Paediatric arterial ischaemic stroke: functional outcome and risk factors

Aim To study functional outcome in children aged 1 month to 18 years after paediatric arterial ischaemic stroke (PAIS) and to identify risk factors influencing their quality of life. Method In a consecutive series of 76 children (35 males 41 females, median age at diagnosis 2y 6mo, range 1mo–17y 2mo; median length of follow‐up 2y 4mo, range [7mo–10y 6mo]) with PAIS diagnosed at the Erasmus Medical Centre Sophia Children's Hospital between 1997 and 2006, we collected clinical, biochemical, and radiological data prospectively. In 66 children surviving at least 1 year after PAIS, functional outcome could be evaluated with the World Health Organization’s International Classification of Impairments, Disabilities and Handicaps. Results Significant risk factors at presentation for a poor neurological outcome were young age, infarction in the right middle cerebral artery territory, and fever at presentation. Fifty‐four % of children had severe neurological impairments at 12 months after PAIS, and at last follow‐up more than half needed remedial teaching, special education, or institutionalization. Health‐related quality of life (HRQOL) questionnaires showed a significantly lower HRQOL in all age groups. Children with a longer follow‐up had a lower HRQOL in the cognitive functioning domain. Interpretation Our study shows significant morbidity and mortality and a reduced HRQOL after PAIS depending on age, fever at presentation, and infarction in the right middle cerebral artery territory.     

Evidence of impaired neurocognitive functioning in school‐age children awaiting cardiac surgery

Aim Children with congenital heart disease (CHD) are at risk of developing neurocognitive problems. However, as these problems are usually identified after cardiac surgery, it is unclear whether they resulted from the surgery or whether they pre‐existed and hence might be explained by complications and events associated with the heart disease itself. The purpose of this study was to examine whether neurocognitive deficits commonly reported after cardiac surgery are present before surgery. Method Forty‐five children (22 males, 23 females; mean age 11y 6mo, SD 3y 0mo) with cyanotic and acyanotic heart diseases scheduled for elective cardiac surgery were compared with 41 healthy peers (17 males, 24 females; mean age 11y 10mo, SD 2y 10mo) for attention and processing speed, construction, motor speed, motor planning and fluency, and visual memory. Twenty‐three children in the patient group were awaiting their first cardiac surgery and 22 were awaiting follow‐up surgery. Results The patients showed manifest neurocognitive difficulties. Their performance was inferior to that of the healthy comparison group for motor planning (p=0.02) and visual memory (p=0.01). The same neurocognitive profile was found in the group of patients awaiting their first cardiac operation. Interpretation School‐age children with various forms of CHD are at risk of neurocognitive impairments before cardiac surgery.     

Developmental delay of finger torque control in children with developmental coordination disorder

Aim We examined whether the behavioral impairments in finger torque control evident in children with developmental coordination disorder (DCD) follow a delayed or different developmental trajectory compared with their typically developing peers. Method Children with DCD (n=36; 18 males, 18 females; mean age 9y 7mo, SD 1y 8mo) and 36 typically developing children (15 males, 21 females; mean age 9y 7mo, SD 2y), between 6 years 10 months and 12 years 7 months of age were recruited from schools in Porto Alegre, Brazil. Particpants completed finger torque control and maximum finger torque production tasks. The inclusion criterion for children with DCD was a Movement Assessment Battery for Children score below the fifth centile. Group means and cross‐sectional age‐related landscapes of the two groups were compared. Results Children with DCD were more variable (p<0.001), less accurate (p=0.007), and less irregular (p<0.001), on average, in their finger torque control than their typically developing peers, despite producing nearly equivalent levels of maximum torque (p=0.49). Despite these mean differences, the cross‐sectional age‐related changes in torque control were similar in the two groups (all p>0.05). Interpretation The developmental trajectory of finger torque control in children with DCD, compared with typically developing children, is delayed. This suggests the behavioral deficits in finger torque control in children with DCD persist as a function of age, rather than progressing or resolving.     

