Lynsey Diane Duffell

Introduction: Spinal cord injury (SCI) results in severe autonomic dysfunction, across cardiovascular, bladder, bowel and sexual domains, negatively affecting quality of life. Recently, there has been growing interest in the application of spinal cord stimulation (SCS) to restore or modulate autonomic functions in people with SCI. This review systematically evaluated the evidence for spinal cord and/or root stimulation, delivered via epidural (eSCS), transcutaneous (tSCS) spinal cord stimulation, or sacral (posterior) anterior root stimulation (SARS/SPARS) – in managing autonomic dysfunction after SCI. Methods: A systematic search of OVID Medline, OVID Embase, and Web of Science, was completed in September 2024. Eligible studies included adults with SCI (≥18 years old) receiving eSCS, tSCS, or SARS, reporting at least one quantitative autonomic outcome measure. Extracted data were synthesised by autonomic domain (cardiovascular, urinary, bowel, sexual), intervention type (eSCS, tSCS, or SARS) and duration of stimulation (acute vs. chronic). Results: Fifty-seven articles were identified, evaluating eSCS (30 studies, n = 151), tSCS (10 studies, n = 48), and SARS (17 studies, n = 1,249) effects on cardiovascular (22 studies), bladder (23 studies), bowel (14 studies), and sexual function (13 studies). Acute application of eSCS or tSCS consistently elevated blood pressure and mitigated orthostatic hypotension, with variable effects on suppressing autonomic dysreflexia. Acute application of eSCS, tSCS or SPARS, improved bladder capacity and voiding efficiency, although not consistently and often outcomes did not reach clinically acceptable levels. eSCS, tSCS and SARS consistently reduced bowel management times. In most participants, erections could be achieved or were improved with eSCS or SARS. Chronic interventions, particularly SARS with dorsal root deafferentation, produced long term bladder and bowel improvements, whereas chronic eSCS and tSCS evidence was limited. Stimulation was most often applied to lumbosacral segments (L1–S1) at 30–60 Hz, although some studies used systematic mapping approaches. Conclusion: Electrical stimulation of the spinal cord and/or nerve roots is a promising method for modulating or restoring autonomic function after SCI. However, current evidence is based on small cohort or case studies, or retrospective reporting. Larger controlled studies are recommended to establish efficacy and long-term safety, and further mechanistic investigations are required. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420250621447 , identifier PROSPERO (CRD420250621447).

Background: Transcutaneous spinal cord stimulation (tSCS) is a promising avenue in spinal cord injury (SCI) rehabilitation; however, high currents are required to excite afferents in the spinal cord roots, which patients may not tolerate. Modulating tSCS pulses with a kHz carrier frequency (kHz‐tSCS) may be used to reduce discomfort; however, the way that kHz‐tSCS interacts with neural networks, compared to unmodulated pulses (conv‐tSCS), is largely unknown. Method: Ten able‐bodied participants received conv‐tSCS, kHz‐tSCS, and sham interventions for 20 min over the C7/T1 vertebrae. Charge delivery of both waveforms was measured. Posterior root reflexes (PRRs) and motor‐evoked potentials (MEPs) were recorded from the Flexor Carpi Radialis (FCR), Extensor Carpi Radialis Longus (ECRL), Flexor Carpi Ulnaris (FCU), and Brachioradialis (BR). PRR and MEP peak‐peak amplitudes were measured at baseline, 0‐, 15‐, and 30‐min post‐intervention. Results: The charge required to activate posterior roots with kHz‐tSCS was 3.8 times higher than with conv‐tSCS ( p < 0.001). Differences in PRR amplitude were found in the FCR between conv‐tSCS and kHz‐tSCS at 0‐ and 15‐min post‐intervention ( p < 0.028). PRR inhibition was found in the FCR between baseline and 30‐min post‐intervention with conv‐tSCS and the sham intervention ( p < 0.037). No change in PRR amplitudes was found for kHz‐tSCS. No other muscle showed any differences in PRR responses between intervention groups. Neither intervention caused any effect in MEP responses across time or between intervention groups. Conclusions: kHz‐tSCS was a less efficient waveform for stimulation. Differences in effects on spinal excitability were found to be inconclusive, and conv‐tSCS and kHz‐tSCS had no effect on corticospinal excitability. Significant PRR inhibition in the FCR was found with this experimental setup even when no stimulation was applied, suggesting a natural reduction in spinal excitability caused by participants laying supine for an extended period. Future research should consider how participant positioning could affect neural excitability.

