Synchronous Aberrant Cerebellar and Opercular Development in Fetuses and Neonates with Congenital Heart Disease: Correlation with Early Communicative Neurodevelopmental Outcomes, Initial Experience

Patients with congenital heart disease (CHD) demonstrate multidomain cognitive delays. Cingulo-opercular and cerebellar brain networks are critical to language functions. This is a description of our initial experience aiming to identify an anatomic correlate for CHD patients with expressive language delays. Fetal CHD patients, prospectively enrolled, underwent serial fetal (1.5T), postnatal pre- and postoperative (3T) MRI. Non-CHD patients were enrolled retrospectively from the same epoch. Comparable fetal and neonatal T2 contrast was used for manual linear cross-sectional measurement. Multivariable analysis was used for adjustments and curve fitting. Neurodevelopment was assessed with Battelle Developmental Inventory, 2nd ed. between 9 and 36 months of age. This interim analysis included patients from our longitudinal CHD study who had fetal, postnatal imaging and neurodevelopmental data—yielding a total of 62 mothers (11 CHD fetuses and 51 non-CHD fetuses). Altered brain trajectories were seen in selected cerebellar and opercular measurements in CHD patients compared with the non-CHD group. Smaller inferior cerebellar vermis measurements were associated with multiple communication-related abnormalities. Altered early structural development of the cerebellum and operculum is present in patients with CHD, which correlates with specific neurodevelopmental abnormalities.

[1]  C Büchel,et al.  Brain regions involved in articulation , 1999, The Lancet.

[2]  Floris Groenendaal,et al.  New reference values for the neonatal cerebral ventricles. , 2012, Radiology.

[3]  Bethanie Parrish,et al.  MR of the cerebral operculum: topographic identification and measurement of interopercular distances in healthy infants and children. , 1995, AJNR. American journal of neuroradiology.

[4]  Rita Moretti,et al.  Language impairments in patients with cerebellar lesions , 2000, Journal of Neurolinguistics.

[5]  Georgina Peacock,et al.  Neurodevelopmental Outcomes in Children With Congenital Heart Disease: Evaluation , 2012 .

[6]  E. Gratacós,et al.  Brainstem and cerebellar differences and their association with neurobehavior in term small-for-gestational-age fetuses assessed by fetal MRI. , 2014, American journal of obstetrics and gynecology.

[7]  Ralf Minkenberg,et al.  Long-term neurodevelopmental outcome and exercise capacity after corrective surgery for tetralogy of Fallot or ventricular septal defect in infancy. , 2006, The Annals of thoracic surgery.

[8]  Alan C. Evans,et al.  Delayed cortical development in fetuses with complex congenital heart disease. , 2013, Cerebral cortex.

[9]  W. Tatum,et al.  The open opercular sign: Diagnosis and significance , 1989, Annals of neurology.

[10]  M. Donofrio,et al.  Prevalence and Spectrum of In Utero Structural Brain Abnormalities in Fetuses with Complex Congenital Heart Disease , 2014, American Journal of Neuroradiology.

[11]  R. Shprintzen,et al.  Brain anomalies in velo-cardio-facial syndrome. , 1994, American journal of medical genetics.

[12]  H. Powell Developmental Pathology of the Neonate , 1977 .

[13]  H. Smet,et al.  The cerebellum: Its role in language and related cognitive and affective functions , 2013, Brain and Language.

[14]  R A Zimmerman,et al.  MR of the cerebral operculum: abnormal opercular formation in infants and children. , 1996, AJNR. American journal of neuroradiology.

[15]  Julia A. Scott,et al.  Local Tissue Growth Patterns Underlying Normal Fetal Human Brain Gyrification Quantified In Utero , 2011, The Journal of Neuroscience.

[16]  Equations to describe brain size across the continuum of human lifespan , 2012, Brain Structure and Function.

[17]  D. Cabrol,et al.  Cerebral biometry in fetal magnetic resonance imaging: new reference data , 2009, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[18]  C. Garel MRI of the Fetal Brain , 2012, Springer Berlin Heidelberg.

[19]  Andrea Righini,et al.  MRI of fetal and neonatal cerebellar development. , 2005, Seminars in fetal & neonatal medicine.

[20]  Dinggang Shen,et al.  Mapping longitudinal hemispheric structural asymmetries of the human cerebral cortex from birth to 2 years of age. , 2014, Cerebral cortex.

