Journal of Education, Health and Sport

Introduction and purpose: Spinal cord injury may be associated with loss of motor and sensory functions, autonomic system functions and chronic pain. The development of technology has enabled the emergence of invasive and non-invasive methods of electrical and magnetic stimulation of the nervous system, which show a growing potential in the treatment of these symptoms in human and animal studies.

The purpose of the study is a presentation of the most current studies about the selected methods of neuromodulation of the nervous system in the treatment of symptoms of spinal cord injury.
Description of the state of knowledge: Neuromodulatory methods improve the functioning of patients affected by spinal cord injury. Studies on epidural stimulation of the spinal cord, transcranial magnetic stimulation, transcranial direct current stimulation transcutaneous spinal cord, and use of neuromodulation methods in combination with brain-machine interfaces stimulation show a reduction of chronic pain resistant to pharmacotherapy, improvement of motor limb function, respiratory function and bladder function. However, there are few large randomized studies with higher evidence strength.

Conclusions: Neuromodulation is effective in the treatment of symptoms of spinal cord injury. Promising results should lead to further research to increase the strength of evidence for the effectiveness of these therapies, improve technology and a deeper understanding of the mechanisms behind their effectiveness.

GBD 2016 Neurology Collaborators (2019). Global, regional, and national burden of neurological disorders, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016, The Lancet. Neurology, 2016;18(5):459–480.

Ahuja CS, Nori S, Tetreault L, Wilson J, Kwon B, Harrop J, Choi D, Fehlings MG. Traumatic Spinal Cord Injury-Repair and Regeneration, Neurosurgery, 2017;80(3S):S9-S22.

Sandrow-Feinberg HR, Houlé JD. Exercise after spinal cord injury as an agent for neuroprotection, regeneration and rehabilitation, Brain Research, 2015;1619:12-21.

Venkatesh K, Ghosh SK, Mullick M, Manivasagam G, Sen D. Spinal cord injury: pathophysiology, treatment strategies, associated challenges, and future implications, Cell and Tissue Research, 2019;377:125–151.

James ND, McMahon SB, Field-Fote EC, Bradbury EJ. Neuromodulation in the restoration of function after spinal cord injury, The Lancet. Neurology, 2018 Oct;17(10): 905-917.

Angeli CA, Edgerton VR, Gerasimenko YP, Harkema SJ. Altering spinal cord excitability enables voluntary movements after chronic complete paralysis in humans, Brain, 2015 May;137(5):1394–1409.

Hofmeister M, Memedovich A, Brown S, Saini M, Dowsett LE, Lorenzetti DL, McCarron TL, MacKean G, Clement F. Effectiveness of Neurostimulation Technologies for the Management of Chronic Pain: A Systematic Review, Neuromodulation : journal of the International Neuromodulation Society, 2020;23(2): 150–157.

Schwedt TJ, Vargas B. Neurostimulation for Treatment of Migraine and Cluster Headache, Pain medicine (Malden, Mass.), 2015;16(9):1827–1834.

Abell TL, Chen J, Emmanuel A, Jolley C, Sarela AI, Törnblom H. Neurostimulation of the gastrointestinal tract: review of recent developments, Neuromodulation: journal of the International Neuromodulation Society, 2015;18(3):221–227.

Starnes K, Miller K, Wong-Kisiel L, Lundstrom BN. A Review of Neurostimulation for Epilepsy in Pediatrics, Brain sciences, 2019;9(10):283.

Milev RV, Giacobbe P, Kennedy SH, Blumberger DM, Daskalakis ZJ, Downar J, Modirrousta M, Patry S, Vila-Rodriguez F, Lam RW, MacQueen GM, Parikh SV, Ravindran AV, CANMAT Depression Work Group. Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 4, Neurostimulation Treatments, Canadian journal of psychiatry, Revue canadienne de psychiatrie, 2016;61(9):561–575.

Martin JH. Harnessing neural activity to promote repair of the damaged corticospinal system after spinal cord injury, Neural Regeneration Research, 2016 Sep; 11(9):1389–1391.

Jamil A, Batsikadze G, Kuo HI, Labruna L, Hasan A, Paulus W, Nitsche MA. Systematic evaluation of the impact of stimulation intensity on neuroplastic after-effects induced by transcranial direct current stimulation, The Journal of Physiology, 2016 Oct; 595(4):1273-1288.

