The study aimed to identify significant antenatal risk factors for cerebral palsy (CP) among extremely preterm infants with a matched case-control design. Infants born between 1989 and 1996 at 24 to 27 weeks' gestation who survived to hospital discharge were evaluated: 30 with a proven diagnosis of CP at 2 years corrected for prematurity and 120 control children matched for gestational age without CP. Information on maternal obstetric risk factors and medication was obtained. Matched analyses were performed and odds ratios (OR) and 95% confidence intervals (CI) were calculated. An antenatal diagnosis of intrauterine growth restriction was associated with an increased risk of CP (OR 6.6; 95% CI 1.8 to 25.2), while maternal administration of corticosteroids was associated with a reduced risk of CP (OR 0.4; 95% CI 0.1 to 0.98). A high rate of placental histopathology was achieved but no relation between clinical or histological chorioamnionitis or funisitis and CP was demonstrated. Maternal preeclampsia was not associated with a statistically significant reduction in the risk of CP. It is concluded that a reduced risk of CP in extremely preterm infants is associated with the antenatal use of corticosteroids.

Timed performance in specific motor tasks is an essential component of a neurological examination applied to children with motor dysfunctions. This article provides centile curves describing normal developmental course and interindividual variation of timed performances of non-disabled children from 5 to 18 years. In a cross-sectional study (n=662) the following motor tasks were investigated: repetitive finger movements, hand and foot movements, alternating hand and foot movements, sequential finger movements, pegboard, and dynamic and static balance. Intraobserver, interobserver, and test–retest reliability for timed measurements were moderate to high. Timed performances improved throughout the entire prepubertal period, but differed among various motor tasks with respect to increase in speed and when the ‘adolescent plateau’ was reached. Centile curves of timed performance displayed large interindividual variation for all motor tasks. At no age were clinically relevant sex differences noted, nor did socioeconomic status significantly correlate with timed performance. Our results demonstrate that timed motor performances between 5 and 18 years are characterized by a long-lasting developmental change and a large interindividual variation. Therefore, a well standardized test instrument, and age-specific standards for motor performances are necessary preconditions for a reliable assessment of motor competence in school-age children.

In this study of 118 children (median age 5.1 years; range 6 months to 17 years) with ischaemic stroke or transient ischaemic attack (TIA), 22 children (19%) were homozygous for the thermolabile variant of the methylenetetrahydrofolate reductase allele (t-MTHFR), compared with nine of 78 (12%) of a reference population (p=0.18, OR 1.76, 95% CI 0.76 to 4.04). Of those with cerebrovascular disease (CVD), 17 of 84 were homozygous for the t-MTHFR allele (p=0.13 compared with the reference population (OR 1.95, 95% CI 0.81 to 4.65). There was a significant (p<0.025) increment of plasma total homocysteine concentration in homozygotes for the t-MTHFR allele compared with heterozygotes, negatives for the t-MTHFR allele, and control children with no history of stroke. In four of 12 homozygotes for the t-MTHFR allele, plasma homocysteine levels were raised, compared with three of 38 of those who were negative or heterozygous (p=0.047; OR 5.8, 95% CI 1.1 to 31.2). Homozygotes for the t-MTHFR allele were significantly more likely to have a recurrent event than those who were negative or heterozygous (Cox regression p=0.031, hazard ratio 2.18, 95% CI 1.08 to 4.42). These data suggest that homozygosity for the t-MTHFR allele is associated with raised homocysteine levels in children and is a risk factor for primary and secondary stroke and TIA.

Children with cerebral palsy (CP) have often been described as passive communicators. Their familiar conversation partners tend to direct and control interaction. Such conversation patterns may have various precursors: children's motor impairment, their intelligibility difficulties, and/ or their level of cognitive development. To test the comparative influence of these factors, measures of motor function, speech, communication, cognitive and language skills were applied in 40 children (18 males, 22 females) with CP who were aged from 2 years 8 months to 10 years. These variables were correlated with measures relating to interaction patterns to investigate whether individual features predicted communication style. In this group, poor speech intelligibility was the main predictor of restrictive communication patterns, such as fewer child-initiated conversation exchanges, more simple child communicative acts such as yes/no answers and acknowledgements of the other partner's messages. Results support the provision of therapy to increase children's intelligibility, whether spoken or augmented, such as the introduction of communication aids and training programmes for parents.

