The objective of the American Academy for Cerebral Palsy and Developmental Medicine (AACPDM) evidence reports is to provide the biomedical research and clinical practice communities with the current state of evidence about various interventions for the management of developmental disabilities. The AACPDM evidence reports aggregate all that has been published about outcomes of an intervention for a medical condition, gauge the credibility (i.e. strength of the internal validity) of that evidence, and identify gaps in our scientific knowledge. Methodology for developing and procedures for approving these systematic reviews can be found on the internet at www.aacpdm.org in the AACPDM Database of Evidence Reports, which contains initial and updated reports.

A 21-year-old male presented with occipital lobes that were extensively damaged by bilateral infarcts present at birth. The absence of the striate cortex was confirmed with anatomic and functional MRI and high-resolution EEG. His cortical visual impairment was severe, but he retained a remarkable ability to see fast-moving stimuli. Horizontal optokinetic nystagmus could be elicited from either eye. Resolution acuity was close to normal providing the patient was allowed to move his head and eyes. The direction of motion in random-dot patterns could be discriminated with perfect accuracy at speeds above 2 deg/s, and the patient reported that he could ‘see’ the motion at fast but not at slow speeds. This conscious residual vision for motion is known as Riddoch's phenomenon, but it has never been reported in the complete absence of the striate cortex. Functional neuroimaging revealed activation that was outside the motion-responsive regions of the extrastriate cortex. This case demonstrates remarkable plasticity in the human visual system and may have implications for understanding the functional organization of the motion pathways.

Attention-deficit–hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with a high degree of associated behavioural problems. In order to study characteristics of ADHD with and without oppositional defiant disorder (ODD) in a representative group of young children with clinical impairment in Sweden, 131 children (101 males, 30 females) with ADHD (mean age 5 years, SD 1 year 5 months; range 3 to 7 years) were clinically examined, and their parents interviewed. Independent questionnaire data (Child Behavior Checklist, ADHD Rating Scale-IV, ODD Rating Scale-IV, Conners Hyperactivity Index) were collected. For comparison 131 children without ADHD were matched for sex, age, marital status, and socioeconomic status (115 males, 16 females; mean age 4 years 10 months, SD 1 year 5 months; range 3 to 7 years). Sixty percent of those with ADHD met full DSM-IV criteria for ODD. Only 10 of the 131 children with ADHD had no symptoms of ODD at all. The rate of children meeting full diagnostic criteria for ODD was similar across all age cohorts. Males were overrepresented in ODD, as were children of divorced parents and of mothers with low socioeconomic status. ADHD combined subtype was a stable independent factor influencing the diagnosis of ODD, regardless of psychosocial factors. Those with ADHD with ODD consistently showed higher rates of ADHD symptoms than did those with ADHD without ODD. The prevalent comorbidity of ADHD with ODD indicates that all children presenting with ADHD or ODD symptoms need to be assessed with a view to exploring both types of problem behaviours. The link between ODD and some psychosocial variables indicates the need to address these, possibly by measures such as parent training and network support.

Systematic data from a multidisciplinary clinical assessment of a large series of females with Rett syndrome (RS; n=87) is presented. Participants' ages ranged from 2 years 1 month to 44 years 10 months. Areas assessed included oromotor skills, feeding problems, growth, breathing abnormalities, mobility, postural abnormalities and joint deformities, epilepsy, hand use and stereotypies, self-care, and cognitive and communication skills. Many previously reported trends in the presentation of RS over time were confirmed, notably the increasingly poor growth and near pervasiveness of fixed joint deformities and scoliosis in adulthood. In contrast, there was a slight trend towards improved autonomic function in adulthood, whereas feeding difficulties increased into middle childhood and then reached a plateau. Improvements in mobility into adolescence were followed by a decline in those skills in adulthood. Levels of dependency were high, confirming findings from previous studies. Despite the presence of repetitive hand movements, a range of hand-use skills was seen in individuals of all ages. Cognitive and communication skills were limited, but there was little evidence of deterioration of these abilities with age. These findings confirm that RS is not a degenerative condition and indicate that intervention and support to maintain and increase motor skills, daily living skills, and cognitive and communicative functioning are appropriate targets for individuals with RS.