Cognitive functions in classic phenylketonuria and mild hyperphenylalaninaemia: experience in a paediatric population

A study of 37 individuals with phenylketonuria (PKU; 17 females and 20 males, mean age 9y 9mo (standard deviation [SD] 5y 3mo), range 2y 8mo to 19y 4mo; and 35 individuals with hyperphenylalaninaemia (HPA; 20 females, 15 males, mean age 7y 10mo [SD 3y 2mo], range 2y 8mo to 17y 3mo) compared with 29 healthy controls (14 females and 15 males, mean age 9y 8mo [SD 4y 9mo], range 2y 6mo to 18y 10mo) was performed. The aim was to assess cognitive function in persons with HPA and to investigate the relation between cognitive function in PKU and the metabolic control of patients. A wide variety of neuropsychological tests was employed. Those with PKU showed lower values in intelligence and in visuo-spatial, fine motor, executive, and attention functions when compared with a control population. Plasma phenylalanine values from the first 6 years of life were negatively associated with intelligence and other cognitive functions. Executive function scores were significantly lower when comparing HPA patients with the control group. It was concluded that individuals with PKU under dietary treatment may present slightly decreased cognitive function scores when compared with control individuals, while those with HPA have scores mostly similar to those of controls, except for executive function tests. Good metabolic control of PKU seems necessary to prevent cognitive function impairments, especially during the first 6 years of life.     

Psychosocial problems and seizure-related factors in children with epilepsy

In this study we describe psychosocial functions and seizure-related factors in a population-based sample of children with epilepsy. Psychosocial problems (Achenbach scales), cognitive function, and socioeconomic status were studied in 117 children with epilepsy aged between 6 and 13 years (mean age 11y [SD 2y 1mo] and 10y 8mo [SD 2y]; 71 males, 46 females) and in randomly selected controls matched with 117 children for sex and age (mean age 11y 2mo [SD 2y 1mo] and 10y 5mo [SD 2y 4mo]; 69 males, 48 females). The children had partial (n=67), generalized (n=43), or undetermined (n=7) epilepsy syndromes, and partial (n=68), generalized (n=47), or other (n=2) main seizure types. Psychosocial problems were more common among children with epilepsy than controls (odds ratio 5-9) and significantly related to epilepsy syndrome, main seizure type, age at onset, and seizure frequency. Mothers and teachers reported males with epilepsy as having more problems than females. Females self-reported psychosocial problems, males did not. Psychosocial problems were common in childhood epilepsy. Females appreciated the problems more realistically than males. Psychosocial problems should be considered an integral part of epilepsy management.     

No association between the 2D:4D fetal testosterone marker and multidimensional attentional abilities in children with ADHD

Aim It has been suggested that high levels of prenatal testosterone exposure are implied in the aetiology of attention‐deficit–hyperactivity disorder (ADHD). This study examined the association between the ratio of the length of the second and fourth digits (2D:4D ratio), a marker of fetal testosterone exposure, and the presence of ADHD‐related cognitive and behavioural problems in children with ADHD and in typically developing comparison individuals. Method A clinically referred group of 64 children who fulfilled DSM‐IV‐TR criteria for ADHD (47 males, 17 females; mean age 8y 8mo, SD 1y 8mo, range 7–12y) and 46 comparison children (25 males, 21 females; mean age 9y 2mo; SD 1y 10mo, range 7–12y) were included in the study. The length of the second and fourth digits was measured by two independent raters. The Child Behaviour Checklist (CBCL) and the Test of Everyday Attention for Children (TEA‐Ch) were used to assess behavioural problems and different aspects of attention. Results No group differences in 2D:4D ratio were observed between children with (combined, inattentive, or hyperactive‐impulsive subtype of) ADHD and comparison children. The ratio did not show the postulated relation with cognitive and behavioural aspects of ADHD. Interpretation These findings challenge the hypothesis that fetal testosterone exposure plays a prominent role in the aetiology of ADHD.     

