Richard L Robertson

Harvard Medical School, Boston, Massachusetts, United States

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Publications (53)244.03 Total impact

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    ABSTRACT: Brain injury is a major complication in neonates with complex congenital heart disease. Preliminary evidence suggests that fetuses with congenital heart disease are at greater risk for brain abnormalities. However, the nature and frequency of these brain abnormalities detected by conventional fetal MR imaging has not been examined prospectively. Our primary objective was to determine the prevalence and spectrum of brain abnormalities detected on conventional clinical MR imaging in fetuses with complex congenital heart disease and, second, to compare the congenital heart disease cohort with a control group of fetuses from healthy pregnancies. We prospectively recruited pregnant women with a confirmed fetal congenital heart disease diagnosis and healthy volunteers with normal fetal echocardiogram findings who underwent a fetal MR imaging between 18 and 39 weeks gestational age. A total of 338 fetuses (194 controls; 144 with congenital heart disease) were studied at a mean gestational age of 30.61 ± 4.67 weeks. Brain abnormalities were present in 23% of the congenital heart disease group compared with 1.5% in the control group (P < .001). The most common abnormalities in the congenital heart disease group were mild unilateral ventriculomegaly in 12/33 (36.4%) and increased extra-axial spaces in 10/33 (30.3%). Subgroup analyses comparing the type and frequency of brain abnormalities based on cardiac physiology did not reveal significant associations, suggesting that the brain abnormalities were not limited to those with the most severe congenital heart disease. This is the first large prospective study reporting conventional MR imaging findings in fetuses with congenital heart disease. Our results suggest that brain abnormalities are prevalent but relatively mild antenatally in fetuses with congenital heart disease. The long-term predictive value of these findings awaits further study.
    American Journal of Neuroradiology 03/2014; · 3.17 Impact Factor
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    ABSTRACT: Background: Few data are available on the neuropsychological, behavioural, or structural brain imaging outcomes in adolescents who underwent corrective surgery in infancy for tetralogy of Fallot. Methods: In this single-centre cross-sectional study, we enrolled 91 adolescents (13-16 years old) with tetralogy of Fallot and 87 referent subjects. Assessments included tests of academic achievement, memory, executive functions, visual-spatial skills, attention, and social cognition, as well as brain magnetic resonance imaging. Results: Genetic abnormalities or syndromes were present in 25% of tetralogy of Fallot patients, who had markedly greater neuropsychological morbidities than did patients without a syndrome. However, even patients without a syndrome performed significantly worse than the referent group or population norms in all of the neuropsychological domains assessed. In multivariable regression in those without a genetic/phenotypic syndrome, the strongest predictors of adverse late neurodevelopmental outcomes included a greater number of complications at the first operation, more total surgical complications across all operations, and occurrence of post-operative seizures. The presence of at least one abnormality on structural magnetic resonance imaging was more frequent in tetralogy of Fallot patients than the referent group (42% versus 8%). Conclusions: Adolescents with tetralogy of Fallot are at increased neurodevelopmental risk and would benefit from ongoing surveillance and educational supports even after childhood.
    Cardiology in the Young 02/2014; · 0.95 Impact Factor
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    ABSTRACT: Isolated inferior vermian hypoplasia (iiVH) is one of the most common fetal cerebellar anomalies presenting for fetal neurological counselling with controversial postnatal neurodevelopmental outcome. In the present study, we characterised the long-term neurodevelopmental outcome of prenatally diagnosed iiVH at school age. We prospectively followed 20 children with fetal MRI diagnosis of iiVH including their postnatal MRI result and developmental outcome at school age (mean 6.1 years±1.9 years SD) using a comprehensive age-appropriate developmental testing battery, which encompassed cognitive, language, social and behavioural domains. Parental stress level and socioeconomic status were also evaluated. All children with postnatally confirmed iiVH had a normal neurodevelopmental outcome. A subgroup of children (2/20) who demonstrated cognitive delays and behavioural impairments had more extensive cerebellar malformation. Despite a normal developmental outcome, the parents of children with postnatally confirmed iiVH had higher parental stress compared with those parents whose children had normal postnatal MRI. Children with postnatally confirmed iiVH show age appropriate functioning at school age. Postnatal MRI is important to confirm the diagnosis of iiVH and to exclude associated anomalies that impact neurodevelopmental outcome. A diagnosis of iiVH is associated with persistent elevated parental stress despite normal developmental outcomes in these children suggesting the need for ongoing parental support.
