Recent advances in managing a spinal cord injury secondary to trauma.

F1000Research

Volumn 5, Issue , 2016, Pages

  Ahuja, Christopher S ^a   Martin, Allan R ^a   Fehlings, Michael ^a,b  

^a UNIVERSITY OF TORONTO   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

AC 105; ATI 355; CETHRIN; FIBROBLAST GROWTH FACTOR; GRANULOCYTE COLONY STIMULATING FACTOR; INFUSION FLUID; MAGNESIUM; METHYLPREDNISOLONE; MINOCYCLINE; MONOCLONAL ANTIBODY; NORADRENALIN; PHENYLEPHRINE; RILUZOLE; SUN 13837; UNCLASSIFIED DRUG; VX 210;

BONE MARROW CELL; EMBRYONIC STEM CELL; EPIDURAL STIMULATION; EVIDENCE BASED PRACTICE; FLUID THERAPY; FOLLOW UP; FUNCTIONAL ELECTRICAL STIMULATION; HUMAN; INDUCED HYPOTHERMIA; INDUCED PLURIPOTENT STEM CELL; MEAN ARTERIAL PRESSURE; MESENCHYMAL STEM CELL; META ANALYSIS (TOPIC); MULTICENTER STUDY (TOPIC); NERVE REGENERATION; NERVE STIMULATION; NEUROPROTECTION; NEUROREHABILITATION; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; OLFACTORY ENSHEATHING CELL; PATIENT CARE; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SCHWANN CELL; SPINAL CORD DECOMPRESSION; SPINAL CORD INJURY; STEM CELL TRANSPLANTATION;

EID: 85010918251     PISSN: None     EISSN: 20461402     Source Type: Journal    
DOI: 10.12688/F1000RESEARCH.7586.1     Document Type: Review

References (108)

