An implantable system to restore hemodynamic stability after spinal cord injury
Aaron A. Phillips, Aasta P. Gandhi, Nicolas Hankov, Sergio Daniel Hernandez‐Charpak, Julien Rimok, Anthony V. Incognito, Anouk E.J. Nijland, Marina D’Ercole, Anne Watrin, Maxime Berney, Aikaterini Damianaki, Grégory Dumont, Nicolò Macellari, Laura De Herde, Nadine Intering, Donovan Smith, Ryan Miller, M. Smith, Jordan B. Lee, Edeny Baaklini, Jean‐Baptiste Ledoux, Javier G. Ordonnez, Taylor Newton, Ettore Flavio Meliadò, Léa Duguet, Charlotte Jacquet, Léa Bole-Feysot, Markus Rieger, Kristen Gelenitis, Yoann Dumeny, Miroslav Caban, Damien Ganty, Edoardo Paoles, Thomas G. Baumgartner, Lorraine Aviolat, Nadia Bérard, Julie Brancato, Krystel Bruyère, Rebecca Charbonneau, Chris Drummond-Main, Sean P. Dukelow, Grégoire Eberle, John Gaudet, Natacha Herrmann, Julie Hervé, Jamie Johnston, Valentin Lupi, John-Paul Miroz, Aurélie Paley, Julie Pillonel, Carole Poulin-Kella, Mélanie Ramirez, Katrien Van Den Keybus, Camille Varescon, Molywan Vat, Xiuzhi Pham, Laurence Wenger, Patrick S. J. Koomen, Onward Team, Francesco Acquati, Pierre Bessot, Julien Dedelley, Erika Ross, Anahita Kyani, Hendrik Lambert, Sebastien Morand, Chloé Picq, Jared Pradarelli, Francesca Stradolini, Rosanne B. van Dijsseldonk, Cathal Harte, Charles David Sasportes, Julie Brancato, Tristan Vouga, Jemina Fasola, Jimmy Ravier, Matthieu Gautier, Frédéric Merlos, J. Gaudet, Tomislav Milekovic, Andreas Rowald, Stefano Mandija, Cornelis A. T. van den Berg, Niels Kuster, Esra Neufeld, Étienne Pralong, Lorenz Hirt, Stefano Carda, Fabio Becce, Etienne Aleton, Kyle Rogan, Patrick Schoettker, Grégoire Wuerzner, Nelleke G. Langerak, Noël Keijsers, Brian K. Kwon, James D. Guest, Erika Ross, John Murphy, Erkan Kurt
Abstract
A spinal cord injury (SCI) causes immediate and sustained hemodynamic instability that threatens neurological recovery and impacts quality of life. Here we establish the clinical burden of chronic hypotensive complications due to SCI in 1,479 participants and expose the ineffective treatment of these complications with conservative measures. To address this clinical burden, we developed a purpose-built implantable system based on biomimetic epidural electrical stimulation (EES) of the spinal cord that immediately triggered robust pressor responses. The system durably reduced the severity of hypotensive complications in people with SCI, removed the necessity for conservative treatments, improved quality of life and enabled superior engagement in activities of daily living. Central to the development of this therapy was the head-to-head demonstration in the same participants that EES must target the last three thoracic segments, and not the lumbosacral segments, to achieve the safe and effective regulation of blood pressure in people with SCI. These findings in 14 participants establish the path to designing a pivotal device trial that will evaluate the safety and efficacy of EES to treat the underappreciated, treatment-resistant hypotensive complications due to SCI.