Background: Spinal cord injury (SCI) causes impairment to bladder function. As current management strategies are not fully effective, there remains a need for alternative or adjunctive management options. Dorsal genital nerve stimulation (DGNS) has been shown to effectively inhibit unwanted bladder contractions in people with SCI. However, the acceptance and beneficial effects of home‐based DGNS have not yet been proven. Methods: This pilot trial investigated the feasibility and user acceptance of a novel DGNS device, UCon (InnoCon Medical, Denmark) when used at home by people with SCI for 8 weeks. Cystometry with and without DGNS was performed before and after the intervention. Outcome measures included 3‐day bladder diaries (3DBD), quality of life, and user acceptance questionnaires, and a semi‐structured interview. Results: Ten people with chronic SCI and neurogenic detrusor overactivity participated in the trial and used the device at home for 8 weeks. When tested at baseline, DGNS significantly increased maximum cystometric capacity (MCC) from 276 (125) to 394 (147) ml with DGNS applied ( p < 0.001). After the 8‐week intervention, no change in MCC without stimulation was noted. No change in bladder capacity or incontinence episodes was found from 3DBDs and quality of life was not significantly changed. User acceptance of the device was high, with some issues noted, particularly around device disconnection. Conclusions: Our results support the application of DGNS to increase bladder capacity after SCI, and user acceptance of home‐based DGNS was high. This therapy should be studied in a larger subject group to prove the effectiveness of home‐based DGNS.

Transcutaneous spinal cord stimulation (TSCS) has been shown to improve motor recovery in people with spinal cord injury (SCI). Some groups deliver TSCS modulated with a kHz‐frequency (TSCS–kHz); the intensity used for TSCS–kHz is usually set based on the motor threshold for TSCS, even though TSCS–kHz threshold is considerably higher than TSCS. As a result, TSCS–kHz interventions tend to be delivered at low intensities with respect to the motor threshold (~40%). In this study, we compared the effects of sub‐threshold TSCS and TSCS–kHz, when delivered at similar intensity relative to their own motor threshold. Experiment I compared the after‐effects of 20 min of sub‐threshold (40% threshold) TSCS and TSCS–kHz on spinal and corticospinal excitability in able‐bodied participants. Experiment II assessed the dose–response relationship of delivering short (10‐pulse) trains of TSCS and TSCS–kHz at three different current intensities relative to the threshold (40%, 60%, and 80%). Experiment I found that 20 min of TSCS–kHz at a 40% threshold decreased posterior root reflex amplitude (p < 0.05), whereas TSCS did not. In experiment II, motor‐evoked potential (MEP) amplitude increased following short trains of TSCS and TSCS–kHz of increasing intensity. MEP amplitude was significantly greater for TSCS–kHz compared with TSCS when delivered at 80% of the threshold (p < 0.05). These results suggest that TSCS and TSCS–kHz have different effects when delivered at similar intensity relative to their own threshold; both for immediate effects on corticospinal excitability and following prolonged stimulation on spinal excitability. These different effects may be utilized for optimal rehabilitation in people with SCI.

