Purpose of Review
Spinal cord stimulation (SCS) is an exciting new area of research in the field of spinal cord injury (SCI) medicine. This review aims to provide an overview of recent advances in SCS related to motor control, neurogenic bladder, and cardiovascular effects and discuss future directions.
Epidural spinal stimulation (spES) and transcutaneous stimulation (TSS) have been shown to improve lower and upper-extremity motor control after SCI. Similarly, SCS has shown to impact bladder function and blood pressure control after SCI. Future directions include gaining a better understanding of the associated mechanism, further optimization of stimulation parameters, coordinating the multisystem effects of SCS, and enhancing our knowledge of the benefits and limitations of spES versus TSS.
Clinicians should be aware of the growing evidence supporting the potential for multisystem effects of SCS after SCI.
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National Spinal Cord Injury Statistical Center. Facts and figures at a glance. Birmingham: University of Alabama at Birmingham; 2020.
Anderson KD. Targeting recovery: priorities of the spinal cord-injured population. J Neurotrauma. 2004;21(10):1371–83.
Herrity AN, Williams CS, Angeli CA, Harkema SJ, Hubscher CH. Lumbosacral spinal cord epidural stimulation improves voiding function after human spinal cord injury. Sci Rep. 2018;8(1):8688.
Kreydin E, Zhong H, Latack K, Ye S, Edgerton VR, Gad P. Transcutaneous electrical spinal cord neuromodulator (TESCoN) improves symptoms of overactive bladder. Front Syst Neurosci. 2020;14:1.
Harkema S, Gerasimenko Y, Hodes J, Burdick J, Angeli C, Chen Y, et al. Effect of epidural stimulation of the lumbosacral spinal cord on voluntary movement, standing, and assisted stepping after motor complete paraplegia: a case study. Lancet. 2011;377(9781):1938–47.
Angeli CA, Edgerton VR, Gerasimenko YP, Harkema SJ. Altering spinal cord excitability enables voluntary movements after chronic complete paralysis in humans. Brain. 2014;137(Pt 5):1394–409.
Grahn PJ, Lavrov IA, Sayenko DG, Van Straaten MG, Gill ML, Strommen JA, et al. Enabling task-specific volitional motor functions via spinal cord neuromodulation in a human with paraplegia. Mayo Clin Proc. 2017;92(4):544–54.
Gill ML, Grahn PJ, Calvert JS, Linde MB, Lavrov IA, Strommen JA, et al. Neuromodulation of lumbosacral spinal networks enables independent stepping after complete paraplegia. Nat Med. 2018;24(11):1677–82.
Angeli CA, Boakye M, Morton RA, Vogt J, Benton K, Chen Y, et al. Recovery of over-ground walking after chronic motor complete spinal cord injury. N Engl J Med. 2018;379(13):1244–50.
Wagner FB, Mignardot J-B, Le Goff-Mignardot CG, Demesmaeker R, Komi S, Capogrosso M, et al. Targeted neurotechnology restores walking in humans with spinal cord injury. Nature. 2018;563(7729):65–71.
Rejc E, Angeli CA, Bryant N, Harkema SJ. Effects of stand and step training with epidural stimulation on motor function for standing in chronic complete paraplegics. J Neurotrauma. 2017;34(9):1787–802.
Gerasimenko Y, Roy RR, Edgerton VR. Epidural stimulation: comparison of the spinal circuits that generate and control locomotion in rats, cats and humans. Exp Neurol. 2008;209(2):417–25.
Minassian K, Hofstoetter US, Danner SM, Mayr W, McKay WB, Tansey K, et al. Mechanisms of rhythm generation of the human lumbar spinal cord in response to tonic stimulation without and with step-related sensory feedback. Biomed Tech (Berl). 2013;58 Suppl 1. https://doi.org/10.1515/bmt-2013-4013.
