Trajectories of brain development in school-age children born preterm with very low birth weight.

Preterm birth (gestational age < 37 weeks) with very low birth weight (VLBW, birth weight ≤ 1500 g) is associated with lifelong cognitive deficits, including in executive function, and persistent alterations in cortical and subcortical structures. However, it remains unclear whether "catch-up" growth is possible in the preterm/VLBW brain. Longitudinal structural MRI was conducted with children born preterm with VLBW (n = 41) and term-born peers participating in the Norwegian Mother and Child Cohort Study (MoBa) (n = 128) at two timepoints in early school age (mean ages 8.0 and 9.3 years). Images were analyzed with the FreeSurfer 5.3.0 longitudinal stream to assess differences in development of cortical thickness, surface area, and brain structure volumes, as well as associations with executive function development (NEPSY Statue and WMS-III Spatial Span scores) and perinatal health markers. No longitudinal group × time effects in cortical thickness, surface area, or subcortical volumes were seen, indicating similar brain growth trajectories in the groups over an approximately 16-month period in middle childhood. Higher IQ scores within the VLBW group were associated with greater surface area in left parieto-occipital and inferior temporal regions. Among VLBW preterm-born children, cortical surface area was smaller across the cortical mantle, and cortical thickness was thicker occipitally and frontally and thinner in lateral parietal and posterior temporal areas. Smaller volumes of corpus callosum, right globus pallidus, and right thalamus persisted in the VLBW group from timepoint 1 to 2. VLBW children had on average IQ 1 SD below term-born MoBa peers and significantly worse scores on WMS-III Spatial Span. Executive function scores did not show differential associations with morphometry between groups cross-sectionally or longitudinally. This study investigated divergent or "catch-up" growth in terms of cortical thickness, surface area, and volumes of subcortical gray matter structures and corpus callosum in children born preterm/VLBW and did not find group × time interactions. Greater surface area at mean age 9.3 in left parieto-occipital and inferior temporal cortex was associated with higher IQ in the VLBW group. These results suggest that preterm VLBW children may have altered cognitive networks, yet have structural growth trajectories that appear generally similar to their term-born peers in this early school age window.

Neural correlates of working memory training in HIV patients: study protocol for a randomized controlled trial.

BACKGROUND: Potent combined antiretroviral therapy decreased the incidence and severity of HIV-associated neurocognitive disorders (HAND); however, no specific effective pharmacotherapy exists for HAND. Patients with HIV commonly have deficits in working memory and attention, which may negatively impact many other cognitive domains, leading to HAND. Since HAND may lead to loss of independence in activities of daily living and negative emotional well-being, and incur a high economic burden, effective treatments for HAND are urgently needed. This study aims to determine whether adaptive working memory training might improve cognitive functions and neural network efficiency and possibly decrease neuroinflammation. This study also aims to assess whether subjects with the LMX1A-rs4657412 TT(AA) genotype show greater training effects from working memory training than TC(AG) or CC(GG)-carriers. METHODS/DESIGN: 60 HIV-infected and 60 seronegative control participants will be randomized to a double-blind active-controlled study, using adaptive versus non-adaptive Cogmed Working Memory Training® (CWMT), 20-25 sessions over 5-8 weeks. Each subject will be assessed with near- and far-transfer cognitive tasks, self-reported mood and executive function questionnaires, and blood-oxygenation level-dependent functional MRI during working memory (n-back) and visual attention (ball tracking) tasks, at baseline, 1-month, and 6-months after CWMT. Furthermore, genotyping for LMX1A-rs4657412 will be performed to identify whether subjects with the TT(AA)-genotype show greater gain or neural efficiency after CWMT than those with other genotypes. Lastly, cerebrospinal fluid will be obtained before and after CWMT to explore changes in levels of inflammatory proteins (cytokines and chemokines) and monoamines. DISCUSSION: Improving working memory in HIV patients, using CWMT, might slow the progression or delay the onset of HAND. Observation of decreased brain activation or normalized neural networks, using fMRI, after CWMT would lead to a better understanding of how neural networks are modulated by CWMT. Moreover, validating the greater training gain in subjects with the LMX1A-TT(AA) genotype could lead to a personalized approach for future working memory training studies. Demonstrating and understanding the neural correlates of the efficacy of CWMT in HIV patients could lead to a safe adjunctive therapy for HAND, and possibly other brain disorders. TRIAL REGISTRATION: ClinicalTrial.gov, NCT02602418.

Bone mineral density and vitamin D status in ambulatory and non-ambulatory children with cerebral palsy.

