Marie Brossard-Racine

Developmental Cerebellar Cognitive Affective Syndrome in Ex-preterm Survivors Following Cerebellar Injury

Cerebellar injury is increasingly recognized as an important complication of very preterm birth. However, the neurodevelopmental consequences of early life cerebellar injury in prematurely born infants have not been well elucidated. We performed a literature search of studies published between 1997 and 2014 describing neurodevelopmental outcomes of preterm infants following direct cerebellar injury or indirect cerebellar injury/underdevelopment. Available data suggests that both direct and indirect mechanisms of cerebellar injury appear to stunt cerebellar growth and adversely affect neurodevelopment. This review also provides important insights into the highly integrated cerebral-cerebellar structural and functional correlates. Finally, this review highlights that early life impairment of cerebellar growth extends far beyond motor impairments and plays a critical, previously underrecognized role in the long-term cognitive, behavioral, and social deficits associated with brain injury among premature infants. These data point to a developmental form of the cerebellar cognitive affective syndrome previously described in adults. Longitudinal prospective studies using serial advanced magnetic resonance imaging techniques are needed to better delineate the full extent of the role of prematurity-related cerebellar injury and topography in the genesis of cognitive, social-behavioral dysfunction.

Handwriting capacity in children newly diagnosed with Attention Deficit Hyperactivity Disorder

UNLABELLED Preliminary evidence suggests that children with Attention Deficit Hyperactivity Disorder (ADHD) may exhibit handwriting difficulties. However, the exact nature of these difficulties and the extent to which they may relate to motor or behavioural difficulties remains unclear. The aim of this study was to describe handwriting capacity in children newly diagnosed with ADHD and identify predictors of performance. Forty medication-naïve children with ADHD (mean age 8.1 years) were evaluated with the Evaluation Tool of Childrens Handwriting-Manuscript, the Movement Assessment Battery for Children (M-ABC), the Developmental Test of Visual Motor Integration (VMI) and the Conner Global Index. An important subset (85.0%) exhibited manual dexterity difficulties. Handwriting performance was extremely variable in terms of speed and legibility. VMI was the most important predictor of legibility. Upper extremity coordination, as measured by the M-ABC ball skills subtest, was also a good predictor of word legibility. CONCLUSION Poor handwriting legibility and slow writing speed were common in children newly diagnosed with ADHD and were associated with motor abilities. Future studies are needed to determine whether interventions, including stimulant medications, can improve handwriting performance and related motor functioning.

Prevalence and spectrum of in utero structural brain abnormalities in fetuses with complex congenital heart disease

BACKGROUND AND PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Third Trimester Brain Growth in Preterm Infants Compared With In Utero Healthy Fetuses

BACKGROUND AND OBJECTIVES: Compared with term infants, preterm infants have impaired brain development at term-equivalent age, even in the absence of structural brain injury. However, details regarding the onset and progression of impaired preterm brain development over the third trimester are unknown. Our primary objective was to compare third-trimester brain volumes and brain growth trajectories in ex utero preterm infants without structural brain injury and in healthy in utero fetuses. As a secondary objective, we examined risk factors associated with brain volumes in preterm infants over the third-trimester postconception. METHODS: Preterm infants born before 32 weeks of gestational age (GA) and weighing <1500 g with no evidence of structural brain injury on conventional MRI and healthy pregnant women were prospectively recruited. Anatomic T2-weighted brain images of preterm infants and healthy fetuses were parcellated into the following regions: cerebrum, cerebellum, brainstem, and intracranial cavity. RESULTS: We studied 205 participants (75 preterm infants and 130 healthy control fetuses) between 27 and 39 weeks’ GA. Third-trimester brain volumes were reduced and brain growth trajectories were slower in the ex utero preterm group compared with the in utero healthy fetuses in the cerebrum, cerebellum, brainstem, and intracranial cavity. Clinical risk factors associated with reduced brain volumes included dexamethasone treatment, the presence of extra-axial blood on brain MRI, confirmed sepsis, and duration of oxygen support. CONCLUSIONS: These preterm infants exhibited impaired third-trimester global and regional brain growth in the absence of cerebral/cerebellar parenchymal injury detected by using conventional MRI.

Cerebellar Microstructural Organization is Altered by Complications of Premature Birth: A Case-Control Study

Objectives To compare regional cerebellar microstructure, as measured by diffusion tensor imaging (DTI), between preterm infants at term‐equivalent age and healthy term‐born control neonates, and to explore associations between DTI findings and clinical risk factors. Study design In this case‐control study, DTI studies were performed in 73 premature infants born ≤32 weeks and ≤1500 g birth weight and 73 full‐term‐born controls from healthy pregnancies. Using a region of interest approach, fractional anisotropy (FA) and mean diffusivity (MD) were extracted in 7 cerebellar regions including the anterior vermis, the right/left superior cerebellar peduncles, the middle cerebellar peduncle, and the dentate nuclei. To validate further our DTI measurements, we measured FA and MD in the genu of the corpus callosum and splenium. FA and MD were compared between groups using analyses of multiple linear regression models. Results Preterm infants at term‐equivalent age presented with higher FA in the dentate nuclei (<.001) and middle cerebellar peduncle (.028), and lower MD in the vermis (.023) compared with controls. Conversely, preterm infants showed reduced FA and increased MD in both the genu of the corpus callosum and splenium (P < .001). Independent risk factors associated with altered FA and MD in the cerebellum included low Apgar score, supratentorial injury, compromised cardiorespiratory function, and surgery for necrotizing enterocolitis and patent ductus arteriosus. Conclusions This DTI study provides evidence that complications of premature birth are associated with altered cerebellar microstructural organization when compared with term‐born control infants.

