- Department of Neurosurgery, Detroit Medical Center, Wayne State University, Detroit, Michigan,
- Department of Surgery, Swedish Neuroscience Institute, Seattle, WA, United States.
Correspondence Address:
Dia Radi Halalmeh
Department of Neurosurgery, Detroit Medical Center, Wayne State University, Detroit, Michigan,
DOI:10.25259/SNI_568_2019
Copyright: © 2020 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.How to cite this article: Manan Shah, Catherine Peterson, Emre Yilmaz, Dia Radi Halalmeh, Marc Moisi. Current advancements in the management of spinal cord injury: A comprehensive review of literature. 03-Jan-2020;11:2
How to cite this URL: Manan Shah, Catherine Peterson, Emre Yilmaz, Dia Radi Halalmeh, Marc Moisi. Current advancements in the management of spinal cord injury: A comprehensive review of literature. 03-Jan-2020;11:2. Available from: https://surgicalneurologyint.com/surgicalint-articles/9833/
Abstract
Background: Spinal cord injury (SCI) carries debilitating lifelong consequences and, therefore, requires careful review of different treatment strategies.
Methods: An extensive review of the English literature (PubMed 1990 and 2019) was performed regarding recent advances in the treatment of SCI; this included 46 articles written over 28 years.
Results: Results of this search were divided into five major modalities; neuroprotective and neuroregenerative pharmaceuticals, neuromodulation, stem cell-based therapies, and various external prosthetic devices. Lately, therapeutic strategies were mainly focused on two major areas: neuroregeneration and neuroprotection.
Conclusion: Despite recent advancements, more clinical trials on a larger scale and further research are needed to provide better treatment modalities of this devastating neurological disease.
Keywords: Exoskeleton, Neuromodulation, Spinal cord injury, Spine, Stem cells, Trauma
INTRODUCTION
Spinal cord injury (SCI) is a devastating illness resulting in neurological deficits and poor quality of life. It has an annual incidence of 15–40 cases per million and a prevalence of more than 1 million cases in North America.[
This literature review focuses on the advances in pharmacology, stem cell technologies, neuromodulation, and external prosthetics. Several pharmacological therapies have already been tested in the past and are currently being investigated. Further, both neuroprotective and neuroregenerative drugs are being implemented in clinical trials.[
MATERIALS AND METHODS
Peer-reviewed articles were searched through PubMed using search terms “acute SCI,” “SCI treatment,” “neuromodulation,” “stem cell therapy for SCI,” “SCI pharmaceuticals,” and “SCI exoskeleton from 1990 to 2019 (English journals). Using appropriate inclusion and exclusion criteria, 46 peer-reviewed articles were used. All studies focused on current advancements in the management of SCI, including stem cell therapies, neuromodulation, and external prosthetics.
RESULTS AND DISCUSSION
Neuroprotective and neuroregenerative pharmaceuticals [ Tables 1 and 2 ]
Methylprednisolone
Several neuroprotective and neuroregenerative pharmaceutical drugs have been investigated for SCI management. A well-known neuroprotective agent, methylprednisolone, has been associated with improved neurological outcomes. It decreases the peroxidation of membrane lipids and posttraumatic inflammation.[
Naloxone, tirilazad, and nimodipine
Three drugs, naloxone, tirilazad, and nimodipine, were studied for their neuroprotective abilities. They all have Phase III randomized controlled trials which have not shown any difference in NASCIS motor score recovery or the American Spinal Injury Association (ASIA) motor score between treatment and placebo groups.[
Riluzole
Riluzole, a sodium channel blocker approved for the treatment of amyotrophic lateral sclerosis, has been studied in preclinical models of SCI. It diminishes secondary injury by blocking activation of sodium channels and reducing release of neuronal glutamate.[
Minocycline
Minocycline, a modified form of tetracycline, is another neuroprotective agent that has shown some promise in animal models.[
Fibroblast growth factor
Basic fibroblast growth factor has shown to provide neuroprotection by improving functional and respiratory parameters in animal models by reducing glutamate-mediated excitotoxicity.[
GM-1 ganglioside (Sygen)
A neuroregenerative agent, GM-1 ganglioside (Sygen) has been shown to enhance axonal regeneration in laboratory studies.[
Cethrin
Cethrin is a permeable paste that can be applied to spinal cord dura postinjury that is a combination of a bacterial-derived toxin, BA-210, and a biohemostatic adhesive. It inhibits the Rho pathway of inhibitory proteins and promotes axonal growth in vitro.[
Anti-Nogo
Another neuroregenerative drug, anti-Nogo, is a monoclonal antibody made to bind to Nogo-A, and has been shown to promote neural regeneration.[
Neuromodulation [ Table 3 ]
It is well known that neuromodulation, the use of electrical stimulation to alter neuronal circuitry, has been tried in various neurological disorders including SCI. Neuroplasticity-mediated functional recruitment of axons (particularly spared axons) to potentiate sprouting, regeneration, and formation of new interconnections between neurons forms the basis of modern neuromodulation techniques. This is complemented with the presence of some intact ascending and descending circuits in patients with SCI, making neuromodulation a feasible option.[
Activity-dependent plasticity
Moreover, the concept of activity-dependent plasticity has been recently employed to achieve substantial improvements in motor function, based on the recent finding that neurorehabilitation is the only treatment option which can be offered to SCI patients for long-term improvement in motor function.[
Spinal cord stimulation
With respect to spinal cord stimulation, epidural spinal stimulation has well been tested in patients with chronic pain and most recently in patients with SCI. This method involves surgical placement of electrodes onto the dorsal surface of the spinal cord.[
Brain stimulation for SCI
Brain stimulation for SCI is also currently being employed. Transcranial direct current stimulation and transcranial magnetic stimulation are two main approaches that are being used to augment the neuronal plasticity between the spinal cord and the brain in individuals with SCI.[
Brain–machine interfaces
Brain–machine interfaces are another modern tool for patients with SCI. These devices, which can be used to control various prosthetic devices such as the exoskeleton as well as directly stimulate paralyzed muscles, have already demonstrated improved outcomes in patients with SCI through several recent studies.[
Stem cell-based therapies [ Table 3 ]
Stem cell-based therapies and cellular scaffolds have yielded promising progress with respect to neuronal repair.[
In vitro manipulation of the embryonic stem cells (ESCs)
Recently, in vitro manipulation of the ESCs differentiation to neuronal and glial lineages under controlled conditions has shown promising results after transplantation in animal models of acute SCI.[
Various cell-based therapies
Despite extensive research exploring various cell-based therapies such as transplantation of oligodendrocyte precursors, induced pluripotent stem cells, bone marrow-derived (BM-MSCs), adipose-derived (AD-MSCs), and umbilical cord (U-MSCs),[
Prosthetic devices [ Table 3 ]
Robotic exoskeletons or powered exoskeletons have emerged as an advantageous rehabilitation tool for certain disabled individuals with SCI. The studies provided preliminary evidence on efficacy of exoskeletons on cardiovascular health, energy expenditure, body composition, gait parameters, level of physical activity, neuropathic pain level, and quality of life. They can be used to restore a certain level of physical activity years after injury.[
CONCLUSION
We investigated the advancements in neuroprotective pharmacology, stem cell technologies, neuromodulation, and various external prosthetics for the treatment of SCI. However, more clinical trials and research will continue to establish their efficacy.
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