https://orcid.org/0000-0003-3602-4197
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ABSTRACT
Introduction
Spinal cord injuries (SCI) often result in motor impairment and lifelong disability.
Methods
This systematic review, conducted in agreement with PRISMA guidelines, aimed to evaluate the effects of cortico-spinal paired associative stimulation (PAS) on motor outcomes in individuals with SCI. PubMed, Scopus/EMBASE, Pedro, and Cochrane databases were consulted from inception to 2023/01/12.
Results
In 1021 articles, 10 studies involving 84 patients meet the inclusion criteria, 7 case series/study, and 3 clinical trials. Despite light differences, the included studies performed a cortico-peripheral PAS using a single transcranial magnetic stimulation and high frequency electrical peripheral nerve stimulation for a consistent number of sessions (>20). All included studies reported improvement in motor outcomes recorded via clinical and/or neurophysiological assessment.
Conclusion
Available evidence showed an increase in motor outcomes after PAS stimulation. Indeed, both clinical and neurophysiological outcomes suggest the effectiveness of a high number of PAS sessions in chronic individuals with SCI. Due to a limited number of studies and an unsatisfactory study design, well-designed RCTs are needed to confirm the potentiality of these approaches and clarify the adequate dose-response of PAS in the SCI population.
Registration ID
The protocol was registered on the PROSPERO database (CRD42023485703).
Article highlights
A consistent number of PAS sessions could improve motor outcomes in chronic individuals with SCI.
PAS induces long-term cortico-spinal excitability changes in chronic individuals with SCI.
High-frequency PNS trains of stimuli coupled to a single TMS pulse are the most used PAS protocol.
The ISI between cortical and peripheral stimuli is calculated for each muscle to collide at spinal cord level and promote STDP.
The stimulation can be associated with conventional or robot-assisted therapy.
A decrease in neuropathic pain intensity and frequency seems to be related to PAS intervention.
No serious adverse events due to PAS were recorded during the study period.
The PAS seems not to improve sensory functions and spasticity.
The duration of the single session can be long and generate patient discomfort.
Combined stimulation protocols without interdependence between stimuli are often mistakenly identified with the term PAS.
Abbreviation list
| AEs | = | Adverse events |
| cpPAS | = | Cortical-peripheral paired associative stimulation |
| csPAS | = | Cortico-spinal paired associative stimulation |
| ISI | = | Interstimulus interval |
| M1 | = | Primary motor cortex |
| MEP | = | Motor evoked potential |
| PAS | = | Paired associative stimulation |
| PNS | = | Peripheral nerve stimulation |
| RCT | = | Randomized clinical trial. |
| SCI | = | Spinal cord injury |
| STDP | = | Spike-timing-dependent plasticity |
| TMS | = | Transcranial magnetic stimulation |
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewers disclosure
Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/17434440.2024.2358048