Daniela Ricci

Head Growth in Infants With Hypoxic–Ischemic Encephalopathy: Correlation With Neonatal Magnetic Resonance Imaging

Objectives. The aims of the study were to establish the relationship between head growth in the first year of life with the pattern on injury on neonatal magnetic resonance imaging (MRI) in infants with hypoxic–ischemic encephalopathy (HIE) and to relate these to the neurodevelopmental outcome. Methods. Fifty-two term infants who presented at birth with a neonatal encephalopathy consistent with HIE and who had neonatal brain MRI were entered into the study. Head circumference charts were evaluated retrospectively and the head growth over the first year of life compared with the pattern of brain lesions on MRI and with the neurodevelopmental outcome at 1 year of age. Suboptimal head growth was classified as a drop of >2 standard deviations across the percentiles with or without the development of microcephaly, which was classified as a head circumference below the third percentile. Results. There was no statistical difference between the neonatal head circumferences of the infants presenting with HIE and control infants. At 12 months, microcephaly was present in 48% of the infants with HIE, compared with 3% of the controls. Suboptimal head growth was documented in 53% of the infants with HIE, compared with 3% of the controls. Suboptimal head growth was significantly associated with the pattern of brain lesions, in particular to involvement of severe white matter and to severe basal ganglia and thalamic lesions. Suboptimal head growth predicted abnormal neurodevelopmental outcome with a sensitivity of 79% and a specificity of 78%, compared with the presence of microcephaly at 1 year of age, which had a sensitivity of only 65% and a specificity of 73%. The exceptions were explained by infants with only moderate white matter abnormalities who had suboptimal head growth but normal outcome at 1 year of age and by infants with moderate basal ganglia and thalamic lesions only who had normal head growth but significant motor abnormality.

Does cranial ultrasound imaging identify arterial cerebral infarction in term neonates

Objective: To evaluate the diagnostic accuracy of cranial ultrasound (CUS) for detection of neonatal arterial territory cerebral infarction in term infants. Methods: CUS scans from term infants with neonatal magnetic resonance imaging (MRI) evidence of neonatal infarction were reviewed. The scans were grouped by acquisition time after birth: 1–3 days (early) or 4–14 days (late). Results: Brain MRI showed infarction in the territory of the middle cerebral artery in 43 of 47 infants, anterior cerebral artery in one, and posterior cerebral artery in three. Twelve of the 47 had minor changes on MRI in the white matter in the contralateral hemisphere, and four infants had bilateral infarctions. The early CUS scans were abnormal in 68% of the infants; the late CUS scans were abnormal in 87%. The late CUS scans were correct for laterality and site of lesion in 25/47 (53%) infants. In six infants with smaller lesions of the cortical middle cerebral artery branch or lesions in the posterior cerebral artery territory, the CUS scans were persistently normal. Conclusion: Normal early CUS scans do not exclude a diagnosis of neonatal stroke, although most scans are abnormal. CUS scans performed after day 3 were abnormal in 87% of infants. CUS scan findings were accurate for lesion laterality and site in 53%, and, in 34%, the scans showed abnormality strongly suggestive of infarction but not always site specific. For optimal prognostic information, infants with clinical histories or CUS scan findings suggestive of infarction should have a neonatal brain MRI scan.

Cognitive Outcome at Early School Age in Term-Born Children With Perinatally Acquired Middle Cerebral Artery Territory Infarction

Background and Purpose— To assess cognitive outcome at early school age in term-born children with middle cerebral arterial (MCA) territory infarction of perinatal onset and examine the correlation between cognitive abilities and the extent of lesions as seen on neonatal MRI, epilepsy, and hemiplegia. Methods— Thirty-one children were seen as newborns with an acutely evolving MCA territory infarction documented on neonatal MRI scan. IQ was assessed (WIPPSI/WISC where appropriate) and they had a standardized neurological examination at early school age. Lesion(s) site was recorded from the neonatal images. Results— Twenty-eight of 31 children were assessed (median age 5.75 range 5.33 to 10.33 years); 1 child died and 2 were abroad. IQ was within the normal range (mean 104, range 82 to 144) in 21 (78%); 1 child did not complete all tests but had a normal PIQ; 3 had a low and 3 an exceptionally low IQ. Verbal IQs were more varied and lower than performance IQs especially in children from multilingual backgrounds. There was no consistent association between cognitive impairment, side, or extent of the MCA lesion. Cognitive impairments were more frequent in children with seizures or hemiplegia. All 6 children with low IQ also had behavioral problems or unusual associated clinical or scan features. Conclusions— In our cohort a low IQ at early school age did not occur in children with the common presentation of neonatal unilateral MCA territory infarction. Cognitive impairment appeared more frequently when an MCA arterial territory infarction, even if relatively small, was associated with other risk factors.

