PRECISION-TBI: a study protocol for a vanguard prospective cohort study to enhance understanding and management of moderate to severe traumatic brain injury in Australia.

INTRODUCTION: Traumatic brain injury (TBI) is a heterogeneous condition in terms of pathophysiology and clinical course. Outcomes from moderate to severe TBI (msTBI) remain poor despite concerted research efforts. The heterogeneity of clinical management represents a barrier to progress in this area. PRECISION-TBI is a prospective, observational, cohort study that will establish a clinical research network across major neurotrauma centres in Australia. This network will enable the ongoing collection of injury and clinical management data from patients with msTBI, to quantify variations in processes of care between sites. It will also pilot high-frequency data collection and analysis techniques, novel clinical interventions, and comparative effectiveness methodology. METHODS AND ANALYSIS: PRECISION-TBI will initially enrol 300 patients with msTBI with Glasgow Coma Scale (GCS) <13 requiring intensive care unit (ICU) admission for invasive neuromonitoring from 10 Australian neurotrauma centres. Demographic data and process of care data (eg, prehospital, emergency and surgical intervention variables) will be collected. Clinical data will include prehospital and emergency department vital signs, and ICU physiological variables in the form of high frequency neuromonitoring data. ICU treatment data will also be collected for specific aspects of msTBI care. Six-month extended Glasgow Outcome Scores (GOSE) will be collected as the key outcome. Statistical analysis will focus on measures of between and within-site variation. Reports documenting performance on selected key quality indicators will be provided to participating sites. ETHICS AND DISSEMINATION: Ethics approval has been obtained from The Alfred Human Research Ethics Committee (Alfred Health, Melbourne, Australia). All eligible participants will be included in the study under a waiver of consent (hospital data collection) and opt-out (6 months follow-up). Brochures explaining the rationale of the study will be provided to all participants and/or an appropriate medical treatment decision-maker, who can act on the patient's behalf if they lack capacity. Study findings will be disseminated by peer-review publications. TRIAL REGISTRATION NUMBER: NCT05855252.

Immediate Cooling and Early Decompression for the Treatment of Cervical Spinal Cord Injury: A Safety and Feasibility Study.

Cervical spinal cord injury (SCI) usually results in severe, long-term disability. Early therapeutic hypothermia (33-34°C) has been used to improve outcomes in preclinical studies, but previous clinical studies have commenced cooling after arrival at hospital. The objective of the study is to determine the feasibility and safety of early therapeutic hypothermia initiated by paramedics and maintained for up to 24 hours in hospital in patients with SCI. This is a pilot clinical study. The study was undertaken at Ambulance Victoria and The Alfred Hospital, Victoria, Australia. A total of 17 consecutive patients with suspected acute traumatic cervical SCI were enrolled. Patients with suspected cervical SCI were administered a bolus (up to 20 mL/kg) intravenous (IV) cold (4°C) normal saline in the prehospital phase of care. After hospital admission and spinal imaging, further cooling used IV catheter temperature control or surface cooling. Major complications and long-term outcomes were compared with historical controls admitted to the same center before the study. A decrease in core temperature of 1.1°C was achieved during prehospital care and the target temperature was achieved in 6 hours with mechanical temperature management devices in the hospital. There were no major safety concerns. Patients with motor complete SCI who underwent early decompressive surgery had a favorable rate of partial spinal cord recovery compared with historical controls. Therapeutic hypothermia induced using bolus, large-volume, ice-cold saline prehospital and maintained for 24 hours using mechanical devices appears to be feasible and safe in patients with SCI. Larger trials need to be undertaken to determine whether prehospital cooling combined with early decompressive surgery improves outcomes in patients with complete cervical SCI. Australian and New Zealand Clinical Trials Registry (ACTRN12616001086459).

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

STUDY DESIGN: Retrospective cohort. OBJECTIVES: Pneumonia 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. SETTING: Alfred and Austin Hospitals (Melbourne, Australia). METHODS: Data 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. RESULTS: A 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). CONCLUSIONS: This 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.

Acute Thoracolumbar Spinal Cord Injury: Relationship of Cord Compression to Neurological Outcome.

