title: Spinal cord injury: how can we improve the classification and quantification of its severity and prognosis?
abstract: The preservation of functional neural tissue after spinal cord injury (SCI) is the basis for spontaneous neurological recovery. Some injured patients in the acute phase have more potential for recovery than others. This fact is problematic for the construction of clinical trials because enrollment of subjects with variable recovery potential makes it difficult to detect effects, requires large sample sizes, and risks Type II errors. In addition, the current methods to assess injury and recovery are non-quantitative and not sensitive. It is likely that therapeutic combinations will be necessary to cause substantially improved function after SCI, thus we need highly sensitive techniques to evaluate changes in motor, sensory, autonomic and other functions. We review several emerging neurophysiological techniques with high sensitivity. Quantitative methods to evaluate residual tissue sparing after severe acute SCI have not entered widespread clinical use. This reduces the ability to correlate structural preservation with clinical outcome following SCI resulting in enrollment of subjects with varying patterns of tissue preservation and injury into clinical trials. We propose that the inclusion of additional measures of injury severity, pattern, and individual genetic characteristics may enable stratification in clinical trials to make the testing of therapeutic interventions more effective and efficient. New imaging techniques to assess tract injury and demyelination and methods to quantify tissue injury, inflammatory markers, and neuroglial biochemical changes may improve the evaluation of injury severity, and the correlation with neurological outcome, and measure the effects of treatment more robustly than is currently possible. The ability to test such a multimodality approach will require a high degree of collaboration between clinical and research centers and government research support. When the most informative of these assessments is determined, it may be possible to identify patients with substantial recovery potential, improve selection criteria and conduct more efficient clinical trials.
authors.affiliation: 1 Department of Neurosciences, Medical University of South Carolina , Charleston, South Carolina.
authors.forename: Vibhor
authors.initials: V
authors.lastname: Krishna
authors.forename: Hampton
authors.initials: H
authors.lastname: Andrews
authors.forename: Abhay
authors.initials: A
authors.lastname: Varma
authors.forename: Jacobo
authors.initials: J
authors.lastname: Mintzer
authors.forename: Mark S
authors.initials: MS
authors.lastname: Kindy
authors.forename: James
authors.initials: J
authors.lastname: Guest
mesh_terms: D006801:Humans; D018579:Patient Selection; D011379:Prognosis; D020127:Recovery of Function; D012720:Severity of Illness Index; D013119:Spinal Cord Injuries / Q000145:classification* / Q000473:pathology*
references.citation: Spine (Phila Pa 1976). 2010 Sep 15;35(20):1880-6
references.pmid: 20802388
references.citation: J Trauma. 2011 Apr;70(4):E56-61
references.pmid: 20805767
references.citation: Spinal Cord. 2011 Mar;49(3):333-6
references.pmid: 20805831
references.citation: Crit Care Med. 2009 Jan;37(1 Suppl):S129-35
references.pmid: 19104212
references.citation: Magn Reson Med. 1989 Apr;10(1):135-44
references.pmid: 2547135
references.citation: J Neurotrauma. 2010 Nov;27(11):2033-40
references.pmid: 20822462
references.citation: Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9459-64
references.pmid: 19470644
references.citation: Neurorehabil Neural Repair. 2004 Sep;18(3):144-53
references.pmid: 15375274
references.citation: Neuroimage. 2011 Apr 1;55(3):1024-33
references.pmid: 21232610
