The aim of this study was to evaluate cognitive development at the onset of West syndrome (WS) with regard to electroencephalogram (EEG) patterns and visual function. Twenty-five patients (14 males, 11 females) at the onset of spasms (T0) in WS and 2 months later (T1) underwent a full clinical evaluation, including neuroimaging, cognitive assessment, video-EEG, and visual function. Mean age of the patients at spasm onset was 5.9 months (SD 2.5; range 2 to 13mo). Cognitive development, assessed with Griffiths Mental Development Scales (GMDS), was generally impaired at T0 and was significantly related to visual function (p<0.001) at both T0 and T1. In general, there was a specific major impairment in the eye–hand coordination scale of the GMDS which tended to disappear after 2 months in less severe cases. At the onset of spasms, sleep EEG organization seemed to be better related to cognitive abilities than awake hypsarrhythmia. These results support a close link between visual function and cognitive competence in WS and provide additional information to improve the understanding of possible mechanisms underlying cognitive impairment.

Clinical data on Duchenne muscular dystrophy (DMD) are lacking in developing countries. The objective of this study was to delineate the demographic characteristics, investigations, and outcome of 21 Malaysian males diagnosed with DMD over a period of 10 years. Mean age presentation was 3 years 8 months (SD 23mo; range 10 to 84mo), mean duration from first presentation to diagnosis was 3y 7mo (SD 26mo; range 5 to 84) and the mean age for loss of ambulation was 11 years (SD 25mo; range 102 to 168). There was family history of DMD in five of the 21 patients. Muscle biopsy showed confirmatory findings of DMD in the 16 patients tested. Molecular genetic analysis showed dystrophin gene deletions in 11 of these 16 patients. Four and seven of the students stopped schooling and had learning difficulties, respectively; only nine had satisfactory school performances. Eight out of 14 patients evaluated were classified as having severe to total dependency levels on the modified Barthel Index for activities of daily living assessment. DMD is associated with significant medical and social needs for a developing country such as Malaysia. Earlier referral, genetic counselling, and provision of support and rehabilitative services are the main priorities.

This study investigated the effect of functional electrical stimulation (FES), applied during walking, on the gait of children with spastic cerebral palsy (CP). Eight children (five males, three females; mean age 13y 2mo, SD 2y 2m; range 8y 11mo to 17y 6mo) diagnosed with diplegic (n=6) or hemiplegic (n=2) spastic CP completed the study. All participants were ambulant. Core FES strategies based on common CP gait deviations were developed and tailored for each child. FES strategies for each child were evaluated in two separate test sessions. Effects of FES on gait were monitored with three-dimensional motion analysis. Within each test session each child's gait was assessed when walking without FES (phase A) and with FES (phase B). An A–B–A–B test sequence was employed allowing the effects of the withdrawal and reinstatement of FES to be assessed. All children performed 10 consecutive walks in each phase. Replication of this sequence on a separate day allowed the repeatability of the intervention to be evaluated. Outcome measures, including summary variables of kinematic data, temporal–spatial variables, and mode of initial contact, were predefined for each child and targets for clinical significance were set for these outcome measures. Comparisons were performed between these targets and the actual outcomes. Consistent clinically significant improvements were recorded for three children: one child showed some improvement that was statistically significant but not clinically significant. Results for one child were mixed. There was no change in the remaining three children. Gait analysis proved to be a useful tool in both developing and determining the effectiveness of FES strategies.

