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Wahman, Kerstin. "Cardiovascular disease prevention after spinal cord injury : a new challenge /." Stockholm, 2010. http://diss.kib.ki.se/2010/978-91-7409-936-2/.
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Nelvagal, Hemanth Ramesh. "Spinal cord pathology in CLN1 disease : a novel therapeutic target." Thesis, King's College London (University of London), 2017. https://kclpure.kcl.ac.uk/portal/en/theses/spinal-cord-pathology-in-cln1-disease(8b1dc3ed-dfd9-442d-a427-43ded0d82a6a).html.
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The neuronal ceroid lipofuscinoses (NCLs) are a group of up to 14 inherited progressive neurodegenerative lysosomal storage disorders affecting children and young adults. Together, they are the most common pediatric neurodegenerative storage disorders. Symptoms include loss of vision, epileptic seizures and the loss of cognitive and motor function. A lack of any effective therapies means that all forms are fatal. CLN1 disease or Infantile NCL is one of the most rapidly progressing forms of the disease and is caused by a deficiency of the lysosomal enzyme palmitoyl protein thioesterase – 1 (PPT1). Ppt1 deficient (Ppt1-/-) mice recapitulate features of the human disease and have proved to be a useful tool in characterizing disease progression and pathology in the brain. However, these pathological changes fail to fully explain the sensorimotor deficits seen in this mouse model as well as in human CLN1 disease. Along with the limited success of various brain directed therapies, this led us to analyze the spinal cord. Our analysis revealed unexpectedly profound and rapidly progressing disease pathology in the spinal cords of these mice, which occurs earlier than similar events in the brain. This included regional atrophy, neuroinflammation, and significant neuron loss at all levels of the cord as well as novel phenotypes indicating a postnatal developmental delay and significant white matter pathology. Automated gait analysis also showed novel early phenotypes in these mice including an increased dependence on the forelimbs for locomotion. Similar spinal cord pathology was also demonstrated in human INCL autopsy samples as well as in mouse models of the other major forms of NCL. Targeting the spinal cords of Ppt1-/-mice with enzyme replacement therapy (ERT) and gene therapy significantly improved disease pathology, motor function and lifespan in these mice, demonstrating the clinical significance of spinal cord pathology in these mice. Furthermore, combining intracranial and intrathecal gene therapy showed a synergistic effect, showing the greatest improvements for any CLN1 disease therapy to date. Taken together, these findings highlight the spinal cord as not only being significantly affected in CLN1 disease, but also as a novel and effective therapeutic target.
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Rogers, A. T. "Spinal cord cell culture : a model for neuronal development and disease." Thesis, University of Bath, 1988. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.234048.
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Flank, Peter. "Spinal cord injuries in Sweden : studies on clinical follow-ups." Doctoral thesis, Umeå universitet, Rehabiliteringsmedicin, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-125202.
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A spinal cord injury is a serious medical condition, often caused by a physical trauma. An injury to the spinal cord affects the neurotransmission between the brain and spinal cord segments below the level of injury. The SCI causes a loss of motor function, sensory function and autonomic regulation of the body, temporary or permanent. Significantly improved acute care, primary comprehensive rehabilitation and life-long structured follow-up has led to persons with spinal cord injury (SCI) living longer than ever before. However, increased long-time survival has allowed secondary conditions to emerge, like diabetes mellitus and where cardiovascular disease (CVD) now is the most common cause of death among SCI patients. Other possible CVD-related comorbidities in this patient group have been reported to be pain and mood disturbances. There is still lack of, and need for more knowledge in the field of CVD-related screening and prevention after SCI. The overall aim of this thesis was to contribute to a scientific ground regarding the need for CVD-related screening and prevention after SCI. In Paper I and Paper II, patients with wheelchair-dependent post-traumatic SCI (paraplegia) were assessed. The results in paper I showed that 80% of the examined patients had at least one cardiovascular disease risk marker irrespective of body mass index (BMI). Dyslipidemia was common for both men and women at all BMI categories. The study also showed a high prevalence of hypertension, especially in men. Paper II showed a low frequency of self-reported physical activity, where only one out of 5 persons reported undertaking physical activity >30 min/day. The physically active had lower diastolic blood pressure but no significant difference in blood lipids. In paper III and IV, patients with SCI (tetraplegia and paraplegia) participated in the studies. Eighty-one percent of the patients had dyslipidemia, where also a majority of the patients with normal abdominal clinical measures had dyslipidemia. Self-reported physical activity >30min/day was reported by one third of the patients. No differences were found between physically active and not physically active patients when it came to blood glucose, serum lipid values and clinical measures (paper III). Pain was common in the patient group, however, most often on a mild to moderate level. Anxiety and depression was less common than reported in other studies (paper IV).
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Paulson, Thomas A. W. "Supporting the prescription of exercise in spinal cord injured populations." Thesis, Loughborough University, 2013. https://dspace.lboro.ac.uk/2134/13454.
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Following a spinal cord injury (SCI), participation in regular exercise can enhance physical capacity and performance in activities of daily living. With this in mind, the use of subjective ratings of perceived exertion (RPE) may provide an easy-to-administer alternative to traditional methods of regulating exercise intensity (e.g. heart rate and power output (PO)). A physically active lifestyle is also associated with a reduced risk of cardiovascular disease, in part because exercise exerts anti-inflammatory effects. Examining the plasma response of inflammation-mediating chemical messengers, known as cytokines, to traditional and novel exercise modalities may help maximise the anti-inflammatory potential of regular exercise. Participants with a cervical level SCI successfully self-regulated a 20 min bout of moderate intensity wheelchair propulsion (Chapter three). No differences in physiological or PO responses were observed during the imposed-intensity and self-regulated wheelchair propulsion in the trained population group. In a non-SCI group of novice wheelchair-users, a differentiated RPE specific to the exercising muscle mass (RPEP) was the dominant perceptual signal during submaximal wheelchair propulsion (Chapter four). The novice group successfully self-regulated a 12 min bout of moderate intensity wheelchair propulsion, comprising of a discontinuous 3 x 4 min protocol, using differentiated RPEP. In contrast, a more accurate self-regulation of light intensity wheelchair propulsion was observed when employing traditional overall RPE compared to RPEP. Following strenuous wheelchair propulsion, plasma concentrations of the inflammation-mediating cytokine interleukin-6 (IL-6) were significantly elevated in non-SCI and thoracic level SCI participants (Chapter five). Impaired sympathetic nervous system (SNS) function was associated with a reduced IL-6 response in participants with a cervical level SCI. The plasma IL-6 response to 30 min moderate intensity (60% VO2peak) arm-crank ergometry (ACE) was associated with an elevation in the anti-inflammatory cytokine IL-1 receptor antagonist (IL-1ra) independent of SNS activation (Chapter six). Light intensity ACE resulted in a small, significant plasma IL-6 response but no IL-1ra response. The addition of functional electrical stimulation-evoked lower-limb cycling to concurrent hand cycling, termed hybrid exercise, resulted in a greater plasma IL-6 response compared to moderate intensity hand cycling alone in participants with a thoracic level SCI (Chapter seven).
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Davies, Diane Susan. "Effects of lifestyle risks on three major disease outcomes in spinal cord injured adults." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp04/mq22296.pdf.
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Erschbamer, Matthias. "Spinal cord injury : development of protection and repair strategies in rats /." Stockholm : Karolinska institutet, 2007. http://diss.kib.ki.se/2007/978-91-7357-267-5/.
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López, Serrano Clara. "Role of lysophosphatidic acid receptors in spinal cord injury physiopathology." Doctoral thesis, Universitat Autònoma de Barcelona, 2017. http://hdl.handle.net/10803/458682.
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La médula espinal, la cual constituye una parte vital para el sistema nervioso central (SNC), puede resultar dañada a pesar de estar muy bien protegida por la columna vertebral, dando lugar a importantes consecuencias. La lesión medular provoca una alteración de las redes neuronales que están involucradas en diversas funciones fisiológicas. De hecho, dado que los axones del SNC de mamíferos adultos no pueden regenerarse tras una lesión, y que las células dañadas no pueden ser reparadas, esta patología viene acompañada de una pérdida funcional irreversible para los pacientes afectados.
La fisiopatología de la lesión medular se compone de dos fases degenerativas. La fase primaria es consecuencia directa del trauma en la médula, la cual provoca muerte celular, daño axonal y pérdida de mielina. Esta primera fase es sucedida por una secundaria, en la cual se produce un proceso inflamatorio, crucial para el desarrollo de la enfermedad. Aunque la regeneración de los axones dañados y el reemplazo de las neuronas perdidas tras la lesión son objetivos importantes, minimizar el daño secundario a axones, neuronas, mielina y células gliales que sigue al trauma inicial es posiblemente más interesante desde un punto de vista terapéutico. En concreto, la respuesta inflamatoria de esta fase secundaria juega un papel muy importante en la lesión, siendo, por tanto, una buena diana para la búsqueda de una terapia efectiva.
Una de las moléculas involucradas en el proceso inflamatorio es el ácido lisofosfatídico (del inglés, LPA), el cual es un lípido bioactivo extracelular que juega un papel importante en diversas funciones fisiológicas. El LPA señaliza a través de seis receptores acoplados a proteína G (LPA1-6), los cuales se clasifican en dos familias: la familia del gen de diferenciación endotelial (del inglés, Edg), que comprende los receptores LPA1-3, y la familia de receptores que no pertenecen a la familia Edg, es decir, Non-Edg (LPA4-6). El LPA se sintetiza a partir de dos vías principales: (i) mediante la acción de la enzima autotaxina (ATX), la cual es la responsable de la síntesis de LPA en plasma, y (ii) mediante la acción de fosfolipasas de tipo de A2 (PLA2), las cuales se encargan de la síntesis en tejido.
El LPA juega un papel importante en la fase secundaria de la lesión medular, ya que sus niveles se ven aumentados en el parénquima medular tras el trauma, dando lugar a desmielinización y pérdida de la función locomotora. De hecho, la ausencia de los receptores LPA1 y LPA2 tras la lesión medular mejora la recuperación funcional de los animales y la preservación mielínica en la médula. En esta tesis, revelamos que la activación de los receptores LPA1 y LPA2 microgliales provoca la muerte de los oligodendrocitos. Además, mostramos que los efectos citotóxicos que se desencadenan tras la estimulación de dichos receptores son mediados por la secreción de purinas y la subsecuente activación del receptor P2X7 en oligodendrocitos. Por otro lado, también demostramos que, al contrario de los receptores LPA1 y LPA2, los receptores LPA4 y LPA5 no contribuyen a la fisiopatología de la lesión medular.
En el presente trabajo, también mostramos que la inhibición farmacológica de la ATX no tiene ningún efecto en la recuperación funcional ni el daño secundario tras la lesión medular, lo cual sugiere que la fuente principal de LPA en esta patología no es la síntesis en plasma. Además, demostramos que el bloqueo combinado de LPA1 y LPA2 no tiene efectos aditivos en la lesión medular.
En general, los resultados de esta tesis sugieren que la inhibición farmacológica del LPA1 y, preferiblemente el LPA2, abren una nueva ventana terapéutica para el tratamiento de la lesión medularThe spinal cord is an extremely vital part of the central nervous system (CNS) and, although it is well protected by the spinal column, it can be damaged, resulting in serious consequences. Spinal cord injury (SCI) leads to a disruption of the neuronal networks that are involved in many physiological functions. Since CNS axons of adult mammals do not regenerate following the lesion, and dead neurons and glial cells are not successfully replaced, this results in an irreversible functional loss in patients suffering from SCI. The pathophysiology of SCI involves two degenerative stages, known as primary and secondary injury. The first one results from the direct mechanical trauma to the spinal cord, directly causing cell death, damage to axons, and loss of myelin. This is followed by a secondary wave of tissue degeneration that can extend for several weeks, in which inflammation plays a crucial role. Although regeneration of damaged axons and replacement of lost neurons and glial cells are important goals for the restoration of the injured spinal cord, minimizing secondary damage to axons, neuronal cell bodies, myelin and glial cells that follows the initial trauma is likely to be more easily amenable to treatment. Since inflammation is a major contribution to secondary damage in SCI, targeting the detrimental actions of this physiological response could result in the development of novel approaches for the treatment of this pathology. Lysophosphatidic acid (LPA) is an extracellular bioactive lipid with many physiological functions. It signals through six known G-protein coupled receptors (LPA1-6), which are classified into two families: Endothelial differentiation family gene (Edg) LPA receptors (LPA1-3) and Non-Edg family gene LPA receptors (LPA4-6). LPA synthesis is carried out by two different pathways: (i) by the action of the enzyme named autotaxin (ATX), which is the main responsible in synthesis of this lipid in plasma, and (ii) by action of the phospholipase A2 (PLA2) family enzymes, which are the main route of LPA synthesis in tissues. LPA is a key trigger of secondary damage after SCI, since its increased levels in the spinal cord parenchyma following injury leads to demyelination. Indeed, the lack of LPA1 and LPA2 signalling after SCI enhances functional recovery and myelin sparing. In this thesis, we show that activation of microglial LPA1 and LPA2 leads to oligodendrocyte cell death. We reveal that the cytotoxic actions underlying by microglial cells stimulated with LPA are mediated by the release of purines and the subsequent activation of P2X7 in oligodendrocytes. We also show that, unlike LPA1 and LPA2, LPA4 and LPA5 receptors do not contribute to SCI physiopathology. In the present thesis, we also show that pharmacological inhibition of ATX does not have any effect in functional outcomes and secondary tissue damage after SCI, suggesting that this enzyme is unlikely to be involved in the production of LPA in the spinal cord parenchyma after injury. We also demonstrate that combinatory targeting of LPA1 and LPA2 does not results in additive effects in SCI. Overall, the results shown here suggest that pharmacological inhibition of LPA1, and preferably LPA2, may open a new therapeutic avenue for the treatment of SCI.
