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Abstract
Epidural electrical stimulation (EES) targeting the dorsal roots of lumbosacral segments restores walking in people with spinal cord injury (SCI). However, EES is delivered with multielectrode paddle leads that were originally designed to target the dorsal column of the spinal cord. Here, we hypothesized that an arrangement of electrodes targeting the ensemble of dorsal roots involved in leg and trunk movements would result in superior efficacy, restoring more diverse motor activities after the most severe SCI. To test this hypothesis, we established a computational framework that informed the optimal arrangement of electrodes on a new paddle lead and guided its neurosurgical positioning. We also developed software supporting the rapid configuration of activity-specific stimulation programs that reproduced the natural activation of motor neurons underlying each activity. We tested these neurotechnologies in three individuals with complete sensorimotor paralysis as part of an ongoing clinical trial (www.clinicaltrials.gov identifier NCT02936453). Within a single day, activity-specific stimulation programs enabled these three individuals to stand, walk, cycle, swim and control trunk movements. Neurorehabilitation mediated sufficient improvement to restore these activities in community settings, opening a realistic path to support everyday mobility with EES in people with SCI.
Implantation of a multielectrode paddle that allows personalized electrical stimulation to all regions of the spinal cord involved in leg and trunk movements rapidly restores motor function in patients with spinal cord injury with complete paralysis.
Details
Title
Activity-dependent spinal cord neuromodulation rapidly restores trunk and leg motor functions after complete paralysis
Author
Rowald Andreas 1 ; Salif, Komi 1 ; Demesmaeker, Robin 1
; Baaklini Edeny 1
; Hernandez-Charpak Sergio Daniel 1
; Paoles Edoardo 2 ; Montanaro Hazael 3
; Cassara Antonino 4 ; Becce Fabio 5
; Lloyd, Bryn 4 ; Taylor, Newton 4 ; Ravier Jimmy 1 ; Kinany Nawal 6 ; D’Ercole Marina 7 ; Paley Aurélie 8 ; Hankov Nicolas 1 ; Varescon Camille 1 ; McCracken, Laura 1 ; Molywan, Vat 8 ; Caban Miroslav 9 ; Watrin, Anne 2 ; Jacquet, Charlotte 2 ; Bole-Feysot Léa 1 ; Harte Cathal 1 ; Lorach Henri 1 ; Galvez, Andrea 1 ; Tschopp Manon 10 ; Herrmann, Natacha 10 ; Wacker Moïra 10 ; Geernaert Lionel 10 ; Fodor, Isabelle 10 ; Radevich Valentin 10 ; Van Den Keybus Katrien 10 ; Eberle Grégoire 10 ; Pralong Etienne 11 ; Roulet Maxime 12 ; Ledoux Jean-Baptiste 13 ; Fornari Eleonora 13 ; Mandija Stefano 14
; Mattera Loan 15 ; Martuzzi Roberto 15
; Nazarian, Bruno 16 ; Benkler, Stefan 4 ; Callegari, Simone 17
; Greiner, Nathan 1 ; Fuhrer, Benjamin 18
; Froeling Martijn 14
; Buse Nik 19 ; Denison, Tim 20 ; Buschman Rik 19 ; Wende, Christian 21 ; Ganty Damien 22 ; Bakker Jurriaan 22 ; Delattre, Vincent 22 ; Lambert, Hendrik 22 ; Minassian, Karen 23
; van den Berg Cornelis A T 14 ; Kavounoudias, Anne 24
; Silvestro, Micera 25
; Van De Ville Dimitri 26
; Barraud Quentin 1
; Erkan, Kurt 27 ; Kuster Niels 28 ; Neufeld Esra 28
; Capogrosso Marco 29 ; Asboth Leonie 1
; Wagner, Fabien B 30
; Bloch Jocelyne 31
; Courtine Grégoire 31
1 Swiss Federal Institute of Technology (EPFL), Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049); Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Department of Clinical Neuroscience, Lausanne, Switzerland (GRID:grid.8515.9) (ISNI:0000 0001 0423 4662); EPFL/CHUV/UNIL, Defitech Center for Interventional Neurotherapies (NeuroRestore), Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049)
