Spinal cord epidural stimulation for motor and autonomic function recovery after chronic spinal cord injury: A case series and technical note
- Department of Neurosurgery, University of Louisville, Louisville, Kentucky,
- Department of Neurosurgery, Vanderbilt University, Nashville,
- Department of Physical Medicine Rehabilitation, Rutgers, Newark, New Jersey,
- Department of Infectious Diseases, University of Louisville, Louisville, United States.
Nicholas Dietz, Department of Neurosurgery, University of Louisville, Louisville KY 40202, United States.
DOI:10.25259/SNI_1074_2022Copyright: © 2023 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
How to cite this article: Maxwell Boakye1, Tyler Ball2, Nicholas Dietz1, Mayur Sharma1, Claudia Angeli1, Enrico Rejc1, Steven Kirshblum3, Gail Forrest3, Forest W. Arnold4, Susan Harkema1. Spinal cord epidural stimulation for motor and autonomic function recovery after chronic spinal cord injury: A case series and technical note. 17-Mar-2023;14:87
How to cite this URL: Maxwell Boakye1, Tyler Ball2, Nicholas Dietz1, Mayur Sharma1, Claudia Angeli1, Enrico Rejc1, Steven Kirshblum3, Gail Forrest3, Forest W. Arnold4, Susan Harkema1. Spinal cord epidural stimulation for motor and autonomic function recovery after chronic spinal cord injury: A case series and technical note. 17-Mar-2023;14:87. Available from: https://surgicalneurologyint.com/?post_type=surgicalint_articles&p=12201
Background: Traumatic spinal cord injury (tSCI) is a debilitating condition, leading to chronic morbidity and mortality. In recent peer-reviewed studies, spinal cord epidural stimulation (scES) enabled voluntary movement and return of over-ground walking in a small number of patients with motor complete SCI. Using the most extensive case series (n = 25) for chronic SCI, the present report describes our motor and cardiovascular and functional outcomes, surgical and training complication rates, quality of life (QOL) improvements, and patient satisfaction results after scES.
Methods: This prospective study occurred at the University of Louisville from 2009 to 2020. scES interventions began 2–3 weeks after surgical implantation of the scES device. Perioperative complications were recorded as well as long-term complications during training and device related events. QOL outcomes and patient satisfaction were evaluated using the impairment domains model and a global patient satisfaction scale, respectively.
Results: Twenty-five patients (80% male, mean age of 30.9 ± 9.4 years) with chronic motor complete tSCI underwent scES using an epidural paddle electrode and internal pulse generator. The interval from SCI to scES implantation was 5.9 ± 3.4 years. Two participants (8%) developed infections, and three additional patients required washouts (12%). All participants achieved voluntary movement after implantation. A total of 17 research participants (85%) reported that the procedure either met (n = 9) or exceeded (n = 8) their expectations, and 100% would undergo the operation again.
Conclusion: scES in this series was safe and achieved numerous benefits on motor and cardiovascular regulation and improved patient-reported QOL in multiple domains, with a high degree of patient satisfaction. The multiple previously unreported benefits beyond improvements in motor function render scES a promising option for improving QOL after motor complete SCI. Further studies may quantify these other benefits and clarify scES’s role in SCI patients.
Keywords: Epidural stimulation, Functional recovery, Neuromodulation, Rehabilitation, Spinal cord injury, Spinal cord stimulation, Spinal surgery, Technical note
Traumatic spinal cord injury (tSCI) is a debilitating condition with an annual incidence of 54 cases/million people and an estimated prevalence from 252,000 to 373,000 persons in the United States in 2020.[
Reports in the literature have focused on neurological and physiological outcomes in small numbers of patients.[
MATERIALS AND METHODS
After approval from our local institutional review board (IRB), we monitored and recorded all adverse events (as per the local IRB, Food and Drug Administration standards, and the appointed Data Safety and Monitoring Board reporting requirements). This report describes data from the initial 25 participants with motor complete injuries, graded as American Spinal Injury Association, Impairment Scale A or B, and satisfying the inclusion and exclusion criteria listed in
Each participant enrolled in one of three cohorts [
Training protocols for spinal cord epidural stimulation (scES) studies. Cohort 1 (n = 8) was implanted to evaluate motor and functional outcomes, including standing, stepping, and voluntary movement. Cohort 2 n = 5) was implanted to assess cardiovascular function. This cohort also trained for voluntary movement and standing. Individuals in Cohort 3 (n = 12) were implanted as part of a prospective randomized control trial evaluating the effect of scES on cardiovascular function and voluntary movement.