    Archives of Disease in Childhood - Fetal and Neonatal Edition 08/2013; · 3.45 Impact Factor
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    ABSTRACT: BACKGROUND: The experience in the newborn intensive care nursery results in premature infants' neurobehavioral and neurophysiological dysfunction and poorer brain structure. Preterms with severe intrauterine growth restriction are doubly jeopardized given their compromised brains. The Newborn Individualized Developmental Care and Assessment Program improved outcome at early school-age for preterms with appropriate intrauterine growth. It also showed effectiveness to nine months for preterms with intrauterine growth restriction. The current study tested effectiveness into school-age for preterms with intrauterine growth restriction regarding executive function (EF), electrophysiology (EEG) and neurostructure (MRI). METHODS: Twenty-three 9-year-old former growth-restricted preterms, randomized at birth to standard care (14 controls) or to the Newborn Individualized Developmental Care and Assessment Program (9 experimentals) were assessed with standardized measures of cognition, achievement, executive function, electroencephalography, and magnetic resonance imaging. The participating children were comparable to those lost to follow-up, and the controls to the experimentals, in terms of newborn background health and demographics. All outcome measures were corrected for mother's intelligence. Analysis techniques included two-group analysis of variance and stepwise discriminate analysis for the outcome measures, Wilks' lambda and jackknifed classification to ascertain two-group classification success per and across domains; canonical correlation analysis to explore relationships among neuropsychological, electrophysiological and neurostructural domains at school-age, and from the newborn period to school-age. RESULTS: Controls and experimentals were comparable in age at testing, anthropometric and health parameters, and in cognitive and achievement scores. Experimentals scored better in executive function, spectral coherence, and cerebellar volumes. Furthermore, executive function, spectral coherence and brain structural measures discriminated controls from experimentals. Executive function correlated with coherence and brain structure measures, and with newborn-period neurobehavioral assessment. CONCLUSION: The intervention in the intensive care nursery improved executive function as well as spectral coherence between occipital and frontal as well as parietal regions. The experimentals' cerebella were significantly larger than the controls'. These results, while preliminary, point to the possibility of long-term brain improvement even of intrauterine growth compromised preterms if individualized intervention begins with admission to the NICU and extends throughout transition home. Larger sample replications are required in order to confirm these results.Clinical trial registration: The study is registered as a clinical trial. The trial registration number is NCT00914108.
    BMC Pediatrics 02/2013; 13(1):25. · 1.98 Impact Factor
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    ABSTRACT: OBJECTIVE: Our objective was to use diffusion tensor imaging (DTI) to compare white matter microstructure in adolescents with d-transposition of the great arteries (d-TGA) who underwent the arterial switch operation in early infancy with typically developing control adolescents. We also examined correlates between patient demographic and medical risk factors and white matter as assessed by regional fractional anisotropy (FA) values. METHODS: We used with magnetic resonance imaging (MRI) to study 49 adolescents with d-TGA and 29 control adolescents. MRI data, including whole brain DTI and conventional anatomic MRI, were acquired from each subject. Each subject's data were analyzed using random effects analysis to evaluate regional white matter differences in FA between d-TGA and control adolescents. RESULTS: While multifocal punctate MRI hypointensities on T1-weighted (T1W) imaging suggestive of mineralization were found, other evidence of gross white matter injury was absent. Eighteen discrete regions of significantly reduced FA in d-TGA adolescents compared with controls were observed in deep white matter of cerebral hemispheres, cerebellum, and midbrain. Among d-TGA adolescents, lower FA correlated with younger gestational age, shorter duration of intraoperative cooling, higher intraoperative minimum tympanic temperature, longer intensive care unit stay after repair, and greater total number of open cardiac operations. CONCLUSIONS: Despite scant white matter injury evident on conventional brain MRI, adolescents with d-TGA repaired in infancy demonstrate significant white matter FA reduction that may relate to their reported neurocognitive deficits. Among adolescents with d-TGA, FA values are associated with patient and perioperative factors, some of which are modifiable.