UNLABELLED: This study assessed distal femur and lumbar spine bone mineral density (BMD) Z-scores in children with cerebral palsy. BMD z-score was lower in non-ambulatory than in ambulatory children. Somewhat surprisingly, among ambulatory children, those with better walking abilities had higher BMD z-score than those with more impaired walking ability. INTRODUCTION: Children with cerebral palsy (CP) have increased risk for low bone mineral density (BMD). The aim was to explore the difference in BMD at the distal femur and lumbar spine between ambulatory and non-ambulatory children with CP and the relationship between vitamin D status and BMD. METHODS: Fifty-one children (age range 8-18 years; 20 girls) with CP participated. Their BMD Z-scores were measured in the lumbar spine and the distal femur using dual X-ray absorptiometry, and 25-hydroxy-vitamin D (25-OHD) concentrations were measured in serum. Children with GMFCS level I-III were defined as 'walkers' while children with level IV-V were defined as 'non-walkers. RESULTS: Non-walkers had lower mean BMD Z-scores (range -1.7 to -5.4) than walkers at all sites (range -0.8 to -1.5). Among walkers, BMD Z-scores at the distal femur were lower in those with GMFCS level II than with level I (p values < 0.004). A similar difference was found between the affected and unaffected limb in children with hemiplegia. Mean 25-OHD concentration was 45 nmol/L (SD = 18); lower in walkers (mean = 41 nmol/L; SD = 18) than in non-walkers (mean = 53 nmol/L; SD = 19; p = 0.041). There were no correlations between 25-OHD and BMD z-scores. CONCLUSIONS: The main predictor of low BMD Z-scores in the distal femur was the inability to walk, but the results suggest that the degree of the neuromotor impairment may also be a significant predictor. Vitamin D status did not correlate with BMD z-scores.

Hypothermia makes cerebral resistance index a poor prognostic tool in encephalopathic newborns.

BACKGROUND: Severe neonatal encephalopathy (NE) of hypoxic-ischaemic origin may cause death or life-long disability. Acute encephalopathy may also affect cerebrovascular control. Pourcelot's cerebrovascular resistance index (RI) ≤0.55 was predictive of poor outcome in normothermic NE infants. Recent studies have questioned its predictive power during therapeutic hypothermia (HT). OBJECTIVE: To assess the predictive power of RI during HT and after rewarming. METHODS: 45 infants with NE treated with HT for 72 h had their RI calculated during early (median 11 h) and late (median 62 h) cooling and after rewarming (median 89 h). Poor outcome was defined as death or abnormalities on day 10 magnetic resonance imaging shown to predict severe neuromotor disability. RESULTS: RI ≤0.55 during cooling did not differentiate between good and poor outcome (late cooling, p = 0.08), but was powerful after rewarming (p = 0.004). RI ≤0.55 predicted true poor outcome in 43% (95% confidence interval (CI): 12, 80) during late cooling and in 100% (95% CI: 31, 100) after rewarming. RI >0.55 predicted good outcome in 86% (95% CI: 69, 95) during late cooling and in 89% (95% CI: 74, 96) after rewarming. CONCLUSIONS: Low RI is not predictive of poor outcome during HT in NE infants, but regains the predictive power seen in normothermic infants after rewarming.

Clinical findings and white matter abnormalities seen on diffusion tensor imaging in adolescents with very low birth weight.

Very low birth weight (VLBW) children are at high risk of perinatal white matter injury, which, when subtle, may not be seen using conventional magnetic resonance imaging. The relationship between clinical findings and fractional anisotropy (FA) measurements in white matter of adolescents born prematurely with VLBW was studied in 34 subjects (age = 15 years, birth weight

Cerebral cortex thickness in 15-year-old adolescents with low birth weight measured by an automated MRI-based method.

Infants with low birth weight are at increased risk of perinatal brain injury. Disruption of normal cortical development may have consequences for later motor, behavioural and cognitive development. The aim of this study was to measure cerebral cortical thickness, area and volume with an automated MRI technique in 15-year-old adolescents who had low birth weight. Cerebral MRI for morphometric analysis was performed on 50 very low birth weight (VLBW, birth weight

Generalized dystrophic epidermolysis bullosa: identification of a novel, homozygous glycine substitution, G2031S, in exon 73 of COL7A1 in monozygous triplets.

We report monozygous triplets affected with dystrophic epidermolysis bullosa (DEB). The female triplets were delivered by Caesarean section and skin fragility of each child, which was partly induced by trauma, was apparent from the third to fourth day of life. Clinically, the triplets were equally affected. Mutation analysis in this family revealed a novel recessively expressed glycine substitution, G2031S, in exon 73 of the collagen VII gene COL7A1. Most glycine substitutions in this gene region encoding for the triple helical domain of collagen VII are associated with milder, dominantly inherited phenotypes. By contrast, the novel point mutation of this study is clinically silent in the heterozygous state and leads to a severe DEB subtype when homozygous.