All research participants underwent scES surgery using a 16-electrode epidural paddle and internal pulse generator (IPG) (Medtronic RestoreAdvanced™ or Intellis™). One surgeon performed the first four procedures, and the first author Maxwell Boakye performed the subsequent 21.
To reduce infection risk, 11 essential personnel were allowed in the operating room (OR): the anesthesiology attending, anesthesiology resident or nurse anesthetist, attending neurosurgeon, resident neurosurgeon, surgical technologist, circulating nurse, fluoroscopy technician, research principal investigator, research acquisition technician, research engineer, and the Medtronic representative. After surgical incision, only nurses and the anesthesiologist could exit/enter the OR for essential activities. Antibiotics were administered within 30 min of the incision.
Following intubation and induction of anesthesia, the participant was positioned prone on a radiolucent Jackson table with a Wilson frame. A midline incision extending from T11-L2, typically centered on the L1-L2 disc space, was marked using anterior-posterior and lateral fluoroscopy. A subperiosteal exposure of the lamina from T12 to L2 was performed. Fluoroscopy confirmed the L1-L2 disc space. Bilateral laminotomies were executed, usually at L1-L2, though this varied by 1-2 levels based on the level of the conus medullaris. The ligamentum flavum was removed. The caudal edge of the L1 lamina was undercut to enable a shallower approach angle for smooth passage of the electrode array (Medtronic Specify® 5-6-5 lead) into the epidural space [
Surgical techniques. Illustration of surgical technique. A laminotomy is performed L1-2 (or adjacent level depending on the level of the conus) to allow passage of the paddle electrode into the epidural space (ribs not depicted). Intraoperative fluoroscopic image showing final midline positioning of the electrode between T11 and L1 vertebrae. Epidural stimulator sleeves shown exiting the epidural space. White silicon anchors secure the leads. A strain relief loop was left between the anchors and the exit point of the epidural space when possible. 2-0 silk sutures anchored the leads to the fascia, where a strain relief loop was typically placed. Leads were tunneled to a posterior flank site for the internal pulse generator Image showing postoperative incisions in midline and posterior flank.
Tisseel® fibrin sealant (Baxter, Deerfield, IL, USA) was applied on top of the paddle as an additional means of securing it. Vancomycin-saline irrigation was used throughout the case and before closure. The IPG was placed in a TYRX™ antibacterial envelope (contains Minocycline and Rifampin) starting with patient 12.[
Intraoperative electrophysiological testing
In the preoperative area on the day of surgery, the electrophysiology team placed bilateral surface electrodes over the muscle bellies of the soleus, medial gastrocnemius, tibialis anterior, medial hamstrings, rectus femoris, and vastus lateralis.[
Intraoperative electrophysiology testing. Initial testing of Rostral and Caudal electrode configurations to assess activation sequence of lower extremity muscles. Fluoroscopy shows initial placement of the electrode paddle. Re-testing of rostral and caudal electrode configurations following movement of electrode paddle to optimize activation of rostral muscles. Fluoroscopy shows final placement of electrode paddle. Muscles: IL: Iliopsoas, RF: Rectus femoris, VL: Vastus lateralis, MH: Medial hamstrings, TA: Tibialis anterior, MG: Medial gastrocnemius, SOL: Soleus, STIM: Stimulation pulse.
Postoperative protocol and follow-up
Perioperative complications are included in
Following clearance, spatial-temporal neurophysiological mapping was performed every other day. Functional and physiological mapping were performed as previously described.[
After the laboratory training portion of the study, participants were assessed for their ability to perform tasks independently outside the laboratory environment. Each participant was asked to demonstrate the safe performance of each task without the assistance of the research team. Stimulation programs for functional and physiological outcomes that they could perform safely and independently were loaded into the participant’s IPG for home use.