Congenital heart disease affects local gyrification in 22q11.2 deletion syndrome

22q11.2 deletion syndrome (22q11.2DS) is a common genetic condition associated with cognitive and learning impairments. In this study, we applied a three-dimensional method for quantifying gyrification at thousands of points over the cortical surface to imaging data from 44 children, adolescents, and young adults with 22q11.2DS (17 males, 27 females; mean age 17y 2mo [SD 9y 1mo], range 6–37y), and 53 healthy participants (21 males, 32 females; mean age 15y 4mo [SD 8y 6mo]; range 6–40y). Several clusters of reduced gyrification were observed, further substantiating the pattern of cerebral alterations presented by children with the syndrome. Comparisons within 22q11.2DS demonstrated an effect of congenital heart disease (CHD) on cortical gyrification, with reduced gyrification at the parieto-temporo-occipital junction in patients with CHD, as compared with patients without CHD. Reductions in gyrification can resemble mild polymicrogyria, suggesting early abnormal neuronal proliferation or migration and providing support for an effect of hemodynamic factors on brain development in 22q11.2DS. The results also shed light on the pathophysiology of acquired brain injury in other populations with CHD.     

Motor coordination, empathy, and social behaviour in school-aged children

Children with motor coordination problems are known to have emotional difficulties and poor social skills. The current study investigated whether children with poor motor ability have poor emotion recognition skills, and whether these could be linked to problems in social behaviour. It was hypothesized that difficulties in empathic ability might be related to the poor visuo-spatial processing ability identified in children with developmental coordination disorder (as defined by the American Psychiatric Association). The relationship between motor coordination, emotion recognition, and social behaviour was examined in a sample of 234 children (113 males, 121 females; mean age 9y 7mo, [SD 1y 8mo] age range 6y 8mo to 12y 11mo). From this sample two groups of 39 children each (17 females, 22 males), one group with motor difficulties (mean age 9y 11mo [SD 2y], range 6y 11mo to 12y 11mo) and the other of control children (mean age 10y [SD ly 11mo], range 6y 11mo to 12y 11mo), matched for age and sex, were compared using a set of six emotion recognition scales that measured both verbal and perceptual aspects of empathic ability. Children with motor difficulties were found to perform more poorly on scales measuring the ability to recognize static and changing facial expressions of emotion. This difference remained even when visuo-spatial processing was controlled. When controlling for emotion recognition and visuo-spatial organization, a child's motor ability remained a significant predictor of social behaviour.     

Refractive errors in infancy predict reduced performance on the movement assessment battery for children at 3 1/2 and 5 1/2 years

We have previously reported that significant hyperopia at 9 months predicts mild deficits on visuocognitive and visuomotor measures between 2 years and 5 years 6 months. Here we compare the motor skills of children who had been hyperopic in infancy (hyperopic group) with those who had been emmetropic (control group), using the Movement Assessment Battery for Children (Movement ABC). Children were tested at 3 years 6 months (hyperopic group: 47 males, 63 females, mean age 3 y 7 mo, SD 1.6 mo; control group: 61 males, 70 females, mean age 3 y 7 mo, SD 1.2 mo) and at 5 years 6 months (hyperopic group: 43 males, 56 females, mean age 5 y 4 mo, SD 1.7 mo; control group: 51 males, 62 females, mean age 5 y 3 mo, SD 1.6 mo). The hyperopic group performed significantly worse at both ages, overall and on at least one test from each category of motor skill (manual dexterity, balance, and ball skills). Distributions of scores showed that these differences were not due to poor performance by a minority but to a widespread mild deficit in the hyperopic group. This study also provides the first normative data on the Movement ABC for children below 4 years of age, and shows that it provides a useful measure of motor development at this young age.     