As the largest interhemispheric commissure in the brain, the corpus callosum is of particular interest in disorders that may preferentially affect white matter development such as Williams syndrome (WS). Individuals with WS possess a remarkable array of neurobehavioral peaks and valleys, including deficits in visuospatial ability, mathematics, and attention, but with relative preservation of language and affect. Our study measured the corpus callosum and its primary subdivisions using high-resolution MRI in 20 individuals with WS (13 females and seven males; mean age 28.5, SD 8.3 years; range 19 to 44 years) and 20 age- and sex-matched control participants (mean age 28.5, SD 8.2 years; range 19 to 48 years). Total midsagittal corpus callosum area was reduced (F=4.5, p=0.04, df=36) in the WS population. The area of the splenium (F=12.4, p=0.001, df=36) and isthmus (F=9.4, p=0.004, df=36) were disproportionately reduced in WS beyond the absolute reduction of the entire corpus callosum. These reductions are in concordance with other neuroanatomical findings of decreased parietooccipital volumes as well as the observed visuospatial problems associated with WS.

The purpose of this study was to examine the effectiveness of the hinged ankle–foot orthosis (HAFO), posterior leaf spring (PLS), and solid ankle–foot orthosis (SAFO), in preventing contracture, improving efficiency of gait, and enhancing performance of functional motor skills in 30 children (21 male, 9 female; mean age 9 years 4 months; age range 4 to 18 years,) with spastic hemiplegia. Following a 3-month baseline period of no ankle–foot orthosis (AFO) use, each AFO was worn for 3 months after which ankle range of motion, gait analysis, energy consumption, and functional motor skills were assessed. The HAFO and PLS increased passive ankle dorsiflexion and normalization of ankle rocker function during gait. Normalization of knee motion in stance was dependent upon the knee abnormality present and AFO configuration. The HAFO was the most effective in controlling knee hyperextension in stance, while PLS was the most effective in promoting knee extension in children with >10° knee flexion in stance. Energy efficiency was improved in 21 of the children, with 13 of these children demonstrating the greatest improvement in HAFO and PLS. Improvements in functional mobility were greatest in the HAFO and PLS.

The aims of this study were to determine the relation between gait kinematics (center of mass excursions) and measures of oxygen consumption and oxygen cost. Fourteen independent ambulating children with myelomeningocele (nine females, five males; mean age 8 years 7 months) and thirteen children with no history of neuromuscular disorder were evaluated. At their comfortable walking speed all patients exhibited oxygen cost and oxygen consumption values that exceeded the normal level by more than 1 SD. Pelvic obliquity demonstrated the strongest relation with oxygen cost which suggests that ultimately hip abductor strength may play a key role in energy demands during gait. Despite the exaggerated pelvic kinematics, vertical and horizontal center of mass excursions of the trunk and whole-body during the gait cycle were not significantly greater than normal (p>0.05). Decreased self-selected walking velocity at which many of these children consider comfortable and stable may be predicated on an optimal center of mass movement that approximates the magnitude observed in normal gait. The slower walking velocity decreases walking efficiency. Conversely, the increased center of mass movement that would accompany a faster gait would probably impose intolerable oxygen consumption levels. Strengthening programs that focus on the gluteus medius and maximus to decrease compensatory trunk and pelvic motions, allowing the patients to adopt a faster gait without exacerbating kinematic and center of mass motions and which enabled more efficient walking hold promise for these patients.

