Download PDF
Semin Neurol 2021; 41(03): 247-255
DOI: 10.1055/s-0041-1725125
Review Article

Traumatic Spinal Cord Disorders: Current Topics and Future Directions

Kevin T. Huang 
1   Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
,
Yi Lu
1   Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
› Author Affiliations
› Further Information
    Permissions and Reprints

Abstract

Traumatic spinal cord injury (tSCI) is a life-changing and potentially overwhelming event. The sudden disruption of the spinal cord's integrity necessitates rapid attention at a specialized medical center, and involves a multilateral collaboration between neurologists, spine surgeons, critical care physicians, and trauma specialists. Even with care under ideal conditions, many tSCI patients have significant disability that persists for the rest of their lives. However, recently, we have seen a proliferation in clinical and translational trials that offer the promise that new treatments may be available soon.

Keywords

spinal cord injury - spine surgery - traumatic spinal cord injury


Publication History

Article published online:
19 May 2021

© 2021. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Jain NB, Ayers GD, Peterson EN. et al. Traumatic spinal cord injury in the United States, 1993-2012. JAMA 2015; 313 (22) 2236-2243
    CrossrefPubMedGoogle Scholar
  • 2 Jazayeri SB, Beygi S, Shokraneh F, Hagen EM, Rahimi-Movaghar V. Incidence of traumatic spinal cord injury worldwide: a systematic review. Eur Spine J 2015; 24 (05) 905-918
    CrossrefPubMedGoogle Scholar
  • 3 Lee BB, Cripps RA, Fitzharris M, Wing PC. The global map for traumatic spinal cord injury epidemiology: update 2011, global incidence rate. Spinal Cord 2014; 52 (02) 110-116
    CrossrefPubMedGoogle Scholar
  • 4 Singh A, Tetreault L, Kalsi-Ryan S, Nouri A, Fehlings MG. Global prevalence and incidence of traumatic spinal cord injury. Clin Epidemiol 2014; 6: 309-331
    Google Scholar
  • 5 GBD 2016 Traumatic Brain Injury and Spinal Cord Injury Collaborators. Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2019; 18 (01) 56-87
    CrossrefPubMedGoogle Scholar
  • 6 Chen Y, He Y, DeVivo MJ. Changing demographics and injury profile of new traumatic spinal cord injuries in the United States, 1972-2014. Arch Phys Med Rehabil 2016; 97 (10) 1610-1619
    CrossrefPubMedGoogle Scholar
  • 7 Devivo MJ. Epidemiology of traumatic spinal cord injury: trends and future implications. Spinal Cord 2012; 50 (05) 365-372
    CrossrefPubMedGoogle Scholar
  • 8 Strauss DJ, Devivo MJ, Paculdo DR, Shavelle RM. Trends in life expectancy after spinal cord injury. Arch Phys Med Rehabil 2006; 87 (08) 1079-1085
    CrossrefPubMedGoogle Scholar
  • 9 Antevil JL, Sise MJ, Sack DI, Kidder B, Hopper A, Brown CV. Spiral computed tomography for the initial evaluation of spine trauma: a new standard of care?. J Trauma 2006; 61 (02) 382-387
    CrossrefPubMedGoogle Scholar
  • 10 Alderson P, Roberts I. Corticosteroids for acute traumatic brain injury. Cochrane Database Syst Rev 2005; (01) CD000196
    PubMedGoogle Scholar
  • 11 Bracken MB, Shepard MJ, Collins WF. et al. A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study. N Engl J Med 1990; 322 (20) 1405-1411
    CrossrefPubMedGoogle Scholar
  • 12 Bracken MB, Shepard MJ, Holford TR. et al. Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study. JAMA 1997; 277 (20) 1597-1604
    CrossrefPubMedGoogle Scholar
  • 13 Hurlbert RJ, Hadley MN, Walters BC. et al. Pharmacological therapy for acute spinal cord injury. Neurosurgery 2015; 76 (Suppl. 01) S71-S83
    CrossrefPubMedGoogle Scholar
  • 14 Coleman WP, Benzel D, Cahill DW. et al. A critical appraisal of the reporting of the National Acute Spinal Cord Injury Studies (II and III) of methylprednisolone in acute spinal cord injury. J Spinal Disord 2000; 13 (03) 185-199