A longitudinal comparison was made between development of verbal and visuo-spatial short-term memory and vocabulary in children with Down syndrome (DS), children with specific language impairment (SLI), and typically developing children as a control group. Participants were 12 children with DS (6 males, 6 females; mean chronological age 9y 9mo [SD 2.8mo], range 8y 6mo to 11y 4mo); nine children with SLI (4 males, 5 females; mean chronological age 3y 9mo [SD 4.8mo], range 3y 3mo to 4y 5mo); and 12 typically developing children (5 males, 7 females; mean chronological age 4y 4mo [SD 3.9mo], range 3y 3mo to 4y 3mo). Participants were matched on mental age (mean mental age 4y 3mo). All participants completed verbal short-term memory, visuo-spatial short-term memory, and expressive and receptive vocabulary tasks on three occasions over 1 year. Similarities were seen in the clinical groups for verbal short-term memory. There was some evidence of difficulty in visuo-spatial short-term memory in the children with SLI relative to the other groups, but all three groups showed overlap in visuo-spatial short-term memory performance. At the final time-point vocabulary performance in the clinical groups was similar; the typically developing children showed higher vocabulary abilities than both clinical groups.

To test whether the presence of indolyl-3-acryloylglycine (IAG) is associated with autism, we analyzed urine from population-based, blinded cohorts. All children in York, UK with autism spectrum disorders (ASDs), diagnosed using ICD-10 research diagnostic criteria, were invited to participate. Fifty-six children on the autism spectrum (mean age 9y 8mo, SD3y 8mo; 79% male) agreed to participate, as did 155 children without ASDs (mean age 10y, SD3y 2mo; 54% male) in mainstream and special schools (56 of whom were age-, sex-, and school-matched to children with ASDs). IAG was found at similar levels in the urine of all children, whether IAG concentrations or IAG:creatinine ratios were compared. There was no significant difference between the ASD and the comparison group, and no difference between children at mainstream schools and those at special schools. There is no association between presence of IAG in urine and autism; therefore, it is unlikely to be of help either diagnostically or as a basis for recommending therapeutic intervention with dietary manipulation. The significance of the presence of IAG in urine has yet to be determined.

The aim of this study was to evaluate the effects of a modified version of constraint-induced (CI) movement therapy on bimanual hand-use in children with hemiplegic cerebral palsy (CP; age range 18mo to 4y) and to make a comparison with conventional paediatric treatment. Twenty-one children (13 females, eight males) completed the CI therapy programme and 20 children (12 males, eight females) served as a control group. Children in the CI therapy group were expected to wear a restraint glove for 2 hours each day over a period of 2 months. The training was based on principles of motor learning used in play and in motivational settings. To evaluate the effect of treatment, the Assisting Hand Assessment (AHA) was used. Assessments took place on three occasions: at onset, after 2 months, and 6 months after the first assessment. A significant interaction was found between group and AHA measure (ANOVA, F2,74=5.64, p=0.005). The children who received CI therapy improved their ability to use their hemiplegic hand significantly more than the children in the control group after 2 months, i.e. after treatment. Effect size was high after treatment and remained medium at 6 months. As the treatment was tailored to each child's capacity and interests, little frustration was experienced by the children.

the feasibility of percutaneous intramuscular functional electrical stimulation (p-fes) in children with cerebral palsy (cp) for immediate improvement of ankle kinematics during gait has not previously been reported. eight children with cp (six with diplegia, two with hemiplegia; mean age 9 years 1 month [sd 1y 4mo; range 7y 11mo to 11y 10mo]) had percutaneous intramuscular electrodes implanted into the gastrocnemius (ga) and tibialis anterior (ta) muscles of their involved limbs. stimulation was provided during appropriate phases of the gait cycle in three conditions (ga only, ta only, and ga/ta). immediately after a week of practice for each stimulation condition, a gait analysis was performed with and without stimulation. a significant improvement in peak dorsiflexion in swing for the more affected extremity and dorsiflexion at initial contact for the less affected extremity were found in the ga/ta condition. clinically meaningful trends were evident for improvements in dorsiflexion kinematics for the more and less affected extremities in the ta only and ga/ta conditions. the results suggest that p-fes might immediately improve ankle kinematics in children with cp.

