Hydrocephalus in children has many aetiologies, and can cause multiple ophthalmic and visual disorders. This study sets out to detect and quantify visual and visuoperceptual dysfunction in children who have received surgical treatment for hydrocephalus with and without myelomeningocele, and to relate the results to the associated diagnoses and results from a comparison group. Seventy-five school-aged children (41 males, 34 females) with surgically-treated hydrocephalus and 140 comparison children (76 males, 64 females) matched for age and sex underwent comprehensive ophthalmologic examination. Median age at examination was 9 years and 4 months (range 7y 4mo–12y 10mo). Visual function deficits were identified in 83% (62/75) of the children with hydrocephalus. Visual impairment (binocular visual acuity <0.3) was found in 15% (11/73; comparison group 0%) but in none with myelomeningocele. Strabismus was found in 69% (51/74; comparison group 4% [5/140], p<0.001), and refractive errors were found in 67% (47/70; comparison group 20% [28/140], p<0.001). Cognitive visual dysfunction was identified in 59% (38/64; comparison group 3% [4/140], p<0.001). These disorders were identified in various combinations and comprised impaired ability to plan movement through depth (e.g. going down a stair), impaired simultaneous perception, impaired perception of movement, impaired orientation, and (least frequently) impaired recognition. In this study, children with hydrocephalus associated with myelomeningocele were least commonly affected. Visual disorders were most frequent in those with epilepsy, cerebral palsy, and/or cognitive disability.

The aim of this study was to illustrate the difficulties in establishing a diagnosis of mitochondrial respiratory chain (MRC) disorders based on clinical grounds in combination with intermediate activities of the MRC enzyme complexes. We reviewed retrospectively all medical and laboratory records of patients initially considered likely to have MRC disorders on clinical grounds, and subsequently diagnosed with other disorders (n=20; 11 males, 9 females). Data were retrieved from hospital records, referral letters, and results of enzymatic analysis at a reference laboratory. Clinical symptoms included developmental delay, epilepsy, hypotonia, movement disorder, spastic quadriplegia, tetany, microcephaly, visual problems, carpopedal spasms, dysmorphism, hearing loss, muscle weakness and rhabdomyolysis, and fulminant hepatitis. Blood and cerebrospinal fluid lactate levels were elevated in 13/20 and 9/20 respectively. One or more MRC complex activities (expressed as ratios relative to citrate synthase and/or complex II activity) were less than 50% of control mean activity in 11/20 patients (including patients with deficiencies of pyruvate dehydrogenase complex, pantothenate kinase, holocarboxylase synthetase, long-chain hydroxy acyl-CoA dehydrogenase, molybdenum co-factor, and neonatal haemochromatosis). One patient had a pattern suggestive of mitochondrial proliferation. We conclude that intermediate results of MRC enzymes should be interpreted with caution and clinicians should be actively looking for other underlying diagnoses.

Individual rhythms of suck, swallow, and respiration are disrupted in preterm infants with bronchopulmonary dysplasia (BPD). Integration of respiration into suck–swallow efforts is critical for establishing coordinated suckle feeding. This study quantitatively assessed the coordination of respiration and swallow in infants with and without BPD. Thirty-four preterm infants of 26 to 33 weeks' gestational age were included: 14 participants with BPD (eight males, six females)and 20 comparison participants without BDP (10 males, 10 females). Participants were studied at postmenstrual age 32 to 40 weeks and postnatal age 2 to 12 weeks using digital recordings of pharyngeal pressure, nasal thermistor flow, and thoraco-abdominal plethysmography. The coefficients of variation (COV; standard deviation/mean) of the swallow–breath (SW–BR) and breath–breath (BR–BR) intervals during swallow runs, the percentage of ‘apneic swallows’ (runs of [ges ]3 swallows without interposed breaths), and phase relationships of respiration and swallow were used to quantify rhythmic coordination and integration of respiration into feeding episodes. Apneic swallows were significantly increased after 35 weeks in infants with BPD (mean 13.4% [SE 2.4]) compared with non-BDP infants (6.7% [SE 1.8]; p<0.05), as were SW–BR phase relationships involving apnea. The BPD cohort also had significantly higher SW–BR COV and BR–BR COV than non-BPD infants, indicating less rhythmic coordination of swallowing and respiration during feeding. Results emphasize the need for frequent rests and closer monitoring when feeding infants with respiratory compromise. Quantitative assessment of the underlying rhythms involved in feeding may be predictive of longer-term feeding and neurological problems.