    The Journal of thoracic and cardiovascular surgery 01/2013; · 3.41 Impact Factor
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    ABSTRACT: Cerebellar injury is an important complication of preterm birth with far-reaching neuropsychiatric sequelae. We have previously shown a significant association between isolated injury to the premature cerebellum and subsequent impairment of regional volumetric growth in the contralateral cerebrum. In the current study, we examine the relationship between these remote regional impairments of cerebral volumetric growth and domain-specific functional deficits in these children. In 40 ex-preterm infants with isolated cerebellar injury, we performed neurodevelopmental evaluations and quantitative magnetic resonance imaging (MRI) studies at a mean age of 34 months. We measured cortical gray matter volumes in 8 parcellated regions of each cerebral hemisphere, as well as right and left cerebellar volumes. We show highly significant associations between early signs of autism and dorsolateral prefrontal cortex volume (P < 0.001); gross motor scores and sensorimotor cortical volumes (P < 0.001); and cognitive and expressive language scores and premotor and mid-temporal cortical volumes (P < 0.001). By multivariate analyses, each unit increase in the corresponding regional cerebral volume was associated with lower odds of abnormal outcome score, adjusted for age at MRI and contralateral cerebellar volume. This is the first report linking secondary impairment of remote cerebral cortical growth and functional disabilities in survivors of prematurity-related cerebellar brain injury.
    Cerebral Cortex 11/2012; · 6.83 Impact Factor
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    ABSTRACT: Objective:The effect of NIDCAP (Newborn Individualized Developmental Care and Assessment Program) was examined on the neurobehavioral, electrophysiological and neurostructural development of preterm infants with severe intrauterine growth restriction (IUGR).Study Design:A total of 30 infants, 27-33 weeks gestation, were randomized to control (C; N=17) or NIDCAP/experimental (E; N=13) care. Baseline health and demographics were assessed at intake; electroencephalography (EEG) and magnetic resonance imaging (MRI) at 35 and 42 weeks postmenstrual age; and health, growth and neurobehavior at 42 weeks and 9 months corrected age (9 months).Results:C and E infants were comparable in health and demographics at baseline. At follow-up, E infants were healthier, showed significantly improved brain development and better neurobehavior. Neurobehavior, EEG and MRI discriminated between C and E infants. Neurobehavior at 42 weeks correlated with EEG and MRI at 42 weeks and neurobehavior at 9 months.Conclusion:NIDCAP significantly improved IUGR preterm infants' neurobehavior, electrophysiology and brain structure. Longer-term outcome assessment and larger samples are recommended.
    Journal of perinatology: official journal of the California Perinatal Association 02/2012; 32(10):797-803. · 1.59 Impact Factor
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    ABSTRACT: The aim of this study was to compare total and regional cerebral volumes in children with isolated cerebellar malformations (CBMs) with those in typically developing children, and to examine the extent to which cerebellar volumetric reductions are associated with total and regional cerebral volumes. This is a case-control study of children diagnosed with isolated CBMs. Each child was matched on age and sex to two typically developing children. Using advanced three-dimensional volumetric magnetic resonance imaging, the cerebrum was segmented into tissue classes and partitioned into eight regions. Analysis of variance was used to compare cerebral volumes between children with CBMs and control children, and linear regressions to examine the impact of cerebellar volume reduction on cerebral volumes. Magnetic resonance imaging was performed at a mean age of 27 months in 20 children (10 males, 10 females) with CBMs and 40 typically developing children. Children with CBMs showed significantly smaller deep grey matter nuclei (p < 0.001), subgenual white matter (p = 0.03), midtemporal white matter (p = 0.02), and inferior occipital grey matter (p = 0.03) volumes than typically developing children. Greater cerebellar volumetric reduction in children with CBMs was associated with decreased total cerebral volume and deep grey matter nuclei (p = 0.02), subgenual white/grey matter (p = 0.001), midtemporal white (p = 0.02) and grey matter (p = 0.01), and parieto-occipital grey matter (p = 0.004). CBMs are associated with impaired regional cerebral growth, suggesting deactivation of principal cerebello-cerebral pathways.