Patient-reported QOL outcomes
Patient-reported QOL outcomes were collected using an in-house designed survey of impairment domains based on the International Classification of Functioning, Disability, and Health (ICF) model.[
Assessment of patient satisfaction
Patient satisfaction was assessed using the validated North American Spine Society outcomes questionnaire,[
Rank biserial correlation coefficient was used to evaluate the correlation of patient satisfaction (ordinal variables) with functional outcomes and complications (binary variables). Spearman’s rank-order correlation coefficient was used to assess the correlation of satisfaction with the number of functional outcomes and complications (count variable). The tests were two-sided, and the significance level was set to 5%. Correlation analysis was performed in SAS 9.4 (SAS Inc., Cary, NC).
Of the 25 participants, most (n = 20, 80%) were male with a mean age of 30.9 years (range 19–60 years) [
Perioperative complications within the first 30 days
Two participants (8%) developed infections requiring washout of pus, both approximately 1 month postoperatively [
Long-term complications after 30 days during training
One participant in Cohort 1b sustained a femoral neck fracture during the ninth step training session. Their postoperative course was complicated by an infected hematoma at the hip surgical site approximately 2 weeks postoperatively in the setting of a supratherapeutic INR (5.71) while on coumadin for deep venous thrombosis prophylaxis following hemiarthroplasty. This participant required a washout and was treated with 6 weeks of IV antibiotics. Subsequently, this person was placed on medical hold and was followed by the orthopedic service for an additional 9 months, during which time they had multiple washouts and also sustained a peri-prosthetic femoral fracture. After resolution of infection and revision hemiarthroplasty, they returned to training and completed the protocol without any additional complications.
Two participants had their IPGs upgraded due to end of battery life (EBL) 9 years after implantation. Two additional participants had their entire systems replaced after 7 years due to electrode malfunctions and EBL. Another participant had an IPG surgically repositioned due to the inability to recharge.
The primary outcomes in these research studies were improvements in motor ability and cardiovascular regulation. Improvements in motor function and blood pressure regulation have been described in the previous papers from our center in a much smaller subset of the patients described here.[
QOL improvements and correlation with training, functional improvement, and complications
Impairment domain survey results were available in 20 research participants [
All participants in Cohort 1 had their expectations either met (33.3%) or exceeded (66.7%) in an upward trend, compared to other groups, yielding a significant low positive correlation (rank-biserial correlation r = 0.452, P = 0.0452). One participant elected not to continue practice of voluntary leg movement. The expectations were not met; however, they reported that QOL had increased and would undergo the procedure again. Those who gained this function had higher probabilities of having their expectations met. There was also one participant who did not gain voluntary core function. This individual reported that the expectations were exceeded, that QOL had increased, and that they would undergo the procedure again. Forty-seven percentages (47%) of those who gained the voluntary core function (n = 19) had their expectations met, and for 36.8%, was exceeded.
There were six participants with one complications and one with two complications (a total of 7/20). Six of them had their expectations met or exceed; for three, QOL improved less than they hoped; but they would all undergo the surgery again. There were three individuals for whom expectations were not met. They felt better after the procedure and would all undergo the procedure again. Only one of them had a complication (infection requiring washout and resulting in permanent antibiotic treatment). Overall, there was no correlation between satisfaction and occurrence of complications. For dehiscence resulting in wound washout and seroma complications, the distribution of QOL improvement yielded a high negative correlation between the two events (rank-biserial correlation r = −0.842, P < 0.0001), that is, higher probability of having QOL improved as or more than hoped for those who did not experience those complications.