Angeli CA, Forrest GF, Ferreira CK, Harkema SJ. Motor activation pattern and loading plantar pressures during stepping following electrical stimulation and loading training paradigms. Soc Neurosci 2009; Chicago, IL. http://www.abstractsonline.com/Plan/ViewAbstract.aspx?mID=2285&sKey=75ca4c19-c609-472e-aefac00bef8e599f&cKey=40629d89-e05b-44c2-8dd2-0aa1b13a0f88&mKey=%7b081F7976-E4CD-4F3D-A0AFE8387992A658%7d.
Rejc E, Angeli C, Harkema S. Effects of lumbosacral spinal cord epidural stimulation for standing after chronic complete paralysis in humans. PLoS One. 2015;10(7):e0133998. https://doi.org/10.1371/journal.pone.0133998.
Hofstoetter US, Hofer C, Kern H, Danner SM, Mayr W, Dimitrijevic MR, et al. Effects of transcutaneous spinal cord stimulation on voluntary locomotor activity in an incomplete spinaal cord injured individual. Biomed Tech (Berl). 2013;58 Suppl 1. https://doi.org/10.1515/bmt-2013-4014.
Gad PN, Kreydin E, Zhong H, Latack K, Edgerton VR. Non-invasive neuromodulation of spinal cord restores lower urinary tract function after paralysis. Front Neurosci. 2018;12:432.
Zhang F MK, Ramanujam A, Ravi M, Carnahan J, Kirshblum S, Forrest GF. Cervical transcutaneous spinal stimulation improves upper extremity and hand function in people with complete spinal cord injury, IEEE transactions on neural systems and rehabilitation engineering, Uner review 2020.
Gerasimenko YP, Lu DC, Modaber M, Zdunowski S, Gad P, Sayenko DG, et al. Noninvasive reactivation of motor descending control after paralysis. J Neurotrauma. 2015;32(24):1968–80.
Gad P, Gerasimenko Y, Zdunowski S, Turner A, Sayenko D, Lu DC, et al. Weight bearing over-ground stepping in an exoskeleton with non-invasive spinal cord neuromodulation after motor complete paraplegia. Front Neurosci. 2017;11:333.
Sayenko DG, Rath M, Ferguson AR, Burdick JW, Havton LA, Edgerton VR, et al. Self-assisted standing enabled by non-invasive spinal stimulation after spinal cord injury. J Neurotrauma. 2019;36(9):1435–50.
Hofstoetter US, Freundl B, Binder H, Minassian K. Common neural structures activated by epidural and transcutaneous lumbar spinal cord stimulation: elicitation of posterior root-muscle reflexes. PLoS One. 2018;13(1):e0192013.
Hofstoetter US, Freundl B, Danner SM, Krenn MJ, Mayr W, Binder H, et al. Transcutaneous spinal cord stimulation induces temporary attenuation of spasticity in individuals with spinal cord injury. J Neurotrauma. 2020;37(3):481–93.
Gad P, Lee S, Terrafranca N, Zhong H, Turner A, Gerasimenko Y, et al. Non-invasive activation of cervical spinal networks after severe paralysis. J Neurotrauma. 2018;35(18):2145–58.
Inanici F, Samejima S, Gad P, Edgerton VR, Hofstetter CP, Moritz CT. Transcutaneous electrical spinal stimulation promotes long-term recovery of upper extremity function in chronic tetraplegia. IEEE Trans Neural Syst Rehabil Eng. 2018;26(6):1272–8.
Lu DC, Edgerton VR, Modaber M, AuYong N, Morikawa E, Zdunowski S, et al. Engaging cervical spinal cord networks to reenable volitional control of hand function in tetraplegic patients. Neurorehabil Neural Repair. 2016;30(10):951–62.
Ditunno PL, Patrick M, Stineman M, Ditunno JF. Who wants to walk? Preferences for recovery after SCI: a longitudinal and cross-sectional study. Spinal Cord. 2008;46(7):500–6.
Simpson LA, Eng JJ, Hsieh JTC, Wolfe DL. The health and life priorities of individuals with spinal cord injury: a systematic review. J Neurotrauma. 2012;29(8):1548–55.