    Developmental Medicine & Child Neurology 11/2011; 53(12):1128-34. · 2.68 Impact Factor
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    ABSTRACT: The cerebellum has recently been recognized for its role in high-order functions, including cognition, language, and behavior. Recent studies have also begun to describe a functional topography of the mature cerebellum that includes organization on a mediolateral axis. However, no study to date has examined the relationship between regional cerebellar volume and developmental disabilities in children with cerebellar malformations. The objective of this study was to estimate the extent to which total and regional cerebellar volumes are associated with developmental disabilities in a cohort of children with cerebellar malformations. Children aged 1 to 6 years with a diagnosis of cerebellar malformation underwent standardized outcome measures and quantitative magnetic resonance scanning. The cerebellum was parcellated into seven mediolateral zones (three for each hemisphere plus the vermis) for regional volume analysis. In children with cerebellar malformations, decreased total cerebellar volume was associated with delays in global development, expressive language, cognition, as well as gross and fine motor function. Decreased volume in the right lateral cerebellar hemisphere was related to impaired cognition, expressive language, and gross motor function. Additionally, reduced vermis volume was associated with impaired global development, cognition, expressive language, and gross and fine motor skills, as well as behavior problems and a higher rate of positive autism spectrum screening test. These results begin to define the structural topography of functional outcome in children with cerebellar malformations and should lead to greater accuracy of prognostication as well as timely early developmental interventions.
    The Cerebellum 09/2011; 11(2):531-42. · 2.60 Impact Factor
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    ABSTRACT: We report neuropsychological and structural brain imaging assessments in children 16 years of age with d-transposition of the great arteries who underwent the arterial switch operation as infants. Children were randomly assigned to a vital organ support method, deep hypothermia with either total circulatory arrest or continuous low-flow cardiopulmonary bypass. Of 159 eligible adolescents, 139 (87%) participated. Academic achievement, memory, executive functions, visual-spatial skills, attention, and social cognition were assessed. Few significant treatment group differences were found. The occurrence of seizures in the postoperative period was the medical variable most consistently related to worse outcomes. The scores of both treatment groups tended to be lower than those of the test normative populations, with substantial proportions scoring ≥1 SDs below the expected mean. Although the test scores of most adolescents in this trial cohort are in the average range, a substantial proportion have received remedial academic or behavioral services (65%). Magnetic resonance imaging abnormalities were more frequent in the d-transposition of the great arteries group (33%) than in a referent group (4%). Adolescents with d-transposition of the great arteries who have undergone the arterial switch operation are at increased neurodevelopmental risk. These data suggest that children with congenital heart disease may benefit from ongoing surveillance to identify emerging difficulties. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000470.
    Circulation 08/2011; 124(12):1361-9. · 15.20 Impact Factor
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    ABSTRACT: The purpose of this study was to assess the conspicuity of brain cortical maturation with sonography and MRI of fetuses referred because of ventriculomegaly and to determine whether sulcal visualization can be used to predict postnatal outcome. Women with 374 fetuses referred because of ventriculomegaly underwent sonography and MRI. Four to six radiologists rated visualization of 19 fissures or sulci. Majority opinion regarding sulcal visualization was compared among fetuses categorized by CNS abnormality: normal, isolated ventriculomegaly, and ventriculomegaly with additional CNS abnormalities. Live-born infants were categorized as having normal or abnormal development. Logistic regression analysis was used to correlate sulcal visualization and postnatal development. A subanalysis was performed with fetuses who had been classified prenatally as having a normal brain or isolated ventriculomegaly. Cortical sulci were visualized more frequently and at an earlier gestational age with MRI than with ultrasound. In the entire cohort, the odds ratio of normal development ranged from 3.1 to 10.0 whenever the calcarine, parietooccipital, cingulate, superior temporal, precentral, or postcentral sulcus was seen on MR images. In fetuses categorized as having a normal brain or having isolated ventriculomegaly, the odds ratio of normal development ranged from 3.5 to 9.0 whenever the parietooccipital, cingulate, or superior temporal sulcus was seen. Visualization of the sulci in fetal brains depends on the imaging modality used and the gestational age at imaging. Information regarding sulcal visualization may aid in counseling patients carrying fetuses with ventriculomegaly.