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Pahuta, Markian. "Decision Analysis of Surgical Treatment Indications for Metastatic Epidural Spinal Cord Compression." Thesis, Université d'Ottawa / University of Ottawa, 2019. http://hdl.handle.net/10393/39390.
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Metastatic epidural spinal cord compression (MESCC) occurs when tumour invades the epidural space and compresses the spinal cord. Despite Level 1 evidence that surgery is the most effective treatment for MESCC, there is controversy regarding the role of surgery because of fear that patients who have a short survival will spend a large fraction of their remaining life recovering from surgery and potential complications. This controversy could be resolved by decision-analysis of MESCC treatments using quality-adjusted-life-years (QALYs).
There have been two barriers to conducting decision-analysis of QALYs for MESCC: (a) lack of utility data, and (b) skepticism regarding decision-analysis. The first four research chapters in this thesis address these barriers. The final research chapter reports a decision-analysis of QALYs on the role of surgery in MESCC.
Chapter 1 provides background information on the controversy regarding surgical treatment for MESCC and the rationale for each of the subsequent chapters. Chapter 2 reports a psychometric validation study of a web-based utility valuation module for MESCC. In Chapter 3, application of this module to a general population utility valuation study with a market research panel is described. In Chapter 4, the beneficial properties of Bayesian statistical analysis to minimizing “arbitrariness” in probabilistic sensitivity analysis are described in relation to prognostication for MESCC. Chapter 5 presents a strategy for simplifying and enhancing the transparency of Markov cohort simulation. Finally, the work presented in the research chapters is applied in Chapter 6 to conduct Markov cohort simulation to determine if patients with short survival derive net health-related quality-of-life benefit from surgery.
Pragmatic research around barriers to decision-analysis of QALYs for MESCC was conducted to resolve the controversy regarding the role of surgery in the treatment of MESCC. Under most circumstances, MESCC patients who can ambulate prior to treatment derive net HRQoL benefit from surgery, even if prognosis is poor. Non-ambulatory patients can derive net HRQoL benefit but only if the morbidity of surgery is relatively low. It is my hope that the work used to address barriers to decision-analysis of QALYs will be disseminated and applied in other clinical problems.
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Cooper, Cindy L. "Neuropeptides, amines and amine receptors in the human spinal cord : the effects of Parkinson's disease." Thesis, University of Nottingham, 1989. http://eprints.nottingham.ac.uk/13218/.
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The aims of this study were to investigate (i) the levels of catecholamines, indoleamines, substance P and thyrotrophin-releasing hormone (TRH) in the post-mortem spinal cord of subjects who had died with Parkinson's disease and to compare them with those of control subjects (ii) adrenergic and serotonergic receptors in the post-mortem Parkinsonian and control spinal cord and (iii) the effects of subject age and sex and the interval between death and post-mortem (PMI) on the levels of neurotransmitters and neuropeptides and on receptor binding in post-mortem tissue. To perform these investigations (i) a sensitive radioimmunoassay which is specific for substance P and has low cross-reactivity with other similar peptides and (ii) a common extraction medium for the concomitant extraction of catecholamines, indoleamines, substance P and TRH from CNS tissue were developed. The main findings were: There were significant correlations between the levels of 5HT, TRH and α2-adrenoceptor binding and both subject age and the PMI. In Parkinson's disease compared with control subjects: (i) the levels of noradrenaline were significantly reduced in the thoracic ventral region of the spinal cord,(ii) dopamine levels were higher in the thoracic ventral and dorsal spinal cord,(iii) in the lumbar spinal cord 5HT levels were significantly reduced in the dorsal horn with an increase in the ratio of 5HIAA/5HT, (iv) noradrenaline levels were reduced in both dorsal and ventral horns of the lumbar spinal cord and (v) there were no differences between the levels of substance P and TRH in any spinal cord region. There were no measurable 5HT1A or 5HT2 binding sites in the human spinal cord under the conditions used. However, specific α2-adrenoceptor binding was defined in terms of binding affinity and number of receptors in the spinal cord.
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Jones, Page. "Enzymatic and proteomic analysis of spinal cord in a G93A ALS mouse model." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2008. https://www.mhsl.uab.edu/dt/2008r/jonesp.pdf.
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Zbogar, Dominik. "Cardiovascular disease risk and central and peripheral responses to exercise in individuals with spinal cord injury." Thesis, University of British Columbia, 2009. http://hdl.handle.net/2429/15888.
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Introduction: Persons with spinal cord injury (SCI) are often physically inactive and as such are at increased risk of cardiovascular morbidity. Fortunately, exercise training in SCI can provide
improve health-related physical fitness and alleviate medical complications associated with deconditioning. To optimize health-related fitness gains of exercise in SCI and maximize the potential for chronic disease prevention it is necessary to understand the acute responses (central and peripheral) to exercise. Purposes: The primary purposes of this research were to: 1) determine the contribution of central/peripheral limitations to exercise capacity and 2) examine vascular health in SCI. Methods: Seven persons with paraplegia and seven able-bodied (AB) individuals participated in
two testing days. Testing day one consisted of incremental arm crank ergometry to exhaustion with measures of cardiac output, muscle oxygenation, and expired gas and ventilatory parameters. Testing day two involved the measurement of arterial compliance and endothelial function.
Results: There was a significant difference for small artery compliance between SCI and AB(6.9±3.7 versus 10.5±1.7ml mmHg⁻¹x100, p< 0.05). Arm total haemoglobin increased significantly throughout exercise. Arm oxygenation decreased until 60% of maximal wattage after which values did not change. Though non-significant, the large effect size (eta²=.142) suggests a trend for higher
aerobic power in AB (28.6±5.7mL.kg⁻¹min-1)than in SCI (23.7±2.77mL.kg⁻¹min⁻¹)due to a trend for higher cardiac output values in AB (18.0±5.7L.min⁻¹)than SCI (15.8±3.4L.min⁻¹)at maximal exercise.
Conclusions: Small artery compliance is lower in SCI than AB. Leveling off of deoxygenated haemoglobin with total haemoglobin increasing throughout exercise suggests a peripheral limitation to arm ergometry in both groups. A trend for higher cardiac output in AB suggests a central limitation in SCI.
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Mulugeta, Ezra. "Muscarinic M₁ and M₄ receptor subtypes in normal and pathological conditions in the central nervous system : studies on human and animal tissues using subtype selective ligands /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-643-X/.
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Naidoo, Marc Anton. "The risk for cardiovascular disease following traumatic spinal cord injuries in the Cape Metropolitan in South Africa." University of the Western Cape, 2018. http://hdl.handle.net/11394/6885.
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Philosophiae Doctor - PhDGiven the devastating and debilitating impact of spinal cord injuries (SCI) globally and the effects on any population, its impact extends far beyond just the victim to people and institutions surrounding them and supporting them post-injury. Of growing concern is the increased risk that individuals with SCI have been seen to have a three-fold greater risk of developing cardio-vascular disease (CVD) than their able-bodied counterparts. Prevention strategies to curtail the onset of CVD in the SCI population is limited, and often developed for individuals from developed countries. The overall aim of this study was to assess and explore the need to implement CVD prevention programmes in a regional South African population with individuals after sustaining a traumatic spinal cord injury (TSCI). The study employed a mixed methods approach and was conducted in four (4) phases. Permission and ethics clearance were obtained from the Research Ethics Committee at the University of the Western Cape (UWC) and the Western Cape Department of Health. Phase One of the study utilized a questionnaire to collect TSCI incidence data of which 108 of the eligible 132 cases consented to take part in the study. The demographic findings of this study indicated that a person sustaining a TSCI in the Cape Metropolitan area in South Africa is most likely to be a male, young (20 to 29 years of age), from a Black African or Coloured race group and living in the Cape Flats suburbs. The male to female ratio was 6.2:1. The main cause of TSCI was assault at 58.33% (n=63) with males accounting for the majority of cases (88.89%, n=65). According to the AIS classification, ASIA A and D were the most common classification seen in 38.89% (n=42) and 39.81% (n=43) of the cohort respectively. Phase Two utilized a questionnaire and looked at CVD risk factors of the original cohort. A large portion of the cohort was engaged in high-risk behaviours, i.e. smoking and alcohol consumption. A low number of individuals reported a baseline history of hypertension diagnosis prior to their TSCI (5.56%, n=6). Phase Three of the study emplored semi-structured interviews and a focus group discussion to explore the experiences of persons with a TSCI regarding their ability to be physically active once reintegrated back into the community. Despite understanding the associated benefits of physical activity, several barriers to being physically active were reported; factors within their homes, access within their community, and transportation. The present study’s findings illustrated a growing concern among the SCI population for increased risk for developing CVD due to decreased physical activity. Phase Four of the study utilised a scoping review to identify CVD prevention programmes for individuals with a TSCI. Physical activity has been shown to have numerous health benefits of which reducing the risk of CVD is one. Engaging in physical activity, whether it be structured, unstructred or through a sporting activity can play a major role in combating the onset of CVD. Other tools used in reducing the onset of CVD were seen to be self-management strategies of which contrayer views were seen both for and against their use. Conclusion: Better education during the rehabilitation phase might be a key component to individuals with TSCI injury making more informed decisions about prioritising physical activity as they attempt to reintegrate back into their respective communities. The removal of socio-environmental barriers could allow motivated TSCI individuals better access to choosing how to increase their physical activity levels.
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Jensen, Victoria N. "V2a neurons pattern respiratory muscle activity in health and disease." University of Cincinnati / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1583155179498357.
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Ahlsén, Maria. "Gene expression in human skeletal muscle : effects of activity, fibre type and inheritance for diabetes /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-733-2/.
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Song, Rachel B. "Utility and repeatability of quantitative outcome measures to assess recovery after canine spinal cord injury." The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1429298773.
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O'Riordan, Elizabeth Fitzgerald. "Comparison of serial manual muscle test performance in children and adults with spina bifida who undergo and do not undergo surgical tethered cord release." Oklahoma City : [s.n.], 2009.
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Querin, Giorgia. "Unravelling the tangle of motor neuron diseases : insights from neuroimaging and neurophysiology Spinal cord multi-parametric magnetic resonance imaging for survival prediction in amyotrophic lateral sclerosis Multimodal spinal cord MRI offers accurate diagnostic classification in ALS The spinal and cerebral profile of adult spinal-muscular atrophy: a multimodal imaging study The motor unit number index (MUNIX) profile of patients with adult spinal muscular atrophy Presymptomatic longitudinal cord pathology in c9orf72 mutation carriers: longitudinal neuroimaging study." Thesis, Sorbonne université, 2019. http://www.theses.fr/2019SORUS329.
