TY - JOUR
T1 - Activity-dependent spinal cord neuromodulation rapidly restores trunk and leg motor functions after complete paralysis
AU - Rowald, Andreas
AU - Komi, Salif
AU - Demesmaeker, Robin
AU - Baaklini, Edeny
AU - Hernandez-Charpak, Sergio Daniel
AU - Paoles, Edoardo
AU - Montanaro, Hazael
AU - Cassara, Antonino
AU - Becce, Fabio
AU - Lloyd, Bryn
AU - Newton, Taylor
AU - Ravier, Jimmy
AU - Kinany, Nawal
AU - D'Ercole, Marina
AU - Paley, Aurélie
AU - Hankov, Nicolas
AU - Varescon, Camille
AU - McCracken, Laura
AU - Vat, Molywan
AU - Caban, Miroslav
AU - Watrin, Anne
AU - Jacquet, Charlotte
AU - Bole-Feysot, Léa
AU - Harte, Cathal
AU - Lorach, Henri
AU - Galvez, Andrea
AU - Tschopp, Manon
AU - Herrmann, Natacha
AU - Wacker, Moïra
AU - Geernaert, Lionel
AU - Fodor, Isabelle
AU - Radevich, Valentin
AU - Van Den Keybus, Katrien
AU - Eberle, Grégoire
AU - Pralong, Etienne
AU - Roulet, Maxime
AU - Ledoux, Jean-Baptiste
AU - Fornari, Eleonora
AU - Mandija, Stefano
AU - Mattera, Loan
AU - Martuzzi, Roberto
AU - Nazarian, Bruno
AU - Benkler, Stefan
AU - Callegari, Simone
AU - Greiner, Nathan
AU - Fuhrer, Benjamin
AU - Froeling, Martijn
AU - Buse, Nik
AU - Denison, Tim
AU - Buschman, Rik
AU - Wende, Christian
AU - Ganty, Damien
AU - Bakker, Jurriaan
AU - Delattre, Vincent
AU - Lambert, Hendrik
AU - Minassian, Karen
AU - van den Berg, Cornelis A T
AU - Kavounoudias, Anne
AU - Micera, Silvestro
AU - Van De Ville, Dimitri
AU - Barraud, Quentin
AU - Kurt, Erkan
AU - Kuster, Niels
AU - Neufeld, Esra
AU - Capogrosso, Marco
AU - Asboth, Leonie
AU - Wagner, Fabien B
AU - Bloch, Jocelyne
AU - Courtine, Grégoire
N1 - Funding Information:
We thank our study participants for their commitment and trust. All participants gave their informed consent for publication of their images. We thank A. Curt for support; A. van der Kolk and F. Visser for support in imaging data collection and inspection; and many students, interns and former employees for various contributions, including R. Wang, C. Puffay, Y. L. R. Wan, I. Perret, E. Revol, M. Van Campenhoudt, I. Youssef, I. Turcu, F. Sellet, G. Carparelli, C. Moerman, D. Scherrer-Ma, F. Magaud, M. Damiani and N. Regazzi. Investigational implantable stimulators and paddle leads were donated by Medtronic and ONWARD Medical. This work was supported by Wings for Life, the Defitech Foundation, the International Foundation for Research in Paraplegia, Rolex for Enterprise, Carigest Promex, Riders4Riders, ALARME, the Panacée Foundation, the Pictet Group Charitable Foundation, the Firmenich Foundation, ONWARD Medical, European Union’s Horizon 2020 (785907 Human Brain Project SGA2), RESTORE: Eurostars E10889, CONFIRM!: Eurostars E!12743, the Swiss National Science Foundation (NCCR Robotics), the European Research Council (ERC-2015-CoG HOW2WALKAGAIN 682999), the Commission of Technology and Innovation Innosuisse (CTI 41871.1 IP_LS and CTI 25761.1) and the H2020-MSCACOFUND-2015 EPFL fellows program (grant 665667 to F.B.W.).
Funding Information:
We thank our study participants for their commitment and trust. All participants gave their informed consent for publication of their images. We thank A. Curt for support; A. van der Kolk and F. Visser for support in imaging data collection and inspection; and many students, interns and former employees for various contributions, including R. Wang, C. Puffay, Y. L. R. Wan, I. Perret, E. Revol, M. Van Campenhoudt, I. Youssef, I. Turcu, F. Sellet, G. Carparelli, C. Moerman, D. Scherrer-Ma, F. Magaud, M. Damiani and N. Regazzi. Investigational implantable stimulators and paddle leads were donated by Medtronic and ONWARD Medical. This work was supported by Wings for Life, the Defitech Foundation, the International Foundation for Research in Paraplegia, Rolex for Enterprise, Carigest Promex, Riders4Riders, ALARME, the Panacée Foundation, the Pictet Group Charitable Foundation, the Firmenich Foundation, ONWARD Medical, European Union’s Horizon 2020 (785907 Human Brain Project SGA2), RESTORE: Eurostars E10889, CONFIRM!: Eurostars E!12743, the Swiss National Science Foundation (NCCR Robotics), the European Research Council (ERC-2015-CoG HOW2WALKAGAIN 682999), the Commission of Technology and Innovation Innosuisse (CTI 41871.1 IP_LS and CTI 25761.1) and the H2020-MSCACOFUND-2015 EPFL fellows program (grant 665667 to F.B.W.).
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2022/2
Y1 - 2022/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85124368817&partnerID=8YFLogxK
U2 - 10.1038/s41591-021-01663-5
DO - 10.1038/s41591-021-01663-5
M3 - Article
C2 - 35132264
SN - 1078-8956
VL - 28
SP - 260
EP - 271
JO - Nature Medicine
JF - Nature Medicine
IS - 2
ER -