Feb 7, 2022
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 Cassarà, 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, and Grégoire Courtine, Nature Medicine 2022, online 7 February 2022; doi: https://doi.org/10.1038/s41591-021-01663-5
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.
The scientific and technical impact of the study can be summarized as:
- Biomimetic EES helped three patients with complete sensorimotor paralysis due to SCI recover standing, walking, cycling, swimming, and trunk control capabilities and the progressive recovery of full-weight bearing capacities
- EES may potentially be applied to induce neuroplasticity post-injury to augment neurological recovery by immediately generating active and sustained movements in the early stages after SCI, as well as to regulate associated specific neurological functions, such as bladder and bowel control and hemodynamics
- The radically increased efficacy of EES was due in part to the newly designed and validated paddle lead consisting of 16 optimally arranged electrodes that target the sacral, lumbar, and low-thoracic dorsal root ensemble associated with leg and trunk movements
- High-end computational modeling in Sim4Life enables the generation of detailed, realistic, and personalized computational models of the interactions between EES and the spinal cord neural activity array arrangements, which were used to optimize in silico the implant design and ensure proper coverage of the relevant patient population
- Patient-specific treatment modeling with Sim4Life is key for identifying the safest and most effective surgical positioning of the electrode array, and interoperative test stimulations are instrumental for confirming personalized and activity-specific stimulation programs
