Claudia Brogna

Neuropsychological development in children with Dravet syndrome.

PURPOSE Aim of this study is to report a detailed profile of neuropsychological development in children with Dravet syndrome. METHODS Twelve children with Dravet syndrome were longitudinally assessed using a detailed clinical and neuropsychological evaluation. Six had typical features of severe myoclonic epilepsy in infancy (SMEI) whereas the other six resulted borderline. All twelve underwent serial neuropsychological assessments with neurodevelopmental scales and further assessment of specific cognitive abilities. RESULTS Our results reported an apparent normal development before disease onset, a general evolution in two main stages, more active the first one and with a general trend towards a clinical stabilization afterwards. The onset of cognitive decline was generally later than what is reported in other series; furthermore, the impairment of cognitive development is less severe, especially in borderline cases. As to specific cognitive competence, attention, visual motor integration, visual perception as well as executive functions are the most impaired abilities; language appears less involved, with a predominance of phonological defects. CONCLUSIONS In our cohort the global development of patients appear less affected than in previous studies. Furthermore, our study points out an impairment of several specific cognitive skills even in patients with a developmental quotient apparently in the normal range. Language and other cognitive skill impairment such as attention, visuo-spatial organization, working memory and executive function appear consistent with what is usually found in cerebellar disorders.

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.

Application of the Sleep Disturbance Scale for Children (SDSC) in preschool age

BACKGROUND The Sleep Disturbance Scale for Children (SDSC) was originally validated on a sample of healthy children aged 6-16 years, investigating the occurrence of sleep disorders during the previous 6 months. AIMS The aim of this new study was to assess the psychometric properties of the SDSC in an Italian population of preschool children. METHODS The SDSC was distributed to the primary caregivers of children recruited via nurseries. Letters describing the study design and requesting the co-operation of the caregivers (parents) and co-signed by the investigators and by the head teacher were distributed with the questionnaire and collected by the teachers. Reliability analysis for evaluating internal consistency and item-total correlation coefficients, and factor analysis were performed. RESULTS During a 12-months study period, 601 questionnaires from healthy preschool age children (range 3-6 years) were collected. SDSC in preschool children showed a good level of internal consistency (Cronbachs alpha: 0.83) and six factors were derived from the factor analysis by using the principal component method of extraction and rotated with the varimax method: Parasomnias, Difficulty in initiating and maintaining sleep, Sleep disordered breathing, Disorders of excessive somnolence, Sleep hyperhydrosis and Non-restorative Sleep. CONCLUSIONS The statistical analysis, the internal consistency and the factor analysis support the use of SDSC as an evaluation tool even at preschool age. A different factorial structure from the original SDSC was found due to a different prevalence of the sleep disturbances in younger children, but with similar cut-off total SDSC score.

Use of the Hammersmith Infant Neurological Examination in infants with cerebral palsy: a critical review of the literature

The Hammersmith Infant Neurological Examination (HINE) has been proposed as one of the early neurological examination tools for the diagnosis of cerebral palsy (CP). The aim of the present study was to critically review the existing literature and our experience with the use of the HINE in infants at risk of CP. The published papers confirm that the HINE can play an important role in the diagnosis and prognosis of infants at risk of developing CP, and provide information on aspects of neurological findings impaired in different forms of CP and brain lesions.

Longitudinal cognitive assessment in healthy late preterm infants.

BACKGROUND Longitudinal cognitive development in late preterm (LP) infants has not been previously evaluated, using structured assessments. AIM To assess longitudinally cognitive development in a population of healthy LP infants from 12 months to preschool age. METHODS Sixty-two low-risk LP infants (33-36 weeks gestation) with normal or only minor findings on their cranial ultrasound scans were included in the study. They were assessed at 12 and 18 months corrected age using the Bayley Scales of Infant Development II to obtain the mental development index (MDI) and then at preschool age (mean age 62 ± 7 months) using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-R). RESULTS The MDI scores obtained at both 12 and 18 months corrected age were within the reported normative range. Using uncorrected ages, their scores were lower at both ages than those obtained using CA (p < 0.01). Full-scale IQ scores within the reported normal range were obtained at 5 years using the WPPSI-R for all but 6 children. Females had significantly higher scores than males (p < 0.001) for the MDI at both 12 and 18 months corrected and uncorrected age. No gender differences were found at preschool age using the WPPSI-R. CONCLUSIONS Our results suggest that over 90% of the low-risk late preterms reach an MDI and IQ at preschool age within normal range.

Cortical visual function in preterm infants in the first year.

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.

Sleep disturbances in preschool age children with cerebral palsy: a questionnaire study

OBJECTIVES The study aimed to analyze (i) the prevalence of sleep disorders in pre-school children with cerebral palsy (CP) using the Sleep Disturbance Scale for Children (SDSC), (ii) the possible association with motor, cognitive and behavioral problems, and (iii) the possible differences with typically developing children matched for age and gender. METHODS One-hundred children with CP (age range: 3-5 years, mean: 3.8 years) were assessed using the SDSC, the Gross Motor Function Classification System (GMFCS), the Wechsler Preschool and Primary Scale of Intelligence, and the Child Behaviour Check List (CBCL) to assess sleep, motor, cognitive, and behavioral problems, respectively. Further 100 healthy children matched for age and sex were assessed using the SDSC. RESULTS An abnormal total sleep score was found in 13% of children with CP while 35% had an abnormal score on at least one SDSC factor. SDSC total score was significantly associated with pathological internalizing scores on CBCL and active epilepsy on multivariate analysis. CP group reported higher significant median scores on SDSC total, parasomnias, and difficulty in initiating and maintaining sleep factors. CONCLUSIONS In pre-school children sleep disorders are more common in children with CP than in healthy control group and are often associated with epilepsy and behavioral problems.

