No / Sport as a whole has recently been under greater scrutiny over the safety of its participants. The tragic death of Australian Test Cricketer Philip Hughes brought into stark focus the risk of head injury but there has also been greater awareness of hypertrophic cardiomyopathy, concussion and use of performance enhancing drugs. Much of the research around concussion arises from what could be described as “collision” sports such as American football and ice hockey. The catalyst for discussions around concussion has tended to originate from these American sport. The significance of this increased awareness of safety has not been lost on the sport of rugby which has caused changes in practice in terms of concussion management but what appears not to have been fully appreciated is the additional risk of cervical spine injury associated with the sport.

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Adolescent Idiopathic Scoliosis (AIS) is typically treated surgically by Posterior Spinal Fusion (PSF) surgery. Intravenous analgesics and oral opioids are commonly used for pain management. Several adjunct therapies are used in addition to the standard treatments. One of these therapies is the use of dexmedetomidine (dex). Though dex has been found to be an effective sedative for post‐operative patients, there are also several adverse effects that are associated with its use. The purpose of this study was to investigate the effectiveness and overall benefit of using dex for pain control for patients undergoing PSF for AIS. IRB approval was obtained. A group of 43 patients with AIS undergoing PSF and using Dex for adjunctive pain control were matched with 43 patients who did not use Dex. The groups were matched based on gender, age, height, weight, and level of spinal fusion. During the patients’ post‐operative hospital stay, the total opioid use and clinical pain scores were compared between the two groups using t‐tests, with significance set at p<0.05. Total opiate use was 239.6 morphine equivalent doses in the non‐Dex (control) group and 246.2 in the group that received Dex (p=0.72). The average pain score in the control group was 2.3, and the group that received Dex was 2.6 (p =0.43). There were no differences in the complication rate between the two groups, specifically the oversedation rates and pulmonary complications. Lastly, the average length of stay for the control group was 4.8 days compared to the dex group, which was 5.0 days (p=0.35). Although adjunctive pain modalities may be very useful in the treatment of postoperative pain after PSF in patients with AIS, the use of Dex in this cohort did not improve pain scores, lower opioid use, or lower the LOS. Based on these results, we do not recommend the routine use of dexmedetomidine as an adjunctive pain control modality. Adjunctive modalities are important in pain control in patients with AIS undergoing PSF, but the use of dexmedotomidine was not effective in improving pain control.

Magister Scientiae (Physiotherapy) - MSc(Physio) / The distressing event of Spinal Cord Injury (SCI) leads to complete or incomplete injury, and results in many complications such as such as neurogenic shock, cardiovascular disease, temperature regulatory problems, respiratory complications, dysphagia, thromboembolism, and pressure ulcers amongst others. These complications limit the individual’s functioning and participation. Participation is fruitful and meaningful when you are actively involved in a specific activity. To understand the lack of participation within a specific setting, it is important to know what the limitations in activities are, and what causes these limitations. The goal of rehabilitation should be to reintegrate patients back into the community so that they can fulfil their roles. Aim: The aim of the study was (1) To determine included participants’ socio-demographic and injury characteristics; (2) To describe healthcare services received by people living with long-term Traumatic Spinal Cord Injury (TCSI) over the past 12 months; (3) To determine the point prevalence of common activity limitations of survivors of TSCI four years after injury; (4) To determine the point prevalence of participation restrictions of survivors of TSCI four years after injury; and (5) To determine factors associated with activity limitations and selected participation restrictions four years after injury.

Dissertation submitted to the Faculty of Health Sciences, University of the Witwatersrand, in fulfilment of the requirements for the degree of Master of Science in Medicine 2015 / Spinal cord injury (SCI) is a devastating injury affecting many South Africans. The purpose of the study was to investigate the relationship between SCI pain and sleep issues during acute inpatient rehabilitation. Seventeen participants were recruited. There were 2 interviews in the study; the 1st interview was done on the day participants were recruited. The 2nd interview was conducted a day before participants were discharged. The time elapsed between the first and second interview was 7.9±2.4. The patients were discharged from the Auckland Rehabilitation hospital (Hope ward). In the 2nd interview the questionnaires for pain, sleep and mood measures were repeated, and two additional questions were asked and the answers recorded for analysis of content. The key findings were; majority of the participants were Black, male (82%). The main cause of traumatic SCI was motor vehicle accident (59%). The common sites of injury were in the legs and neck/shoulder areas in both assessment (admission and discharge). The verbal descriptors that were commonly chosen in both assessments were, “sharp, shooting and tight.” Below level neuropathic pain, followed by musculoskeletal pain were the common types of pain reported. Pain interference was reported greatest in sleep and on average pain intensity was moderate (4-6 on 11-point Numerical Rating Scale). Strong correlations and positive relationships between Pain Catastrophizing Scale and subscales, and with the Pittsburgh Insomnia Rating total scale and subscales were reported in this study. Environmental factors were reported to affect sleep. A high incidence of Restless Leg Syndrome was reported in this study (24%). Depression was commonly reported by participants in both assessments. No significant association was found for the measures of sleep, Restless Leg Syndrome, depression and quality of life and the injury characteristics that were assessed. Significant associations were found at the 95% confidence levels for pain scores and injury characteristics (completeness of injury, level of injury and pain sites). Further studies in this area of pain and sleep management is warranted. It is important that clinicians and researchers in this area find appropriate management for secondary issues which have a severe impact on the daily activities of SCI people, decreasing their quality of life. Key words: SCI pain, sleep disturbances, mood / MT2016