Linsenmeyer TA. Urologic management and renal disease in spinal cord injury. In: Kirshblum S, Lin VW, editors. Spinal cord medicine. 3rd ed. New York: Demos Medical Publishing; 2018. p. 332–86.
Madersbacher H. Conservative therapy of neurogenic disorders of micturition. Urologe A. 1999;38(1):24–9.
Tanagho EA, Schmidt RA. Electrical stimulation in the clinical management of the neurogenic bladder. J Urol. 1988;140(6):1331–9.
Brindley GS. The first 500 patients with sacral anterior root stimulator implants: general description. Paraplegia. 1994;32(12):795–805.
Goldman HB, Amundsen CL, Mangel J, Grill J, Bennett M, Gustafson KJ, et al. Dorsal genital nerve stimulation for the treatment of overactive bladder symptoms. Neurourol Urodyn. 2008;27(6):499–503.
Redshaw JD, Lenherr SM, Elliott SP, Stoffel JT, Rosenbluth JP, Presson AP, et al. Protocol for a randomized clinical trial investigating early sacral nerve stimulation as an adjunct to standard neurogenic bladder management following acute spinal cord injury. BMC Urol. 2018;18(1):72.
McGee MJ, Amundsen CL, Grill WM. Electrical stimulation for the treatment of lower urinary tract dysfunction after spinal cord injury. J Spinal Cord Med. 2015;38(2):135–46.
Stampas A, Korupolu R, Zhu L, Smith CP, Gustafson K. Safety, feasibility, and efficacy of transcutaneous tibial nerve stimulation in acute spinal cord injury neurogenic bladder: a randomized control pilot trial. Neuromodulation. 2019;22(6):716–22.
Pettigrew RI, Heetderks WJ, Kelley CA, Peng GCY, Krosnick SH, Jakeman LB, et al. Epidural spinal stimulation to improve bladder, bowel, and sexual function in individuals with spinal cord injuries: a framework for clinical research. IEEE Trans Biomed Eng. 2017;64(2):253–62.
de Groat WC, Yoshimura N. Pharmacology of the lower urinary tract. Annu Rev Pharmacol Toxicol. 2001;41:691–721.
Suskind AM. The aging overactive bladder: a review of aging-related changes from the brain to the bladder. Curr Bladder Dysfunct Rep. 2017;12(1):42–7.
Weissbart SJ, Rupal B, Hengyi R, Wein AJ, Detre JA, Arya LA, et al. Specific changes in brain activity during urgency in women with overactive bladder after successful sacral neuromodulation: a functional magnetic resonance imaging study. J Urol. 2018;200(2):382–8.
Gad PN, Roy RR, Zhong H, Lu DC, Gerasimenko YP, Edgerton VR. Initiation of bladder voiding with epidural stimulation in paralyzed, step trained rats. PLoS One. 2014;9(9):e108184.
Gad PN, Roy RR, Zhong H, Gerasimenko YP, Taccola G, Edgerton VR. Neuromodulation of the neural circuits controlling the lower urinary tract. Exp Neurol. 2016;285(Pt B):182–9.
Abud EM, Ichiyama RM, Havton LA, Chang HH. Spinal stimulation of the upper lumbar spinal cord modulates urethral sphincter activity in rats after spinal cord injury. Am J Physiol Ren Physiol. 2015;308(9):F1032–40.
Ren J, Chew DJ, Biers S, Thiruchelvam N. Electrical nerve stimulation to promote micturition in spinal cord injury patients: a review of current attempts. Neurourol Urodyn. 2016;35(3):365–70.
Havton LA, Christe KL, Edgerton VR, Gad PN. Noninvasive spinal neuromodulation to map and augment lower urinary tract function in rhesus macaques. Exp Neurol. 2019;322:113033.
Doherty S, Vanhoestenberghe A, Duffell L, Hamid R, Knight S. A urodynamic comparison of neural targets for transcutaneous electrical stimulation to acutely suppress detrusor contractions following spinal cord injury. Front Neurosci. 2019;13:1360.