references.citation: Exp Neurol. 1995 Apr;132(2):220-8
references.pmid: 7789460
references.citation: Brain. 2012 Apr;135(Pt 4):1224-36
references.pmid: 22505632
references.citation: Exp Neurol. 1996 Jun;139(2):244-56
references.pmid: 8654527
references.citation: Value Health. 2008 Jul-Aug;11(4):680-8
references.pmid: 18194406
references.citation: Spinal Cord. 2013 Aug;51(8):623-9
references.pmid: 23689388
references.citation: Neurosurgery. 2002 Mar;50(3 Suppl):S58-62
references.pmid: 12431288
references.citation: Spinal Cord. 2010 May;48(5):356-62
references.pmid: 19935758
references.citation: Spinal Cord. 1999 Jan;37(1):58-61
references.pmid: 10025698
references.citation: World Neurosurg. 2015 May;83(5):867-78
references.pmid: 23524031
references.citation: Neurosurgery. 2006 Nov;59(5):957-82; discussion 982-7
references.pmid: 17143232
references.citation: Neurobiol Aging. 2011 Dec;32 Suppl 1:S4-9
references.pmid: 22078172
references.citation: Handb Clin Neurol. 2012;109:47-62
references.pmid: 23098705
references.citation: J Neurotrauma. 2011 Aug;28(8):1479-95
references.pmid: 20030558
references.citation: J Bone Joint Surg Am. 2011 Oct 5;93(19):1781-9
references.pmid: 22005863
references.citation: Neurorehabil Neural Repair. 2012 Oct;26(8):939-48
references.pmid: 22460611
references.citation: J Thorac Cardiovasc Surg. 2001 Feb;121(2):316-23
references.pmid: 11174737
references.citation: J Neurosci Methods. 2010 Nov 30;193(2):210-6
references.pmid: 20832429
references.citation: J Neurotrauma. 2009 Nov;26(11):2027-36
references.pmid: 19456213
references.citation: Spinal Cord. 2006 Sep;44(9):560-6
references.pmid: 16568143
references.citation: Arch Phys Med Rehabil. 1998 Jan;79(1):81-6
references.pmid: 9440423
references.citation: J Neurotrauma. 2011 May;28(5):787-96
references.pmid: 21381984
references.citation: Spinal Cord. 2013 Apr;51(4):282-8
references.pmid: 23184026
references.citation: J Thorac Cardiovasc Surg. 2001 Apr;121(4):762-72
references.pmid: 11279419
references.citation: J Spinal Cord Med. 2007;30(3):205-14
references.pmid: 17684886
references.citation: Spinal Cord. 1997 Jun;35(6):368-73
references.pmid: 9194259
references.citation: J Neurosurg Spine. 2012 Sep;17(3):243-50
references.pmid: 22794535
references.citation: Top Spinal Cord Inj Rehabil. 2013 Spring;19(2):121-8
references.pmid: 23671382
references.citation: J Neurotrauma. 2008 Sep;25(9):1079-85
references.pmid: 18729720
references.citation: Spinal Cord. 2013 May;51(5):375-8
references.pmid: 23318558
references.citation: Magn Reson Med. 2013 May;69(5):1253-60
references.pmid: 22745036
references.citation: Neuroimage. 2013 Aug 15;77:262-7
references.pmid: 23583425
references.citation: J Spinal Cord Med. 2008;31(2):171-6
references.pmid: 18581664
references.citation: J Neurotrauma. 2012 Jun 10;29(9):1770-8
references.pmid: 22435839
references.citation: J Thorac Cardiovasc Surg. 2010 Aug;140(2):400-7
references.pmid: 20537355
references.citation: Clin Neurophysiol. 2011 Dec;122(12):2452-61
references.pmid: 21600843
references.citation: Clin Neurophysiol. 2012 Mar;123(3):598-604
references.pmid: 21852190
references.citation: J Neurol Neurosurg Psychiatry. 2012 Jun;83(6):629-37
references.pmid: 22492214
references.citation: J Spinal Cord Med. 2008;31(5):538-42
references.pmid: 19086711
references.citation: Spine (Phila Pa 1976). 2012 Jan 1;37(1):48-56
references.pmid: 21228747
references.citation: J Neurotrauma. 2012 Jul 1;29(10):1829-37
references.pmid: 22519951
references.citation: Surg Neurol. 2006 Nov;66(5):475-83; discussion 483
references.pmid: 17084191
references.citation: J Spinal Cord Med. 2012 Jul;35(4):201-10
references.pmid: 22925746
references.citation: Am J Phys Med Rehabil. 2005 Nov;84(11 Suppl):S77-97; quiz S98-100
references.pmid: 16251838
references.citation: Spinal Cord. 2007 Mar;45(3):190-205