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Les maladies du motoneurone (MNDs) et notamment la Sclérose Latérale Amyotrophique (SLA) et l’Amyotrophie Spinale liée aux mutations du gène SMN1 (SMA), sont caractérisées par une perte progressive des neurones moteurs au niveau de la moelle épinière. L’imagerie par résonance magnétique (IRM) est actuellement l’approche la plus performante pour quantifier la dégénérescence spinale. De plus, les explorations de neurophysiologie pourraient être des biomarqueurs sensibles de progression de la maladie. L’objectif de cette thèse a été d’associer l’IRM de la moelle épinière aux techniques d’évaluation neurophysiologique servant à analyser la dégénérescence dans les MNDs. Dans la SLA, nous avons montré que l’IRM cervicale est un outil efficace pour le diagnostic et la prédiction de la survie et qu’elle permet d’apprécier les patterns précoces de dégénérescence chez les sujets pre-symptomatiques porteurs de la mutation c9orf72. Dans une cohorte de patients adultes atteints de SMA, ce protocole d’IRM a été couplée à une technique de neurophysiologie servant à calculer un index de la perte d’unités motrices (MUNIX). Avec cette méthode nous avons mis en évidence une atrophie isolée de la substance grise cervicale associée à des modifications longitudinales significatives des valeurs du MUNIX. Cet index semble être le biomarqueur le plus pertinent de progression de la maladieMotor neuron diseases (MNDs) are characterized by dysfunction and loss of ventral horn MNs in the spinal grey matter (GM). Nevertheless, different MNDs such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) present with specific clinical presentations. Magnetic resonance imaging (MRI) is the most powerful approach at the brain and spinal cord (SC) level to extract quantitative data on degeneration. At the same time, neurophysiological techniques including motor unit number index (MUNIX) could represent a useful tool to map MN loss. The objective of this project was to combine SC and brain MRI with MUNIX to better characterize degeneration in MNDs, with the aim of identifying possible markers of disease progression. In ALS patients, we showed that SC MRI parameters improve diagnostic and prognostic prediction. Secondly, we longitudinally analyzed a wide population of pre-symptomatic carriers of the c9orf72 mutation, detecting early and progressive cervical WM degeneration. Finally, we considered a cohort of SMN1-related adult SMA patients who underwent a SC and brain MRI protocol combined with MUNIX. We detected isolated cervical GM atrophy not associated with WM pathology. After 24 months observation time, significant MUNIX modifications were demonstrated, suggesting that neurophysiological techniques could be an effective biomarker of disease progression
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Wyatt, Laura, and Ephron Rosenzweig. "Possible T Cell Immune Response to AAV Treatment in non-Human Primates with Spinal Cord Injury." Scholarship @ Claremont, 2013. http://scholarship.claremont.edu/scripps_theses/163.
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Neurons in the spinal cord do not spontaneously regenerate, which often leads to debilitating injuries. One method proposed to promote axonal regeneration is the injection of viruses carrying genes for growth factors into the injured spinal cord. One such virus, the adeno-associated virus (AAV), has shown promise in gene therapy medical research. However, injecting AAV into rhesus macaques with C7 spinal cord hemisection lesions actually leads to motor neuron loss in the gray matter of the spinal cord, rather than contributing to the preservation or regeneration of axons. This unexpected result highlights the necessity of further testing with therapeutic approaches for axon regeneration in nonhuman primate models before moving into clinical trials. It is possible that an immune-related T cell response to the AAV-transfected cells causes this motor neuron loss. T cells are white blood cells that play a role in attacking cells infected with viruses. It is unknown whether such a response of the immune system to respond with an up-regulation of T cells may be taking place over a relatively short period (weeks) or over many months. This question was tested here: T cells were stained in spinal cord sections caudal (below) the lesion in the spinal cord and near AAV injection sites to determine whether there was a greater quantity of T cells in these areas compared to the subject’s baseline levels. Subjects that had AAV therapeutic injections and that were examined 6 months after the injection were found to have greater quantities of T cells than those who did not have injections containing AAV. It was also found that the AAV-injected subjects examined only 6 weeks post injection did not have greater quantities of T cells than control subjects. These results suggest that there may be a delayed immune response to the AAV injections in nonhuman primates with spinal cord injury, which occurs over a period of months. Pinpointing the mechanism that causes this cell death would allow researchers to create a safer therapeutic that could promote axonal growth in people with spinal cord injuries.
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Jorge, Salomé Mariana Candeias. "Traumatismos medulares em canídeos." Bachelor's thesis, Universidade Técnica de Lisboa. Faculdade de Medicina Veterinária, 2009. http://hdl.handle.net/10400.5/1004.
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Dissertação de Mestrado Integrado em Medicina VeterináriaOs traumatismos medulares representam uma parte importante da casuística de um hospital veterinário. As causas destes traumatismos podem ser intrínsecas e extrínsecas. A principal causa intrínseca é a extrusão do material do disco intervertebral (Hérnia discal tipo I de Hansen). As principais causas extrínsecas são fracturas, luxações e subluxações vertebrais secundárias a eventos traumáticos. As lesões de origem vascular (tromboembolismo de uma artéria medular terminal ou embolismo fibrocartilaginoso) são incluídas nos traumatismos medulares porque a patofisiologia destas lesões é semelhante à das lesões de origem mecânica. A fisiopatologia dos traumatismos medulares caracteriza-se pela existência de uma lesão primária mecânica (compressão e/ou concussão) que desencadeia uma avalanche de lesões secundárias mediadas pela existência de radicais livres de oxigénio, alteração das concentrações de neurotransmissores, iões e ácidos aminados excitatórios e pela alterações de outros factores bioquímicos, culminando em redução do fluxo sanguíneo medular, isquémia e necrose. O diagnóstico diferencial das causas de traumatismo medular deve ser feito com base nas informações recolhidas na história pregressa, no exame físico e no exame neurológico. Os principais meios auxiliares de diagnóstico utilizados são o exame radiográfico da coluna vertebral, com recurso a mielografia na maioria dos casos, e a análise do líquido cefaloraquidiano. Ocasionalmente são utilizadas técnicas de imagem avançadas como TAC e RM. O diagnóstico de embolia fibrocartilaginosa pode ser feito por RM e a confirmação com exame histopatológico post mortem da medula espinhal lesada. O tratamento inicial dos traumatismos medulares envolvia em regra a administração de doses elevadas de corticosteróides nas primeiras horas após o trauma, no entanto, actualmente, este conceito está a cair em desuso devido à falta de ensaios clínicos que demonstrem com clareza os efeitos desta terapêutica. As fracturas, luxações e subluxações vertebrais, e as hérnias discais de tipo I podem ter uma terapêutica médica ou cirúrgica dependendo das características de cada caso. Nas embolias fibrocartilaginosas o tratamento é sempre médico. A fisioterapia é uma parte importante da terapêutica dos casos de traumatismo medular. O estudo de novas terapêuticas para as lesões medulares é uma área em constante expansão que tem o potencial de beneficiar pacientes humanos através da realização de ensaios clínicos em canídeos.
ABSTRACT - Spinal trauma represents an important part of a veterinary hospital’s case load. Its causes can be of internal or external sources. The main internal source of acute spinal injury is acute intervertebral disk disease (herniation of the nucleus pulposus), also know as Hansen’s type I disk disease. The main external sources of acute spinal injury are vertebral fractures, luxations and subluxations secondary to traumatic events. Vascular spinal injuries (terminal spinal cord artery thromboembolism or fibrocartilaginous embolism) are also referred to when discussing spinal trauma because of the similar pathophysiology. Spinal trauma pathophysiology includes the primary mechanical injury (compression and/or concussion) which unleashes a chain of secondary lesions, mediated by excessive oxygen free radicals, alteration in neurotransmitters, electrolytes and excitotoxic amino acids concentrations and by changes in various other biochemical factors that collectively result in reduced spinal cord blood flow, ischemia and necrosis. The differential diagnosis for spinal trauma is made based on the information obtained from the owner, from the physical examination and from the neurologic examination. The main ancillary methods used for the diagnosis of spinal trauma are the radiographic examination, myelography in most cases, and cerebrospinal fluid analysis. Advanced imaging techniques like CT and MRI can be used occasionally. The diagnosis of fibrocartilaginous embolism is made by MRI and confirmed by post-mortem histopathologic examination of the damaged spinal cord. The initial treatment for acute spinal injury was usually performed by administrating high doses of corticosteroids during the first hours after the onset of the injury, however, this idea is currently being refuted due to lack of clinical studies that clearly demonstrate this treatment’s effectiveness. Vertebral fractures, luxations and subluxations, and Hansen’s type I disk disease may have a medical or surgical treatment. The treatment for fibrocartilaginous embolism is medical. Physical therapy represents a very important role in the recovery of acute spinal cord injury patients. The development of new therapies for acute spinal cord injury in dogs may benefit human patients with the same pathology.
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Bose, Prodip Kumar. "Wobbler mouse : early detection of motoneuron disease, therapeutic evaluation of nutrition, neuropeptides & their antagonists, and the effects on neuronal sprouting in cervical spinal cord /." Hong Kong : University of Hong Kong, 1997. http://sunzi.lib.hku.hk/hkuto/record.jsp?B19118168.
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Iwagaki, Noboru. "Modulation of mammalian spinal motor networks by group I metabotropic glutamate receptors : implications for locomotor control and the motor neuron disease amyotrophic lateral sclerosis." Thesis, University of St Andrews, 2012. http://hdl.handle.net/10023/3023.
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The present study examined the role of group I metabotropic glutamate receptors (mGluRs) in mammalian spinal motor networks and investigated the potential role of mGluRs in the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS). Group I mGluR activation was found to modulate locomotor-related activity recorded from ventral roots of in vitro mouse spinal cord preparations. Activation of group I mGluRs led to an increase in the frequency of locomotor-related bursts and a decrease in their amplitude. The cellular mechanisms underlying group I mGluR-mediated modulation were investigated using whole-cell patch-clamp recordings from spinal neurons. Recordings from motoneurons revealed a wide range of effects, some of which were expected to increase motoneuron excitability, such as membrane depolarisation and hyperpolarisation of action potential thresholds. However, the net modulatory effect of group I mGluR activation was a reduction in motoneuron excitability, likely reflecting a reduction in the density of fast inactivating Na+ currents. The activation of group I mGluRs also reduced excitatory synaptic input to motoneurons, suggesting that modulation of motoneuron properties and synaptic transmission both contribute to group I mGluR-mediated reductions in locomotor motoneuron output. Recordings from spinal interneurons revealed a smaller range of modulatory effects for group I mGluRs. The clearest effect on interneurons, membrane depolarisation, may underlie group I mGluR-mediated increases in the frequency of locomotor activity. Finally, the potential role of group I mGluRs in the pathogenesis of ALS was investigated using a mouse model of the disease. Although no major perturbations in group I mGluR-mediated modulation were demonstrated in ALS affected spinal cords, there appeared to be a difference in the intrinsic excitability of spinal interneurons between wild type and ALS affected animals. Together these data highlight group I mGluRs as important sources of neuromodulation within the spinal cord and potential targets for the treatment of ALS.
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Pan-Montojo, Francisco, Oleg Anichtchik, Yanina Dening, Lilla Knels, Stefan Pursche, Roland Jung, Sandra Jackson, et al. "Progression of Parkinson's Disease Pathology is Reproduced by Intragastric Administration of Rotenone in Mice." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-185435.
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In patients with Parkinson's disease (PD), the associated pathology follows a characteristic pattern involving inter alia the enteric nervous system (ENS), the dorsal motor nucleus of the vagus (DMV), the intermediolateral nucleus of the spinal cord and the substantia nigra, providing the basis for the neuropathological staging of the disease. Here we report that intragastrically administered rotenone, a commonly used pesticide that inhibits Complex I of the mitochondrial respiratory chain, is able to reproduce PD pathological staging as found in patients. Our results show that low doses of chronically and intragastrically administered rotenone induce alpha-synuclein accumulation in all the above-mentioned nervous system structures of wild-type mice. Moreover, we also observed inflammation and alpha-synuclein phosphorylation in the ENS and DMV. HPLC analysis showed no rotenone levels in the systemic blood or the central nervous system (detection limit [rotenone]<20 nM) and mitochondrial Complex I measurements showed no systemic Complex I inhibition after 1.5 months of treatment. These alterations are sequential, appearing only in synaptically connected nervous structures, treatment time-dependent and accompanied by inflammatory signs and motor dysfunctions. These results strongly suggest that the local effect of pesticides on the ENS might be sufficient to induce PD-like progression and to reproduce the neuroanatomical and neurochemical features of PD staging. It provides new insight into how environmental factors could trigger PD and suggests a transsynaptic mechanism by which PD might spread throughout the central nervous system.
