Immature Spinal Locomotor Output in Children with Cerebral Palsy

Abstract

Detailed descriptions of gait impairments have been reported in cerebral palsy (CP), but it is still unclear how maturation of the spinal motoneuron output is affected. Spatiotemporal alpha-motoneuron activation during walking can be assessed by mapping the electromyographic activity profiles from several, simultaneously recorded muscles onto the anatomical rostrocaudal location of the motoneuron pools in the spinal cord, and by means of factor analysis of the muscle activity profiles. Here, we analyzed gait kinematics and EMG activity of 11 pairs of bilateral muscles with lumbosacral innervation in 35 children with CP (19 diplegic, 16 hemiplegic, 2-12 years) and 33 typically developing (TD) children (1-12 years). TD children showed a progressive reduction of EMG burst durations and a gradual reorganization of the spatiotemporal motoneuron output with increasing age. By contrast, children with CP showed very limited age-related changes of EMG durations and motoneuron output, as well as of limb intersegmental coordination and foot trajectory control (on both sides for diplegic children and the affected side for hemiplegic children). Factorization of the EMG signals revealed a comparable structure of the motor output in children with CP and TD children, but significantly wider temporal activation patterns in children with CP, resembling the patterns of much younger TD infants. A similar picture emerged when considering the spatiotemporal maps of alpha-motoneuron activation. Overall, the results are consistent with the idea that early injuries to developing motor regions of the brain substantially affect the maturation of the spinal locomotor output and consequently the future locomotor behavior.

Keywords: abnormal development; basic muscle activation patterns; cerebral palsy; gait; spinal locomotor output.

Figure 1

Experimental setup and recorded spatiotemporal gait parameters. (A) Schematic view of the experimental setup and recorded body landmarks and angles. Elb, elbow; GH, gleno-humeral joint; HE, heel; IL, ilium; LE, lateral femur epicondyle; LM, lateral malleolus; Wri, wrist. (B) Examples of vertical ground reaction forces in one representative child with hemiplegia (9.9 years), one diplegia (6.1 years) and one TD (11.8 years) child. The data from several strides were superimposed. Since children typically made more than one foot placement on the force plate (so that we could not isolate the force of one leg throughout the whole stance phase), the ground reaction forces in the first and second half of the stance were taken from different strides (and separated by the vertical dashed line). (C) Example of the spatiotemporal patterns of muscle and motoneuron activity along the rostrocaudal axis of the spinal cord during walking in one child with hemiplegic. Recorded EMG waveforms were used to reconstruct muscle modules (m_i) and output pattern of each segment of each side of the lumbosacral enlargement (blue curves). Same pattern is plotted in a color scale (right calibration bar) using a filled contour plot (middle). Patterns are plotted vs. the normalized gait cycle.

Figure 2

Foot trajectory and vertical hip displacement characteristics. (A), Correlation coefficient (mean + SD) between vertical foot displacements (5MT_y, swing phase) in children with CP and TD toddlers and ensemble average in older TD children. (B–D) Averaged across all strides individual foot trajectories (5MT_y, ordered according to age from top to bottom) for children with hemiplegia (more affected and least affected sides), diplegia (right and left sides) and TD (right and left sides) children. TD children were divided into two subgroups: 7 toddlers aged 1–1.2 years and 26 older children aged 2.1–11.8 years. The lower curves in B-D illustrate ensemble-averaged (across subjects, ± SD) foot movements. 5MT_y is expressed in relative units (normalized by the limb length L). (E) Vertical hip (GT_y, averaged for right and left legs) displacements averaged across subjects (mean ± SD, left panel) and correlation coefficients between GT_y data in children with CP and TD toddlers and corresponding ensemble averaged GT_y in older TD children (right panel). Horizontal lines denote significant differences with older TD children.

Figure 3

Planar covariation of limb segment elevation angles during walking. (A) Ensemble-averaged (mean ± SD) foot, thigh and shank elevation angles plotted vs. normalized gait cycle. As the relative duration of stance varied across strides and subjects, a hatched region indicates an amount of variability in the stance phase duration. Examples of 3-dimensional gait loops and interpolation planes are shown on the bottom from left to right for one child with hemiplegia (9.9 years) and one diplegia (8.8 years), as well as for one toddler (1.1 year) and one TD child (6.2 years). Gait loops are obtained by plotting the thigh waveform vs. the shank and foot waveforms (after mean values subtraction). Gait cycle paths progress in time in the counter-clockwise direction, touch-down and toe-off phases corresponding roughly to the top and bottom of the loops, respectively. The interpolation planes result from orthogonal planar regression. (B) Percentage of total variation explained by 2nd and 3rd principal components (PV₂ and PV₃, respectively) and u_3t parameter that characterizes the orientation of the normal to the plane are indicated for each group of children (mean ± SD). Horizontal lines denote significant differences with older TD children.