1. National Spinal Cord Injury Statistical Center: Spinal cord injury facts and figures at a glance. J Spinal Cord Med. 2014; 37(1): 117-8.
2. Foundation CaDR: One degree of separation: paralysis and spinal cord injury in the United States. 2010.
3. Dvorak MF, Noonan VK, Fallah N, et al.: 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(9): 645-54.
4. Wilson JR, Forgione N, Fehlings MG: Emerging therapies for acute traumatic spinal cord injury. CMAJ. 2013; 185(6): 485-92.
5. LaPlaca MC, Simon CM, Prado GR, et al.: CNS injury biomechanics and experimental models. Prog Brain Res. 2007; 161: 13-26.
6. Choo AM, Liu J, Lam CK, et al.: Contusion, dislocation, and distraction: primary hemorrhage and membrane permeability in distinct mechanisms of spinal cord injury. J Neurosurg Spine. 2007; 6(3): 255-66.
7. Whetstone WD, Hsu JY, Eisenberg M, et al.: Blood-spinal cord barrier after spinal cord injury: relation to revascularization and wound healing. J Neurosci Res. 2003; 74(2): 227-39.
8. Mautes AE, Weinzierl MR, Donovan F, et al.: Vascular events after spinal cord injury: contribution to secondary pathogenesis. Phys Ther. 2000; 80(7): 673-87.
9. Li S, Mealing GA, Morley P, et al.: Novel injury mechanism in anoxia and trauma of spinal cord white matter: glutamate release via reverse Na+-dependent glutamate transport. J Neurosci. 1999; 19(14): RC16.
10. Li S, Stys PK: Mechanisms of ionotropic glutamate receptor-mediated excitotoxicity in isolated spinal cord white matter. J Neurosci. 2000; 20(3): 1190-8.
11. Milhorat TH, Capocelli AL Jr, Anzil AP, et al.: Pathological basis of spinal cord cavitation in syringomyelia: analysis of 105 autopsy cases. J Neurosurg. 1995; 82(5): 802-12.
12. Yuan YM, He C: The glial scar in spinal cord injury and repair. Neurosci Bull. 2013; 29(4): 421-35.
13. Snow DM, Lemmon V, Carrino DA, et al.: Sulfated proteoglycans in astroglial barriers inhibit neurite outgrowth in vitro. Exp Neurol. 1990; 109(1): 111-30.
14. Höke A, Silver J: Proteoglycans and other repulsive molecules in glial boundaries during development and regeneration of the nervous system. Prog Brain Res. 1996; 108: 149-63.
15. Butt AM, Duncan A, Hornby MF, et al.: Cells expressing the NG2 antigen contact nodes of Ranvier in adult CNS white matter. Glia. 1999; 26(1): 84-91.
16. Silver J: Inhibitory molecules in development and regeneration. J Neurol. 1994; 242(1 Suppl 1): S22-4.
17. Forgione N, Fehlings MG: Rho-ROCK inhibition in the treatment of spinal cord injury. World Neurosurg. 2014; 82(3-4): e535-9.
18. Popa C, Popa F, Grigorean VT, et al.: Vascular dysfunctions following spinal cord injury. J Med Life. 2010; 3(3): 275-85.
19. Guha A, Tator CH, Rochon J: Spinal cord blood flow and systemic blood pressure after experimental spinal cord injury in rats. Stroke. 1989; 20(3): 372-7.
20. Riegger T, Conrad S, Schluesener HJ, et al.: Immune depression syndrome following human spinal cord injury (SCI): a pilot study. Neuroscience. 2009; 158(3): 1194-9.
21. Berlly M, Shem K: Respiratory management during the first five days after spinal cord injury. J Spinal Cord Med. 2007; 30(4): 309-18.
22. Resnick DK: Updated Guidelines for the Management of Acute Cervical Spine and Spinal Cord Injury. Neurosurgery. 2013; 72(Suppl 2): 1.
23. 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(2): e32037.
24. Wilson JR, Singh A, Craven C, et al.: Early versus late surgery for traumatic spinal cord injury: the results of a prospective Canadian cohort study. Spinal Cord. 2012; 50(11): 840-3.
25. Bracken MB, Collins WF, Freeman DF, et al.: Efficacy of methylprednisolone in acute spinal cord injury. JAMA. 1984; 251(1): 45-52.
26. 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): 1405-11.
27. 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): 1597-604.
28. Fehlings MG, Wilson JR, Cho N: Methylprednisolone for the treatment of acute spinal cord injury: counterpoint. Neurosurgery. 2014; 61(Suppl 1): 36-42.
29. Ryken TC, Hadley MN, Walters BC, et al.: Radiographic assessment. Neurosurgery. 2013; 72(Suppl 2): 54-72.
30. Sixta S, Moore FO, Ditillo MF, et al.: Screening for thoracolumbar spinal injuries in blunt trauma: an Eastern Association for the Surgery of Trauma practice management guideline. J Trauma Acute Care Surg. 2012; 73(5 Suppl 4): S326-32.
31. Bozzo A, Marcoux J, Radhakrishna M, et al.: The role of magnetic resonance imaging in the management of acute spinal cord injury. J Neurotrauma. 2011; 28(8): 1401-11.
32. Clinical Trials.gov. 2015; Accessed December 21, 2015.
