale IQ 99.9, and performance subscale IQ 91.6. Nevertheless, the control group had significantly better results than the VLBW group which could be attributed to the greater variability of the VLBW group, with a larger proportion falling in the lower area of the IQ distribution, especially on the performance subscale. Likewise, the control group displayed better executive function (Nepsy). Paternal education was equal in the two groups and was the single most important predictor of IQ, possibly acting as a protective factor. The need for glasses or lenses was inversely associated with all IQ measures and severe retinopathy of prematurity (ROP) had the most negative impact on full-scale and performance IQ. These two IQ measures were also negatively associated with intrauterine growth retardation late in pregnancy. We conclude that VLBW children, in the absence of these identified risk factors, have normal cognitive development.

This study was undertaken to test the hypothesis that children with autistic spectrum disorders often have macrocephalus, and that those without comorbid learning disability are most frequently affected. Fifty consecutive children with Asperger syndrome (45 males, five females; mean age 9 years, range 1 year 6 months to 16 years) without indications of underlying medical disorders were matched for birth year and sex with 50 children (45 males, five females; mean age 6 years 4 months, range 1 year 4 months to 13 years 11 months) who met criteria for autistic disorder (a lower-functioning disorder within the autism spectrum) and with 50 children (45 males, five females; mean age 8 years 4 months, range 1 year 6 months to 15 years 5 months) who met criteria for attention-deficit–hyperactivity disorder. Birth and neuropsychiatric follow-up records were examined and data relating to occipitofrontal circumference, weight, and height were detailed. The group with Asperger syndrome included a subset of individuals with macrocephalus recorded both at birth and at follow-up after the first year of life. Another subgroup developed macrocephalus during early childhood. Autistic spectrum disorders include a subgroup with macrocephalus characterized by a relatively high level of functioning and a clinical presentation most often consistent with a diagnosis of Asperger syndrome.

The purpose of this study was to determine the effect clinically prescribed ankle–foot orthoses (AFOs) have on the temporal-spatial parameters of gait, as compared with barefoot walking in children with cerebral palsy. A retrospective chart review of data collected between 1995 and 1999 in our motion analysis laboratory was performed. A retrospective chart review of 700 patients revealed 115 patients (mean age 9 years) who had a primary diagnosis of CP (diplegia n=97, hemiplegia n=18). All were wearing clinically prescribed hinged or solid AFOs at the time of undergoing a three dimensional gait analysis. In line with our standard clinical practice, data for both conditions (braced and barefoot walking) were collected the same day by the same examiner. Statistical analyses indicated the temporal and spatial gait parameters of velocity, stride length, step length, and single limb stance were significantly increased (p<0.001) with the use of AFOs versus barefoot walking. Cadence was the only parameter found to not be statistically different.

Periventricular flaring (PVF) or periventricular leukomalacia (PVL) was diagnosed by brain ultrasound during the neonatal period in 44 infants (34 males, 10 females; mean gestational age 31 weeks 2 days, SD 2 weeks 1 day) admitted between 1995 and 1997. The infants were divided into three groups according to the severity of their condition. At 0, 3, and 6 months' corrected age an age-adequate neurological examination with special emphasis on the relation between active and passive muscle power was performed and symmetry between right and left sides was assessed. Results for the whole body, as well as for the shoulders, trunk, and legs were classified as optimal, suspect, or abnormal. Motor outcome at 18 months' corrected age was graded in the same way. An overall optimal muscle power regulation was found in one infant at 0, two at 3, and one at 6 months. Suspect outcome was found at all ages in the three groups. At 0 months muscle power regulation did not differ between the three groups. At 3 and 6 months overall poor muscle power, primarily caused by poor muscle power regulation in the shoulders and trunk, was found in infants with PVL grades III or IV. At 18 months' corrected age 24 infants showed no neurological impairment, eight infants had minor impairment, and 12 infants had severe impairment, including all 10 infants categorized as having PVL grades III or IV. The best predictors of impairment at 18 months were the combined results of muscle power in the shoulders and trunk at 3 months with those of the shoulders at 6 months.

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.

Poor nutritional status and growth failure are common in children with cerebral palsy (CP). The aim of this study was to assess, within a subgroup of a large and clearly defined population of children with disabilities, the impact of feeding difficulties on (1) the quality (micronutrient intake) and quantity (macronutrient intake) of their diet and (2) their growth. One hundred children with disabilities (40 females, 60 males; mean age 9 years, SD 2 years 5 months; range 4 years 6 months to 13 years 7 months) underwent a detailed dietetic analysis and a comprehensive anthropometric assessment. Diagnostic categories of disability were: CP (n=90); global developmental delay (n=3); Marfan syndrome (n=1); intractable epilepsy (n=2); agenesis of the corpus callosum (n=2); methyl malonic aciduria (n=1); and congenital rubella (n=1). Neurological impairment was classified according to difficulty with mobility which was graded as mild (little or no difficulty walking), moderate (difficulty walking but does not need aids or a helper), and severe (needs aids and/or a helper or cannot walk). Results confirmed the significant impact of neurological impairment in children on body growth and nutritional status becoming worse in those with a greater degree of motor impairment. The major nutritional deficit was in energy intake, with only one fifth reportedly regularly achieving over 100% estimated average requirement (EAR), whilst micronutrient intake was less markedly impaired and protein intake was normal in this group (96% above EAR). Many children with neurological impairment would benefit from individual nutritional assessment and management as part of their overall care.

The purpose of this study was to identify group differences in children with attention-deficit–hyperactivity disorder and motor dysfunction (ADHD-MD) and ADHD only, and to evaluate the medication responsiveness of ADHD-MD. Sixty-three children (49 males and 14 females; mean age 9 years 10 months, SD 2 years 10 months) underwent a triple blind, placebo-controlled crossover study evaluating two dose levels of methylphenidate (0.3 mg/kg and 0.05 mg/kg, twice daily) and placebo. Forty-nine trials were completed. Nineteen were children with ADHD-MD, 44 had ADHD only. Behavior and functioning were assessed at home and at school. Treatment effects were assessed using the Abbreviated Symptom Questionnaire for Parents and Teachers. Children with ADHD-MD were more likely to have severe ADHD-combined type and other neurodevelopmental and behavioral problems. Both groups of children had a linear dose response to medication (placebo, low, high) and there was no evidence of a group by dose interaction or an overall group effect at home or school. The lack of group effect suggests that these children responded to medication like the other subgroups.