Patients with acute spinal cord injury (SCI) have a high risk of venous thromboembolism (VTE) despite receiving thromboprophylaxis. The current standard of care recommended by guidelines is to use low-molecular-weight heparin (LMWH) for thromboprophylaxis for 90 days. This entails once- or twice-daily subcutaneous injections of LMWH for this duration, which is inconvenient for the patients and only partially effective. There are uncertainties about risk factors and the true incidence of SCI-associated VTE, the optimal time to commence thromboprophylaxis, and the optimal duration of thromboprophylaxis. Furthermore, there are currently no studies on the use of direct oral anticoagulants (DOACs) for thromboprophylaxis in patients with SCI. The use of DOACs for prophylaxis in this group can eliminate the inconvenience associated with daily subcutaneous injections for 3 months. To examine the incidence and risk factors of SCI-associated VTE, we performed a retrospective chart review of consecutive adult patients with acute SCI admitted to Hamilton General hospital from 2009 to 2015. The incidence of symptomatic VTE despite the use of thromboprophylaxis was 11% within 90 days of acute SCI; age and presence of other sites of injuries (such as lower limb fractures or pelvic fractures) along with SCI were independent risk factors for symptomatic VTE. To determine the opinion of Canadian spine surgeons about the optimal timing of starting LMWH after acute SCI, a short 5-question electronic survey was sent to the Canadian Spine Society. Data from our survey showed that the understanding about thromboprophylaxis after acute SCI was variable and that most spine surgeons were comfortable with starting LMWH after consultation with the surgeon. Future studies should focus on educational strategies to improve the knowledge base in this area. We will perform a pilot study at the Hamilton General Hospital comparing apixaban versus LMWH for thromboprophylaxis in patients with acute SCI. The use of apixaban for this indication can contribute to cost savings for the healthcare system and increased convenience for the patient. The protocol for the pilot study as well as steps towards a multi-center randomized controlled trial will be detailed in this thesis. / Thesis / Master of Science (MSc)

The internal vertebral venous plexus (IVVP) is an extensive vascular network recently implicated in various human and canine spinal disorders. Nevertheless, little recent information is available regarding normal anatomy of canine IVVP and its role in acute spinal injuries. The objectives of the study were; (1) to describe the normal IVVP morphology in the canine cervical region using transverse anatomy sections and computed tomography (CT), (2) to develop a technique for CT examination of the IVVP in vivo, (3) to analyze the quantitative characteristics of the IVVP, and (4) to assess the effect of acute experimental spinal cord compression on IVVP morphology. In the first experiment, CT of the cervical vertebral canal was performed in 6, normal, adult mixed-breed dogs. After dogs were euthanized, a gelatin and iothalamate mixture was injected into the right external jugular vein. Cadavers were then frozen to â 8°C, sliced into transverse sections, and compared with CT images. Vascular components such as the IVVP, interarcuate veins, intervertebral veins, and vertebral veins were accurately depicted on CT images. In the second experiment, CT venography was performed using a biphasic IV injection of iodinated contrast medium. Dimensions of the IVVP and other vertebral canal components were calculated for the C3-C7 vertebral region. Sagittal diameters of the IVVP ranged from 0.6 mm to 3.2 mm. The IVVP area occupied 30.61% of the cervical vertebral epidural space area. When C3-C7 segments were considered as a group, IVVP area dimensions were significantly correlated (r > 0.7, p < 0.0001) with vertebral canal area and dural sac area. In the last experiment, acute spinal cord compression (ASCC) was induced and maintained for 10 minutes using an angioplasty balloon catheter device over the C3/4 vertebral region in 6 dogs. Dogs were evaluated prior to, during, and after compression using digital subtraction venography (DSV) and CT venography. Results showed that ASCC produced a significant change in diameter of the IVVP at the site of compression. This effect persisted during the post-compression period. In conclusion, findings indicate that CT venography and DSV accurately depict the IVVP in dogs, and that significant changes of the IVVP morphology occur under ASCC conditions. / Ph. D.