33. Bracken MB: Steroids for acute spinal cord injury. Cochrane Database Syst Rev. John Wiley & Sons, Ltd; 2012; 1: CD001046.
34. Stroman PW, Wheeler-Kingshott C, Bacon M, et al.: The current state-of-the-art of spinal cord imaging: methods. Neuroimage. 2014; 84: 1070-81.
35. Martin AR, Aleksanderek I, Cohen-Adad J, et al.: Translating state-of-the-art spinal cord MRI techniques to clinical use: A systematic review of clinical studies utilizing DTI, MT, MWF, MRS, and fMRI. Neuroimage Clin. 2016; 10: 192-238.
36. Kwon BK, Mann C, Sohn HM, et al.: Hypothermia for spinal cord injury. Spine J. 2008; 8(6): 859-74.
37. Hypothermia after Cardiac Arrest Study Group: Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002; 346(8): 549-56.
38. Dehaes M, Aggarwal A, Lin PY, et al.: Cerebral oxygen metabolism in neonatal hypoxic ischemic encephalopathy during and after therapeutic hypothermia. J Cereb Blood Flow Metab. 2014; 34(1): 87-94.
39. Dingley J, Tooley J, Liu X, et al.: Xenon ventilation during therapeutic hypothermia in neonatal encephalopathy: a feasibility study. Pediatrics. 2014; 133(5): 809-18.
40. Lo TP Jr, Cho KS, Garg MS, et al.: Systemic hypothermia improves histological and functional outcome after cervical spinal cord contusion in rats. J Comp Neurol. 2009; 514(5): 433-48.
41. Levi AD, Green BA, Wang MY, et al.: Clinical application of modest hypothermia after spinal cord injury. J Neurotrauma. 2009; 26(3): 407-15.
42. Paralysis TMPtC: Neuroprotection-therapeutic hypothermia. 2014; Accessed October 15, 2015.
43. Schwartz G, Fehlings MG: Evaluation of the neuroprotective effects of sodium channel blockers after spinal cord injury: improved behavioral and neuroanatomical recovery with riluzole. J Neurosurg. 2001; 94(2 Suppl): 245-56.
44. Bensimon G, Lacomblez L, Meininger V: A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group. N Engl J Med. 1994; 330(9): 585-91.
45. 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(3): 239-55.
46. Wells JE, Hurlbert RJ, Fehlings MG, et al.: Neuroprotection by minocycline facilitates significant recovery from spinal cord injury in mice. Brain. 2003; 126(Pt 7): 1628-37.
47. Festoff BW, Ameenuddin S, Arnold PM, et al.: Minocycline neuroprotects, reduces microgliosis, and inhibits caspase protease expression early after spinal cord injury. J Neurochem. 2006; 97(5): 1314-26.
48. Casha S, Zygun D, McGowan MD, et al.: Results of a phase II placebocontrolled randomized trial of minocycline in acute spinal cord injury. Brain. 2012; 135(Pt 4): 1224-36.
49. Siddiqui AM, Khazaei M, Fehlings MG: Translating mechanisms of neuroprotection, regeneration, and repair to treatment of spinal cord injury. Prog Brain Res. 2015; 218: 15-54.
50. Kawabe J, Koda M, Hashimoto M, et al.: Neuroprotective effects of granulocyte colony-stimulating factor and relationship to promotion of angiogenesis after spinal cord injury in rats: laboratory investigation. J Neurosurg Spine. 2011; 15(4): 414-21.
51. 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(5): 963-7.
52. 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): 2580-7.
53. Kwon BK, Roy J, Lee JH, et al.: Magnesium chloride in a polyethylene glycol formulation as a neuroprotective therapy for acute spinal cord injury: preclinical refinement and optimization. J Neurotrauma. 2009; 26(8): 1379-93.
54. Luo J, Borgens R, Shi R: Polyethylene glycol immediately repairs neuronal membranes and inhibits free radical production after acute spinal cord injury. J Neurochem. 2002; 83(2): 471-80.
55. Kaptanoglu E, Beskonakli E, Solaroglu I, et al.: Magnesium sulfate treatment in experimental spinal cord injury: emphasis on vascular changes and early clinical results. Neurosurg Rev. 2003; 26(4): 283-7.
56. Liebscher T, Schnell L, Schnell D, et al.: Nogo-A antibody improves regeneration and locomotion of spinal cord-injured rats. Ann Neurol. 2005; 58(5): 706-19.
57. Freund P, Schmidlin E, Wannier T, et al.: Nogo-A-specific antibody treatment enhances sprouting and functional recovery after cervical lesion in adult primates. Nat Med. 2006; 12(7): 790-2.
58. 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(5): 787-96.
59. Bradbury EJ, Moon LD, Popat RJ, et al.: Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature. 2002; 416(6881): 636-40.
60. Karimi-Abdolrezaee S, Eftekharpour E, Wang J, et al.: Synergistic effects of transplanted adult neural stem/progenitor cells, chondroitinase, and growth factors promote functional repair and plasticity of the chronically injured spinal cord. J Neurosci. 2010; 30(5): 1657-76.
