Subtle hemorrhagic brain injury is associated with neurodevelopmental impairment in infants with repaired congenital heart disease

Abstract

Objective: Perioperative stroke and periventricular leukomalacia have been reported to occur commonly in infants with congenital heart disease. We aimed to determine the incidence and type of brain injury in infants undergoing 2-ventricle repair in infancy and to determine risk factors associated with such injury.

Methods: Forty-eight infants enrolled in a trial comparing 2 different hematocrits during surgical repair of congenital heart disease underwent brain magnetic resonance imaging scans and neurodevelopmental testing at 1 year of age.

Results: Eighteen (38%) of our subjects had tiny foci of hemosiderin by susceptibility imaging, without evidence of abnormalities in corresponding regions on conventional magnetic resonance imaging sequences. Subjects with foci of hemosiderin had a significantly lower Psychomotor Developmental Index at 1 year of age (79.6 +/- 16.5, mean +/- standard deviation) compared with subjects without these foci (89.5 +/- 15.3; P = .04). Older age at surgery and diagnostic group were significantly associated with the presence of hemosiderin foci. Only 1 subject had a small stroke (2%), and 2 subjects had periventricular leukomalacia (4%).

Conclusion: Foci of hemosiderin without radiologic evidence of ischemic brain injury are an abnormality associated with adverse neurodevelopmental outcome not previously described in magnetic resonance imaging studies of children with surgically repaired congenital heart disease. The association of hemosiderin foci with older age at surgery and cardiac diagnosis, and not with risk factors associated with brain injury, in previous studies suggests that the cause and pathogenesis of this abnormality are different from ischemic brain lesions reported previously.

Trial registration: ClinicalTrials.gov NCT00006183.

Figures

Figure 1

Focus of hemosiderin in left parieto-occipital cortex (arrow) seen on axial MPGR sequence (A) without corresponding abnormality on axial T2w FSE sequence (B)

Figure 2

Small area of focal encephalomalacia seen as T2 hyperintensity in left insular region (arrow), consistent with old focal stroke

Figure 3

PVL in a subject with VSD (3A & B) and in a subject with TOF (3C & D) demonstrated by T2w imaging as patchy areas of T2 hyperintensity in the cerebral white matter dorsolateral to the frontal horns and occipital horns of the lateral ventricles (arrows)

Figure 4

Boxplot of Psychomotor (PDI) and Mental (MDI) Development Index scores for subjects with and without foci of hemosiderin. The limits of the box indicate the 25th and 75th percentiles and the median is marked by the line within the box. The whiskers indicate the 10th and 90th percentiles and the observations outside of this range are shown as solid circles.