Tiagabine, developed as an anti-epileptic medication, has the potential to reduce spasticity. The purpose of the present study was to assess the effectiveness of tiagabine in decreasing spasticity and improving the functional abilities of children with spastic cerebral palsy (CP). Nine children (seven females, two males) with CP (six spastic quadriplegia, three moderate to severe spastic diplegia) were treated with tiagabine for a mean of 7.2 months. Median age was 4y 5mo (range 3y 2mo–10y). All children were non-ambulatory. According to the Gross Motor Function Classification System, six were Level IV and three were Level V. Only one child showed a median decrease [ges ]1.0 grade on the modified Ashworth scale in upper extremities, lower extremities, and overall. Another child had significant improvement in the Pediatric Evaluation of Disability Inventory Self-care score and improved feeding. None of the participants was found to have a significant improvement in motor function or a decrease in the number of motions (passive range of motion and muscle length test) that were limited. Reduction of nocturnal awakenings from painful spasms was reported in one child. Eight of the nine children experienced adverse side-effects during treatment. Although tiagabine was not found to be effective in decreasing children's spasticity or improving their function, its potential use in the relief of painful spasms associated with neurological conditions in the pediatric population warrants further investigation.

The reliability of visual interpretation of electroencephalograms (EEG) is of great importance in assessing the value of this diagnostic tool. We prospectively obtained 50 standard EEGs and 61 EEGs after partial sleep deprivation from 93 children (56 males, 37 females) with a mean age of 6 years 10 months (SE 5mo; range 4mo–15y 7mo) with one or more newly diagnosed, unprovoked seizures. Two clinical neurophysiologists independently classified the background pattern and the presence of epileptiform discharges or focal non-epileptiform abnormalities of each EEG. The agreement was substantial for the interpretation of the EEG as normal or abnormal (kappa 0.66), almost perfect for the presence of epileptiform discharges (kappa 0.83), substantial for the occurrence of an abnormal background pattern (kappa 0.73), and moderate for the presence of focal non-epileptiform discharges (kappa 0.54). In conclusion, the reliability of the visual interpretation of EEGs in children is almost perfect as regards the presence of epileptiform abnormalities, and moderate to substantial for the presence of other abnormalities.

Language disorders have been reported after severe falciparum malaria but the deficits have not been described in detail. We assessed language outcome in three groups of children aged 6 to 9 years (n=487): those previously admitted to Kilifi District Hospital, Kenya, with cerebral malaria (CM; n=152; mean age 7y 4 mo [SD 1y 1mo]; 77 males, 75 females); or those with malaria and complicated seizures (M/S; n=156; mean age 7y 4mo [SD 1y 2mo]; 72 males, 84 females); and those unexposed to either condition (n=179; mean age 7y 6mo [SD 1y 1mo]; 93 males, 86 females). Median age at hospital admission was 28 months (interquartile range [IQR] 19 to 44 mo) among children with a history of CM and 23 months (IQR 12 to 35mo) among children with a history of M/S. A battery of eight assessments covering the major facets of speech and language was used to measure language performance. Cognitive performance, neurological/motor skills, behaviour, hearing, and vision were also measured. Eighteen (11.8%) of the CM group, 14 (9%) of the M/S group, and four (2.2%) of the unexposed group were found to have a language impairment. CM (odds ratio 3.68, 95% confidence interval 1.09 to 12.4, p=0.04) was associated with significantly increased odds of an impairment-level score relative to the unexposed group. The results suggest that falciparum malaria is one of the most common causes of acquired language disorders in the tropics.

