Neuroplasticity modulating strategies
Nervous system stimulation (central, peripheral, and mixed) utilising transcutaneous, epidural, or magnetic approaches allows for motor and non-motor neuronal activation to be used in the context of therapeutic interventions.[115]Rossini PM, Burke D, Chen R, et al. Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee. Clin Neurophysiol. 2015 Jun;126(6):1071-107.
https://www.doi.org/10.1016/j.clinph.2015.02.001
http://www.ncbi.nlm.nih.gov/pubmed/25797650?tool=bestpractice.com
[116]Wagner FB, Mignardot JB, Le Goff-Mignardot CG, et al. Targeted neurotechnology restores walking in humans with spinal cord injury. Nature. 2018 Nov;563(7729):65-71.
http://www.ncbi.nlm.nih.gov/pubmed/30382197?tool=bestpractice.com
[117]Martin R. Utility and feasibility of transcutaneous spinal cord stimulation for patients with incomplete SCI in therapeutic settings: a review of topic. Front. Rehabilit. Sci. 2021;2:724003.
https://www.frontiersin.org/articles/10.3389/fresc.2021.724003/full
Acute hypoxia
Acute intermittent hypoxia has been consistently shown to improve function in patients with incomplete motor injuries.[118]Hayes HB, Jayaraman A, Herrmann M, et al. Daily intermittent hypoxia enhances walking after chronic spinal cord injury: a randomized trial. Neurology. 2014 Jan 14;82(2):104-13.
https://www.doi.org/10.1212/01.WNL.0000437416.34298.43
http://www.ncbi.nlm.nih.gov/pubmed/24285617?tool=bestpractice.com
Transplantation strategies
The transplantation of several cell types has been investigated as potential therapy for spinal cord injury (SCI); these include Schwann cells, neural stem cells or progenitor cells, olfactory ensheathing cells, oligodendrocyte precursor cells, and mesenchymal stem cells. Strategies are focused on neuroprotection, immunomodulation, and neural reconstruction.[119]Assinck P, Duncan GJ, Hilton BJ, et al. Cell transplantation therapy for spinal cord injury. Nat Neurosci. 2017 Apr 25;20(5):637-47.
http://www.ncbi.nlm.nih.gov/pubmed/28440805?tool=bestpractice.com
[120]Hu XC, Lu YB, Yang YN, et al. Progress in clinical trials of cell transplantation for the treatment of spinal cord injury: how many questions remain unanswered? Neural Regen Res. 2021 Mar;16(3):405-13.
https://www.doi.org/10.4103/1673-5374.293130
http://www.ncbi.nlm.nih.gov/pubmed/32985458?tool=bestpractice.com
However, despite demonstration of safety and effectiveness in animal models, sufficient evidence of efficacy in a clinical setting is still lacking.[120]Hu XC, Lu YB, Yang YN, et al. Progress in clinical trials of cell transplantation for the treatment of spinal cord injury: how many questions remain unanswered? Neural Regen Res. 2021 Mar;16(3):405-13.
https://www.doi.org/10.4103/1673-5374.293130
http://www.ncbi.nlm.nih.gov/pubmed/32985458?tool=bestpractice.com
Chondroitinase ABC
Studies in animals revealed that chondroitinase-induced plasticity improved the dexterity associated with trained skills, but had adverse effects on non-trained motor activities.[121]Garcia-Alias G, Barkhuysen S, Buckle M, et al. Chondroitinase ABC treatment opens a window of opportunity for task-specific rehabilitation. Nat Neurosci. 2009 Sep;12(9):1145-51.
http://www.ncbi.nlm.nih.gov/pubmed/19668200?tool=bestpractice.com
[122]Zhao RR, Fawcett JW. Combination treatment with chondroitinase ABC in spinal cord injury--breaking the barrier. Neurosci Bull. 2013 Aug;29(4):477-83.
http://www.ncbi.nlm.nih.gov/pubmed/23839053?tool=bestpractice.com
There are no studies in humans at this time.
Electrical stimulation
Simultaneous chemical and electrical stimulation of receptors has a synergistic effect. This has led to the development of combined electrical and pharmacological strategies for improving locomotor function.[123]Canadian Agency for Drugs and Technologies in Health. Functional electrical stimulation for children with spinal cord injuries or cerebral palsy: Update of review of clinical effectiveness. August 2015 [internet publication].
https://www.cadth.ca/functional-electrical-stimulation-fes-children-spinal-cord-injuries-or-cerebral-palsy-update-review
[124]Sadowsky CL, Sayenko DG. Editorial: harnessing neuroplasticity in the injured central nervous system using spinal neuromodulation. Front. Rehabilit. Sci. 2022;3:841014.
https://www.frontiersin.org/articles/10.3389/fresc.2022.841014/full#B2
Preliminary results from a trial of combined locomotor treadmill training, weight support, and epidural electrical stimulation showed an increase in voluntary movement among participants.[125]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 Sep 27;379(13):1244-50.
http://www.ncbi.nlm.nih.gov/pubmed/30247091?tool=bestpractice.com
One systematic review concluded that functional electrical stimulation cycling exercise improves lower-body muscle health in adults with SCI, and may increase power output and aerobic fitness.[126]van der Scheer JW, Goosey-Tolfrey VL, Valentino SE, et al. Functional electrical stimulation cycling exercise after spinal cord injury: a systematic review of health and fitness-related outcomes. J Neuroeng Rehabil. 2021 Jun 12;18(1):99.
https://www.doi.org/10.1186/s12984-021-00882-8
http://www.ncbi.nlm.nih.gov/pubmed/34118958?tool=bestpractice.com
Cranial electrotherapy stimulation improved pain intensity and pain interference with daily life, with few side effects, in patients with SCI.[127]Tan G, Rintala DH, Jensen MP, et al. Efficacy of cranial electrotherapy stimulation for neuropathic pain following spinal cord injury: a multi-site randomized controlled trial with a secondary 6-month open-label phase. J Spinal Cord Med. 2011;34(3):285-96.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3127367
http://www.ncbi.nlm.nih.gov/pubmed/21756567?tool=bestpractice.com
Botulinum toxin
Preliminary evidence indicates that botulinum toxin type A (known as onabotulinumtoxinA, incabotulinumtoxinA, or abobotulinumtoxinA in the US) may reduce intractable chronic neuropathic pain in patients with SCI. Further study is warranted, given the difficulty of treating neuropathic pain.[128]Han ZA, Song DH, Oh HM, et al. Botulinum toxin type A for neuropathic pain in patients with spinal cord injury. Ann Neurol. 2016 Apr;79(4):569-78.
https://onlinelibrary.wiley.com/doi/10.1002/ana.24605/full
http://www.ncbi.nlm.nih.gov/pubmed/26814620?tool=bestpractice.com
[129]Chun A, Levy I, Yang A, et al. Treatment of at-level spinal cord injury pain with botulinum toxin A. Spinal Cord Ser Cases. 2019;5:77.
https://www.doi.org/10.1038/s41394-019-0221-9
http://www.ncbi.nlm.nih.gov/pubmed/31632735?tool=bestpractice.com
[130]Ling HQ, Chen ZH, He L, et al. Comparative efficacy and safety of 11 drugs as therapies for adults with neuropathic pain after spinal cord injury: a Bayesian network analysis based on 20 randomized controlled trials. Front Neurol. 2022;13:818522.
https://www.doi.org/10.3389/fneur.2022.818522
http://www.ncbi.nlm.nih.gov/pubmed/35386408?tool=bestpractice.com