The dawn of cardiovascular neuroprosthetics: Epidural spinal cord stimulation acutely restores cardiovascular function in persons with clinically complete spinal cord injury
Authors: Phillips Aaron A , West Christopher R , Squair Jordan W , Harkema Susan , Angeli Claudia , Krassioukov Andrei V 
Published: November 2023

INTRODUCTIONNeuroprosthetic electrical stimulation of the lumbosacral spinal cord with surgical implants has the capacity to excite dormant neuronal circuitry that has lost supraspinal control due to a spinal cord injury. Very recently, this intervention was even shown to elicit involuntary and voluntary stepping‐like movement of skeletal muscles previously thought to be paralyzed.OBJECTIVEConsidering that autonomic and cardiovascular dysfunctions are the leading cause of death after spinal cord injury, and a higher health priority than walking again by these individuals, we set out to explore if lumbosacral electrical stimulation of the spinal cord could be harnessed to regulate the cardiovascular system after spinal cord injury.METHODSThree of the first individuals with cervical spinal cord injury to be implanted worldwide were assessed in the present study, all of whom presented with cardiovascular dysfunction, in the form of severe orthostatic hypotension as well as impaired cardiac and cerebral regulation. A 16‐electrode array (Fig A) paddle was implanted over the lower lumbar/sacral spinal cord segments and connected to an electrical stimulation unit (both Medtronic). At least one month after implantation, we developed a cardiovascular optimized stimulation paradigm, that excited sympathetic preganglionic neurons but did not elicit skeletal muscle contraction (confirmed with electromyography; Fig A). We measured beat‐by‐beat blood pressure (photoplethysmography), cardiac function (echocardiography), and cerebral blood flow regulation (transcranial Doppler), in the supine position and in response to sit‐up, as well as cognitive function (Stroop test) with and without (in randomized order) cardiovascular optimized stimulation. Statistics on only one to three individuals is not typically recommended and was not performed.RESULTSTargeted cardiovascular electrical stimulation resulted in: [1] abrogated orthostatic hypotension (–39mmHg and severe presyncope vs. −8mmHg and absence of symptoms; Fig A,B); [2] maintained stroke volume (−32ml vs. −8ml; Fig 1E) and cerebral blood flow (−25 cm/s vs. −6cm/s; Fig B) during sit‐up; and [3] restored neurovascular coupling Fig C (+0% vs. 18%); and Stroop performance (P3–P2 time: 42s vs. 21s). Increased low‐frequency power of systolic blood pressure oscillations suggest supraspinal medullary sympathetic control of blood pressure is restored Fig D.CONCLUSIONSNeuroprosthetic modulation of spinal cord circuitry caudal to injury can restore normal autonomic control, which challenges our dogmatic understanding of the inherent functionality of the autonomic pathways in the spinal cord after injury. This data may represent the dawn of a new age for neuroprosthetic management of autonomic and cardiovascular heath.Support or Funding InformationCraig Neilsen Foundation, Rick Hansen Institute, Helmsley Foundation Research Trust.