    American Journal of Roentgenology 06/2011; 196(6):1457-67. · 2.90 Impact Factor
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    ABSTRACT: Advances in perinatal care and neuroimaging techniques have increased the detection of cerebellar malformations (CBMs) in the fetus and young infant. As a result, this has necessitated a greater understanding of the neurodevelopmental consequences of CBMs on child development. The aim of this study was to delineate the impact of CBMs on long-term neurodevelopmental outcomes. We conducted a cross-sectional study and systematically identified children with CBMs born between December 2000 and December 2006. We then performed follow-up magnetic resonance imaging studies, neurologic examination, and standardized neurodevelopmental outcome testing (Mullen Scales of Early Learning, Vineland Adaptive Behavior Scale, Child Behavior Checklist, Modified Checklist for Autism in Toddlers, and the Pediatric Quality of Life Inventory). Our sample comprised 49 children (29 males, 20 females; mean age, 28.4 mo, SD 16.4) with a CBM. Infants with evidence of acquired fetal or neonatal brain injury, intracranial birth trauma, inherited metabolic disease, or major pre- or postnatal cerebral ischemia were excluded. Our findings highlight that children with CBMs experience a high prevalence of neurologic, developmental, and functional disabilities including motor, cognitive, language, and social-behavioral deficits, as well as poor quality of life. The associated supratentorial anomalies, chromosomal findings, and malformations affecting the cerebellar vermis were significant independent predictors of neurodevelopmental disabilities in young children with CBMs. The associated supratentorial anomalies and chromosomal findings were also predictive of global developmental delay (p=0.01), cognitive impairment (p=0.03), gross and fine motor delay (p=0.02 and p=0.01 respectively), and positive screening for autism spectrum disorder (p=0.01). Additionally, malformations affecting the cerebellar vermis were significant independent predictors of expressive language (p=0.04) and gross motor delays (p=0.02). Developmental surveillance and early intervention programs should be an integral part of the long-term follow-up of survivors of CBM.
    Developmental Medicine & Child Neurology 03/2011; 53(5):409-16. · 2.68 Impact Factor
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    ABSTRACT: We report MRI findings from 2 pediatric clinical trials of diffuse intrinsic brainstem glioma (BSG) incorporating concurrent radiation therapy (RT) with molecularly targeted agents (gefitinib and tipifarnib). We determined associations of MRI variables with progression-free survival and overall survival and investigated effects of treatment on these variables. MRI (including diffusion and perfusion) was done before treatment, every 8 weeks (first year), every 12 weeks (thereafter), and at the end of treatment or disease progression. Reduced tumor volume (P < .0001) and tumor diffusion values (P <.0001) were apparent on the first post-RT/drug studies. Decreases in tumor volume correlated with pre-RT volume (P < .0001) and pre-RT diffusion values (P < .0001); larger decreases were noted for tumors with higher volumes and diffusion values. Patients with larger pre-RT tumors had longer progression-free survival (P < .0001). Patients with ≥ 25% decrease in tumor volume and diffusion values after RT had longer progression-free survival (P = .028) and overall survival (P = .0009). Enhancement at baseline and over time was significantly associated with shorter survival. Tumor diffusion values with baseline enhancement were significantly lower than those without (P = .0002). RT of BSG is associated with decreased tumor volume and intralesional diffusion values; patients with ≥ 25% decrease in values post-RT had relatively longer survival intervals, apparently providing an early imaging-based surrogate for relative outcomes. Patients with larger tumors and greater decreases in tumor volume and diffusion values had longer survival intervals. Tumor enhancement was associated with shorter survival, lower tumor diffusion values (increased cellularity), and a smaller drop in diffusion values after RT (P = .006). These associations justify continued investigation in other large clinical trials of brainstem glioma patients.