Spinal muscular atrophy (SMA) is a chronic illness characterized by loss of motor function. The aim of the study was to investigate behavioural adjustment in 96 children and adolescents with SMA (47 males, 49 females; mean age 11 years 2 months, range 6 to 18 years). Forty-five non-affected siblings (26 males, 19 females; mean age 11 years 6 months, range 6 to 18 years) and 59 normally developing children (33 males, 26 females; mean age 10 years 8 months, range 6 to 18 years) were recruited as control participants. Behavioural symptoms were measured with the Child Behaviour Checklist (CBCL) and disorders were assessed with a structured psychiatric interview (Kinder-DIPS). Of the patients with SMA, 12.5% fulfilled the criteria for an ICD-10 or DSM-IV diagnosis, with separation anxiety disorder being the most common diagnosis. The CBCL total score was in the clinical range for 11.5% of patients, 20% of the siblings, and 11.7% of the control children; the externalizing score rates were 2.1%, 22.2%, and 11.9% respectively; the internalizing score 18.9%, 24.4%, and 13.6% respectively. Comorbid psychopathology was not influenced by sex, IQ, nor severity of SMA, and only externalizing behaviour was correlated to age. In conclusion, children and adolescents with SMA are characterized by a low psychiatric comorbidity not different from control individuals. The group with the highest rate of behavioural problems and with the greatest need for intervention were the non-affected siblings who had a two- to threefold higher rate of behavioural problems than the normative population.

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.

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.

Alternating hemiplegia of childhood is a rare disorder characterized by recurrent attacks of hemiplegia affecting either side of the body, oculomotor and autonomic disturbances, movement disorders, and progressive cognitive impairment. We report on one family with autosomal dominant alternating hemiplegia. The disorder was first recognized in a 9-year-old child, the third son of the family, who presented with learning disability, tonic–clonic seizures, dystonic attacks, and episodes of alternating hemiplegia starting at the age of 2½ years. His mother and three brothers had similar symptoms. The maternal uncle, who has learning disability, had experienced multiple dystonic attacks. Tests performed on the family, including computerized tomography, magnetic resonance imaging, and magnetic resonance angiography of the brain as well as metabolic evaluation, were normal. Cytogenetic analysis was normal and mitochondrial DNA analysis revealed no deletions or mutations in the four affected family members and the grandmother. An autosomal dominant mode of inheritance is suggested by the fact that both sexes are affected in two generations.

This paper reports three females and two males with a distinctive congenital syndrome characterized by severe congenital hypotonia, facial diplegia, jaw ankylosis, velo-pharyngeal incoordination, pyramidal tract signs, and ocular motor apraxia. Patients were followed up at ages ranging from 20 months to 16 years. All cases of this syndrome are sporadic, without dysmorphological features, chromosomal, or MRI brain abnormalities. Electrophysiological studies indicate the brainstem as the site of the neurological dysfunction. Post-mortem CNS study of one of the patients demonstrated neuronal depletion of the IV, VII, VIII, and IX cranial nerve nuclei and intact morphology of the cerebral hemispheres. A vascular accident, early in foetal life, is the most likely cause of the clinical picture. The extent of brainstem involvement and its related clinical findings distinguishes these patients from those with Moebius, Pierre Robin, or Cogan syndromes. Outcome is better than what could be anticipated during the first few months of life given the severity of symptoms. Intelligence or developmental quotients are within the normal range for their age. Facial hypomimia, feeding, and speech articulatory performance difficulties are the main disabilities observed in these patients at follow-up.

A case report of neonatal onset pyridoxine-dependent seizures in a male patient with early diagnosis and treatment is presented. The patient's epilepsy was recognized and treated with pyridoxine (vitamin B6) within 8 hours of birth. Treatment has been nearly continuous since that time. This paper reports the results of a full neuropsychological evaluation at age 37 years and MRI completed at age 31 years. Consistent with other case reports in the literature, there was a significant Performance IQ (PIQ) advantage with decreased Verbal IQ (VIQ) and expressive language skills (Full-Scale IQ 71, VIQ 64, PIQ 85). MRI demonstrated characteristic thinning of the posterior corpus callosum. This report provides an example of early treatment that nonetheless results in a mild mental retardation. The similarity of the structural changes on MRI and the cognitive profile of this patient to those of others reported in the literature suggest that the underlying mechanism for both may be the same.

There are frequent references to marriages between close biological relatives in the Bible, for example, the Patriarch Abraham and his wife Sarah (Genesis 20:12), and Amran and Jochebed, the parents of Aaron and Moses, who were related as nephew and aunt (Exodus 6:20). In both cases the parental couple would be expected to have inherited identical genes from a common ancestor(s) at 25% of all loci and so, on average, their offspring would have been homozygous at 12.5% of loci, equivalent to a coefficient of inbreeding (F) of 0.125.