2 ONWARD Medical, Lausanne, Switzerland (GRID:grid.5333.6)
3 Foundation for Research on Information Technologies in Society, Zurich, Switzerland (GRID:grid.443853.d); Swiss Federal Institute of Technology, Department for Information Technology and Electrical Engineering, Zurich, Switzerland (GRID:grid.5801.c) (ISNI:0000 0001 2156 2780)
4 Foundation for Research on Information Technologies in Society, Zurich, Switzerland (GRID:grid.443853.d)
5 CHUV/UNIL, Department of Diagnostic and Interventional Radiology, Lausanne, Switzerland (GRID:grid.414250.6) (ISNI:0000 0001 2181 4933)
6 Swiss Federal Institute of Technology (EPFL), Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049); EPFL, Institute of Bioengineering, Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049); Scuola Superiore Sant’Anna, The BioRobotics Institute, Pisa, Italy (GRID:grid.263145.7) (ISNI:0000 0004 1762 600X)
7 ONWARD Medical, Lausanne, Switzerland (GRID:grid.263145.7)
8 Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Department of Clinical Neuroscience, Lausanne, Switzerland (GRID:grid.8515.9) (ISNI:0000 0001 0423 4662); EPFL/CHUV/UNIL, Defitech Center for Interventional Neurotherapies (NeuroRestore), Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049)
9 ONWARD Medical, Lausanne, Switzerland (GRID:grid.5333.6); EPFL, Institute of Bioengineering, Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049)
10 Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Department of Clinical Neuroscience, Lausanne, Switzerland (GRID:grid.8515.9) (ISNI:0000 0001 0423 4662)
11 CHUV, Department of Neurosurgery, Lausanne, Switzerland (GRID:grid.8515.9) (ISNI:0000 0001 0423 4662)
12 EPFL/CHUV/UNIL, Defitech Center for Interventional Neurotherapies (NeuroRestore), Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049); CHUV, Department of Neurosurgery, Lausanne, Switzerland (GRID:grid.8515.9) (ISNI:0000 0001 0423 4662)
13 CHUV/UNIL, Department of Diagnostic and Interventional Radiology, Lausanne, Switzerland (GRID:grid.414250.6) (ISNI:0000 0001 2181 4933); CHUV, Biomedical Imaging Center, MR Section, Lausanne, Switzerland (GRID:grid.8515.9) (ISNI:0000 0001 0423 4662)
14 University Medical Center Utrecht, Utrecht, Netherlands (GRID:grid.7692.a) (ISNI:0000000090126352)
15 Fondation Campus Biotech Genève, Geneva, Switzerland (GRID:grid.7692.a)
16 Aix-Marseille University, CNRS, Institut des Neurosciences de la Timone, Marseille, France (GRID:grid.5399.6) (ISNI:0000 0001 2176 4817)
17 ZurichMedTech, Zurich, Switzerland (GRID:grid.443853.d)
18 Swiss Federal Institute of Technology (EPFL), Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049); Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Department of Clinical Neuroscience, Lausanne, Switzerland (GRID:grid.8515.9) (ISNI:0000 0001 0423 4662)
19 Medtronic, Minneapolis, USA (GRID:grid.419673.e) (ISNI:0000 0000 9545 2456)
20 Medtronic, Minneapolis, USA (GRID:grid.419673.e) (ISNI:0000 0000 9545 2456); University of Oxford, Department of Engineering Science, Oxford, United Kingdom (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948)
21 Technical University of Munich, Medical Materials and Implants, Munich, Germany (GRID:grid.6936.a) (ISNI:0000000123222966)
22 ONWARD Medical, Lausanne, Switzerland (GRID:grid.6936.a)
23 Medical University of Vienna, Center for Medical Physics and Biomedical Engineering, Vienna, Austria (GRID:grid.22937.3d) (ISNI:0000 0000 9259 8492)