Following the introduction of combination antiretroviral therapy, children vertically infected with the human immunodeficiency virus (HIV-1) living in the developed world are surviving into adult life. This paper reviews the neurodevelopmental outcomes of 62 consecutively-presenting children with HIV-1 infection diagnosed before 3 years of age (32 males, 30 females; median age at presentation 6mo). Neurological and developmental data are presented with immunological and virological responses to antiretroviral therapy. Fourteen children (22%) had abnormal neurological signs and 25 (40%) demonstrated significant developmental delay on standardized developmental assessments. Children presenting with more severe HIV-1 disease and immune compromise had significantly more abnormal neurological signs and developmental delays than children presenting with milder HIV-1 symptomatology. Immune function, control of HIV-1 viral replication, and growth parameters improved with antiretroviral therapy (median age at last follow-up 7y 3mo); however, abnormal neurological signs and significant gross motor difficulties persisted.

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.

In children with nocturnal enuresis, a higher rate of minor neurological dysfunction has been found. The aim of this study was to assess timed performance (a measure of motor performance speed) and associated movements using a standardized and reliable instrument. The motor function of 37 children with nocturnal enuresis (27 males, 10 females; mean age 10y 7mo [SD 1y 10mo]; age range 8y–14y 8mo) and 40 comparison children without enuresis (17 males, 23 females; mean age 10y 7mo [SD 1y 6mo]; age range 8y–14y 8mo) was assessed using the Zurich Neuromotor Assessment. Children with nocturnal enuresis showed a slower motor performance than comparison children, particularly for repetitive hand and finger movements. This study provides evidence for a maturational deficit in motor performance in children with nocturnal enuresis. In addition to a maturational deficit of the brainstem, it is proposed that there is a possible maturational deficit of the motor cortex circuitry and related cortical areas in children with nocturnal enuresis.

Forty-two infants (20 males, 22 females) with classical phenylketonuria (PKU) entered a prospective, double-blind, randomized study to investigate the effects on biochemical and physiological outcomes of a phenylalanine-free infant formula containing a fat blend supplemented with the long-chain polyunsaturated fatty acids (LC-PUFA), docosahexaenoic acid (DHA, C22:6n–3), and arachidonic acid (AA, C20:4n–6). Between entry and 20 weeks (entry and 1y) of age, median DHA levels in erythrocyte membrane phospholipids decreased by 15% (22%) in the LC-PUFA supplemented group (n=21) and by 61% (64%) in the control group (p<0.001; n=18). A dietary supply of LC-PUFA in infants with PKU prevents the decline in DHA levels associated with a diet supplying minimal sources of LC-PUFA. DHA status in turn, independent of diet, may influence the maturation of the visual system in infants with PKU.

We describe a quantitative and comparative review of a selection of European birthweight standards for gestational age for singletons, to enable appropriate choices to be made for clinical and research use. Differences between median values at term across standards in 10 regions and misclassification of ‘small for gestational age’ (SGA), were studied. Sex and parity differences, exclusion criteria, and methods of construction were considered. There was wide variation between countries in exclusion criteria, methods of calculating standards, and median birthweight at term. The lightest standards (e.g. France's medians are 255g lower than Norway's medians) were associated with fewer exclusion criteria. Up to 20% of the population used in the construction of the Scottish standard would be classified as SGA using the Norwegian standard. Substantial misclassification of SGA is possible. Assumptions about variation used in the construction of some standards were not justified. It is not possible to conclude that there are real differences in birthweight standards between European countries. Country-based standards control for some population features but add misclassification due to the differing ways in which standards are derived. Standards should be chosen to reflect clinical or research need. If standards stratified by sex or parity are not available, adjustments should be made. In multinational studies, comparisons should be made between results using both a common standard and country-based standards.

