Regional cortical volumes and congenital heart disease: a MRI study in 22q11.2 deletion syndrome

Abstract

Children with congenital heart disease (CHD) who survive surgery often present impaired neurodevelopment and qualitative brain anomalies. However, the impact of CHD on total or regional brain volumes only received little attention. We address this question in a sample of patients with 22q11.2 deletion syndrome (22q11DS), a neurogenetic condition frequently associated with CHD. Sixty-one children, adolescents, and young adults with confirmed 22q11.2 deletion were included, as well as 80 healthy participants matched for age and gender. Subsequent subdivision of the patients group according to CHD yielded a subgroup of 27 patients with normal cardiac status and a subgroup of 26 patients who underwent cardiac surgery during their first years of life (eight patients with unclear status were excluded). Regional cortical volumes were extracted using an automated method and the association between regional cortical volumes, and CHD was examined within a three-condition fixed factor. Robust protection against type I error used Bonferroni correction. Smaller total cerebral volumes were observed in patients with CHD compared to both patients without CHD and controls. The pattern of bilateral regional reductions associated with CHD encompassed the superior parietal region, the precuneus, the fusiform gyrus, and the anterior cingulate cortex. Within patients, a significant reduction in the left parahippocampal, the right middle temporal, and the left superior frontal gyri was associated with CHD. The present results of global and regional volumetric reductions suggest a role for disturbed hemodynamic in the pathophysiology of brain alterations in patients with neurodevelopmental disease and cardiac malformations.

Fig. 1

Distribution of cortical reduction associated with 22q11DS plotted on the average study-specific brain. Percentage of volumetric reduction is illustrated using a scale centered at average cerebral reduction (−12%, green). Blue regions demonstrate relative preservation (i.e., less than 12% of reduction) and yellow to red regions indicate regions with the greatest percentage reduction

Fig. 2

Total and regional volumetric differences related to CHD. Patients with 22q11DS and CHD showed more drastic reductions in total brain volume than patients without CHD, compared to typically developing individuals. The regional distribution of the most significant parcels driving average cerebral reduction is also shown: yellow regions demonstrate areas where patients with normal cardiac status show intermediate reductions between normal controls and patients with CHD; red depicts regions where reduction is exclusively related to the presence of CHD

Fig. 3

Variability in the arterial territories (adapted from the article by van der Zwan and Hillen 1991). Territories supplied by the anterior (white), middle (black), and posterior (gray) cerebral are schematically reproduced, illustrating possible variations (from a to d)