Fifty-seven children with cerebral palsy (CP) and imaging evidence of vascular thrombosis (study group) and 167 children with CP and other imaging finds (control group)were selected. Sixty-one per cent of the study group were male and 53 (93%) had spastic hemiplegia compared with the control group, of whom 55% were male and 54 (32%) had a diagnosis of spastic hemiplegia. Mean age was 5 years 11 months (SD 5y 1mo) for the study group and 7 years 7 months (SD 4y 7mo) for the control group. Blood spots on Guthrie cards or buccal swabs were used to test both groups and their mothers for the factor V Leiden (fVL) mutation, which predisposes carriers to thrombophilia. Mothers were interviewed to gather antenatal, perinatal, demographic, and socio-economic data. The frequency of the fVL mutation in children with evidence of vascular thrombosis and their mothers was not statistically different from the frequency in children with CP with other imaging findings and their mothers. The frequency of the fVL mutation was significantly higher than the expected population frequency of 4% in the study group (10.5%, p=0.012) and in mothers of the control group (7.2%, p=0.036).

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.

The aim of this pilot study was to evaluate functional training for children with cerebral palsy (CP). The outcomes examined were goal-achievement, gross motor function, performance of everyday activities, caregiver assistance, parents' perception of family-centredness, and preschool assistants' feeling of competence in the care of the children. The outcome measures used were goal attainment scaling, Gross Motor Function Measure, Pediatric Evaluation of Disability Inventory (functional skills and caregiver assistance scales), Measure of Processes of Care, and a questionnaire. The intervention was carried out in the context of daily life settings, i.e. in an ecological framework. Fourteen children (three females, 11 males; age range 1y 6mo to 6y) with diplegia and tetraplegia, classified at Gross Motor Function Classification System levels II–V, participated in the five-month intervention. Frequency of training towards a specific goal varied between twice a day and 23 times a day, depending on the type of goal. Seventy-seven per cent of goals were fully attained. Gross motor function and performance of daily activities, including social function, improved significantly. A decrease in caregiver assistance was noted in relation to the children's mobility. Parents' perception of family-centredness improved in all domains. Furthermore, the children's preschool assistants felt more competent in their care of the children.

3-phosphoglycerate dehydrogenase deficiency is a severe but treatable disorder of serine synthesis, first described in 1996 (Jaeken et al. 1996a). The patient presented with West syndrome, severe psychomotor delay, failure to thrive, microcephaly, atypical ocular movements, and pyramidal signs. Treatment with oral L-serine abolished seizures and improved psychomotor development, hyperexcitability, head growth, cortical and subcortical hypotrophy, and hypomyelination of the brain on MRI scans. 3-phosphoglyce-rate dehydrogenase deficiency is a treatable congential error that probably leads to West syndrome.

The early development of self-injurious behaviour in three young boys (aged 17, 25, and 30 months at start of study) with Lesch-Nyhan syndrome was examined by means of parental interviews and by direct observations completed at 3 to 4 monthly intervals over an 18-month period. Results suggest that the self-injury began in a different way from that of other young children with autism and/or developmental disabilities in that, from the start, self-injurious responses were sudden and violent, rather than emerging gradually over time. Drastic measures, such as removal of the teeth or provision of tooth guards, were often taken to prevent further tissue damage. Direct observations showed that the boys' self-injury occurred at lower rates, but their carers were highly concerned about the behaviour. Sequential analysis of the observational data indicated that on some occasions the children were more likely to self-injure during periods of low social interaction, suggesting that their self-injury may have been influenced by environmental factors. The theoretical and practical implications of these findings are discussed.

Hypoxic–ischaemic encephalopathy (HIE) was diagnosed in an infant with acidosis. At 7 weeks of age further investigations revealed abnormal neuroimaging (CT and MRI scans) and a raised plasma and CSF lactate. A skeletal–muscle biopsy at 2 months of age confirmed the diagnosis of cytochrome oxidase deficiency. The course of the patient's disorder has taken that of a static encephalopathy (cerebral palsy). Inborn disorders of the respiratory chain should be considered in the differential diagnosis of HIE.

Intermittent electrical stimulation of the cervical vagus nerve (VNS) with an implanted pulse generator is a new adjunctive treatment for severe seizure disorders. In two large, prospective, double-blind randomized controlled trials involving more than 300 patients, VNS reduced seizure rates by 25% within 3 months. A 3-year follow-up study of these and 125 additional patients indicated that efficacy was maintained; seizure rates were reduced by 45%. General reviews on VNS in adults, and mechanisms of action are given by McLachlan and Schachter and Saper.