Gross motor development in children adopted from orphanage settings

Aim This study sought to examine the effect of environmental enrichment on the motor skills of children adopted from orphanage settings. We investigated balance and bilateral coordination skills in 33 internationally adopted postinstitutionalized children (16 males, 17 females; age range 8y 5mo–15y 10mo; mean age 10y 9mo; SD 2y 2mo) and compared them with 34 non‐institutionalized children (21 males, 13 females; age range 8y 3mo–14y 10mo; mean age 11y 2mo; SD 2y 1mo) being raised in their birth families. Method The children were individually administered the balance and bilateral coordination subtests of the Bruininks–Oseretsky Test of Motor Proficiency in a research laboratory. Parents completed questionnaires about developmental history, family environment, and orphanage care. Results Postinstitutionalized children showed motor system delays compared with the non‐institutionalized comparison children (postinstitutionalized balance mean 9.44, SD 5.92, comparison children balance mean 14.12, SD 4.39; postinstitutionalized bilateral coordination mean 11.97, SD 5.43, comparison children mean 19.97, SD 3.97). The length of time that children remained institutionalized before adoption predicted balance delays (b=?1.57, t=?2.33, p=0.027) and the severity of caregiving deprivation the children experienced correlated with bilateral coordination (r=?0.44, p=0.013). Interpretation These findings suggest that institutionalized settings do not provide the early life experiences needed for the development of age‐level motor skills later in childhood and that simple environmental enrichment following adoption is not enough to remediate skills. Children who have experienced early institutional care may benefit from early identification and targeted intervention.     

Cognitive outcome following unilateral arterial ischaemic stroke in childhood: effects of age at stroke and lesion location

Aim Plasticity in the developing brain is a controversial issue. Although language and motor function often recover remarkably well following early brain injury, recent evidence suggests that damage to the developing brain results in significant long‐term neuropsychological impairment. Our aim was to investigate the relationship among age at injury, lesion location and intellectual outcome. Method Using age‐appropriate Wechsler scales of intellectual ability, we explored this issue by evaluating a large group (n=145) of children (89 males, 56 females) who experienced unilateral arterial ischaemic stroke during the perinatal period (diagnosed mean 73d, SD 29d), between the ages of 1 month and 5 years (mean 2y 10mo, SD 1y 9mo), or between the ages of 6 and 16 years (mean 11y 1mo SD 3y 6mo). The mean age at assessment was 8 years (SD 3y 10mo) in the perinatal group, 7 years 5 months (SD 2y 9mo) in the 1 month to 5 years group, and 12 years 5 months (SD 3y 9mo) in the 6 to 16 years group. The mean time interval between stroke and assessment was 8 years (SD 18d) for perinatal, 4 years 6 months (SD 1y 5mo) for 1 month to 5 years, and 1 year 4 months (SD 2y 9mo) for 6 to 16 years. The relationship between age at stroke and lesion location (subcortical, cortical, or combined) as it pertains to cognitive outcome was also examined. Results Measures of overall intelligence, verbal ability, working memory, and processing speed were significantly lower in children who had had a stroke than in the normative sample (all z>2.5, all p<0.01). The perinatal group performed more poorly than the other two groups on most cognitive measures, regardless of lesion location. The combined lesion location group performed more poorly than those with damage to either cortical or subcortical areas alone. Further investigation revealed different periods of peak vulnerability for subcortical lesions (perinatal) and cortical lesions (1mo–5y). Interpretation Lesion location modulates the relationship between age at stroke and cognitive outcome.     

Executive function and theory of mind in school‐aged children after neonatal corrective cardiac surgery for transposition of the great arteries

Aim Cardiac malformations resulting in cyanosis, such as transposition of the great arteries (TGA), have been associated with neurodevelopmental dysfunction. The purpose of this study was to assess, for the first time, theory of mind (ToM), which is a key component of social cognition and executive functions in school‐aged children with TGA. Method Twenty‐one children (14 males, seven females; mean age 7y 4mo; SD 3mo) who underwent neonatal open‐heart surgery for TGA using full‐flow cardiopulmonary bypass were compared with 21 typically developing age‐matched children (12 males, nine females; mean age 7y 6mo; SD 3.8mo) using different neuropsychological measures specifically designed to assess executive function (cognitive and response inhibition, verbal and spatial working memory, and planning). They were also given two ToM tasks (first‐ and second‐order false belief understanding). Results General IQ was within the normal range in both the TGA group and the comparison group (mean IQ 113 [SD 9.3] and 118 [SD 10.1] respectively), but performance on all executive functions and on ToM (first and second level) was significantly lower in the TGA group (p values of 0.02, 0.01, and 0.004 respectively). A discriminant multivariate analysis provided evidence for cognitive and behavioural inhibition as well as performance on false belief tasks as being the most important contributors to the differentiation between the groups (p=0.03). Interpretation Children with TGA demonstrate great difficulties in exerting cognitive and behavioural inhibition. They also present specific deficits in false belief understanding, which were related to immature executive abilities.     