Diagnosing ischaemic stroke and determining its cause is difficult in children. Both are important for selection of treatment and prediction of outcome. This study explored the diagnostic changes that lead to a delay in the correct diagnosis of paediatric stroke. Case histories of 45 children with ischaemic stroke (31 males, 14 females; median age 6y; age range 2mo–16y) were retrospectively reviewed. The initial clinical diagnosis, based on the interpretation of presenting symptoms, was compared with the final aetiological stroke diagnosis after completion and review of diagnostic work-up. The type of diagnostic change, consequent time delay until correct diagnosis, reasons for change of diagnosis, and alterations to management were evaluated. Twenty-four diagnostic changes were identified; 19 in ‘primary stroke diagnosis’ (symptoms initially not attributed to stroke), and five in ‘aetiological diagnosis’ (incorrect initial determination of type or cause of stroke). The median interval between initial and final diagnosis was 7 days (3h–2y). The change in diagnosis led to therapeutic alterations in 17 patients. Risk factors for childhood stroke differ from those in adults. Stroke is frequently not recognized as the cause of the child's symptoms, and the correct determination of stroke aetiology takes time. We recommend that children with stroke be evaluated in a centre with expertize, using standardized diagnostic protocols and careful follow-up.

There has been little exploration of major biologic regulators of cerebral development in autism. We measured insulin-like growth factors (IGF) -1 and -2 from cerebrospinal fluid (CSF) by radio immunoassay in 25 children with autism (median age 5y 5mo; range 1y 11mo–15y 10mo; 20 males, 5 females), and in 16 age-matched comparison children without disability (median age 7y 4mo; range 1y 1mo–15y 2mo; eight males, eight females). IGF-1 and -2 concentrations were further correlated with age of patients and head size. CSF IGF-1 concentration was significantly lower in patients with autism than in the comparison group. The CSF concentrations of children with autism under 5 years of age were significantly lower than their age-matched comparisons. The head circumferences correlated with CSF IGF-1 in children with autism but no such correlation was found in the comparison group. There was no difference between the two groups in CSF IGF-2 concentrations. No patients with autism had macrocephaly. We conclude that low concentrations of CSF IGF-1 at an early age might be linked with the pathogenesis in autism because IGF-1 is important for the survival of Purkinje cells of the cerebellum. The head growth might be explained by the actions of IGF-1 and -2 reflected in CSF concentrations.

The chickenpox virus (varicella zoster virus; VZV) is known to cause large and small vessel central nervous system vasculopathies that may be associated with strokes in both adults and children. We present the case of a female aged 2 years 6 months who developed a chronic progressive small-vessel vasculopathy with radiological features of moyamoya disease as a manifestation of congenital varicella syndrome. Clinically, the condition was characterized by recurrent ischaemic strokes, which were brought under control using intravenous acyclovir. The case is unique in that it is the first report of congenital varicella syndrome to occur after a maternal herpes zoster infection. Furthermore, it is the first case of symptomatic VZV infection in a child to occur after a maternal infection occurring in the third trimester of pregnancy.

Neurofibromatosis type 2 (NF2) remains a challenging diagnosis in childhood where there may be no neurological involvement. A 12-month-old male in whom NF2 was suspected because of characteristic ophthalmological and cutaneous lesions is reported. Cranial MRI showed no tumours. A pathogenic mutation was identified on NF2 gene analysis. The child developed hypertension due to renal vascular disease. Although renal vascular disease is a recognized complication of neurofibromatosis type 1 (NF1), it has not been reported in NF2.

This study reports on a novel methodology using the V-scope to quantify elbow and shoulder movement in young children with obstetric brachial plexus palsy (OBPP), and the intra- and interreliability of this method. The V-scope, a portable, inexpensive movement analysis system, was configured in an L-shape, with two transmitting towers placed on the floor and one 1.35m off the ground. These towers received ultrasonic pulses from buttons that were placed over standardized landmarks of the child's trunk, chest, and upper limb. Two physiotherapists (a paediatric and a generalist) facilitated the maximum range of active elbow flexion/extension and shoulder abduction/flexion in 30 children with OBPP (18 females, 12 males; age range 6mo–4y 7mo; mean age 2y 6mo [SD 1y 2mo]). Assessments were conducted on two occasions, one week apart. The V-scope was found to be feasible to use by a specialist and a generalist physiotherapist, demonstrating moderate to high reliability coefficients, small measurement errors, and lack of missing data. The pediatric physiotherapist was more reliable in measuring elbow and shoulder movement compared with the generalist physiotherapist, which suggests that the same experienced, pediatric physiotherapist should assess elbow and shoulder movement across all occasions of testing.

