A Systematic Review of Experimental Strategies Aimed at Improving Motor Function after Acute and Chronic Spinal Cord Injury

Abstract

While various approaches have been proposed in clinical trials aimed at improving motor function after spinal cord injury in humans, there is still limited information regarding the scope, methodological quality, and evidence associated with single-intervention and multi-intervention approaches. A systematic review performed using the PubMed search engine and the key words ''spinal cord injury motor recovery'' identified 1973 records, of which 39 were selected (18 from the search records and 21 from reference list inspection). Study phase (clinicaltrials.org criteria) and methodological quality (Cochrane criteria) were assessed. Studies included proposed a broad range of single-intervention (encompassing cell therapies, pharmacology, electrical stimulation, rehabilitation) (encompassing cell therapies, pharmacology, electrical stimulation, rehabilitation) and multi-intervention approaches (that combined more than one strategy). The highest evidence level was for Phase III studies supporting the role of multi-intervention approaches that contained a rehabilitation component. Quality appraisal revealed that the percentage of selected studies classified with high risk of bias by Cochrane criteria was as follows: random sequence generation = 64%; allocation concealment = 77%; blinding of participants and personnel = 69%; blinding of outcome assessment = 64%; attrition = 44%; selective reporting = 44%. The current literature contains a high proportion of studies with a limited ability to measure efficacy in a valid manner because of low methodological strength in all items of the Cochrane risk of bias assessment. Recommendations to decrease bias are discussed and include increased methodological rigor in the study design and recruitment of study participants, and the use of electrophysiological and imaging measures that can assess functional integrity of the spinal cord (and may be sufficiently sensitive to detect changes that occur in response to therapeutic interventions).

Rat models of spinal cord injury: from pathology to potential therapies

“…In the United States alone, ∼30 individuals sustain a spinal cord injury every day (Gomes-Osman et al, 2016), typically caused by motor vehicle accidents (38%), falls (>22%), violence (13.5%), and sports and recreational accidents (9%). Diseases can also cause or increase the risk of spinal cord injury (National Spinal Cord Injury Statistical Center, 2016).…”

Nerve growth factor delivery by ultrasound-mediated nanobubble destruction as a treatment for acute spinal cord injury in rats

“…The most common causes of SCI are motor vehicle accidents (38%), falls (22%), violence (13.5%), and sport/recreational accidents (9%). 1 In SCI, structural and functional damage of the spinal cord occurs by primary and secondary injury. This results in loss of movement and sensation and sphincter and autonomic nerve dysfunction below the damaged plane.…”

Supraspinal Control Predicts Locomotor Function and Forecasts Responsiveness to Training after Spinal Cord Injury

“…In addition, for an overview of the available published locomotor training studies in persons with SCI, the reader is referred to a systematic review on this topic. 8 While there is great interest in the potential of pharmacological, biological, and genetic interventions to improve walking function in persons with SCI, 9 at this time the efficacy of these approaches in humans has not been established. A recent systematic review of the experimental strategies aimed at improving motor function in persons with SCI concluded that multi-intervention approaches that contain a rehabilitation component currently have the best evidence to support their value.…”

“…A recent systematic review of the experimental strategies aimed at improving motor function in persons with SCI concluded that multi-intervention approaches that contain a rehabilitation component currently have the best evidence to support their value. 9 While early training approaches to improve locomotor function in persons with SCI focused on activating spinal central pattern generator (CPG) circuits associated with locomotor behavior, 10,11 there has been growing recognition of the role of spared supraspinal pathways in locomotor function. For this reason, recent studies have begun to target supraspinal control mechanisms in both animal models 12,13 and humans.…”