Efficacy of QuadroPulse rTMS for improving motor function after spinal cord injury: Three case studies

Abstract

Context/objective: To examine the effects of repetitive QuadroPulse transcranial magnetic stimulation (rTMS(QP)) on hand/leg function after spinal cord injury (SCI).

Design: Interventional proof-of-concept study.

Setting: University laboratory.

Participants: Three adult subjects with cervical SCI. Interventions Repeated trains of magnetic stimuli were applied to the motor cortical hand/leg area. Several exploratory single-day rTMS(QP) protocols were examined. Ultimately we settled on a protocol using three 5-day trials of (1) rTMS(QP) only; (2) exercise only (targeting hand or leg function); and (3) rTMS(QP) combined with exercise.

Outcome measures: Hand motor function was assessed by Purdue Pegboard and Complete Minnesota Dexterity tests. Walking function was based on treadmill walking and the Timed Up and Go test. Electromyographic recordings were used for neurophysiological testing of cortical (by single- and double-pulse TMS) and spinal (via tendon taps and electrical nerve stimulation) excitability.

Results: Single-day rTMS(QP) application had no clear effect in the 2 subjects whose hand function was targeted, but improved walking speed in the person targeted for walking, accompanied by increased cortical excitability and reduced spinal excitability. All 3 subjects showed functional improvement following the 5-day rTMS(QP) intervention, an effect being even more pronounced after the five-day combined rTMS(QP) + exercise sessions. There were no rTMS(QP)-associated adverse effects.

Conclusion: Our findings suggest a functional benefit of motor cortical rTMS(QP) after SCI. The effect of rTMS(QP) appears to be augmented when stimulation is accompanied by targeted exercises, warranting expansion of this pilot study to a larger subject population.

Keywords: Motor function; Rehabilitation; Repetitive transcranial magnetic stimulation; Spinal cord injury.

Figure 1

Study flow diagram; each box represents delivery of an rTMS_QP session. Two series of experiments–single-day rTMS_QP and five-day interventions–were conducted in each subject. Subjects number 1 and 3 participated in 14 single-day rTMS_QP sessions each; subject number 2 participated in only one single-day session. Vertical arrows indicate when testing was done (e.g. immediately before and after each single-day session; immediately before day-1 and after day-5 sessions). Single-day sessions were separated by at least one week. All subjects underwent three different five-day interventions: rTMS_QP alone; exercises alone; and rTMS_QP + exercises. All 5-day sessions were separated from the next by 4–8 weeks.

Figure 2

The effect of single-day rTMS_QP of the leg motor area on soleus H-reflex low-frequency depression. The tibial nerve was stimulated at the popliteal fossa using square-wave, constant-current pulses (0.2 ms pulse duration). Stimulus intensity was adjusted to cause a constant M-wave, and an H-reflex of the same or slightly larger amplitude, on the rising edge of the stimulus-response curve. Using identical stimulus intensities, three pulses were delivered at each of 7 different rates (0.2, 0.5, 1, 2, 5, 8, and 10 Hz). At least 10 seconds separated each 3-pulse delivery from the next. For each tested frequency of stimulation, the amplitudes (peak-to-peak) of the last (H3) and the first (H1) responses are expressed as H3:H1 ratio. Note that post-rTMS_QP H3:H1 values (filled symbols) at 2–10 Hz are lower than pre rTMS_QP (open symbols) data, indicative of greater H-reflex depression.

Figure 3

The effects of three different 5-day trials utilizing rTMS_QP alone, exercise alone (‘Ex’), and rTMS_QP in combination with exercise on hand dexterity in subject number 1 (A) and subject number 2 (B) and walking in subject number 3 (C). In (A) and (B), the absolute number of pins placed during the Purdue Pegboard dexterity test by the subject immediately after the day-5 rTMS_QP session (black columns) is compared to the value immediately before the day-1 session's score (grey columns). (C) illustrates the absolute maximal treadmill walking speed measured in subject number 3 before (grey columns) and after (black columns) each of the 3 interventions.