BACKGROUND: Spinal cord injury in the cervical spine is commonly accompanied by cord compression and urgent surgical decompression may improve neurological recovery. However, the extent of spinal cord compression and its relationship to neurological recovery following traumatic thoracolumbar spinal cord injury is unclear. The purpose of this study was to quantify maximum cord compression following thoracolumbar spinal cord injury and to assess the relationship among cord compression, cord swelling, and eventual clinical outcome. METHODS: The medical records of patients who were 15 to 70 years of age, were admitted with a traumatic thoracolumbar spinal cord injury (T1 to L1), and underwent a spinal surgical procedure were examined. Patients with penetrating injuries and multitrauma were excluded. Maximal osseous canal compromise and maximal spinal cord compression were measured on preoperative mid-sagittal computed tomography (CT) scans and T2-weighted magnetic resonance imaging (MRI) by observers blinded to patient outcome. The American Spinal Injury Association (ASIA) Impairment Scale (AIS) grades from acute hospital admission (≤24 hours of injury) and rehabilitation discharge were used to measure clinical outcome. Relationships among spinal cord compression, canal compromise, and initial and final AIS grades were assessed via univariate and multivariate analyses. RESULTS: Fifty-three patients with thoracolumbar spinal cord injury were included in this study. The overall mean maximal spinal cord compression (and standard deviation) was 40% ± 21%. There was a significant relationship between median spinal cord compression and final AIS grade, with grade-A patients (complete injury) exhibiting greater compression than grade-C and D patients (incomplete injury) (p < 0.05). Multivariate logistic regression identified mean spinal cord compression as independently influencing the likelihood of complete spinal cord injury (p < 0.01). CONCLUSIONS: Traumatic thoracolumbar spinal cord injury is commonly accompanied by substantial cord compression. Greater cord compression is associated with an increased likelihood of severe neurological deficits (complete injury) following thoracolumbar spinal cord injury. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

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.

Early Spinal Surgery Following Thoracolumbar Spinal Cord Injury: Process of Care From Trauma to Theater.

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.

Early Rapid Neurological Assessment for Acute Spinal Cord Injury Trials.

Clinical trials evaluating early therapies after spinal cord injury (SCI) are challenging because of the absence of a rapid assessment. The aim of this study was to determine whether the severity and level of SCI could be established from a brief neurological assessment capable of being used in an emergency setting. A brief assessment called the SPinal Emergency Evaluation of Deficits (SPEED) was developed and retrospectively evaluated in a cohort of 118 patients with SCI. Foot motor and sensory function was used to indicate injury severity. C3 dermatome sensation, handgrip strength and location of spinal pain were used to indicate the level of injury. With regard to injury severity, a high proportion of patients (94%) with no foot movement at the time of injury were initially diagnosed as motor complete (American Spinal Injury Association Impairment Scale [AIS] grade A-B), whereas all patients with foot movement were identified as motor incomplete (AIS grade C-D). This was reflected by a good correlation (rs = 0.79) and agreement (κ = 0.85) between the SPEED motor score and the acute hospital assessment. With respect to injury level, the majority of cases with cervical SCI (92%) had no or weak handgrip at the time of paramedic assessment, whereas all cases with thoracolumbar SCI had a strong handgrip. The location of spinal pain was also in accordance with the level of spinal injury. The SPEED assessment appears capable of accurately determining the severity and level of cervical SCI in the first hours post-injury. A neurological assessment that can be performed rapidly after injury is important for clinical trials of early therapy and to identify patients most likely to benefit from intervention.

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 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.

Effects of aquatic physiotherapy on the improvement of balance and corporal symmetry in stroke survivors.

INTRODUCTION: One of the main problems associate with hemiparesis after stroke is the decrease in balance during static and dynamic postures which can highly affect daily life activities. OBJECTIVE: To assess the effects of aquatic physiotherapy on the balance and quality of life (SS-QoL) of people with pos stroke. METHODS: Chronic stroke participants received at total 18 individual sessions of aquatic physiotherapy using the principle of Halliwick (2x of 40 minutes per week). The outcomes measured were: Berg Balance scale, Timed up & go test (TUG), Stroke Specific Quality of Life Scale (SS-QoL) and baropodometric analysis. These assessment were performed before and one week after intervention. RESULTS: Fifteen participants were included in this study. The mean age was 58.5 and 54% was male. After intervention, participants had a significant improvement on their static balance measured by Berg Balance scale and TUG. Dynamic balance had a significant trend of improvement in mediolateral domain with eyes closed and during sit-to-stand. The mobility domain of the SS-QoL questionnaire was significant higher after intervention. CONCLUSIONS: Our results suggest that aquatic physiotherapy using the method of Halliwick can be a useful tool during stroke rehabilitation to improve balance. However, this improvement may not have significant impact of their quality of life.

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; I(2)=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 r(2)=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.

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.