    CrossrefPubMedGoogle Scholar
  • 15 Nesathurai S. Steroids and spinal cord injury: revisiting the NASCIS 2 and NASCIS 3 trials. J Trauma 1998; 45 (06) 1088-1093
    CrossrefPubMedGoogle Scholar
  • 16 Sunshine JE, Dagal A, Burns SP. et al. Methylprednisolone therapy in acute traumatic spinal cord injury: analysis of a regional spinal cord model systems database. Anesth Analg 2017; 124 (04) 1200-1205
    CrossrefPubMedGoogle Scholar
  • 17 Evaniew N, Noonan VK, Fallah N. et al; RHSCIR Network. Methylprednisolone for the treatment of patients with acute spinal cord injuries: a propensity score-matched cohort study from a Canadian Multi-Center Spinal Cord Injury Registry. J Neurotrauma 2015; 32 (21) 1674-1683
    CrossrefPubMedGoogle Scholar
  • 18 Fehlings MG, Wilson JR, Tetreault LA. et al. A clinical practice guideline for the management of patients with acute spinal cord injury: recommendations on the use of methylprednisolone sodium succinate. Global Spine J 2017; 7 (3, Suppl): 203S-211S
    CrossrefPubMedGoogle Scholar
  • 19 Vale FL, Burns J, Jackson AB, Hadley MN. Combined medical and surgical treatment after acute spinal cord injury: results of a prospective pilot study to assess the merits of aggressive medical resuscitation and blood pressure management. J Neurosurg 1997; 87 (02) 239-246
    CrossrefPubMedGoogle Scholar
  • 20 Wolf A, Levi L, Mirvis S. et al. Operative management of bilateral facet dislocation. J Neurosurg 1991; 75 (06) 883-890
    CrossrefPubMedGoogle Scholar
  • 21 Hawryluk G, Whetstone W, Saigal R. et al. Mean arterial blood pressure correlates with neurological recovery after human spinal cord injury: analysis of high frequency physiologic data. J Neurotrauma 2015; 32 (24) 1958-1967
    CrossrefPubMedGoogle Scholar
  • 22 Levi L, Wolf A, Belzberg H. Hemodynamic parameters in patients with acute cervical cord trauma: description, intervention, and prediction of outcome. Neurosurgery 1993; 33 (06) 1007-1016 , discussion 1016–1017
    PubMedGoogle Scholar
  • 23 Saadeh YS, Smith BW, Joseph JR. et al. The impact of blood pressure management after spinal cord injury: a systematic review of the literature. Neurosurg Focus 2017; 43 (05) E20
    CrossrefPubMedGoogle Scholar
  • 24 O'Toole JE, Kaiser MG, Anderson PA. et al. Congress of neurological surgeons systematic review and evidence-based guidelines on the evaluation and treatment of patients with thoracolumbar spine trauma: executive summary. Neurosurgery 2019; 84 (01) 2-6
    CrossrefPubMedGoogle Scholar
  • 25 Nori S, Ahuja CS, Fehlings MG. Translational advances in the management of acute spinal cord injury: What is new? What is hot?. Neurosurgery 2017; 64 (CN_suppl_1): 119-128
    CrossrefPubMedGoogle Scholar
  • 26 Alkabie S, Boileau AJ. The role of therapeutic hypothermia after traumatic spinal cord injury--a systematic review. World Neurosurg 2016; 86: 432-449
    CrossrefPubMedGoogle Scholar
  • 27 Dididze M, Green BA, Dietrich WD, Vanni S, Wang MY, Levi AD. Systemic hypothermia in acute cervical spinal cord injury: a case-controlled study. Spinal Cord 2013; 51 (05) 395-400
    CrossrefPubMedGoogle Scholar
  • 28 Hansebout RR, Hansebout CR. Local cooling for traumatic spinal cord injury: outcomes in 20 patients and review of the literature. J Neurosurg Spine 2014; 20 (05) 550-561
    CrossrefPubMedGoogle Scholar
  • 29 Fehlings MG, Vaccaro A, Wilson JR. et al. Early versus delayed decompression for traumatic cervical spinal cord injury: results of the Surgical Timing in Acute Spinal Cord Injury Study (STASCIS). PLoS One 2012; 7 (02) e32037
    Google Scholar
