Impaired neuroanatomic development in infants with congenital heart disease

Department of Pediatrics, University of Toyama, Toyama, Japan.
The Journal of thoracic and cardiovascular surgery (Impact Factor: 3.41). 01/2009; 137(1):146-53. DOI: 10.1016/j.jtcvs.2008.06.036
Source: PubMed

ABSTRACT We performed a regional volumetric study of the brain using 3-dimensional magnetic resonance imaging in infants with congenital heart disease to search for variables in anatomic development of the brain that may be associated with functional impairment.
Forty infants with congenital heart disease-17 infants with single ventricle physiology, 5 with transposition of great arteries, and 18 with ventricular septal defect-were studied prospectively by 3-dimensional magnetic resonance imaging of the brain several months after heart surgery.
The global volume of gray matter was significantly reduced in the patients with congenital heart disease compared with normal controls (P < .001), whereas no significant difference in the volume of white matter was observed. Further, the decrease in gray matter volume was more apparent in the frontal lobe than in the temporal lobe, especially in infants with single ventricle physiology or transposition of the great arteries. Multivariate analysis revealed that preoperative hypoxia is strongly associated with decreased frontal gray matter volume (P < .01), as well as a diagnosis of hypoplastic left heart syndrome (P < .05). Of note, frontal gray matter volume, which includes the motor area, correlated weakly with psychomotor developmental index scores (P < .01).
Brain developmental impairment occurs in many infants with congenital heart disease, especially in those who have preoperative hypoxia and critical congenital heart disease. This quantitative volumetric study encourages larger scale and longitudinal follow-up to elucidate the significance of impaired neuroanatomic development on functional outcome.

  • [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the relationship between tissue-specific alterations in brain volume and neurobehavioral status in newborns with complex congenital heart defects preoperatively. Three-dimensional volumetric magnetic resonance imaging was used to calculate tissue-specific brain volumes and a standardized neurobehavioral assessment was performed to assess neurobehavioral status in 35 full-term newborns admitted to the hospital before cardiopulmonary bypass surgery. Multiple linear regression models were performed to evaluate relationships between neurobehavioral status and brain volumes. Reduced subcortical gray matter (SCGM) volume and increased cerebrospinal fluid (CSF) volume were associated with poor behavioral state regulation (SCGM, P = .04; CSF, P = .007) and poor visual orienting (CSF, P = .003). In cyanotic newborns, reduced SCGM was associated with higher overall abnormal scores on the assessment (P = .001) and poor behavioral state regulation (P = .04), and increased CSF volume was associated with poor behavioral state regulation (P = .02), and poor visual orienting (P = .02). Conversely, acyanotic newborns showed associations between reduced cerebellar volume and poor behavioral state regulation (P = .03). Abnormal neurobehavior is associated with impaired volumetric brain growth before open heart surgery in infants with complex congenital heart defects. This study highlights a need for routine preoperative screening and early intervention to improve neurodevelopmental outcomes.
    The Journal of pediatrics 12/2013; 164(5). DOI:10.1016/j.jpeds.2013.11.033 · 4.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This paper aims to update clinicians on “hot topics” in the management of patients with D-loop transposition of the great arteries (D-TGA) in the current surgical era. The arterial switch operation (ASO) has replaced atrial switch procedures for D-TGA, and 90% of patients now reach adulthood. The Adult Congenital and Pediatric Cardiology Council of the American College of Cardiology assembled a team of experts to summarize current knowledge on genetics, pre-natal diagnosis, surgical timing, balloon atrial septostomy, prostaglandin E1 therapy, intraoperative techniques, imaging, coronary obstruction, arrhythmias, sudden death, neoaortic regurgitation and dilation, neurodevelopmental (ND) issues, and lifelong care of D-TGA patients. In simple D-TGA: 1) familial recurrence risk is low; 2) children diagnosed pre-natally have improved cognitive skills compared with those diagnosed post-natally; 3) echocardiography helps to identify risk factors; 4) routine use of BAS and prostaglandin E1 may not be indicated in all cases; 5) early ASO improves outcomes and reduces costs with a low mortality; 6) single or intramural coronary arteries remain risk factors; 7) post-ASO arrhythmias and cardiac dysfunction should raise suspicion of coronary insufficiency; 8) coronary insufficiency and arrhythmias are rare but are associated with sudden death; 9) early- and late-onset ND abnormalities are common; 10) aortic regurgitation and aortic root dilation are well tolerated; and 11) the aging ASO patient may benefit from “exercise-prescription” rather than restriction. Significant strides have been made in understanding risk factors for cardiac, ND, and other important clinical outcomes after ASO.
    Journal of the American College of Cardiology 08/2014; 64(5):498–511. DOI:10.1016/j.jacc.2014.06.1150 · 15.34 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Chronic cyanosis in adults with congenital heart disease (CHD) may cause structural brain changes that could contribute to impaired neurological functioning. The extent of these changes has not been adequately characterized. Hypothesis We hypothesized that adults with cyanotic CHD would have widespread changes including abnormal brain volumetric measures, decreased cortical thickness and an increased burden of small and large vessel ischemic changes. Methods Ten adults with chronic cyanosis from CHD (40 ± 4 years) and mean oxygen saturations of 82 ± 2% were investigated using quantitative MRI. Hematological and biochemical parameters were also assessed. All subjects were free from major physical or intellectual impairment. Brain volumetric results were compared with randomly selected age- and sex-matched controls from our database of normal subjects. Results Five of 10 cyanotic subjects had cortical lacunar infarcts. The white matter (WM) hyperintensity burden was also abnormally high (Scheltens Scale was 8 ± 2). Quantitative MRI revealed evidence of extensive generalized WM and GM volumetric loss: Global GM volume was reduced in cyanosed subjects (630 ± 16 vs: 696 ± 14 mL in controls, p = 0.01). Global WM was also reduced (471 ± 10 vs: 564 ± 18 mL, p = 0.003). Ventricular CSF volume was increased (35 ± 10 vs: 26 ± 5 mL, p = 0.002). There were widespread regions of local cortical thickness reduction observed across the brain. These changes included bilateral thickness reductions in the frontal lobe including the dorsolateral prefrontal cortex and precentral gyrus, the posterior parietal lobe and the middle temporal gyrus. Sub-cortical volume changes were observed in the caudate, putamen and in the thalamus (p ≤ 0.005 for all regions). Cortical GM volume negatively correlated with brain natriuretic peptide (R = − 0.89, p = 0.009), high sensitivity C-reactive protein (R = − 0.964, p < 0.0001) and asymmetric dimethylarginine (R = − 0.75, p = 0.026) but not with oxygen saturations, packed cell volume or viscosity. Conclusions We present the first comprehensive analysis of brain structure in adults with chronic neurocyanosis due to congenital heart disease. We demonstrate clear evidence for marked macro- and microvascular injury. Cyanotic patients show global evidence for reduced brain volume as well as specific foci of cortical thickness reduction. The GM volume loss correlated with hsCRP, BNP and ADMA suggesting that inflammation, neurohormonal activation and endothelial dysfunction may have important roles in its pathogenesis.
    01/2014; 4. DOI:10.1016/j.nicl.2013.12.011


Available from
Jun 2, 2014