references.pmid: 17179973
references.citation: Arch Phys Med Rehabil. 1997 Jan;78(1):39-43
references.pmid: 9014955
references.citation: AJNR Am J Neuroradiol. 1999 May;20(5):926-34
references.pmid: 10369368
references.citation: AJNR Am J Neuroradiol. 2008 Apr;29(4):655-9
references.pmid: 18238846
references.citation: Biophys J. 2011 Mar 2;100(5):1362-71
references.pmid: 21354410
references.citation: Spine J. 2012 May;12(5):389-400.e3
references.pmid: 22572584
references.citation: Spinal Cord. 2012 Sep;50(9):661-71
references.pmid: 22525310
references.citation: N Engl J Med. 1990 May 17;322(20):1405-11
references.pmid: 2278545
references.citation: Stroke. 1989 Mar;20(3):372-7
references.pmid: 2922776
references.citation: Clin Neurol Neurosurg. 2012 Jun;114(5):460-70
references.pmid: 22326716
references.citation: J Spinal Cord Med. 2010;33(4):346-52
references.pmid: 21061894
references.citation: Ann Biomed Eng. 2008 Feb;36(2):224-36
references.pmid: 18066663
references.citation: AJNR Am J Neuroradiol. 2008 May;29(5):1012-6
references.pmid: 18296550
references.citation: J Neurotrauma. 2012 Sep;29(13):2263-71
references.pmid: 22709268
references.citation: J Craniovertebr Junction Spine. 2011 Jan;2(1):17-26
references.pmid: 22013371
references.citation: Spinal Cord. 1997 May;35(5):266-74
references.pmid: 9160449
references.citation: Arch Phys Med Rehabil. 1991 Jul;72(8):546-8
references.pmid: 2059130
references.citation: Orthop Clin North Am. 2012 Jan;43(1):89-96, ix
references.pmid: 22082632
references.citation: Spine J. 2004 Jul-Aug;4(4):373-8
references.pmid: 15246294
references.citation: J Neurotrauma. 2011 Aug;28(8):1401-11
references.pmid: 20388006
references.citation: Spine J. 2013 Aug;13(8):867-76
references.pmid: 23523441
references.citation: Lancet. 2011 Mar 19;377(9770):1004-10
references.pmid: 21377202
references.citation: J Neurol Sci. 1992 Jul;110(1-2):90-8
references.pmid: 1506875
references.citation: J Neurosurg. 1997 Aug;87(2):239-46
references.pmid: 9254087
references.citation: Biochem Biophys Res Commun. 2005 Nov 4;336(4):1268-77
references.pmid: 16176808
references.citation: Spinal Cord. 2010 Sep;48(9):674-84
references.pmid: 20125111
references.citation: Neuroscience. 2012 Dec 27;227:271-82
references.pmid: 23036616
references.citation: Am J Physiol. 1992 Jul;263(1 Pt 2):H285-92
references.pmid: 1636766
references.citation: Prog Brain Res. 2002;137:3-8
references.pmid: 12440355
references.citation: J Neurosurg Spine. 2012 Sep;17(1 Suppl):77-86
references.pmid: 22985373
references.citation: Acta Neurochir (Wien). 2012 Jan;154(1):93-103; discussion 103
references.pmid: 21976236
references.citation: J Auton Nerv Syst. 1996 Nov 6;61(2):175-80
references.pmid: 8946338
references.citation: PLoS One. 2012;7(9):e45560
references.pmid: 23029097
references.citation: Lancet Neurol. 2008 Aug;7(8):715-27
references.pmid: 18635020
references.citation: Spine (Phila Pa 1976). 2012 Aug 1;37(17):1448-55
references.pmid: 22414995
references.citation: J Magn Reson Imaging. 2007 Jul;26(1):41-51
references.pmid: 17659567
references.citation: J Neurotrauma. 2008 Aug;25(8):1019-26
references.pmid: 18687037
references.citation: Acta Neurochir (Wien). 1996;138(3):322-9
references.pmid: 8861702
references.citation: J Neurotrauma. 2012 May 20;29(8):1556-66
references.pmid: 22150011
references.citation: J Spinal Disord. 1997 Aug;10(4):288-95
references.pmid: 9278912
references.citation: Handb Clin Neurol. 2012;109:85-101
references.pmid: 23098708
references.citation: Eur Radiol. 2011 Feb;21(2):426-33
references.pmid: 20725834
references.citation: Stroke. 1986 Nov-Dec;17(6):1183-9
references.pmid: 3810718
references.citation: Spinal Cord. 2011 Mar;49(3):345-51
references.pmid: 20877332
references.citation: Spinal Cord. 2009 Jul;47(7):555-60
references.pmid: 19104512