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Monteiro, Bianca Andriolo [UNESP]. "Efeitos da terapia com células tronco mesenquimais em afecções do sistema nervoso de cães." Universidade Estadual Paulista (UNESP), 2017. http://hdl.handle.net/11449/151543.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
O trauma raquimedular, a discopatia e a cinomose são distúrbios que se caracterizam por sinais neurológicos, os quais muitas vezes são de difícil tratamento. Nesse contexto, a terapia celular busca minimizar os sinais e as sequelas neurológicas adquiridas pelas afecções, com objetivo de melhorar a qualidade de vida dos pacientes. Desta forma, o objetivo deste trabalho foi avaliar o resultado do tratamento com células tronco mesenquimais de tecido adiposo nas afecções de trauma rquimedular, sequela de cinomose e discopatia de cães atendidos no serviço de Acupuntura e Dor Crônica da FMVZ-UNESP. Foram utilizados 62 animais, sendo 14 com trauma raquimedular, 17 com discopatias e 31 com sequela de cinomose, todos submetidos ao exame neurológico prévio seguido de terapia celular. A comparação entre os graus antes e após o tratamento com CTMs alogênicas de tecido adiposo para cada tipo de lesão foi realizada utilizando o teste de Mann-Whitney para medidas repetidas. Foi observada diferença entre as medianas referentes ao grau de gravidade das enfermidades tratadas. Nos casos de sequela de cinomose 43.3% (13/30) dos animais tratados apresentaram diminuição dos sinais neurológicos com melhora da graduação da doença. Nos animais com trauma raquimedulares a melhora foi observada em 50% (7/14), e 66.7% dos animais (12/18) que apresentavam discopatias tiveram uma melhora de quadro clínico. Concluiu-se que as aplicações de células tronco mesenquimais em animais com distúrbios neurológicos da lesão da medula espinhal, doença do disco intervertebral e sequelas de cinomorfose diminuíram o grau de lesão das demais afecções.
Spinal cord injury, intervertebral disc disease and distemper are disorders characterized by neurological signs, which are often difficult to treat. In this context, cell therapy seeks to minimize the signs and the neurological sequelae acquired by injuries, aiming to improve the patients' quality of life. Thus, the aim of this study was to evaluate the results of treatment with mesenchymal stem cells of adipose tissue in conditions of spinal cord injury, distemper sequelae and intervertebral disc disease of dogs treated at the Acupuncture and Chronic Pain Service of FMVZ-UNESP. Sixty-two animals were used, 14 of them with spinal cord injury, 18 with intervertebral disc disease and 30 with distempersequelae, all submitted to previous neurological examination followed by cell therapy. A comparison between grades before and after treatment with allogenic adipose tissue MSCs for each type of injury was performed using the Mann-Whitney test for repeated measurements. A difference was observed between to the injury degree of the diseases treated. In the case of distemper, 43.3% (13/30) of the treated animals showed decreased neurological signs with a reduction in the injury degree. In animals with spinal cord injury was observed decrease in 50% (7/14) of injury degree, and 66.7% of the intervertebral disc disease animals (12/18) had a reduced injury degree. It can be concluded that mesenchymal stem cells in animals with nervous system injuries, it covers a medical clinic of second-hand products with neurological disorders of spindle trauma, discopathy and sequelae of distemper. It was concluded that the MSCs applications in animals with neurological disorders of spinal cord injury, intervertebral disc disease and distemper sequelae decreased the injury degree of the diseases treated.
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Monteiro, Bianca Andriolo. "Efeitos da terapia com células tronco mesenquimais em afecções do sistema nervoso de cães." Botucatu, 2017. http://hdl.handle.net/11449/151543.
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Orientador: Fernanda da Cruz Landim-AlvarengaResumo: O trauma raquimedular, a discopatia e a cinomose são distúrbios que se caracterizam por sinais neurológicos, os quais muitas vezes são de difícil tratamento. Nesse contexto, a terapia celular busca minimizar os sinais e as sequelas neurológicas adquiridas pelas afecções, com objetivo de melhorar a qualidade de vida dos pacientes. Desta forma, o objetivo deste trabalho foi avaliar o resultado do tratamento com células tronco mesenquimais de tecido adiposo nas afecções de trauma rquimedular, sequela de cinomose e discopatia de cães atendidos no serviço de Acupuntura e Dor Crônica da FMVZ-UNESP. Foram utilizados 62 animais, sendo 14 com trauma raquimedular, 17 com discopatias e 31 com sequela de cinomose, todos submetidos ao exame neurológico prévio seguido de terapia celular. A comparação entre os graus antes e após o tratamento com CTMs alogênicas de tecido adiposo para cada tipo de lesão foi realizada utilizando o teste de Mann-Whitney para medidas repetidas. Foi observada diferença entre as medianas referentes ao grau de gravidade das enfermidades tratadas. Nos casos de sequela de cinomose 43.3% (13/30) dos animais tratados apresentaram diminuição dos sinais neurológicos com melhora da graduação da doença. Nos animais com trauma raquimedulares a melhora foi observada em 50% (7/14), e 66.7% dos animais (12/18) que apresentavam discopatias tiveram uma melhora de quadro clínico. Concluiu-se que as aplicações de células tronco mesenquimais em animais com distúrbios neurológicos... (Resumo completo, clicar acesso eletrônico abaixo)
Doutor
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DiPeri, Timothy P. "Neuromodulation Therapy Mitigates Heart Failure Induced Hippocampal Damage." Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/honors/208.
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Cardiovascular disease (CVD) is the leading cause of death in the United States. Nearly half of the people diagnosed with heart failure (HF) die within 5 years of diagnosis. Brain abnormalities secondary to CVD have been observed in many discrete regions, including the hippocampus. Nearly 25% of patients with CVD also have major depressive disorder (MDD), and hippocampal dysfunction is a characteristic of both diseases. In this study, the hippocampus and an area of the hippocampal formation, the dentate gyrus (DG), were studied in a canine model of HF. Using this canine HF model previously, we have determined that myocardial infarction with mitral valve regurgitation (MI/MR) + spinal cord stimulation (SCS) can preserve cardiac function. The goal of this study was to determine if the SCS can also protect the brain in a similar fashion. Both the entire hippocampus and the DG tissues were dissected from canine brains and analyzed. These findings provide strong evidence that, in addition to the cardioprotective effects observed previously, SCS following MI/MR induces neuroprotective effects in the brain.
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Emami, Khoonsari Payam. "Proteomics Studies of Subjects with Alzheimer’s Disease and Chronic Pain." Doctoral thesis, Uppsala universitet, Klinisk kemi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-331748.
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Alzheimer’s disease (AD) is a neurodegenerative disease and the major cause of dementia, affecting more than 50 million people worldwide. Chronic pain is long-lasting, persistent pain that affects more than 1.5 billion of the world population. Overlapping and heterogenous symptoms of AD and chronic pain conditions complicate their diagnosis, emphasizing the need for more specific biomarkers to improve the diagnosis and understand the disease mechanisms. To characterize disease pathology of AD, we measured the protein changes in the temporal neocortex region of the brain of AD subjects using mass spectrometry (MS). We found proteins involved in exo-endocytic and extracellular vesicle functions displaying altered levels in the AD brain, potentially resulting in neuronal dysfunction and cell death in AD. To detect novel biomarkers for AD, we used MS to analyze cerebrospinal fluid (CSF) of AD patients and found decreased levels of eight proteins compared to controls, potentially indicating abnormal activity of complement system in AD. By integrating new proteomics markers with absolute levels of Aβ42, total tau (t-tau) and p-tau in CSF, we improved the prediction accuracy from 83% to 92% of early diagnosis of AD. We found increased levels of chitinase-3-like protein 1 (CH3L1) and decreased levels of neurosecretory protein VGF (VGF) in AD compared to controls. By exploring the CSF proteome of neuropathic pain patients before and after successful spinal cord stimulation (SCS) treatment, we found altered levels of twelve proteins, involved in neuroprotection, synaptic plasticity, nociceptive signaling and immune regulation. To detect biomarkers for diagnosing a chronic pain state known as fibromyalgia (FM), we analyzed the CSF of FM patients using MS. We found altered levels of four proteins, representing novel biomarkers for diagnosing FM. These proteins are involved in inflammatory mechanisms, energy metabolism and neuropeptide signaling. Finally, to facilitate fast and robust large-scale omics data handling, we developed an e-infrastructure. We demonstrated that the e-infrastructure provides high scalability, flexibility and it can be applied in virtually any fields including proteomics. This thesis demonstrates that proteomics is a promising approach for gaining deeper insight into mechanisms of nervous system disorders and find biomarkers for diagnosis of such diseases.
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Pithon, Karla Rocha. "Avaliação cardiorrespiratoria e da densidade mineral ossea de pacientes com lesão medular." [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/313751.
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Orientador: Alberto Cliquet JuniorTese (doutorado) - Universidade Estadual de Campinas. Faculdade de Ciencias Medicas
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Resumo: Pacientes com lesão medular reconhecidamente desenvolvem muitas adaptações sistêmicas. Condições, como fraqueza da musculatura respiratória, paralisia e alterações na função pulmonar e conseqüentemente o aumento do índice de doenças pulmonares, são observadas. Recentemente, o aumento de doenças cardiovasculares também tem ocorrido entre esses pacientes, além das complicações provenientes da osteoporose que já são bem conhecidas. O objetivo deste trabalho foi avaliar as alterações do sistema cardiorrespiratório e esquelético de pacientes com lesão medular em 4 estudos. O estudo 1 avaliou a variabilidade da frequência cardíaca na posição supina e sentada e arritmia sinusal respiratória (ASR) de 37 homens com e sem lesão medular. Os pacientes tetraplégicos apresentaram uma redução dos valores máximos da frequência cardíaca durante ASR. O estudo 2 avaliou a função pulmonar de 23 pacientes com tetraplegia. Os valores de capacidade vital forçada, volume expiratório forçado 1s e ventilação voluntária máxima mostraram que a capacidade pulmonar dos pacientes com lesão medular foi reduzida. O estudo 3 propôs a adaptação do teste de caminhada de 6 minutos para 9 pacientes com paraplegia completa auxiliados por marcha artificial com eletroestimulação neuromuscular e andador. O estudo 4 investigou a densidade mineral óssea e fatores de risco cardiovascular de 44 homens com e sem lesão medular. Os pacientes com lesão medular apresentaram osteoporose e/ou osteopenia e o espessamento da camada íntima-média da carótida, porém os valores do lipidograma e triglicérides foram dentro da faixa de normalidade. A pressão arterial foi menor nos pacientes tetraplégicos. Análise estatística: Os dados foram apresentados em mediana (intervalo interquartil) e/ou média (±DP) e em Box-plot. Diferenças entre grupos foram demonstradas pelo intervalo de confiança da mediana, nível de significância em 5% ou teste t pareado. Conclusões: A atuação simpática e parassimpática no coração alcançou a homeostase, quando os pacientes foram mantidos nas posições supina ou sentada e o teste de ASR mostrou uma diminuição da atuação parassimpática no coração dos pacientes tetraplégicos, possivelmente para compensar uma diminuição ou ausência da atuação simpática, devido ao comprometimento do sistema autonômico pela lesão medular. O teste de caminhada de 6 minutos foi adaptado para avaliar os pacientes com lesão medular completa e se mostrou eficiente. Já a avaliação da função pulmonar dos pacientes mostrou a necessidade de novas equações de predição baseadas em uma população específica e suas características. Por último, os resultados obtidos através da densitometria mineral óssea comprovaram a presença de osteoporose e/ou osteopenia nos pacientes com lesão medular. E um aumento na espessura da camada intima-média da carótida foi observado através da ultrassonografia de carótida. Esses dados reforçam a hipótese de uma possível associação entre essas duas patologias.
Abstract: It is known that individuals with Spinal Cord Injury (SCI) present systemic adaptation. SCI causes respiratory muscle weakness, paralysis and abnormal pulmonary function. Cardiovascular disease is also increased in spinal cord injured subjects and osteoporosis as well. The aim of this study was to assess cardio respiratory and bone diseases in subjects with SCI. Four studies were performed. The first study assessed heart rate variability in supine and seated position and respiratory sinus arrhythmia (RSA) maneuver in 37 subjects with and without SCI. Tetraplegic subjects showed the lowest values of maximal heart rate during RSA. The second study assessed pulmonary function in 23 tetraplegic subjects. Forced vital capacity, maximal voluntary ventilation, forced expired volume showed that the SCI subjects' pulmonary capacity was reduced when compared with able body subjects. The third study adapted the "6 minutes' walk test" to assess complete patients with SCI during gait therapy. The fourth study investigated the clinical presence of osteoporosis and cardiovascular risk factors in 44 subjects with and without SCI. Subjects showed osteoporosis or osteopenia and increased intima-media thickness, although lipids and triglycerides were with normal ranges. Blood pressure in tetraplegic subjects was lower than in paraplegic and control groups. Statistical Analysis: Data are expressed as median (interquartile interval) and presented in box-plot (median, 1st and 3rd quartiles, minimum and maximum). Differences between groups were demonstrated by confidence interval of median, significance level set at ? = 0.05, or mean (±SD) and paired t test. Conclusions: Sympathetic and parasympathetic nervous system allow homeostasis when the subjects are kept in supine or seated position; RSA maneuver showed a reduction in parasympathetic system action in the heart of tetraplegic subjects to compensate a reduction or loss of sympathetic action in spinal cord lesion. "Six minutes walk test" was well adapted and efficient. Pulmonary function showed the necessity to create new predicts equations based on local population characteristics. Finally, bone mineral density showed osteoporosis or osteopenia in paraplegic and tetraplegic individuals as well as increased carotid intima-media thickness measured through ultrasound exam.