In this series of scES for neuromodulation of motor and blood pressure regulation after tSCI, all participants achieved voluntary control of lower limb movement. Two participants achieved overground ambulation. All participants who initially had blood pressure instability at the end of the study could integrate it into their daily lives and regulate blood pressure independently. Improvements in motor and cardiovascular function were consistent with previously reported preliminary results.[
Due to immunological and inflammatory abnormalities and neurogenic immune system dysfunction, persons with SCI are highly susceptible to infections and wound complications. Infections (n = 2) and wound dehiscence and seroma (n = 3) were the most common complications with one research participant requiring permanent removal of the implant due to infection. The overall infection rate of 8% is comparable to previously reported rates for spinal cord stimulator (SCS) implants in the chronic pain population.[
We have previously published our protocol for reducing infections after scES.[
After any intervention, especially one like scES, it is critical to monitor the direct effect of neurological and functional change on the specific outcome measures proposed. ScES improved motor functions previously,[
The electrode was positioned satisfactorily in most research participants through an L1-L2 laminotomy. Intraoperative electrophysiological mapping guided the optimal position. In addition, and more recently high-resolution, magnetic resonance imaging was used to delineate the conus medullaris [
Overall, except for the hip fracture, most of the complication rates reported here were transient and consistent with reported results after SCS placement for pain.[
In contrast to a recent paper,[
Assessment of risks and benefits is a cornerstone in evaluating neuromodulatory therapies for chronic neurological conditions. Deep brain stimulation, approved for the treatment of movement disorders,[
Strengths and limitations
One of the strengths of this study is the sample size, and it is the first to measure multiple patient-reported outcomes. Although the follow-up was variable, most patients had at least a 1-year follow-up, and 13 had >2-year follow-up. Furthermore, there was 80% survey response rate, so we have no information on outcomes in all participants. Most individuals continue to use the stimulator and report benefits exemplifying the durability of results. Although this is the most extensive series to date, the overall number of research participants is small, and additional multicenter studies are needed. Several other benefits remain to be quantified, including but not limited to benefits on bowel motility, systemic inflammation, metabolic syndromes, bone density, cognitive and mental health, immune health, infection frequency, and overall cost-effectiveness.
scES in patients with tSCI achieved numerous functional benefits on lower extremity function, patient-reported outcomes, and patient satisfaction, making it a most promising therapeutic strategy. Postoperative complications were primarily minor (except the hip fracture) and transient and have not influenced longer-term satisfaction with the procedure. Strict adherence to a preoperative, intraoperative, and postoperative protocol minimized postoperative infections and postoperative seromas. Utilization of high level of body weight support and slow speeds during the initial sessions of Step-scES is recommended to minimize fractures. Well-designed clinical trials are needed to build on these results to elucidate the role of scES in tSCI and ultimately streamline regulatory approval and make scES more accessible to patients with tSCI.
Data availability statement
Data are available on reasonable request from the authors.
Declaration of patient consent
Patient’s consent not required as patients identity is not disclosed or compromised.
Financial support and sponsorship
The National Institutes of Health (NIBIB) in funding under award 1R01EB007615.The Christopher and Dana Reeve Foundation, Kessler Foundation, Leona M. and Harry B. Helmsley Charitable Trust, Craig H. Neilsen Foundation, University of Louisville Hospital UofL Health, and Medtronic plc. Dr. Boakye is supported by the Ole A., Mabel Wise & Wilma Nelson endowment. Dr. Harkema is supported by the Owsley B. Frazier Chair in Neurological Rehabilitation endowment.
Conflicts of interest
There are no conflicts of interest.