Effect of age and sex on maturation of sensory systems and balance control

Maintenance of postural balance requires an active sensorimotor control system. Current data are limited and sometimes conflicting regarding the influence of the proprioceptive, visual, and vestibular afferent systems on posture control in children. This study investigated the development of sensory organization according to each sensory component in relation to age and sex. A total of 140 children (70 males, 70 females; mean age 10y [SD 4y]; age range 3y 5mo-16y 2mo) and 20 adults (10 males, 10 females; mean age 30y 6mo [SD 8y 4mo]; age range 17y 2mo-49y 1mo) were examined using the Sensory Organization Test. Participants were tested in three visual conditions (eyes open, blindfolded, and sway-referenced visual enclosure) while standing on either a fixed or a sway-referenced force platform. Mean equilibrium scores for the six balance conditions showed rapid increases and maturation ceiling levels for age-related development of the sensorimotor control system. Proprioceptive function seemed to mature at 3 to 4 years of age. Visual and vestibular afferent systems reached adult level at 15 to 16 years of age, revealing differences between young males and females. Characterizing balance impairments can contribute to the diagnostic evaluation of neuromotor disorders.     

Efficacy of a hand-arm bimanual intensive therapy (HABIT) in children with hemiplegic cerebral palsy: a randomized control trial

Children with hemiplegic cerebral palsy (CP) have impairments in bimanual coordination above and beyond their unilateral impairments. Recently we developed hand-arm bimanual intensive therapy (HABIT), using the principles of motor learning, and neuroplasticity, to address these bimanual impairments. A single-blinded randomized control study of HABIT was performed to examine its efficacy in children with hemiplegic CP with mild to moderate hand involvement. Twenty children (age range 3 y 6 mo-15 y 6 mo) were randomized to either an intervention (n=10: seven males, three females; mean age 8 y 7 mo, SD 4 y) or a delayed treatment control group (n=10: seven males, three females; mean age 6 y 10 mo, SD 2 y 4 mo). Children were engaged in play and functional activities that provided structured bimanual practice 6 hours per day for 10 days. Each child was evaluated immediately before and after the intervention, and again at 1-month post-intervention. Children in the intervention group demonstrated improved scores on the Assisting Hand Assessment, increased involved extremity use measured using accelerometry and a caregiver survey, bimanual items of the Bruininks-Oseretsky Test of Motor Proficiency, and the simultaneity of completing a draw-opening task with two hands (p<0.05 in all cases). The results suggest that for this carefully selected subgroup of children with hemiplegic CP, HABIT appears to be efficacious in improving bimanual hand use.     

Short-term memory and vocabulary development in children with Down syndrome and children with specific language impairment

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 2.8 mo], 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.     

Motor skill performance of school-age children with visual impairments

The aim of this study was to examine the performance of children with visual impairments (VI) aged 7 to 10 years on different types of motor skills. Furthermore, the association between the degree of the VI and motor performance was examined. The motor performance of 48 children with VI (32 males, 16 females; mean age 8y 10mo [SD 1y 1mo]) was assessed using the Movement Assessment Battery for Children (MABC). Their performance was compared with 48 children without VI (33 males, 15 females; mean age 8y 9mo [SD 1y 1mo]). Children with VI showed the poorest performance compared with peers without VI on unimanual speed, eye-hand coordination, catching, static balance, and dynamic balance while moving slowly. There was no significant difference between children with moderate and severe VI, except for bimanual coordination in 7- to 8-year-olds and eye-hand coordination in both the 7- to 8-year-olds and 9- to 10-year-olds, favouring the children with moderate VI. The poor performance compared with children without VI is related to vision, but the degree of the VI does not appear to relate to motor performance, except when associated with bimanual and eye-hand coordination. For children with VI, it seems very important to adjust the environmental context and task to enhance motor performance.     