Associated movements (AMs) are the most frequently assessed parameters of movement quality in children with motor dysfunctions. In this article, reference curves of duration and degree of AMs from 5 to 18 years are provided. In a cross-sectional study of non-disabled children (n=662) duration and degree of AMs were estimated at six specific ages while children performed repetitive finger, hand, and foot movements, alternating hand and foot movements, diadochokinesis, sequential finger movements, pegboard, stress gaits, and dynamic balance. Moderate-to-high intraobserver and interobserver reliability for the assessment of AMs were noted. Duration and degree of AMs displayed a non-linear developmental course that was a function of the motor task's complexity. AMs decreased most with age in repetitive movements, less in alternating and sequential movements, and least in the pegboard and dynamic balance. Reference curves demonstrated large interindividual variations for duration and degree of AMs. Both the variable developmental course and large interindividual variation need to be taken into account in the assessment of movement quality of school-age children. In contrast to timed performance, considerable sex differences for AMs were observed.

The ketogenic diet is increasingly used for the management of difficult-to-control seizures in children. Here, we describe the first prospective study of the effects of the diet on development, behavior, and parenting stress. Participants were 65 children (36 males, 29 females) with intractable seizures, ages 18 months to 14 years 6 months, enrolled in a prospective study at the Johns Hopkins Hospital, Baltimore, MD, USA, to study the diet's efficacy. Children were assessed before diet initiation and at 1-year follow-up. At follow-up, 52% (34 of 65) children remained on the diet. Mean seizure frequency decreased from 25 per day before diet initiation to less than two per day 1 year later. At follow-up, mean developmental quotient showed statistically significant improvement (p<0.05), with significant behavioral improvements in attention and social functioning. Parental stress was essentially unchanged. No baseline factor examined predicted diet adherence, and the primary reason for diet discontinuation was insufficient seizure control. These preliminary results support prior anecdotal reports of the beneficial effects of the diet on cognition and behavior.

This report describes trends, predictors, and causes of mortality in persons with cerebral palsy (CP) using individuals identified by the Western Australian Cerebral Palsy Register and born between 1958 and 1994. Two thousand and fourteen people were identified (1154 males, 860 females), of whom 225 had died by 1 June 1997. Using date-of-death data, crude and standardized mortality rates were estimated and predictors of mortality sought using survival analysis stratified by decade of birth, description of impairments, and demographic and perinatal variables. For those born after 1967, the cause of death profile was examined over time. Mortality exceeded 1% per annum in the first 5 years and declined to age 15 years after which it remained steady at about 0.35% for the next 20 years. The strongest single predictor was intellectual disability, but all forms of disability contributed to decreased life expectancy. Half of those with IQ/DQ score <20 survived to adulthood, increasing to 76% with IQ/DQ score 20-34, and exceeding 92% for higher scores. Severe motor impairment primarily increased the risk of early mortality. Despite there being 72 persons aged from 25 to 41 years with severe motor impairment in our data set, none had died after the age of 25 years. Infants born after more than 32 weeks' gestation were at significantly higher risk of mortality than very preterm infants, accounted for by their higher rates of intellectual disability. No improvements in survival of persons with CP were seen over the study period despite advances in medical care, improved community awareness, and the increasing proportion of very preterm births among people with CP. This may be the result of improved neonatal care enabling the survival of infants with increasingly severe disabilities.

The aim of this study was to evaluate the effects of intrathecal bacolfen (ITB) on patients with severe generalized dystonia. Eighty-six participants ranging in age from 3 to 42 years (median age 13 years) with generalized dystonia refractory to oral medications were offered treatment with ITB. Dystonia was associated with cerebral palsy in 71% of participants. Response to ITB was tested by continuous infusions in 72%, and by bolus injections in 17% of participants who had both dystonia and spasticity. Ninety-one percent of participants responded to the screening infusion and 93% to the bolus injections. Pumps were implanted in 77 participants. Dystonia scores at 3, 6, 12, and 24 months were significantly decreased (p<0.005) compared with baseline scores. Dystonia scores were significantly lower in those with intrathecal catheters positioned at T4, or higher than in those with catheters at T6 or lower (p=0.005). Ninety-two percent of participants implanted with a pump retained their responses to ITB during a median follow-up of 29 months. Patient questionnaires indicated that quality of life and ease of care improved in 86% and speech improved in 33%. Side effects of ITB occurred in 26% of participants. Surgical complications occurred in 38% and included CSF leaks, infections, and catheter problems. ITB is probably the treatment of choice for generalized dystonia if oral medications are ineffective.

