Spinal cord injury (SCI) leads to gait impairment and loss of motor function and can be traumatic or non-traumatic in nature. Recently there has been important progress in the field of non-invasive central nervous stimulation, which can target the brain or spinal cord. In this review we aim to compare the effect of non-invasive cerebral and spinal cord stimulation on gait recovery and motor strength of lower limbs in subjects with SCI. We conducted a search (from September 2022 until March 2024) using the PubMed, Cochrane, and PEDro databases, including all studies published since the year 2000. The protocol of the review followed PRISMA guidelines and only RCTs scoring above 5 on the PEDro scale were selected. A total of 12 RCTs with 341 participants were included. When all studies were pooled together, non-invasive central nervous system stimulation had significant effects on Lower Extremity Motor Scale (LEMS) score and gait speed. However, data was less apparent when subgrouped by type and level of stimulation. Repetitive transcranial magnetic stimulation (rTMS) showed large effect on LEMS, however transcranial direct current stimulation (tDCS) displayed a small effect on motor strength and gait speed. No meta-analysis could be performed for non-invasive spinal cord stimulation due to a lack of studies. When all non-invasive stimulation techniques were pooled together, significant effects on motor strength and gait function were observed. However, subgroup analyses based on stimulation types and levels revealed a significant reduction in these effects, particularly when categorized by stimulation type (rTMS and tDCS). Furthermore, a meta-analysis could not be conducted for non-invasive spinal cord stimulation due to a lack of studies (only one study each on tsDCS and tSCS). Therefore, more randomized controlled trials are needed to evaluate neuromodulation interventions in spinal cord injury, particularly at the spinal cord level. Registration This systematic review with meta-analysis was registered in PROSPERO under the ID 512864.

Recovery from traumatic spinal cord injury (tSCI) is challenging due to the limited regenerative capacity of the central nervous system to restore cells, myelin, and neural connections. At the clinical level, the fundamental pillars of treatment are the reduction in secondary damage (neuroprotection) and rehabilitation; these are the tools we have to mitigate the disability caused by spinal cord injury (SCI). To date, the treatments on which neuroprotection has been based are the prevention of acute respiratory failure to avoid hypoxia, early hemodynamic control, neuroprotective drugs and surgical management. Optimizing early hemodynamic control to ensure adequate spinal cord perfusion may be key to the management of SCI. While neuroprotective agents like methylprednisolone have fallen into disuse, several promising therapies are currently being tested in clinical trials. In terms of surgical treatment, although their impact on neurological recovery remains debated, appropriate early bone decompression followed by duroplasty in selected cases is increasingly recommended. Advances in cell therapies hold significant potential for enhancing both clinical and functional outcomes in SCI patients. Moreover, emerging neuromodulation techniques, such as transcutaneous and epidural stimulation, along with innovations in rehabilitation technologies—such as robotic systems and exoskeletons—are becoming indispensable tools for improving locomotion and overall mobility in individuals with SCI. This article provides an update on the advances in neuroprotection against secondary damage caused by tSCI, in cellular therapies, and in new rehabilitation therapies.

Transcutaneous multisegmental spinal cord stimulation (tSCS) has shown superior efficacy in modulating spinal locomotor circuits compared to single-site stimulation in individuals with spinal cord injury (SCI). Building on these findings, we hypothesized that administering a single session of tSCS at multiple spinal segments may yield greater enhancements in muscle strength and gait function during stimulation compared to tSCS at only one or two segments. In our study, tSCS was applied at single segments (C5, L1, and Coc1), two segments (C5-L1, C5-Coc1, and L1-Coc1), or multisegments (C5-L1-Coc1) in a randomized order. We evaluated the 6-m walking test (6MWT) and maximum voluntary contraction (MVC) and assessed the Hmax/Mmax ratio during stimulation in ten individuals with incomplete motor SCI. Our findings indicate that multisegmental tSCS improved walking time and reduced spinal cord excitability, as measured by the Hmax/Mmax ratio, similar to some single or two-site tSCS interventions. However, only multisegmental tSCS resulted in increased tibialis anterior (TA) muscle strength. These results suggest that multisegmental tSCS holds promise for enhancing walking capacity, increasing muscle strength, and altering spinal cord excitability in individuals with incomplete SCI.

Background/Objectives: Respiratory impairment is the leading cause of morbidity and mortality in participants with spinal cord injury (SCI). Cervical SCI (cSCI) severely compromises respiratory function due to paralysis and weakness of the respiratory muscles. Recent evidence suggests that transcutaneous electrical spinal cord stimulation (tSCS) may enhance motor strength and promote functional recovery. Therefore, cervical tSCS, applied at cervical segments, holds potential as a therapeutic strategy to improve respiratory function in participants with cervical SCI. Methods: This randomized controlled trial with a partial crossover design included participants with both complete and incomplete cSCI. Neurological assessments were used, as well as tests to evaluate pulmonary function maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), and spirometric measurements. These assessments were conducted at baseline and after the last session. The experimental group received tSCS at the C3–C4 and C6–C7 cervical spinal levels, delivered at a frequency of 30 Hz during occupational therapy. The control group underwent identical occupational therapy sessions without stimulation. Each session lasted 30 min and was conducted over eight days. Results: Fifteen participants with cSCI received tSCS, while 11 cSCI participants were included in the control group. Seven participants took part in both groups. Only the tSCS group showed significant improvements in MIP, MEP, and forced vital capacity (p < 0.05), while no significant changes were observed in the control group. Conclusions: tSCS applied at the cervical segments can promote respiratory function following cervical SCI. This approach may support neuroplasticity and help reduce long-term respiratory complications in participants with cervical SCI. However, to confirm these effects, long-term stimulation protocols and follow-up studies in larger SCI populations are required.

Background: Transcutaneous spinal cord stimulation (tSCS) is a promising approach to enhance functional recovery after spinal cord injury (SCI). However, evidence on repeated sessions and their effects on gait and lower-limb strength remains limited. This study evaluated the effects of multisegmental tSCS on walking ability, muscle strength, and functional independence in individuals with SCI. Methods: In this randomized controlled trial with a partial crossover design, twelve individuals received tSCS combined with gait rehabilitation, while ten underwent gait rehabilitation alone, for three weeks. Four participants crossed over to the tSCS group after a minimum one-week washout period following the control intervention. We assessed the American Spinal Injury Association Impairment Scale (AIS), Total Motor Score (TMS), Lower Extremity Motor Score (LEMS), Walking Index for Spinal Cord Injury II (WISCI-II), 10- and 6-Meter Walking Tests (10MWT, 6meterWT), Timed Up and Go (TUG) test, maximal voluntary contraction (MVC) of the quadriceps (QM) and tibialis anterior (TA), and the Spinal Cord Independence Measure (SCIM-III); tSCS was applied at three spinal segments during gait rehabilitation over 15 sessions. Results: tSCS significantly improved MVC in both muscles, as well as SCIM-III and TUG, and these improvements were maintained at follow-up, with no significant adverse events reported. Other clinical assessments also showed significant improvement in both groups. Conclusions: tSCS was well tolerated and conferred additional benefits in lower-limb muscle strength, walking ability (as assessed by TUG), and functional independence, supporting its potential as a valuable adjunct to rehabilitation.