Foreword 2

Recent trends in neurodisability: implications for research and prevention 4

Genetic contribution to neurodevelopmental disability: an overview 6

Normal and abnormal development of the central nervous system I 7

Normal and abnormal development of the central nervous system II 8

Neurodisability and the channelopathies 12

Neurodisability: metabolic and hormonal aspects 14

Studies of children in developing countries 18

Likely changes in obstetric practice – the next 10 years 25

The role of neuroimaging over the next 10 years 29

Cerebral palsy: can we prevent it? 30

Autism: known and unknown 31

Prevention of severe learning disability 35

Childhood epilepsy: secondary prevention is crucial 38

Specific learning disorders: primary and secondary prevention 42

The spectrum of language regression in childhood is incompletely understood. To describe the features of this disorder more fully, we reviewed the records of 196 consecutive children (143 males and 53 females) with language regression or perceived plateau evaluated between 1988 and 1994 by a child neurologist. Mean age at regression was 21.2 months and the mean interval to referral was 34.8 months. A trigger for the regression was identified in 74 of the children (38%) and was associated with a more rapid regression. Mean age at follow-up was 64 months (SD 55). Seventy per cent of the children became nonverbal, and 75% were cognitively impaired. Language regression was associated with a more global autistic regression in 93% of children. There was a history of seizures in 15% of the children. Some recovery occurred in 61% but only one child recovered fully. Improvement was more likely in the 49% who were entirely developmentally normal before the regression. We conclude that language regression in childhood is a serious disorder with significant long-term morbidity.

Three groups of children with communication disorders were examined using a series of psycholinguistic markers to explore whether the tasks could identify children with impairments other than specific language impairment (SLI), and to examine whether the different groups within this clinical population could be distinguished reliably from one another. The groups comprised children with autistic spectrum disorders (ASD; n=13, all males; mean age 10 years 10 months, range 10 years 2 months to 12 years 6 months); children with primary pragmatic language impairment (PLI) but who did not have definite ASD diagnoses (n=25, 22 males, three females; mean age 11 years 3 months, range 10 years 2 months to 12 years 5 months); and children with specific language impairment (SLI) without marked pragmatic language difficulties (n=29, 25 males, 4 females; mean age 10 years 10 months, range 10 years 2 months to 11 years 9 months). Clinical markers examined were: the Children's Non-Word Repetition (CNRep), the Past Tense Task (PTT), and the Clinical Evaluation of Language Fundamentals, Recalling Sentences. First, it was found that the a priori groupings were not sufficiently defined and that four groups were actually present. The PLI group was in fact two separate samples: those with PLI pure and those with some autistic-like behaviours (referred to here as PLI plus, following Bishop 1998). Second, group comparisons indicated that CNRep was significantly lower for children with SLI than all other groups (although this measure was not such a good discriminator using a specificity analysis). Third, the markers were able to discriminate between all types of communication impairment in normal control participants (n=100; 51 females, 49 males; mean age 11 years, range 10 years 5 months to 11 years 6 months) with sensitivity levels of at least 75% and specificity of 80%. Recalling Sentences was the most efficient marker for all groups. Finally, analysis showed that children with PLI plus could be accurately distinguished from all others, scoring most favourably overall on communication markers and on performance IQ scores.

In the this study, both fine and gross motor ability of males with attention-deficit–hyperactivity disorder (ADHD) were compared with a group of control children. Three groups of males with the following ADHD subtypes: predominantly inattentive (ADHD-PI; n=50), hyperactive/impulsive (ADHD-HI; n=16), or combined (ADHD-C; n=38) were compared with 39 control males. Mean ages for the control group were 10 years 4 months (SD 1 year 4 months, range 7 years 8 months to 12 years 11 months); for the ADHD-PI group, 10 years (SD 1 year 2 months, range 7 years 10 months to 13 years); for the ADHD-HI group, 9 years 11 months (SD 1 year 2 months), range 7 years 11 months to 12 years 6 months); and for the ADHD-C group 10 years 2 months (SD 1 year 4 months, range 8 to 13 years). The Australian Disruptive Behaviours Scale and Connors' Parent Rating Scale-Revised were used to assess ADHD symptomatology. Verbal IQ was estimated using two verbal subtests of the Wechsler Intelligence Scale for Children, and movement ability was assessed using the Movement Assessment Battery for Children (MABC) and the Purdue Pegboard test. Findings demonstrated that the children with ADHD had significantly poorer movement ability than control children. A high percentage of these children displayed movement difficulties consistent with developmental coordination disorder (DCD). In addition, the current study found that the type and degree of movement difficulty differed between subtypes. The Total Impairment score, as derived from the MABC, was less severe for the ADHD-HI group than the other two ADHD groups, but more severe than for the control group. Males with ADHD-PI and ADHD-C had significantly poorer fine motor ability (p<0.001) than control males, whereas the ADHD-HI group did not differ significantly from any of the other groups. As children with ADHD only and the control group did not differ significantly on fine motor ability but were significantly better than children categorized with both ADHD and DCD, it was argued that poorer fine motor ability found in children with ADHD could not be attributed to deficits in attention and concentration, but rather to factors relating to their motor ability.

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.