references.citation: Magn Reson Med. 2000 Oct;44(4):625-32
references.pmid: 11025519
references.citation: J Neurotrauma. 2003 May;20(5):477-82
references.pmid: 12803979
references.citation: Eur Spine J. 2011 Mar;20(3):422-8
references.pmid: 20938788
references.citation: Spinal Cord. 2009 Feb;47(2):122-7
references.pmid: 18663374
references.citation: J Neurotrauma. 2008 Nov;25(11):1273-301
references.pmid: 19061373
references.citation: J Trauma Acute Care Surg. 2012 Jul;73(1):137-45
references.pmid: 22743383
references.citation: J Thorac Cardiovasc Surg. 2006 Nov;132(5):1150-5
references.pmid: 17059937
references.citation: J Neurotrauma. 2010 Apr;27(4):669-82
references.pmid: 20038240
references.citation: J Spinal Cord Med. 2003 Spring;26 Suppl 1:S50-6
references.pmid: 16296564
references.citation: Spinal Cord. 2012 Apr;50(4):315-9
references.pmid: 22182851
references.citation: Neurosurgery. 2011 Feb;68(2):329-36
references.pmid: 21135722
references.citation: Pain. 2013 Feb;154(2):204-212
references.pmid: 23141478
references.citation: J Spinal Cord Med. 2006;29(1):39-45
references.pmid: 16572564
references.citation: J Rehabil Res Dev. 2007;44(1):77-82
references.pmid: 17551861
references.citation: Clin Chem Lab Med. 2011 Mar;49(3):425-33
references.pmid: 21175377
references.citation: J Neurotrauma. 2012 Feb 10;29(3):499-513
references.pmid: 22029501
references.citation: Spinal Cord. 2007 Jun;45(6):444-51
references.pmid: 17387316
references.citation: AJNR Am J Neuroradiol. 2013 Feb;34(2):471-8
references.pmid: 22821918
references.citation: Neurorehabil Neural Repair. 2012 Jun;26(5):497-506
references.pmid: 22179075
references.citation: Spinal Cord. 1999 Mar;37(3):157-65
references.pmid: 10213324
references.citation: Spinal Cord. 2009 Feb;47(2):171-5
references.pmid: 18504448
references.citation: Magn Reson Med. 2008 Mar;59(3):499-506
references.pmid: 18219631
references.citation: Radiology. 1996 Dec;201(3):649-55
references.pmid: 8939210
references.citation: Spinal Cord. 2012 Jul;50(7):493-6
references.pmid: 22270191
references.citation: J Neurosurg Spine. 2009 Mar;10(3):194-200
references.pmid: 19320577
references.citation: J Neurosurg Spine. 2011 Jan;14(1):122-30
references.pmid: 21166485
references.citation: Neuroimage. 2013 Feb 1;66:103-9
references.pmid: 23110887
references.citation: Spine (Phila Pa 1976). 2001 Dec 15;26(24 Suppl):S58-67
references.pmid: 11805612
references.citation: Handb Clin Neurol. 2012;109:63-75
references.pmid: 23098706
references.citation: Spinal Cord. 2009 Nov;47(11):809-16
references.pmid: 19468282
references.citation: Spinal Cord. 2011 Jan;49(1):70-5
references.pmid: 20697420
references.citation: Radiology. 2007 Jun;243(3):820-7
references.pmid: 17431129
references.citation: J Clin Neurophysiol. 2002 Oct;19(5):409-15
references.pmid: 12477986
references.citation: Spinal Cord. 2013 Jul;51(7):558-63
references.pmid: 23588574
references.citation: J Neurosurg. 1979 Feb;50(2):198-206
references.pmid: 430132
references.citation: Clin Neurophysiol. 2012 Mar;123(3):582-9
references.pmid: 21963320
references.citation: J Neurotrauma. 2013 Feb 1;30(3):142-59
references.pmid: 23316955
references.citation: J Neurotrauma. 2010 Jan;27(1):241-52
references.pmid: 19645527
references.citation: NMR Biomed. 2010 Feb;23(2):207-17
references.pmid: 19924726
references.citation: Spinal Cord. 2012 Jun;50(6):426-31
references.pmid: 22310317
references.citation: J Comp Neurol. 2009 Jun 10;514(5):433-48
references.pmid: 19350644
references.citation: Arch Phys Med Rehabil. 1996 Jan;77(1):48-53
references.pmid: 8554473
references.citation: Neurosurgery. 2013 Mar;72 Suppl 2:1
references.pmid: 23417171
references.citation: Arch Phys Med Rehabil. 1997 Jun;78(6):644-50
references.pmid: 9196473
references.citation: Spinal Cord. 2013 Jul;51(7):532-7
references.pmid: 23608812