  • 30 Grassner L, Wutte C, Klein B. et al. Early decompression (< 8 h) after traumatic cervical spinal cord injury improves functional outcome as assessed by spinal cord independence measure after one year. J Neurotrauma 2016; 33 (18) 1658-1666
    CrossrefPubMedGoogle Scholar
  • 31 Jug M, Kejžar N, Vesel M. et al. Neurological recovery after traumatic cervical spinal cord injury is superior if surgical decompression and instrumented fusion are performed within 8 hours versus 8 to 24 hours after injury: a single center experience. J Neurotrauma 2015; 32 (18) 1385-1392
    CrossrefPubMedGoogle Scholar
  • 32 Dvorak MF, Noonan VK, Fallah N. et al; RHSCIR Network. The influence of time from injury to surgery on motor recovery and length of hospital stay in acute traumatic spinal cord injury: an observational Canadian cohort study. J Neurotrauma 2015; 32 (09) 645-654
    CrossrefPubMedGoogle Scholar
  • 33 Bourassa-Moreau É, Mac-Thiong J-M, Li A. et al. Do patients with complete spinal cord injury benefit from early surgical decompression? Analysis of neurological improvement in a prospective cohort study. J Neurotrauma 2016; 33 (03) 301-306
    CrossrefPubMedGoogle Scholar
  • 34 Fehlings MG, Rabin D, Sears W, Cadotte DW, Aarabi B. Current practice in the timing of surgical intervention in spinal cord injury. Spine 2010; 35 (21, Suppl): S166-S173
    CrossrefPubMedGoogle Scholar
  • 35 Geisler FH, Dorsey FC, Coleman WP. Recovery of motor function after spinal-cord injury--a randomized, placebo-controlled trial with GM-1 ganglioside. N Engl J Med 1991; 324 (26) 1829-1838
    CrossrefPubMedGoogle Scholar
  • 36 Geisler FH, Coleman WP, Grieco G, Poonian D. Sygen Study Group. The Sygen multicenter acute spinal cord injury study. Spine 2001; 26 (24, Suppl): S87-S98
    CrossrefPubMedGoogle Scholar
  • 37 Grossman RG, Fehlings MG, Frankowski RF. et al. A prospective, multicenter, phase I matched-comparison group trial of safety, pharmacokinetics, and preliminary efficacy of riluzole in patients with traumatic spinal cord injury. J Neurotrauma 2014; 31 (03) 239-255
    CrossrefPubMedGoogle Scholar
  • 38 Fehlings MG, Nakashima H, Nagoshi N, Chow DS, Grossman RG, Kopjar B. Rationale, design and critical end points for the Riluzole in Acute Spinal Cord Injury Study (RISCIS): a randomized, double-blinded, placebo-controlled parallel multi-center trial. Spinal Cord 2016; 54 (01) 8-15
    CrossrefPubMedGoogle Scholar
  • 39 Stirling DP, Khodarahmi K, Liu J. et al. Minocycline treatment reduces delayed oligodendrocyte death, attenuates axonal dieback, and improves functional outcome after spinal cord injury. J Neurosci 2004; 24 (09) 2182-2190
    CrossrefPubMedGoogle Scholar
  • 40 Teng YD, Choi H, Onario RC. et al. Minocycline inhibits contusion-triggered mitochondrial cytochrome c release and mitigates functional deficits after spinal cord injury. Proc Natl Acad Sci U S A 2004; 101 (09) 3071-3076
    CrossrefPubMedGoogle Scholar
  • 41 Casha S, Zygun D, McGowan MD, Bains I, Yong VW, Hurlbert RJ. Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury. Brain 2012; 135 (Pt 4): 1224-1236
    CrossrefPubMedGoogle Scholar
  • 42 Dergham P, Ellezam B, Essagian C, Avedissian H, Lubell WD, McKerracher L. Rho signaling pathway targeted to promote spinal cord repair. J Neurosci 2002; 22 (15) 6570-6577
    CrossrefPubMedGoogle Scholar
  • 43 Fehlings MG, Theodore N, Harrop J. et al. A phase I/IIa clinical trial of a recombinant Rho protein antagonist in acute spinal cord injury. J Neurotrauma 2011; 28 (05) 787-796
    CrossrefPubMedGoogle Scholar
  • 44 Fehlings MG, Kim KD, Aarabi B. et al. Rho inhibitor VX-210 in acute traumatic subaxial cervical spinal cord injury: design of the SPinal Cord Injury Rho INhibition InvestiGation (SPRING) clinical trial. J Neurotrauma 2018; 35 (09) 1049-1056