Doutorado
Pesquisa Experimental
Doutor em Cirurgia
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Pirolla, Eduardo Henrique. "\"Incidência de pancreatite aguda em pacientes com traumatismo raquimedular agudo\"." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/5/5140/tde-14092006-133959/.
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A pancreatite é o resultado da atividade corrosiva das enzimas digestivas pancreáticas e, independente dos vários agentes etiológicos e dos mecanismos etiopatogênicos, tem como resultado a ativação enzimática intra-parenquimatosa, a destruição tecidual e a necrose isquêmica. Trata-se de uma afecção, grave, com incidência aumentada em vítimas de traumatismo raquimedular. Nesses doentes, a suspeita clínica de pancreatite pode ser difícil, pois os sinais e sintomas podem estar diminuídos ou ausentes em decorrência do déficit sensorial esplâncnico. Avaliaram-se, prospectivamente, 78 doentes com traumatismo raquimedular internados no IOT-HCFMUSP, dosando-se os níveis séricos das enzimas amilase e lipase em 3 períodos de tempo pré-determinados, entre os dias de 1 a 3, de 10 a 12 e de 15 a 20 após o traumatismo. A incidência de pancreatite aguda foi maior nos pacientes com traumatismo raquimedular ASIA A e que apresentaram íleo adinâmicoAcute pancreatitis is a result of corrosive activity of pancreatic digestive enzymes, and many etiologic agents trigger acute pancreatitis by a variety of different mechanisms, but the ultimate result is a tissue destruction. The incidence in spinal cord injury patients is higher than the normal population. The clinical diagnosis of acute pancreatitis in spinal cord injury patients is hampered by a lower or lost visceral sensitivity, as a result in a necessity of laboratory investigations to confirm diagnosis. A prospective study with 78 acute spinal cord injury patients of The Clinical Hospital of the College of Medicine of University of São Paulo is performed. The incidence of pancreatitis is larger in patients of spinal cord injury ASIA A and with ileus paralytic
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Pan-Montojo, Francisco, Oleg Anichtchik, Yanina Dening, Lilla Knels, Stefan Pursche, Roland Jung, Sandra Jackson, et al. "Progression of Parkinson's Disease Pathology is Reproduced by Intragastric Administration of Rotenone in Mice." PloS ONE, 2010. https://tud.qucosa.de/id/qucosa%3A29010.
Full textAbstract:
In patients with Parkinson's disease (PD), the associated pathology follows a characteristic pattern involving inter alia the enteric nervous system (ENS), the dorsal motor nucleus of the vagus (DMV), the intermediolateral nucleus of the spinal cord and the substantia nigra, providing the basis for the neuropathological staging of the disease. Here we report that intragastrically administered rotenone, a commonly used pesticide that inhibits Complex I of the mitochondrial respiratory chain, is able to reproduce PD pathological staging as found in patients. Our results show that low doses of chronically and intragastrically administered rotenone induce alpha-synuclein accumulation in all the above-mentioned nervous system structures of wild-type mice. Moreover, we also observed inflammation and alpha-synuclein phosphorylation in the ENS and DMV. HPLC analysis showed no rotenone levels in the systemic blood or the central nervous system (detection limit [rotenone]<20 nM) and mitochondrial Complex I measurements showed no systemic Complex I inhibition after 1.5 months of treatment. These alterations are sequential, appearing only in synaptically connected nervous structures, treatment time-dependent and accompanied by inflammatory signs and motor dysfunctions. These results strongly suggest that the local effect of pesticides on the ENS might be sufficient to induce PD-like progression and to reproduce the neuroanatomical and neurochemical features of PD staging. It provides new insight into how environmental factors could trigger PD and suggests a transsynaptic mechanism by which PD might spread throughout the central nervous system.
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Frakes, Ashley E. "The Role of Neuroinflammation in the Pathogenesis of Amyotrophic Lateral Sclerosis." The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1417649954.
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Lunn, Julian Alexander. "Canine Neural Angiostrongyliasis." Thesis, The University of Sydney, 2006. http://hdl.handle.net/2123/2077.
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Summary Canine Neural Angiostrongyliasis (CNA) is caused by the obligatory neural migration of Angiostrongylus cantonensis larvae in dogs. Characteristically, cases are juvenile dogs with progressive CNS dysfunction characterised by hyperaesthesia and often associated with eosinophilic pleocytosis of the CSF. In Australia, most cases occur between March and June. The rat lungworm, A cantonensis was first described by Chen in 1935 in Canton, China. While initially called Pulmonema cantonensis the parasite was later reclassified as A cantonensis. A disease diagnosed as eosinophilic meningoencephalitis was first described in 1944 in Taiwan. The same disease was reported in 1948 in the East Caroline Islands but it was not until 1961 that A cantonensis was confirmed as the aetiological agent when a patient in a Hawaiian mental institution, who had died of eosinophilic meningoencephalitis, had A cantonensis larvae recovered from the brain and spinal cord. The first reports of animals infected with A cantonensis were made by Mason in 1976 when he described a syndrome occurring in puppies in the Brisbane area, characterised by urinary incontinence, hind limb paresis and hyperaesthesia, often associated with eosinophilic pleocytosis of the CSF. Reports of infection in other species followed including macropods, bats, horses, primates and birds. Twenty-two cases of suspected CNA were collected prospectively to compare with those previously described, including 37 cases published by Mason in 1983, and to examine the accuracy of an ELISA used to diagnose human neural angiostrongyliasis in Australia. Samples were collected from two control populations in an attempt to validate the ELISA results. In the prospective series of cases, there was a significantly older subpopulation of dogs in addition to “classical” young dogs, suggesting that this syndrome can occur at any age and should be considered a differential in any dog with progressive neurological disease. The mortality rate in the prospective group was lower than in the published group, which is a reflection of the severity of the disease in younger animals as is the case with human patients. Definitive diagnosis of neural angiostrongyliasis in human patients has been achieved by identifying A cantonensis larvae within the CSF or aqueous humour. In dogs, the only definitive way to diagnose CNA has been via necropsy. While many cases of CNA are characteristic and presumptive diagnosis can be made based on typical history, signalment, clinical signs, CSF analysis and response to glucocorticoids, there appear to be an increasing number of cases occurring in older dogs, that displaying focal, atypical clinical signs or that develop permanent sequelae. Serology has been a useful tool in diagnosing neural angiostrongyliasis in humans. In its current form the ELISA is not sensitive or specific enough to allow a definitive diagnosis of CNA to be made using serum but is useful when applied to CSF specimens. Further refinement of the antigen or using monoclonal rather than polyclonal antibodies may improve the accuracy of the serology. Alternatively, methods such as Western Blot, Immuno-PCR or dot-blot ELISA, which have been successfully used to diagnoses angiostrongyliasis in humans, may be worthy of investigation The major differential diagnosis for CNA is neosporosis. Other differential diagnoses include idiopathic eosinophilic meningoencephalitis, parasitic infections including Toxoplasma gondii, Taenia solium, Gnathostoma spinigerum, visceral larval migrans (Toxocara canis) and schistosomiasis, fungal, bacterial, viral and rickettsial infections as well as neoplasia, trauma, drug reactions and toxicities. Treatment of CNA has been limited to glucocorticoids, however there may be adjunct therapies including anthelmintices, cyclosporine, and matrix metalloproteinase inhibitors. In Mason’s series of cases the use of anthelmintics significantly worsened the clinical outcome for patients. It does not appear, however, that the use of these agents in species other than the dog exacerbates clinical signs. Acquired immunity is short lived in rats and mice, which would suggest the same is true in dogs. Routine heartworm and intestinal parasite prophylaxis appears to have no influence on the occurrence of CNA.
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Mendes, Eva Raquel Baltazar. "A influência de factores intrínsecos e extrínsecos na recuperação de canídeos com hérnias de disco." Bachelor's thesis, Universidade Técnica de Lisboa. Faculdade de Medicina Veterinária, 2008. http://hdl.handle.net/10400.5/951.
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Dissertação de Mestrado Integrado em Medicina VeterináriaA Hérnia de Disco é a causa mais frequente de patologia da medula espinhal em cães. As hérnias de disco estão associadas a degenerescência dos discos intervertebrais, cujas causas não são totalmente conhecidas, resultando na extrusão ou protusão de material de disco para o interior canal medular causando a compressão da medula espinhal ou das raízes nervosas. Os sinais clínicos associados são variados e podem variar desde apenas dor espinhal até quadriplegia. O diagnóstico pode ser feito com base na idade, espécie, raça, história e sinais clínicos do doente colhidos no exame neurológico, exigindo a realização de exames complementares de radiologia simples e contrastada, para se estabelecer um diagnóstico definitivo de hérnia de disco. A terapêutica mais apropriada depende do quadro clínico que o doente apresenta. O prognóstico está na dependência do grau de défices neurológicos existentes, da duração do processo patológico e da terapêutica instituída. Com o ensaio realizado, foi possível concluir que 22,9% (8/35) dos doentes apresentaram discopatia de localização cervical e 77,1% (27/35) toracolombar, sendo a dor o principal sinal clínico e ocorrendo na maioria em animais condrodistróficos (62,9%; 22/35), sendo maior a incidência nos doentes da raça Caniche (48,6%; 17/35) e depois nos doentes de raça indeterminada (20,0%; 7/35). O quadro neurológico dos animais da amostra variou entre o grau de lesão 1 até ao 5, e a duração dos sinais clínicos entre 4 a 185 dias. O disco intervertebral mais afectado na coluna cervical foi C6-C7 (22,22%; 2/9) e na coluna toracolombar L1-L2 (9,7%; 3/31). O tempo médio de recuperação após início da terapêutica foi de 18,5 dias, e 94,3% (33/35) dos doentes recuperaram totalmente as funções neurológicas.
ABSTRACT - Intervertebral disc disease is the most frequent cause of spinal cord disease in dogs. It is associated with degeneration of the intervertebral discs, whose causes are not fully known, resulting in extrusion or protrusion of the disc material into the spinal canal causing spinal cord or nerve roots compression. Signs associated include paraspinal pain to paralysis. The diagnosis is based on age, species, race, history and clinical signs presented at neurological examination, but execution of survey radiography and myelography is required to establish a definitive diagnosis of intervertebral disc disease. The most appropriate therapy depends on the severity and duration of the clinical signs. The prognosis is dependent on the rate of onset, the degree and duration of clinical signs and on the therapy established. With the clinical test, it was possible to conclude that 22,9% (8/35) of intervertebral disc disease occurs in the cervical region and 77,1% (27/35) in the thoracolumbar region, with pain being the most significant sign. It is most commonly in chondrodytrophic dogs (62,9%; 22/35), with the biggest incidence on Poodles (48,6%; 17/35) and mixed-breed dogs (20,0%; 7/35). The presented neurological deficits ranged from 1 to 5 degrees of medullar injury, and duration of clinical signs from 4 to 185 days. The most affected intervertebral disc in the cervical spine was C6-C7 (22,2%; 2/9) and in the thoracolumbar spine was L1-L2 (9,7%; 3/31). The mean time for recovery after starting therapy was 18.5 days and 94.3% (33/35) of the patients recovered fully the neurological functions.
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Ribeiro, Catarina Isabel da Silva. "Tratamento cirúrgico de hérnias discais Tipo I de Hansen : estudo retrospetivo sobre os fatores que poderão influenciar o tempo até à recuperação." Master's thesis, Universidade de Lisboa, Faculdade de Medicina Veterinária, 2019. http://hdl.handle.net/10400.5/17740.