[Neurologic follow up of premature infants and other neonatal at-risk patients in Norway]. / Nevrologisk oppfølging av for tidlig fødte barn og andre neonatale risikopasienter i Norge.

BACKGROUND: Infants with very low birthweight (< 1,500 grams) are at increased risk of neurological disabilities and impairments later in childhood. We wanted to study whether the paediatric departments in Norway had organised routine neurological follow-up programmes for these patients, and in particular whether the child habilitation departments participated in the follow-up. MATERIAL AND METHODS: A questionnaire was returned from 19 of 23 pediatric departments. The questionnaire also included other neonatal risk groups. The results showed that one senior paediatrician was in charge of the follow-up at most departments. The neonatologists worked in collaboration with the child neurologists, and most often the child habilitation department was consulted in the neonatal period. RESULTS: Only seven departments used a standardised follow-up programme. Main high risk groups were infants with birthweight < 1,500 grams and infants with birth asphyxia. There was a lack of consensus with regard to other inclusion criteria, time for follow-up and type of examinations. Only a few of the departments had performed follow-up studies concerning neurological sequelae and quality of life for this group of patients. INTERPRETATION: Registration of neurological disease in premature children should be mandatory for every department with neonatal intensive medicine.

Cerebral MRI of very low birth weight children at 6 years of age compared with the findings at 1 year.

BACKGROUND: We have previously reported the results of cerebral MRI examinations in an unselected year cohort of very low birth weight (VLBW) infants at one year of corrected age. Twenty-one (78 %) of 27 infants had abnormal myelination, mainly in the central occipital white matter (COWM) and in the centrum semiovale (CS), seen on T2-weighted images. Twelve infants had irregular and dilated lateral ventricles. We speculated whether these findings indicated perinatal periventricular leukomalacia (PVL). Only two infants had completely normal MRI at age 1 year. OBJECTIVE: To determine whether the abnormal myelination seen at 1 year of age, was still present, either as delayed myelination or as gliosis caused by perinatal PVL. MATERIALS AND METHODS: In the present study, we report the results of follow-up cerebral MRI in 20 of these infants at 6 years of age. RESULTS: Most of the children with MRI deviations at 1 year still had abnormalities at 6 years. Abnormal myelination in the central occipital white matter combined with abnormalities in the CS or with ventricular dilatation at age 1 year, presented as gliosis in 12 of 13 children at 6 years of age. Abnormalities solely in the COWM at age 1 year had normalised in two of five children and persisted as delayed myelination in three at age 6 years. Gliotic changes in periventricular white matter were found in 12 of 20 children (60 %). Areas most affected were the CS (11 children) and the COWM (9 children). Delayed myelination in COWM was found in six children (30 %), combined with gliosis in CS in three children. Twelve infants had ventricular dilatation both at 1 and 6 years of age. CONCLUSIONS: The MRI correlates of PVL, i. e. gliosis and ventricular dilatation, are common findings on cerebral MRI at 6 years of age in VLBW infants.

Can cerebral MRI at age 1 year predict motor and intellectual outcomes in very-low-birthweight children?

This follow-up study reports on cerebral MRI findings in 20 very-low-birthweight (VLBW) infants without disabilities at age 1 year in relation to motor, intellectual, and perceptual function at age 6 years. MRI findings, anthropometrics, and Bayley Scales of Infant Development scores at age 1 year as predictors of psychomotor status at age 6 years are also evaluated and compared. Outcome parameters were the Peabody Developmental Motor Scales and the Wechsler Preschool and Primary Scale of Intelligence. The results show that infants with myelin hyperintensities including the centrum semiovale or with occipital hyperintensities with associated ventricular dilatation at age 1 scored lower on the Peabody Gross Motor Locomotion Scale at age 6 than infants with normal myelination or with isolated occipital hyperintensities. This may indicate damage to motor fibers caused by perinatal periventricular leukomalacia. No relation was found between abnormal MRI findings at age 1 and later fine motor, intellectual, and perceptual function. Comparing different age 1-year predictors, an abnormality score defined by MRI was used as an independent predictor of gross motor locomotion function at age 6 years. However, the Bayley Mental Development Index scores and weight at age 1 were more important predictors of later motor and intellectual outcome, respectively, than MRI findings. It is recommended that cerebral MRI should not be used routinely to examine VLBW infants without disabilities at 1 year of age.

Cerebral magnetic resonance imaging and mental and motor function of very low birth weight children at six years of age.