Purpose To characterize differences in autonomic cardiovascular regulation after spinal cord injury compared to people without spinal cord injury through objective laboratory and subjective survey data, and to determine the component contribution of group III and group IV muscle afferents to overall autonomic integrity after spinal cord injury. Methods Individuals with spinal cord injury (n = 36), aged 18 years or older, and similarly age and gender matched individuals without spinal cord injury (n = 44) completed the Autonomic Dysfunction After Spinal Cord Injury (ADFSCI) survey. To test physiologic responses to a well-characterized, autonomic test as well as pilot another objective test, seven individuals with spinal cord injury and 10 individuals from the uninjured control group then completed further laboratory testing, including Valsalva maneuvers and ischemic hand grip. Results Individuals with spinal cord injury had neurological levels of injury C3-T12 and injuries graded A-D on the American Spinal Injury Association Impairment Scale (AIS). Individuals with spinal cord injury scored significantly higher by endorsing more daily symptoms of autonomic dysfunction on the ADFSCI survey compared to their uninjured peers (W = 272, p < 0.0001). However, in the group with spinal cord injury, higher ADFSCI scores were only weakly positively correlated with higher neurological level injury (R = 0.37, n = 36, p = 0.03) and more complete (AIS A or B) injury (R = 0.46, p = 0.01). Furthermore, the subgroup with spinal cord injury (n = 7) who completed laboratory testing displayed significantly altered blood pressure response during late phase II of the Valsalva maneuver compared to controls (p = 0.02). The same group of individuals with spinal cord injury also demonstrated a significantly lower maximal diastolic blood pressure in response to ischemic hand grip when compared to the control group (p = 0.04). Conclusion Self-reported daily symptoms of autonomic dysfunction are markedly higher after spinal cord injury. However, the relationship between these symptoms and neurological level of injury and AIS are only weakly correlated. This nonlinear relationship between ADFSCI scores and clinical injury characteristics emphasizes the need for further characterization of autonomic integrity. Physiologic laboratory tests more completely capture these alterations after spinal cord injury and point to developing bedside exams. / 2026-10-30T00:00:00Z

published_or_final_version / Orthopaedics and Traumatology / Master / Master of Philosophy

Research has begun to explore the presence and role of health-related injustice perceptions in samples of individuals who experience chronic pain associated with traumatic injury. Existing studies indicate that higher level of injustice perception is associated with poorer physical and psychosocial outcomes. However, to date, few clinical populations have been addressed. The aim of the current study was to explore injustice perceptions in a sample of individuals who have sustained a spinal cord injury (SCI), as research suggests that such individuals are likely to experience cognitive elements characteristic of injustice perception (e.g., perceptions of irreparable loss, blame, and unfairness). The study explored the relationship between participants’ level of perceived injustice and several variables associated with outcomes following SCI (depression, pain, and disability) at initial admission to a rehabilitation unit and at three months following discharge. The Injustice Experience Questionnaire was used to measure injustice perceptions. IEQ was found to significantly contribute to depression and anger at baseline. IEQ significantly contributed to depression, present pain intensity, and anger at follow-up. The implication of these preliminary findings may be beneficial for development of future interventions, as many individuals in the United States experience the lifelong physical and psychological consequences of SCI at a high personal and public cost.

Advances in health care science are enabling greater numbers of spinal cord injured persons to live to old age. As these persons grow older, there may be additional problems in coping due to stressors such as decreasing health and income and loss of significant others. The purpose of this study was to determine those factors that contribute to the well-being of middle-aged and elderly community-residing spinal cord injured persons. One hundred spinal cord injured persons ranging in age from 40 to 73 were interviewed. Extensive data were collected in order to investigate the relationship among social support, types of social comparisons made, perceived control, health status and psychological well-being and life satisfaction. In general, respondents reported a degree of well-being that was slightly lower than that reported in studies of nondisabled populations on the same measures of psychological well-being, life satisfaction, and depression. Pearson correlations and multiple linear regressions showed that persons reporting high levels of well-being made favorable social comparisons, reported high levels of perceived control over their lives, had high levels of social support, and judged their health status to be good. They also viewed their disability more favorably and tended to have higher incomes, more education, to be employed, and to be more religious than those indicating lower levels of well-being. The severity of the spinal cord injury was not correlated highly with subjective well-being, although there was a tendency for persons with greater disabilities to report lower levels of well-being. Persons who were younger and who incurred their disability at a younger age also tended to report higher levels of well-being. A model of well-being is proposed. This model suggests that social support fosters the perception of control and the making of favorable social comparisons which, in turn, foster a sense of well-being and satisfaction with life. This model provides direction for future research and has valuable implications for clinical application.

