The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Neuromodulation of lumbosacral spinal networks enables independent stepping after complete paraplegia
Abstract
Spinal sensorimotor networks that are functionally disconnected from the brain because of spinal cord injury (SCI) can be facilitated via epidural electrical stimulation (EES) to restore robust, coordinated motor activity in humans with paralysis 1-3. Previously, we reported a clinical case of complete sensorimotor paralysis of the lower extremities in which EES restored the ability to stand and the ability to control step-like activity while side-lying or suspended vertically in a body-weight support system (BWS)4. Since then, dynamic task-specific training in the presence of EES, termed multimodal rehabilitation (MMR), was performed for 43 weeks and resulted in bilateral stepping on a treadmill, independent from trainer assistance or BWS. Additionally, MMR enabled independent stepping over ground while using a front-wheeled walker with trainer assistance at the hips to maintain balance. Furthermore, MMR engaged sensorimotor networks to achieve dynamic performance of standing and stepping. To our knowledge, this is the first report of independent stepping enabled by task-specific training in the presence of EES by a human with complete loss of lower extremity sensorimotor function due to SCI.
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“This recovery has been documented in various independent studies, including in participants with complete sensorimotor paralysis5,6,30–34.”
From Walking naturally after spinal cord injury using a brain–spine interface (2023) · cites this paper as [33]
In the citing paper
“The delivery of epidural electrical stimulation over the lumbar spinal cord has enabled many individuals with spinal cord injury to regain adaptive control over the activity of otherwise paralysed muscles.”
From Walking naturally after spinal cord injury using a brain–spine interface (2023) · cites this paper as [33]
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Capogrosso, M., Balaguer, J.-M., Prat-Ortega, G., Verma, N., Yadav, P., Sorensen, E., de Freitas, R., Ensel, S., Borda, L., Donadio, S., et al. (2024) · Research Square · doi:10.21203/rs.3.rs-3650257/v1 · Cited by 7
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“40 In the present study, a robotic-enhanced standing environment was utilized in which free hands upright postural control could be practiced and investigated among individulas with SCI who were unable to stand independently.”
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“Spinal cord epidural stimulation (scES) along with activity-based training has been proven to be effective in re-enabling independent standing, walking over ground and voluntary movements in individuals with severe spinal cord injury (SCI) [1-5].”
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“Indeed, neural stimulation of the peripheral somatic nerves (PNS) 7–10 , spinal cord 11–15 or somatosensory cortex (S1) 16–18 showed the ability to restore missing sensations, resulting in closed-loop neuroprostheses able to establish a bidirectional link between humans and machines.”
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Self-citationTowards precise synthetic neural codes: high-dimensional stimulation with flexible electrodes
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“Finally, patients whose primary impairment is severe spasticity without voluntary motor capacity may not be ideal candidates, as ESCS is primarily designed to facilitate volitional motor control rather than directly treat spasticity [ 99, 118, 219 ].”
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“During a longer follow-up with 1-year additional multimodel rehabilitation, the same subject improved further to regain stepping on the treadmill with minimal support or independently [37].”
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“We intend to investigate the input-output properties of TVMS and its neurophysiological impacts on the spinal locomotor circuitry in individuals with SCI to develop a new rehabilitation therapy.”
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Self-citationNeuromodulation as a basic platform for neuroprotection and repair after spinal cord injury
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InfluentialSpinal stimulation and physical therapy helps paraplegic patients to walk again
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Walking after Spinal Cord Injury: Current Clinical Approaches and Future Directions
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Real-time brain-computer interface control of walking exoskeleton with bilateral sensory feedback
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“SCS has been used to augment motor rehabilitation in several populations, including spinal cord injury, stroke, spinal muscular atrophy, and Parkinson’s disease [40–42, 44, 51–56].”
Sun, X.-P., Shi, J.-J., Bao, Y., Zhang, J., Pan, H.-J., Li, D.-Y., Li, D., & Xie, Q. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.353507 · Cited by 6
“Effectiveness of epidural electrical stimulation on SCI has been reported (Angeli et al., 2018; Aslan et al., 2018; Gill et al., 2018; Harkema et al., 2018; Herrity et al., 2018; Straaten et al., 2018; Wagner et al., 2018; Watrin et al., 2018).”
Kaneshige, M., Obara, K., Suzuki, M., Tazoe, T., & Nishimura, Y. (2022) · eLife · doi:10.7554/elife.78346 · Cited by 4
Hormonal computing: a conceptual approach
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“identifies and adjusts the most effective combination of electrodes in the implanted array connected to the implant controller (Gill et al., 2018).”
BackgroundNeurorehabilitation Based on Spinal Cord Stimulation and Motor Training
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“After similar interventions, a patient with paraplegia was able to walk independently on a treadmill, as well as walk on a level surface using a front-wheeled walker with the help of a trainer to maintain balance [42].”
