Activity-dependent spinal cord neuromodulation rapidly restores trunk and leg motor functions after complete paralysis

Andreas Rowald, Salif Komi, Robin Demesmaeker, Edeny Baaklini, Sergio Daniel Hernandez-Charpak, Edoardo Paoles, Hazael Montanaro, Antonino Cassara, Fabio Becce, Bryn Lloyd, Taylor Newton, Jimmy Ravier, Nawal Kinany, Marina D’Ercole, Aurélie Paley, Nicolas Hankov, Camille Varescon, Laura McCracken, Molywan Vat, Miroslav Caban, Anne Watrin, Charlotte Jacquet, Léa Bole-Feysot, Cathal Harte, Henri Lorach, Andrea Galvez, Manon Tschopp, Natacha Herrmann, Moïra Wacker, Lionel Geernaert, Isabelle Fodor, Valentin Radevich, Katrien Van Den Keybus, Grégoire Eberle, Etienne Pralong, Maxime Roulet, Jean-Baptiste Ledoux, Eleonora Fornari, Stefano Mandija, Loan Mattera, Roberto Martuzzi, Bruno Nazarian, Stefan Benkler, Simone Callegari, Nathan Greiner, Benjamin Fuhrer, Martijn Froeling, Nik Buse, Tim Denison, Rik Buschman, Christian Wende, Damien Ganty, Jurriaan Bakker, Vincent Delattre, Hendrik Lambert, Karen Minassian, Cornelis A. T. van den Berg, Anne Kavounoudias, Silvestro Micera, Dimitri Van De Ville, Quentin Barraud, Erkan Kurt, Niels Kuster, Esra Neufeld, Marco Capogrosso, Leonie Asboth, Fabien B. Wagner, Jocelyne Bloch, Grégoire Courtine
Nat Med. 2022-02-07; :
DOI: 10.1038/s41591-021-01663-5

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Rowald A(#)(1)(2)(3), Komi S(#)(1)(2)(3), Demesmaeker R(#)(1)(2)(3), Baaklini E(1)(2)(3), Hernandez-Charpak SD(1)(2)(3), Paoles E(4), Montanaro H(5)(6), Cassara A(5), Becce F(7), Lloyd B(5), Newton T(5), Ravier J(1)(2)(3), Kinany N(1)(8)(9), D’Ercole M(4), Paley A(2)(3), Hankov N(1)(2)(3), Varescon C(1)(2)(3), McCracken L(1)(2)(3), Vat M(2)(3), Caban M(4)(8), Watrin A(4), Jacquet C(4), Bole-Feysot L(1)(2)(3), Harte C(1)(2)(3), Lorach H(1)(2)(3), Galvez A(1)(2)(3), Tschopp M(2), Herrmann N(2), Wacker M(2), Geernaert L(2), Fodor I(2), Radevich V(2), Van Den Keybus K(2), Eberle G(2), Pralong E(10), Roulet M(3)(10), Ledoux JB(7)(11), Fornari E(7)(11), Mandija S(12), Mattera L(13), Martuzzi R(13), Nazarian B(14), Benkler S(5), Callegari S(15), Greiner N(1)(2)(3), Fuhrer B(1)(2), Froeling M(12), Buse N(16), Denison T(16)(17), Buschman R(16), Wende C(18), Ganty D(4), Bakker J(4), Delattre V(4), Lambert H(4), Minassian K(19), van den Berg CAT(12), Kavounoudias A(20), Micera S(9)(21), Van De Ville D(8)(22), Barraud Q(1)(2)(3), Kurt E(23), Kuster N(5)(6)(15), Neufeld E(5)(6)(15), Capogrosso M(1)(24)(25), Asboth L(1)(2)(3), Wagner FB(1)(2)(3)(26), Bloch J(27)(28)(29)(30), Courtine G(31)(32)(33)(34).

Author information:
(1)Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences,
Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
(2)Department of Clinical Neuroscience, Lausanne University Hospital (CHUV) and
University of Lausanne (UNIL), Lausanne, Switzerland.
(3)Defitech Center for Interventional Neurotherapies (NeuroRestore),
EPFL/CHUV/UNIL, Lausanne, Switzerland.
(4)ONWARD Medical, Lausanne, Switzerland.
(5)Foundation for Research on Information Technologies in Society, Zurich,
Switzerland.
(6)Department for Information Technology and Electrical Engineering, Swiss
Federal Institute of Technology, Zurich, Switzerland.
(7)Department of Diagnostic and Interventional Radiology, CHUV/UNIL, Lausanne,
Switzerland.
(8)Institute of Bioengineering, EPFL, Lausanne, Switzerland.
(9)The BioRobotics Institute, Scuola Superiore Sant’Anna, Pisa, Italy.
(10)Department of Neurosurgery, CHUV, Lausanne, Switzerland.
(11)Biomedical Imaging Center, MR Section, CHUV, Lausanne, Switzerland.
(12)University Medical Center Utrecht, Utrecht, Netherlands.
(13)Fondation Campus Biotech Genève, Geneva, Switzerland.
(14)Institut des Neurosciences de la Timone, Aix-Marseille University, CNRS,
Marseille, France.
(15)ZurichMedTech, Zurich, Switzerland.
(16)Medtronic, Minneapolis, MN, USA.
(17)Department of Engineering Science, University of Oxford, Oxford, United
Kingdom.
(18)Medical Materials and Implants, Technical University of Munich, Munich,
Germany.
(19)Center for Medical Physics and Biomedical Engineering, Medical University of
Vienna, Vienna, Austria.
(20)Laboratoire de Neurosciences Cognitives, Aix-Marseille University, CNRS,
Marseille, France.
(21)Bertarelli Foundation, Translational Neuroengineering, Center for
Neuroprosthetics and Institute of Bioengineering, School of Bioengineering, EPFL,
Lausanne, Switzerland.
(22)Department of Radiology and Medical Informatics, University of Geneva,
Geneva, Switzerland.
(23)Department of Neurosurgery, Radboud University Medical Center Nijmegen,
Nijmegen, Netherlands.
(24)Department of Neuroscience and Movement Science, University of Fribourg,
Fribourg, Switzerland.
(25)Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, PA,
USA.
(26)Institut des Maladies Neurodégénératives (CNRS UMR 5293), Université de
Bordeaux, Bordeaux, France.
(27)Center for Neuroprosthetics and Brain Mind Institute, School of Life
Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
.
(28)Department of Clinical Neuroscience, Lausanne University Hospital (CHUV) and
University of Lausanne (UNIL), Lausanne, Switzerland. .
(29)Defitech Center for Interventional Neurotherapies (NeuroRestore),
EPFL/CHUV/UNIL, Lausanne, Switzerland. .
(30)Department of Neurosurgery, CHUV, Lausanne, Switzerland.
.
(31)Center for Neuroprosthetics and Brain Mind Institute, School of Life
Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
.
(32)Department of Clinical Neuroscience, Lausanne University Hospital (CHUV) and
University of Lausanne (UNIL), Lausanne, Switzerland. .
(33)Defitech Center for Interventional Neurotherapies (NeuroRestore),
EPFL/CHUV/UNIL, Lausanne, Switzerland. .
(34)Department of Neurosurgery, CHUV, Lausanne, Switzerland.
.
(#)Contributed equally

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.

© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.

 

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