Camila R. Battistuzzo

A Systematic Review of Exercise Training To Promote Locomotor Recovery in Animal Models of Spinal Cord Injury

In the early 1980s experiments on spinalized cats showed that exercise training on the treadmill could enhance locomotor recovery after spinal cord injury (SCI). In this review, we summarize the evidence for the effectiveness of exercise training aimed at promoting locomotor recovery in animal models of SCI. We performed a systematic search of the literature using Medline, Web of Science, and Embase. Of the 362 studies screened, 41 were included. The adult female rat was the most widely used animal model. The majority of studies (73%) reported that exercise training had a positive effect on some aspect of locomotor recovery. Studies employing a complete SCI were less likely to have positive outcomes. For incomplete SCI models, contusion was the most frequently employed method of lesion induction, and the degree of recovery depended on injury severity. Positive outcomes were associated with training regimens that involved partial weight-bearing activity, commenced within a critical period of 1-2 weeks after SCI, and maintained training for at least 8 weeks. Considerable heterogeneity in training paradigms and methods used to assess or quantify recovery was observed. A 13-item checklist was developed and employed to assess the quality of reporting and study design; only 15% of the studies had high methodological quality. We recommend that future studies include control groups, randomize animals to groups, conduct blinded assessments, report the extent of the SCI lesion, and report sample size calculations. A small battery of objective assessment methods including assessment of over-ground stepping should also be developed and routinely employed. This would allow future meta-analyses of the effectiveness of exercise interventions on locomotor recovery.

Meta-Analysis of Pre-Clinical Studies of Early Decompression in Acute Spinal Cord Injury: A Battle of Time and Pressure

Background The use of early decompression in the management of acute spinal cord injury (SCI) remains contentious despite many pre-clinical studies demonstrating benefits and a small number of supportive clinical studies. Although the pre-clinical literature favours the concept of early decompression, translation is hindered by uncertainties regarding overall treatment efficacy and timing of decompression. Methods We performed meta-analysis to examine the pre-clinical literature on acute decompression of the injured spinal cord. Three databases were utilised; PubMed, ISI Web of Science and Embase. Our inclusion criteria consisted of (i) the reporting of efficacy of decompression at various time intervals (ii) number of animals and (iii) the mean outcome and variance in each group. Random effects meta-analysis was used and the impact of study design characteristics assessed with meta-regression. Results Overall, decompression improved behavioural outcome by 35.1% (95%CI 27.4-42.8; I2=94%, p<0.001). Measures to minimise bias were not routinely reported with blinding associated with a smaller but still significant benefit. Publication bias likely also contributed to an overestimation of efficacy. Meta-regression demonstrated a number of factors affecting outcome, notably compressive pressure and duration (adjusted r2=0.204, p<0.002), with increased pressure and longer durations of compression associated with smaller treatment effects. Plotting the compressive pressure against the duration of compression resulting in paraplegia in individual studies revealed a power law relationship; high compressive forces quickly resulted in paraplegia, while low compressive forces accompanying canal narrowing resulted in paresis over many hours. Conclusion These data suggest early decompression improves neurobehavioural deficits in animal models of SCI. Although much of the literature had limited internal validity, benefit was maintained across high quality studies. The close relationship of compressive pressure to the rate of development of severe neurological injury suggests that pressure local to the site of injury might be a useful parameter determining the urgency of decompression.

Functional changes in deep dorsal horn interneurons following spinal cord injury are enhanced with different durations of exercise training

Exercise training after spinal cord injury (SCI) enhances collateral sprouting from axons near the injury and is thought to promote intraspinal circuit reorganisation that effectively bridges the SCI. The effects of exercise training, and its duration, on interneurons in these de novo intraspinal circuits are poorly understood. In an adult mouse hemisection model of SCI, we used whole‐cell patch‐clamp electrophysiology to examine changes in the intrinsic and synaptic properties of deep dorsal horn interneurons in the vicinity of a SCI in response to the injury, and after 3 and 6 weeks of treadmill exercise training. SCI alone exerted powerful effects on the intrinsic and synaptic properties of interneurons near the lesion. Importantly, synaptic activity, both local and descending, was preferentially enhanced by exercise training, suggesting that exercise promotes synaptic plasticity in spinal cord interneurons that are ideally placed to form new intraspinal circuits after SCI.

Early decompression following cervical spinal cord injury: examining the process of care from accident scene to surgery

Early decompression may improve neurological outcome after spinal cord injury (SCI), but is often difficult to achieve because of logistical issues. The aims of this study were to 1) determine the time to decompression in cases of isolated cervical SCI in Australia and New Zealand and 2) determine where substantial delays occur as patients move from the accident scene to surgery. Data were extracted from medical records of patients aged 15-70 years with C3-T1 traumatic SCI between 2010 and 2013. A total of 192 patients were included. The median time from accident scene to decompression was 21 h, with the fastest times associated with closed reduction (6 h). A significant decrease in the time to decompression occurred from 2010 (31 h) to 2013 (19 h, p = 0.008). Patients undergoing direct surgical hospital admission had a significantly lower time to decompression, compared with patients undergoing pre-surgical hospital admission (12 h vs. 26 h, p < 0.0001). Medical stabilization and radiological investigation appeared not to influence the timing of surgery. The time taken to organize the operating theater following surgical hospital admission was a further factor delaying decompression (12.5 h). There was a relationship between the timing of decompression and the proportion of patients demonstrating substantial recovery (2-3 American Spinal Injury Association Impairment Scale grades). In conclusion, the time of cervical spine decompression markedly improved over the study period. Neurological recovery appeared to be promoted by rapid decompression. Direct surgical hospital admission, rapid organization of theater, and where possible, use of closed reduction, are likely to be effective strategies to reduce the time to decompression.