The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Journal or its management. The information contained in this article should not be considered to be medical advice; patients should consult their own physicians for advice as to their specific medical needs.
1. Abdullah KG, Chen HI, Lucas TH. Safety of topical vancomycin powder in neurosurgery. Surg Neurol Int. 2016. 7: S919-26
2. Alizadeh A, Dyck SM, Karimi-Abdolrezaee S. Traumatic spinal cord injury: An overview of pathophysiology, models and acute injury mechanisms. Front Neurol. 2019. 10: 282
3. Angeli CA, Boakye M, Morton RA, Vogt J, Benton K, Chen Y. Recovery of over-ground walking after chronic motor complete spinal cord injury. N Engl J Med. 2018. 379: 1244-50
4. Arnold FW, Bishop S, Johnson D, Scott L, Heishman C, Oppy L. Root cause analysis of epidural spinal cord stimulator implant infections with resolution after implementation of an improved protocol for surgical placement. J Infect Prev. 2019. 20: 185-90
5. Aslan SC, Ditterline BE, Park MC, Angeli CA, Rejc E, Chen Y. 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
6. Beck L, Veith D, Linde M, Gill M, Calvert J, Grahn P. 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. p. 1-6
7. Bendel MA, O’Brien T, Hoelzer BC, Deer TR, Pittelkow TP, Costandi S. Spinal cord stimulator related infections: Findings From a multicenter retrospective analysis of 2737 implants. Neuromodulation. 2017. 20: 553-7
8. Binder H. Traumatic spinal cord injury. Handb Clin Neurol. 2013. 110: 411-26
9. Carlozzi NE, Fyffe D, Morin KG, Byrne R, Tulsky DS, Victorson D. 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: 1721-30
10. Chiaravalloti ND, Weber E, Wylie G, Dyson-Hudson T, Wecht JM. Patterns of cognitive deficits in persons with spinal cord injury as compared with both age-matched and older individuals without spinal cord injury. J Spinal Cord Med. 2020. 43: 88-97
11. Darrow D, Balser D, Netoff TI, Krassioukov A, Phillips A, Parr A. 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: 2325-36
12. Dietz N, Neimat J. Neuromodulation: Deep brain stimulation for treatment of dystonia. Neurosurg Clin N Am. 2019. 30: 161-8
13. Dietz N, Sharma M, Adams S, Alhourani A, Ugiliweneza B, Wang D. Enhanced recovery after surgery (ERAS) for spine surgery: A systematic review. World Neurosurg. 2019. 130: 415-26
14. Dietz N, Vaitheesh J, Alkin V, Mettille J, Boakye M, Drazin D. Machine learning in clinical diagnosis, prognostication, and management of acute traumatic spinal cord injury (SCI): A systematic review. J Clin Orthop Trauma. 2022. 35: 102046
15. Dietz N, Wagers S, Harkema SJ, D’Amico JM. Intrathecal and oral baclofen use in adults with spinal cord injury: A systematic review of efficacy in spasticity reduction, functional changes, dosing, and adverse events. Arch Phys Med Rehabil. 2022. 104: 119-31
16. Dohrmann GJ, Mansour N. Long-term results of various operations for lumbar disc herniation: Analysis of over 39,000 patients. Med Princ Pract. 2015. 24: 285-90
17. Doshi PK, Rai N, Das D. Surgical and hardware complications of deep brain stimulation-a single surgeon experience of 519 cases over 20 years. Neuromodulation. 2021. 25: 895-903
18. Edgerton VR, Harkema S. Epidural stimulation of the spinal cord in spinal cord injury: Current status and future challenges. Expert Rev Neurother. 2011. 11: 1351-3
19. Eldahan KC, Rabchevsky AG. Autonomic dysreflexia after spinal cord injury: Systemic pathophysiology and methods of management. Auton Neurosci. 2018. 209: 59-70
20. Engel K, Huckhagel T, Gulberti A, Potter-Nerger M, Vettorazzi E, Hidding U. Towards unambiguous reporting of complications related to deep brain stimulation surgery: A retrospective single-center analysis and systematic review of the literature. PLoS One. 2018. 13: e0198529
21. Forrest GF, Sisto SA, Barbeau H, Kirshblum SC, Wilen J, Bond Q. Neuromotor and musculoskeletal responses to locomotor training for an individual with chronic motor complete AIS-B spinal cord injury. J Spinal Cord Med. 2008. 31: 509-21
22. Gill ML, Grahn PJ, Calvert JS, Linde MB, Lavrov IA, Strommen JA. Neuromodulation of lumbosacral spinal networks enables independent stepping after complete paraplegia. Nat Med. 2018. 24: 1677-82
23. Gosset N, Dietz N. Unlocking pain: Deep brain stimulation might be the key to easing depression and chronic pain. IEEE Pulse. 2015. 6: 16-20
24. Harkema S, Gerasimenko Y, Hodes J, Burdick J, Angeli C, Chen Y. 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: 1938-47
