Enabling and promoting walking rehabilitation by paired associative stimulation after incomplete paraplegia: a case report

Abstract

Introduction Paired associative stimulation (PAS) is a combination of transcranial magnetic stimulation (TMS) and peripheral nerve stimulation (PNS) and induces plastic changes in the human corticospinal tract. We have previously shown that PAS consisting of TMS pulses given at 100% of stimulator output and high-frequency PNS is beneficial for motor rehabilitation of patients with a chronic incomplete spinal cord injury (SCI). The therapeutic possibilities of this PAS variant for walking rehabilitation of paraplegic patients are unexplored. Case presentation A 47-year old man with traumatic incomplete paraplegia (AIS D, neurological level T7) received PAS to his left leg for 3 months at 12 months post injury (PAS1) and for an additional 3 months at 24 months post injury (PAS2). The right leg had normal AIS scores and was not stimulated. Before PAS, the patient was nonambulatory, could not stand without weight support, and was consequently not eligible for conventional walking rehabilitation. After PAS1, the patient could stand for 1.5 min and take 13 steps (24 steps in follow up) on parallel bars without weight support and was enrolled into conventional walking rehabilitation. He achieved independent walking ability with a rollator. During PAS2, walking distance increased 2.4 times faster than during the preceding year. The left leg AIS score and spinal cord independence measure mobility subscore increased. No adverse effects were detected. Discussion This is the first report of PAS with a high-frequency peripheral component that enabled and promoted walking rehabilitation. Together with previous reports on this technique, this result encourages further research into its therapeutic potential and mechanism.

A novel paired associative stimulation protocol with a high‐frequency peripheral component: A review on results in spinal cord injury rehabilitation

“…No serious adverse effects were observed in any of our studies (Rodionov et al, 2019(Rodionov et al, , 2020Shulga et al, 2020;Tolmacheva, Savolainen, et al, 2019;Tolmacheva et al, 2017).…”

“…Eight of 20 patients had neuropathic pain, which was mild to moderate in 7 patients (Rodionov et al., 2019, 2020; Shulga, Lioumis, et al., 2016; Shulga et al., 2020; Tolmacheva et al., 2017) and severe in 1 (Vaalto et al., submitted). Neuropathic pain decreased or unpleasant sensations disappeared in seven patients.…”

“…Video from (Tolmacheva, Savolainen et al, 2019) demonstrating a rapid improvement after 10 days of high-PAS in a patient with milder non-traumatic tetraplegia: https://ars.els-cdn.com/conte nt/image/ 1-s2.0-S2467 981X1 93002 90-mmc2.mp4 Lower limb function A series of videos in (Shulga et al, 2020) demonstrating the progress of the patient with traumatic paraplegia from nonambulatory to ambulating independently with a walker: https://www.nature.com/artic les/s4139 4-020-0320-7#Sec4…”

“…The clinical characteristics of these patients are summarized in Table S1. PAS can be applied to upper (Rodionov et al, 2019;Tolmacheva, Savolainen, et al, 2019;Tolmacheva et al, 2017) and lower (Rodionov et al, 2020;Shulga et al, 2020) limbs. It increases manual muscle test (MMT) scores in both traumatic (Rodionov et al, 2019(Rodionov et al, , 2020Shulga et al, 2020;Tolmacheva et al, 2017) and neurological (Rodionov et al, 2020;Tolmacheva, Savolainen, et al, 2019) SCI and in both paraplegic Shulga et al, 2020) and tetraplegic (Rodionov et al, 2019(Rodionov et al, , 2020 patients.…”

The Immediate and Short-Term Effects of Transcutaneous Spinal Cord Stimulation and Peripheral Nerve Stimulation on Corticospinal Excitability

“…When the two inputs coincided at a spinal level, H-reflex amplitude was either facilitated ( Cortes et al, 2011 ) or unaffected ( Leukel et al, 2012 ), and H-Reflexes conditioned by both cortical and cervicomedullary stimulation were increased, suggesting that (at least some) neural plasticity was induced within the spinal cord ( Leukel et al, 2012 ). One group has reported that PAS with a high-frequency peripheral component (0.2 Hz TMS paired with 100Hz PNS, timed to coincide at the spinal cord level) enhanced motor output in healthy subjects ( Shulga et al, 2016 ; Mezes et al, 2020 ) and in pilot studies of people living with SCI ( Tolmacheva et al, 2017 , 2019 ; Rodionov et al, 2020 ; Shulga et al, 2020 ). However, as a therapeutic tool, this is limited by the relatively few spinal segments, and therefore muscles, that are targeted by the PNS approach.…”