The aim of this study was to determine the extent of ankle muscle weakness in children with cerebral palsy (CP) and to identify potential causes. Maximal voluntary contractions of plantar (PF) and dorsiflexors (DF) were determined at optimal angles in knee flexion and extension in both legs of 14 children with hemiplegia (7 males, 7 females) and 14 with diplegia (8 males, 6 females). Their results were compared to 14 age- and weight-matched control participants (5 males, 9 females). Muscle cross-sectional areas of soleus, posterior, and anterior compartment muscles were determined from MRIs in 14 children with CP (eight diplegia, six hemiplegia) and 18 control children. Specific tension (torque/unit area) of PF and DF was determined from torque and cross-sectional area results. Muscle volumes of PF and DF were also determined in both legs of five control children and five with hemiplegia. Muscle EMG was recorded from soleus, medial gastrocnemius, and tibialis anterior during each maximal voluntary contraction. Mean amplitude was significantly reduced in PF and DF in both CP groups and significantly higher levels of coactivation of antagonists were found compared to control participants. Strength of PF and DF was significantly reduced in both CP groups, but more importantly the muscles were found to be weak based on significantly reduced specific tensions. The PF were most affected, particularly in the group with hemiplegia. It is believed that an inability to maximally activate their muscles contributed to this weakness. A combination of incomplete activation and high levels of PF coactivation are thought to have contributed to DF weakness.

The aim of this study was to determine the long-term outcome of neurosurgical untethering on neurosegmental motor level and ambulation level in children with tethered spinal cord syndrome. Forty-four children were operated on (17 males, 27 females; mean age at operation 6 years 2 months, SD 5 years). Sixteen patients had myelomeningocele, nine had lipomyelomeningocele, and 19 had other types of spinal dysraphism. Motor level and ambulation level were assessed pre- and three times postsurgery (mean duration of follow-up 7 years 1 month, SD 1 year 8 months). Deterioration of motor level was seen in five of 44 patients, 36 of 44 remained stable, while improvement was seen in three of 44 patients. Deterioration of ambulation level was seen in five of 44 patients, and remained stable in 26 of 44. Thirteen of 44 children were too young to ambulate at time of operation (<2 years 6 months). Late deterioration of motor or ambulation level was only seen in (lipo)myelomeningocele patients. Deterioration of ambulatory status was strongly associated with obesity and retethering. Revision of the initial tethered cord release was performed in nine of 44 patients, mainly in those with lipomyelomeningocele.

Animal studies suggest that psychological factors may interfere with the development of brain asymmetry during gestation. We evaluated whether psychological exposure in pregnancy was associated with mixed-handedness in the offspring. In a follow-up design study, 824 Danish-speaking women with singleton pregnancies provided information on psychological distress and the occurrence of life events in the early second and third trimesters of pregnancy. Handedness of the children was based on maternal reports when the children were 3 years of age. Among the 419 males and 405 females, 7% and 5% respectively were mixed-handed whereas mixed-handedness was found in 3% of the parents. Psychological distress in the third trimester as well as higher levels of stressful life events were related to a higher prevalence of mixed-handedness in the offspring. About 16% of the women reported more than one life event in the third trimester of pregnancy and among the offspring of these women 11% were mixed-handed(odds ratio=2.3; 95% confidence interval 1.2 to 4.4). Women who at the same time reported a high level of distress and stressful life events, had a three- to four-fold higher prevalence of mixed-handedness in their offspring.

Visual masking assesses visual perception and attention; it occurs when a visual stimulus (mask) interferes with the perception of a stimulus that the participant is trying to identify (target). A backward masking study (target presented before mask) was performed on 662 children without disabilities (338 females), aged between 6 and 17 years, in order to evaluate if performance varies with age. In the masking procedure 10 letters were presented through a tachistoscope as target stimuli. Fragments of letters oriented at random (‘noise’) represented the mask. A slight improvement of visual performance from the beginning of school age to 9–12 years of age was found. This paper gives normative data for the most important parameters which can be used as a standardized reference for the procedure employed. We also studied 113 children with epilepsy (56 females), aged between 5 and 19 years, who attended a mainstream school and had been seizure free for at least 2 years. Children were tested just before starting antiepileptic drug withdrawal and re-tested 1 year later; they were drug free for 3 months before the second test. These children showed, during and after treatment, only slightly worse results when compared with healthy children of the same age; after therapy withdrawal, their visual performance slightly improved but this was not statistically significant.

A female child presenting with acute flaccid paraparesis at 18 months was found to have a dermal sinus in combination with a dermoid cyst and a myxopapillary ependymoma of the cauda equina and conus medullaris. A possible embryologic relation between these lesions is discussed.

As previously described, the subject of consanguineous marriage became a source of major scientific and public interest in the UK and the USA from the mid-19th century onwards. Much of this interest centred on the claimed deleterious outcomes of consanguinity, although there were also scientists and clinicians who denied any adverse effects and instead argued that inbreeding offered major biological advantages. A large majority of studies have indicated that early mortality is increased in the progeny of consanguineous unions when compared with children born to unrelated parents. However, most of these studies failed to control for the potential effects of sociodemographic variables. Where such control was attempted, as in extensive post-World War II surveys conducted in Japan, the adverse biological effects of consanguinity were still present but were much less obvious, and similar findings have been reported in more recent studies in the Indian sub-continent.