25. Harkema SJ, Wang S, Angeli CA, Chen Y, Boakye M, Ugiliweneza B. Normalization of blood pressure with spinal cord epidural stimulation after severe spinal cord injury. Front Hum Neurosci. 2018. 12: 83
26. Herman R, He J, D’Luzansky S, Willis W, Dilli S. Spinal cord stimulation facilitates functional walking in a chronic, incomplete spinal cord injured. Spinal Cord. 2002. 40: 65-8
27. Jain NB, Ayers GD, Peterson EN, Harris MB, Morse L, O’Connor KC. Traumatic spinal cord injury in the United States, 1993-2012. JAMA. 2015. 313: 2236-43
28. Kantzanou M, Korfias S, Panourias I, Sakas DE, Karalexi MA. Deep brain stimulation-related surgical site infections: A systematic review and meta-analysis. Neuromodulation. 2021. 24: 197-211
29. Kostanjsek N. Use of The international classification of functioning, disability and health (ICF) as a conceptual framework and common language for disability statistics and health information systems. BMC Public Health. 2011. 11: S3
30. Lasfargues JE, Custis D, Morrone F, Carswell J, Nguyen T. A model for estimating spinal cord injury prevalence in the United States. Paraplegia. 1995. 33: 62-8
31. Lattig F, Grob D, Kleinstueck FS, Porchet F, Jeszenszky D, Bartanusz V. Ratings of global outcome at the first postoperative assessment after spinal surgery: How often do the surgeon and patient agree?. Eur Spine J. 2009. 18: 386-94
32. Maher JL, McMillan DW, Nash MS. Exercise and health-related risks of physical deconditioning after spinal cord injury. Top Spinal Cord Inj Rehabil. 2017. 23: 175-87
33. Mesbah S, Ball T, Angeli C, Rejc E, Dietz N, Ugiliweneza B. Predictors of volitional motor recovery with epidural stimulation in individuals with chronic spinal cord injury. Brain. 2020. 144: 420-33
34. Molina B, Segura A, Serrano JP, Alonso FJ, Molina L, Perez-Borrego YA. Cognitive performance of people with traumatic spinal cord injury: A cross-sectional study comparing people with subacute and chronic injuries. Spinal Cord. 2018. 56: 796-805
35. Molina-Gallego B, Gomez-Cantarino S, UgarteGurrutxaga MI, Molina-Gallego L, Mordillo-Mateos L. Neuropsychological study in patients with spinal cord injuries. Healthcare (Basel). 2021. 9: 241
36. National Spinal Cord Injury Statistical Center. Facts and Figures at a Glance. Available from: https://www.nscisc.uab.edu/public/factsandfigures-2021.pdf [Last accessed on 2023 Feb 04].
37. Nightingale TE, Zheng MM, Sachdeva R, Phillips AA, Krassioukov AV. Diverse cognitive impairment after spinal cord injury is associated with orthostatic hypotension symptom burden. Physiol Behav. 2020. 213: 112742
38. Parker SL, Devin CJ. Commentary on: Sterile seroma resulting from multilevel XLIF procedure as possible adverse effect of prophylactic vancomycin powder: A case report. Evid Based Spine Care J. 2014. 5: 134-5
39. Pose B, Sangha O, Peters A, Wildner M. Validation of the North American Spine Society Instrument for assessment of health status in patients with chronic backache. Z Orthop Ihre Grenzgeb. 1999. 137: 437-41
40. 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: e0133998
41. 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: 1787-802
42. Sarasqueta C, Gabaldon O, Iza I, Beland F, Paz PM. Cross-cultural adaptation and validation of the NASS outcomes instrument in Spanish patients with low back pain. Eur Spine J. 2005. 14: 586-94
43. Sdrulla AD, Guan Y, Raja SN. Spinal cord stimulation: Clinical efficacy and potential mechanisms. Pain Pract. 2018. 18: 1048-67
44. Shamji MF, Westwick HJ, Heary RF. Complications related to the use of spinal cord stimulation for managing persistent postoperative neuropathic pain after lumbar spinal surgery. Neurosurg Focus. 2015. 39: E15
45. Sigmundsson FG, Jonsson B, Stromqvist B. Determinants of patient satisfaction after surgery for central spinal stenosis without concomitant spondylolisthesis: A register study of 5100 patients. Eur Spine J. 2017. 26: 473-80
46. Taccola G, Barber S, Horner PJ, Bazo HA, Sayenko D. Complications of epidural spinal stimulation: lessons from the past and alternatives for the future. Spinal Cord. 2020. 58: 1049-59
47. Wagner FB, Mignardot JB, Le Goff-Mignardot CG, Demesmaeker R, Komi S, Capogrosso M. Targeted neurotechnology restores walking in humans with spinal cord injury. Nature. 2018. 563: 65-71
48. West CR, Phillips AA, Squair JW, Williams AM, Walter M, Lam T. Association of epidural stimulation with cardiovascular function in an individual with spinal cord injury. JAMA Neurol. 2018. 75: 630-2