Cognitive decline in Dravet syndrome: is there a cerebellar role?

PURPOSE The aim of the study was to perform a detailed assessment of cognitive abilities and behaviour in a series of epileptic patients with Dravet syndrome (DS) in order to establish a possible cerebellar-like pattern. METHODS Nine children with DS without major behavioural disturbances and with cognitive abilities compatible with the assessment of specific cognitive skills (IQ>45) were enrolled in the study, in parallel with another group of nine epileptic patients (cryptogenic or symptomatic with minor brain injuries) consecutively admitted into the hospital matched for chronological age and IQ. All cases underwent neurological examination, long term EEG monitoring, neuroimaging and genetic analysis as well as a neuropsychological assessment including specific cognitive skills. RESULTS On neurological examination 8 of the 9 DS patients had cerebellar signs, which were mild in six and more severe in the other two cases. DS patients had a constant discrepancy between verbal and performance items scales (verbal better than visual-spatial) that was not found in the control group. As to specific cognitive competence, the DS patients differ from the control group in the pattern of cognitive defects involving four main areas of cognitive abilities (a) expressive language with relatively spared comprehension, (b) visual-spatial organization, (c) executive function defects, (d) behavioural disorders. CUNCLUSIONS The pattern of cognitive difficulties found in DS patients is consistent with what is reported in literature as cerebellar cognitive syndrome and may account for a possible cerebellar origin (at least as co-factor) of the cognitive decline observed in DS patients, as suggested by other clinical and experimental studies.

Neurological examination of late-preterm infants at term age

BACKGROUND Late-preterm infants represent 70% of the whole preterm population. AIMS To establish the range and frequency distribution of neonatal neurological scores in a large cohort of low risk late-preterm infants and the possible differences with full-term infants. METHODS Three hundred-seventy-five healthy infants born between 34 and 36 weeks gestational age (GA) without major brain lesions were assessed between 39 and 41 weeks post-menstrual age using the Hammersmith Neonatal Neurologic Assessment and compared to the scores obtained using the same examination in full-term infants. RESULTS Infants born at 35 and 36 weeks GA had similar median scores in 32 of the 34 items. Infants born at 34 weeks GA had a different profile of scores compared to those born at 35 and 36 weeks, mainly in the tone items. While in infants born at 34 weeks the assessment at term age showed similar median scores to those obtained in full-term infants in 25/34 items, in those born at 35 and 36 GA the number of scores similar to full-term infants increased to 29/34. The main differences involved the tone items, with more marked flexor tone in the limbs and better head control for those born at 35 and 36 weeks. CONCLUSIONS This data can help as reference data when examining late-preterm infants at term age to see where the individual child stands compared to age matched low risk infants and to identify signs that are outside the reported range in infants with lesions or other risk factors.

Glyburide ameliorates motor coordination and glucose homeostasis in a child with diabetes associated with the KCNJ11/S225T, del226-232 mutation

Gain‐of‐function mutations of KCNJ11 can cause permanent neonatal diabetes mellitus, but only rarely after 6 months of age. Specific uncommon mutations KCNJ11give rise to a syndrome defined as developmental delay, epilepsy, and neonatal diabetes (DEND), or – more frequently – to a milder sub‐type lacking epilepsy, denoted as intermediate‐DEND (iDEND). Our aim was to consider a possible monogenic etiology in a 12‐yr‐old boy with early onset diabetes and mild neurological features. We studied a subject diagnosed with diabetes at 21 months of age, and negative to type 1 diabetes autoantibodies testing. He had learning difficulties during primary school, and a single episode of seizures at the age of 10 yr. We performed direct DNA sequencing of the KCNJ11 gene with subsequent functional study of mutated channels in COSm6 cells. The patients clinical response to oral glyburide (Glyb) was assessed. Motor coordination was evaluated before and after 6 and 12 months of Glyb therapy. Sequencing of the KCNJ11 gene detected the novel, spontaneous mutation S225T, combined with deletion of amino acids 226–232. In vitro studies revealed that the mutation results in a KATP channel with reduced sensitivity to the inhibitory action of ATP. Glyb improved diabetes control (hemoglobin A1c on insulin: 52 mmol/mol/6.9%; on Glyb: 36 mmol/mol/5.4%) and also performance on motor coordination tests that were impaired before the switch of therapy. We conclude that KCNJ11/S225T, del226‐232 mutation caused a mild iDEND form in our patient. KCNJ11 should be considered as the etiology of diabetes even beyond the neonatal period if present in combination with negative autoantibody testing and even mild neurological symptoms.