Calvert JS, Grahn PJ, Zhao KD, Lee KH. Emergence of Epidural Electrical Stimulation to Facilitate Sensorimotor Network Functionality After Spinal Cord Injury, Neuromodulation, 2019;22(3):244–252.

Li G, Fan ZK, Gu GF, Jia ZQ, Zhang QQ, Dai JY, He SS. Epidural Spinal Cord Stimulation Promotes Motor Functional Recovery by Enhancing Oligodendrocyte Survival and Differentiation and by Protecting Myelin after Spinal Cord Injury in Rats, https://doi.org/10.1007/s12264-019-00442-0, Published online ahead of print, 2019 Nov 16.

Kapural L, Yu C, Doust MW, Gliner BE, Vallejo R, Sitzman BT, Amirdelfan K, Morgan DM, Yearwood TL, Bundschu R, Yang T, Benyamin R, Burgher AH. Comparison of 10-kHz High-Frequency and Traditional Low-Frequency Spinal Cord Stimulation for the Treatment of Chronic Back and Leg Pain: 24-Month Results From a Multicenter, Randomized, Controlled Pivotal Trial, Neurosurgery, 2016;79(5):667–677.

Angeli CA., Boakye M., Morton RA., Vogt J., Benton K., Chen Y., Ferreira CK., Harkema SJ., Recovery of Over-Ground Walking after Chronic Motor Complete Spinal Cord Injury, New England Journal of Medicine, 2018;379(13):1244–1250.

Darrow D, Balser D, Netoff TI, Krassioukov A, Phillips A, Ann Parr, Samadani U. Epidural Spinal Cord Stimulation Facilitates Immediate Restoration of Dormant Motor and Autonomic Supraspinal Pathways after Chronic Neurologically Complete Spinal Cord Injury, Journal of Neurotrauma, 2019;36(15):2325–2336.

Walter M, Lee AHX, Kavanagh A, Phillips AA, Krassioukov AV. Epidural Spinal Cord Stimulation Acutely Modulates Lower Urinary Tract and Bowel Function Following Spinal Cord Injury: A Case Report, Frontiers in Physiology, 2018;9:1816.

Aslan SC, Legg Ditterline BE, Park MC, Angeli CA, Rejc E, Chen Y, Ovechkin AV, Krassioukov A, Harkema SJ. Epidural Spinal Cord Stimulation of Lumbosacral Networks Modulates Arterial Blood Pressure in Individuals With Spinal Cord Injury-Induced Cardiovascular Deficits, Frontiers in Physiology, 2018;9:565.

Harkema SJ, Wang S, Angeli CA, Chen Y, Boakye M, Ugiliweneza B, Hirsch GA. Normalization of Blood Pressure With Spinal Cord Epidural Stimulation After Severe Spinal Cord Injury, Frontiers in Human Neuroscience, 2018;12:83.

Harkema SJ, Legg Ditterline B, Wang S, Aslan S, Angeli CA, Ovechkin A, Hirsch GA. Epidural Spinal Cord Stimulation Training and Sustained Recovery of Cardiovascular Function in Individuals With Chronic Cervical Spinal Cord Injury, JAMA Neurology, 2018;75(12):1569–1571.

Formento E, Minassian K, Wagner F, Mignardot JB, Le Goff CG, Rowald A, Bloch J, Micera S, Capogrosso M, Courtine G. Electrical spinal cord stimulation must preserve proprioception to enable locomotion in humans with spinal cord injury, Nature Neuroscience, 2018;21(12):1728–1741.

Gerasimenko Y, Gorodnichev R, Moshonkina T, Sayenko D, Gad P, Reggie Edgerton V. Transcutaneous electrical spinal-cord stimulation in humans, Annals of Physical and Rehabilitation Medicine, 2015;58(4):225–231.

Gerasimenko Y, Gorodnichev R, Puhov A, Moshonkina T, Savochin A, Selionov V, Roy RR, Lu DC, Edgerton V. Initiation and modulation of locomotor circuitry output with multisite transcutaneous electrical stimulation of the spinal cord in noninjured humans, Journal of Neurophysiology, 2015;113:834–42.

Hofstoetter US, McKay WB, Tansey KE, Mayr W, Kern H, Minassian K. Modification of spasticity by transcutaneous spinal cord stimulation in individuals with incomplete spinal cord injury, The Journal of Spinal Cord Medicine, 2014;37(2):202–211.

