Lesion mapping and functional characterization of hemiplegic children with different patterns of hand manipulation

Abstract

Brain damage in children with unilateral cerebral palsy (UCP) affects motor function, with varying severity, making it difficult the performance of daily actions. Recently, qualitative and semi-quantitative methods have been developed for lesion classification, but studies on mild to moderate hand impairment are lacking. The present study aimed to characterize lesion topography and preserved brain areas in UCP children with specific patterns of hand manipulation. A homogeneous sample of 16 UCP children, aged 9 to 14 years, was enrolled in the study. Motor assessment included the characterization of the specific pattern of hand manipulation, by means of unimanual and bimanual measures (Kinematic Hand Classification, KHC; Manual Ability Classification System, MACS; House Functional Classification System, HFCS; Melbourne Unilateral Upper Limb Assessment, MUUL; Assisting Hand Assessment, AHA). The MRI morphological study included multiple methods: (a) qualitative lesion classification, (b) semi-quantitative classification (sq-MRI), (c) voxel-based morphometry comparing UCP and typically developed children (VBM-DARTEL), and (d) quantitative brain tissue segmentation (q-BTS). In addition, functional MRI was used to assess spared functional activations and cluster lateralization in the ipsilesional and contralesional hemispheres of UCP children during the execution of simple movements and grasping actions with the more affected hand. Lesions most frequently involved the periventricular white matter, corpus callosum, posterior limb of the internal capsule, thalamus, basal ganglia and brainstem. VMB-DARTEL analysis allowed to detect mainly white matter lesions. Both sq-MRI classification and q-BTS identified lesions of thalamus, brainstem, and basal ganglia. In particular, UCP patients with synergic hand pattern showed larger involvement of subcortical structures, as compared to those with semi-functional hand. Furthermore, sparing of gray matter in basal ganglia and thalamus was positively correlated with MUUL and AHA scores. Concerning white matter, q-BTS revealed a larger damage of fronto-striatal connections in patients with synergic hand, as compared to those with semi-functional hand. The volume of these connections was correlated to unimanual function (MUUL score). The fMRI results showed that all patients, but one, including those with cortical lesions, had activation in ipsilesional areas, regardless of lesion timing. Children with synergic hand showed more lateralized activation in the ipsilesional hemisphere both during grasping and simple movements, while children with semi-functional hand exhibited more bilateral activation during grasping. The study demonstrates that lesion localization, rather than lesion type based on the timing of their occurrence, is more associated with the functional level of hand manipulation. Overall, the preservation of subcortical structures and white matter can predict a better functional outcome. Future studies integrating different techniques (structural and functional imaging, TMS) could provide further evidence on the relation between brain reorganization and specific pattern of manipulation in UCP children.

Keywords: Action execution; Cerebral palsy; Functional reorganization; Lesion classification; Upper limb; Voxel-based morphometry.

Graphical abstract

Fig. 1

Overview of the study pipeline. AHA = Assisting Hand Assessment; HFCS = House Functional Classification System; KHC = Kinematic Hand Classification; MACS = Manual Ability Classification System; MUUL = Melbourne Unilateral Upper Limb assessment; q-BTS = quantitative Brain Tissue Segmentation; sq-MRI = semi-quantitative MRI-based classification; VBM = voxel-based morphometry.

Fig. 2

Lesion overlap maps calculated separately for UCP patients with semi-functional and synergic hand, respectively, projected on a standard MNI pediatric template (Fonov et al., 2011). Maps are overlaid on the axial view of six representative slices (corresponding to those used in sq-MRI classification) and three sections at the level of basal ganglia (axial view), corpus callosum (sagittal view) and brain stem (axial view), respectively.

Fig. 3

Sq-mri classification results. (A) Lesion severity is reported both as global score and specific score for the ipsilesional (IL) hemisphere, IL subcortical structures, and corpus callosum. (B) Scatterplot showing the negative linear relation between MUUL score and sq-MRI subcortical score. (C) Linear negative relation between AHA score (bimanual function) and sq-MRI subcortical score. (D) Bar graph showing the difference of sq-MRI Subcortical score in patients with synergic and semi-functional hand. Error bars represent standard deviation.

Fig. 4

VBM-DARTEL results. Differential map of the gray and white matter loss in UCP children, as compared with TD children, overlaid into six axial slices of a standard MNI pediatric template.

Fig. 5

Results of regression analysis performed on q-BTS based on subcortical nuclei segmentation. (A) Average map of gray matter distribution related to subcortical structures (FIRST-FSL segmentation) in UCP patients. The map is visualized on two axial and one coronal representative sections of subcortical nuclei. (B) Scatterplots show significant linear relation between volume of subcortical structures and unimanual ability (MUUL score). (C) Linear regressions between volume of subcortical structures and bimanual function (AHA score). (D) Difference in subcortical nuclei volume in patients with synergic and semi-functional hand. Abbreviations: IL = ipsilesional hemisphere; CL = contralesional hemisphere.

Fig. 6

Results of regression analysis performed on q-BTS based on white matter ROIs. (A) Average map of white matter distribution in UCP patients. (B) Scatterplots showing significant linear relation between volume of four white matter ROIs and unimanual ability (MUUL score). Abbreviations: IL = ipsilesional hemisphere; CL = contralesional hemisphere; CS = corticospinal tract; WM = white matter.

Fig. 7

Single-subject activations during execution of grasping acts (Exe Grasp) overlaid on individual coronal sections of T1-w images. Orange arrows indicate the prevalent activated side, considering cluster peak at the level of the primary sensorimotor cortex. Patients are also grouped according with lesion type classification by Cioni et al. (1999). IL = ipsilesional hemisphere.

Fig. 8

Brain activation in UCP children during motor task. (A) Statistical parametric maps of activation are overlaid into a standard MNI pediatric template. IL = ipsilesional hemisphere; CL = contralesional hemisphere. (B) Laterality index (LI) related to the activation of sensorimotor cortex during Exe Grasp and Exe Move conditions in the whole sample. A significant difference was present between the two tasks, with activations more lateralized during Exe Move as compared with Exe Grasp. (C) LI calculated in UCP children with synergic hand (syn) and semi-functional hand (sem) kinematic pattern. Non-parametric ANOVA showed that UCP children with semi-functional hand had more bilateral activations during Exe Grasp as compared with Exe Move. On the contrary, no significant difference was found in UCP children with synergic hand, showing a comparable lateralization during both tasks. (D-E) Significant linear relation between LI during Exe Grasp and MUUL score and AHA score, respectively. This indicates that patients with better motor abilities showed more bilateral activations.

Fig. 9

Upper panel, schematic representation of the most common types of motor reorganization observed in UCP children. Red circles indicate the location of the main lesion, and the circle diameter represents lesions with different size. In the contralateral reorganization, motor function reorganizes in the ipsilesional hemisphere. Red arrows represent structural connections controlling the more affected hand, while blue arrows represent connections to the less affected hand. In bilateral type of reorganization, a significant number of monosynaptic fast conducting projections from the undamaged cortex persists. Dotted arrows represent the spared connections between the ipsilesional hemisphere and the more affected hand, plus fast conducting projections from the undamaged cortex, typically described in this form of motor reorganization. In cases of complete ipsilateral reorganization, the more affected hand is mainly controlled by the ipsilateral undamaged cortex. Lower panel, functional activations observed in patients with semi-functional and synergic manipulation pattern during grasping execution. IL = ipsilesional hemisphere, CL = contralesional hemisphere.