[21]  Gil Wernovsky,et al.  Neurodevelopmental status at eight years in children with dextro-transposition of the great arteries: the Boston Circulatory Arrest Trial. , 2003, The Journal of thoracic and cardiovascular surgery.

[22]  A. L. Leiner,et al.  Reappraising the cerebellum: what does the hindbrain contribute to the forebrain? , 1989, Behavioral neuroscience.

[23]  Nicolas Guizard,et al.  Brain Volume and Metabolism in Fetuses With Congenital Heart Disease: Evaluation With Quantitative Magnetic Resonance Imaging and Spectroscopy , 2010, Circulation.

[24]  P. Weinberg,et al.  Congenital brain anomalies associated with the hypoplastic left heart syndrome. , 1990, Pediatrics.

[25]  E. Zackai,et al.  Cerebellar atrophy in a patient with velocardiofacial syndrome. , 1995, Journal of medical genetics.

[26]  S. Lam,et al.  Posterior fossa syndrome in children following tumor resection: Knowledge update , 2016, Surgical neurology international.

[27]  Bruce E. Murdoch,et al.  The cerebellum and language: Historical perspective and review , 2010, Cortex.

[28]  Catherine J. Stoodley,et al.  The Cerebellum and Cognition: Evidence from Functional Imaging Studies , 2011, The Cerebellum.

[29]  Y. Zalel,et al.  Development of the human fetal pons: in utero ultrasonographic study , 2004, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[30]  B. Schoch,et al.  Cerebellar mutism , 2004, Brain and Language.

[31]  J. Desmond,et al.  Dissociation of Frontal and Cerebellar Activity in a Cognitive Task: Evidence for a Distinction between Selection and Search , 1998, NeuroImage.

[32]  R A Zimmerman,et al.  Enlarged Sylvian fissures in infants with interstitial deletion of chromosome 22q11. , 1997, American journal of medical genetics.

[33]  T. Gursoy,et al.  Does being born small-for-gestational-age affect cerebellar size in neonates? , 2016, The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians.

[34]  Hilla Peretz,et al.  Ju n 20 03 Schrödinger ’ s Cat : The rules of engagement , 2003 .

[35]  Greg Allen,et al.  Magnetic resonance imaging of cerebellar–prefrontal and cerebellar–parietal functional connectivity , 2005, NeuroImage.

[36]  D. Dierker,et al.  Cortical folding is altered before surgery in infants with congenital heart disease. , 2013, The Journal of pediatrics.

[37]  A. Khalil,et al.  Brain abnormalities and neurodevelopmental delay in congenital heart disease: systematic review and meta‐analysis , 2014, Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology.

[38]  Peter Mariën,et al.  Cerebellar neurocognition: Insights into the bottom of the brain , 2008, Clinical Neurology and Neurosurgery.

[39]  D. Lev,et al.  The fetal cerebellar vermis: normal development as shown by transvaginal ultrasound , 2001, Prenatal diagnosis.

[40]  Robert A. Zimmerman,et al.  An MRI Study of Neurological Injury Before and After Congenital Heart Surgery , 2002, Circulation.

[41]  Colin Studholme,et al.  3D Morphometric Analysis of Human Fetal Cerebellar Development , 2011, Cerebellum.

[42]  Gil Wernovsky,et al.  Brain maturation is delayed in infants with complex congenital heart defects. , 2009, The Journal of thoracic and cardiovascular surgery.

[43]  N. Boddaert,et al.  Injuries to inferior vermis and dentate nuclei predict poor neurological and neuropsychological outcome in children with malignant posterior fossa tumors , 2009, Cancer.

[44]  W. Mahle,et al.  Neurodevelopmental outcome and lifestyle assessment in school-aged and adolescent children with hypoplastic left heart syndrome. , 2000, Pediatrics.

[45]  R. Achiron,et al.  Vermian Biometric Parameters in the Normal and Abnormal Fetal Posterior Fossa , 2011, Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine.

[46]  L. Doyle,et al.  A Novel Quantitative Simple Brain Metric Using MR Imaging for Preterm Infants , 2008, American Journal of Neuroradiology.

[47]  Jeremy D. Schmahmann,et al.  Enhancing the Temporal Complexity of Distributed Brain Networks with Patterned Cerebellar Stimulation , 2016, Scientific Reports.