    Neuro-Oncology 02/2011; 13(4):417-27. · 6.18 Impact Factor
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    ABSTRACT: The objective of this study was to assess the outcomes of the prenatal diagnosis of septal leaflet abnormalities in fetuses referred for prenatal imaging with a finding of ventriculomegaly. This study is a retrospective review of fetuses with a diagnostic code of septal leaflet abnormalities from a larger prospective study. Four hundred twenty-five pregnant women with 433 fetuses referred for ventriculomegaly were imaged with ultrasound and MRI between July 1, 2003, and May 15, 2009. Four to six radiologists independently reviewed sonographic and MR images and recorded lateral ventricular diameters at the atrium and frontal horns, ventricular configuration, and the presence of ventriculomegaly and of other CNS abnormalities. Final prenatal ultrasound, MRI, and overall diagnoses were decided by consensus. Fetuses with a diagnostic code of septal leaflet abnormalities were identified, and birth outcome, autopsy findings, postnatal imaging, and postnatal follow-up examinations were obtained. The analysis of covariance, controlling for gestational age, was used to compare ventricular dimensions between fetuses with septal leaflet abnormalities and fetuses with isolated ventriculomegaly. Interrater agreement for the detection of septal leaflet abnormalities was assessed with kappa statistics. Interrater agreement and intrarater agreement for frontal horn measurements were assessed by variance components analysis. Twenty-three fetuses had septal leaflet abnormalities and 229 had isolated ventriculomegaly. Atrial and frontal horn diameters, adjusted for gestational age, were 77% and 98% larger, respectively, in fetuses with septal leaflet abnormalities than in fetuses with isolated ventriculomegaly (p < 0.0001). Before the consensus conference, agreement among ultrasound readers was moderate (κ = 0.54) and among MR readers, good (κ = 0.69). Additional CNS findings were seen on MRI in 12 of 23 fetuses (52%). Eleven pregnancies with septal leaflet abnormalities underwent termination and 12 progressed to livebirth; of the 12 livebirths, three neonates died. Neurodevelopmental follow-up was abnormal in all surviving children. A septal leaflet abnormality in the setting of ventriculomegaly is most frequently associated with other CNS abnormalities and is associated with postnatal developmental delay.
    American Journal of Roentgenology 01/2011; 196(1):W83-92. · 2.90 Impact Factor
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    ABSTRACT: The purposes of this feasibility study were to assess: (1) the potential utility of early brain MRI in asphyxiated newborns treated with hypothermia; (2) whether early MRI predicts later brain injury observed in these newborns after hypothermia has been completed; and (3) whether early MRI indicators of brain injury in these newborns represent reversible changes. All consecutive asphyxiated term newborns meeting the criteria for therapeutic hypothermia were enrolled prospectively. Each newborn underwent one or two early MRI scans while receiving hypothermia, on day of life (DOL) 1 and DOL 2-3 and also one or two late MRI scans on DOL 8-13 and at 1 month of age. 37 MRI scans were obtained in 12 asphyxiated neonates treated with induced hypothermia. Four newborns developed MRI evidence of brain injury, already visible on early MRI scans. The remaining eight newborns did not develop significant MRI evidence of brain injury on any of the MRI scans. In addition, two patients displayed unexpected findings on early MRIs, leading to early termination of hypothermia treatment. MRI scans obtained on DOL 2-3 during hypothermia seem to predict later brain injuries in asphyxiated newborns. Brain injuries identified during this early time appear to represent irreversible changes. Early MRI scans might also be useful to demonstrate unexpected findings not related to hypoxic-ischaemic encephalopathy, which could potentially be exacerbated by induced hypothermia. Additional studies with larger numbers of patients will be useful to confirm these results.