    CrossrefPubMedGoogle Scholar
  • 45 Vertex Reports Third-Quarter 2018 Financial Results. BUSINESS WIRE 2018 October 24, 2018
    Google Scholar
  • 46 Ahuja CS, Fehlings M. Concise review: bridging the gap: novel neuroregenerative and neuroprotective strategies in spinal cord injury. Stem Cells Transl Med 2016; 5 (07) 914-924
    CrossrefPubMedGoogle Scholar
  • 47 Kamiya K, Koda M, Furuya T. et al. Neuroprotective therapy with granulocyte colony-stimulating factor in acute spinal cord injury: a comparison with high-dose methylprednisolone as a historical control. Eur Spine J 2015; 24 (05) 963-967
    CrossrefPubMedGoogle Scholar
  • 48 Takahashi H, Yamazaki M, Okawa A. et al. Neuroprotective therapy using granulocyte colony-stimulating factor for acute spinal cord injury: a phase I/IIa clinical trial. Eur Spine J 2012; 21 (12) 2580-2587
    CrossrefPubMedGoogle Scholar
  • 49 Derakhshanrad N, Saberi H, Yekaninejad MS, Joghataei MT, Sheikhrezaei A. Granulocyte-colony stimulating factor administration for neurological improvement in patients with postrehabilitation chronic incomplete traumatic spinal cord injuries: a double-blind randomized controlled clinical trial. J Neurosurg Spine 2018; 29 (01) 97-107
    CrossrefPubMedGoogle Scholar
  • 50 Koda M, Hanaoka H, Sato T. et al. Study protocol for the G-SPIRIT trial: a randomised, placebo-controlled, double-blinded phase III trial of granulocyte colony-stimulating factor-mediated neuroprotection for acute spinal cord injury. BMJ Open 2018; 8 (05) e019083
    CrossrefPubMedGoogle Scholar
  • 51 Ahuja CS, Nori S, Tetreault L. et al. Traumatic spinal cord injury-repair and regeneration. Neurosurgery 2017; 80 (3S): S9-S22
    CrossrefPubMedGoogle Scholar
  • 52 Badhiwala JH, Wilson JR, Kwon BK, Casha S, Fehlings MG. A review of clinical trials in spinal cord injury including biomarkers. J Neurotrauma 2018; 35 (16) 1906-1917
    CrossrefPubMedGoogle Scholar
  • 53 Lukovic D, Stojkovic M, Moreno-Manzano V, Bhattacharya SS, Erceg S. Perspectives and future directions of human pluripotent stem cell-based therapies: lessons from Geron's clinical trial for spinal cord injury. Stem Cells Dev 2014; 23 (01) 1-4
    CrossrefPubMedGoogle Scholar
  • 54 Jin MC, Medress ZA, Azad TD, Doulames VM, Veeravagu A. Stem cell therapies for acute spinal cord injury in humans: a review. Neurosurg Focus 2019; 46 (03) E10
    CrossrefPubMedGoogle Scholar
  • 55 Levi AD, Okonkwo DO, Park P. et al. Emerging safety of intramedullary transplantation of human neural stem cells in chronic cervical and thoracic spinal cord injury. Neurosurgery 2018; 82 (04) 562-575
    CrossrefPubMedGoogle Scholar
  • 56 Cummings BJ, Uchida N, Tamaki SJ. et al. Human neural stem cells differentiate and promote locomotor recovery in spinal cord-injured mice. Proc Natl Acad Sci U S A 2005; 102 (39) 14069-14074
    CrossrefPubMedGoogle Scholar
  • 57 Ghobrial GM, Anderson KD, Dididze M. et al. Human neural stem cell transplantation in chronic cervical spinal cord injury: functional outcomes at 12 months in a phase II clinical trial. Neurosurgery 2017; 64 (CN_suppl_1): 87-91
    CrossrefPubMedGoogle Scholar
  • 58 Levi AD, Anderson KD, Okonkwo DO. et al. Clinical outcomes from a multi-center study of human neural stem cell transplantation in chronic cervical spinal cord injury. J Neurotrauma 2019; 36 (06) 891-902
    CrossrefPubMedGoogle Scholar
  • 59 Temple S, Studer L. Lessons learned from pioneering neural stem cell studies. Stem Cell Reports 2017; 8 (02) 191-193
    CrossrefPubMedGoogle Scholar
  • 60 Dai G, Liu X, Zhang Z, Yang Z, Dai Y, Xu R. Transplantation of autologous bone marrow mesenchymal stem cells in the treatment of complete and chronic cervical spinal cord injury. Brain Res 2013; 1533: 73-79
