Spinal cord injury (SCI) is damage to any part of the spinal cord resulting in paralysis, bowel and/or bladder incontinence, and loss of sensation and other bodily functions. Current treatments for chronic SCI are focused on managing symptoms and preventing further damage to the spinal cord with limited neuro-restorative interventions. Recent research and independent clinical trials of spinal cord stimulation (SCS) or intensive neuro-rehabilitation including neuro-robotics in participants with SCI have suggested potential malleability of the neuronal networks for neurological recovery. We hypothesize that epidural electrical stimulation (EES) delivered via SCS in conjunction with mental imagery practice and robotic neuro-rehabilitation can synergistically improve volitional motor function below the level of injury in participants with chronic clinically motor-complete SCI. In our pilot clinical RESTORES trial (RESToration Of Rehabilitative function with Epidural spinal Stimulation), we investigate the feasibility of this combined multi-modal approach in restoring volitional motor control and achieving independent overground locomotion in participants with chronic motor complete thoracic SCI. Secondary aims are to assess the safety of this combination therapy including the off-label SCS usage as well as improving functional outcome measures. To our knowledge, this is the first clinical trial that investigates the combined impact of this multi-modal EES and rehabilitation strategy in participants with chronic motor complete SCI. Two participants with chronic motor-complete thoracic SCI were recruited for this pilot trial. Both participants have successfully regained volitional motor control below their level of SCI injury and achieved independent overground walking within a month of post-operative stimulation and rehabilitation. There were no adverse events noted in our trial and there was an improvement in post-operative truncal stability score. Results from this pilot study demonstrates the feasibility of combining EES, mental imagery practice and robotic rehabilitation in improving volitional motor control below level of SCI injury and restoring independent overground walking for participants with chronic motor-complete SCI. Our team believes that this provides very exciting promise in a field currently devoid of disease-modifying therapies.

Recruiting participants for clinical trials targeting specific populations, like patients with chronic motor complete spinal cord injuries (SCIs), is challenging. The RESTORES trial evaluated spinal cord stimulation (SCS) combined with robotic neurorehabilitation for motor recovery in this population. This feasibility study enrolled three participants to assess SCS implant safety, synergistic effects of SCS and robotic rehabilitation, and clinical outcomes. Key recruitment barriers included the small patient pool, stringent eligibility criteria, patient skepticism, and logistical and emotional challenges. Strategies to address these challenges encompassed multidisciplinary collaborations with clinical centers, SCI associations, and patient support groups, including pre-surgical counselling and transparent communication. A dedicated clinical research coordinator ensured ethical compliance, logistical support, and participant engagement. Travel reimbursements, family involvement, and peer advocacy fostered accessibility and trust. Of the 115 patients screened, only 3 met the strict eligibility criteria, due to high screening failure rates and participant apprehension. Peer testimonials and family support helped enhance motivation and adherence. Ethical safeguards, like a data safety monitoring board, ensured participant safety and transparency. The RESTORES trial underscores the complexity of recruiting for pioneering interventions while highlighting the importance of tailored, patient-centric strategies. Insights gained will inform future trials and contribute to advancing SCI rehabilitation, offering hope for enhanced neurological recovery and quality of life for individuals with chronic motor complete SCI.

Objective: To present the rehabilitation considerations in prehabilitation and the rehabilitation phase post spinal cord stimulator implantation; and to evaluate the efficacy of synergistic combination of epidural spinal cord stimulation (SCS) with motor imagery, trunk rehabilitation, robotic and overground gait training in improving mobility in persons with sensorimotor complete spinal cord injury (SCI). Design: A non-controlled before-after clinical trial. Methods: Epidural spinal cord stimulators were implanted into 3 participants with complete thoracic SCI (Thoracic 4, Thoracic 2 and Thoracic 10 respectively). They underwent 1 month of prehabilitation, followed by 7 months of daily rehabilitation post-implantation, consisting of SCS, motor imagery, trunk rehabilitation, robotic therapy and overground gait training. Pre-post assessments include the American Spinal Injury Association Impairment Scale (AIS) examination, Spinal Cord Independence Measure version III (Mobility subscale) (SCIM-III), Walking Index for Spinal Cord Injury II (WISCI-II), Trunk Assessment Scale for Spinal Cord Injury (TASS), Five Times Sit-to-Stand (5×STS) and 2-minute Walk Test (2mWT). Results: Post rehabilitation, there were improvements in WISCI-II, TASS, 5×STS and 2mWT in all 3 participants; and no change in AIS sensory scores. Only participants 2 and 3 exhibited slight improvement in SCIM-III. The WISCI-II of all participants improved, ranging from 3 levels to 9 levels, which was considered a clinically meaningful change. Furthermore, the change in TASS exceeded the minimal clinically important difference (MCID) of 4 points for two participants. The change in 5×STS exceeded the MCID of 2.27 seconds for all participants. These significant improvements translated into the participants’ ability to perform sit-to-stand independently and ambulate with a rollator frame under supervision of a carer. Conclusion: This clinical trial demonstrated proof-of-concept and promising findings that support our rehabilitation protocol in improving functional mobility of people with sensorimotor complete SCI, which may be replicated in future studies. *The study protocol was registered with Clinical-trials.gov (NCT05644171; Registered 13 November 2022. https://clinicaltrials.gov/ct2/show/NCT05644171 )