Brain Injury in Neonates with Complex Congenital Heart Disease: What Is the Predictive Value of MRI in the Fetal Period?

BACKGROUND AND PURPOSE: Brain injury in neonates with congenital heart disease is an important predictor of adverse neurodevelopmental outcome. Impaired brain development in congenital heart disease may have a prenatal origin, but the sensitivity and specificity of fetal brain MR imaging for predicting neonatal brain lesions are currently unknown. We sought to determine the value of conventional fetal MR imaging for predicting abnormal findings on neonatal preoperative MR imaging in neonates with complex congenital heart disease. MATERIALS AND METHODS: MR imaging studies were performed in 103 fetuses with confirmed congenital heart disease (mean gestational age, 31.57 ± 3.86 weeks) and were repeated postnatally before cardiac surgery (mean age, 6.8 ± 12.2 days). Each MR imaging study was read by a pediatric neuroradiologist. RESULTS: Brain abnormalities were detected in 17/103 (16%) fetuses by fetal MR imaging and in 33/103 (32%) neonates by neonatal MR imaging. Only 9/33 studies with abnormal neonatal findings were preceded by abnormal findings on fetal MR imaging. The sensitivity and specificity of conventional fetal brain MR imaging for predicting neonatal brain abnormalities were 27% and 89%, respectively. CONCLUSIONS: Brain abnormalities detected by in utero MR imaging in fetuses with congenital heart disease are associated with higher risk of postnatal preoperative brain injury. However, a substantial proportion of anomalies on postnatal MR imaging were not present on fetal MR imaging; this result is likely due to the limitations of conventional fetal MR imaging and the emergence of new lesions that occurred after the fetal studies. Postnatal brain MR imaging studies are needed to confirm the presence of injury before open heart surgery.

Altered Cerebral Perfusion in Infants Born Preterm Compared with Infants Born Full Term.

Objectives To compare regional cerebral cortical blood flow (CBF) in infants born very preterm at term‐equivalent age (TEA) and healthy newborns born full term and to examine the impact of clinical risk factors on CBF in the cohort born preterm. Study design This prospective, cross‐sectional study included infants born very preterm (gestational age at birth <32 weeks; birth weight <1500 g) and healthy infants born full term. Using noninvasive 3T arterial spin labeling magnetic resonance imaging, we quantified regional CBF in the cerebral cortex: sensorimotor/auditory/visual cortex, superior medial/dorsolateral prefrontal cortex, anterior cingulate cortex (ACC)/posterior cingulate cortex, insula, and lateral posterior parietal cortex, as well as in the brainstem, and deep gray matter. Analyses were performed controlling for sex, gestational age, and age at magnetic resonance imaging. Results We studied 202 infants: 98 born preterm and 104 born full term at TEA. Infants born preterm demonstrated greater global CBF (&bgr; = 9.03; P < .0001) and greater absolute regional CBF in all brain regions except the insula. Relative CBF in the insula, ACC and auditory cortex were decreased significantly in infants born preterm compared with their peers born at full term (P < .0001; P = .026; P = .036, respectively). In addition, the presence of parenchymal brain injury correlated with lower global and regional CBF (insula, ACC, sensorimotor, auditory, and visual cortices) whereas the need for cardiac vasopressor support correlated with lower regional CBF in the insula and visual cortex. Conclusions Altered regional cortical CBF in infants born very preterm at TEA may reflect early brain dysmaturation despite the absence of cerebral cortical injury. Furthermore, specific cerebral cortical areas may be vulnerable to early hemodynamic instability and parenchymal brain injury.

Normal Cerebellar Development by Qualitative and Quantitative MR Imaging: From the Fetus to the Adolescent

This article presents an overview of published studies using conventional and quantitative MR imaging to describe normal development of the cerebellum prenatally and postnatally through 18 years of age. Normal cerebellar development and maturational processes are described here within the context of MR imaging morphology, microstructure, metabolism, and functional connectivity. In addition, strengths and weaknesses of these reviewed studies are critically appraised and new directions for future cerebellar MR imaging investigation are made.

Altered Cerebellar Biochemical Profiles in Infants Born Prematurely

This study aims to compare the cerebellar biochemical profiles in preterm (PT) infants evaluated at term equivalent age (TEA) and healthy full-term newborns using proton magnetic resonance spectroscopy (1H-MRS). We explore the associations between altered cerebellar metabolite profiles and brain injury topography, severity of injury, and prematurity-related clinical complications. We prospectively collected high quality 1H-MRS in 59 premature infants born ≤32 weeks and 61 healthy full term controls. 1H-MRS data were processed using LCModel software to calculate absolute metabolite concentration for N-acetyl-aspartate (NAA), choline (Cho) and creatine (Cr). PT infants had significantly lower cerebellar NAA (p < 0.025) and higher Cho (p < 0.001) at TEA when compared to healthy controls. Creatine was not different between the two groups. The presence of cerebellar injury was consistently associated with reduced concentrations for NAA, Cho, and Cr. Postnatal infection was negatively associated with NAA and Cr (p < 005), while cerebral cortical brain injury severity was inversely associated with both Cho and Cr (p < 0.01). We report for the first time that premature birth is associated with altered cerebellar metabolite profiles when compared to term born controls. Infection, cerebellar injury and supratentorial injury are important risk factors for impaired preterm cerebellar biochemistry.

Author Correction: Altered Cerebellar Biochemical Profiles in Infants Born Prematurely

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