    CrossrefPubMedGoogle Scholar
  • 61 Karamouzian S, Nematollahi-Mahani SN, Nakhaee N, Eskandary H. Clinical safety and primary efficacy of bone marrow mesenchymal cell transplantation in subacute spinal cord injured patients. Clin Neurol Neurosurg 2012; 114 (07) 935-939
    CrossrefPubMedGoogle Scholar
  • 62 Kang KS, Kim SW, Oh YH. et al. A 37-year-old spinal cord-injured female patient, transplanted of multipotent stem cells from human UC blood, with improved sensory perception and mobility, both functionally and morphologically: a case study. Cytotherapy 2005; 7 (04) 368-373
    CrossrefPubMedGoogle Scholar
  • 63 Nori S, Okada Y, Yasuda A. et al. Grafted human-induced pluripotent stem-cell-derived neurospheres promote motor functional recovery after spinal cord injury in mice. Proc Natl Acad Sci U S A 2011; 108 (40) 16825-16830
    CrossrefPubMedGoogle Scholar
  • 64 Strnadel J, Carromeu C, Bardy C. et al. Survival of syngeneic and allogeneic iPSC-derived neural precursors after spinal grafting in minipigs. Sci Transl Med 2018; 10 (440) 10
    CrossrefPubMedGoogle Scholar
  • 65 Wiliams RR, Bunge MB. Schwann cell transplantation: a repair strategy for spinal cord injury?. Prog Brain Res 2012; 201: 295-312
    CrossrefPubMedGoogle Scholar
  • 66 Anderson KD, Guest JD, Dietrich WD. et al. Safety of autologous human Schwann cell transplantation in subacute thoracic spinal cord injury. J Neurotrauma 2017; 34 (21) 2950-2963
    CrossrefPubMedGoogle Scholar
  • 67 Li L, Adnan H, Xu B. et al. Effects of transplantation of olfactory ensheathing cells in chronic spinal cord injury: a systematic review and meta-analysis. Eur Spine J 2015; 24 (05) 919-930
    CrossrefPubMedGoogle Scholar
  • 68 Teng YD, Lavik EB, Qu X. et al. Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells. Proc Natl Acad Sci U S A 2002; 99 (05) 3024-3029
    CrossrefPubMedGoogle Scholar
  • 69 Theodore N, Hlubek R, Danielson J. et al. First human implantation of a bioresorbable polymer scaffold for acute traumatic spinal cord injury: a clinical pilot study for safety and feasibility. Neurosurgery 2016; 79 (02) E305-E312
    CrossrefPubMedGoogle Scholar
  • 70 Capogrosso M, Milekovic T, Borton D. et al. A brain-spine interface alleviating gait deficits after spinal cord injury in primates. Nature 2016; 539 (7628): 284-288
    CrossrefPubMedGoogle Scholar
  • 71 van den Brand R, Heutschi J, Barraud Q. et al. Restoring voluntary control of locomotion after paralyzing spinal cord injury. Science 2012; 336 (6085): 1182-1185
    CrossrefPubMedGoogle Scholar
  • 72 Gill ML, Grahn PJ, Calvert JS. et al. Neuromodulation of lumbosacral spinal networks enables independent stepping after complete paraplegia. Nat Med 2018; 24 (11) 1677-1682
    CrossrefPubMedGoogle Scholar
  • 73 Angeli CA, Boakye M, Morton RA. et al. Recovery of over-ground walking after chronic motor complete spinal cord injury. N Engl J Med 2018; 379 (13) 1244-1250
    CrossrefPubMedGoogle Scholar
  • 74 Ajiboye AB, Willett FR, Young DR. et al. Restoration of reaching and grasping movements through brain-controlled muscle stimulation in a person with tetraplegia: a proof-of-concept demonstration. Lancet 2017; 389 (10081): 1821-1830
    CrossrefPubMedGoogle Scholar
  • 75 Collinger JL, Boninger ML, Bruns TM, Curley K, Wang W, Weber DJ. Functional priorities, assistive technology, and brain-computer interfaces after spinal cord injury. J Rehabil Res Dev 2013; 50 (02) 145-160
    CrossrefPubMedGoogle Scholar
  • 76 Wolpaw JR, McFarland DJ. Control of a two-dimensional movement signal by a noninvasive brain-computer interface in humans. Proc Natl Acad Sci U S A 2004; 101 (51) 17849-17854
    CrossrefPubMedGoogle Scholar