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Udgivelsesdato: 2007-Jan-6 BACKGROUND: The risk of cerebral palsy, the commonest physical disability of children in western Europe, is higher in infants of very low birthweight (VLBW)--those born weighing less than 1500 g--and those from multiple pregnancies than in infants of normal birthweight. An increasing proportion of infants from both of these groups survive into childhood. This paper describes changes in the frequency and distribution of cerebral palsy by sex and neurological subtype in infants with a birthweight below 1000 g and 1000-1499 g in the period 1980-96. METHODS: A group of 16 European centres, Surveillance of Cerebral Palsy in Europe, agreed a standard definition of cerebral palsy and inclusion and exclusion criteria. Data for children with cerebral palsy born in the years 1980-96 were pooled. The data were analysed to describe the distribution and prevalence of cerebral palsy in VLBW infants. Prevalence trends were expressed as both per 1000 livebirths and per 1000 neonatal survivors. FINDINGS: There were 1575 VLBW infants born with cerebral palsy; 414 (26%) were of birthweight less than 1000 g and 317 (20%) were from multiple pregnancies. 1426 (94%) had spastic cerebral palsy, which was unilateral (hemiplegic) in 336 (24%). The birth prevalence fell from 60.6 (99%CI 37.8-91.4) per 1000 liveborn VLBW infants in 1980 to 39.5 (28.6-53.0) per 1000 VLBW infants in 1996. This decline was related to a reduction in the frequency of bilateral spastic cerebral palsy among infants of birthweight 1000-1499 g. The frequency of cerebral palsy was higher in male than female babies in the group of birthweight 1000-1499 g (61.0 [53.8-68..2] vs 49.5 [42.8-56.2] per 1000 livebirths; p=0.0025) but not in the group of birthweight below 1000 g. INTERPRETATION: These data from a large population base provide evidence that the prevalence of cerebral palsy in children of birthweight less than 1500 g has fallen, which has important implications for parents, health services, and society.

Aim The aim of this study was to assess the onset of forward parachute reaction (FPR) in infants with brain lesions and its correlation with age of walking. Method FPR was assessed at 6, 9, and 12 months in 140 infants with brain lesions (78 males, 62 females; mean gestational age 31wks; SD 3.6wks; mean birthweight 1450g, SD 252g). On cranial ultrasound 62 infants had mild and 78 had major abnormalities; 86 developed cerebral palsy. All were followed for 5 years, and the age at which each child achieved independent walking was recorded. Infants who had been born small for gestational age (weight

Objective To assess visual function in low-risk preterm infants at 3, 5, and 12 months corrected age to determine whether the maturation of visual function in the first year is similar to that reported in term-born infants. Study design Seventy-five low-risk infants (25.0-30.9 weeks gestation) underwent ophthalmological examinations and a battery of tests (fix and follow, visual fields, acuity, attention at distance, and fixation shift) designed to assess various aspects of visual function at 3, 5, and 12 months corrected age. Results The results were comparable with normative data from term-born infants in all tests but fixation shift, suggesting that maturation of most aspects of visual function is not significantly affected by preterm birth. In contrast, >25% of preterm infants failed the fixation shift test at 3 months, with a higher percentage of failing at 5 and 12 months. Conclusions There is a specific profile of early visual behavior in low-risk preterm infants, with a high percentage of infants failing a test that specifically assesses visual attention and provides a measure of cortical processing.

Objective: To explore the impact of early-onset bipolar disorder (pediatric bipolar disorder [PBD]) on ADHD. Method: We compared ADHD symptom severity, ADHD subtype distribution, and rates of comorbid and familial psychiatric disorders between 49 ADHD children with comorbid PBD and 320 ADHD children without PBD. Results: Children with ADHD and PBD showed higher scores in the Hyperactive and Inattentive subscales of the ADHD Rating Scale, than children with ADHD alone. The frequency of combined subtype was significantly higher in ADHD children with PBD, than in those with ADHD alone. ADHD children with PBD showed a higher rate of familial psychiatric disorders than ADHD children without PBD. The rate of conduct disorder was significantly greater in children with PBD and ADHD compared with children with ADHD alone. Conclusion: ADHD along with PBD presents with several characteristics that distinguish it from ADHD alone, suggesting that these may be distinct disorders.

Thirty-six children born preterm with very low birth weight without neonatal brain disorders and normal cerebral ultrasound findings were examined at pre-school age: visual, perceptual motor, attention, behaviour and cognitive assessments were performed in the study group as well as in a control group of term children matched for age, sex and parental educational and occupational status. The results showed a significant lower scoring in perceptual motor skills in the study group, associated with a defect of accuracy in spatial attention and a higher incidence of stereopsis impairment related with perceptual motor disabilities. Behavioural disorders, in terms of emotional maturation and hyperactivity, were significantly more frequent in the study group. To prevent behavioural and learning problems at school, a complete longitudinal assessment including visual functions and perceptual motor abilities seems mandatory in preterm born children, even in the absence of neonatal brain disorders including abnormal cerebral ultrasound findings.

