Neuromodulation of lumbosacral spinal networks enables independent stepping after complete paraplegia


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 paralysis1,2,3. 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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Fig. 1: Progression of EES-enabled stepping performance on a treadmill.
Fig. 2: Progression of EES-enabled stepping performance over ground.
Fig. 3: Step cycle characteristics during EES-enabled stepping over ground.
Fig. 4: Independent standing and stepping during a single MMR session.

Data availability

Raw and processed datasets are available from the corresponding author upon request.

Change history

  • 23 October 2018

    In the version of this article originally published, Dimitry G. Sayenko’s affiliations were not correct. The following affiliation for this author was missing: Department of Neurosurgery, Center for Neuroregeneration, Houston Methodist Research Institute, Houston, TX, USA. This affiliation has been added for the author, and the rest of the affiliations have been renumbered accordingly. The error has been corrected in the HTML and PDF versions of this article.


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We thank the participant for his time, effort, and continuous feedback throughout the study. We also thank C. Blaha, J. Chen, B. Cloud, T. Gardner, D. Hare, Y. Li, A. Mendez, C. Mitrovich, A. Schmeling, T. Scrabeck, M. Shaft, C. Stoppel, B. Wessel, and L. Zoecklein as well as the surgical team for their support during EES system implantation. K.H.L. received funding from The Grainger Foundation. K.H.L. and K.D.Z. received funding from the Jack Jablonski Bel13ve in Miracles Foundation, Mayo Clinic Rehabilitation Medicine Research Center, Mayo Clinic Transform the Practice, and Craig H. Neilsen Foundation. P.J.G. was supported by Regenerative Medicine Minnesota and the Mayo Clinic Center for Regenerative Medicine. J.S.C. was supported by the Mayo Clinic Graduate School of Biomedical Sciences. V.R.E. received funding from the Dana and Albert R. Broccoli Charitable Foundation, the Christopher and Dana Reeve Foundation, and the Walkabout Foundation.

Author information




V.R.E., P.J.G., M.L.G., K.H.L., and K.D.Z. initiated the project. V.R.E., D.I.D., Y.P.G., M.L.G., P.J.G., I.A.L., K.H.L., A.R.T., D.G.S., J.A.S., M.G.v.S., and K.D.Z. designed the experiments with contributions from all authors. L.A.B., J.S.C., M.L.G., I.A.L., M.B.L., J.A.S., and K.H.L. performed clinical assessments. L.A.B., M.L.G., M.B.L., J.A.S., D.D.V., and M.G.V.S. designed and performed rehabilitation. V.R.E., Y.P.G., P.J.G., I.A.L., J.A.S., L.A.B., K.H.L., and D.G.S. performed intraoperative assessments, and K.H.L. performed surgical implantation of the device. L.A.B., J.S.C., M.L.G., P.J.G., M.B.L., I.A.L., A.R.T., M.G.V.S., D.D.V., D.G.S., Y.P.G., and V.R.E. contributed to stimulation setting refinement. L.A.B., J.S.C., P.J.G., A.R.T., C.L., M.G.V.S., D.D.V., D.G.S., Y.P.G., V.R.E., M.L.G., I.A.L., K.H.L., K.D.Z., and J.A.S. contributed to data collection, analysis, and interpretation. J.S.C., M.L.G., P.J.G., M.B.L., and I.A.L. drafted the manuscript with subsequent contribution from all authors. K.H.L. and K.D.Z. supervised all aspects of the work.

Corresponding authors

Correspondence to Kendall H. Lee or Kristin D. Zhao.

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Competing interests

V.R.E. and Y.G. are shareholders in NeuroRecovery Technologies and hold inventorship rights on intellectual property licensed by the regents of the University of California to NeuroRecovery Technologies and its subsidiaries. K.H.L. previously served as a consultant to Medtronic’s Department of Technology Development focused on deep brain stimulation.

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Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–8

Reporting Summary

Supplementary Video 1

Comparison of trainer-assisted

Supplementary Video 2

Progression of EES-enabled stepping performance over ground

Supplementary Video 3

EES-enabled standing and stepping during a single MMR session

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Gill, M.L., Grahn, P.J., Calvert, J.S. et al. Neuromodulation of lumbosacral spinal networks enables independent stepping after complete paraplegia. Nat Med 24, 1677–1682 (2018).

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