In this follow-up study, 20 of a geographically based year cohort of 31 surviving non-disabled VLBW (birthweight < 1500 g) children were examined at six years of age. The aim of the study was to relate cerebral MRI findings to neuro-development in these non-disabled children at six years of age. All MRI scans were evaluated for myelination pattern, periventricular gliosis, ventricular dilation and cortical atrophy. The Peabody motor test and the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) were used in the evaluation of motor, mental and perceptual function. A diagnosis of attention deficit disorder with hyperactivity was made based on the examiner's impression of the child during the examination and based on the parent's history. We found that ten (50%) of the children had periventricular gliosis, mainly in centrum semiovale (CS) (nine children) and in central occipital white matter (COW) (six children). Gliosis in CS was related to lower scores on the Peabody gross motor test for locomotion, indicating involvement of corticospinal tracts. Additional gliosis in COW was related to both fine motor and gross motor impairments. We speculate that this indicates damage to both motor and visual pathways, affecting eye-hand coordination and balance function. No relationship between MRI deviations at six years and mental function based on performance, verbal and total IQ scores was found. However, there was a significant relationship between periventricular gliosis in COW and C5 and low scores on the WPPSI performance subtests: Picture completion test and Block design test. This may indicate visual and spatial perception problems, caused by damage to posterior visual pathways and occipito-thalamic tracts dealing with visuo-motor integration.

Cerebral magnetic resonance imaging (MRI) and mental and motor function of very low birth weight infants at one year of corrected age.

Thirty-one (77.5%) of a year cohort of 40 surviving infants with birth weight < 1500 grams were seen on follow-up examination at one year of corrected age. At neurological evaluation 20 infants were normal (Group 1), seven infants were considered at risk (Group 2), and four infants had cerebral palsy (Group 3). Assessment on the Bayley Scales gave significantly lower mean scores in Group 3 compared with Group 1, both on the Mental Index (63 versus 102, p < 0.001) and on the Psychomotor Index (PDI) (60 versus 94, p < 0.005). Mean PDI score in Group 2 was significantly lower than in Group 1 (74 versus 94, p < 0.005). Cerebral MRI was performed in 27 infants. Of the 19 infants in Group 1 examined with MRI, 14 infants showed deviating changes in both myelin deposition and maturation (2). In all 14 infants the central occipital white matter was affected and in three infants also the centrum semiovale, both areas correspond to predilection sites for periventricular leukomalacia (PVL). Five infants had irregular shape of the occipital horns of the lateral ventricles. These findings may also represent the end stages of PVL (4). Only four out of seven infants were examined with MRI in Group 2. However, three infants had deviating myelination and three had irregular shape of the posterior horns. In Group 3 all infants were examined with MRI and all had deviating myelination and irregular and slightly dilated posterior horn. There was a significant correlation between abnormally dilated occipital horns seen with MRI, and cerebral palsy and low scores on the Denver and the Bayley tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral magnetic resonance imaging (MRI) of very low birth weight infants at one year of corrected age.

Cerebral MRI was performed at 1.5 T in 27 infants with birth weight below 1500 grams at 1 year of corrected age. The images were compared to those reported on normal development at the same age. On T1 weighted images, 20 (74.1%) of the 27 infants showed myelin deposition different from what has been reported to be normal. Areas most affected were the central occipital white matter and the centrum semiovale. Both correspond to "watershed areas" known to be at risk for periventricular leukomalacia in preterm infants. T2-weighted images showed delayed myelination in the same areas as described for T1. In addition, two infants showed delayed myelination in the central occipital white matter and one in the centrum semiovale. Patchy focal abnormalities involving the white matter were seen in seven (25.9%) infants. Mild cerebral atrophy, mainly of the cortex was found in 10 (37.0%) infants. Irregular shape of the lateral ventricles, especially of the occipital horns was present in 12 infants (44.4%). 11 of these infants also had deviating changes in myelination. Only 2 infants (7.4%) had a normal MRI examination. Follow-up MRI examinations are needed to determine whether the high percentage of changes in myelination represent delayed development or brain damage in preterm infants.

[Assistance work in Romania. A multidisciplinary study of institutionalized children]. / Hjelpearbeid i Romania. En tverrfaglig undersøkelse av institusjonsbarn.

In October/November 1990 a health team worked in an institution for mentally retarded children in Rumania. The team diagnosed 154 children and encountered children with undernourishment, retarded growth, skin infections, injuries and untreated physical deformities. 11 children were in need of acute medical attention. Cerebral palsy and motoric, auditive and visual handicaps were not attended to. The children showed signs of deprivation, anxiety and behavioural maladjustment. They were mentally retarded, but receptive to stimulation. To conclude, the children suffered from physical, psychological, pedagogic and social neglect. The article provides information on the needs for further assistance to children in institutions in Rumania.