An Autonomic Neuroprosthesis: Noninvasive Electrical Spinal Cord Stimulation Restores Autonomic Cardiovascular Function in Individuals with Spinal Cord Injury

Abstract

Despite autonomic dysfunction after spinal cord injury (SCI) being the major cause of death and a top health priority, the clinical management options for these conditions are limited to drugs with delayed onset and nonpharmacological interventions with equivocal effectiveness. We tested the capacity of electrical stimulation, applied transcutaneously over the spinal cord, to manage autonomic dysfunction in the form of orthostatic hypotension after SCI. We assessed beat-by-beat blood pressure (BP), stroke volume, and cardiac contractility (dP/dt; Finometer), as well as cerebral blood flow (transcranial Doppler) in 5 individuals with motor-complete SCI (4 cervical, 1 thoracic) during an orthostatic challenge with and without transcutaneous electrical stimulation applied at the TVII level. During the orthostatic challenge, all individuals experienced hypotension characterized by a 37 ± 4 mm Hg decrease in systolic BP, a 52 ± 10% reduction in cardiac contractility, and a 23 ± 6% reduction in cerebral blood flow (all p < 0.05), along with severe self-reported symptoms. Electrical stimulation completely normalized BP, cardiac contractility, cerebral blood flow, and abrogated all symptoms. Noninvasive transcutaneous electrical spinal cord stimulation may be a viable therapy for restoring autonomic cardiovascular control after SCI.

Transcutaneous Electrical Spinal Cord Neuromodulator (TESCoN) Improves Symptoms of Overactive Bladder

“…To briefly expand on some of these points, it is obvious that using the transcutaneous approach, multiple organ systems can be targeted simply by moving the electrode along the length of the spinal cord (Gad et al, 2018a,b;Gad P. et al, 2018;Inanici et al, 2018;Phillips et al, 2018;Rath et al, FIGURE 6 | Changes in NBSS parameters after TESCoN therapy (A) Neurogenic Bladder Symptom Score (NBSS) at Pre-Therapy and Post-Therapy for the 14 patients tested. (B) Mean ± SE (n = 14 patients) NBSS scores at Pre-Therapy and Post-Therapy.…”

The relationship between maximum tolerance and motor activation during transcutaneous spinal stimulation is unaffected by the carrier frequency or vibration

“…Regardless of the exact mechanism, the ratio between tolerance and spinally evoked motor potentials has to be considered when choosing a stimulation paradigm for studies that require TSS‐induced motor activation for functional outcomes (e.g., for standing such as in Sayenko et al, 2019). On the other hand, previous studies have demonstrated the TSS can be used to facilitate other functions such as rhythmic motions (Gerasimenko et al, 2015), trunk stability (Rath et al, 2018), cardiovascular function (Phillips et al, 2018), and bladder function (Gad et al, 2018) in individuals with spinal cord injury, without directly inducing motor responses. These studies used the carrier frequency stimulation paradigm in an attempt to increase stimulation intensity and engage spinal interneural networks while reducing stimulation‐related pain.…”

“…As such, mechanisms of spinal neuromodulation may also include activation of spinal interneural networks and antidromic activation of ascending fibers in the dorsal columns. TSS has been used to increase excitability at multiple levels of the spinal neuraxis to enable motor and autonomic functions in individuals with chronic spinal cord injury (SCI) (Gad et al, 2018; Hofstoetter et al, 2013, 2015; Minassian et al, 2013, 2016; Phillips et al, 2018; Rath et al, 2018; Sayenko et al, 2019). Although TSS has been examined as a possible clinical intervention for individuals with SCI, the promising findings with regard to motor recovery and the noninvasive nature of the technique could make TSS suitable for use with other neurologically‐impaired populations.…”

Human Dorsal Root Ganglion Stimulation Reduces Sympathetic Outflow and Long-Term Blood Pressure

“…Phillips et al. ( 29 ) have shown that, in patients with spinal cord injury, transcutaneous SCS can reverse the orthostatic fall in BP and have proposed an “autonomic neuroprosthesis.” It thus appears that standard SCS may have a hypertensive effect that is beneficial in spinal cord injury, whereas DRGS has a hypotensive effect, and it is likely that the mechanisms of BP change are different for SCS and DRGS as they stimulate different neural pathways.…”