    Archives of Disease in Childhood - Fetal and Neonatal Edition 01/2011; 96(1):F36-44. · 3.45 Impact Factor
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    ABSTRACT: Near-infrared spectroscopy monitoring of cerebral oxygen saturation (rSo(2)) has become routine in many centers, but no studies have reported the relationship of intraoperative near-infrared spectroscopy to long-term neurodevelopmental outcomes after cardiac surgery. Of 104 infants undergoing biventricular repair without aortic arch reconstruction, 89 (86%) returned for neurodevelopmental testing at 1 year of age. The primary near-infrared spectroscopy variable was the integrated rSo(2) (area under the curve) for rSo(2) <or=45%; secondary variables were the average and minimum rSo(2) by perfusion phase and at specific time points. Psychomotor and mental development indexes of the Bayley scales, head circumference, neurological examination, and abnormalities on brain magnetic resonance imaging did not differ between subjects according to a threshold level for rSo(2) of 45%. Lower Psychomotor Development Index scores were modestly associated with lower average (r=0.23, P=0.03) and minimum (r=0.22, P=0.04) rSo(2) during the 60-minute period after cardiopulmonary bypass but not with other perfusion phases. Hemosiderin foci on brain magnetic resonance imaging were associated with lower average rSo(2) from postinduction to 60 minutes post cardiopulmonary bypass (71+/-10% versus 78+/-6%, P=0.01) and with lower average rSO(2) during the rewarming phase (72+/-12% versus 83+/-9%, P=.003) and during the 60-minute period following cardiopulmonary bypass (65+/-11% versus 75+/-10%, P=0.009). In regression analyses that adjusted for age <or=30 days, Psychomotor Development Index score (P=0.02) and brain hemosiderin (P=0.04) remained significantly associated with rSo(2) during the 60-minute period following cardiopulmonary bypass. Perioperative periods of diminished cerebral oxygen delivery, as indicated by rSo(2), are associated with 1-year Psychomotor Development Index and brain magnetic resonance imaging abnormalities among infants undergoing reparative heart surgery. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique identifier: NCT00006183.
    Circulation 07/2010; 122(3):245-54. · 15.20 Impact Factor
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    ABSTRACT: We have shown that cerebellar injury in the premature infant is followed by significant growth impairment of the contralateral cerebral hemisphere evident as early as term adjusted age. In this study, we hypothesize that this remote growth restriction is region specific in the cerebrum. In a prospectively enrolled cohort of 38 expreterm infants with isolated cerebellar injury by neonatal MRI, we performed follow-up volumetric MRI studies at a mean postnatal age of 35.5 +/- 13.8 mo. We measured volumes of cortical and subcortical gray matter, and cerebral white matter within eight parcellated regions for each cerebral hemisphere. Unilateral cerebellar injury (n = 24) was associated with significantly smaller volumes of cortical gray and cerebral white matter in the following regions of the contralateral (versus ipsilateral) cerebral hemisphere: dorsolateral prefrontal, premotor (PM), sensorimotor, and midtemporal regions (p < 0.001 for all except midtemporal cortical gray, p = 0.01), as well as subcortical gray matter in the PM region (p < 0.001). Conversely, in cases of bilateral cerebellar injury (n = 14), there was no significant interhemispheric difference in tissue volumes for any of the cerebral regions studied. These findings suggest that regional cerebral growth impairment results from interruption of cerebellocerebral connectivity and loss of neuronal activation critical for development.