Barss TS, Parhizi B, Mushahwar VK. Transcutaneous spinal cord stimulation of the cervical cord modulates lumbar networks, Journal of Neurophysiology, 2020 Jan 1;123(1):158-166.

Santos Ferreira I, Teixeira Costa B, Lima Ramos C, Lucena P, Thibaut A, Fregni F. Searching for the optimal tDCS target for motor rehabilitation, Journal of Neuroengineering and Rehabilitation, 2019;16(1):90. Published 2019 Jul 17.

Budzisz J, Szczepanowski R, Kruk P. Przezczaszkowa stymulacja stałoprądowa tDCS w badaniach naukowych mózgu człowieka, Przegląd Elektrotechniczny, 2017;93(4):42–45.

Potter-Baker KA, Janini DP, Lin YL, Sankarasubramanian V, Cunningham DA, Varnerin NM, Chabra P, Kilgore KL, Richmond MA, Frost FS, Plow EB. Transcranial direct current stimulation (tDCS) paired with massed practice training to promote adaptive plasticity and motor recovery in chronic incomplete tetraplegia: A pilot study, The Journal of Spinal Cord Medicine, 2018;41(5):503–517.

Yozbatiran N, Keser Z, Davis M, Stampas A, O'Malley MK, Cooper-Hay C, Frontera J, Fregni F, Francisco GE. Transcranial direct current stimulation (tDCS) of the primary motor cortex and robot-assisted arm training in chronic incomplete cervical spinal cord injury: A proof of concept sham-randomized clinical study, NeuroRehabilitation, 2016;39(3):401–411.

Cortes M, Medeiros AH, Gandhi A, Lee P, Krebs HI, Thickbroom G, Edwards D. Improved grasp function with transcranial direct current stimulation in chronic spinal cord injury, NeuroRehabilitation, 2017;41(1):51–59.

Yozbatiran N, Keser Z, Hasan K, Stampas A, Korupolu R, Kim S, O'Malley MK, Fregni F, Francisco GE. White matter changes in corticospinal tract associated with improvement in arm and hand functions in incomplete cervical spinal cord injury: pilot case series, Spinal Cord Series and Cases, 2017;3:17028.

Kumru H, Murillo N, Benito-Penalva J, Tormos JM, Vidal J. Transcranial direct current stimulation is not effective in the motor strength and gait recovery following motor incomplete spinal cord injury during Lokomat(®) gait training, Neuroscience Letters, 2016;620:143–147.

de Araújo AVL, Ribeiro FPG, Massetti T, Potter-Baker KA, Cortes M, Plow EB, da Silva TD, Tonks J, Anghinah R, Magalhães FH, Fregni F, de Mello Monteiro CB. Effectiveness of anodal transcranial direct current stimulation to improve muscle strength and motor functionality after incomplete spinal cord injury: a systematic review and meta-analysis, https://doi:10.1038/s41393-020-0438-2, Published online ahead of print, 2020 Feb 17.

da Silva FTG, Browne RAV, Pinto CB, Saleh Velez FG, do Egito EST, do Rêgo JTP, da Silva MR, Dantas PMS, Fregni F. Transcranial direct current stimulation in individuals with spinal cord injury: Assessment of autonomic nervous system activity, Restorative Neurology and Neuroscience, 2017;35(2):159–169.

Terranova C, Rizzo V, Cacciola A, Chillemi G, Calamuneri A, Milardi D, Quartarone A. Is There a Future for Non-invasive Brain Stimulation as a Therapeutic Tool?, Frontiers Neurology, 2019;9:1146.

Nardone R, Langthaler PB, Orioli A, Höller P, Höller Y, Frey VN, Brigo F, Trinka E. Effects of intermittent theta burst stimulation on spasticity after spinal cord injury, Restorative Neurology and Neuroscience, 2017;35(3):287–294.

Korzhova J, Sinitsyn D, Chervyakov A, Poydasheva A, Zakharova M, Suponeva N, Chernikova L, Piradov M. Transcranial and spinal cord magnetic stimulation in treatment of spasticity: a literature review and meta-analysis, European Journal of Physical and Rehabilitation Medicine, 2018;54(1):75–84.

Gao F, Chu H, Li J, Yang M, DU L, Li J, Chen L, Yang D, Zhang H, Chan C. Repetitive transcranial magnetic stimulation for pain after spinal cord injury: a systematic review and meta-analysis, Journal of Neurosurgical Sciences, 2017;61(5):514–522.