Neurodevelopmental outcome at 12 and 18 months in late preterm infants

BACKGROUND Late-preterms represent the 70% of the whole preterm population and are reported to be at higher risk for mortality and morbidity than term infants. AIMS To assess neurodevelopmental outcome in low-risk late-preterm infants at 12 and 18 months corrected age, to compare results of corrected and uncorrected age to those of term-born infants, to analyse the possible influence of gender on outcome. METHODS Sixty-one healthy infants born between 33 and 36 weeks gestational age without major brain lesions were assessed at 12 and 18 months corrected age using the Bayley II scale. A control group of 60 low-risk term born infants underwent the same assessment. RESULTS At 12 and 18 months corrected age late preterms showed a mean mental developmental index (MDI) similar to term infants. Comparing the results of the uncorrected age with term infants, the scores were significantly lower at both 12 and 18 months. No gender differences were observed in term-born infants, while male late-preterm infants showed lower MDI than peer females at both ages. CONCLUSIONS When correcting age for prematurity late-preterms have similar MDI scores to those obtained in term-born infants at 12 and 18 months. In contrast, when using chronological age there is a number of infants with low MDI. As cognitive abnormalities are reported at school age in late preterm infants, our findings raise the question on whether the results obtained using scores uncorrected for age may early identify the infants who will show cognitive difficulties at school age.

Maturation of cerebral electrical activity and development of cortical folding in young very preterm infants.

OBJECTIVE The aim of this study was to examine the relationship between cortical development and cerebral electrical activity at early gestational ages. METHODS We obtained EEGs (7.2+/-3.8 days) and MR brain images (3.2+/-2.9 days) after birth in 17<30 week gestation infants without evidence of focal brain injury The EEGs were assessed for discontinuity and characteristic maturational features (delta brush, occipital and temporal sawtooth); cortical development was quantified from MR scans using a specially designed computer programme to measure cortical folding. RESULTS The inter-burst interval shortened and cortical folding increased with increasing post-menstrual age (PMA). In contrast, the minimum duration of bursts was independent of PMA and cortical folding. Delta brush (8-20 Hz activities) was seen at all PMAs; temporal and occipital sawtooth activities were always more prominent than delta brush but were seen less frequently with increasing PMA and complexity of cortical folding. CONCLUSION There was a positive correlation between some but not all maturational features of the preterm neonatal EEG and the complexity of whole brain cortical folding and PMA. These relationships were strong for the inter-burst interval, a global measure of maturation, but not strongly seen for regional features such as occipital and temporal sawtooth within this gestational age range. SIGNIFICANCE Combining neurophysiological examination with detailed neuroimaging gives insights into developmental changes occurring in the very preterm brains and suggests further comparative studies focusing on measures of focal brain development at different gestational ages.

Cognitive profile of disorders associated with dysregulation of the RAS/MAPK signaling cascade

Mutations in genes coding for transducers participating in the RAS/MAPK pathway have been identified as the molecular cause underlying a group of clinically related developmental disorders with cognitive deficits of variable severity. To determine the spectrum of cognitive defects associated with dysregulation of this signal cascade, we studied the profile of cognitive abilities in patients with mutations affecting the PTPN11, SOS1, HRAS, KRAS, BRAF, RAF1, and MEK1 genes and phenotype–genotype correlations. Our findings support the observation that heterogeneity in cognitive abilities can be at least partially ascribed to the individual affected genes and type of mutation involved. While mutations affecting transducers upstream of RAS were less frequently associated with mental retardation, mutations in downstream components of the pathway were generally associated with a more severe cognitive impairment. Among patients with a heterozygous PTPN11 mutation, the T468M substitution was associated with a mean IQ significantly higher compared to that of individuals carrying the N308D change. Our study provides insights on the range of cognitive abilities in patients with gene mutations causing dysregulation of RAS signaling suggesting that the presence and severity of cognitive involvement can be predicted in part by the gene involved.