Beck L, Veith D, Linde M, Gill M, Calvert J, Grahn P, et al. Impact of long-term epidural electrical stimulation enabled task-specific training on secondary conditions of chronic paraplegia in two humans. J Spinal Cord Med. 2020:1–6.
Teasell RW, Arnold JM, Krassioukov A, Delaney GA. Cardiovascular consequences of loss of supraspinal control of the sympathetic nervous system after spinal cord injury. Arch Phys Med Rehabil. 2000;81(4):506–16.
Phillips AA, Krassioukov AV. Contemporary cardiovascular concerns after spinal cord injury: mechanisms, maladaptations, and management. J Neurotrauma. 2015;32(24):1927–42.
Dolinak D, Balraj E. Autonomic dysreflexia and sudden death in people with traumatic spinal cord injury. Am J Forensic Med Pathol. 2007;28(2):95–8.
Carlozzi NE, Fyffe D, Morin KG, Byrne R, Tulsky DS, Victorson D, et al. Impact of blood pressure dysregulation on health-related quality of life in persons with spinal cord injury: development of a conceptual model. Arch Phys Med Rehabil. 2013;94(9):1721–30.
Illman A, Stiller K, Williams M. The prevalence of orthostatic hypotension during physiotherapy treatment in patients with an acute spinal cord injury. Spinal Cord. 2000;38(12):741–7.
Claydon VE, Steeves JD, Krassioukov A. Orthostatic hypotension following spinal cord injury: understanding clinical pathophysiology. Spinal Cord. 2006;44(6):341–51.
The Consensus Committee of the American Autonomic Society and the American Academy of Neurology. Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. Neurology. 1996;46(5):1470.
Piatt JA, Nagata S, Zahl M, Li J, Rosenbluth JP. Problematic secondary health conditions among adults with spinal cord injury and its impact on social participation and daily life. J Spinal Cord Med. 2016;39(6):693–8.
Duschek S, Matthias E, Schandry R. Essential hypotension is accompanied by deficits in attention and working memory. Behav Med. 2005;30(4):149–58.
Duschek S, Weisz N, Schandry R. Reduced cognitive performance and prolonged reaction time accompany moderate hypotension. Clin Auton Res Off J Clin Auton Res Soc. 2003;13(6):427–32.
Jegede AB, Rosado-Rivera D, Bauman WA, Cardozo CP, Sano M, Moyer JM, et al. Cognitive performance in hypotensive persons with spinal cord injury. Clin Auton Res Off J Clin Auton Res Soc. 2010;20(1):3–9.
Phillips AA, Warburton DER, Ainslie PN, Krassioukov AV. Regional neurovascular coupling and cognitive performance in those with low blood pressure secondary to high-level spinal cord injury: improved by alpha-1 agonist midodrine hydrochloride. J Cereb Blood Flow Metab. 2014;34(5):794–801.
Wecht JM, Weir JP, Katzelnick CG, Wylie G, Eraifej M, Nguyen N, et al. Systemic and cerebral hemodynamic contribution to cognitive performance in spinal cord injury. J Neurotrauma. 2018;35(24):2957–64.
Chopra AS, Miyatani M, Craven BC. Cardiovascular disease risk in individuals with chronic spinal cord injury: prevalence of untreated risk factors and poor adherence to treatment guidelines. J Spinal Cord Med. 2018;41(1):2–9.
Wecht JM, Bauman WA. Implication of altered autonomic control for orthostatic tolerance in SCI. Auton Neurosci. 2018;209:51–8.
Wu JC, Chen YC, Liu L, Chen TJ, Huang WC, Cheng H, et al. Increased risk of stroke after spinal cord injury: a nationwide 4-year follow-up cohort study. Neurology. 2012;78(14):1051–7.
Cragg JJ, Noonan VK, Krassioukov A, Borisoff J. Cardiovascular disease and spinal cord injury: results from a national population health survey. Neurology. 2013;81(8):723–8.
Zhu C, Galea M, Livote E, Signor D, Wecht JM. A retrospective chart review of heart rate and blood pressure abnormalities in veterans with spinal cord injury. J Spinal Cord Med. 2013;36(5):463–75.