A male child, born at 37+5 gestational weeks (GWs) (birthweight 2000g) after intrauterine growth retardation (IUG; –3 SD), to a mother treated during pregnancy for asthma, developed periventricular leukomalacia and retinopathy with total retinal detachment in the left eye and partial detachment in the right eye. Apart from basic asthma treatment with terbutalin, budesonid, and fenoterolhydrobromid throughout the pregnancy, she was treated with intravenous or oral cortisone for 6.5 weeks from 28+5 GWs. In addition she developed deep venous thrombosis at 29 GWs and was treated with heparin until delivery. Psychotic symptoms during the 31st GW were treated with diazepam, haloperidol, and levomepromazin. Functional sequelae for the child were visual impairment (visual acuity 5/60), uneven intellectual profile (Wechsler Pre-school and Primary Scale of Intelligence, Verbal IQ 94 and Performance IQ 32 at 8y of age), and autistic-like behaviour. The possibility that pre- and perinatal risk factors (e.g. severe maternal illness, IUGR, and cortisone treatment) in a term infant may create conditions for developing eye and brain pathologies commonly closely related to preterm birth should be considered.

Evaluation of the cognitive repercussions of an epileptic disorder and its treatment are important issues in clinical follow-up. This especially holds true for temporal lobe epilepsy (TLE) where resective surgery can be a valid treatment option. However, in patients where TLE coexists with another neurocognitive disorder, questions can arise about the precise nature of the neuropsychological deficits. The aim of the present study was to evaluate memory impairments, found in a male aged 12 years who had the dual pathology of fragile X syndrome and refractory TLE. Memory functions of this child were compared with those of a male aged 11 years 7 months with fragile X syndrome matched for intellectual functioning as indicated by highly comparable verbal (5y 5mo vs 5y 9mo) and non-verbal (7y 2mo vs 6y 1mo) cognitive age equivalents. Performance on each neuropsychological measure was evaluated twice, separately with normative data based on chronological age and on verbal or non-verbal cognitive level. A specific, distinguishable profile of task performance could be found only when controlling for general level of cognitive functioning. This made it possible to accurately evaluate neuropsychological abilities before and 6 months after anterior temporal lobe resection even in this male with a complex neurological pathology.

This study sought to investigate the relationship between parental psychopathology and health-related quality of life in a group of Nigerian adolescents with epilepsy. The participants were 86 adolescents with epilepsy (50 males, 36 females; mean age 14y 5mo [SD 2y 1mo]; age range 12–18y). There were 54 (62.8%) adolescents with complex partial seizures, six (7.0%) with simple partial seizures, 14 (16.3%) with generalized tonic–clonic seizures, four (4.7%) with absence seizures, and eight (9.2%) with other types of seizure. They completed the Quality of Life in Epilepsy Inventory for Adolescents (QOLIE-AD-48). Parents also completed the General Health Questionnaire, Zung's Self-Rating Anxiety Scale, and Zung's Self-Rating Depressive Scale as measures of their psychopathology. Factors correlating with poor overall quality of life in the adolescents include longer duration of illness, large number of antiepileptic drugs, more severe medication toxicity, and psychopathology in the parents. General psychopathology in parents is significantly associated with QOLIE-AD-48 subscales of Epilepsy Impact (r=0.527, p<0.001), Attitude (r=0.214, p=0.047), Physical Function (r=0.417, p<0.001), Stigma (r=0.305, p=0.004), Social Support (r=0.365, p=0.001), and School Behaviour (r=0.220, p=0.042). There is a possibility of a cross-cultural difference on the effect of epilepsy on the quality of life of adolescents. Psychopathology in parents is significantly associated with poorer quality of life of these adolescents. Physicians should consider this, therefore, when planning intervention strategies in improving the quality of life in adolescents 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.