Stuttering, or stammering as it is also referred to, is a developmental speech disorder, which usually appears in children between the ages of 3 and 8 years. More often than not it remits before puberty, but it can persist into adult life. Stuttering is characterized by involuntary syllable repetitions, syllable prolongations, or interruptions (blocks) in the smooth flow of speech. There may sometimes be difficulty in differentiating infants who definitely stutter from those who show the dysfluency often seen in infancy as a normal stage of speech development. However, the two are distinct. The overall frequency of dysfluency, the proportion and duration of dysfluency types, and the associated behaviours not directly related to speech such as eye, head, and body movements, can help to distinguish between the two. There has certainly been controversy over the exact definition of stuttering when selecting participants for research studies. Wingate criticized Yairi and coworkers for not being strict enough in their selection of affected children and for including those who were classified as having stutter-like dysfluencies, especially whole-word repetitions. However, Yairi and colleagues refuted these claims, stating that although syllable repetitions are the most common component of stuttering, whole-word repetitions do occur in stuttering and therefore this is not a criteria for exclusion. In fact, whole-word repetitions seem to be more common when the onset of stuttering is early in life.

The purpose of this study was to determine and measure the factors that affect the remodeling of the proximal femur after varus osteotomy in children with spastic cerebral palsy (CP). Seventy-five varus proximal osteotomies were performed on 44 children (26 females, 18 males) for hip dysplasia. Thirty-nine patients had spastic CP and five had spastic diplegia; 35 patients used a wheelchair for mobility and nine could walk. Mean age at time of surgery was 8 years (SD 4 years), range 2 years 6 months to 15 years. Preoperative, immediate postoperative, and follow-up (0 to 6 months, 6 months to <1 year, 1 year to <2 years, 2 years to <4 years, 4 years to <6 years, and 6 years to <8 years) radiographs were reviewed. Neck-shaft angles were measured. Correlations to examine the relationship between age at time of surgery and ambulatory status with postoperative changes in neck-shaft angles were reviewed. Remodeling of the proximal femur does occur after varus osteotomy as long as the physes of the proximal femur show growth potential. Remodeling was quite variable between patients: children younger than 4 years old at the time of surgery remodeled more than children who were older than 4 years. Ambulatory status has little effect on the magnitude of remodeling. This study reinforces the need to follow these patients with periodic hip radiographs until completion of growth.

Developmental dysphasia, a severe childhood learning disorder, is thought to result from problems in hemispheric specialization involving both left and right cerebral hemispheres. Regional cerebral blood flow (rCBF) was measured at rest and during stimulation of both hemispheres independently: dichotic listening for the left, dichaptic palpation for the right. Eight right-handed boys with expressive dysphasia, aged 8 to 12 years, were investigated using SPECT and compared with eight right-handed age-matched boys with Duchenne muscular dystrophy with reading disorders but normal speech. rCBF values at rest were also compared with those of five right-handed age-matched normal boys. In the dichotic task, children with dysphasia differed from children with dystrophia by failure to increase rCBF in the left hemisphere, in Broca's area, but rCBF increased in the right hemisphere, in the region homologous to Broca's area. In the dichaptic task, rCBF increased bilaterally for children with dysphasia whereas in children with dystrophia rCBF increased only in the right hemisphere. At rest the physiological asymmetry was reversed in favor of the right hemisphere in all areas except Broca's area. Surprisingly, the same applied at rest and for all areas in children with dystrophia. These results confirm that functional specialization of both hemispheres is impaired in developmental dysphasia. Moreover, they suggest that learning disabilities associated with Duchenne muscular dystrophy could also be related to abnormal hemispheric specialization.

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.

A population-based study of children with hemiplegic cerebral palsy (CP) was performed to investigate whether thrombophilic tendencies are implicated in the aetiology of the condition. Thirty-eight children (23 males, 15 females; mean age 8.7 years, SD 4.1 years) with hemiplegic CP were ascertained. Twenty-seven children (18 males, nine females; mean age 8.4 years, SD 4.3) gave consent for inclusion. The non-study group comprised five males and six females; mean age 9.4 years, SD 4.1. In six children, seven thrombophilic ‘abnormalities’ were identified. Five of these abnormalities were of an equivocal nature and probably did not represent true clinical thrombophilia; reasons for this interpretation are discussed. Contrary to other published non-population-based studies, we have not shown an association between thrombophilia and hemiplegic CP. More studies, including maternal studies, are required to explore this complex subject further.