Joie Jie Wang. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1993. / Includes bibliographical references (leaves 121-132). / ABSTRACT --- p.i / ACKNOWLEDGEMENTS --- p.iii / LIST OF TABLE --- p.vii / LIST OF FIGURES --- p.viii / LIST OF ABBREVIATIONS --- p.xii / Chapter CHAPTER I. --- INTRODUCTION --- p.1 / Chapter I.1. --- Fibre tracts of the rat spinal cord --- p.1 / Chapter I.2. --- Histopathological responses to spinal cord injuries --- p.2 / Chapter I.3. --- Failure of CNS regeneration --- p.4 / Intrinsic inability of CNS neurons themselves to regenerate --- p.4 / Inappropriate synapse without normal functioning --- p.5 / Progressive necrosis and cystic cavities --- p.5 / Autoimmune explanation for the failure of regeneration --- p.6 / Glial scarring --- p.6 / Absence of Schwann cells in the CNS --- p.7 / Lack of requisite growth factors --- p.8 / Chapter I.4. --- The use of transplants --- p.9 / Transplants of fetal nerve tissues --- p.9 / Transplants of peripheral nerve tissues --- p.10 / Transplants of neuroglial cells --- p.11 / Transplants of central neurons --- p.12 / Chapter I.5. --- Objectives of the present study --- p.13 / Chapter CHAPTER II. --- METERIALS AND METHODS --- p.15 / Chapter II.1. --- Hemisection of rats --- p.15 / Chapter II.2. --- Preparation of purified cortical astrocytes --- p.15 / Chapter II.3. --- Scanning electron microscopy (SEM) --- p.18 / Chapter II.4. --- HistologýؤLight microscopy --- p.19 / Chapter II.5. --- Measurement of volume of scar tissue --- p.19 / Chapter II.6. --- Immunofluorescence staining --- p.20 / Chapter II.7. --- Transmission electron microscopy --- p.23 / Chapter II.8. --- Comparison of expression of various proteins in the spinal cord --- p.24 / Polyacrylainide gel electrophoresis --- p.24 / Western blotting --- p.26 / Chapter CHAPTER III. --- RESULTS --- p.28 / Chapter III.1. --- Survival of cultured astrocytes --- p.28 / Chapter III.2. --- Light microscopy --- p.28 / Hemotoxylin and Eosin staining --- p.28 / Toluidine Blue staining --- p.30 / PHAL labelled astrocytes --- p.31 / Immunofluorescence staining --- p.32 / N-CAM --- p.32 / GFAP --- p.33 / NF --- p.34 / Chapter III.3. --- Transmission electron microscopy (TEM) --- p.35 / Chapter III.4. --- Determination of the volume of scar tissue --- p.37 / Chapter III.5. --- Gel electrophoresis --- p.38 / Chapter III.6. --- Immunoblotting and densitometry --- p.38 / Chapter CHAPTER IV. --- DISCUSSION AND CONCLUSIONS --- p.115 / REFERENCES --- p.121

Pedicle screw breakage and loosening remain as clinical complications of short segment instrumentation procedures for spinal stabilization. This study has directly visualized and measured elastic, plastic and total vertebral pedicle trabecular bone full-field strains in the regions immediately surrounding the pedicle screw during pedicle screw insertion by utilizing functional microCT imaging and digital volume correlation. Human, porcine and polyurethane foam samples were analyzed and compared. Analysis showed that when osteoporotic human, normal human and porcine pedicle trabecular bone samples were compared, osteoporotic samples showed higher peak plastic strains and greater variability of these strains from their means. This suggests that osteoporotic human samples are non-uniformly elastic and plastic, while normal human and porcine samples are more uniformly elastic and plastic throughout the trabecular structure. PU-foams are not appropriate as models for pedicle trabecular bone in the in vivo environment since strain results showed dissimilar plastic and elastic strain magnitudes than human and porcine pedicle trabecular bone. This study may aid in the development of performance criteria for new PU-foams and improved pedicle screw designs. / Graduation date: 2004