Doctor of Philosophy / The general aim of this current work was to examine spinal cord injury (SCI), and in particular to examine the pathology of injury as it relates to changes in sensory transmission. Due to the limited possibilities for experimentation in humans, a range of animal models of SCI have been developed and are reviewed here. The weight drop SCI model is the most similar to the clinical presentation of SCI in humans and has been widely used in the rat. It was selected for the series of experiments reported in this thesis. Many of the functional deficits produced by SCI result from a cascade of biochemical events set into motion by the injury. Included amongst these is the activation of the enzyme nitric oxide synthase which produces the gaseous neuromodulator, nitric oxide (NO). NO is amongst the most widely distributed and widely utilised molecule in virtually all living organisms, and it is an important signalling molecule in the nervous system. One of the major functions performed by NO appears to relate to sensory transmission, and thus alterations in sensory transmission observed as a result of SCI may involve alterations to NO synthesis. One of the principal aims of this thesis was to examine the effect of SCI on the NO producing cells of the spinal cord and to consider what any changes in NO synthesis may suggest in regards to sensation. NO producing cells were examined using NADPH diaphorase (NADPH-d) histochemistry. As the symptoms of SCI such as motor loss and changes in sensory processing are functional changes, it was also useful to examine changes in neuronal function as a result of SCI. Widespread neuronal function was examined via immunohistochemical detection of the gene product of the immediate early gene, c-fos. It is not known how extensive the biochemical changes resulting from SCI may be, thus another of the aims of the present thesis was to examine the effects of SCI on NO synthesis not only at the level of injury, but also distant to the injury. Findings of the present thesis indicated that traumatic SCI resulted in a decrease in the number of NADPH-d positive cells from the superficial dorsal horn (SDH) of the spinal cord, while the number of these cells are increased in the ventral horn. These changes were restricted to spinal segments adjacent to the injury. Fos expression was also altered by injury and was found to decrease. The most profound changes were found to occur in lamina III, although the other laminae also demonstrated similar changes. Changes in fos expression however were notably more widespread than those for NADPH-d and were not restricted to the level of the injury, occurring at all levels of the spinal cord examined. It was interpreted that alterations in NO synthesis appear to be modulated by the local injury-induced environment while fos expression may be altered by widespread changes to the global level of activity within the central nervous system. Having observed that the number of NADPH-d positive cells of the SDH is reduced following injury, it was of interest to determine whether these cells were in fact killed, or whether they were still present but with reduced NADPH-d activity. Cell counts suggested that the NADPH-d positive cells, which were likely to represent a population of inhibitory interneurons, were not killed following injury, but rather are disrupted such that their normal biochemistry is altered. Since these cells were likely to be inhibitory and were located in laminae involved in sensory transmission, the question arose how disruption of these cells may relate to the neuropathic pain observed to develop following SCI. Thus both NADPH-d and fos expression were again examined, but this time in conjunction with the sensory function of the rats. Sensory thresholds to pain-like behaviour were determined prior to and after injury using Von Frey filaments. Rats that demonstrated a decrease in sensory threshold of at least two Von Frey filament gradations (>70%) were classed as allodynic, while those with a less than a 70% decrease in threshold were classed as non-allodynic. A subpopulation of each of the groups of rats (uninjured, non-allodynic and allodynic) underwent a somatic stimulation paradigm. It was found that stimulation resulted in an increase in the number of NO producing cells but only in the allodynic group of animals. Since this group of animals by definition would perceive this stimulation as noxious, it is likely that the noxious nature of the stimulation resulted in the increased number of NO producing cells observed. This effect occurred only in segments adjacent to the injury. When fos expression was examined in the uninjured animals it was noted that somatic stimulation resulted in a decrease in fos expression, almost exclusively in lamina III. Following injury, there was no change in fos expression in lamina III observed. Instead the only change observed was an increase in fos expression in the deep dorsal horn (DDH, lamina IV and V). This occurred most profoundly in the allodynic group. These results suggested that SCI may lead to misprocessing of sensory signals such that non-noxious somatic stimuli are processed in the DDH rather than lamina III following SCI. It is proposed here that this change in laminae processing may be responsible for the perception of pain towards a non-noxious stimulus, and that the reported injury-induced loss of NO producing inhibitory interneurons in the SDH may be responsible for this alteration in sensory processing following SCI. Sensation is also processed by a number of supraspinal structures and a number of these have been implicated in the development of neuropathic pain states. The effects of SCI on neuronal activity as well as NO synthesis were examined in the periaqueductal grey region of the mid brain (PAG). SCI was shown to result in reduced neuronal activity in the PAG. This reduction in activity did not follow the somatotopy of the lateral column of the PAG (lPAG). It was suggested the reduced activity may not be solely caused by reduced spinal input as a result of SCI. Reduced neuronal activity in the PAG may indicate reduced PAG function, which includes descending modulation of spinal sensory transmission. Injury was not found to alter NADPH-d expression in the PAG. The effect of traumatic lumbar SCI on the parietal (sensorimotor) cortex of the rat was also examined, as loss of inputs following SCI have been shown to result in a profound reorganisation of the cortex. Results indicated that SCI results in a virtual cessation of neuronal activity in areas 1 and 2 of the parietal cortex, likely as a result of lost afferent drive. Theories of cortical plasticity suggest that while the primary inputs via the lumbar spinal cord may be lost following SCI, other less dominants input will remain and become more dominant. It has been proposed previously that cortical reorganisation involves a rapid reorganisation of the entire sensory system. It was interpreted that a similar process may explain the system-wide reduction in neuronal activity observed in the present series of studies.

Thesis (Ph. D.)--University of Washington, 2002. / Vita. Includes bibliographical references (leaves 120-128).

Source: Masters Abstracts International, Volume: 47-06, page: 3500. Adviser: Lu-Yu Hwang. Includes bibliographical references.

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