Lesch–Nyhan syndrome (LNS) is an X-linked recessive disorder resulting from a deficiency of the metabolic enzyme hypozanthine–guanine phosphoribosyltransferase (HPRT). This syndrome presents with abnormal metabolic and neurological manifestations including hyperuricemia, mental retardation, spastic cerebral palsy (CP), dystonia, and self-mutilation. The mechanism behind the severe self-mutilating behavior exhibited by patients with LNS is unknown and remains one of the greatest obstacles in providing care to these patients. This report describes a 10-year-old male child with confirmed LNS who was treated for self-mutilation of his hands, tongue, and lips with repeated botulinum toxin A (BTX-A) injections into the bilateral masseters. Our findings suggest that treatment with BTX-A affects both the central and peripheral nervous systems, resulting in reduced self-abusive behavior in this patient.

Four dimensions of motor competence were evaluated in 4-year-old term and preterm children and were related to academic achievement and use of school services at age 8 years. The objective of the study was to evaluate a graduated ‘stair-step’ effect between perinatal morbidity, mild motor delay, and later school outcomes in 168 children (88 females, 80 males) stratified into four study groups: 134 healthy term infants [ges ] 37 weeks' gestation, birthweight [ges ] 2500g); 134 preterm infants [les ]37 weeks' gestation divided into healthy preterm (n=41), clinically ill preterms (n=59), and preterm infants with neurological illness (n=34). Significant differences were found in total, fine and gross motor performance, and visual–motor integration at age 4 years. Scores for the preterm groups decreased with increasing morbidity. At age 4 years, mild motor delay was found in all preterm groups. Children with mild motor delay had lower academic achievement scores (Wide Range Achievement Test-3) and higher rates of school service use at age 8 years. Perinatal morbidity and compromised motor performance are important precursors of educational underachievement.

Seventy-five families of children with intractable epilepsy but without a severe learning disability (mean age 7 years 1 month, SD 2 years 6 months; range 2 to 12 years) who attended a regional paediatric neurology service, were surveyed. A postal questionnaire was used which included standardized measures of child and family adjustment; forty-eight families responded (64%; 31 males, 17 females). There was no significant difference between responders and non-responders in terms of age, sex, number of other chronic illnesses and disabilities, age at epilepsy diagnosis, seizure type, nor number of antiepileptic drugs currently prescribed (p>0.05). The importance of including multidimensional measures of outcome was highlighted by the finding that epilepsy, pharmacological, and psychosocial factors were differentially associated with specific adjustment difficulties. Two factors appeared to be most pervasively implicated across a range of adjustment problems: frequency of rectal diazepam administration and family patterns of relating to each other (p<0.05). It appeared that duration of seizures (as indicated by frequency of rectal diazepam administration), rather than the frequency of seizures per se, was more pernicious in terms of poor adjustment. Intrafamilial relations (degree of conflict/cohesion and so on) were not only associated with adjustment difficulties in the child, but also with the frequency of seizures themselves. Implications for psychological interventions in intractable epilepsy in childhood are highlighted.

The study aimed to determine whether degree of participation of children with cerebral palsy (CP) is influenced by where they live, as predicted by the social model of disability. Ninety-two per cent children with CP resident in Northern England and born 1991–1996 were entered into the study. Participation was measured by the Lifestyle Assessment Score and its six component domain scores. Regression analysis was used to investigate variations in participation. There were 443 children (265 male, 178 female; mean age 4 years 8 months [SD 1 year 1 month] at time of assessment) in the study. In the regression analysis the following factors remained significant with regard to level of participation: type of CP (167 with hemiplegia, and of those remaining 240 with bilateral spasticity); intellectual impairment (105 with IQ<50, 113 with IQ 50 to 70, and 225 with IQ>70); presence of seizures (115 with active epilepsy); walking disability (114 unable to walk, 81 restricted and needing aids, 186 restricted but unaided, 62 unrestricted); communication problems (61 no formal communication, 51 use alternative formal methods, 126 some delay or difficulty, 205 no communication problems). After adjustment for these factors, there were significant variations with regard to level of participation in the Lifestyle Assessment Score by district of residence. The magnitude of these variations in Lifestyle Assessment Score between districts is similar to that accounted for by severe intellectual impairment. Similar models were obtained for four of the six domain scores. For one of these four, restriction of social interaction, the significant variation between districts was minimally influenced by the underlying type of CP, walking ability, or presence of seizures. Higher levels of participation among children with CP are associated with residence in certain districts. This is not attributable to variations in case-mix or functional capacity of the children. Participation of children with disability is partly a product of their environment.