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Dissertação de Mestrado Integrado em Medicina VeterináriaAs hérnias discais intervertebrais são causa comum de disfunção da medula espinhal no cão. Esta patologia está associada à degeneração do disco intervertebral e resulta na extrusão (Hansen tipo I) ou protusão (Hansen tipo II) de material do núcleo pulposo para o canal vertebral, provocando compressão da medula espinhal e/ou das raízes nervosas e dando origem aos sinais clínicos. A apresentação clínica varia desde apenas dor espinhal a plégia sem sensibilidade à dor profunda. Lesões toracolombares são mais frequentes que lesões cervicais, ambas ocorrem usualmente em canídeos de raças condrodistróficas e de pequeno porte, no entanto podem desenvolver-se animais de qualquer raça ou porte. O diagnóstico deve ser feito partindo de um exame físico e neurológico completo seguidos de exames imagiológicos avançados, como a tomografia computorizada ou a ressonância magnética para confirmação e localização do disco herniado. O tratamento apropriado depende do quadro clínico e da duração do mesmo, podendo optar-se por terapêutica médica ou terapêutica cirúrgica. O prognóstico está, maioritariamente, dependente da presença de perceção à dor profunda e, no caso da sua ausência, da sua duração. O propósito deste estudo retrospetivo foi determinar indicadores de prognóstico relacionados com o tempo necessário para a recuperação da locomoção normal em cães submetidos a resolução cirúrgica de hérnia discal, numa população de 100 cães. Verificou-se que pacientes condrodistróficos e pacientes de porte pequeno foram os mais afetados, em particular o Bulldog francês. A região toracolombar foi a mais lesada, com 72% dos casos clínicos em estudo. O tempo médio necessário para recuperação da locomoção foi de 18 dias, com uma taxa de sucesso de 89%. Os fatores tipo de raça, presença de propriocepção, função motora normal, perceção à dor profunda, menor grau de lesão medular de acordo com a escala modificada de Frankel, localização cervical da hérnia discal, menor número de espaços intervencionados na cirurgia, capacidade de controlo da micção e controlo da defecação, e menor período tempo de internamento aparentaram ter uma influência positiva (p<0,05) no tempo necessário para a recuperação. Contrariamente, os fatores sexo, idade, porte, reflexos espinhais, o disco cervical afetado, o disco toracolombar e número de hérnias, presentes não mostraram ter influência (p>0,05) na recuperação.
ABSTRACT - Surgical treatment of Hansen Type I disc disease : a retrospective study on the factors that may influence the time to recovery - Intervertebral disc disease is a common cause of spinal cord dysfunction observed in dogs. This pathology is associated with the degeneration of the intervertebral disc and results in extrusion (Hansen type I) or protrusion (Hansen type II) of the nucleus pulposus to the vertebral canal, causing compression of the spinal cord and/or nerve roots and leading to the clinics signs. Clinical presentation varies from solely neck/back pain to paralysis without deep pain perception. Thoracolumbar lesions are more frequent than cervical lesions, both usually occur in chondrodystrophic breeds and in small breeds, however they can develop in animals of any race or size. Diagnosis is made based on physical and neurologic examination, followed by advanced imaging, such as computed tomography or magnetic resonance for confirmation and location of the herniated disc. The appropriate treatment depends mainly on clinical presentation and its duration, and it can be conservative or surgical. The prognosis is mostly dependent on the presence of deep pain perception and, in the case of its absence, on its duration. The purpose of this retrospective study was to determine prognostic indicators related to the time required to regain normal ambulation in dogs submitted to surgical treatment of disc disease, in a population of 100 dogs. Chondrodystrophic and small breeds were the most affected, especially the French Bulldog. Thoracolumbar region was the most affected, with 72% of the clinical cases being studied. The mean time required for ambulation recovery was 18 days, with a success rate of 89%. The factors type of race, presence of proprioception, normal motor function, perception of deep pain, lower degree of spinal cord lesion according to the modified Frankel scale, cervical localization of the herniated disc, fewer spaces intervened in the surgery, capacity to control micturition and defecation, and shorter length of hospital stay appeared to have a positive influence (p< 0,05) in the time required for recovery. For the contrary, factors such as gender, age, size, spinal reflexes, the location of the cervical disk, the location of the thoracolumbar disc and number of herniations, had no influence (p >0,05) on recovery.
N/A
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Rodrigues, F?bio Barreto. "Efeito da nata??o e do basquetebol em cadeira de rodas sobre o colesterol HDL: uma investiga??o em indiv?duos com les?o medular." Universidade Federal do Rio Grande do Norte, 2007. http://repositorio.ufrn.br:8080/jspui/handle/123456789/13180.
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Previous issue date: 2007-12-20Despite the observation of an increase in life expectancy in individuals with Spinal cord injury (SCI), it is lower than that of the general population. Studies have shown that affected individuals have a sedentary lifestyle that reflects negatively on health and quality of life. Studies have demonstrated that HDL cholesterol (HDL-C) levels, a high-density lipoprotein and important predictor of cardiovascular disease, are lower in this population exposing these people to a greater incidence of heart disease from atherosclerotic process In the general population, exercise increases HDL-C serum levels, but this phenomenon is not very clear in people with spinal cord injury (SCI). The present study examined the effect of both swimming and wheelchair basketball in the lipid profile of eleven men and seven women with SCI. The subjects included in regular exercise programs showed increases in HDL-C levels and decreases in CT/HDL-C and LDL-C/HDL-C ratios. We found better results mainly in men with lower levels of SCI and in those that sustained exercise intensities above 60% of the heart rate reserve. The duration of training sessions can be an essential factor in these results. The results suggest that both the exercise prescription and the personal characteristics of people with SCI influence changes in the lipid profile mediated through exercise. The elaboration of this work is an attempt to clarify uncertainties about health and the longevity of people with SCI generated in discussion of all members of the interdisciplinary rehabilitation team, especially the physiotherapists, nutritionists, nurses and physicians that contributed considerably in all phases of the research
Apesar do aumento da expectativa de vida das pessoas com les?o medular (LM), esta ? ainda inferior ? da popula??o em geral. Pesquisas demonstram que os indiv?duos acometidos pela LM levam um estilo de vida sedent?rio, o que repercute negativamente na sa?de e na qualidade de vida. Os n?veis do colesterol HDL (HDL-C), cada vez mais se consolidam como importantes preditores de doen?a cardiovascular. Na popula??o com LM, os n?veis destas lipoprote?nas encontram-se significativamente diminu?dos, expondo estes indiv?duos a uma maior incid?ncia de doen?as cardiovasculares ligadas ao processo ateroscler?tico. Estudos na popula??o geral assinalam que o exerc?cio f?sico regular eleva os n?veis s?ricos de HDL-C. Por?m, este fen?meno n?o ? muito claro para aqueles com LM. O presente estudo analisou o efeito da nata??o e do basquetebol em cadeira de rodas no perfillip?dico de 11 homens e sete mulheres com LM inclu?dos em um programa regular de atividade f?sica. Os participantes mostraram modifica??es entre a primeira e a segunda coleta que sugerem aumento nos n?veis de HDL-C e diminui??es nas rela??es CT/HDL-C e LDL-C/HDL-C. Verificaram-se melhores resultados nos homens com LM em n?veis mais baixos e que se submeteram a intensidade de esfor?o superior a 60% da freq??ncia card?aca de reserva. O tempo de dura??o da sess?o de treinamento pode ser uma vari?vel fundamental nestes resultados. Estes resultados sugerem que tanto a prescri??o do exerc?cio quanto caracter?sticas individuais das pessoas com LM influenciam modifica??es no perfil lip?dico mediadas pelo exerc?cio. A elabora??o deste trabalho ? uma tentativa de esclarecer questionamentos relacionados ? sa?de e a longevidade de pessoas com LM gerados atrav?s da discuss?o de todos integrantes da equipe interdisciplinar de reabilita??o, especialmente os fisioterapeutas,nutricionistas,enfermeiros e m?dicos, que contribu?ram consideravelmente em todas as fases da pesquisa
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Chaves, Rafael Oliveira. "Tratamento clínico ou cirúrgico em cães com extrusão de disco intervertebral (Hansen tipo I) toracolombar." Universidade Federal de Santa Maria, 2017. http://repositorio.ufsm.br/handle/1/11299.
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Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqThe extrusion of the intervertebral disc is the most common cause of neurological disorders in dogs. Extrusion (Hansen type I) or protrusion (Hansen type II) of the disc may occur and consequent compression of the spinal cord and / or nerve roots. The objective of this thesis was, in a first step, to carry out a retrospective study for the epidemiological survey of the disease and to evaluate dogs in different degrees of neurological dysfunction after surgical decompression of the spinal cord. In article 1, of the 110 dogs with thoracolumbar DDIV submitted to surgical decompression, 74 (67.3%) improved clinical signs, 54 (49.1%) considered satisfactory and 20 (18.2%) were partially satisfactory. In article 2, of the 17 dogs with extrusion (Hansen type I) of thoracolumbar intervertebral disc without perception to deep pain (PDP) submitted to clinical treatment, nine (52.9%) presented satisfactory functional recovery, one (5.9%) satisfactory recovery without pain (Spinal walk) and seven (41.2%) were unsatisfactory. Of the 20 dogs submitted to surgical treatment, 10 (50%) presented satisfactory functional recovery, three (15%) satisfactory recovery without deep pain (spinal gait) and seven (35%) were unsatisfactory. There was no significant difference in functional recovery between dogs undergoing clinical or surgical treatment. In view of the results, the surgical treatment promotes a satisfactory functional recovery in the most of dogs with thoracolumbar disc extrusion, being the percentage of relapse in animals submitted to this type of therapy low. The functional clinical recovery in dogs with paraplegic thoracolumbar intervertebral disc extrusion and without perception to deep pain over 48 hours can occur independently of the treatment instituted. Other studies are needed with more cases to reinforce the evidence found.
A extrusão do disco intervertebral é uma das causas mais comuns de alterações neurológicas em cães, sendo provocada pela degeneração do disco intervertebral. Pode ocorrer extrusão (Hansen tipo I) ou protrusão (Hansen tipo II) do disco e consequente compressão da medula espinhal e/ou raízes nervosas. O objetivo desta tese foi, em uma primeira etapa, realizar um estudo retrospectivo para levantamento epidemiológico da doença e avaliar clinicamente os cães submetidos a descompressão cirúrgica da medula espinhal em diferentes graus de disfunção neurológica. Na segunda etapa avaliou, mediante estudo prospectivo, a recuperação funcional de cães paraplégicos e sem percepção à dor profunda por mais de 48 horas em decorrência de extrusão de disco intervertebral toracolombar (Hansen tipo I) submetidos ao tratamento clínico ou cirúrgico. No artigo 1, dos 110 cães com DDIV toracolombar submetidos a descompressão cirúrgica, 74 (67,3%) tiveram melhora dos sinais clínicos, sendo 54 (49,1%) considerados satisfatórios e 20 (18,2%) parcialmente satisfatórios. No artigo 2, dos 17 cães com extrusão (Hansen tipo I) de disco intervertebral toracolombar sem percepção à dor profunda (PDP) submetidos ao tratamento clínico, nove (52,9%) apresentaram recuperação funcional satisfatória, um (5,9%) recuperação satisfatória sem dor profunda (andar espinhal) e sete (41,2%) insatisfatória. Já, dos 20 cães submetidos ao tratamento cirúrgico, 10 (50%) apresentaram recuperação funcional satisfatória, três (15%) recuperação satisfatória sem dor profunda (andar espinhal) e sete (35%) insatisfatória. Não houve diferença significativa em relação a recuperação funcional entre em cães submetidos ao tratamento clínico ou cirúrgico. Diante dos resultados, o tratamento cirúrgico promove recuperação funcional satisfatória na maioria dos cães com extrusão de disco toracolombar, sendo baixo o percentual de recidiva em animais submetidos a este tipo de terapia. A recuperação clínica funcional em cães com extrusão de disco intervertebral toracolombar paraplégicos e sem percepção à dor profunda superior a 48 horas pode ocorrer independente do tratamento instituído. Outros estudos são necessários com maior número de casos para reforçar as evidências encontradas.
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Li, Ting-hung Darrell, and 李廷雄. "Ultrastructural imaging of the cervical spinal cord." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B43572285.
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Chan, Koon-ho, and 陳灌豪. "Clinical features, diagnosis and immunopathogenesis of neuromyelitis optica spectrum disorders." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B48521681.
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Neuromyelitis optica (NMO) is a central nervous system inflammatory demyelinating disorders (CNS IDD) characterized by acute myelitis (AM) and optic neuritis (ON), especially clinically severe longitudinally extensive transverse myelitis (LETM) and simultaneous bilateral ON. Patients with recurrent AM especially LETM without ON, and patients with recurrent ON without AM may have disorders belonging to the spectrum of NMO, neuromyelitis optica spectrum disorders (NMOSD). NMO is likely autoimmune in nature as a significant proportion of patients are seropositive for aquaporin-4 (AQP4) autoantibodies. I studied the clinical features of local Chinese NMOSD patients and their AQP4 autoantibodies seropositivity rates of by indirect immunofluorescence using tissue slides containing primate cerebellum (tissued-based immunofluorescence assay) in patients with 1) NMO, 2) classical multiple sclerosis (CMS), 3) acute disseminated encephalomyelitis (ADEM), 4) single attack or relapsing AM, 5) single attack or relapsing ON, and 6) other neurological disorders. The results showed that NMOSD are severe CNS IDD affecting patients with a wide range of onset ages. Chinese NMOSD patients predominantly have relapsing NMO and relapsing LETM with severe attack of LETM and/or ON. The six-year mortality rate of patients with NMO or relapsing myelitis with LETM was about 12%. Two-thirds of patients have poor neurological outcome at a mean duration of 6.0 years. The results confirmed that AQP4 autoantibodies are specific for NMOSD, and detection of AQP4 autoantibodies is clinically useful for early diagnosis of NMOSD and distinction from CMS. I proceeded to study a cell-based immunofluorescence assay using transfected human embryonic kidney cells overexpressing human AQP4 on cell membrane and found that cell-based assay has higher sensitivity than tissue-based assay in detection of AQP4 autoantibodies in NMO (78% versus 61%). As our NMOSD patients frequently presented clinically with severe brainstem symptoms and signs and lesions in brainstem and other brain regions on magnetic resonance imaging (MRI), I studied the clinical and neuroradiological characteristics of Chinese NMOSD patients with brain involvement. I found that 59% of NMOSD patients have clinical and/or radiological evidence of brain involvement. Importantly, brainstem is the most frequently affected brain region and 24% of NMOSD patients had clinical manifestation of brainstem encephalitis.