Does attention‐deficit–hyperactivity disorder exacerbate executive dysfunction in children with neurofibromatosis type 1?

Aim Although approximately 40% of children with neurofibromatosis type 1 (NF1) meet diagnostic criteria for attention‐deficit–hyperactivity disorder (ADHD), the impact of ADHD on the executive functioning of children with NF1 is not understood. We investigated whether spatial working memory and response inhibition are impaired in children with NF1 without a diagnosis of ADHD and whether executive deficits are exacerbated in children with a comorbid diagnosis. Method Forty‐nine children aged 7 to 15 years with NF1 only (31 males, 18 females; mean age 11y, SD 2y 4mo) or 35 with NF1 and ADHD (18 males, 17 females; mean age 10y 8mo, SD 2y 4mo) and 30 typically developing comparison children (16 males, 14 females; mean age 10y, SD 2y 8mo) were compared on measures of spatial working memory and response inhibition. Group differences in IQ and visuospatial ability were controlled for as required. Results Compared with typically developing children, children with NF1 with or without comorbid ADHD demonstrated significant impairment of both spatial working memory (both p<0.004) and inhibitory control (both p<0.010). There were, however, no differences between the two NF1 groups in spatial working memory (p=0.91) or response inhibition (p=0.78). Interpretation Executive dysfunction occurs with the same severity in children with NF1, whether or not they have a comorbid diagnosis of ADHD, suggesting that executive impairments are not unique contributors to ADHD symptomatology in NF1. The findings are discussed within the context of recent evidence in Nf1 optic glioma (OPG) mice, in which a mechanistic connection between NF1 gene expression, executive system failure, and dopaminergic pathway integrity has been established.     

Cognitive function in idiopathic generalized epilepsy of childhood

This study evaluated the cognitive profiles of children with idiopathic generalized epilepsy (IGE), uniformly treated with valproic acid with well-controlled seizures. Twenty-four were neuropsychologically evaluated. They comprised: 14 females, 10 males: 12 with generalized tonic-clonic seizures (GTCS), mean age 14y 4mo, SD ly 7mo, range 12y to 16y 4 mo; 12 with absence seizures (AS]) mean age 14y 5mo, SD ly 10mo, range 11y to 16y 4mo, with intellectual abilities within the normal range and age-appropriate scholastic skills, and 20 healthy controls (12 females, 8 males; mean age 14y 5mo, SD 1y 10mo, range 10y 7mo to 16y 7mo). As a group, children with IGE performed significantly poorer in all tests (non-verbal and verbal attention, verbal learning and memory, word fluency, and controlled sequential fine motor responses) excluding non-verbal memory. Analysis according to type of seizure revealed that both patient groups (AS and GTCS) had an attention deficit, whereas only children with AS showed deficits in verbal learning and memory, word fluency, and controlled fine motor responses. These results suggest a long-term risk of learning impairment for children with IGE, even if they have normal intelligence and their seizures are well controlled.     

Sex differences in tactile defensiveness in children with ADHD and their siblings

Tactile defensiveness (TD) is a disturbance in sensory processing and is observed in some children with attention-deficit-hyperactivity disorder (ADHD). TD has been examined in male children with ADHD and in children with ADHD without differentiating by sex. As males and females with ADHD may differ in the clinical expression of the disorder and associated deficits, the aim of this study was to examine sex differences in TD in males and females with ADHD. Non-affected siblings were also examined to investigate familiality of TD. The Touch Inventory for Elementary-School-Aged Children was administered to 47 children with ADHD (35 males, 12 females; mean age 9y 8mo [SD 1y 11mo]), 36 non-affected siblings (21 males, 15 females; mean age 8y 10mo [SD 2y 4mo]), and 35 control children (16 males, 19 females; mean age 9y 5mo [SD 6mo]). Results indicated that females with ADHD displayed higher levels of TD than males with ADHD (who did not differ from control males). This suggests that TD is sex specific and may contribute to the identification of ADHD in females, thus improving diagnostic and therapeutic strength in this under-referred group. Non-affected siblings were unimpaired, regardless of sex, which suggests that TD is specific to the disorder and not part of a familial risk for ADHD.