Prolonged convulsive seizures are a common neurological emergency and a potential cause of neuronal damage and functional sequelae. We explored the role of seizure duration and various background factors for neurological sequelae in children with prolonged convulsive seizures. The population-base of this study was all children (age <16 years) who had been admitted to the Tampere University Hospital, Finland between 1993 and 1999 with convulsive seizures lasting more than 5 minutes. Patients were followed up individually (mean length of follow-up 2 years 1 month, range 0 to 7 years 8 months). All available data on the prolonged seizure episodes and clinical follow-up were analyzed retrospectively by a detailed review of all medical charts and records. In 186 children (94 males, 92 females; mean age 4 years 5 months, SD 3 years 10 months, range 1 month to 15 years 4 months) there were 279 separate convulsive seizure episodes lasting over 5 minutes, yielding an annual incidence of 47.5 out of every 100000 episodes. Seizure aetiology was idiopathic in 26.2% of episodes, febrile in 41.9%, remote symptomatic in 28%, and acute symptomatic in 3.9% of episodes. Mean duration of all seizure episodes was 42.5 minutes (SD 46.1 minutes) and was significantly correlated with the aetiology: shortest in the febrile group (mean 35.4 minutes) and longest in the acute symptomatic group (mean 88.6 minutes; p<0.001). There was no mortality related directly to these acute seizure episodes. The most common sequela was an onset of epilepsy in 40 children (22%). Permanent neurological sequelae were noted in only four patients (2.2%; mean seizure duration 16 minutes) and non-permanent sequelae in six patients (3.2%; mean seizure duration 38 minutes). Neurological sequelae of prolonged convulsive seizures in children are rare and are related to aetiological factors rather than the duration of a single seizure. The role of acute seizures in the evolution of epilepsy in children remains obscure.

The aim of the study was to compare the development of children with and without a programme of psychosocial stimulation in ‘control’ and ‘intervention’ sites in a poorly resourced area of northeast Brazil. The sample (n=156, born 1998) was from a larger cohort. The cohort was tested at 12 months (baseline) with the Bayley Scales of Infant Development. All children in the intervention site with a mental development index (MDI) and/or psychomotor development index (PDI) [les ]100 were enrolled. Each time such a child was enrolled, the next child tested in that site of the same sex and with an index of 101 to 115 was also enrolled, and the next two children matched for sex and scores of [les ]100 and 101 to 115 in the control sites were recruited in parallel. The intervention comprised 14 contacts between 13 and 17 months of age. All children were tested again at age 18 months. The intervention and control groups were similar at baseline for a range of socioeconomic, demographic, environmental, and biological variables, and their MDI and PDI were also similar. At 18 months, the mean differences between the intervention and control groups were +9.4 points for MDI and +8.2 points for PDI (p<0.001 in each case). For children with an initial score of [les ]100, the mean difference between the intervened and control groups was +11.2 points for MDI (p<0.001), and +10.8 points for PDI (p=0.001). The intervention was thus associated with significant improvements in cognitive and motor development.

This prospective study examined the relation of neonatal sucking to later feeding, postnatal growth, maternal postpartum depression, and feeding practices. Healthy infants of at least 37 weeks gestational age were recruited. At 1 week of age, a strain-gage device was attached to the infant's cheeks during sucking to identify sucking efficiency. Two-hundred and two infants (100 males, 102 females; mean age 39.6 weeks, SD 1.1 weeks) with efficient sucking and 207 (101 males, 106 females; mean gestational age 39.4 weeks, SD 1.2 weeks) with inefficient sucking were identified. Growth was measured at 2, 6, 10, and 14 months. Mothers completed a feeding questionnaire and the Edinburgh Postnatal Depression Scale at the same testing points. While 18 infants (5%) showed a downward shift in growth, their clinical picture did not present as non-organic failure to thrive (NFTT). Inefficient neonatal sucking did not predict postnatal growth, later feeding difficulties, nor maternal feeding practices, but concurrent inefficient feeding did. Maternal depression did not affect feeding practices, infant feeding abilities, nor growth, suggesting that the importance of maternal postpartum depression in association with feeding may be less than previously assumed. The term NFTT, therefore, merits reexamination and a more focused definition.

Major conceptual advances in the area of paediatric neurosciences have been made in the last few years, mainly due to both molecular genetics, whereby the neurological phenotypes are now tentatively correlated with specific genotypes, and functional neuroimaging, whereby the neurological signs can be mapped to specific regions or circuits in the brain.

