Neuroplasticity modulating strategies
Nervous system stimulation (central, peripheral, and mixed) utilizing transcutaneous, epidural, or magnetic approaches allows for motor and nonmotor neuronal activation to be used in the context of therapeutic interventions.[114]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
[115]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
[116]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.[117]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.[118]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
[119]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.[119]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 nontrained motor activities.[120]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
[121]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 pharmacologic strategies for improving locomotor function.[122]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
[123]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.[124]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.[125]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.[126]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.[127]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
[128]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
[129]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