Rehabilitative interventions involving electrical stimulation show promise for neuroplastic recovery in people living with Spinal Cord Injury (SCI). However, the understanding of how stimulation interacts with descending and spinal excitability remain unclear. In this study we compared the immediate and short-term (within a few minutes) effects of pairing Transcranial Magnetic Stimulation (TMS) with transcutaneous Spinal Cord stimulation (tSCS) and Peripheral Nerve Stimulation (PNS) on Corticospinal excitability in healthy subjects. Three separate experimental conditions were assessed. In Experiment I, paired associative stimulation (PAS) was applied, involving repeated pairing of single pulses of TMS and tSCS, either arriving simultaneously at the spinal motoneurones (PAS_0ms) or slightly delayed (PAS_5ms). Corticospinal and spinal excitability, and motor performance, were assessed before and after the PAS interventions in 24 subjects. Experiment II compared the immediate effects of tSCS and PNS on corticospinal excitability in 20 subjects. Experiment III compared the immediate effects of tSCS with tSCS delivered at the same stimulation amplitude but modulated with a carrier frequency (in the kHz range) on corticospinal excitability in 10 subjects. Electromyography (EMG) electrodes were placed over the Tibialis Anterior (TA) soleus (SOL) and vastus medialis (VM) muscles and stimulation electrodes (cathodes) were placed on the lumbar spine (tSCS) and lateral to the popliteal fossa (PNS). TMS over the primary motor cortex (M1) was paired with tSCS or PNS to produce Motor Evoked Potentials (MEPs) in the TA and SOL muscles. Simultaneous delivery of repetitive PAS (PAS_0ms) increased corticospinal excitability and H-reflex amplitude at least 5 min after the intervention, and dorsiflexion force was increased in a force-matching task. When comparing effects on descending excitability between tSCS and PNS, a subsequent facilitation in MEPs was observed following tSCS at 30-50 ms which was not present following PNS. To a lesser extent this facilitatory effect was also observed with HF- tSCS at subthreshold currents. Here we have shown that repeated pairing of TMS and tSCS can increase corticospinal excitability when timed to arrive simultaneously at the alpha-motoneurone and can influence functional motor output. These results may be useful in optimizing stimulation parameters for neuroplasticity in people living with SCI.

Spinal cord stimulation may enable recovery of volitional motor control in people with chronic Spinal Cord Injury (SCI). In this study we explored the effects of adding SCS, applied transcutaneously (tSCS) at vertebral levels T10/11, to a sit-to-stand training intervention in people with motor complete and incomplete SCI. Nine people with chronic SCI (six motor complete; three motor incomplete) participated in an 8-week intervention, incorporating three training sessions per week. Participants received either tSCS combined with sit-to-stand training (STIM) or sit-to-stand training alone (NON-STIM). Outcome measures were carried out before and after the intervention. Seven participants completed the intervention (STIM N = 5; NON-STIM N = 2). Post training, improvements in International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) motor scores were noted in three STIM participants (range 1.0–7.0), with no change in NON-STIM participants. Recovery of volitional lower limb muscle activity and/or movement (with tSCS off) was noted in three STIM participants. Unassisted standing was not achieved in any participant, although standing with minimal assistance was achieved in one STIM participant. This pilot study has shown that the recruitment of participants, intervention and outcome measures were all feasible in this study design. However, some modifications are recommended for a larger trial.

There is increasing evidence that neuroplastic changes can occur even years after spinal cord injury, leading to reduced disability and better health which should reduce the cost of healthcare. In motor-incomplete spinal cord injury, recovery of leg function may occur if repetitive training causes afferent input to the lumbar spinal cord. The afferent input may be due to activity-based therapy without electrical stimulation but we present evidence that it is faster with electrical stimulation. This may be spinal cord stimulation or peripheral nerve stimulation. Recovery is faster if the stimulation is phasic and that the patient is trying to use their legs during the training. All the published studies are small, so all conclusions are provisional, but it appears that patients with more disability (AIS A and B) may need to continue using stimulation and for them, an implanted stimulator is likely to be convenient. Patients with less disability (AIS C and D) may make useful recovery and improve their quality of life from a course of therapy. This might be locomotion therapy but we argue that cycling with electrical stimulation, which uses biofeedback to encourage descending drive, causes rapid recovery and might be used with little supervision at home, making it much less expensive. Such an electrical therapy followed by conventional physiotherapy might be affordable for the many people living with chronic SCI. To put this in perspective, we present some information about what treatments are funded in the UK and the US.