24 Aix-Marseille University, CNRS, Laboratoire de Neurosciences Cognitives, Marseille, France (GRID:grid.5399.6) (ISNI:0000 0001 2176 4817)
25 Scuola Superiore Sant’Anna, The BioRobotics Institute, Pisa, Italy (GRID:grid.263145.7) (ISNI:0000 0004 1762 600X); School of Bioengineering, EPFL, Bertarelli Foundation, Translational Neuroengineering, Center for Neuroprosthetics and Institute of Bioengineering, Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049)
26 EPFL, Institute of Bioengineering, Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049); University of Geneva, Department of Radiology and Medical Informatics, Geneva, Switzerland (GRID:grid.8591.5) (ISNI:0000 0001 2322 4988)
27 Radboud University Medical Center Nijmegen, Department of Neurosurgery, Nijmegen, Netherlands (GRID:grid.10417.33) (ISNI:0000 0004 0444 9382)
28 Foundation for Research on Information Technologies in Society, Zurich, Switzerland (GRID:grid.443853.d); Swiss Federal Institute of Technology, Department for Information Technology and Electrical Engineering, Zurich, Switzerland (GRID:grid.5801.c) (ISNI:0000 0001 2156 2780); ZurichMedTech, Zurich, Switzerland (GRID:grid.5801.c)
29 Swiss Federal Institute of Technology (EPFL), Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049); University of Fribourg, Department of Neuroscience and Movement Science, Fribourg, Switzerland (GRID:grid.8534.a) (ISNI:0000 0004 0478 1713); University of Pittsburgh, Department of Neurological Surgery, Pittsburgh, USA (GRID:grid.21925.3d) (ISNI:0000 0004 1936 9000)
30 Swiss Federal Institute of Technology (EPFL), Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049); Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Department of Clinical Neuroscience, Lausanne, Switzerland (GRID:grid.8515.9) (ISNI:0000 0001 0423 4662); EPFL/CHUV/UNIL, Defitech Center for Interventional Neurotherapies (NeuroRestore), Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049); Université de Bordeaux, Institut des Maladies Neurodégénératives (CNRS UMR 5293), Bordeaux, France (GRID:grid.412041.2) (ISNI:0000 0001 2106 639X)
31 Swiss Federal Institute of Technology (EPFL), Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049); Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Department of Clinical Neuroscience, Lausanne, Switzerland (GRID:grid.8515.9) (ISNI:0000 0001 0423 4662); EPFL/CHUV/UNIL, Defitech Center for Interventional Neurotherapies (NeuroRestore), Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049); CHUV, Department of Neurosurgery, Lausanne, Switzerland (GRID:grid.8515.9) (ISNI:0000 0001 0423 4662)
; Baaklini Edeny 1
; Hernandez-Charpak Sergio Daniel 1
; Paoles Edoardo 2 ; Montanaro Hazael 3
; Cassara Antonino 4 ; Becce Fabio 5
; Lloyd, Bryn 4 ; Taylor, Newton 4 ; Ravier Jimmy 1 ; Kinany Nawal 6 ; D’Ercole Marina 7 ; Paley Aurélie 8 ; Hankov Nicolas 1 ; Varescon Camille 1 ; McCracken, Laura 1 ; Molywan, Vat 8 ; Caban Miroslav 9 ; Watrin, Anne 2 ; Jacquet, Charlotte 2 ; Bole-Feysot Léa 1 ; Harte Cathal 1 ; Lorach Henri 1 ; Galvez, Andrea 1 ; Tschopp Manon 10 ; Herrmann, Natacha 10 ; Wacker Moïra 10 ; Geernaert Lionel 10 ; Fodor, Isabelle 10 ; Radevich Valentin 10 ; Van Den Keybus Katrien 10 ; Eberle Grégoire 10 ; Pralong Etienne 11 ; Roulet Maxime 12 ; Ledoux Jean-Baptiste 13 ; Fornari Eleonora 13 ; Mandija Stefano 14
; Mattera Loan 15 ; Martuzzi Roberto 15
; Nazarian, Bruno 16 ; Benkler, Stefan 4 ; Callegari, Simone 17
; Greiner, Nathan 1 ; Fuhrer, Benjamin 18
; Froeling Martijn 14