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Litigation risks despite guideline adherence for acute spinal cord injury: time is spine
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Interactions between descending and spinal circuits on motor output
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“Subsequently, independent stepping was also noticed in a person with SCI (7) and intentional overground walking in two persons with American Spinal Injury Association Impairment Scale B (AIS-B) SCI (8) after sEES (while stimulator is on) with locomotor training.”
Artificial nerve systems for use in bio-interactive prostheses
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“This technology has contributed to the rehabilitation of patients with neurological conditions such as paraplegia 28 , quadriplegia 15 and limb amputations 29 .”
Non-invasive closed-loop spinal stimulation restores leg stepping control in humans with paraplegia
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Hybrid 12-Month Exoskeleton Training with Percutaneous Epidural Stimulation After Spinal Cord Injury
Deitrich, J. N., Rehman, M. U., Trainer, R. J., Cifu, D. X., & Gorgey, A. S. (2026) · Life · doi:10.3390/life16010077 · Cited by 3
“However, our sample size is not different from other well-established clinical trials in the field [28–30].”
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Chronic Adaptations in the Dorsal Horn Following a Cervical Spinal Cord Injury in Primates
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Role of Epidural Electrode Stimulation in Three Patients with Incomplete AIS D Spinal Cord Injury
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“…electrodes at a sampling rate of 2000 Hz (Delsys Trigno Avanti, Delsys Inc., Boston, MA, USA); a custom-written MATLAB script (MATLAB 2019 Mathworks, Inc., Natick, MA, USA) was used for analysis. sEMG recordings included the RF, medial hamstring (MH), TA, and medial gastrocnemius (MG) [19,22].”
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“…by Gill et al. demonstrated that patients with the same complete spinal cord injury were able to initiate physical positions such as independent standing, different sensorimotor engagement between stepping and standing, as well as bilateral stepping on a treadmill with the addition of EES [27].”
Keesey, R., Hofstoetter, U. S., Hu, Z., Lombardi, L., Hawthorn, R., Bryson, N. K., Alashqar, A., Rowald, A., Minassian, K., & Seáñez, I. (2026) · Nature Biomedical Engineering · doi:10.1038/s41551-026-01684-w · Cited by 14
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“Several groups have published on the potential beneficial role of techniques ranging from minimally invasive transcutaneous spinal cord stimulation (6,7) to more invasive techniques such as epidural electrical stimulation (EES), delivered either tonically (4,5) or with spatiotemporal patterns (3).”
BackgroundSurface electromyography to identify top-down modulation in complete chronic spinal cord injury
SIMÃO, C. R., de Holanda, L. J., URBINI, L. F., LACERDA, M. O., FERNANDES, K., SILVA, P. M. D., MORYA, E., & LINDQUIST, A. R. (2021) · European Journal of Physical and Rehabilitation Medicine · doi:10.23736/s1973-9087.21.06878-7 · Cited by 3
Metadata
- Authors
- Gill, M. L., Grahn, P. J., Calvert, J. S., Linde, M. B., Lavrov, I. A., Strommen, J. A., Beck, L. A., Sayenko, D. G., Van Straaten, M. G., Drubach, D. I., Veith, D. D., Thoreson, A. R., Lopez, C., Gerasimenko, Y. P., Edgerton, V. R., Lee, K. H., & Zhao, K. D.
- Affiliations
- Mayo Clinic (US)
- Houston Methodist (US)
- Russian Academy of Sciences (RU)
- University of California, Los Angeles (US)
- Corresponding author
- Lee, Kendall H.
- Zhao, Kristin D.
- ORCID
- Venue
- Nature Medicine
- Published
- 2018-09-24
- Volume
- 24
- Issue
- 11
- Pages
- 1677-1682
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2892074957
- Cited by
- 574
- References
- 43
- Citations by year
- 2026: 51 · 2025: 63 · 2024: 58 · 2023: 81 · 2022: 87 · 2021: 94 · 2020: 72 · 2019: 50 · 2018: 16
- FWCI
- 44.13
- Type
- journal article
- Language
- en
- Update notices
- correction (2018-10-23)
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Nature
- Topics
- Health Sciences › Medicine › Clinical Neurology › Spinal Cord Injury Research
- Health Sciences › Medicine › Rehabilitation › Stroke Rehabilitation and Recovery
- Physical Sciences › Engineering › Biomedical Engineering › Prosthetics and Rehabilitation Robotics
- Keywords
- spinal cord injury, complete paraplegia, epidural stimulation, multimodal rehabilitation, task-oriented training, body weight support, standing, paraplegia
- MeSH terms
- Adult, Electric Stimulation, Transcutaneous Electric Nerve Stimulation, Electromyography, Humans, Male, Motor Activity, Nerve Net, Paralysis, Paraplegia, Spinal Cord Injuries, Muscle, Skeletal
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