Many experimental therapies have been used in the search for effective approaches to improve recovery after spinal cord injury (SCI). One of the most promising approaches is the augmentation of spontaneously occurring plasticity in uninjured neural pathways. Acute intermittent hypoxia (AIH-brief exposures to reduced O2 levels alternating with normal O2 levels) elicits plasticity in respiratory and non-respiratory spinal systems in experimental animals. AIH treatment has also been shown to improve walking abilities in persons with chronic incomplete SCI. In this thesis, I first examined the effect of AIH treatment, alone or in combination with motor training, on functional recovery in a rat model of incomplete cervical SCI. Second, I examined the effect of AIH on the expression of plasticity- and hypoxia-related proteins in the spinal cords of SCI rats. In a randomized, blinded, normoxia-controlled study, rats were trained to cross a horizontal ladder and footslip errors were measured before surgery for SCI, 4 wks post-surgery, each day of daily AIH treatment, and 1, 2, 4 and 8 weeks after treatment. dAIH treatment consisted of 10 episodes of AIH: (5 min 11% O2: 5 min 21% O2) for 7 days beginning at 4 wks post-SCI. AIH-treated rats made fewer footslips on the ladder task compared to normoxia-treated control rats after 4 days of treatment and this improvement was sustained for 8 wks post-treatment. Importantly, daily ladder training was required for AIH treatment to facilitate recovery. AIH treatment + motor training also increased the expression of Hypoxia-inducible factor-1α (HIF-1α), Vascular endothelial growth factor (VEGF), Brain-derived neurotrophic factor (BDNF), tyrosine kinase B receptors (trkB) and phospho-trkB in spinal motor neurons in SCI rats compared to normoxia-treated SCI rats. In particular these hypoxia- and plasticity-related proteins were differentially expressed both temporally and spatially in the spinal cord during AIH treatment. These findings demonstrate that AIH + motor training can augment neural plasticity and improve motor recovery in an animal model of SCI. Taken together with the promising findings from human SCI studies, the results of this thesis suggest that AIH has potential as an effective therapy to restore motor function after nervous system injury.

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Objectives: Theoretical models have helped conceptualise how individuals appraise and make sense of chronic illness and its psychological impact. Little attention has been given to the impact of uncertainty on this process. The objective was to investigate the relationship between levels of uncertainty, illness representations, coping, psychological and physical functioning in two chronic illnesses. The Self-Regulatory Model (SRM, Leventhal, Meyer & Nerenz, 1980) was used as a theoretical framework. Design: A cross-sectional design was used. It was hypothesised that a clear medical diagnosis would reduce levels of uncertainty and increase illness representations regarding control of symptoms. It was also hypothesised that high levels of uncertainty would independently predict increased psychological distress. Method: Patients suffering from chronic spinal pain and rheumatoid arthritis were recruited from local clinical departments. The levels of uncertainty, illness representations, coping strategies, mood and physical functioning of 85 participants were assessed using standardised questionnaires. Results: Chronic pain patients were found to have greater levels of uncertainty and psychological distress than rheumatoid arthritis patients. Rheumatoid arthritis patients had stronger beliefs about control of their condition. Uncertainty was not found to be a significant independent predictor of anxiety or depression. However, there appeared to be a degree of overlap between the variables of uncertainty and control beliefs. Conclusions: The findings highlight a complex relationship between the aspects of the SRM and uncertainty, with many components impacting on each other. Although levels of uncertainty were not found to be predictive of psychological distress, it is an area that warrants further investigation in order to understand how patients manage uncertainty. Within a clinical setting, issues of uncertainty should be addressed at all levels of care, maximising the patient's control beliefs, reducing the impact of uncertainty on their cognitive, emotional and physical functioning.

The incidence of lumbar spinal stenosis (LSS) is steadily rising, mostly because of a noticeably older age structure. In Sweden, LSS surgery has increased continuously over the years and is presently the most common argument to undergo spine surgery. The purpose of the surgery is to decompress the neural elements in the stenotic spinal canal. To avoid instability, there has been a tradition to do the decompression with a complementary fusion, especially if degenerative spondylolisthesis is present preoperatively. The overall aims of this thesis were to evaluate which method of surgery that generally can be considered to give sufficiently good clinical results with least cost to society and risk of complications and to determine whether there is a difference in outcome between smokers and non-smokers. The Swespine Register was used to collect data on clinical outcome after LSS surgery. In two of the studies, large cohorts were observed prospectively with follow-up after 2 years. Data were analysed in a multivariate model and logistic regression. In a randomised controlled trial (RCT, the Swedish Spinal Stenosis Study), 233 patients were randomised to either decompression with fusion or decompression alone and then followed for 2 years. The consequence of preoperative degenerative spondylolisthesis on the results was analysed and a health economic evaluation performed. The three-dimensional CT technique was used in a radiologic biomechanical pilot study to evaluate the stabilising role of the segmental midline structures in LSS with preoperative degenerative spondylolisthesis by comparing laminectomy with bilateral laminotomies. Smokers, in comparison with non-smokers, showed less improvement after surgery for LSS. Decompression with fusion did not lead to better results compared with decompression alone, no matter if degenerative spondylolisthesis was present preoperatively or not; nor was decompression with fusion found to be more cost-effective than decomression alone. The instability caused by a decompression proved to be minimal and removal of the midline structures by laminectomy did not result in increased instability compared with the preservation of these structures by bilateral laminotomies. In LSS surgery, decompression without fusion should generally be the treatment of choice, regardless of whether preoperative degenerative spondylolisthesis is present or not. Special efforts should be targeted towards smoking cessation prior to surgery.

