Transcutaneous Spinal Cord Stimulation Enhances Walking Performance and Reduces Spasticity in Individuals with Multiple Sclerosis

Ursula S Hofstoetter, Brigitta Freundl, Peter Lackner, Heinrich Binder, Ursula S Hofstoetter, Brigitta Freundl, Peter Lackner, Heinrich Binder

Abstract

Gait dysfunction and spasticity are common debilitating consequences of multiple sclerosis (MS). Improvements of these motor impairments by lumbar transcutaneous spinal cord stimulation (tSCS) have been demonstrated in spinal cord injury. Here, we explored for the first time the motor effects of lumbar tSCS applied at 50 Hz for 30 min in 16 individuals with MS and investigated their temporal persistence post-intervention. We used a comprehensive protocol assessing walking ability, different presentations of spasticity, standing ability, manual dexterity, and trunk control. Walking ability, including walking speed and endurance, was significantly improved for two hours beyond the intervention and returned to baseline after 24 h. Muscle spasms, clonus duration, and exaggerated stretch reflexes were reduced for two hours, and clinically assessed lower-extremity muscle hypertonia remained at improved levels for 24 h post-intervention. Further, postural sway during normal standing with eyes open was decreased for two hours. No changes were detected in manual dexterity and trunk control. Our results suggest that transcutaneous lumbar SCS can serve as a clinically accessible method without known side effects that holds the potential for substantial clinical benefit across the disability spectrum of MS.