Objectives: To assess and compare the effect of transcutaneous Dorsal Genital Nerve Stimulation (DGNS), Tibial Nerve Stimulation (TNS), Sacral Nerve Stimulation (SNS), and Spinal Stimulation (SS) on Neurogenic Detrusor Overactivity (NDO) and bladder capacity in people with Spinal Cord Injuries (SCI). Materials and Methods: Seven male participants with supra-sacral SCI were tested. Standard cystometry (CMG) was performed to assess bladder activity at baseline and with stimulation applied at each site. This was conducted over four separate sessions. All stimulation was monophasic, 15 Hz, 200 μS pulses and applied at maximum tolerable amplitude. Results were analysed against individual control results from within the same session. Results: Dorsal Genital Nerve Stimulation increased bladder capacity by 153 ± 146 ml (p = 0.016) or 117 ± 201%. DGNS, TNS and SNS all increased the volume held following the first reflex contraction, by 161 ± 175, 46 ± 62, and 34 ± 33 ml (p = 0.016, p = 0.031, p = 0.016), respectively. SS results showed small reduction of 33 ± 26 ml (p = 0.063) from baseline bladder capacity in five participants. Maximum Detrusor Pressure before leakage was increased during TNS, by 10 ± 13 cmH₂O (p = 0.031) but was unchanged during stimulation of other sites. DGNS only was able to suppress at least one detrusor contraction in five participants and reduced first peak detrusor pressure below 40 cmH₂O in these 5. Continuous TNS, SNS, and SS produced non-significant changes in bladder capacity from baseline, comparable to conditional stimulation. Increase in bladder capacity correlated with stimulation amplitude for DGNS but not TNS, SNS or SS. Conclusion: In this pilot study DGNS acutely suppressed detrusor contractions and increased bladder capacity whereas TNS, SNS, and SS did not. This is the first within individual comparison of surface stimulation sites for management of NDO in SCI individuals.

Background: Functional Electrical Stimulation (FES) cycling can benefit health and may lead to neuroplastic changes following incomplete spinal cord injury (SCI). Our theory is that greater neurological recovery occurs when electrical stimulation of peripheral nerves is combined with voluntary effort. In this pilot study, we investigated the effects of a one-month training programme using a novel device, the iCycle, in which voluntary effort is encouraged by virtual reality biofeedback during FES cycling. Methods: Eleven participants (C1-T12) with incomplete SCI (5 sub-acute; 6 chronic) were recruited and completed 12-sessions of iCycle training. Function was assessed before and after training using the bilateral International Standards for Neurological Classification of SCI (ISNC-SCI) motor score, Oxford power grading, Modified Ashworth Score, Spinal Cord Independence Measure, the Walking Index for Spinal Cord Injury and 10 m-walk test. Power output (PO) was measured during all training sessions. Results: Two of the 6 participants with chronic injuries, and 4 of the 5 participants with sub-acute injuries, showed improvements in ISNC-SCI motor score > 8 points. Median (IQR) improvements were 3.5 (6.8) points for participants with a chronic SCI, and 8.0 (6.0) points for those with sub-acute SCI. Improvements were unrelated to other measured variables (age, time since injury, baseline ISNC-SCI motor score, baseline voluntary PO, time spent training and stimulation amplitude; p > 0.05 for all variables). Five out of 11 participants showed moderate improvements in voluntary cycling PO, which did not correlate with changes in ISNC-SCI motor score. Improvement in PO during cycling was positively correlated with baseline voluntary PO (R² = 0.50; p < 0.05), but was unrelated to all other variables (p > 0.05). The iCycle was not suitable for participants who were too weak to generate a detectable voluntary torque or whose effort resulted in a negative torque. Conclusions: Improved ISNC-SCI motor scores in chronic participants may be attributable to the iCycle training. In sub-acute participants, early spontaneous recovery and changes due to iCycle training could not be distinguished. The iCycle is an innovative progression from existing FES cycling systems, and positive results should be verified in an adequately powered controlled trial. Trial registration: ClinicalTrials.gov, NCT03834324. Registered 06 February 2019 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03834324. Protocol V03, dated 06.08.2015.