Aim: To show that conversion reactions should be suspected when symptomatology or instrumental checking does not conform to a precise pathological pattern in its anatomical and physiological keys. Methods: We report the case of a 14-y-old girl who presented with signs and symptoms of Guillain-Barre polyradiculonevritis. Negative instrumental and laboratory tests led us to consider a possible diagnosis of conversion reaction. Results: After a more detailed history emphasizing the close bond between the patient and her father, a poor peer-relation exchange and psychological stress, we were able to identify conversion reactions through the patient's motor signs. Conclusion: Conversion symptoms must be suspected and searched for when the neurologic outline is difficult to clarify, and also in the case of Guillain-Barre syndrome that does not respond to plasmapheresis.

The aim of this study was to assess the onset of forward parachute reaction (FPR) in infants with brain lesions and its correlation with age of walking.FPR was assessed at 6, 9, and 12 months in 140 infants with brain lesions (78 males, 62 females; mean gestational age 31 wks; SD 3.6 wks; mean birthweight 1450 g, SD 252 g). On cranial ultrasound 62 infants had mild and 78 had major abnormalities; 86 developed cerebral palsy. All were followed for 5 years, and the age at which each child achieved independent walking was recorded. Infants who had been born small for gestational age (weight10th centile) were excluded, as were those who had major congenital malformations, severe postnatal infectious diseases, or metabolic or haematological complications.A complete FPR was present in eight infants at 6 months, in 42 at 9 months, and in 71 at 12 months. At 12 months, 29 infants presented incomplete FPR and 40 presented absent FPR. Seventy-three infants were able to walk independently between the ages of 11 months and 60 months (67 with complete FPR and six with incomplete FPR at 12 mo). A complete FPR at 12 months was a good predictor of independent walking. The age at onset of complete FPR was also a good predictor of age of walking.The late acquisition of a complete FPR appears to be an early sign of a more general delayed maturation of functional abilities.

International audience; Fragile X syndrome (FXS) is an X-linked condition associated with intellectual disability and behavioral problems. It is caused by expansion of a CGG repeat in the 5' untranslated region of the fragile X mental retardation 1 (FMR1) gene. This mutation is associated with hypermethylation at the FMR1 promoter and resultant transcriptional silencing. FMR1 silencing has many consequences, including up-regulation of metabotropic glutamate receptor 5 (mGluR5)-mediated signaling. mGluR5 receptor antagonists have shown promise in preclinical FXS models and in one small open-label study of FXS. We examined whether a receptor subtype-selective inhibitor of mGluR5, AFQ056, improves the behavioral symptoms of FXS in a randomized, double-blind, two-treatment, two-period, crossover study of 30 male FXS patients aged 18 to 35 years. We detected no significant effects of treatment on the primary outcome measure, the Aberrant Behavior Checklist-Community Edition (ABC-C) score, at day 19 or 20 of treatment. In an exploratory analysis, however, seven patients with full FMR1 promoter methylation and no detectable FMR1 messenger RNA improved, as measured with the ABC-C, significantly more after AFQ056 treatment than with placebo (P < 0.001). We detected no response in 18 patients with partial promoter methylation. Twenty-four patients experienced an adverse event, which was mostly mild to moderately severe fatigue or headache. If confirmed in larger and longer-term studies, these results suggest that blockade of the mGluR5 receptor in patients with full methylation at the FMR1 promoter may show improvement in the behavioral attributes of FXS.

Fragile X syndrome (FXS) is the leading cause of inherited mental retardation, due to expansion and methylation of the CGG sequence at the 5' UTR of the FMR1 gene. Around 90% of affected boys present with attention deficit hyperactivity disorder (ADHD), while this percentage is lower in FXS girls (35-47%). Treatment of these behavioral symptoms is critical for many families. In an attempt at identifying drugs capable of restoring the activity of the FMR1 gene, we investigated the use of valproic acid (VPA), a well-known antiepileptic drug, also used as a mood stabilizer and in migraine therapy. It is described as an inhibitor of histone deacetylase (HDAC) and, possibly, as a DNA demethylating agent. In an in vitro study we observed that treatment of lymphoblastoid cells from FXS patients with VPA caused a modest reactivation of FMR1 transcription and increased levels of histone acetylation, confirming the histone hyperacetylating effect, but not its putative DNA demethylating activity. On the basis of these findings, we decided to evaluate the in vivo efficacy of VPA on ADHD symptoms in FXS patients. We observed an improvement in the adaptive behavior, defined as the performance of daily activities required for personal and social competence, due to a significant reduction in hyperactivity after VPA treatment. This treatment could be considered as an alternative to that with stimulants, whose efficacy in patients with FXS needs to be confirmed by further studies.