Keywords: gait dysfunction; human; multiple sclerosis; neuromodulation; non-invasive; spasticity; spinal cord stimulation; standing ability; transcutaneous; walking function.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure A1
Figure A1
Verification of afferent fiber stimulation during transcutaneous spinal cord stimulation at 50 Hz by the elicitation of paraesthesias in L2 to S2 innervated lower-extremity dermatomes. Exemplary distribution of paraesthesias (shaded areas) as perceived by participants 1, 5, and 10 during the intervention.
Figure 1
Figure 1
Overview of the methodology. (a) Study protocol comprising a baseline evaluation (Base) with two assessments, one conducted ~24 h (B1) and the other one immediately (B2) before a 30-min session of 50-Hz transcutaneous (transcut.) spinal cord stimulation; an evaluation of intermediate carry-over effects (Inter) with two assessments, one conducted immediately (I1) and the other one two hours (I2) post-intervention; and an evaluation of longer-lasting carry-over effects (Long) of the stimulation conducted ~24 h post-intervention. Each assessment included, as core tests, the clinical determination of lower-extremity muscle hypertonia based on the Modified Ashworth Scale (MAS) and, in the ambulatory participants, the timed 10-m walk test, the timed up-and-go test, and the 2-min walk test. Supplementary (supplem.) tests were conducted as indicated in B1 or B2 as well as in I1 and I2, and included standing tasks, the trunk control test, the timed nine-hole-peg test, and a surface-EMG (sEMG) based assessment of lower-extremity spasticity. Transcutaneous spinal cord stimulation was applied with the participants lying supine. First, effective electrode (el.) placement (cf. (b)) over the lumbosacral spinal cord was confirmed based on the elicitation of posterior root-muscle reflexes (PRMRs; cf. (c)) in lower-extremity myotomes. Second, for the intervention, transcutaneous spinal cord stimulation was applied for 30 min at 50 Hz and with an amplitude corresponding to 90% of the lowest PRMR threshold. n.t., not tested. (b) Electrode setup with the active paraspinal electrode placed longitudinally over the spine, covering T11 and T12 spinal processes, and a pair of interconnected indifferent electrodes on the lower abdomen. (c) Verification of effective stimulation site over the lumbosacral spinal cord by the elicitation of PRMRs in rectus femoris (RF), biceps femoris (BF), tibialis anterior (TA), and triceps surae (TS), which demonstrate a characteristic suppression at interstimulus-intervals (ISIs) of 30 ms and 50 ms when tested by paired pulses [39]. At interstimulus-intervals of 100 ms, the responses to the second stimulus had partially recovered. Shaded backgrounds mark times of stimulus application. Three repetitions each superimposed; participant 5.
Figure 2
Figure 2
Intermediate and longer-lasting carry-over effects of transcutaneous spinal cord stimulation on the Modified Ashworth Scale (MAS)-based evaluation of lower-extremity muscle hypertonia. (a) Group results of (i) MAS sum scores obtained in Base, Inter, and Long; and (ii) changes in MAS sum scores per participant in Inter and Long compared to Base, illustrated by box plots. Bold horizontal lines within boxes are medians; boxes span the interquartile range. Whiskers extend to the lowest and largest values that are not outliers (illustrated as circles; see Methods). Brackets and asterisks denote significant results of post-hoc pairwise comparisons (*, p < 0.05; **, p < 0.001). (b) Changes in individual MAS scores (one score per movement, limb, and participant) in Inter and Long compared to Base. Stacked bar charts show percentage of changes classified as clinically meaningful improvement (reduction by ≥ 1; magenta sections of bars); improvement (reduction by 0.5; light magenta); unchanged (grey); and increase (black). Base, baseline evaluation comprising two assessments conducted ~24 h and immediately pre-intervention; Inter, evaluation of intermediate carry-over effects comprising two assessments immediately and two hours post-intervention; Long, evaluation of longer-lasting carry-over effects conducted ~24 h after the stimulation session; MAS, Modified Ashworth Scale.
Figure 3
Figure 3
Intermediate and longer-lasting carry-over effects of transcutaneous spinal cord stimulation on walking function. Group results of the evaluations Base, Inter, and Long of (a) the timed 10-m walk test; (b) the timed up-and-go test; and (c) (i) distance of the 2-min walk test as well as (ii) time required to cover the first 20-m course length, illustrated by box plots. Bold horizontal lines within boxes are medians; boxes span the interquartile range. Whiskers extend to the lowest and largest values that are not outliers (illustrated as circles; see Methods). Brackets and asterisks denote significant results of post-hoc pairwise comparisons (*, p < 0.05). (d) Individual changes in walk tests in (i) Inter and (ii) Long compared to Base. Stacked bar charts of the timed 10-m meter walk test (10mWT), the timed up-and-go test (TUG) and the 2-min walk test (2minWT) show percentage of changes classified as clinically relevant improvement (10mWT, increase of walking speed by ≥ 0.05 m/s; TUG, time reduced by ≥ 15%; and 2minWT, distance increased by ≥ 6.8 m), improvement, and decrease. Base, baseline evaluation comprising two assessments conducted ~24 h and immediately pre-intervention; Inter, evaluation of intermediate carry-over effects comprising two assessments conducted immediately and two hours post-intervention; Long, evaluation of longer-lasting carry-over effects conducted ~24 h post-intervention.
Figure 4
Figure 4
Intermediate carry-over effects of transcutaneous spinal cord stimulation on standing ability. (a) (i) Trajectories of the center of pressure in anterior–posterior and medial–lateral directions recorded during 30 s of normal standing with eyes open in B1 and assessments I1 and I2 of Inter; participant 10. Group results in B1 and Inter of postural sway during (ii) normal standing and (iii) Romberg’s test for 30 s with eyes open and eyes closed as indicated. (b) Difference in weight distribution (percentage of body weight) between lower extremities during 30 s of normal standing with eyes open shown for B1 and Inter. B1, baseline assessment conducted ~24 h pre-intervention; Base, baseline evaluation; Inter, evaluation of intermediate carry-over effects comprising two assessments conducted immediately (I1) and two hours (I2) post-intervention. All group results are illustrated by box plots. Bold horizontal lines within boxes are medians; boxes span the interquartile range. Whiskers extend to the lowest and largest values that are neither outliers (illustrated as circles) nor extreme values (asterisks). Bracket and asterisk denote significant results of post-hoc pairwise comparisons (*, p < 0.05; **, p < 0.001).
Figure 5
Figure 5
Intermediate carry-over effects of transcutaneous spinal cord stimulation on various presentations of lower-extremity spasticity assessed with surface-electromyography. (a) Lower-extremity muscle activation through tonic stretch reflexes during passive unilateral hip and knee flexion (flex.) and extension (ext.) movements. (i) Electromyographic (EMG) recordings derived from rectus femoris (RF), biceps femoris (BF), tibialis anterior (TA), and triceps surae (TS) in assessments B2 as well as I1 and I2; participant 2. (ii) Group results of the root mean square (RMS) values of the EMG in B2 and Inter. (b) Achilles clonus elicited by a brisk manual dorsiflexion. (i) EMG recordings of TS in B2 as well as I1 and I2; participant 12. Arrows mark onsets of the tests. (ii) Group results of the EMG-RMS values (left) and clonus duration (right) in B2 and Inter. (c) Cutaneous-input evoked lower-extremity spasms. (i) EMG recordings of TA and TS in B2 as well as I1 and I2; participant 1. Arrows mark onsets of the tests. (ii) Group results of the EMG-RMS values in B2 and Inter. B2, baseline assessment conducted immediately pre-intervention; Base, baseline evaluation; Inter, evaluation of intermediate carry-over effects comprising two assessments immediately (I1) and two hours (I2) post-intervention. All group results are illustrated by box plots. Bold horizontal lines within boxes are medians; boxes span the interquartile range. Whiskers extend to the lowest and largest values that are not outliers (illustrated as circles; see Methods) or extreme values (asterisks). Brackets and asterisks denote significant results of post-hoc pairwise comparisons (*, p < 0.05).

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