Australian Spinal Research Foundation

Damage to the axonal white matter tracts within the brain is a key cause of neurological impairment and long-term disability following traumatic brain injury (TBI). Understanding how axonal injury develops following TBI requires gyrencephalic models that undergo shear strain and tissue deformation similar to the clinical situation and investigation of the effects of post-injury insults like hypoxia. The aim of this study was to determine the effect of post-traumatic hypoxia on axonal injury and inflammation in a sheep model of TBI. Fourteen male Merino sheep were allocated to receive a single TBI via a modified humane captive bolt animal stunner, or sham surgery, followed by either a 15 min period of hypoxia or maintenance of normoxia. Head kinematics were measured in injured animals. Brains were assessed for axonal damage, microglia and astrocyte accumulation and inflammatory cytokine expression at 4 hrs following injury. Early axonal injury was characterised by calpain activation, with significantly increased SNTF immunoreactivity, a proteolytic fragment of alpha-II spectrin, but not with impaired axonal transport, as measured by amyloid precursor protein (APP) immunoreactivity. Early axonal injury was associated with an increase in GFAP levels within the CSF, but not with increases in IBA1 or GFAP+ve cells, nor in levels of TNFα, IL1β or IL6 within the cerebrospinal fluid or white matter. No additive effect of post-injury hypoxia was noted on axonal injury or inflammation. This study provides further support that axonal injury post-TBI is driven by different pathophysiological mechanisms, and detection requires specific markers targeting multiple injury mechanisms. Treatment may also need to be tailored for injury severity and timing post-injury to target the correct injury pathway.

BackgroundAssessment of functional impairment following ischaemic stroke is essential to determine outcome and efficacy of intervention in both clinical patients and pre-clinical models. Although paradigms are well described for rodents, comparable methods for large animals, such as sheep, remain limited. This study aimed to develop methods to assess function in an ovine model of ischaemic stroke using composite neurological scoring and gait kinematics from motion capture.MethodsMerino sheep (n = 26) were anaesthetised and subjected to 2 hours middle cerebral artery occlusion. Animals underwent functional assessment at baseline (8-, 5-, and 1-day pre-stroke), and 3 days post-stroke. Neurological scoring was carried out to determine changes in neurological status. Ten infrared cameras measured the trajectories of 42 retro-reflective markers for calculation of gait kinematics. Magnetic resonance imaging (MRI) was performed at 3 days post-stroke to determine infarct volume. Intraclass Correlation Coefficients (ICC's) were used to assess the repeatability of neurological scoring and gait kinematics across baseline trials. The average of all baselines was used to compare changes in neurological scoring and kinematics at 3 days post-stroke. A principal component analysis (PCA) was performed to determine the relationship between neurological score, gait kinematics, and infarct volume post-stroke.ResultsNeurological scoring was moderately repeatable across baseline trials (ICC > 0.50) and detected marked impairment post-stroke (p < 0.05). Baseline gait measures showed moderate to good repeatability for the majority of assessed variables (ICC > 0.50). Following stroke, kinematic measures indicative of stroke deficit were detected including an increase in stance and stride duration (p < 0.05). MRI demonstrated infarction involving the cortex and/or thalamus (median 2.7 cm3, IQR 1.4 to 11.9). PCA produced two components, although association between variables was inconclusive.ConclusionThis study developed repeatable methods to assess function in sheep using composite scoring and gait kinematics, allowing for the evaluation of deficit 3 days post-stroke. Despite utility of each method independently, there was poor association observed between gait kinematics, composite scoring, and infarct volume on PCA. This suggests that each of these measures has discreet utility for the assessment of stroke deficit, and that multimodal approaches are necessary to comprehensively characterise functional impairment.

# Presentation CPSS1: Spinal insufficiency fracture in the geriatric pediatric spine {#article-title-2} Regular corticosteroid has become standard for slowing disease progression in Duchenne muscular dystrophy (DMD). However, patients must contend with the insidious side effect of osteopenia and

Prospective, double-blind, randomised, placebo-controlled, cross-over trial of nasal decongestion in tetraplegia. Tetraplegia is complicated by severe, predominantly obstructive, sleep apnoea. First-line therapy for obstructive sleep apnoea is nasal continuous positive airway pressure, but this is poorly tolerated. High nasal resistance associated with unopposed parasympathetic activation of the upper airway contributes to poor adherence. This preliminary study tested whether reducing nasal decongestion improved sleep. Participants' homes in Melbourne and Sydney, Australia. Two sleep studies were performed in participants' homes separated by 1 week. Participants were given a nasal spray (0.5 mL of 5% phenylephrine or placebo) in random order and posterior nasal resistance measured immediately. Outcomes included sleep apnoea severity, perceived nasal congestion, sleep quality and oxygenation during sleep. Twelve middle-aged (average (SD) 52 (12) years) overweight (body mass index 25.3 (6.7) kg/m2) men (C4-6, AIS A and B) participated. Nasal resistance was reduced following administration of phenylephrine (p = 0.02; mean between treatment group difference -5.20: 95% confidence interval -9.09, -1.32 cmH2O/L/s). No differences were observed in the apnoea hypopnoea index (p = 0.15; -6.37: -33.3, 20.6 events/h), total sleep time (p = 0.49; -1.33: -51.8, 49.1 min), REM sleep% (p = 0.50; 2.37: -5.6, 10.3), arousal index (p = 0.76; 1.15: -17.45, 19.75), 4% oxygen desaturation index (p = 0.88; 0.63: -23.5, 24.7 events/h), or the percentage of mouth breathing events (p = 0.4; -8.07: -29.2, 13.0) between treatments. The apnoea hypopnoea index did differ between groups, however, all except one participant had proportionally more hypopnoeas than apnoeas during sleep after decongestion. These preliminary data found that phenylephrine acutely reduced nasal resistance but did not significantly change sleep-disordered breathing severity.

International collaboration in spinal cord injury (SCI) research is necessary to overcome the challenges often encountered by clinicians and researchers, including participant recruitment, high cost, and the need for specialized expertise. However, international collaboration poses its own obstacles. The objective of this study was to conduct an international online survey to assess barriers and facilitators to international SCI clinical research, potential initiatives to facilitate future collaborations, and the use of SCI-specific data sets and standards. Results were analyzed using descriptive statistics. Of 364 total respondents, 213 completed the survey, with the majority of these participants based in North America (38%), Asia (22%), Europe (18%), and Oceania (16%). Over half had more than 10 years of experience in SCI research or clinical practice (57%) and 60% had previous experience with international collaborations. Funding was identified as a top barrier (82%), a facilitator (93%), and a proposed future initiative (97%). Communication and technology were also identified as strong facilitators and proposed future initiatives. The International Standards for Neurological Classification of SCI were used by 69% of participants, the International Standards to document remaining Autonomic Function after SCI by 13% of participants, and the International SCI Data Sets by 45% of participants. As the need for international collaborations in SCI research increases, it is important to identify how clinicians and researchers can be supported by SCI consumer and professional organizations, funders, and networks. Furthermore, unique solutions to overcome modifiable barriers and creation of new facilitators are also needed.

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.