I also studied the pathogenicity of AQP4 autoantibodies in the absence of complement activation by passive transfer of IgG isolated from sera of NMOSD patients into mice pretreated with complete Freund’s adjuvant (CFA, containing heat-killed mycobacterium tuberculosis) and pertussis toxin (PTx). I observed that pretreatment with CFA and PTx led to breach of BBB in mouse, and IgG isolated from sera of NMOSD patients seropositive for AQP4 autoantibodies led to asymptomatic loss of AQP4 in gray and white matter in mouse spinal cord without inflammatory cell infiltration, demyelination or astrocytic loss in the absence of complement activation (human IgG cannot activate mouse complements). My findings support that 1) AQP4 autoantibodies binding to astrocytic AQP4 per se can cause downregulation of AQP4 in the absence of complement activation, and 2) complement activation with resultant complement activation products play key roles in the inflammation, demyelination and astrocyte cytotoxicity in NMO.published_or_final_version
Medicine
Doctoral
Doctor of Philosophy
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Jee, Larry Donald. "The urological management of children with spinal dysraphism." Master's thesis, University of Cape Town, 1990. http://hdl.handle.net/11427/25677.
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This project was undertaken with the following aims: 1) To generate a data base concerning the management of children with congenital spinal anomalies, who are known to form a significant proportion of the patients being treated in the Department of Paediatric Urology at Red Cross Hospital. 2) To assess the results of the management of these children, with special attention to the goals of therapy, namely preservation of renal function, establishment of urinary continence and protection from urinary tract infection. 3) To compare the treatment methods and results obtained to those reported in the literature. 4) To evaluate critically the treatment methods and results obtained with a view to identifying areas where improvements are possible.
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Laird, Angela S. Medical Sciences Faculty of Medicine UNSW. "Autonomic dysreflexia following high level spinal cord injury: time course, mechanisms and possible intervention." Awarded by:University of New South Wales. School of Medical Sciences, 2007. http://handle.unsw.edu.au/1959.4/31523.
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Following cervical or upper thoracic level spinal cord injury (SCI), motor, sensory and autonomic systems are disrupted. One form of this autonomic dysfunction is the condition autonomic dysreflexia (AD), which is characterised by episodes of high blood pressure in response to afferent input from regions below the injury level. An animal model of autonomic dysreflexia, the T4 transected rat, was used in this thesis to gain insight into the cardiovascular and temperature components of the disorder, possible peripheral mechanisms and interventions to prevent its development. Chapter 2 of the thesis includes the charaterisation of a T4 transection rat model of spinal cord injury. This characterisation includes confirmation of decreased baseline mean arterial pressure (MAP, 71 down from 117 mmHg) and elevated heart rate (HR, 431 bpm from 366 bpm) for 6 weeks post injury (p.i.). Documentation of the development of AD found that hypertensive responses were fully developed (+20 mmHg) by 4 weeks p.i. Further, during episodes of AD at Weeks 4 and 5 p.i., tail surface temperatures decreased significantly (mid-tail, -1.7oC), indicative of extensive vasoconstriction. Comparison of vascular responses of intact and SCI animals to adrenergic agonists (phenylephrine, PHE and methoxamine, METH) following ganglionic blockade in vivo found that SCI animals experienced prolonged vasoconstriction in blood vessels above and below injury level in response to PHE but not METH. Possible mechanisms of this change included decreased neuronal reuptake of PHE (METH is not a substrate for neuronal reuptake). The presence of prolonged vasoconstriction in blood vessels throughout the body, not just regions below injury level, suggests a widespread mechanism for the change, such as the decreased basal MAP, norepinephrine levels or neural activity present following injury. Thus, it was hypothesised that increased activity from an early stage post injury may prevent the peripheral adaptation and perhaps hinder development of AD. For this, the common rehabilitation technique, treadmill training, was used. Surprisingly, rather than preventing AD, the training actually accelerated its development, producing exaggerated hypertensive responses to colorectal distension (CRD) at Weeks 3 and 4 post-injury (Week 4, Trained: +38.5 ?? 1.5 mmHg; Sedentary: 23.4 ?? 3.1mmHg). Comparison of vascular responses of both groups to PHE injection found no significant difference indicating that the enhanced responses were not a result of peripheral vascular changes. Investigation of the central morphology following SCI, made via immunohistochemical processing of the post-mortem spinal cords, found that Treadmill Trained SCI animals had elevated calcitonin gene related peptide (CGRP) immunoreactivity within lamina III/IV of lumbar segments, compared to intact cords. It is possible that this finding indicates afferent sprouting that may have accelerated the development of AD in Treadmill Trained animals. The results within this thesis highlight the importance of awareness and examination of autonomic function in SCI patients, especially those undergoing rehabilitative training.
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Uys, Martha-Marie. "Towards the development of a coping model for the well-being of patients with transverse myelitis." Thesis, University of Pretoria, 2013. http://hdl.handle.net/2263/32047.
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Transverse myelitis (TM) is a rare auto-immune inflammatory disease in which the patient’s immune system attacks their spinal cord resulting in an unpredictable degree of neurologic disability, ranging from complete recovery to quadriplegia. TM patients often experience insufficient assistance towards understanding causes of the illness and have little to depend on in trying to deal with it. This study explores psychological strengths and coping strategies used by TM patients in coping with the illness.
A theoretical framework of positive psychology with a strong focus on seven constructs, namely positive coping, searching for meaning, benefit finding, hope, sense of humour, resilience, as well as religion and spirituality is presented. The main data collection strategy for this study was the gathering of stories as a form of conversation. These were subjected to thematic analysis by interpretative phenomenological analysis (IPA) focused on identifiable themes and patterns of living and behaviour.
The emerging patterns and identified fortigenic qualities were then considered, analysed and argued in relation to corresponding coping strategies. A model for the psychological coping and well-being of TM patients, based on emphasising the positive and constructive and considering existing models and strategies for the well-being of patients, was developed. The strategic and therapeutic model is presented in easily understandable language for the benefit of any care-giver (e.g. family member, friend or nurse) or the patient him/herself.Thesis (PhD)--University of Pretoria, 2013.
lk2013
Psychology
unrestricted
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Nock, Bonnie J. (Bonnie Jean). "Echocardiographic Assessment of the Left Ventricle in the Spinal Cord Injured Patient." Thesis, University of North Texas, 1989. https://digital.library.unt.edu/ark:/67531/metadc500420/.
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Ten caucasian male quadriplegics were compared with eight sedentary caucasian male controls in regards to left ventricular dimensions and mass obtained from echocardiograrns. The interventricular septum (IVS), left ventricular posterior wall (LVPW) and left ventricular internal diameter (LVII) were within normal limits for both groups. However, the INS in the SCI were significantly thicker than controls (p <0.05). Myocardial thickness was larger in SCI subjects (p <0.05). Absolute left ventricular mass (LVM) and total left ventricular volume was not different ( p > 0.05), but SCI subjects had significantly greater LVM to lean body mass ratios. Echocardiographically, SCI patients demonstrate concentric hypertrophy. This suggests adaptive response to chronic increase in afterload pressure secondary to their daily activities and muscle spasticity.
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Werry, Eryn Louise. "Identification of novel ATP and interleukin-10 sources in the spinal cord." Thesis, The University of Sydney, 2008. https://hdl.handle.net/2123/28127.
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Chronic pain has a large individual and societal impact. Although effective
treatments for acute pain exist, a specific and effective treatment for chronic pain is
still to be discovered. Recent use of genetic techniques has revealed that spinal ATP
plays a role in the generation of allodynia and hyperalgesia, two symptoms of chronic
pain. Furthermore, it has been shown that the symptoms of chronic pain can be
alleviated by increasing spinal levels of the anti-inflammatory cytokine interleukin-10
(IL-10). These observations suggest that decreasing the spinal release of ATP and
increasing the spinal release of IL-10 may be novel approaches to chronic pain
treatment. Yet knowledge of the endogenous sources of spinal ATP and IL—10 is
limited. Therefore, the aim of this thesis was to identify novel sources of ATP and
IL—10 in the spinal cord.
The first series of experiments (Chapter 3) investigated whether spinal cord astrocytes
could be a source“ of ATP in response to the nociceptive neurotransmitters glutamate
and substance P. Glutamate stimulated ATP release from cultured spinal cord
astrocytes and this release was greatly potentiated by substance P, even though
substance P alone did not elicit ATP release. Substance P also potentiated glutamateinduced
inward currents without alone causing such currents. Glutamate, when
applied on its own, acted exclusively through AMPA receptors to stimulate Ca2+
influx-dependent ATP release. However when substance P was co—applied with
glutamate, ATP release could be elicited by activation of NMDA and metabotropic
glutamate receptors. ‘ ATP release resulting from AMPA and kainate receptor
stimulation was not affected by substance P. Activation of neurokinin receptor
subtypes, protein kinase C and phospholipase A2, C and D were required for
substance P to bring about its effects.
The second series of experiments (Chapter 4) explored whether spinal cord astrocytes
could be a source of IL-10 in response to glutamate and stimulation of the Toll-like
receptor 4 (TLR4), which is known to occur in chronic pain. TLR4 stimulation
increased IL—lO release from cultured spinal cord astrocytes. TLR4-stimulated IL—lO
release was enhanced in the presence of glutamate. Glutamate potentiated TLR4—
stimulated IL—lO release by upregulating IL-10 mRNA and worked synergistically
through metabotropic glutamate receptor groups I, II and possibly III.
The third series of experiments (Chapter 5) examined whether spinal cord microglia
could be a source of IL-10 in response to glutamate and stimulation of the TLR4.
TLR4 stimulation enhanced both IL—10 transcription and translation, resulting in an
increase in IL-lO release from cultured spinal cord microglia. Glutamate significantly
increased TLR4-stimulated IL-lO release from microglia by binding NMDA, AMPA,
metabotropic glutamate receptors and possibly kainate receptors and enhancing
TLR4-induced IL-lO mRNA expression.
The results of this thesis suggest that astrocytes may be a major source of ATP in the
spinal cord on activation of nerve fibres that co-release substance P and glutamate.
The results of this thesis also suggest that when glutamate and TLR4 agonists are
released into the spinal cord after noxious stimulation, astrocytes and microglia may
be a major source of IL-10. These results implicate spinal cord glia in both pronociceptive
and anti-nociceptive responses to pain—related substances.
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Chan, Ka-man, and 陳嘉雯. "Detection of anti-aquaporin (AQP4) autoantibodies in the diagnosis of neuromyelitis optica (NMO)." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B44659192.
Full text
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Lo, Yuk-fai, and 盧育輝. "Comparison between tissue-based indirect immunofluorescence andenzyme-linked immunosorbent assays, two detection methods for anti-aquaporin-4 antibodies in neuromyelitis optica spectrum disorders." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B46579266.
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Crowdus, Meyer Carolyn A. "Dietary Selenium Supplementation: Effects on Neurodegeneration Following Traumatic Brain and Spinal Cord Injury." UKnowledge, 2015. http://uknowledge.uky.edu/neurobio_etds/11.
Full textAbstract:
Traumatic brain and spinal cord injury continue to be substantial clinical problems with few available treatment strategies. Individuals who are at a greater risk for sustaining a central nervous system (CNS) injury, such as professional athletes and military personnel, may benefit from a prophylactic supplement that would intervene in the neurodegenerative pathways immediately following injury. The high demand for selenium within the central nervous system, as well as the synthesis of selenoproteins by neurons and astrocytes suggests a critical role of selenium within the brain and spinal cord. Studies were designed to test the efficacy of enriched dietary selenium status in providing neuroprotective benefits in rodent models of spinal cord and traumatic brain injury. Levels of selenium storage within the CNS are increased relative to the amount of selenium present in the diet, indicating that selenium compounds effectively cross the blood brain barrier.