Although premonitory sensory phenomena (PSP) and suppressibility of tics (SPT) are important in Tourette syndrome not only when behavioural therapeutic approaches in children are considered, there is a lack of developmental information on these phenomena. Therefore, a cross-sectional survey of these factors in children and adolescents was carried out. Rates of PSP and SPT were gathered using a questionnaire for the assessment of Tourette syndrome. The 254 outpatients (212 males, 42 females) with Tourette syndrome investigated had an age range of 8 to 19 years, normal intelligence, and diagnosis according to DSM-IV-TR/ICD-10. To test for developmental effects, the total group was stratified into three age groups (8 to 10, 11 to 14, and 15 to 19 years). Data were statistically evaluated using χ2 tests. Of the 254 participants, 37% reported PSP, while 64% were able to suppress their tics. Only a subgroup of 119 patients gave unequivocal answers to both questions and only 60% of these experienced both PSP and SPT. Statistically significant stepwise increases were found at two different age levels. One was around 10 years (PSP ‘Yes’ or ‘No’ and SPT), the other around age 14 (PSP ‘Yes’). There was no influence of tic duration and age at tic onset on PSP/SPT. The reported data suggest that PSP is experienced rarely in younger children with Tourette syndrome and is not a necessary prerequisite for SPT. Increasing PSP with age merely seems to reflect cognitive development rather than intrinsic aspects of Tourette syndrome. In children under 10 years of age, SPT might require more awareness of tics than in older age groups. Developmental aspects of PSP and SPT should be taken into consideration when studies of cognitive behavioural treatment for children and adolescents with Tourette syndrome are planned.

Patients with congenital varicella syndrome (CVS) typically present with clinical symptoms consisting of skin lesions, neurological defects, eye diseases, and/or limb hypoplasia. In rare cases, isolated manifestations in the brain or eye have been reported. The varicella-zoster virus (VZV), as the causative agent of CVS, could only be detected in a few infants with CVS. In addition, there is little in the literature on antiviral treatment of infants born with signs of CVS. We report a case of CVS in a male infant who presented with generalized clonic cerebral seizures at age 4 months. An endogenous intracerebral viral reactivation following intrauterine VZV infection was assumed. After the diagnosis was confirmed virologically, acyclovir was administered intravenously for 10 days and afterwards orally for 3 weeks. This antiviral treatment was aimed at preventing progression of the disease. We concluded from this case that infants with intrauterine VZV infection can suffer intracerebral VZV reactivations that require antiviral treatment.

The aim of this study was to describe child health and well-being across the spectrum of cerebral palsy (CP) and to report on psychometric properties of the Child Health Questionnaire (CHQ) in this population. Parents of 80 individuals (45 males, 35 females; mean age 11 years 4 months, SD 3 years 6 months; range 5 to 18 years) attending a CP clinic in Victoria, Australia were surveyed. Measures included the CHQ PF-50, a 50-item parent-reported heath status measure; severity of CP, based on the Gross Motor Function Classification System; and cognitive status and presence of epilepsy. CHQ data were compared with normative data collected in Victoria two years earlier. The CHQ demonstrated good psychometric properties for children with CP. Children with CP had markedly poorer health on every CHQ scale than those in the normative sample. Health status did not vary by cognitive status or epilepsy. Children with severe CP had the poorest physical health, but psychosocial health and emotional impact on parents were similar for mild and severe CP showing that these should not be assumed to be less prevalent when CP is mild.

Attention-deficit–hyperactivity disorder (ADHD) has been associated with childhood epilepsy; prevalence figures have ranged from 8 to 77%, depending on the sample studied and the criteria used for diagnosis. In the general population the prevalence of ADHD is approximately 5%, with the majority of affected children having ADHD combined type. As part of a larger study of behavioral problems in children with epilepsy, we assessed 175 children (90 males, 85 females; age range 9 to 14 years, mean age was 11 years 10 months, SD 1 year 8 months) for evidence of ADHD. The children had at least a 6-month history of epilepsy. The primary caregiver completed both the Child Behavior Checklist (CBCL) and the Child Symptom Inventory-4 (CSI) or Adolescent Symptom Inventory-4 (ASI). On the CBCL, the mean attention problem T score was 64.6 (SD 10.5) for adolescents and 67.9 (SD 11.6) for children. On the CSI or ASI, 20 of 175 children met DSM-IV criteria for ADHD combined type; 42 of 175 had ADHD predominantly inattentive type; and 4 of 175 met criteria for ADHD predominantly hyperactive–impulsive type. There were significant correlations between the CBCL attention score and inattention (r=0.68) and hyperactivity–impulsivity (r=0.59). Sex, seizure type, and focus of seizure discharge were not predictors of symptoms of ADHD. Children with epilepsy are at risk for symptoms of ADHD. They differ from other samples of children with ADHD by the higher proportion of children with ADHD predominantly inattentive type and by an equal male:female ratio.

