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      Established and Emerging Therapies in Acute Spinal Cord Injury

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          Abstract

          Acute spinal cord injury (SCI) is devastating for patients and their caretakers and has an annual incidence of 20–50 per million people. Following initial assessment with appropriate physical examination and imaging, patients who are deemed surgical candidates should undergo decompression with stabilization. Earlier intervention can improve neurological recovery in the post-operative period while allowing earlier mobilization. Optimized medical management is paramount to improve outcomes. Emerging strategies for managing SCI in the acute period stem from an evolving understanding of the pathophysiology of the injury. General areas of focus include ischemia prevention, reduction of secondary injury due to inflammation, modulation of the cytotoxic and immune response, and promotion of cellular regeneration. In this article, we review established, emerging, and novel experimental therapies. Continued translational research on these methods will improve the feasibility of bench-to-bedside innovations in treating patients with acute SCI.

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          Traumatic Spinal Cord Injury: An Overview of Pathophysiology, Models and Acute Injury Mechanisms

          Traumatic spinal cord injury (SCI) is a life changing neurological condition with substantial socioeconomic implications for patients and their care-givers. Recent advances in medical management of SCI has significantly improved diagnosis, stabilization, survival rate and well-being of SCI patients. However, there has been small progress on treatment options for improving the neurological outcomes of SCI patients. This incremental success mainly reflects the complexity of SCI pathophysiology and the diverse biochemical and physiological changes that occur in the injured spinal cord. Therefore, in the past few decades, considerable efforts have been made by SCI researchers to elucidate the pathophysiology of SCI and unravel the underlying cellular and molecular mechanisms of tissue degeneration and repair in the injured spinal cord. To this end, a number of preclinical animal and injury models have been developed to more closely recapitulate the primary and secondary injury processes of SCI. In this review, we will provide a comprehensive overview of the recent advances in our understanding of the pathophysiology of SCI. We will also discuss the neurological outcomes of human SCI and the available experimental model systems that have been employed to identify SCI mechanisms and develop therapeutic strategies for this condition.
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            Global prevalence and incidence of traumatic spinal cord injury

            Background Spinal cord injury (SCI) is a traumatic event that impacts a patient’s physical, psychological, and social well-being and places substantial financial burden on health care systems. To determine the true impact of SCI, this systematic review aims to summarize literature reporting on either the incidence or prevalence of SCI. Methods A systematic search was conducted using PubMed, MEDLINE, MEDLINE in process, EMBASE, Cochrane Controlled Trial Register, and Cochrane Database of Systematic Reviews to identify relevant literature published through June 2013. We sought studies that provided regional, provincial/state, or national data on the incidence of SCI or reported estimates of disease prevalence. The level of evidence of each study was rated using a scale that evaluated study design, methodology, sampling bias, and precision of estimates. Results The initial search yielded 5,874 articles, 48 of which met the inclusion criteria. Forty-four studies estimated the incidence of SCI and nine reported the prevalence, with five discussing both. Of the incidence studies, 14 provided figures at a regional, ten at a state or provincial level and 21 at a national level. The prevalence of SCI was highest in the United States of America (906 per million) and lowest in the Rhone-Alpes region, France (250 per million) and Helsinki, Finland (280 per million). With respect to states and provinces in North America, the crude annual incidence of SCI was highest in Alaska (83 per million) and Mississippi (77 per million) and lowest in Alabama (29.4 per million), despite a large percentage of violence injuries (21.2%). Annual incidences were above 50 per million in the Hualien County in Taiwan (56.1 per million), the central Portugal region (58 per million), and Olmsted County in Minnesota (54.8 per million) and were lower than 20 per million in Taipei, Taiwan (14.6 per million), the Rhone-Alpes region in France (12.7 per million), Aragon, Spain (12.1 per million), Southeast Turkey (16.9 per million), and Stockholm, Sweden (19.5 per million). The highest national incidence was 49.1 per million in New Zealand, and the lowest incidences were in Fiji (10.0 per million) and Spain (8.0 per million). The majority of studies showed a high male-to-female ratio and an age of peak incidence of younger than 30 years old. Traffic accidents were typically the most common cause of SCI, followed by falls in the elderly population. Conclusion This review demonstrates that the incidence, prevalence, and causation of SCI differs between developing and developed countries and suggests that management and preventative strategies need to be tailored to regional trends. The rising aging population in westernized countries also indicates that traumatic SCI secondary to falls may become an increasing public health challenge and that incidence among the elderly may rise with increasing life expectancy.
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              Recovery of Over-Ground Walking after Chronic Motor Complete Spinal Cord Injury

              Persons with motor complete spinal cord injury, signifying no voluntary movement or sphincter function below the level of injury but including retention of some sensation, do not recover independent walking. We tested intense locomotor treadmill training with weight support and simultaneous spinal cord epidural stimulation in four patients 2.5 to 3.3 years after traumatic spinal injury and after failure to improve with locomotor training alone. Two patients, one with damage to the mid-cervical region and one with damage to the high-thoracic region, achieved over-ground walking (not on a treadmill) after 278 sessions of epidural stimulation and gait training over a period of 85 weeks and 81 sessions over a period of 15 weeks, respectively, and all four achieved independent standing and trunk stability. One patient had a hip fracture during training. (Funded by the Leona M. and Harry B. Helmsley Charitable Trust and others; ClinicalTrials.gov number, NCT02339233 .).
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                Author and article information

                Journal
                Neurospine
                Neurospine
                NS
                Neurospine
                Korean Spinal Neurosurgery Society
                2586-6583
                2586-6591
                June 2022
                30 June 2022
                : 19
                : 2
                : 283-296
                Affiliations
                Department of Neurosurgery, Baylor College of Medicine, Houston, TX, USA
                Author notes
                Corresponding Author Alexander E. Ropper Department of Neurosurgery, Baylor College of Medicine, 7200 Cambridge St. Suite 9A, Houston, TX, USA Email: alexander.ropper@ 123456bcm.edu
                Author information
                http://orcid.org/0000-0001-6480-3521
                http://orcid.org/0000-0002-4084-9522
                Article
                ns-2244176-088
                10.14245/ns.2244176.088
                9260540
                35793931
                dd03d155-838f-45ca-ab40-6826523f2558
                Copyright © 2022 by the Korean Spinal Neurosurgery Society

                This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 2 March 2022
                : 14 April 2022
                : 5 May 2022
                Categories
                Review Article

                spinal cord injury,acute,pathophysiology,therapeutics
                spinal cord injury, acute, pathophysiology, therapeutics

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