From studies within the USA, Israel, Norway and France, it has been estimated that the incidence of brain injury in children up to 14 years of age is 180 out of 100 000 per annum. Between 40 and 50% of children dying from acute traumatic injuries in the USA during 1991 had brain injury as part of their diagnosis and this proportion has been born out by other reports. However, death rates of children admitted for brain injury from whatever cause, which range from 2–3% to 14%, are not very helpful as the aetiology and admission criteria can vary widely.

The aim of the study was to test the hypotheses that elevated cerebral lactate, detected by proton spectroscopy performed within 18 hours of suspected birth asphyxia, is associated with adverse outcome, and that increased lactate can be used to predict adverse outcome. Thirty-one term infants suspected of having had birth asphyxia and seven control infants underwent proton magnetic resonance spectroscopy, using three-dimensional chemical shift imaging, within 18 hours of birth. Adverse outcome was defined as death or neurodevelopmental impairment at 1 year of age or more. Nine infants had an adverse outcome. The other 22 and all of the control infants remained normal. Median (range) lactate/creatine plus phosphocreatine (lactate/creatine) ratios in the abnormal, the normal, and the control group were 1.14 (0.17 to 3.81), 0.33 (0 to 1.51), and 0.05 (0 to 0.6) respectively (P=0.003). Lactate/creatine >1.0 predicted neurodevelopmental impairment at 1 year of age with sensitivity of 66% and specificity of 95%, positive and negative predictive values of 86% and 88%, and a likelihood ratio of 13.2. Elevated cerebral lactate/creatine within 18 hours of birth asphyxia predicts adverse outcome.

Handedness is the most prominent manifestation of behavioural lateralization in the human population. However, little is known about its ontogeny. This study examined the prenatal development of behavioural lateralization by observing, longitudinally, the occurrence of left- and right-arm movements in 17 human fetuses at 3-week intervals from 12 to 27 weeks gestational age. Fetuses exhibited significantly more right-arm movements than left-arm movements at every gestational age. Throughout all periods of observation, 83.3% of fetuses showed more right-arm than left-arm movements. The number of arm movements observed peaked at 15 to 18 weeks' gestation and declined rapidly in mid-gestation. The occurrence of laterality in early gestation indicates that asymmetric behaviour is probably under muscular or spinal, rather than cortical, control and points to a ‘genetic’ origin for such behaviour. The presence of lateralized motor behaviour in early gestation suggests it may have a potential causative role for subsequent lateralized behaviour and asymmetric brain development.

Two-hundred infants of <30 weeks gestational age were included in a randomized double-blind controlled trial to study the effect of thyroxine administration on neurodevelopmental outcome in very preterm children. The infants were given either a fixed dose of thyroxine (8 µg/kg birthweight/day) or placebo for the first 6 weeks of life. This paper evaluates the effect of thyroxine administration on behavioural outcome at the age of 2 years. More externalizing, especially destructive, behaviours were found in the group given thyroxine than in the placebo group. This difference was more pronounced in boys and in children born after 27 weeks' gestation. The thyroxine-treated children with behavioural problems had lower plasma-free thyroxine levels than the thyroxine-treated children without behavioural problems. This finding suggests that the presence of more behavioural problems in the group given thyroxine was not an immediate consequence of the treatment.

The prevalence of intellectual-, language-, and prereading-skill deficits was investigated in a geographically defined whole-population sample of very preterm children at 6 years of age in southern Germany. The sample consisted of the following: 264 very preterm children (75.6% of German-speaking survivors); 264 term controls (matched for sex, socioeconomic status [SES], marital status and age of mother); and a representative normative sample for Bavaria (N=311). Compared with term peers, very preterm children scored significantly lower (approximately −1 SD) on the measures of cognitive and language skills and had major cognitive deficits (<−2 SD) 10 to 35 times more often than the controls. Deficits in speech articulation and prereading skills (<10th centile) were three to five times more frequent in very preterm children. More than 18% of very preterm children had cognitive deficits in more than five areas of functioning, compared with no control children. The differences between very preterm children and controls remained highly significant when only very preterm children (N=229) and controls (N=261) without major neurosensory impairment were considered. Little evidence for specific cognitive deficits was found once mental processing measured in the Kaufman Assessment Battery for Children (K-ABC) was controlled for. The effect of preterm birth on cognitive abilities was found to be larger than the influence of SES. In conclusion, there was a high prevalence of long-term multiple cognitive problems in very preterm children. These persistent cognitive problems appear to be of pre- or neonatal (treatment) rather than postnatal social origin.