RP-HPLC-ESI-MS profile of naturally occurring salivary peptides of subjects with autistic spectrum disorder [ASD; N = 27:12 with diagnosis of autism, 1 with diagnosis of Asperger, 14 with diagnosis of pervasive developmental disorders not otherwise specified (PDD-NOS)] was compared to that of age-matched controls with the goal of identifying differences that could turn out to become hallmarks of at least a subgroup of ASD individuals. Phosphorylation level of four specific salivary phospho-peptides, namely statherin, histatin 1 (both, p < 0.0001) and acidic proline-rich proteins (both entire and truncated isoforms) (p < 0.005) was found significantly lower in autistic patients, with hypo-phosphorylation of at least one peptide observed in 18 ASD subjects (66%). Developmental scale assessment (Griffith or WISC-R) carried out on 14 ASD subjects highlighted a normal to borderline cognitive development in 10 of them, all included in the hypo-phosphorylated group. Phosphorylation of salivary peptides involves a Golgi casein kinase common to many organs and tissues, CNS included, whose expression seems to be synchronized during fetal development. Hypo-phosphorylation of salivary peptides suggests potential asynchronies in the phosphorylation of other secretory proteins, which could be relevant in CNS development either during embryonic development or in early infancy. These results suggest that analysis of salivary phospho-peptides might help to discriminate a considerable subgroup of ASD patients.

In developed countries, cerebral palsy (CP) remains the most common form of severe physical disability in children. Approximately 25 years ago, the rate of CP was found to be substantially increased in low-birth-weight children, but the cause of CP still is poorly understood. The authors report a survey of 10 European registers totaling 4503 singleton children with CP who were born in the years 1976 through 1990. The goal was to learn whether altered intrauterine growth is a pathologic factor in the origin of CP. CP was defined as a group of disorders that involve disordered movement, posture, or both as well as motor dysfunction. It is a permanent condition that can change but is not progressive. Using conventional fetal growth standards, infants born at 32 to 42 weeks gestation whose birth weight for gestational age was below the 10th percentile were 4 to 6 times more likely to have CP than were reference children with birth weights between the 25th and 75th percentiles. The increase in risk was considerably less (1.6- to 3.1-fold)-but still significant-in children whose birth weights were above the 97th percentile. The risk of CP was lowest in children whose birth weights were approximately 1 standard deviation above average. Similar findings were obtained for infants having unilateral or bilateral spasticity, and also for those who were dyskinetic or ataxic. The relationship between birth weight and risk of CP, if any, was less clear in children who were born before 32 weeks gestation. As is the case for perinatal death, the risk of CP is lowest in infants who at birth are above average weight for gestational age. However, the risk of CP increases not only when birth weight is well below normal, but also when it is well above normal. Possibly an abnormal growth pattern causes CP, or vice versa, or there could be some factor that is linked independently to both growth and the risk of CP. Conceivably, brain damage or impaired development in utero triggers an abnormal growth pattern through an endocrine pathway or some other mechanism. An alternative explanation is that abnormal growth renders the fetus more vulnerable physiologically, and that the brain is exposed to irreparable darnage during or after delivery.

A patient who underwent early removal of the left hemisphere because of Sturge-Weber syndrome was submitted to detailed linguistic and visuospatial batteries. The performances were compared to performances of subjects matched for age, education and IQ, but without focal cerebral lesions. Language was mildly impaired but to the same extent as in IQ controls. On the contrary, visuospatial abilities were clearly worse than in IQ controls, and the most preserved visuospatial abilities seemed to be the less sophisticated ones. Non literal comprehension of language, a function generally attributed to the right hemisphere, was intact. This same pattern, that is, preservation of language and impairment of visuospatial abilities, also seems to occur in subjects who have undergone surgical removal of the right hemisphere; in other words, the cognitive pattern seems the same regardless of which hemisphere is removed. These observations suggest that no matter which hemisphere is removed, functional reorganisation follows a hierarchical criterion which privileges the linguistic function, and the visuospatial functions most essential for independent survival.

We describe a child with trigonocephaly, strabismus, upslanting palpebral fissures, nasal bridge hypoplasia, hypertrophic alveolar ridges and large gingivo-labial frenula, short neck, hip "dysplasia," equinovarus deformities, cryptorchidism, atrial septal defect ostium secundum, and severe mental retardation, findings consistent with C syndrome. The patient also had a Dandy-Walker malformation, complete callosal agenesis, and occipital meningocele. These structural defects are independent of the premature closure of the metopic suture, and confirm that midline brain anomalies are part of C syndrome. The hypothesis that the basic developmental defect in this syndrome primarily affects the midline field is supported by the concomitance of other anomalies, such as conotruncal heart defects, omphalocele, and genital anomalies.