Children with bilateral cerebral palsy (CP) born during 1989 to 1992 (n=346) to a geographically defined population were ascertained and followed up to age 5 years. The aims of the study were to monitor hip development by serial X-rays; to record gross locomotor development, aspects of physical management, and any hip-related orthotics or surgery; to learn more of the natural history of hip development in this condition; and to provide guidelines for a surveillance protocol for those clinically managing children with bilateral CP. Children were X-rayed at 18, 24, 30, 48, and 60 months. X-rays were taken in a standardized position and measured to record migration percentage, acetabular index, Sharp's angle, and Smith's diaphyseal ratios. Relationships between the measures were investigated and a natural history of the children's hip development suggested. At as early as 18 months, migration percentages were significantly greater than in the normally developing population, although no measured CP factor could be identified to be the cause of this early change. Two possible factors affecting early hip development are described, neither of which is clinically apparent: the first separates the bilateral CP population as a whole from the normal population; but there is an additional presdisposing factor affecting some children only which in the presence of the motor disorder, has a significant influence on early hip development and subsequent dysplasia. The study confirms that, when measured correctly, migration percentage is the best guide to hip surveillance and the need for treatment. It is suggested that all children with bilateral CP should be X-rayed in a standardized position at 30 months (corrected for gestational age).

Neuropsychological outcome at 14 to 15 years of age of a cohort of 75 participants(39 male, 36 female) born at <33 weeks' gestation was investigated. Research was conducted parallel to a recent MRI study by Stewart and colleagues which reported that 55% of this cohort had evidence of brain abnormality. One aim of the study was to compare neuropsychological function in those very preterm children with and without MRI abnormality. Compared to a control sample of term adolescents, very preterm participants had impairment only on a measure of word production. On measures of attention, memory, perceptual skill, and visuomotor and executive function, the adolescents born very preterm performed in the normal range, whether or not they had evidence of MRI abnormality. Our findings are encouraging as the neuropsychological consequences of damage to the very preterm brain, still evident on MRI at 14 to 15 years of age, appear to be minor.

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 fascicle 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 fascicle diameter.

Video-EEG monitoring was performed to evaluate 193 children (91 females, 102 males; mean age 9.6 years, SD 5.7) who presented with paroxysmal events of uncertain etiology. Diagnosis of the type of event, i.e. epileptic or non-epileptic, was successfully established in 130 of 193 patients (67.3%). Seventy children (36%) had mental retardation (MR). Children with MR were more likely (p<0.05) than children without MR to have events during the studies. Children with and without MR had strikingly similar frequencies of epileptic and non-epileptic events. In participants who had events recorded and characterized, epileptic seizures were identified in 67 children (51.5%), non-epileptic events in 54 children (41.5%), and both epileptic and non-epileptic events in nine children (7%). Improved diagnosis prompted appropriate management. This should encourage more frequent use of video-EEG in children, especially in those with MR, to differentiate epilepsy from behavioral disturbances so that specific treatment can be provided.

It has been suggested that autism may arise as the result of exposure to high concentrations of prenatal testosterone. There is evidence that the ratio of the lengths of the 2nd and 4th digit (2D:4D) may be negatively correlated with prenatal testosterone. We measured 2D:4D in 95 families recruited via the National Autistic Society, UK. The sample comprised a total 72 children with autism (62 males, 10 females; age range 2 to 14 years), including 23 children (20 males, three females) with Asperger syndrome (AS), 34 siblings, 88 fathers, 88 mothers and sex- and age-matched control participants. We found that the 2D:4D ratios of children with autism, their siblings, fathers and mothers were lower than population normative values. Children with AS, who share the social and communicative symptoms of autism but have normal or even high IQ, had higher 2D:4D ratios than children with autism but lower ratios than population normative values. There were positive associations between 2D:4D ratios of children with autism and the ratios of their relatives. Children with autism had lower than expected 2D:4D ratios and children with AS higher ratios than expected in relation to their fathers' 2D:4D ratio. It was concluded that 2D:4D ratio may be a possible marker for autism which could implicate prenatal testosterone in its aetiology.