61. Zhang T, Shen Y, Lu L, et al.: [Effect of chondroitinase ABC on axonal myelination and glial scar after spinal cord injury in rats]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2013; 27(2): 145-50.
62. Ikegami T, Nakamura M, Yamane J, et al.: Chondroitinase ABC combined with neural stem/progenitor cell transplantation enhances graft cell migration and outgrowth of growth-associated protein-43-positive fibers after rat spinal cord injury. Eur J Neurosci. 2005; 22(12): 3036-46.
63. Arriola A, Kiel ME, Shi Y, et al.: Adjunctive MSCs enhance myelin formation by xenogenic oligodendrocyte precursors transplanted in the retina. Cell Res. 2010; 20(6): 728-31.
64. Wang L, Shi J, van Ginkel FW, et al.: Neural stem/progenitor cells modulate immune responses by suppressing T lymphocytes with nitric oxide and prostaglandin E2. Exp Neurol. 2009; 216(1): 177-83.
65. Okamura RM, Lebkowski J, Au M, et al.: Immunological properties of human embryonic stem cell-derived oligodendrocyte progenitor cells. J Neuroimmunol. 2007; 192(1-2): 134-44.
66. Shi Y, Desponts C, Do JT, et al.: Induction of pluripotent stem cells from mouse embryonic fibroblasts by Oct4 and Klf4 with small-molecule compounds. Cell Stem Cell. 2008; 3(5): 568-74.
67. Medvedev SP, Shevchenko AI, Zakian SM: Induced Pluripotent Stem Cells: Problems and Advantages when Applying them in Regenerative Medicine. Acta Naturae. 2010; 2(2): 18-28.
68. Iwasaki M, Wilcox JT, Nishimura Y, et al.: Synergistic effects of self-assembling peptide and neural stem/progenitor cells to promote tissue repair and forelimb functional recovery in cervical spinal cord injury. Biomaterials. 2014; 35(9): 2617-29.
69. Karimi-Abdolrezaee S, Eftekharpour E, Wang J, et al.: Delayed transplantation of adult neural precursor cells promotes remyelination and functional neurological recovery after spinal cord injury. J Neurosci. 2006; 26(13): 3377-89.
70. Blesch A, Tuszynski MH: Cellular GDNF delivery promotes growth of motor and dorsal column sensory axons after partial and complete spinal cord transections and induces remyelination. J Comp Neurol. 2003; 467(3): 403-17.
71. Najm FJ, Madhavan M, Zaremba A, et al.: Drug-based modulation of endogenous stem cells promotes functional remyelination in vivo. Nature. 2015; 522(7555): 216-20.
72. Zhang YJ, Zhang W, Lin CG, et al.: Neurotrophin-3 gene modified mesenchymal stem cells promote remyelination and functional recovery in the demyelinated spinal cord of rats. J Neurol Sci. 2012; 313(1-2): 64-74.
73. Salewski RP, Eftekharpour E, Fehlings MG: Are induced pluripotent stem cells the future of cell-based regenerative therapies for spinal cord injury? J Cell Physiol. 2010; 222(3): 515-21.
74. Curt A, Casha S, Fehlings M, et al.: Phase I/II clinical trial of HuCNS-SC cells in chronic thoracic spinal cord injury-interim analysis. 2014; Accessed October 15, 2015.
75. Wiliams RR, Bunge MB: Schwann cell transplantation: a repair strategy for spinal cord injury? Prog Brain Res. 2012; 201: 295-312.
76. Windus LC, Lineburg KE, Scott SE, et al.: Lamellipodia mediate the heterogeneity of central olfactory ensheathing cell interactions. Cell Mol Life Sci. 2010; 67(10): 1735-50.
77. Silva NA, Cooke MJ, Tam RY, et al.: The effects of peptide modified gellan gum and olfactory ensheathing glia cells on neural stem/progenitor cell fate. Biomaterials. 2012; 33(27): 6345-54.
78. Zhang J, Chen H, Duan Z, et al.: The Effects of Co-transplantation of Olfactory Ensheathing Cells and Schwann Cells on Local Inflammation Environment in the Contused Spinal Cord of Rats. Mol Neurobiol. 2016.
79. Ekberg JA, St John JA: Olfactory ensheathing cells for spinal cord repair: crucial differences between subpopulations of the glia. Neural Regen Res. 2015; 10(9): 1395-6.
80. Liu J, Chen P, Wang Q, et al.: Meta analysis of olfactory ensheathing cell transplantation promoting functional recovery of motor nerves in rats with complete spinal cord transection. Neural Regen Res. 2014; 9(20): 1850-8.
81. Li L, Adnan H, Xu B, et al.: Effects of transplantation of olfactory ensheathing cells in chronic spinal cord injury: a systematic review and metaanalysis. Eur Spine J. 2015; 24(5): 919-30.
82. Dasari VR, Veeravalli KK, Dinh DH: Mesenchymal stem cells in the treatment of spinal cord injuries: A review. World J Stem Cells. 2014; 6(2): 120-33.
83. Swartzlander MD, Blakney AK, Amer LD, et al.: Immunomodulation by mesenchymal stem cells combats the foreign body response to cell-laden synthetic hydrogels. Biomaterials. 2015; 41: 79-88.
