Anomalous development of brain structure and function in spina bifida myelomeningocele

Abstract

Spina bifida myelomeningocele (SBM) is a specific type of neural tube defect whereby the open neural tube at the level of the spinal cord alters brain development during early stages of gestation. Some structural anomalies are virtually unique to individuals with SBM, including a complex pattern of cerebellar dysplasia known as the Chiari II malformation. Other structural anomalies are not necessarily unique to SBM, including altered development of the corpus callosum and posterior fossa. Within SBM, tremendous heterogeneity is reflected in the degree to which brain structures are atypical in qualitative appearance and quantitative measures of morphometry. Hallmark structural features of SBM include overall reductions in posterior fossa and cerebellum size and volume. Studies of the corpus callosum have shown complex patterns of agenesis or hypoplasia along its rostral-caudal axis, with rostrum and splenium regions particularly susceptible to agenesis. Studies of cortical regions have demonstrated complex patterns of thickening, thinning, and gyrification. Diffusion tensor imaging studies have reported compromised integrity of some specific white matter pathways. Given equally complex ocular motor, motor, and cognitive phenotypes consisting of relative strengths and weaknesses that seem to align with altered structural development, studies of SBM provide new insights to our current understanding of brain structure-function associations.

Figure 1

T1-weighted midsagittal MRI in a child with Chiari type II malformation illustrating herniation of the inferior cerebellar vermis (horizontal arrow) and tectal beaking (vertical arrow). The fourth ventricle is small in size.

Figure 2

T1-weighted axial MRI at the level of the pons in a child with Chiari type II malformation illustrating wrapping of the cerebellar hemispheres around the brainstem (arrow).

Figure 3

The cerebellum has been parcellated into three primarily gray matter compartments as shown in sagittal (left panels) and coronal (right panels) views. Boundary demarcations between compartments are indicated by bright white lines (anterior lobe, superior-posterior, and inferior-posterior subdivisions) in three representative subjects (A–B). A: Typically-developing child with cerebellar subdivisions numbered as 1=anterior lobe, 2=superior-posterior, 3=inferior-posterior. B: Child with SBM. The central corpus medullare was also parceled separate from the other three parcels for quantitative analyses. The smaller cerebellum observed in individuals with SBM is not simply linearly reduced equally across all regions, but rather disproportionately enlarged in the anterior lobe, reduced in the posterior-inferior subdivision, and not significantly different in the corpus medullare or the posterior-superior subdivision.

Figure 4

Significant group differences in cortical thickness between individuals with SBM (n=74) and a comparison group of typically-developing (TD) study participants (n=31). “Hot” colors indicate cortical thickness is greater in the SBM group relative to the TD group; “cold” colors indicate cortical thickness is reduced in the SBM group relative to the TD group. Color scale bar indicates significance values (corrected for multiple comparisons) ranging from p<0.0001 to p<0.01. In frontal regions, the SBM group exhibits increased cortical thickness bilaterally in the following regions: inferior frontal, middle frontal, medial orbitofrontal, rostral anterior cingulate, and superior frontal. In bilateral inferior parietal and posterior temporal areas, the SBM group displays significant cortical thinning.

Figure 5

Significant group differences in cortical complexity between individuals with SBM (n=74) and a comparison group of typically-developing (TD) study participants (n=31). “Hot” colors indicate cortical complexity is greater in the SBM group relative to the TD group; “cold” colors indicate cortical complexity is reduced in the SBM group relative to the TD group. In bilateral inferior parietal and posterior temporal areas, the SBM group displays significantly increased cortical complexity. In bilateral inferior frontal and orbitofrontal regions, the SBM group shows significantly reduced cortical complexity.