Early Spinal Surgery following Thoracolumbar Spinal Cord Injury: Process of Care From Trauma to Theatre.

Study Design. A retrospective cohort study. Objective. The aims of this study were to (1) determine the timing of surgery for traumatic thoracolumbar spinal cord injury (TLSCI) between 2010 and 2014 and (2) identify major delays in the process of care from accident scene to surgery. Summary of Background Data. Early spinal surgery may promote neurological recovery and reduce acute complications after TLSCI; however, it is difficult to achieve due to logistical issues and the frequent presence of other nonlife-threatening injuries. Methods. Data were extracted from the medical records of 46 cases of acute traumatic TLSCI (AIS level T1–L1) aged between 15 and 70 years. Patients with life-threatening injuries, not requiring spinal surgery or with poor general health, were excluded. Results. The median time to surgery was 27 hours [interquartile range (IQR): 20–43 hours] and improved from 27 hours in 2010 to 22 hours in 2014. Cases admitted via a pre-surgical hospital had a longer median time to surgery than direct surgical hospital admissions (28 vs. 24 hours, respectively). The median time from completion of radiological investigations to surgery was 18 hours, suggesting that theater access and organization of a surgical team were the major factors contributing to surgical delay. Number of vertebral levels fractured (≥5) and upper thoracic level of injury (T1–8) were also found to be associated with surgical delay. Conclusion. Earlier spinal surgery in TLSCI would be facilitated by direct surgical hospital admission and improved access to the operating theater and surgical teams. Level of Evidence: 3

Effects of treadmill training on hindlimb muscles of spinal cord injured mice

Introduction: Treadmill training is known to prevent muscle atrophy after spinal cord injury (SCI), but the training duration required to optimize recovery has not been investigated. Methods: Hemisected mice were randomized to 3, 6, or 9 weeks of training or no training. Muscle fiber type composition and fiber cross‐sectional area (CSA) of medial gastrocnemius (MG), soleus (SOL), and tibialis anterior (TA) were assessed using ATPase histochemistry. Results: Muscle fiber type composition of SCI animals did not change with training. However, 9 weeks of training increased the CSA of type IIB and IIX fibers in TA and MG muscles. Conclusions: Nine weeks of training after incomplete SCI was effective in preventing atrophy of fast‐twitch muscles, but there were limited effects on slow‐twitch muscles and muscle fiber type composition. These data provide important evidence of the benefits of exercising paralyzed limbs after SCI. Muscle Nerve, 2016 Muscle Nerve 55: 232–242, 2017

Gait recovery following spinal cord injury in mice: Limited effect of treadmill training

Background: Several studies in rodents with complete spinal cord transections have demonstrated that treadmill training improves stepping movements. However, results from studies in incomplete spinal cord injured animals have been conflicting and questions regarding the training dosage after injury remain unresolved. Objectives: To assess the effects of treadmill-training regimen (20 minutes daily, 5 days a week) for 3, 6 or 9 weeks on the recovery of locomotion in hemisected SCI mice. Methods: A randomized and blinded controlled experimental trial used a mouse model of incomplete spinal cord injury (SCI). After a left hemisection at T10, adult male mice were randomized to trained or untrained groups. The trained group commenced treadmill training one week after surgery and continued for 3, 6 or 9 weeks. Quantitative kinematic gait analysis was used to assess the spatiotemporal characteristics of the left hindlimb prior to injury and at 1, 4, 7 and 10 weeks post-injury. Results: One week after injury there was no movement of the left hindlimb and some animals dragged their foot. Treadmill training led to significant improvements in step duration, but had limited effect on the hindlimb movement pattern. Locomotor improvements in trained animals were most evident at the hip and knee joints whereas recovery of ankle movement was limited, even after 9 weeks of treadmill training. Conclusion: These results demonstrate that treadmill training may lead to only modest improvement in recovery of hindlimb movement after incomplete spinal cord injury in mice.

Early clinical predictors of pneumonia in critically ill spinal cord injured individuals: a retrospective cohort study

Study designRetrospective cohort.ObjectivesPneumonia is the dominant complication following traumatic spinal cord injury (SCI) and profoundly impacts morbidity by prolonging length of stay and worsening neurological outcome. The aims of this study were to determine the key predictors of clinically important pneumonia (CIP); and to examine the impact of CIP on resource utilisation in critically ill acute traumatic SCI individuals between 2010 and 2015.SettingAlfred and Austin Hospitals (Melbourne, Australia).MethodsData were extracted from the medical records of 93 cases of acute traumatic SCI resulting in ISNCSCI C3–L1 level of injury requiring admission to the intensive care unit and aged between 15 and 70 years. Patients with life-threatening injuries, not requiring spinal surgery, palliated within 7 days of injury, diagnosis of traumatic central cord syndrome or with poor general health, were excluded.ResultsA total of 33 episodes of CIP were observed. Median time to CIP diagnosis was 65 h (IQR: 42–93) and median time to spinal surgery was 22 h (IQR: 12–32). Four key predictors were identified; male gender (OR: 18.3, CI: 1.9–174.9, p = 0.001), motor complete injury (OR: 10.1, CI: 1.1–92.1, p = 0.011), presence of chest trauma (OR: 4.5, CI: 1.4–14.4, p = 0.007) and delayed intubation (HR: 6.8, CI: 1.6–28.6, p = 0.009).ConclusionsThis study identifies four key predictors involved in elevated pneumonia risk; male gender, motor complete injury, presence of chest trauma and delayed intubation, enabling the future synthesis of a pneumonia prediction tool for use in the acute postinjury period.