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.

The reliability of classification of cerebral palsy (CP) in low-birthweight children was assessed by using clinical and research study records sampled from population-based cohort studies in the USA, the Netherlands, Canada, and Germany. Records of neurological examination findings and functional motor assessments were submitted to up to five pediatricians with expertize in CP diagnosis, who grouped children into categories referred to as ‘disabling’ CP, ‘non-disabling’ CP, and no CP. Each study provided between 31 and 51 records of children assessed between 2 and 8 years of age, approximately equally divided among the three groupings. The discrimination between ‘any CP’ and ‘no CP’ was only fair (mean Kappa coefficients 0.37 to 0.69). However, when more detailed information describing motor function was used, children with ‘disabling’ CP could be distinguished, on the basis of records, from those without CP or with ‘non-disabling’ CP with good to excellent reliability (mean Kappa coefficients 0.69 to 0.88). Because of the substantially higher agreement observed when these functional distinctions are made, we recommend that reports or comparisons of rates of CP should include levels of motor function of children with CP, and not simply total CP, among the outcomes of interest.

This study examined the auditory status of females with Rett syndrome (RS) using auditory brainstem response (ABR) testing and measures of acoustic admittance. Prevalence of hearing impairment in 81 female patients (age range 1 year 3 months to 39 years 8 months; mean age 8 years 7 months, SD 6 years 4 months) was evaluated with ABR measurements. If the ABR latencies at 20dB nHL exceeded those of the normative group, a slight hearing loss was diagnosed. For ABR thresholds in the range 30 to 40dB nHL, a mild hearing loss was determined; moderate hearing loss was diagnosed for ABR thresholds in the range 50 to 60dB nHL. Bilateral hearing loss was found in 16 (19.3%) patients and unilateral hearing loss in 13 (16%) patients. Bilateral hearing loss of moderate degree was found in one patient. No patient was found with severe hearing loss (ABR threshold of 70dB nHL and above) in either ear. Slight hearing loss was found in 10.5% of ears (17 of 162), mild hearing loss in 14.2% of ears(23 of 162), and moderate hearing loss in 3.1% of ears (5 of 162). In 72.2% of ears (117 of 162), findings indicated the presence of normal peripheral auditory sensitivity. Prevalence of sensorineural hearing loss was 17.3% (28 of 162). Evidence of conductive involvement (conductive and mixed hearing loss) was observed in 9.9% of ears (16 of 162). In this cross-sectional study, the prevalence of hearing loss was increased in older RS participants and in those with seizures requiring the use of anticonvulsants. Neither the type of hearing loss nor the presence of preserved speech seemed to be correlated with the type of mutation in methyl-CpG-binding protein 2 (MeCP2) gene that is associated with RS.

The effects of mother–infant skin-to-skin contact (Kangaroo Care; KC) on autonomic functioning, state regulation, and neurobehavioural status was examined in 70 preterm infants, half of whom received KC over 24.31 days (SD 7.24) for a total of 29.76 hours (SD 12.86). Infants were matched for sex (19 males and 16 females in each group); birthweight (KC, 1229.95g [SD 320.21]; controls, 1232.17g [SD 322.15]); gestational age (GA) (KC, 30.28 weeks [SD 2.54]; controls, 30.19 weeks [SD 2.65]); medical risk; and family demographics. Vagal tone was calculated from 10 minutes of heart rate before KC and again at 37 weeks' GA. Infant state was observed in 10-second epochs during four consecutive hours before KC and again at 37 weeks' GA. Neurobehavioural status was assessed at 37 weeks' GA with the Neonatal Behavioral Assessment Scale (NBAS). Infants receiving KC showed a more rapid maturation of vagal tone between 32 and 37 weeks' GA (p=0.029). More rapid improvement in state organization was observed in KC infants, in terms of longer periods of quiet sleep (p=0.016) and alert wakefulness (p=0.013) and shorter periods of active sleep (p=0.023). Neurodevelopmental profile was more mature for KC infants, particularly habituation (p=0.032) and orientation (p=0.007). Results underscore the role of early skin-to-skin contact in the maturation of the autonomic and circadian systems in preterm infants.