Spinal Cord Imaging Markers and Recovery of Volitional Leg Movement With Spinal Cord Epidural Stimulation in Individuals With Clinically Motor Complete Spinal Cord Injury

Enrico Rejc, Andrew C Smith, Kenneth A Weber 2nd, Beatrice Ugiliweneza, Robert J Bert, Mohammadjavad Negahdar, Maxwell Boakye, Susan J Harkema, Claudia A Angeli, Enrico Rejc, Andrew C Smith, Kenneth A Weber 2nd, Beatrice Ugiliweneza, Robert J Bert, Mohammadjavad Negahdar, Maxwell Boakye, Susan J Harkema, Claudia A Angeli

Abstract

Previous studies have shown that epidural stimulation of the lumbosacral spinal cord (scES) can re-enable lower limb volitional motor control in individuals with chronic, clinically motor complete spinal cord injury (SCI). This observation entails that residual supraspinal connectivity to the lumbosacral spinal circuitry still persisted after SCI, although it was non-detectable when scES was not provided. In the present study, we aimed at exploring further the mechanisms underlying scES-promoted recovery of volitional lower limb motor control by investigating neuroimaging markers at the spinal cord lesion site via magnetic resonance imaging (MRI). Spinal cord MRI was collected prior to epidural stimulator implantation in 13 individuals with chronic, clinically motor complete SCI, and the spared tissue of specific regions of the spinal cord (anterior, posterior, right, left, and total cord) was assessed. After epidural stimulator implantation, and prior to any training, volitional motor control was evaluated during left and right lower limb flexion and ankle dorsiflexion attempts. The ability to generate force exertion and movement was not correlated to any neuroimaging marker. On the other hand, spared tissue of specific cord regions significantly and importantly correlated with some aspects of motor control that include activation amplitude of antagonist (negative correlation) muscles during left ankle dorsiflexion, and electromyographic coordination patterns during right lower limb flexion. The fact that amount and location of spared spinal cord tissue at the lesion site were not related to the ability to generate volitional lower limb movements may suggest that supraspinal inputs through spared spinal cord regions that differ across individuals can result in the generation of lower limb volitional motor output prior to any training when epidural stimulation is provided.

Keywords: epidural stimulation; spinal cord MRI; spinal cord injury; spinal cord lesion; spinal tracts; voluntary movement.

Copyright © 2020 Rejc, Smith, Weber, Ugiliweneza, Bert, Negahdar, Boakye, Harkema and Angeli.

Figures

FIGURE 1
FIGURE 1
Imaging analysis methods. (A) Sagittal and axial slices of the T2-weighted image of a representative participant with a severe lesion. The lesion is identified as the hyperintensity in the spinal cord. (B) A blinded experimenter manually segmented the spinal cord (blue) and lesion (red) from the T2-weighted image. (C) The PAM50 T2-weighted template was then registered to the T2-weighted image using the manually draw spinal cord mask. The transformation was then applied to lesion mask to bring the lesion into template space. The spinal cord mask and lesion mask from (B) are shown transformed to the PAM50 spinal cord template. (D,E) To quantify the axial extent of the spinal cord lesion, the lesion mask in template space was then projected onto the axial plane to create one projected axial image of the composite lesion.
FIGURE 2
FIGURE 2
Imaging results from three representative research participants. (A) Participant A99, with no spared tissue of the spinal cord remaining. (B) Participant B21, who shows minimal spared spinal cord tissue. (C) Participant A110, who presents considerable spared spinal cord tissue. Red, spinal cord damage; blue, spared spinal cord tissue.
FIGURE 3
FIGURE 3
Spinal cord white matter regions and exemplary percent spared tissue. The left column depicts the four white matter regions that were used to quantify the spared tissue correlated with motor outcomes. The right column shows four representative research subjects’ spinal cord damage as well as the percentage of the corresponding white matter region that was spared. The red area indicates the lesioned tissue in each region.
FIGURE 4
FIGURE 4
Number of motor tasks successfully performed are plotted against the amount of spared tissue of representative cord regions.
FIGURE 5
FIGURE 5
Plots of statistically significant and important correlations between amount of spared tissue of specific cord regions and muscle activation outcomes. R, right side; L, left side; RMS, root mean square; SOL, soleus; JPD R MH, amount of isolated activation of R medial hamstrings; JPD Co-co-Low, amount of co-contraction at lower level of activation between right MH and iliopsoas.
FIGURE 6
FIGURE 6
Representative EMG activity modulation and force generation during isometric ankle dorsiflexion attempts performed without (A) and with (B) spinal cord epidural stimulation (scES) by two research participants (A110 and A80). Vertical gray dotted lines: attempt duration. (C) Spared tissue of the anterior cord, which was found inversely correlated with EMG amplitude of L SOL (antagonist muscle) during left ankle dorsiflexion attempts, and of the total cord for the same two participants. L, left side; VL, vastus lateralis; MH, medial hamstrings; TA, tibialis anterior; SOL, soleus. The gray arrow points out the decrease in L SOL EMG activity in response to the volitional attempt. Epidural stimulation electrode configuration (cathodes in black, anodes in red, inactive in white), frequency, pulse width and intensity are reported.
FIGURE 7
FIGURE 7
Representative EMG activity modulation and hip joint movement during right lower limb flexion attempts performed without (A) and with (B) spinal cord epidural stimulation (scES) by two research participants (A101 and B21). Vertical gray dotted lines: attempt duration. (C) Probability density distribution (JPD) of normalized EMG amplitudes between right (R) iliopsoas (IL) and medial hamstrings (MH) calculated during the volitional attempts, and related data points distribution in each of the four identified areas [co-contraction at lower (JPD Co-co-Low) or higher (JPD Co-co-Hi) level of activation; isolated activation of R IL (JPD R IL) or R MH (JPD R MH)]. (D) Spared tissue of the right and total cord, which were found correlated with JPD R MH and JPD Co-co-Low, respectively, during right lower limb flexion attempts. RF, rectus femoris; VL, vastus lateralis; TA, tibialis anterior; SOL, soleus. Epidural stimulation electrode configuration (cathodes in black, anodes in red, inactive in white), frequency, pulse width and intensity are reported.

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