Restoration of hand function with long-term paired associative stimulation after chronic incomplete tetraplegia: a case study

Abstract

Introduction: This case study explores the gains in hand function in an individual with a chronic spinal cord injury (SCI). The intervention was long-term paired associative simulation (PAS). We aimed to provide PAS until full recovery of hand muscle strength occurred, or until improvements ceased.

Case presentation: A 46-year-old man with traumatic C7 AIS B tetraplegia was administered PAS three times per week. After 24 weeks, PAS was combined with concomitant motor training of the remaining weak hand muscles. Outcome measures included the manual muscle test (MMT), motor-evoked potentials (MEPs), F-responses, hand functional tests, and the spinal cord independence measure (SCIM).

Discussion: After 47 weeks of PAS the subject had improved self-care and indoor mobility and was able to perform complex motor tasks (SCIM score improved from 40 to 56). His left hand regained maximum MMT score (total 75; increase of score from baseline condition 19); the effect remained stable in the 32-week follow up. In the right-hand muscles, MMT scores of 4-5 were observed in follow up (total 71; increase from baseline 48). Improved values were also observed in other outcomes. This is the first demonstration of long-term PAS restoring muscle strength corresponding to MMT scores of 4-5 in an individual with chronic SCI. The effect persisted for several months, indicating that PAS induces stable plastic changes in the corticospinal pathway.

Keywords: Long-term potentiation; Medical research; Motor control; Spinal cord injury; Spine plasticity.

Conflict of interest statement

Conflict of interestJPM reports receiving travel expenses for lectures from NexStim Inc. outside the submitted work. All other authors declare that they have no conflict of interest.

© The Author(s) 2019.

Figures

Fig. 1

a Stimulation setup for long-term PAS therapy, b, c stimulation sites, and d basic principle of PAS. The upper motor neurons in the left primary motor cortex were stimulated with the TMS coil placed over the subject’s head (marked with blue squares). The electric field and a stimulated hotspot in the brain were visualized online using a 3D MRI-based model (b) that ensures accuracy and repeatability of stimulation. c High-frequency electrical stimulation was delivered to a peripheral nerve of the contralateral hand (marked with green squares). d The interstimulus interval was adjusted for collision of multiple descending volleys propagating along the upper motor neurons within the corticospinal tract (dark blue line) and ascending volleys travelling along the lower motor neurons within the peripheral nerve (yellow line) at the level of their synaptic contacts (red circle) in the cervical segment of the spinal cord (shown in enlarged form in d)

Fig. 2

Time course of the intervention

Fig. 3

Manual muscle test (MMT) score measured before intervention, and at the end of follow up in the left (a) and right (b) hand (full MMT data is shown in Supplementary Table 2 parts 1, 2). Y-axis depicts the MMT score (the highest possible MMT score for all muscles evaluated is 75). Solid black line and spheres indicate the sum of MMT score calculated for all evaluated muscles. Solid grey line and squares indicate the sum of MMT score for the muscles innervated by median nerve, ulnar nerve values are indicated by dotted line and triangles, and radial nerve values by dashed line and diamonds (see Supplementary Table 2 parts 1, 2)

Fig. 4

Changes in hand strength between pre-intervention and the end of the follow-up period. a The sum of tip, key, and palmar pinch tests results in the right (red) and left (blue) hand. b Grip tests in both hands (red, right hand; blue, left hand). Y-axis represents weight in kg. See Supplementary Table 4 for full pinch tests results

Fig. 5

Spinal cord independence measure (SCIM) scores (Y-axis) before intervention and at the end of follow up. Black bars indicate self-care, bars with diagonal lines indicate mobility (room and toilet), white bars indicate mobility (indoors and outdoors) subscales, and black line depicts change in total SCIM scores. See Supplementary Table 6 for details

Fig. 6

Representative motor-evoked potentials (MEPs) elicited by magnetic stimulation of the motor cortex hotspots used for PAS therapy. Responses from the right (a) and left brachioradialis (b), right (c) and left abductor digiti minimi (d), and right (e) and left abductor pollicis brevis (f) muscles recorded before the intervention and at the end of follow up. Each image consists of 1–10 superimposed MEPs. X-axis indicates time in ms (zero value corresponds to TMS onset; note the stimulus artefact). Y-axis indicates MEP amplitude in µV. Amplitude scales differ between responses from different muscles