Activity-dependent spinal cord neuromodulation rapidly restores trunk and leg motor functions after complete paralysis
Rowald, Andreas; Komi, Salif; Demesmaeker, Robin; Baaklini, Edeny; Hernandez-Charpak, Sergio Daniel; Paoles, Edoardo; Montanaro, Hazael; Cassara, Antonino; Becce, Fabio; Lloyd, Bryn; Newton, Taylor; Ravier, Jimmy; Kinany, Nawal; D'Ercole, Marina; Paley, Aurélie; Hankov, Nicolas; Varescon, Camille; McCracken, Laura; Vat, Molywan; Caban, Miroslav; Watrin, Anne; Jacquet, Charlotte; Bole-Feysot, Léa; Harte, Cathal; Lorach, Henri; Galvez, Andrea; Tschopp, Manon; Herrmann, Natacha; Wacker, Moïra; Geernaert, Lionel; Fodor, Isabelle; Radevich, Valentin; Van Den Keybus, Katrien; Eberle, Grégoire; Pralong, Etienne; Roulet, Maxime; Ledoux, Jean-Baptiste; Fornari, Eleonora; Mandija, Stefano; Mattera, Loan; Martuzzi, Roberto; Nazarian, Bruno; Benkler, Stefan; Callegari, Simone; Greiner, Nathan; Fuhrer, Benjamin; Froeling, Martijn; Buse, Nik; Denison, Tim; Buschman, Rik; Wende, Christian; Ganty, Damien; Bakker, Jurriaan; Delattre, Vincent; Lambert, Hendrik; Minassian, Karen; van den Berg, Cornelis A T; Kavounoudias, Anne; Micera, Silvestro; Van De Ville, Dimitri; Barraud, Quentin; Kurt, Erkan; Kuster, Niels; Neufeld, Esra; Capogrosso, Marco; Asboth, Leonie; Wagner, Fabien B; Bloch, Jocelyne; Courtine, Grégoire
(2022) Nature Medicine, volume 28, issue 2, pp. 260 - 271
(Article)
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
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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.
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Keywords: General Biochemistry,Genetics and Molecular Biology, Journal Article
ISSN: 1078-8956
Publisher: Nature Publishing Group
Note: 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.
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