Hemiconvulsions-hemiplegia-epilepsy syndrome (HH/HHE) is a rare epileptic syndrome consisting of a prolonged unilateral convulsion producing a persisting hemiplegia, sometimes followed by epilepsy. We report on a 13-month-old male who presented with febrile left-sided HH syndrome with right hemispheric unilateral cytotoxic oedema followed by hemispheric atrophy on magnetic resonance imaging (MRI). Six months later the child progressively developed refractory focal epilepsy, including right hemiclonic seizures, and nearly continuous left frontal rhythmic spikes, suggesting the presence of a focal cortical dysplasia (FCD). A repeat MRI at 2 years of age showed left frontal FCD. This unusual case of dual pathology – right HH syndrome and left FCD – suggests that some other factor than the malformation determined the prolonged status and brain atrophy. The kinetics of regional cortical maturation could explain this unusual condition.

The suggested link between autism and cerebellar dysfunction formed the background for a Swedish clinical study in 2001. Thirty-two children (17 females, 15 males; mean age 12y, SD 3y 10mo; range 6 to 21y) with a clinical suspicion of non-progressive congenital ataxia were examined, and parents were interviewed about the presence of neuropsychiatric problems in the child. Twelve children had simple ataxia, eight had ataxic diplegia, and 12 had ‘borderline’ ataxia. All but one of the 32 children had a mild to moderate gross motor disability according to Gross Motor Function Classification System (15 were categorized as level I, 16 as level II, and one child as level IV). Neuroimaging and neuropsychological testing were achieved in most cases. There was a strong association between learning disability and autism spectrum disorder (often combined with hyperactivity disorder) on the one hand, and both simple and borderline ‘ataxia’ on the other, but a weaker link between ataxic diplegia and neuropsychiatric disorders. A correlation between cerebellar macropathology on neuroimaging and neuropsychiatric disorders was not supported. Congenital ataxia might not be a clear-cut syndrome of cerebellar disease, but one of many signs of prenatal events or syndromes, leading to a complex neurodevelopmental disorder including autism and learning disability.

Ring chromosome 20 (r[20]) syndrome is characterized by mild to moderate learning disability, behavioural disorders, epilepsy, and various dysmorphic features. Although still considered rare, r(20) syndrome is being increasingly diagnosed. More than 30 cases have been described in the literature since 1976. Here we report an additional case of a 14-year-old male with r(20). He had moderate to severe learning disability and epileptic seizures manifesting at about 18 months of age. During the 13 years' follow-up period he showed intractable epileptic seizures, behavioural disorders, and mild dysmorphological features including microcephaly, strabismus, micrognathia, down-slanting eyelids, and ear abnormalities. Frequent episodes of atypical absence or non-convulsive status associated with electroencephalogram changes were seen in follow-up. He was treated with several classical and new antiepileptic drugs, including intravenous immunoglobulin, corticotropin, and vagal nerve stimulation, with unsuccessful control of seizures. Finally, surgical treatment (corpus callosotomy) was performed at the age of 13 years; severity of tonic seizures was diminished, but frequency was unchanged. Although his behavioural problems, e.g. hyperactivity, were mild in early childhood they became more severe when he was 11 years old. Aggressiveness, compulsiveness with self-injury, and panic attacks developed at the age of 13 years, and were more pronounced after callosotomy. This case report provides the first description of deterioration in psychological situation in patients with r(20) intractable epilepsy. The patient was diagnosed with r(20) syndrome after 13 years of clinical follow-up. Karyotype analysis should, therefore, be performed in every patient with intractable epilepsy of unknown aetiology.

