Long-Term Spinal Cord Stimulation After Chronic Complete Spinal Cord Injury Enables Volitional Movement in the Absence of Stimulation

Abstract

Background: Chronic spinal cord injury (SCI) portends a low probability of recovery, especially in the most severe subset of motor-complete injuries. Active spinal cord stimulation with or without intensive locomotor training has been reported to restore movement after traumatic SCI. Only three cases have been reported where participants developed restored volitional movement with active stimulation turned off after a period of chronic stimulation and only after intensive rehabilitation with locomotor training. It is unknown whether restoration of movement without stimulation is possible after stimulation alone. Objective: We describe the development of spontaneous volitional movement (SVM) without active stimulation in a subset of participants in the Epidural Stimulation After Neurologic Damage (ESTAND) trial, in which locomotor training is not prescribed as part of the study protocol, and subject's rehabilitation therapies are not modified. Methods: Volitional movement was evaluated with the Brain Motor Control Assessment using sEMG recordings and visual examination at baseline and at follow-up visits with and without stimulation. Additional functional assessment with a motor-assisted bicycle exercise at follow-up with and without stimulation identified generated work with and without effort. Results: The first seven participants had ASIA Impairment Scale (AIS) A or B thoracic SCI, a mean age of 42 years, and 7.7 years post-injury on average. Four patients developed evidence of sustained volitional movement, even in the absence of active stimulation after undergoing chronic epidural spinal cord stimulation (eSCS). Significant increases in volitional power were found between those observed to spontaneously move without stimulation and those unable (p < 0.0005). The likelihood of recovery of spontaneous volitional control was correlated with spasticity scores prior to the start of eSCS therapy (p = 0.048). Volitional power progressively improved over time (p = 0.016). Additionally, cycling was possible without stimulation (p < 0.005). Conclusion: While some SVM after eSCS has been reported in the literature, this study demonstrates sustained restoration without active stimulation after long-term eSCS stimulation in chronic and complete SCI in a subset of participants. This finding supports previous studies suggesting that "complete" SCI is likely not as common as previously believed, if it exists at all in the absence of transection and that preserved pathways are substrates for eSCS-mediated recovery in clinically motor-complete SCI. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03026816.

Keywords: human; neuromodulation; spinal cord injury; spinal cord stimulation; traumatic spinal cord injury; volitional movement.

Copyright © 2020 Peña Pino, Hoover, Venkatesh, Ahmadi, Sturtevant, Patrick, Freeman, Parr, Samadani, Balser, Krassioukov, Phillips, Netoff and Darrow.

Figures

FIGURE 1

T2 sagittal thoracic magnetic resonance imaging (MRI) obtained prior to enrollment. (A) Subject 1: spinal cord changes include dorsal tethering at T7 and syrinx from T8 to T10. (B) Subject 2: syrinx at T7. Owing to coronal scoliosis, a single sagittal image did not provide a full view of the spinal canal. A composite image of three different slices with the midline of the central canal kept as the axis is shown. (C) Subject 3: T8 cord injury with cystic changes at the same level. (D) Subject 4: T5 cord injury. (E) Subject 5: T5 cord injury and syrinx extending from T5 to T7. (F) Subject 6: T5 cord injury. (G) Subject 7: T4 cord injury.

FIGURE 2

Placement of 5-6-5 epidural paddle lead through a T12 laminectomy, overlying the T12–L1 epidural space. Final lead placement is guided by intraoperative electromyogram (EMG).

FIGURE 3

Differences in baseline Modified Ashworth Scale scores between the spontaneous volitional movement (SVM) group (Yes) and non-SVM group (No). Participants in the SVM group had significantly higher spasticity MAS scores than those in the non-SVM group. These differences were present before the start of continuous eSCS therapy. *p < 0.05.

FIGURE 4

Brain Motor Control Assessment (BMCA) documented muscle activation without stimulation (A) and with stimulation (B) in the SVM group. Joint movements are color coded as follows: (1) red, ankle dorsiflexion and orange, ankle plantarflexion. (2) Yellow, knee flexion and green, knee extension. (3) Purple, hip flexion and black, hip extension. Follow-up visits 1–5 and Subject 5 are not included as the BMCA CRF had not been implemented yet. Each subject’s introduction of the CRF form is color-coded by gray boxes. Movements observed prior to the implementation of the BMCA CRF have not been included here. Recorded movements only occurred during the volitional task windows of the BMCA (A). Recorded movements during BMCA in the absence of stimulation. Subject 3 demonstrated persistent movement in the absence of stimulation the earliest and across the most muscle groups among the SVM group. (B) Recorded movements during BMCA with stimulation on are included in order to exemplify how movement with stimulation is more prevalent earlier on in the study and across more muscle groups than movement without stimulation.

FIGURE 5

BMCA at Subject 2’s follow-up visit 13: surface EMG electrical activity recorded in volts over time for eight bilateral lower extremity muscle groups. Orange traces include left muscle groups and blue traces include right muscle groups. Gray boxes indicate volitional task events signaled by auditory cues. This subsample of EMG recording includes three cues for bilateral hip flexion, right hip flexion, and left hip flexion, respectively. EMG bursts can be seen to be synchronized with the auditory cue followed by silent periods at rest, demonstrating volitional activity.

FIGURE 6

Observations during BMCA. Differences in volitional power without stimulation (dB) when movement was observed and recorded on case report forms. High volitional power outliers when movement was not observed demonstrate the lower sensitivity of researcher observations. For reference, volitional power of 3 dB represents an increase in muscle activity during volitional tasks of two times (200%) that of muscle activity at baseline. Volitional power of 10 represents an increase in muscle activity during volitional tasks of 10 times (1000%) that of the muscle activity at baseline. ***p < 0.001.

FIGURE 7

Average volitional power without stimulation (dB) at each study follow-up visit including all seven participants. It is apparent that Subject 3 demonstrated volitional movement the earliest in the study (follow-up visit 4) and with the greatest magnitude on sEMG, reaching volitional muscle activity 10 times greater (1000%) than that at baseline on follow-up visit 13.

FIGURE 8

Average volitional power without stimulation (dB) during three follow-up study periods. Study period 1 included follow-up visits 1–5. Study period 2 included follow-up visits 6–9. Study period 3 included follow-up visits 10–13. An improvement over time is apparent only in the SVM group and is statistically significant between study periods 1 and 3 (p = 0.008) and between study periods 2 and 3 (p = 0.03). Volitional power between SVM and non-SVM groups is significantly greater in study period 3 (p < 0.001). *p < 0.05, **p < 0.01, ***p < 0.001.

FIGURE 9

Functional movement without stimulation: graphs demonstrate differences between Groups (0: non-SVM group and 1: SVM group) and between volitional effort (n = no effort, y = with effort). Means are symbolized by black points. (A) Distance traveled without assistance of the bicycle motor is plotted, when correcting for zero inflated data. There is a significant positive effect on distance when participants from the SVM group attempted to pedal. (B) Pedaling work exerted is plotted, when correcting for zero inflated data. Participants in the SVM group significantly achieved greater work when they provided effort compared to the non-SVM group. *** refers to a p-value of <0.001.