Paired associative stimulation to enhance motor outcome in spinal cord injury: a systematic review of first evidence

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).