Results of surgery to correct fixed flexion contracture of the knee and improve voluntary knee extension in 39 knees in 20 children (11 females, 9 males; mean age 12 years 8 months, age range 5 to 20 years) with cerebral palsy were analyzed. All patients had neuromotor disease and 18 children had spastic diplegia or quadriplegia. All patients could initiate voluntary knee extension but lacked full passive extension. Five patients (10 knees) were free walkers with a mean motor severity index of 19 and mean fixed knee contracture of 20 degrees. Fifteen patients (29 knees) were not free walkers and 13 were wheelchair ambulators. They had a mean motor severity index of 8 and mean fixed knee contractures of 30 degrees. Surgical procedures included various combinations of hamstring lengthening and/or posterior capsulotomy to allow free passive knee extension, with or without quadriceps mechanism shortening, to enhance voluntary extension. The best results were in patients who had hamstring lengthening, posterior capsulotomy, and quadriceps mechanism shortening.

Infants with bronchopulmonary dysplasia (BPD) often have difficulty achieving coordinated suckle feeding. To analyze rhythmic differences during feeding in infants with BPD we performed weekly studies of 14 infants with BPD (eight male, six female; postmenstrual age [PMA] 32.1 to 39.7 weeks); and a PMA-matched control group without BPD (n=20), from initiation of bottle feeding until discharge, with simultaneous digital recordings of pharyngeal and nipple (teat) pressure. Unlike the control group, there was no significant correlation between PMA and stability of suckle rhythm, aggregation of suckles or swallows into runs, or length of suckle runs. Comparing those infants >35 weeks' PMA, the group with BPD had significantly decreased stability of suckle rhythm (increased coefficient of variation of suckle–suckle intervals: 0.34, SE 0.02 vs 0.254, SE 0.014; p=0.003), decreased aggregation into suckle runs (71.1, SE 3.4% vs 85.4, SE 2%; p=0.001), and decreased length of suckle runs (7.2, SE 0.9 vs 13.1, SE 1.9 suckles/run; p=0.003). Percentage of swallows in runs was also decreased in the cohort with BPD (58, SE 3.8% vs 77.2, SE 3.5%; p<0.001), as was length of swallow run (5.3, SE 0.5 vs 10.7, SE 1.1; p<0.001). Thus, in infants with BPD, anticipated maturational patterns of suckle and swallow rhythms did not occur. Delay in attainment of stable suckle and swallow rhythms in preterm infants, especially after 35 weeks' PMA, may predict subsequent feeding and neurological problems.

The study aimed to determine if melatonin could reliably induce sleep in children undergoing sleep EEG without affecting the usefulness of the EEG itself. One hundred and sixty three children (112 males, 51 females; mean age 8 years, range 1 to 16 years) referred for sleep EEG were studied. The children were given 2 to 10mg of melatonin, depending on age, just before EEG recording. Measurements included sleep-onset latency, adverse effects, and acceptability of the EEG. Usefulness and acceptability of melatonin-induced sleep EEG were compared with the standard technique of sleep EEG following sleep deprivation in 30 children (matched for sex and age). Sleep was obtained in 79% of the 163 children who received melatonin after an average of 33 minutes. Yield of epileptiform abnormalities demonstrated in the melatonin sleep EEG was similar to that reported in the literature for sleep-deprived EEGs. There was no significant adverse effect. When compared, a melatonin-induced sleep EEG was as useful as a sleep-deprived EEG. However, the children's behaviour on the day of the melatonin-induced sleep EEG recording was more acceptable to parents.