The recently proposed definition and classification of cerebral palsy (CP) is still up for debate – see the correspondence in this issue – and additional comments via the Castang website are warmly invited before the final version is completed next month (www.castangfoundation.net/workshops_washington_public.asp). The Castang Foundation funds ‘research into the causes of CP and other neurodevelopmental disorders leading to their prevention’. Rightly, the document does not specify the ‘non-progressive disturbances’ to which CP is attributed, with the exception of cerebral dysplasia. It is unclear why this should be picked out since in developed countries white matter disorders and perinatal vascular events currently appear more common. Data from other parts of the world are less available, but emphasize the continuing importance of post-neonatal causes. As the relative importance of different disturbances changes with medical knowledge, geography, and over time, a non-specific definition is understandable.

A randomized double-blind placebo-controlled clinical trial was carried out to determine whether a group of stable children with cerebral palsy (36 males, 21 females; mean age 10 years 11 months, range 5 to 18 years) would improve their motor skills after 12 months of threshold electrical stimulation (TES). Two thirds received active and one third received inactive stimulators. For the primary outcome we constructed a set of plausible motor function tests and studied the change in summary indices of the performance measurements. Tests were videotaped and assessed blindly to record qualitative changes that might not be reflected in performance measurements. We also judged range of motion, degree of spasticity, and muscle growth measured by CT. Fifty seven of 82 outpatients who were able to walk at least with a walker, completed all 12 months of treatment (hemiplegia n=25, diplegia n=32). There was no significant difference between active and placebo treatment in any of the tested groups, nor combined. Visual and subjective assessments favoured TES (ns), whereas objective indices showed the opposite trend. We conclude that TES in these patients did not have any significant clinical effect during the test period.

A preliminary cross-sectional study of 72 Hong Kong Chinese infants suggested that these infants learn to roll from supine-to-prone before rolling from prone-to-supine i.e. the opposite to teaching in most western texts. Three-hundred and sixty mothers were recruited postpartum and asked to record, on a chart, information related to the developmental milestone of rolling over for their infants (49% male) during the next 9 months. Telephone reminders were given at 4 and 8 months and, by the end of the study, information had been obtained from 240 mothers (67% of original sample, 51% male infants). Mean ages of rolling over were 5.1 months (SD1.5) for supine-to-prone and 5.7 months (SD1.3) for prone-to-supine. Age of rolling over from supine-to-prone was not influenced by usual sleep position, infant's sex, mother's intention to breastfeed infant, number of siblings, marital status, main daytime caregiver, or feeding method over 9 months. Hong Kong Chinese infants roll from supine-to-prone before they roll from prone-to-supine.

Severe congenital myotonic dystrophy (CMD) is an autosomal dominant condition characterized by hypotonia and respiratory insufficiency at birth. Terminal outcome has been reported in infants requiring ventilation for longer than 30 days. The case is reported of an infant born at 34 weeks' gestation with severe CMD. Infant survived following ventilatory support from birth until day 67 of life. Subcutaneous erythropoietin (600 units, three times weekly) was commenced on day 6 as the Jehovah's Witness parents were strongly opposed to blood transfusions. Haemoglobin fell to 5.8g/dL without adverse effects and then progressively rose to 15.4g/dL. No blood transfusions were necessary. This case illustrates that infants with severe CMD requiring ventilation for more than 30 days do not have a universally fatal outcome. Low haemoglobin was well tolerated which calls for re-examination of the indications for blood transfusions in ventilated neonates.

Status epilepticus is a common neurological emergency in children admitted to hospitals in resource-poor countries where it has a high mortality and is associated with a significant morbidity. In the last 5 years, some pharmaceutical companies have announced their intention to stop manufacturing parenteral preparations of phenobarbitone and chlormethaziole, and the supply of paraldehyde has been erratic. Paraldehyde and phenobarbitone are recommended for the management of status epilepticus in the recently published Advanced Paediatric Life Support guidelines. Their withdrawal would have serious repercussions for the management of status epilepticus in resource-poor countries as these drugs are relatively cheap and easy to administer in these settings.

‘Normal’ comes from the latin norma, a carpenter's square, and in mediaeval times meant something at a right angle or perpendicular. A few centuries later it came to mean conforming to a standard and was used in physics to refer to the average of a set of variables. If the variable concerned, such as head size or IQ, is continuous and has a normal distribution, by convention the normal range has come to include values falling within two standard deviations either side of the mean – defining about 4.6% of the population as abnormal. By a similar approach, if the variable has a skewed distribution, such as the age of walking, those lying outside the 2nd and 98th centiles are often defined as abnormal, while the normal is equated to the average. This can also lead to misunderstandings, as, for example, in some child-rearing books when parents are told that the normal age of walking is 12 months, which can mistakenly imply that the 50% of children, who by definition are not walking at that age, are abnormal.