Autism and Rett syndrome (RS) are both developmental disorders of unknown origin. Autism is a behaviourally defined syndrome. RS, which affects girls only, is characterized by a profound learning disability following early normal development, with a consistent cluster of clinical features. Differentiation of RS from infantile autism in the very early stages of the disorders is not always easy. Both syndromes still lack discriminative laboratory markers for accurate diagnosis and differentiation. We decided to compare the CSF nerve-growth factor (NGF) levels of children with infantile autism and children with RS using enzyme-linked immunosorbent assay (ELISA). Our findings of mainly normal CSF NGF in autism and low to negligible values in RS are in agreement with the different morphological and neurochemical findings (brain growth, affected brain areas, neurotransmitter metabolism) in the two syndromes. CSF NGF could be used as a biochemical marker for differentiation of patients with autism from those with RS.

Dichotic listening performance was studied in children who at an early age had undergone a myringotomy with insertion of ventilating tubes for persistent middle ear infections (otitis media with effusion; OME) and compared with age-equivalent children who had no history of otitis media or hearing problems. The OME group consisted of 19 children with a median age of 9 years; 15 of whom were right-handed, and 14 were boys. The comparison sample comprised 18 children with a median age was 9 years 4 months. Hand preference and sex were matched with the OME group. Both groups were tested with dichotic listening to consonant–vowel syllables and additional forced-attention tasks. The comparison sample showed a weak right-ear advantage, and age-adequate attentional modulations. The children in the OME group showed a strong right-ear advantage, but were not able to modulate the ear advantage during directed-attention tasks. Models for interpreting the result are discussed.

The aims of this study were to assess the characteristics of three-dimensional displacement of the centre of mass of the body (CMb) during walking in healthy children and to compare it with those of young adults. Twenty-one children (11 males, 10 females; age range 1 to 9 years) were recruited from the nursery and school attached to the Université catholique de Louvain, Brussels, Belgium; and three young adults (one male, two females; mean age 26 years 4 months) were recruited from the Rehabilitation and Physical Medicine Unit of the same university. Displacement of CMb was assessed at different walking velocities in the children and adults by two successive mathematical integrations of ground reaction forces, measured by a large strain-gauge force platform. Displacement of CMb was controlled for leg length of the participant to eliminate the scaling effect that is dependent on growth. Results showed that vertical and lateral amplitudes of the CMb when controlled for leg length were greater for children before 4 years of age and that the forward amplitude when controlled for leg length was greater for children before 7 years of age. We conclude that the development of mature human CMb displacement during independent walking is a gradual neural process, evolving until the age of 7 years.

The 1999 British Child and Adolescent Mental Health Survey, a nationwide epidemiological study of rates of psychiatric disorder in children aged 5 to 15 years, provided the opportunity to investigate the mental health of children with epilepsy. These children and their families experience disability specifically because of additional emotional, behavioural, and relationship problems, and this is the first epidemiological study that directly measures these impairments. Information was obtained by interviewing a main carer and teacher for 10316 children; 67 children with epilepsy were identified (35 males, 32 females; mean age 10 years 2 months, SD 2 years 11 months, range 5 to 15 years), and compared with the 47 children with diabetes (27 females, 20 males; mean age 10 years 4 months, SD 3 years 4 months, range 5 to 15 years) and 10202 controls (50% male; mean age 9 years 11 months, SD 3 years 1 month, range 5 to 15 years). DSM-IV psychiatric diagnoses were derived from the Development and Well-Being Assessment in combination with the interview and a specialist clinician rating. Parental reports of emotional and behavioural problems, their impact, and associated peer problems were also obtained. Rates of psychiatric disorder were 37% (95% confidence interval [CI] 22 to 49) in epilepsy, 11% (95% CI 2 to 19%) in diabetes, and 9% (95% CI 9 to 10%) in control children. Parents of children with epilepsy consistently reported more problems, with greater impact and associated peer problems. Epilepsy, but not diabetes, was independently (adjusted for age, sex, and severe learning difficulties) associated with all behavioural variables in regression analyses. Emotional, behavioural, and relationship difficulties are common in children with epilepsy, and constitute a significant burden to the children and their families, indicating the need for effective mental health services for these children.