Children with infantile nephropathic cystinosis have evidence of visuospatial and arithmetic deficits on a background of normal intellectual and verbal skills. This study aimed to define further their behavioral phenotype. The Achenbach Child Behavior Checklist was completed by parents of: 64 children and adolescents with cystinosis (33 females, 31 males; mean age 8y 8mo, range 4 to 16y, SD 2y 11mo); 101 healthy controls (47 females, 54 males; mean age 8y 4mo, range 4 to 16y, SD2y 11mo); 21 children and adolescents with cystic fibrosis (CF), termed chronic-disease controls (9 females, 12 males; mean age 11y 3mo, age range 4 to 17y, SD3y 5mo). Compared with healthy controls, individuals with cystinosis had evidence of a significantly higher incidence of behavioral problems, including social problems, somatic complaints, and attention problems. Compared with the chronic-disease control group, the cystinosis group differed only on the Social Problems scale, with 22% of participants with cystinosis scoring in the ‘at risk’ range whereas no participant with CF received an elevated score on this scale. We conclude that children and adolescents with cystinosis have evidence of a significant incidence of social difficulties compared with individuals with another chronic illness and healthy participants. The combination of visuospatial problems, difficulty with arithmetic, attention problems, and social difficulties seen in the cystinosis group constitutes a behavioral phenotype of this genetic disorder. This cluster of cognitive and behavioral symptoms is also seen in the nonverbal learning disabilities syndrome, and suggests a possible early difference in brain development in children with cystinosis compared with children who do not share this genetic disorder.

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.

In 1997, Miura et al. isolated a novel homeobox gene in zebrafish and mice with striking homology to the Drosophila gene aristaless. They called this gene Arx (aristaless-related homeobox gene) and showed that it was highly conserved between zebrafish and mice and expressed in the developing central nervous system. The human orthologue of this gene, ARX, is located on the short arm of the X chromosome (Xp22.13). It consists of five exons and encodes a 562 amino acid protein that may be a nuclear transcriptional regulator. It is expressed in the fetal and adult brain, with much higher expression in the fetal brain. In the fetal brain the ARX gene is primarily expressed in neuronal precursors in the germinal matrix and ventricular zone at all stages of development but also in the subventricular zone, cortical plate, caudate nucleus, putamen, substantia nigra, cingulate, and hippocampus. It is also expressed in fetal testes and adult heart, skeletal muscle, and liver.

cerebellar hypoplasia is a rare malformation caused by a variety of etiologies. it usually manifests clinically as non-progressive cerebellar ataxia with or without mental retardation. we further characterize a syndrome of autosomal recessive cerebellar hypoplasia in the hutterite population, referred to as dysequilibrium syndrome (des). we reviewed 12 patients (eight females, four males; age range 4 to 33y) with this syndrome. patients were examined and underwent a standard set of investigations to characterize better the clinical features, natural history, and neuroimaging of this syndrome. des is an autosomal recessive disorder with distinct clinical features including global developmental delay, late ambulation (after age 6y), truncal ataxia, and a static clinical course. neuroimaging is characterized by hypoplasia of the inferior portion of the cerebellar hemispheres and vermis, and mild simplification of cortical gyri.

This study aimed to: classify a cohort of children and adolescents with myotonic dystrophy (dystrophia myotonica: DM) into congenital and childhood onset forms; estimate CTG expansion size; and quantify muscle strength, contractures, and motor function in children with DM and compare results with those of controls. Participants were clinically examined, medical records were reviewed, and isometric muscle strength, contractures, and motor function were measured. Participants were: 42 children with DM (18 females, 24 males; mean age 8y 9mo [SD 4y 7mo], range 10mo to 17y) and 42 age- and sex-matched, healthy controls. Children with DM were divided into three groups: severe congenital (n=13), mild congenital (n=15), and childhood (n=14). Children with childhood DM were significantly weaker than controls (wrist and ankle dorsiflexors [p=0.0044, p=0.0044 respectively]; hip abductors and flexors [p=0.0464, p=0.0217]; and knee flexors and extensors: [p=0.0382, p=0.0033]). Children with mild congenital DM were significantly weaker than controls in all assessed muscle groups. Contractures and skeletal deformities were more frequent at time of investigation than at birth, suggesting that foot and spine deformities in particular increase over time. Motor function score was significantly lower for children with DM than for controls. Children with severe congenital DM had the lowest motor function, with correlation between motor function and size of CTG repeat (ρ=–0.743). Children found jumping, heel standing, and head lifting the most difficult items to perform but few had difficulty walking, running, or stair climbing. DM in children is a heterogeneous disorder with a wide spectrum of muscle involvement, and owing to increased risk of contractures and skeletal deformities, regular follow-ups are recommended.