Figure 4

MG muscle activity. (A–C) Stride-averaged MG muscle activity for each subject (ordered by age) in children with hemiplegia, diplegia and TD children, respectively. (D) Center of activity (CoA) of the MG muscle in individual subjects as a function of age (left panels) and averaged across children (right panel). Continuous lines on the left panels represent exponential fittings. (E), FWHM of MG activity as a function of age (left panels) and averaged across children (right panel). FWHM was calculated as the duration of the interval (in percent of gait cycle) in which EMG activity exceeded half of its maximum (see insert on the top). Horizontal lines denote significant differences compared with older TD children. Note a monotonic shift of the CoA toward later stance and a monotonic decrement of the FWHM in TD children with age, a lack of these changes in children with diplegia and their differential maturation on the affected and least affected sides in children with hemiplegia.

Figure 5

Characteristics of EMG activity. (A) Ensemble averaged (mean + SD) EMG activity patterns of 22 bilateral leg muscles recorded in children with CP and TD children. EMG data are plotted vs. normalized gait cycle. (B) FWHM of EMGs as a function of age in children with hemiplegia, diplegia and TD children. Continuous lines represent exponential fittings. Note a monotonic decrement of FWHM in TD children. (C) CoA, FWHM and mean leg muscle EMGs (means + SD) for children with CP and TD children. (D) Co-activation index (CI) for RF-VL-VM vs. ST-BF and MG-LG-SOL vs. TA pairs of antagonist muscles. Asterisks denote significant differences with older TD children.

Figure 6

Statistical analysis of EMG patterns using non-negative matrix factorization. The data for the most affected and less affected sides of children with hemiplegia and for TD toddlers and older children are shown separately. (A) Cumulative percent of variance (VAF) (±SD) explained by basic EMG components in hemiplegic (left), diplegic (center) and TD (right) children. (B) The number of modules needed to account for cycle-by-cycle variability of muscle activity estimated using the “best linear fit” method (left) and the normalized CH index (Caliñski and Harabasz, 1974) to evaluate the number of clusters in each group (right). Even if three to five modules were sufficiently representative in a few children, EMG activity in most children was well accounted for by four modules (>80% of VAF, A). (C) Comparison of muscle module (basic activation patterns) structures across different groups. Each curve represents the mean (across strides) pattern for an individual child. Common (across children) basic patterns were plotted in a “chronological” order (with respect to the timing of the main peak) and modules were ranked based on their best similarities (see Materials and Methods). Note that synergies with low structural consistency across children (NC, Not Classified) were plotted separately on the bottom in toned-down colors. (D) Group mean weights (synergies). (E,F) mean (+SD) FWHM and CoA of consistent basic activation patterns (P1–P4). Horizontal lines denote significant differences compared with older TD children. Note wider P2 and P4 patterns in children with CP and toddlers with respect to older children (E), consistent with wider EMGs (Figure 5C, bottom).

Figure 7

Spatiotemporal maps of motoneuron activity of the lumbosacral enlargement in children with CP and TD children. (A) Output pattern of each segment is shown in the top panels (thick traces, means; thin traces, means + 1SD), while the same pattern is plotted in a color scale (using a filled contour plot) at the bottom. Motor output (averaged across children, reported in units of number of MNs) is plotted as a function of gait cycle and spinal segment level (L2 − S2). (B), Depicted are mean (+SD) activation of lumbosacral activity (averaged across both gait cycle and spinal level). (C) Timing of maximum activation of lumbar (L3 + L4) and sacral (S1 + S2) segments. The values represent the mean + SD. Lines over bars denote significant differences compared with older TD children.

Figure 8

Spatiotemporal maps of motoneuron activity of the lumbosacral enlargement for each subject (ordered by age) in children with hemiplegia (A), diplegia (B), and TD children (C). The pattern is plotted in a color scale (using a filled contour plot) for both sides of the spinal cord. Motor output (averaged across strides, reported in units of μV × number of MNs) is plotted as a function of gait cycle and spinal segment level (L2-S2).