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Introduction Many chiropractic articles and textbooks discuss gait, but there actually has been little research into the effects of chiropractic adjustment on gait. This pilot study used a quantitative method of gait evaluation before and after a series of chiropractic visits. Hypotheses: (1) adults with chronic low back pain (CLBP) would show increased variability in vertical ground reaction forces (VGRF) while walking, as compared to healthy control subjects, and (2) that, following chiropractic care, will show decreased variability. Methods VGRF data were collected for 6 controls and compared to 9 CLBP participants, who were also evaluated before and after the first visit of care and over 7 visits. Data were analyzed by Mean Standard Deviation (MSD), Mean Coefficient of Variation (MCV), and the Coefficient of Variation of loading rate. Chiropractic care consisted of “high velocity low amplitude” thrust type procedures, flexion-distraction, pelvic wedges, light mobilization, and stretching. Results CLBP participants had somewhat greater variability and became slightly less variable post-care; differences were not significant. Limitations: Some participants had no impairment of walking at baseline; MSD is an uncommon measure, and more research is needed; these results (small group seen by a single doctor) may not be generalizable. Conclusions Participants with CLBP had slightly more variability and had slight decreases in variability following chiropractic care. Differences were not statistically significant. With this small pilot study as a guide, more research should be done with larger groups and improved participant selection.

The research was aimed at the effect of kinesitherapy on children aged 4-7 years with spinal disorders in the frontal and sagital plane. The research took place in kindergarten, 30 children were evaluated and separated in two groups: children with spinal disorders in the frontal plane (scoliosis) and children with spinal disorders in the sagital plane (hiperlordosis, hiperkyphosis). Children with selected features were trained with special active and passive exercises 8 months (3 times per week). The change of spinal disorder degree in the frontal and sagital plane were controlled with special measuring device Sabia’s scoliometer. The measurements were evaluated before training and after it. On the grounds of the findings it can be concluded that kinesitherapy was effective on children with spinal disorders in the frontal plane (I° scoliosis). The degree of scoliosis markedly decreased. The kinesitherapy was less effective on children with spinal disorders in the sagital plane. The quantity of hiperlordosis and hiperkyphosis decreased insignificantly.

SUMMARY Objective of the study. To assess the need of nursing care for patients with spinal cord injury during the early in-patient rehabilitation period. Methods. During the study, thirty-two patients following an acute spinal cord injury, hospitalized in the Neurorehabilitation Unit of the Rehabilitation Division at the Kaunas University of Medicine Hospital, were inquired, examined and cared for. The contingent of studied patients consisted of paraplegic individuals with retained upper limb functions who could fill in themselves a questionnaire, which included 22 questions. Results. The obtained data have shown that 10 women participating in the study were older than 22 men (p £ 0.05): the average age of the women (in the range of 28 to 70 years) was 41 years whereas of the men (in the range of 19 to 52 years), 33.86 years. A reliable correlation according to the Kendall coefficient was determined between the patients self–assessment and the real mobility of the studied individuals. The data of the study have shown that 17 (54.5 percent) of the patients with disturbed urinary function were febrile. The fever was assessed in all 7 patients with continuously indwelled Foley catheters (p £ 0.05), whereas in 15 cases of intermittent catheterization just 5 (33.3 percent) of the patients were febrile (p £ 0.05). The employment of the Fisher criterion has shown that in cases of continuously indwelled Foley catheters for the urinary bladder drainage and the presence of fever... [to full text]

Neuropathic pain is a significant and frequent outcome of spinal cord injury (SCI), and is often refractory to treatment. A better understanding of the pathological processes following injury that contribute to the development of neuropathic pain will aid the search for novel therapeutics. In the second chapter of this thesis a murine model of post-SCI below-lesion neuropathic pain was utilized to investigate changes in GABAergic tone. The gad1:GFP transgenic mouse line allowed the study of a subpopulation of GFPlabeled GABAergic neurons under control of the GABA synthesizing glutamate decarboxylase enzyme. SCI was observed to result in a loss of GABAergic neurons, and secondary markers of GABAergic tone supported this observation. This finding suggests that GABAergic interneuron cell death accounts for the decreased GABAergic tone previously reported post-SCI. In the third chapter of this thesis it was attempted to prevent the death of GABAergic neurons post-SCI using a transgenic mouse line expressing increased levels of the X-linked inhibitor of apoptosis (XIAP) under the ubiquitin C promoter. No differences were observed between ubXIAP and wildtype mice, indicating that increased expression of XIAP is not sufficient to prevent the development of neuropathic pain post- SCI. The fourth chapter of this thesis attempted to prevent the development of neuropathic pain through a novel treatment schedule of the drug pregabalin. Pregabalin administered shortly after SCI prevented the development of neuropathic pain. Pregabalin initiated 1 week post-SCI had no effect. Early pregabalin treatment did not appear to dramatically alter glial activation, or expression of the pregabalin receptor, but we observed changes in markers associated with synaptic plasticity. My findings build upon our knowledge of the mechanisms underlying post-SCI below-lesion neuropathic pain, and suggest new avenues of research, such as the uses of preemptive treatment with pregabalin, that offer promise for translation to clinical use.