In children with a myopathy, muscle biopsy, together with the clinical presentation, can guide further investigations. The presence of centrally located nuclei suggests a myotubular myopathy, and gene testing may confirm this diagnosis. We describe a male child with a mild form of X-linked myotubular myopathy for which repeated muscle biopsy did not show the characteristic pattern of centrally located nuclei. Myotubular myopathy was not contemplated, therefore, until a maternally related relative was shown to have the disorder. Genetic testing showed that the index case carried the same mutation in his MTM1 gene as this relative.

This preliminary study compared the daily living skills of children with and without attention-deficit–hyperactivity disorder (ADHD), and the influence of a social skills training group on these skills. Twenty-seven children with ADHD (2 females, 25 males; age range 5 to 8y, mean 6y 6mo, SD 10mo), and 24 children without ADHD (8 females, 16 males; age range 5 to 8y, mean 6y 11mo, SD 10mo) performed the Assessment of Motor and Process Skills (AMPS). Fourteen of the children with ADHD used medication daily. Nine of the total group with ADHD were randomly selected to attend group treatment which focused on social skills training, through meaningful occupations (e.g. art, games, cooking). Children were evaluated at the beginning of group treatment and after 10 sessions. Ten children without ADHD were evaluated at similar intervals. Children with ADHD initially achieved significantly lower scores on the AMPS in all process skills (p<0.001) and in the coordination motor subtest (p<0.005) than children without ADHD. Children with ADHD significantly improved from the first to the second evaluation and no longer differed from the children without ADHD after treatment (p<0.008). The results emphasize the need for a focus upon occupation in assessment and treatment of children with ADHD.

Homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency may present with variable neurological manifestations. Radiological features include white matter changes (leukoencephalopathy). Clinical, biochemical, and radiological response to treatment may again be variable. Here we present a 12-year follow-up of two siblings on the same treatment regimen, with contrasting long-term findings. The first patient, a female presenting at 15 years, showed a good clinical response, substantial intellectual gain, and complete reversal of leukoencephalopathy. Her brother presented at 13 years 9 months and showed limited clinical and cognitive improvement with persistence of the leukoencephalopathy. Both siblings showed a partial biochemical response to treatment.

The aim of this study was to evaluate the predictive value of corrected head circumference (HC) centiles at 2 years of age with respect to developmental performance in a series of high-risk neonatal intensive care unit (NICU) survivors with microcephaly. The study used a retrospective review of the clinical files of children seen in a clinic devoted to the follow-up of all high-risk survivors of a hospital's level III NICU. All children with microcephaly (occipital–frontal circumference below the 2nd centile for sex) at 2 years of age were identified. The HC obtained at 2 years was corrected to the ages for which the absolute HC corresponded to either the 50th or 2nd centile for the child's sex. Of 312 high-risk patients followed, 38 (12.2%) were microcephalic. Fifteen performed below the 50th age-corrected HC centile (severe developmental delay), 12 performed between the 50th and 2nd age-corrected HC centile (moderate developmental delay), and 11 performed above the 2nd age-corrected HC centile (mild developmental delay). The absolute value of HC measurement was not a predictor of developmental performance. Of all clinical factors evaluated, only coexisting epilepsy was found to be a significant predictor of less than the 50th age-corrected HC centile developmental performance (χ2=6.134, p=0.01). We conclude that in a high-risk population, the presence of microcephaly implies developmental impairment, though neither the absolute HC measurement nor the corrected HC centile is predictive. Coexisting epilepsy in this context appears to worsen developmental outcome.