The control of human locomotion uses afferent information from many sources within the visual, vestibular, and proprioceptive systems: central generators and programmes interacting with peripheral reflexes represent only a portion of the mechanisms involved. Spinal-reflex pathways and descending tracts converge on common spinal interneurons and thus play an integrative role in regulating the input from descending tracts and spinal reflexes. The weakness of studies carried out on humans in this field is due to the fact that human motor-control mechanisms can only usually be surmised by indirect methods such as knowledge gained from animal experiments. Although there are common features between the pattern of activity and the underlying neuronal mechanisms during quadripedal locomotion in cats and that seen during bipedal gait of humans, there are also distinct differences.

Although premonitory sensory phenomena (PSP) and suppressibility of tics (SPT) are important in Tourette syndrome not only when behavioural therapeutic approaches in children are considered, there is a lack of developmental information on these phenomena. Therefore, a cross-sectional survey of these factors in children and adolescents was carried out. Rates of PSP and SPT were gathered using a questionnaire for the assessment of Tourette syndrome. The 254 outpatients (212 males, 42 females) with Tourette syndrome investigated had an age range of 8 to 19 years, normal intelligence, and diagnosis according to DSM-IV-TR/ICD-10. To test for developmental effects, the total group was stratified into three age groups (8 to 10, 11 to 14, and 15 to 19 years). Data were statistically evaluated using χ2 tests. Of the 254 participants, 37% reported PSP, while 64% were able to suppress their tics. Only a subgroup of 119 patients gave unequivocal answers to both questions and only 60% of these experienced both PSP and SPT. Statistically significant stepwise increases were found at two different age levels. One was around 10 years (PSP ‘Yes’ or ‘No’ and SPT), the other around age 14 (PSP ‘Yes’). There was no influence of tic duration and age at tic onset on PSP/SPT. The reported data suggest that PSP is experienced rarely in younger children with Tourette syndrome and is not a necessary prerequisite for SPT. Increasing PSP with age merely seems to reflect cognitive development rather than intrinsic aspects of Tourette syndrome. In children under 10 years of age, SPT might require more awareness of tics than in older age groups. Developmental aspects of PSP and SPT should be taken into consideration when studies of cognitive behavioural treatment for children and adolescents with Tourette syndrome are planned.

This study examined children with an acute encephalopathy illness for evidence of viral infection, disordered blood–brain barrier function, intrathecal immunoglobulin synthesis, and interferon (IFN) production, and related their temporal occurrence to outcome. A prospective study of 22 children (13 males, 9 females; age range 1mo to 13y, median 2y 4mo), recorded clinical details, with serum and cerebrospinal fluid (CSF) analysis near presentation and then on convalescent specimens taken up to day 39 of the neurological illness. Outcome was assessed with standard scales between 18 months and 3 years after presentation. A history consistent with viral infection was given in 17 children but laboratory evidence of viral infection was found in only 7 (7/17). In 18 out of 21 children, an elevated CSF:serum albumin ratio indicative of impairment of the blood–CSF and blood–brain barriers was detected at some stage of the illness. In 14 of the 15 children with a raised immunoglobulin G index, and in 12 of the 14 children where the CSF was positive for oligoclonal bands, this was preceded by, or was observed at the same time as, an abnormal albumin ratio. Sixteen children (16/18) had elevated IFN-α levels in serum, or CSF, or in both. We conclude that these findings indicate an initial disruption of the blood–brain barrier followed by intrathecal antibody production by activated lymphocytes, clonally restricted to a few antigens. This is the first in vivo study to show this as an important pathogenetic mechanism of encephalitis in children. Poor outcome was associated with young age, a deteriorating electroencephalogram pattern from grade 1 to grade 2, and the degree of blood–brain barrier impairment, particularly when prolonged, but not with Glasgow Coma Scale score. The persistence of IFN-α was associated with a good prognosis.

We report on a male infant with pyridoxine dependency and seizures from birth, controlled with pharmacological doses of pyridoxine at 4 months of age. Seizures stopped between 30 and 80 days of age when very-low doses of pyridoxine were given in a multivitamin supplement . Daily dose was 0.5mg that corresponded to 0.08 to 0.16 mg/kg/day when weight gain is considered. In previous reports doses have ranged from 0.2 to 30 mg/kg/day. Another distinctive feature was that this infant went into a coma and developed hypotonia and irregular breathing when pyridoxine was given by enteral tube which has usually been reported when the vitamin is given intravenously. Use of low doses of pyridoxine in multivitamin supplements could be a confounding factor for early diagnosis and appropriate treatment of pyridoxine-dependent seizures.