Abstract The first part of this research was focused on the relationship between injury severity and cell death mechanisms after spinal cord ischemia-reperfusion injury. The major blood supply to the thoracolumbar spinal cord comes from the segmental arteries originating from the thoracoabdominal aorta. Paraplegia cause by spinal cord ischemia is a devastating complication of thoracoabdominal aortic surgery. Previous studies indicated that ischemia-reperfusion injury of the central nervous system causes two distinct types of cell death, necrosis and apoptosis. It was also implicated that the intensity of injury can somehow affect the cell death mechanisms. In the first series of our experiments, by occluding the descending thoracic aorta with or without simultaneously inducing hypovolemic hypotension in rats, we established a model of experimental spinal cord ischemia-reperfusion (SCIR) in which the injury severity can be controlled. Recordings of carotid blood pressure (CBP) and spinal cord blood flow (SCBF) showed that aortic occlusion induced dramatic CBP elevation but SCBF drop in both the normotensive (NT) and hypotensive (HT) groups. However, the HT group demonstrated significantly lower SCBF during aortic occlusion, and much slower elevation of SCBF after reperfusion, and extremely poor neurological performance. Spinal cord lesions were characterized by infarction associated with extensive necrotic cell death, but little apoptosis and caspase-3 activity. In contrast, in the NT group, SCIR resulted in minor tissue destruction associated with persistently abundant apoptosis, augmented caspase-3 activity, and favorable functional outcome. The relative sparing of motoneurons in the ventral horns from apoptosis might have accounted for the minor functional impairment in the NT group. The severity of ischemia-reperfusion (I/R) injury was found to have substantial impact on the histopathological changes and cell death mechanisms, which correlated with neurological performance. These findings implicate that injury severity and duration after injury are two critical factors to be considered in therapeutic intervention. Based on the knowledge that bPrevious studies have implicated both excitotoxicity and apoptosis are involved in the pathogenesis of SCIR injury, we proposedtested the possibility that the N-methyl-D-aspartate (NMDA) receptor antagonist (dizocilpine maleate: (MK801) and the protein synthesis inhibitor (cycloheximide) would produce a synergic effect in the treatment of SCIR injury. In the second series of experiments, I/R iSpinal cord ischemia-reperfusion injury was induced by a thoracic aortic occlusion and blood volume reduction, followed by reperfusion and volume restoration. ischemia-reperfusion Rats were treated with vehicle, MK801, cycloheximide, or combination of MK801 and cycloheximide in combination. The MK801 and combined therapy group got a better recovery of hHind limb motor function recovery was better in the MK801 and combined-therapy groups than in the control and cycloheximide groups. On the 7th day after ischemia-reperfusion injury, all three treated groups showed significantly higher neuronal survival rates (NSR) than that of the control group. Among the three treated groups, the combined-treatment group showed the highest NSR. In addition, the Ttherapeutic effect of the combined-treatment group (27.4% increase of NSR) iwas better than the anticipated by the addition of MK801 and cycloheximide based on NSR data group. The number of apoptotic cells of was significantly reduced in the cycloheximide group and the combined-treatment group, as compared to that of the control group. It was unchanged in the MK-801 group. These results suggest that combined treatments directed at blocking both NMDA receptor-mediated excitotoxic necrosis and caspase-mediated apoptosis might have synergic therapeutic potential in reducing SCIR injury. Mitogen-activated protein kinases (MAPKs) including c-Jun N-terminal kinases (JNK), p38, and extracellular signal-regulated kinases (ERK), play important roles in the transduction of stressful signals and the integration of cellular responses. Although it has been generally held that the JNK and p38 pathways are related to cell death and degeneration, while the ERK pathway, cell proliferation and survival, controversy still exists. The roles of the ERK pathway in I/R injury of the CNS, in particular, remain to be clarified, because contradictory data have been reported by different investigators. Given this controversy, in the third series of experiments, we examined in injured spinal cords the temporal and spatial profiles of ERK1/2 activation following SCIR, and the effects of inhibiting the kinase that phosphorylates ERK1/2, MEK. The results showed that I/R injury induced an immediate phosphorylation of ERK1/2 in the spinal cord, which was alleviated by a MEK inhibitor, U0126. The control group was characterized by poorer neurological outcome, more severe tissue destruction, pronounced apoptosis, and lower neuronal survival. In contrast, the U0126-treated group demonstrated more apparent improvement of hind limb motor function, less tissue destruction, lack of apoptosis, and higher neuronal survival. In addition, administration of U0126 also significantly increased the activation of nuclear factor-£eB (NF-£eB) and the expression of cellular inhibitor of apoptosis protein 2 (c-IAP2). These findings implicate that the mechanisms underlying the neuroprotection afforded by ERK1/2 inhibition may be through the NF-£eB-c-IAP2 axis. The activation of the MEK-ERK signaling pathway appeared to be harmful in SCIR injury. Strategies aimed at blocking this pathway may bear potential therapeutic benefits in the treatment of SCIR injury. The second part of the research was focused on the pathophysiology of surgery-associated paraspinal muscle injury and measures to protect surgically violated paraspinal muscles. The wide dissection and forceful retraction of paraspinal muscles which are often required for posterior spinal sugery may severely jeopardize the muscles structurally and functionally. Immediate posteoperative pathological changes in the surgically violated paraspinal muscles may cause severe pain and a delay of patient ambulation. Long-term sequelae of surgical injury of paraspinal muscles include chronic back pain and impaired back muscle strength. Ironically, being a common complication of posterior spinal surgery, paraspinal muscle injury is so often neglected. Limited previous data indicate that the underlying pathophysiology of muscle damage involve both mechanical and ischemic mechanisms. We hypothesized that surgical dissection and retraction may produce oxidative stress within the paraspinal muscles. Meanwhile, we also proposed that the oxidative stress may trigger certain protective mechanisms within the insulted muscles. The first part of our study was a human study conducted to assess the significance of oxidative stress, and the relationship between it and the stress response mediated by heat shock protein 70 (HSP70) induction within paraspinal muscles under intraoperative retraction. A group of patients with lumbar spondylolisthesis treated with posterolateral lumbar spinal fusion, pedicle fixation and laminectomy were enrolled. Multifidus muscle specimens were harvested intraoperatively before, at designated time points during, and after surgical retraction. Muscle samples were analyzed for HSP70 and malondialdehyde (MDA) levels. Both HSP70 expression and MDA production within multifidus muscle cells were increased significantly by retraction. HSP70 expression then dropped after a peak at 1.5 hr of retraction, whereas MDA levels remained elevated even after release of retractors for reperfusion of the muscles. Histopathological and immunohistochemical evidence indicated that the decline of HSP70 synthesis within muscle cells after prolonged retraction was the result of severe muscle damage. These results highlighted the noxious impact of intraoperative retraction on human paraspinal muscles, and the significance of oxidative stress at the cellular and molecular levels. It is also implicated that intraoperative maneuvers aimed at reducing the oxidative stress within the paraspinal muscles may help attenuating surgery-associated paraspinal muscle damage. Given the findings of the first part of our study, and the knowledge that inflammation is a major postoperative pathological finding in surgically injured paraspinal muscles, we proceeded to examine the roles of two important inflammatory mediators, cyclooxygenase (COX)-2 and nuclear factor (NF)-£eB, in the pathogenesis of retraction-associated paraspinal muscle injury. A rat model of paraspinal muscle dissection and retraction that mimicks the conditions in human posterior spinal surgery was established. In the control group, paraspinal muscles were dissected from the spine through a dorsal incision, and then laterally retracted. Paraspinal muscle specimens were harvested before, and at designated time points during and after persistent retraction. The time course of NF-£eB activation as well as the expression of COX-2 were examined. Severity of inflammation was evaluated based on histopathology and myeloperoxidase (MPO) activity. NF-£eB activation was inhibited by the administration of pyrrolidine dithiolcarbamate (PDTC) in the PDTC-treated group. In the control group, retraction induced an early increase of NF-£eB/DNA binding activity in paraspinal muscle cells, which persited throughout the whole course of retraction. COX-2 expression was not detectable until 1 day after surgery, and reached a peak at 3 days. The time course of COX-2 expression correlated with that of inflammatory pathology and MPO activity. Extensive muscle fiber loss and collagen fiber replacement were observed at 7 days after surgery. Pretreatment with PDTC inhibited intraoperative NF-£eB activation and greatly downregulated postoperative COX-2 expression and inflammation in the muscles. Fibrosis following inflammation was also significantly abolished by PDTC administration. These findings indicate that NF-£eB-regulated COX-2 expression and inflammation play an important role in the pathogenesis of surgery-associated paraspinal muscle injury. Therapeutic strategies involving NF-£eB inhibition may be applicable to the prevention of such injury.

Thesis (Ph. D.)--University of Missouri-Columbia, 1999. / Typescript. Vita. Includes bibliographical references (leaves 138-148). Also available on the Internet.

Thesis (MHlthSc(OccTh))--University of South Australia, 1999

Thesis (MHlthSc(OccTh))--University of South Australia, 1999