In a model of moderate severity spinal cord contusion injury, dietary selenium supplementation reduced the number of days until recovery of independent bladder function following injury. These benefits did not translate to improvements in locomotor function during open field testing or reduction in overall lesion volume in the injured animal groups. Examination of gene expression changes 24 hours after spinal cord injury revealed that dietary selenium enrichment increased expression of genes involved in DNA repair, mitochondrial respiration, and transcriptional regulation. By expanding the scope of these studies to include models of traumatic brain injury, these data show the importance of selenium in the cortex as well. In particular, when compared to diets deficient in selenium, higher levels of dietary selenium improve spatial memory performance and mitochondrial respiration. The results of this dietary study show modest improvements following both traumatic brain and spinal cord injury and suggest that while selenium enrichment may not have a profound effect on the secondary injury cascade immediately following injury, the presence of adequate dietary selenium is critical for mitochondrial respiration. Together the results of these studies suggest that dietary supplementation may play a subtle role in injury mechanisms within the CNS and warrant further investigation.
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Nelson, Merlisa Claudia. "Ultrasound evaluation of the extracranial cerebrospinal venous system and carotid arteries in patients with multiple sclerosis." Thesis, Cape Peninsula University of Technology, 2013. http://hdl.handle.net/20.500.11838/1565.
Full textAbstract:
Thesis submitted in fulfilment of the requirements for the degree
Master of Technology: Radiography
in the Faculty of Health and Wellness Sciences
at the Cape Peninsula University of Technology
Supervisor: Ms. Ferial Isaacs
Co-supervisor: Prof. Susan J. Van Rensburg
Bellville
September 2013Multiple Sclerosis (MS) is characterised by demyelination within the central nervous system (CNS), which may result in neurological disabilities over time, causing considerable hardship to patients and their families, in addition to being costly to treat. Recent studies have linked MS to impaired cerebral blood flow, called chronic cerebrospinal venous insufficiency (CCSVI). Anecdotal evidence has suggested that surgical correction thereof results in improvement of symptoms experienced by MS patients. To my knowledge, no information is available in the literature on carotid artery disease in MS. The USA National MS Society has therefore called for more research to be done in this area. This cross-sectional observational sub-study will determine, by ultrasound (B-Mode, Colour and Pulsed-wave Doppler), the prevalence of chronic venous insufficiency (CCSVI) and carotid artery disease in the selected sample of MS patients within the region of the Western Cape, South Africa. Biochemical data; lifestyle factors such as physical activity and smoking; and nutritional status of MS patients were determined from the main study entitled: “The development of a comprehensive gene-based, pathology supported intervention program for improved quality of life in patients diagnosed with multiple sclerosis” (Division of Chemical Pathology, NHLS, Tygerberg Hospital, and University of Stellenbosch). Twenty-nine (29) patients were aged between 28-64years and they suffered from MS for 0.83-27years. A larger proximal and mid cross-sectional diameter (CSD) of the right IJV compared to the left (differences significant, P= 0.026 and P=0.023) was demonstrated. Increased intima media thickness (IMT) was present in 13.33% of the non-smoking MS group and 20% in the smoking MS group. IJV reflux was evident in 13.33% of the MS group. A significant reduction of cross-sectional diameters of the IJV’s was evident in smoking MS patients; suggesting that smoking is not only a risk factor for atherosclerotic disease but could also be related to narrowing of the major neck veins. This study also supports findings of other studies viz that there’s no significant correlation between extracranial venous abnormalities and MS. Early carotid artery disease was noted in smoking and non-smoking MS patients, however the findings were non-significant.
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Savall, Ana Carolina Rodrigues. "Reabilitação sexual para homens com lesão medular adquirida : da auto-adaptação sexual à intervenção terapêutica." Universidade do Estado de Santa Catarina, 2008. http://tede.udesc.br/handle/handle/403.
Full textAbstract:
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The present research was developed by means of three studies. The first one, composed by 62 men, aimed to evaluate the spinal cord injury impact on human sexuality, trying to identify the significantly affected sexual components. It was possible to verify alterations between the pre and post-injury periods: frequency and number of sexual partners significant reduction; anal sex practice considerable decrease; considerable modifications in the sexual preferences for hugging, vaginal penetration, vibrator use; variation in the pleasure originated in the following erogenous zones: mouth, neck, penis, thighs and legs; alterations in the sexual functions with significant reduction of the levels of desire, arousal and ejaculatory excitement, orgasm, as well as dysfunctions; sexual satisfaction significant reduction, even though some perceived alterations are equal to the general population. The results confirm the importance of giving assistance to the sexual sphere of these patients and found the proposal of sexual rehabilitation, serving as indicator. The second study involved the same population and aimed to analyze the sexual counseling, as well as understanding the post-injury sexual self-adaptation process. Between results, it was observed that less than half of the participants and only about one sixth of the partners received some type of sexual counseling. It was verified that the self-adaptation consists of a process influenced by some factors: age of incidence and time-of-onset, quality of received information, not being always successful, possessing peculiarities, such as the distinction between presence and absence of previous sexual experience before injury. The third study was composed by 25 people among researchers, relatives, health professionals, spinal cord injured men and their partners. It aimed to elaborate a sexual rehabilitation proposal that reflects the target population yearnings, necessities and potentialities. It was developed by means of Grupo Interdisciplinar de Apoio à Sexualidade Adaptada - GIASA, characterized by weekly 90 minutes meetings, divided in two stages: the first one, carried through May to September 2007, aiming to identify the pertinent subjects and the second one, between October and December 2007, with the purpose of presenting and discussing the subjects mentioned in the previous stage and to suggest evaluated strategies for the participants. While the first stage meetings had been marked by the discussion of free subjects, related to the sexuality, the second was composed for two moments: the first one, marked by seminaries, involving theoretical intervention on the previously definite subjects, with posterior opening for discussion, experiences exchange, reflection about the subjects and their respective approach, characterizing the focal group; and a second moment, where strategies characterizing the therapeutical interventions were applied, assessed and carried through interdisciplinarly, trying to involve the participants actively as citizens in the processes of focal discussion and theoretician-therapeutical intervention for the resolution of the diagnosed problem and considered for this research. Finally, based on the stages of the GIASA, it was elaborated a proposal of sexual rehabilitation called Grupo Interdisciplinar de Apoio à Saúde Sexual - GSex, generally directed to the community, and specially directed to the physically challenged people and/or chronic illnesses, being defined: purpose, action methodology, theoretical basis, principles, members functions, actions delineation, attendance process, among others topics.
A pesquisa desenvolveu-se mediante três estudos. O primeiro composto por 62 homens objetivou avaliar o impacto da lesão medular sobre a sexualidade humana, buscando identificar os componentes sexuais significativamente afetados. Verificou-se alterações entre os períodos pré e pós-lesão medular: diminuição significativa da freqüência e número de parceiros sexuais; redução sensível da prática sexual de sexo anal; modificações consideráveis nas preferências sexuais por abraço, penetração vaginal, utilização de vibrador; variação no prazer advindo das zonas erógenas da boca, pescoço, pênis, coxas e pernas; alterações nas funções sexuais com redução significativa dos níveis de desejo, excitação e orgasmo, bem como disfunções erétil e ejaculatória; redução significativa na satisfação sexual, embora algumas alterações percebidas equiparam-se à população em geral. Os resultados confirmam a importância de se prestar assistência à esfera sexual desses pacientes e embasam a proposta de reabilitação sexual, servindo como indicadores. O segundo estudo composto pela mesma população objetivou analisar o aconselhamento sexual e compreender o processo de auto-adaptação sexual pós-lesão medular. Entre os resultados observou-se que menos da metade dos participantes e apenas cerca de um a cada seis parceiros recebeu algum tipo de aconselhamento sexual. Verificou-se que a auto-adaptação consiste em processo influenciado por vários fatores: idade de incidência e tempo de lesão, qualidade das informações recebidas,não sendo sempre exitoso, possuindo peculiaridades como a distinção entre presença e ausência de experiência sexual prévia à lesão. O terceiro estudo foi composto por 25 pessoas entre pesquisadores, profissionais da saúde, homens com lesão medular, parceiras e familiares objetivando elaborar proposta de reabilitação sexual que refletisse os anseios, necessidades e potencialidades da população destinada. Desenvolveu-se por meio do Grupo Interdisciplinar de Apoio à Sexualidade Adaptada GIASA, caracterizado por encontros semanais com 90 minutos de duração, em duas etapas: a primeira realizada entre maio e setembro de 2007 que objetivou identificar os temas pertinentes e a segunda, entre outubro e dezembro, com a finalidade de apresentar e discutir com propriedade os temas propostos pela etapa anterior e sugerir estratégias avaliadas pelos participantes. Enquanto os encontros da primeira etapa foram marcados por discussões de temas livres relacionados à sexualidade, a segunda foi composta por dois momentos: um marcado por seminário, compreendendo intervenção teórica sobre os temas previamente definidos, com posterior abertura para discussão, troca de experiências, reflexão quanto à temática e forma de abordagem, caracterizando o grupo focal; e um segundo momento, onde foram aplicadas e avaliadas as estratégias caracterizando as intervenções terapêuticas, realizadas interdisciplinarmente, procurando-se envolver os participantes ativamente como sujeitos nos processos de discussão focal e intervenção teórico-terapêutica para a resolução do problema diagnosticado e proposto por esta pesquisa. Por fim, baseando-se nas etapas do GIASA, elaborou-se a proposta de reabilitação sexual denominada Grupo Interdisciplinar de Apoio à Saúde Sexual GSex, voltado à comunidade em geral, em especial a pessoas com deficiências físicas e/ou doenças crônicas, sendo definidos: finalidade, metodologia de ação, fundamentação teórica, princípios, funções dos membros, delineamento das ações, processo de atendimento, entre outros tópicos.
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El, Mendili Mohamed-Mounir. "Analysis of the structural integrity of the spinal cord in motor neuron diseases using a multi-parametric MRI approach." Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066575/document.
Full textAbstract:
Les pathologies du motoneurone sont caractérisées par une atteinte progressive des motoneurones au niveau de la corne antérieur de la moelle épinière. Au delà de cette susceptibilité anatomique commune, qui est responsable d’une atteinte motrice progressive et diffuse dans ces pathologies, d’autres systèmes neurologiques sont touchés. La dégénérescence du faisceau corticospinal est une caractéristique classique dans la sclérose latérale amyotrophique, qui est la maladie du motoneurone la plus commune chez l’adulte. Cependant, il est de plus en plus reconnu que la SLA est une maladie multisystémique. En particulier, une atteinte précoce du système sensoriel a été démontrée dans la modèle animal de la SLA ainsi que dans l’amyotrophie spinal liée à la mutation du gène SMN1 (survival motor neuron 1 en anglais). Chez les patients, l’imagerie par résonance magnétique (IRM) a émergé comme l’approche la plus performant à l’étage cérébral, permettant d’extraire des indices quantitatifs sur la perte neuronale, la dégénérescence axonale et la démyélinisation dans les pathologies neurodégénératives. Cependant, l’investigation de l’étage médullaire dans ces pathologies est difficile à mener à cause des nombreux défis techniques et méthodologiques que représente l’IRM de la moelle épinière.L’objectif de ce projet de thèse a été d’utiliser l’approche IRM multiparamétrique au niveau de la moelle épinière pour analyser les structures de la matière grise et blanche qui sont atteintes dans deux des pathologies du motoneurone les plus répondues, c’est-à-dire la SLA et la SMA, leurs altérations au cours du temps et leurs corrélations fonctionnelles avec les données cliniques et électrophysiologiquesDegenerative motor neuron diseases (MND) are characterized by a progressive dysfunction and loss of ventral horn motor neurons of the spinal grey matter. Beyond this common anatomical susceptibility, which is responsible for a progressive and diffuse weakness, other neurological systems are also impaired. The corticospinal tract (CST) degeneration is a classical feature of amyotrophic lateral sclerosis (ALS), which is the most common adult onset motor neuron disease, but a more widespread multisystem involvement is now well recognized. In particular, early sensory system involvement has been demonstrated in animal models of ALS and also of survival motor neuron 1 gene linked spinal muscular atrophy (SMN1-linked SMA). In human patients, magnetic resonance imaging (MRI) has emerged as the most powerful approach at the brain level to extract quantitative data on neuronal loss, axonal degeneration and demyelination in degenerative conditions. Studies at the spinal cord levels are scarce mainly because of technical and methodological difficulties. The objective of the present thesis project was to use a multi-parametric MRI approach at the spinal cord level to analyze grey and white matter structures that are impaired in two most common MND, i.e. ALS and SMN1-linked SMA, their temporal alterations during the disease course and the functional correlates, as assessed by clinical and electrophysiological examinations