; Buse Nik 19 ; Denison, Tim 20 ; Buschman Rik 19 ; Wende, Christian 21 ; Ganty Damien 22 ; Bakker Jurriaan 22 ; Delattre, Vincent 22 ; Lambert, Hendrik 22 ; Minassian, Karen 23
; van den Berg Cornelis A T 14 ; Kavounoudias, Anne 24
; Silvestro, Micera 25
; Van De Ville Dimitri 26
; Barraud Quentin 1
; Erkan, Kurt 27 ; Kuster Niels 28 ; Neufeld Esra 28
; Capogrosso Marco 29 ; Asboth Leonie 1
; Wagner, Fabien B 30
; Bloch Jocelyne 31
; Courtine Grégoire 31
1 Swiss Federal Institute of Technology (EPFL), Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049); Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Department of Clinical Neuroscience, Lausanne, Switzerland (GRID:grid.8515.9) (ISNI:0000 0001 0423 4662); EPFL/CHUV/UNIL, Defitech Center for Interventional Neurotherapies (NeuroRestore), Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049)
2 ONWARD Medical, Lausanne, Switzerland (GRID:grid.5333.6)
3 Foundation for Research on Information Technologies in Society, Zurich, Switzerland (GRID:grid.443853.d); Swiss Federal Institute of Technology, Department for Information Technology and Electrical Engineering, Zurich, Switzerland (GRID:grid.5801.c) (ISNI:0000 0001 2156 2780)
4 Foundation for Research on Information Technologies in Society, Zurich, Switzerland (GRID:grid.443853.d)
5 CHUV/UNIL, Department of Diagnostic and Interventional Radiology, Lausanne, Switzerland (GRID:grid.414250.6) (ISNI:0000 0001 2181 4933)
6 Swiss Federal Institute of Technology (EPFL), Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049); EPFL, Institute of Bioengineering, Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049); Scuola Superiore Sant’Anna, The BioRobotics Institute, Pisa, Italy (GRID:grid.263145.7) (ISNI:0000 0004 1762 600X)
7 ONWARD Medical, Lausanne, Switzerland (GRID:grid.263145.7)
8 Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Department of Clinical Neuroscience, Lausanne, Switzerland (GRID:grid.8515.9) (ISNI:0000 0001 0423 4662); EPFL/CHUV/UNIL, Defitech Center for Interventional Neurotherapies (NeuroRestore), Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049)
9 ONWARD Medical, Lausanne, Switzerland (GRID:grid.5333.6); EPFL, Institute of Bioengineering, Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049)
10 Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Department of Clinical Neuroscience, Lausanne, Switzerland (GRID:grid.8515.9) (ISNI:0000 0001 0423 4662)
11 CHUV, Department of Neurosurgery, Lausanne, Switzerland (GRID:grid.8515.9) (ISNI:0000 0001 0423 4662)
12 EPFL/CHUV/UNIL, Defitech Center for Interventional Neurotherapies (NeuroRestore), Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049); CHUV, Department of Neurosurgery, Lausanne, Switzerland (GRID:grid.8515.9) (ISNI:0000 0001 0423 4662)
13 CHUV/UNIL, Department of Diagnostic and Interventional Radiology, Lausanne, Switzerland (GRID:grid.414250.6) (ISNI:0000 0001 2181 4933); CHUV, Biomedical Imaging Center, MR Section, Lausanne, Switzerland (GRID:grid.8515.9) (ISNI:0000 0001 0423 4662)
14 University Medical Center Utrecht, Utrecht, Netherlands (GRID:grid.7692.a) (ISNI:0000000090126352)
15 Fondation Campus Biotech Genève, Geneva, Switzerland (GRID:grid.7692.a)
16 Aix-Marseille University, CNRS, Institut des Neurosciences de la Timone, Marseille, France (GRID:grid.5399.6) (ISNI:0000 0001 2176 4817)
17 ZurichMedTech, Zurich, Switzerland (GRID:grid.443853.d)
18 Swiss Federal Institute of Technology (EPFL), Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049); Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Department of Clinical Neuroscience, Lausanne, Switzerland (GRID:grid.8515.9) (ISNI:0000 0001 0423 4662)