This study aimed to investigate the validity of disintegrative psychosis (DP) as defined in the ICD-9. The history of epilepsy in 13 subjects with DP was compared with that of 39 subjects with infantile autism (IA) who were matched for sex, age, IQ, and socioeconomic status (SES). The average follow-up time was 22 and 23 years (range 11 to 33 years). A significant difference was found between the DP and IA groups in terms of incidence of epilepsy, 77% versus 33% respectively. The peak period of onset of epilepsy occurred before puberty in both groups. Different types of epilepsy were seen, but the psychomotor variant accounted for 50% in the DP group, while 46% of the IA group had the psychomotor and 62% had the grand mal variant. The types are not mutually exclusive. Individuals without epilepsy had significantly higher IQ scores than those with epilepsy, but only within the IA group. The increased risk of developing epilepsy in the DP group is most likely a reflection of an underlying early brain pathology probably present in most individuals with DP. On the whole our findings can be seen as a contribution to the validation of DP as separate from IA, as these two conditions could be distinguished in terms of the way they develop with reference to epilepsy.

Forty-seven children with non-organic failure to thrive (NOFT) were identified from a whole-population survey of children's growth and development. A significant proportion (N=17) of these 47 children were found to have oral-motor dysfunction (OMD) identified using a previously validated assessment tool. NOFT children with OMD and those with normal oral-motor function (N=30) were compared in order to ascertain whether there were any neurodevelopmental differences which might explain this finding. We hypothesized that children with OMD might have a subtle neurodevelopmental disorder. Few psychosocial variables discriminated the two groups. However, cognitive stimulation within the home and cognitive-growth fostering during mealtimes was much poorer for children with OMD. Some evidence has suggested that NOFT children with OMD may be ‘biologically’ more vulnerable from birth. We suggest that the continued use of the term ‘non-organic’ to describe failure to thrive in such children is questionable and requires redefining.

The results of a therapeutic trial of the use of melatonin in patients with tuberous sclerosis complex who also have severe sleep problems are reported. We used a randomized double-blind placebo-controlled crossover design. Seven patients with confirmed diagnoses of tuberous sclerosis and significant sleep disorder were recruited. We employed three outcome measures: total sleep time, time to sleep onset, and number of awakenings. Patients treated with melatonin had a small but clinically significant improvement in total sleep time (mean improvement 0.55 hours, P<0.05). They also tended to have an improvement in sleep-onset time but this did not reach statistical significance. Melatonin, in this trial, had no discernible effect on sleep fragmentation. We conclude that melatonin does have a beneficial effect in prolonging the total sleep time of patients with tuberous sclerosis and sleep disorder and that further trials are necessary to investigate the issues of optimal dosage, tolerance, and possible interactions with other medications.

A girl with partial lipodystrophy is described presenting with muscle weakness and developmental delay several years before lipoatrophy became apparent. The patient subsequently developed epilepsy, fatty liver, secondary amenorrhoea, hirsutism, insulin-resistant diabetes mellitus, hyperlipidaemia, and hypothyroidism. She remains weak with poor exercise tolerance. This case illustrates an atypical presentation of the Barraquer–Simon syndrome.

Thrombotic and thromboembolic complications are the main causes of morbidity and mortality in patients with homocystinuria. However, it is unusual for thrombosis and infarction to be the presenting feature leading to investigation for homocystinuria and cerebrovascular lesions in the first year of life. We describe a previously healthy 6-month-old infant who presented with a large middle-cerebral-artery territory infarction and died of massive brain swelling. Homocystinuria due to cystathionine β-synthase (CBS) deficiency was diagnosed by metabolite analysis and confirmed by enzymatic activity measurement in a postmortem liver biopsy. Homocystinuria should be considered in the differential diagnosis of venous or arterial thrombosis, regardless of age, even in the absence of other common features of the disease. We recommend systematic metabolic screening for hyperhomocysteinemia in any child presenting with vascular lesions or premature thromboembolism.

Cranial ultrasound abnormalities, especially a white-matter echolucency, predict disability (Paneth and Pinto-Martin 1990, Whitaker et al. 1990, Dammann and Leviton 1997), but with limitations. For example, half of very preterm infants who develop cerebral palsy (CP) do not have any abnormality of the white matter (Pinto-Martin et al. 1995, O'Shea et al. 1998). In addition, echolucencies that predict spastic CP are seldom located with descending fibers from the motor cortex (Rogers et al. 1994). These findings have led to the ‘tip of the iceberg’ hypothesis which postulates that cranial ultrasound scans do not detect the entirety of the white-matter damage (Leviton and Gilles 1996).