Maturation of Corticospinal Tracts in Children With Hemiplegic Cerebral Palsy Assessed by Diffusion Tensor Imaging and Transcranial Magnetic Stimulation

Abstract

Aim: To assess changes in the developmental trajectory of corticospinal tracts (CST) maturation in children with hemiplegic cerebral palsy (HCP). Methods: Neuroimaging data were obtained from 36 children with HCP for both the more affected (MA) and less affected (LA) hemispheres, and, for purposes of direct comparison, between groups, 15 typically developing (TD) children. With diffusion tensor imaging (DTI), we estimated the mean fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) of the corticospinal tract, parameters indicative of factors including myelination and axon density. Transcranial magnetic stimulation (TMS) was performed as a neurophysiologic measure of corticospinal tract integrity and organization. Resting motor threshold (rMT) was obtained per hemisphere, per patient. Results: We observed a significant AD and MD developmental trajectory, both of which were inversely related to age (decrease in AD and diffusivity corresponding to increased age) in both hemispheres of TD children (p < 0.001). This maturation process was absent in both MA and LA hemispheres of children with HCP. Additionally, the TMS-derived previously established rMT developmental trajectory was preserved in the LA hemisphere of children with HCP (n = 26; p < 0.0001) but this trajectory was absent in the MA hemisphere. Conclusions: Corticospinal tract maturation arrests in both hemispheres of children with HCP, possibly reflecting perinatal disruption of corticospinal tract myelination and axonal integrity.

Keywords: corticospinal tracts; development; hemiplegic cerebral palsy; maturation; transcranial magnetic stimulation.

Figure 1

Anatomically defined region of interest (ROI) and corticospinal tracts (CST). (A) The ROIs pre-central gyrus (PrG and cst) and their corresponding CST for a typically developing (TD) child (aged 18 years, upper panel) and a child with hemiplegic cerebral palsy (HCP) overlaid on their magnetic resonance imagings (MRIs). (B) Error bars (mean ± 95% confidence interval) of diffusion parameters [fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD)] for the CST for both hemispheres of TD children and the less affected (LA) and more affected (MA) hemispheres of children with HCP (**p < 0.001).

Figure 2

Developmental trajectories of diffusion parameters. Mean FA, AD, MD, and RD for TD children (Hem1: dark green closed circles, Hem2: light green open circles), and children with HCP (MA: red closed circles, LA: blue closed circles) as a function of age. For FA TD (Hem1; R² = 0.0080, p = 0.7506), TD (Hem2; R² = 0.0001, p = 0.9788), HCP (LA; R² = 0.0258, p = 0.5999), HCP (MA; R² = 0.0019, p = 0.8883). For AD: TD (Hem1; R² = 0.4101, p < 0.001), TD (Hem2; R² = 0.460, p < 0.001), HCP (LA; R² = 0.0395; p = 0.558); HCP (MA; R² = 0.081, p = 0.397). For MD: TD (Hem1; R² = 0.299, p < 0.001), TD (Hem2; R² = 0.419, p < 0.001), HCP (LA; R² = 0.116, p = 0.306); HCP (MA; R² = 0.025, p = 0.639). For RD: TD (Hem1; R² = 0.1931, p = 0.101), TD (Hem2; R² = 0.212, p = 0.085), HCP (LA; R² = 0.0479, p = 0.5437); HCP (MA; R² = 0.0117, p = 0.7665).

Figure 3

Representative transcranial magnetic stimulation (TMS) motor map and resting motor threshold (rMT) measures. (A) An approximation of stimulating electric field induced by TMS is displayed on a 3D reconstruction of the cortical surface (for same subject as shown in Figure 1A), where field center is indicated by the junction between the red and blue arrows indicating the direction of induced current, and corresponding composite map of right hemispheric stimulation sites evoking motor evoked potentials (MEPs) of the left abductor pollicis brevis (APB) muscle. Intensity of response is color-coded from lowest (gray) to highest (white). (B) Representative left APB MEP sample where the vertical line (black) corresponds to stimulus time. (C) rMT of children with HCP for the LA and MA hemispheres (***p < 0.0001).

Figure 4

rMT developmental trajectories. rMT as a function of age in the (A) LA hemisphere (R² = 0.6114, p < 0.0001) and (B) MA hemisphere (R² = 0.0313, p = 0.4991) for patients with HCP who underwent TMS (n = 26).