84. Bessout R, Sémont A, Demarquay C, et al.: Mesenchymal stem cell therapy induces glucocorticoid synthesis in colonic mucosa and suppresses radiation-activated T cells: new insights into MSC immunomodulation. Mucosal Immunol. 2014; 7(3): 656-69.
85. Lim JH, Kim JS, Yoon IH, et al.: Immunomodulation of delayed-type hypersensitivity responses by mesenchymal stem cells is associated with bystander T cell apoptosis in the draining lymph node. J Immunol. 2010; 185(7): 4022-9.
86. Quertainmont R, Cantinieaux D, Botman O, et al.: Mesenchymal stem cell graft improves recovery after spinal cord injury in adult rats through neurotrophic and pro-angiogenic actions. PLoS One. 2012; 7(6): e39500.
87. Kim JW, Ha KY, Molon JN, et al.: Bone marrow-derived mesenchymal stem cell transplantation for chronic spinal cord injury in rats: comparative study between intralesional and intravenous transplantation. Spine (Phila Pa 1976). 2013; 38(17): E1065-74.
88. Gu W, Zhang F, Xue Q, et al.: Transplantation of bone marrow mesenchymal stem cells reduces lesion volume and induces axonal regrowth of injured spinal cord. Neuropathology. 2010; 30(3): 205-17.
89. Sasaki M, Honmou O, Akiyama Y, et al.: Transplantation of an acutely isolated bone marrow fraction repairs demyelinated adult rat spinal cord axons. Glia. 2001; 35(1): 26-34.
90. Chhabra HS, Sarda K, Arora M, et al.: Autologous bone marrow cell transplantation in acute spinal cord injury-an Indian pilot study. Spinal Cord. 2016; 54(1): 57-64.
91. Jarocha D, Milczarek O, Kawecki Z, et al.: Preliminary study of autologous bone marrow nucleated cells transplantation in children with spinal cord injury. Stem Cells Transl Med. 2014; 3(3): 395-404.
92. Caicco MJ, Zahir T, Mothe AJ, et al.: Characterization of hyaluronanmethylcellulose hydrogels for cell delivery to the injured spinal cord. J Biomed Mater Res A. 2013; 101(5): 1472-7.
93. Mothe AJ, Tam RY, Zahir T, et al.: Repair of the injured spinal cord by transplantation of neural stem cells in a hyaluronan-based hydrogel. Biomaterials. 2013; 34(15): 3775-83.
94. Tam RY, Cooke MJ, Shoichet MS: A covalently modified hydrogel blend of hyaluronan-methyl cellulose with peptides and growth factors influences neural stem/progenitor cell fate. J Mater Chem. 2012; 22(37): 19402-19411.
95. Ansorena E, De Berdt P, Ucakar B, et al.: Injectable alginate hydrogel loaded with GDNF promotes functional recovery in a hemisection model of spinal cord injury. Int J Pharm. 2013; 455(1-2): 148-58.
96. Itosaka H, Kuroda S, Shichinohe H, et al.: Fibrin matrix provides a suitable scaffold for bone marrow stromal cells transplanted into injured spinal cord: a novel material for CNS tissue engineering. Neuropathology. 2009; 29(3): 248-57.
97. Taylor SJ, McDonald JW 3rd, Sakiyama-Elbert SE: Controlled release of neurotrophin-3 from fibrin gels for spinal cord injury. J Control Release. 2004; 98(2): 281-94.
98. Vulic K, Shoichet MS: Tunable growth factor delivery from injectable hydrogels for tissue engineering. J Am Chem Soc. 2012; 134(2): 882-5.
99. Liu Y, Ye H, Satkunendrarajah K, et al.: A self-assembling peptide reduces glial scarring, attenuates post-traumatic inflammation and promotes neurological recovery following spinal cord injury. Acta Biomater. 2013; 9(9): 8075-88.
100. Martin R, Sadowsky C, Obst K, et al.: Functional electrical stimulation in spinal cord injury:: from theory to practice. Top Spinal Cord Inj Rehabil. 2012; 18(1): 28-33.
101. Lavrov I, Gerasimenko YP, Ichiyama RM, et al.: Plasticity of spinal cord reflexes after a complete transection in adult rats: relationship to stepping ability. J Neurophysiol. 2006; 96(4): 1699-710.
102. Courtine G, Gerasimenko Y, van den Brand R, et al.: Transformation of nonfunctional spinal circuits into functional states after the loss of brain input. Nat Neurosci. 2009; 12(10): 1333-42.
103. Dietz V, Harkema SJ: Locomotor activity in spinal cord-injured persons. J Appl Physiol (1985). 2004; 96(5): 1954-60.
104. Bhambhani Y, Tuchak C, Burnham R, et al.: Quadriceps muscle deoxygenation during functional electrical stimulation in adults with spinal cord injury. Spinal Cord. 2000; 38(10): 630-8.
105. Kakebeeke TH, Hofer PJ, Frotzler A, et al.: Training and detraining of a tetraplegic subject: high-volume FES cycle training. Am J Phys Med Rehabil. 2008; 87(1): 56-64.
106. Harkema S, Gerasimenko Y, Hodes J, 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. 2009; 377(9781): 1938-47.
107. Pouw MH, Hosman AJ, van Middendorp JJ, et al.: Biomarkers in spinal cord injury. Spinal Cord. 2009; 47(7): 519-25.
108. Cadotte DW, Fehlings MG: Will imaging biomarkers transform spinal cord injury trials? Lancet Neurol. 2013; 12(9): 843-4.