Yu B, Qiu H, Li J, Zhong C, Li J. Noninvasive brain stimulation does not improve neuropathic pain in individuals with spinal cord injury: evidence from a meta-analysis of 11 randomized controlled trials, https://doi:10.23736/S0390-5616.16.03809-1, Published online ahead of print, 2020 Mar 13.

Sivaramakrishnan A, Solomon JM, Manikandan N. Comparison of transcutaneous electrical nerve stimulation (TENS) and functional electrical stimulation (FES) for spasticity in spinal cord injury - A pilot randomized cross-over trial, The Journal of Spinal Cord Medicine, 2018;41(4):397–406.

Garcia MAC, Vargas CD. Is somatosensory electrical stimulation effective in relieving spasticity? A systematic review, Journal of Musculoskeletal and Neuronal Interactions, 2019;19(3):317–325.

Coutaux A. Non-pharmacological treatments for pain relief: TENS and acupuncture, Joint Bone Spine, 2017 Dec;84(6):657-661.

Zeb A, Arsh A, Bahadur S, Ilyas SM. Effectiveness of transcutaneous electrical nerve stimulation in management of neuropathic pain in patients with post traumatic incomplete spinal cord injuries, Pakistan Journal of Medicine Sciences, 2018;34(5):1177–1180.

Mokhtari T, Ren Q, Li N, Wang F, Bi Y, Hu L. Transcutaneous Electrical Nerve Stimulation in Relieving Neuropathic Pain: Basic Mechanisms and Clinical Applications, Current Pain and Headache Reports, 2020 Feb 18;24(4):14.

Peng WW, Tang ZY, Zhang FR, Li H, Kong YZ, Iannetti GD, Hu L. Neurobiological mechanisms of TENS-induced analgesia, Neuroimage, 2019 Jul 15;195: 396-408.

Hahm SC, Yoon YW, Kim J. High-frequency transcutaneous electrical nerve stimulation alleviates spasticity after spinal contusion by inhibiting activated microglia in rats, Neurorehabilitation and Neural Repair, 2015 May;29(4):370-81.

Slutzky MW. Brain-Machine Interfaces: Powerful Tools for Clinical Treatment and Neuroscientific Investigations, The Neuroscientist, 2019;25(2):139–154.

Soekadar SR, Witkowski M, Gómez C, Opisso E, Medina J, Cortese M, Cempini M, Carrozza MC, Cohen LG, Birbaumer N, Vitiello N. Hybrid EEG/EOG-based brain/neural hand exoskeleton restores fully independent daily living activities after quadriplegia, Science Robotics, 2016;1(1):eaag3296-1.

Benabid AL, Costecalde T, Eliseyev A, Charvet G, Verney A, Karakas S, Foerster M, Lambert A,Morinière B, Abroug N, Schaeffer MC, Moly A, Sauter-Starace F, Ratel D, Moro C, Torres-Martinez N, Langar L, Oddoux M, Polosan M, Pezzani S, Auboiroux V, Aksenova T, Mestais C, Chabardes S. An exoskeleton controlled by an epidural wireless brain–machine interface in a tetraplegic patient: a proof-of-concept demonstration, The Lancet Neurology, 2019;18(12):1112-1122.

Ajiboye AB, Willett FR, Young DR, Memberg WD, Murphy BA, Miller JP, Walter BL, Sweet JA, Hoyen HA, Keith MW, Peckham PH, Simeral JD, Donoghue JP, Hochberg LR, Kirsch RF. Restoration of reaching and grasping in a person with tetraplegia through brain-controlled muscle stimulation: a proof-of-concept demonstration, Lancet, 2017;389(10081):1821-1830.

Bouton C, Shaikhouni A, Annetta N, Bockbrader MA, Friedenberg DA, Nielson DM, Sharma G, Sederberg PB, Glenn BC, Mysiw WJ, Morgan AG, Deogaonkar M, Rezai AR. Restoring cortical control of functional movement in a human with quadriplegia, Nature, 2016 May;533(7602):247-250.

Selfslagh A, Shokur S, Campos DS, Donati AR, Almeida S, Yamauti SY, Coelho BD, Bouri M, Nicolelis MA. Non-invasive, brain-controlled functional electrical stimulation for locomotion rehabilitation in individuals with paraplegia, Scientific reports, 2019;9(1):1-17.

Kögel J, Jox RJ, Friedrich O. What is it like to use a BCI? – insights from an interview study with brain-computer interface users, BMC Medical Ethics, 2020;21(1):2.