    Pediatric Research 04/2010; 68(2):145-50. · 2.67 Impact Factor
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    ABSTRACT: We report that eight heterozygous missense mutations in TUBB3, encoding the neuron-specific beta-tubulin isotype III, result in a spectrum of human nervous system disorders that we now call the TUBB3 syndromes. Each mutation causes the ocular motility disorder CFEOM3, whereas some also result in intellectual and behavioral impairments, facial paralysis, and/or later-onset axonal sensorimotor polyneuropathy. Neuroimaging reveals a spectrum of abnormalities including hypoplasia of oculomotor nerves and dysgenesis of the corpus callosum, anterior commissure, and corticospinal tracts. A knock-in disease mouse model reveals axon guidance defects without evidence of cortical cell migration abnormalities. We show that the disease-associated mutations can impair tubulin heterodimer formation in vitro, although folded mutant heterodimers can still polymerize into microtubules. Modeling each mutation in yeast tubulin demonstrates that all alter dynamic instability whereas a subset disrupts the interaction of microtubules with kinesin motors. These findings demonstrate that normal TUBB3 is required for axon guidance and maintenance in mammals.
    Cell 01/2010; 140(1):74-87. · 31.96 Impact Factor
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    ABSTRACT: Adverse neurodevelopmental outcome is an important source of morbidity in children with congenital heart disease (CHD). A significant proportion of newborns with complex CHD have abnormalities of brain size, structure, or function, which suggests that antenatal factors may contribute to childhood neurodevelopmental morbidity. Brain volume and metabolism were compared prospectively between 55 fetuses with CHD and 50 normal fetuses with the use of 3-dimensinal volumetric magnetic resonance imaging and proton magnetic resonance spectroscopy. Fetal intracranial cavity volume, cerebrospinal fluid volume, and total brain volume were measured by manual segmentation. Proton magnetic resonance spectroscopy was used to measure the cerebral N-acetyl aspartate: choline ratio (NAA:choline) and identify cerebral lactate. Complete fetal echocardiograms were performed. Gestational age at magnetic resonance imaging ranged from 25 1/7 to 37 1/7 weeks (median, 30 weeks). During the third trimester, there were progressive and significant declines in gestational age-adjusted total brain volume and intracranial cavity volume in CHD fetuses relative to controls. NAA:choline increased progressively over the third trimester in normal fetuses, but the rate of rise was significantly slower (P<0.001) in CHD fetuses. On multivariable analysis adjusted for gestational age and weight percentile, cardiac diagnosis and percentage of combined ventricular output through the aortic valve were independently associated with total brain volume. Independent predictors of lower NAA:choline included diagnosis, absence of antegrade aortic arch flow, and evidence of cerebral lactate (P<0.001). Third-trimester fetuses with some forms of CHD have smaller gestational age- and weight-adjusted total brain volumes than normal fetuses and evidence of impaired neuroaxonal development and metabolism. Hemodynamic factors may play an important role in this abnormal development.
    Circulation 12/2009; 121(1):26-33. · 15.20 Impact Factor
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    ABSTRACT: We present the neonatal complications of two premature newborn infants whose placentas demonstrated placental thrombosis in the fetal circulation. Both mothers presented with a 3-day history of decreased fetal movements before delivery. The first infant presented with thrombocytopenia and disseminated intravascular coagulation. The second infant had extended bilateral extended hemorrhagic venous infarctions. Severe fetal placental vascular lesions seem to be a predisposing factor for some adverse neonatal outcomes. We present these two cases with a brief review of the literature.
    American Journal of Perinatology 10/2009; 27(3):251-6. · 1.57 Impact Factor

Publication Stats

1k Citations
395 Downloads
244.03 Total Impact Points

Institutions

  • 2003–2013
    • Harvard Medical School
      • • Department of Psychiatry
      • • Department of Radiology
      Boston, Massachusetts, United States
  • 2002–2013
    • Boston Children's Hospital
      • • Department of Radiology
      • • Department of Neurology
      Boston, Massachusetts, United States
  • 2008–2011
    • McGill University
      • • School of Physical and Occupational Therapy
      • • Department of Neurology and Neurosurgery
      Montréal, Quebec, Canada
  • 2006–2008
    • Beth Israel Deaconess Medical Center
      • Department of Radiology
      Boston, MA, United States
  • 2005
    • Childrens Hospital of Pittsburgh
      Pittsburgh, Pennsylvania, United States