Neurological examination of preterm infants at term equivalent age

BACKGROUND We previously reported the neurological findings of the Dubowitz neonatal examination in a cohort of 157 low-risk preterms born between 25 and 33 weeks gestational age (GA) and examined at term equivalent age (TEA). Median and range of scores were wider than those found in term-born infants and preterms showed a different neurological behaviour in specific items. However, the cohort number was too small to draw any definitive conclusion about the distribution of findings. AIMS We provide normative data from a low-risk cohort of 380 preterm infants; we also assess the findings and their relationship to motor outcome in preterms with major cranial ultrasound (US) abnormality. STUDY DESIGN We assessed, at TEA, 380 low-risk preterms born <35 weeks gestation (range 25-34.9, median 29) with normal 2 year motor outcome and 85 preterm infants with major US abnormality. RESULTS At TEA low-risk preterms had less flexor limb tone, poorer head control but better visual following than term-born infants. For 28/34 of the neurological items the range and median scores were similar across gestational ages. In infants with major US lesions the range and median scores differed from low-risk preterms in 20/34 items; 40% of infants developing a diplegia and 80% developing a tetraplegia had >7 items outside the 90th centile; all infants with >12 items outside the 90th centile developed a tetraplegia. CONCLUSIONS We provide reference values for the neurological examination of low-risk preterms at TEA. In infants with major US abnormality the number of items outside the 90th centile was an indicator of outcome severity.

Development of visual attention in West syndrome.

Summary:  Purpose: To study prospectively the evolution of visual attention in children with West syndrome to evaluate its development before the onset of spasms, its possible deterioration as a consequence of epileptic disorders, and its outcome at the age of 2 years, and the possible relation between the impairment of visual attention and cognitive development.

Early development in Dravet syndrome; visual function impairment precedes cognitive decline

Aim of the study was to describe prospectively the early neuropsychological evolution including the first pre-cognitive stages of the Severe Myoclonic Epilepsy in Infancy (SMEI) or Dravet syndrome. Five cases, four of whom since before a diagnostic evidence of the Dravet syndrome, were followed up. Full clinical assessment including developmental, visual function and behaviour assessments were serially performed. In four cases, a variable onset age of cognitive decline assessed with developmental scales was preceded some months before by an impairment of visual function; the remaining patient during all the course of follow-up till 51 months of age showed a normal development without visual impairment. A cognitive decline with variable onset was generally confirmed in Dravet syndrome. The previous early impairment of visual function seems to herald the cognitive decline and provides useful prognostic information; furthermore, it possibly suggests some clues for a better understanding of the mechanisms of cognitive deterioration in this syndrome.

Sleep disorders in children with cerebral palsy: neurodevelopmental and behavioral correlates

OBJECTIVES We aimed to estimate the frequency of sleep disorders in children with cerebral palsy (CP) using the Sleep Disturbance Scale for Children (SDSC) and to evaluate the relations between sleep disorders and motor, cognitive, and behavioral problems. METHODS One hundred and sixty-five children with CP ages 6-16 years (mean age, 11years) were assessed using the SDSC, the Gross Motor Function Classification System (GMFCS), the Wechsler Intelligence Scale for Children and the Child Behavior Check List (CBCL) to assess sleep, motor, cognitive, and behavioral problems, respectively. RESULTS An abnormal total sleep score was found in 19% of children with CP; more than 40% of children had an abnormal score on at least one SDSC factor. The SDSC total score was significantly associated (P<.01) with mental retardation, epilepsy, CBCL scores, and level 5 on the GMFCS. CONCLUSIONS Our results confirm that sleep disorders are common in children with cerebral palsy. The relationship between motor and cognitive behavior and epilepsy should be further explored to better understand how these factors influence one another to identify effective treatments and to improve the well-being of the child.