Multi-Site Spinal Cord Transcutaneous Stimulation Facilitates Upper Limb Sensory and Motor Recovery in Severe Cervical Spinal Cord Injury: A Case Study

Abstract

Individuals with cervical spinal cord injury (SCI) rank regaining arm and hand function as their top rehabilitation priority post-injury. Cervical spinal cord transcutaneous stimulation (scTS) combined with activity-based recovery training (ABRT) is known to effectively facilitate upper extremity sensorimotor recovery in individuals with residual arm and hand function post SCI. However, scTS effectiveness in facilitating upper extremity recovery in individuals with severe SCI with minimal to no sensory and motor preservation below injury level remains largely unknown. We herein introduced a multimodal neuro-rehabilitative approach involving scTS targeting systematically identified various spinal segments combined with ABRT. We hypothesized that multi-site scTS combined with ABRT will effectively neuromodulate the spinal networks, resulting in improved integration of ascending and descending neural information required for sensory and motor recovery in individuals with severe cervical SCI. To test the hypothesis, a 53-year-old male (C2, AIS A, 8 years post-injury) received 60 ABRT sessions combined with continuous multi-site scTS. Post-training assessments revealed improved activation of previously paralyzed upper extremity muscles and sensory improvements over the dorsal and volar aspects of the hand. Most likely, altered spinal cord excitability and improved muscle activation and sensations resulted in observed sensorimotor recovery. However, despite promising neurophysiological evidence pertaining to motor re-activation, we did not observe visually appreciable functional recovery on obtained upper extremity motor assessments.

Keywords: cervical spinal cord injury; motor rehabilitation; neuromodulation; spinal cord excitability; spinal cord transcutaneous stimulation; upper limb.

Figure 1

ISNCSCI examination for research participant A134. (A) Shown are the scorings of ISNCSCI assessment for motor and sensory (light touch and pin prick) components along with the schematic of dermatomes location tested during the assessment. (B) Neurological level of injury for motor and sensory component on the right, left side, and overall. (C) Status of anal contraction and sensations. As seen, except right wrist extensor muscle and left T1 light touch (numericals in green), the participant scored zero on all motor and sensory subcomponents. ISNCSCI: International Standards for Neurological Classification of Spinal Cord Injury; N: No.

Figure 2

Schematics for Volitional movement ability mapping and activity-based recovery training (ABRT) combined with spinal cord transcutaneous stimulation (scTS). Shown is the schematic for (A) Volitional movement ability mapping. In sitting position, participant was instructed to perform various upper extremity movements during a three-second audio cue (wrist extension is shown in the illustration) with scTS during single-site and multi-site mapping. The obtained EMG during rest (gray) and activity (black) from prime mover (ECR) is stored for offline analysis. A rest period of 10–20 s is provided between consecutive events. Shown are the schematics representing (B) elbow flexion-extension (C) wrist flexion-extension (D) finger flexion-extension (E) trunk activities practiced during a typical ABRT session. In sitting position (F) stimulating electrodes targeting cervical and thoracic spinal segments were used to deliver (G) rectangular biphasic, 1 ms pulse duration with 5 kHz modulation pulses (adapted from [38]). Note that the schematics are for illustration purposes and not drawn to the scale. ECR: Extensor Carpi Radialis.

Figure 3

Morphometric analysis of the injured spinal cord. Shown is (A) the sagittal view of T2-weighted MRI of cervical and thoracic spinal cord with injury confined between dashed red lines (B) the sagittal view of T2-weighted image of cervical and thoracic spinal cord with overlaid masks representing normal (blue) and injured (red) spinal cord segments. The vertebral body levels are indicated with texts in white. (C) Shown are the axial slices of the T2-weighted image of cervical spinal cord from C2 to C6 vertebral levels without (top panel) and with (lower panel) overlaid masks representing normal (blue) and injured (red) spinal cord. (D–G) line plots representing various morphometric aspects of the spinal cord to indicate the severity of injury. The pink and green circled points on the line plots correspond to the C2–C3 and C5–C6 intervertebral discs level, respectively. MRI: Magnetic Resonance Imaging; CSA: Cross-sectional Area.