19 Medtronic, Minneapolis, USA (GRID:grid.419673.e) (ISNI:0000 0000 9545 2456)
20 Medtronic, Minneapolis, USA (GRID:grid.419673.e) (ISNI:0000 0000 9545 2456); University of Oxford, Department of Engineering Science, Oxford, United Kingdom (GRID:grid.4991.5) (ISNI:0000 0004 1936 8948)
21 Technical University of Munich, Medical Materials and Implants, Munich, Germany (GRID:grid.6936.a) (ISNI:0000000123222966)
22 ONWARD Medical, Lausanne, Switzerland (GRID:grid.6936.a)
23 Medical University of Vienna, Center for Medical Physics and Biomedical Engineering, Vienna, Austria (GRID:grid.22937.3d) (ISNI:0000 0000 9259 8492)
24 Aix-Marseille University, CNRS, Laboratoire de Neurosciences Cognitives, Marseille, France (GRID:grid.5399.6) (ISNI:0000 0001 2176 4817)
25 Scuola Superiore Sant’Anna, The BioRobotics Institute, Pisa, Italy (GRID:grid.263145.7) (ISNI:0000 0004 1762 600X); School of Bioengineering, EPFL, Bertarelli Foundation, Translational Neuroengineering, Center for Neuroprosthetics and Institute of Bioengineering, Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049)
26 EPFL, Institute of Bioengineering, Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049); University of Geneva, Department of Radiology and Medical Informatics, Geneva, Switzerland (GRID:grid.8591.5) (ISNI:0000 0001 2322 4988)
27 Radboud University Medical Center Nijmegen, Department of Neurosurgery, Nijmegen, Netherlands (GRID:grid.10417.33) (ISNI:0000 0004 0444 9382)
28 Foundation for Research on Information Technologies in Society, Zurich, Switzerland (GRID:grid.443853.d); Swiss Federal Institute of Technology, Department for Information Technology and Electrical Engineering, Zurich, Switzerland (GRID:grid.5801.c) (ISNI:0000 0001 2156 2780); ZurichMedTech, Zurich, Switzerland (GRID:grid.5801.c)
29 Swiss Federal Institute of Technology (EPFL), Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049); University of Fribourg, Department of Neuroscience and Movement Science, Fribourg, Switzerland (GRID:grid.8534.a) (ISNI:0000 0004 0478 1713); University of Pittsburgh, Department of Neurological Surgery, Pittsburgh, USA (GRID:grid.21925.3d) (ISNI:0000 0004 1936 9000)
30 Swiss Federal Institute of Technology (EPFL), Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049); Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Department of Clinical Neuroscience, Lausanne, Switzerland (GRID:grid.8515.9) (ISNI:0000 0001 0423 4662); EPFL/CHUV/UNIL, Defitech Center for Interventional Neurotherapies (NeuroRestore), Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049); Université de Bordeaux, Institut des Maladies Neurodégénératives (CNRS UMR 5293), Bordeaux, France (GRID:grid.412041.2) (ISNI:0000 0001 2106 639X)
31 Swiss Federal Institute of Technology (EPFL), Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049); Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), Department of Clinical Neuroscience, Lausanne, Switzerland (GRID:grid.8515.9) (ISNI:0000 0001 0423 4662); EPFL/CHUV/UNIL, Defitech Center for Interventional Neurotherapies (NeuroRestore), Lausanne, Switzerland (GRID:grid.5333.6) (ISNI:0000000121839049); CHUV, Department of Neurosurgery, Lausanne, Switzerland (GRID:grid.8515.9) (ISNI:0000 0001 0423 4662)
Pages
260-271
Publication year
2022
Publication date
Feb 2022
ISSN
10788956
e-ISSN
1546170X
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2631747634
Copyright
© The Author(s), under exclusive licence to Springer Nature America, Inc. 2022.