Wecht JM, Zhu C, Weir JP, Yen C, Renzi C, Galea M. A prospective report on the prevalence of heart rate and blood pressure abnormalities in veterans with spinal cord injuries. J Spinal Cord Med. 2013;36(5):454–62.
Wecht JM, Weir JP, Bauman WA. Inter-day reliability of blood pressure and cerebral blood flow velocities in persons with spinal cord injury and intact controls. J Spinal Cord Med. 2017;40(2):159–69.
Krassioukov A, Eng JJ, Warburton DE, Teasell R. A systematic review of the management of orthostatic hypotension after spinal cord injury. Arch Phys Med Rehabil. 2009;90(5):876–85.
Wecht JM, Rosado-Rivera D, Handrakis JP, Radulovic M, Bauman WA. Effects of midodrine hydrochloride on blood pressure and cerebral blood flow during orthostasis in persons with chronic tetraplegia. Arch Phys Med Rehabil. 2010;91(9):1429–35.
Mills PB, Fung CK, Travlos A, Krassioukov A. Nonpharmacologic management of orthostatic hypotension: a systematic review. Arch Phys Med Rehabil. 2015;96(2):366–375.e6.
Gillis DJ, Wouda M, Hjeltnes N. Non-pharmacological management of orthostatic hypotension after spinal cord injury: a critical review of the literature. Spinal Cord. 2008;46(10):652–9.
Aslan SC, Legg Ditterline BE, Park MC, Angeli CA, Rejc E, Chen Y, et al. Epidural spinal cord stimulation of lumbosacral networks modulates arterial blood pressure in individuals with spinal cord injury-induced cardiovascular deficits. Front Physiol. 2018;9:565.
West CR, Phillips AA, Squair JW, Williams AM, Walter M, Lam T, et al. Association of epidural stimulation with cardiovascular function in an individual with spinal cord injury. JAMA Neurol. 2018;75(5):630–2.
Harkema SJ, Wang S, Angeli CA, Chen Y, Boakye M, Ugiliweneza B, et al. Normalization of blood pressure with spinal cord epidural stimulation after severe spinal cord injury. Front Hum Neurosci. 2018;12:83.
Harkema SJ, Legg Ditterline B, Wang S, Aslan S, Angeli CA, Ovechkin A, et al. Epidural spinal cord stimulation training and sustained recovery of cardiovascular function in individuals with chronic cervical spinal cord injury. JAMA Neurol. 2018;75(12):1569–71.
Darrow D, Balser D, Netoff TI, Krassioukov A, Phillips A, Parr A, et al. Epidural spinal cord stimulation facilitates immediate restoration of dormant motor and autonomic supraspinal pathways after chronic neurologically complete spinal cord injury. J Neurotrauma. 2019;36(15):2325–36.
Phillips AA, Squair JW, Sayenko DG, Edgerton VR, Gerasimenko Y, Krassioukov AV. An autonomic neuroprosthesis: noninvasive electrical spinal cord stimulation restores autonomic cardiovascular function in individuals with spinal cord injury. J Neurotrauma. 2018;35(3):446–51.
Kirshblum S, Angeli CA, Guest JD, Forrest GF, Wecht J, Harel NY, et al. Documentation of clinical benefits of epidural stimulation and proposal of a new multidimensional outcome measure for individuals with spinal cord injury. Program No. 481.15. 2019 Neuroscience meeting planner.Chicago: Society for Neuroscience, 2019.
Conflict of Interest
The authors declare that they have no conflicts of interest. Dr. Linsenmeyer is a consultant for urological epidural stimulation studies at the University of Louisville, Louisville KY.
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Donovan, J., Forrest, G., Linsenmeyer, T. et al. Spinal Cord Stimulation After Spinal Cord Injury: Promising Multisystem Effects. Curr Phys Med Rehabil Rep 9, 23–31 (2021). https://doi.org/10.1007/s40141-020-00304-1
- Spinal cord injury
- Spinal stimulation
- Motor control
- Neurogenic bladder