Figure 4

Multisegmental motor response (MMR) mapping. (A) Schematic to represent the approximate position of stimulating electrodes in relation to the spinous levels during MMR acquisition. (B) Shown are the representative MMR evoked in FCR muscle secondary to the stimulation at different spinal levels with 90 mA intensity. (C) Shown are the heatmaps representing the normalized peak-peak amplitude for bilateral BB, FCR and FDI muscles secondary to the stimulation of different spinal levels at various stimulation intensities. The white numbers in heatmaps represent spinal level excitability ranking. Inverted red arrows represent the column of peak-peak amplitude for bilateral FCR shown in Figure 3B. As seen, stimulation targeting C3–C4 spinal level resulted in highest MMR amplitudes. (D) Schematic representing the approximate distribution of motoneuronal pool supplying various upper extremity muscles along the spinal cord [45]. (E) Normalized peak-peak amplitude (F) selectivity index of various upper extremity muscles during C3–C4, C5–C6 and C7–T1 spinal stimulation. For normalized peak-peak amplitude, the shaded region denotes the standard deviation with mean value represented by the line in between. scTS: Spinal Cord Transcutaneous Stimulation; BB: Biceps Brachii; TB: Triceps Brachii; ECR: Extensor Carpi Radialis; FCR: Flexor Carpi Radialis; EDP: Extensor Digitorum Profundus; FDP: Flexor Digitorum Profundus; ADM: Abductor Digiti Minimi; FDI: First Dorsal Interossei.

Figure 5

Upper extremity volitional movement ability mapping. Shown are the EMG activity in (A) BB and (B) ECR during elbow flexion and wrist extension, respectively, without scTs and with single or multi-site scTS at specific stimulation intensity and frequency. Upper and lower blue guidelines represent the EMG activity without scTS. (C) Shown are the FFT plots associated with ECR activity during wrist extension without scTs and with single or multi-site scTS. Red lines within FFT plots represent the moving mean of the obtained power at various frequencies. Note that during multi-site stimulation, similar parameters as single site stimulation were used. EMG: Electromyography; BB: Biceps Brachii; ECR: Extensor Carpi Radialis; FFT: Fast Fourier Transform; scTS: Spinal Cord Transcutaneous Stimulation.

Figure 6

Improved primary mover and accessory muscles activation post-training. Shown are the EMG activity in various upper extremity muscles during FNPA engaging various primary mover muscles on the (A) left and (B) right side along with the bar graphs representing Δ change in EMG activity from the baseline during pre and post-training. (C) Shown are the EMG activity in various accessory upper extremity muscles during FNPA engaging left elbow extension along with the bar graphs representing Δ change in EMG activity from the baseline during pre and post-training. The solid and dashed line with the EMG plots represents the start and end of an attempt, respectively. Black and gray dots represent individual data points pre and post-training, respectively. * p < 0.05, Paired t-test. EMG: Electromyography; FNPA: Functional Neurophysiological Assessment; BB: Biceps Brachii; TB: Triceps Brachii; ECR: Extensor Carpi Radialis; FCR: Flexor Carpi Radialis; EDP: Extensor Digitorum Profundus; FDP: Flexor Digitorum Profundus; Lat. Trapz: Lateral Trapezius; Med. Trapz: Medial Trapezius; Ant. Del: Anterior Deltoid; Lat. Del: Lateral Deltoid.

Figure 7

Altered spinal cord excitability post-training. Shown are (A) MMR (B) bar graphs representing raw peak-peak amplitude of MMR secondary to C5–C6 stimulation at various stimulation intensities from various upper extremity muscles on the left and right side pre (black) and post (gray) training. Black and gray dots represent individual data points pre and post-training, respectively. * p < 0.05, Paired t-test. EMG: Electromyography; MMR: Multisegmental Motor Responses; BB: Biceps Brachii; TB: Triceps Brachii; ECR: Extensor Carpi Radialis; FCR: Flexor Carpi Radialis; EDP: Extensor Digitorum Profundus; FDP: Flexor Digitorum Profundus; FDI: First Dorsal Interossei; scTS: Spinal Cord Transcutaneous Stimulation.

Figure 8

Sensory and power sub-component of the Graded Redefined Assessment of Strength, Sensation and Prehension (GRASSP) during pre, mid and post-training. (A) Schematic representing the areas on the dorsal and volar areas of the hand assessed using monofilament during sensory subscore on GRASSP assessment. Line plots representing (B,C) sensory subscore on the dorsal volar areas of the right and left hand and (D) muscle power subscore of the right and left upper extremity, during pre, mid and post-training with (orange) or without (blue) scTS. UE: Upper Extremity; scTS: Spinal Cord Transcutaneous Stimulation; BB: Biceps Brachii; ECR: Extensor Carpi Radialis; 20 d: 20 days training; 40 d: 40 days training.