Long term motor function after neonatal stroke: Lesion localization above all

Abstract

Motor outcome is variable following neonatal arterial ischemic stroke (NAIS). We analyzed the relationship between lesion characteristics on brain MRI and motor function in children who had suffered from NAIS. Thirty eight full term born children with unilateral NAIS were investigated at the age of seven. 3D T1- and 3D FLAIR-weighted MR images were acquired on a 3T MRI scanner. Lesion characteristics were compared between patients with and without cerebral palsy (CP) using the following approaches: lesion localization either using a category-based analysis, lesion mapping as well as voxel-based lesion-symptom mapping (VLSM). Using diffusion-weighted imaging the microstructure of the cortico-spinal tract (CST) was related to the status of CP by measuring DTI parameters. Whereas children with lesions sparing the primary motor system did not develop CP, CP was always present when extensive lesions damaged at least two brain structures involving the motor system. The VLSM approach provided a statistical map that confirmed the cortical lesions in the primary motor system and revealed that CP was highly correlated with lesions in close proximity to the CST. In children with CP, diffusion parameters indicated microstructural changes in the CST at the level of internal capsule and the centrum semiovale. White matter damage of the CST in centrum semiovale was a highly reproducible marker of CP. This is the first description of the implication of this latter region in motor impairment after NAIS. In conclusion, CP in childhood was closely linked to the location of the infarct in the motor system.

Keywords: brain lesion; cerebral palsy; morphometry; motor deficit; neonatal stroke.

Figure 1

Classification‐tree relating presence or absence of unilateral CP with the presence or absence of brain damage. Hemi: unilateral cerebral palsy; BG: basal ganglia; numbers in boxes represent number of subjects. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 2

Lesion overlap plots for the group of: A, patients with unilateral CP (n = 14); B, patients without CP (n = 24). The colour range indicates the number of overlapping lesions by coding increasing frequencies from violet (n = 1 subject) to red (n = maximum number of subjects in the respective group). [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 3

VLSM identified lesioned regions most correlated with unilateral CP (p < 0.05, FDR correction). Voxels lesioned in at least 5% of patients were included. Colours represent z‐scores. Montreal Neurological Institute x, y, and z coordinates are given. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 4

Mean diffusivity (MD, in mm²/s) computed in the corticospinal tract (CST) of patients with CP (n = 11) and without CP (n = 22). Box plots show higher MD in CST ipsilateral to the lesion at the level of the internal capsule and centrum semiovale in stroke children with CP compared to those without CP (* = p < 0.01). Contralateral to the lesion there was no difference between the CP and the non‐CP group. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 5

VLSM‐group‐results (FDR‐thresholded at p < 0.05) co‐registered and overlayed on 3D‐Flair coronal (top) and axial (bottom) slices of a single 7‐year old child with unilateral spastic CP (subject 10, see Table I). The CST of that child is also shown (in blue, estimated from probabilistic fiber tracking using diffusion‐weighted MRI to demonstrate the relationship between critical regions for developing CP and the cortico‐spinal tract. [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]

Figure 6

Imaging follow‐up of child with NAIS on the right hemisphere (subject 10 with unilateral (left) CP, see table I). A, DW Imaging in the neonatal acute phase: While cortical involvement is predominant, ischemic injury also involves subcortical white matter in the centrum semiovale at the location of the fanning of the corticospinal tract (compare to Fig. 5, same subject), B: T1‐weighted image and FLAIR‐image at 7 years of age of the same child: The atrophic lesion closely matches the pattern seen in the neonatal period, with phantom cortical ribbon in the central region, signs of gliosis of the subcortical and deep white matter, encompassing part of the cortico‐spinal tract (in red). [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]