CHARGE syndrome (coloboma, heart disease, atresia of the choanae, retarded growth and mental development, genital anomalies, and ear malformations and hearing loss) is a heterogeneous condition for which early prediction of intellectual outcome is important but difficult. The psychomotor milestones and intellectual outcome of a consecutive series of children with CHARGE syndrome who were observed by the same team from the neonatal period to the time of study were analyzed retrospectively. Twenty-one children (11 males and 10 females, aged from 5 to 12 years, mean 8 years 7 months, SD 2 years 5 months) were included. The influence of 19 early identifiable parameters that could be considered as deleterious for intellectual outcome was recorded. Generally, the main psychomotor milestones (0 to 4 years) were severely delayed, although intellectual outcome (at primary-school age) was satisfactory for half the children in this series. We show that extensive bilateral coloboma resulting in low vision, microcephaly, and brain malformation were the only three parameters that were predictive of poor intellectual outcome. Conversely, severe neonatal medical conditions, such as tracheotomy, conditions requiring long stays in hospital, or cardiac surgery were not predictive of poor intellectual outcome. Severe hearing loss was not found to be negatively correlated with intellectual outcome once coloboma had been taken into account.

Most studies on the frequency of autism have had methodological problems. Most notable of these have been differences in diagnostic criteria between studies, degree of cases overlooked by the initial screening, and type of measurement. This study aimed to replicate the first report on childhood autism to address cumulative incidence as well as prevalence, as defined in the International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10) Diagnostic Criteria for Research. Here, the same methodological accuracy (exactness of a measurement to the true value) as the first study was used, but population size was four times larger to achieve greater precision (reduction of random error). A community-oriented system of early detection and early intervention for developmental disorders was established in the northern part of Yokohama, Japan. The city's routine health checkup for 18-month-old children served as the initial mass screening, and all facilities that provided child care services aimed to detect all cases of childhood autism and refer them to the Yokohama Rehabilitation Center. Cumulative incidence up to age 5 years was calculated for childhood autism among a birth cohort from four successive years (1988 to 1991). Cumulative incidence of childhood autism was 27.2 per 10 000. Cumulative incidences by sex were 38.4 per 10 000 in males, and 15.5 per 10 000 in females. The male:female ratio was 2.5:1. The proportions of children with high-functioning autism who had Binet IQs of 70 and over and those with Binet IQs of 85 and over were 25.3% and 13.7% respectively. Data on cumulative incidence of childhood autism derived from this study are the first to be drawn from an accurate, as well as precise, screening methodology.

In order to test the practicability and safety of whole-body cooling in term neonates with moderate-to-severe hypoxic–ischaemic encephalopathy (HIE) and to report outcomes, a prospective pilot study was carried out in 25 term infants (median postmenstrual age 38 weeks, range 36 to 41 weeks; 20 males, five females). Whole-body cooling, to a target core temperature of 33 to 34°C, started within 6 hours of birth and was maintained for 72 hours. Of the 25 newborn infants (19 Sarnat II and six Sarnat III, 18 outborn), 18 survived, including 13 (72%) with normal cerebral signal by MRI. Temperature instability occurred during cooling in 15 infants, but neither severe haemodynamic instability nor renal failure was seen. Thrombocytopenia developed in 12 infants, including seven with biological disseminated intravascular coagulation. One patient had hypoxaemia with right-to-left shunting through the ductus arteriosus, and seven had limited meningeal or subdural bleeding. Whole-body cooling is feasible in term neonates, with no life-threatening adverse events. Improvements are needed to obtain stable hypothermia for 72 hours.

Despite several trials showing reductions in tone and improvements in gait, the relation between botulinum toxin A (BTX-A) dose and response has rarely been investigated. A double-blind randomized comparison of two doses of BTX-A in children with spastic hemiplegic cerebral palsy (n=48, mean age 7 years 6 months, range 3 to 15 years) was undertaken. The two doses selected were representative of the lower and the higher doses used in clinical practice (24 units/kg body weight and 8 units/kg body weight). Using gait analysis we evaluated hip, knee, and ankle joint kinetics and sagittal kinematics throughout the gait cycle. Gastrocnemius muscle length was calculated at each visit using the method described by Eames and used as our primary outcome measure. Our secondary outcome variable was maximum ankle angle measured during stance and swing phases. In summary, we found that there were indications that 24 units/kg body weight was more effective and lasted longer than 8 units/kg. Analysis in terms of absolute dose suggested that the dose–response correlation was non-linear, and that the optimal range lay between 200 and 500 units BTX-A (Dysport).