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1
Tennant, Maria Elizabeth. "Axonal transport in motor neurone disease." Thesis, King's College London (University of London), 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.424667.
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Aspin, Jacqueline Patricia. "Immunological studies in motor neurone disease." Thesis, University of Bath, 1986. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.376335.
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Costa, Marc Michael John Da. "A zebrafish model of motor neurone disease." Thesis, University of Sheffield, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.548470.
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Mitchell, John Douglas. "Trace element studies in motor neurone disease." Thesis, University of Aberdeen, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.261363.
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The first part of the thesis reviews previous literature relating to motor neurone disease (MND), the cause of which remains obscure more than 150 years after it was first described. Historical aspects are presented drawing attention to the early descriptions of different facets of the clinical picture of MND which preceded its crystallisation into a single disease entity in the teaching and writing of Charcot. Much of this early work depended on knowledge of the toxic effects of lead on the peripheral nervous system. The epidemiology, blood group and HLA associations, pathology, immunology and virology of MND are discussed. Physical factors are also reviewed as are previous biochemical studies of MND. Knowledge regarding lead and mercury in relation to MND is discussed in detail. An analysis of previous literature concerning trace elements in MND is then presented to introduce the experimental section. This concerns the measurement of trace elements in spinal cord, liver, bone and cerebrospinal fluid (CSF) in MND patients and reference subjects by neutron activation analysis. Increased cervical cord, liver and bone selenium concentrations were found in the MND patients. Manganese content was increased in cervical and thoracic cord but reduced in liver. Low CSF cobalt concentration were also found. All other elements measured were striking by their concordance between the two groups in both tissue and CSF samples. These findings of an apparent alteration in the distribution of selenium and manganese in MND suggested that free radical mechanisms might be implicated in the pathogenesis of MND. CSF parameters of free radical activity were therefore studied but no differences found between reference subjects and MND patients. These results are discussed both in relation to the trace element studies and recent work on the possible importance of xenobiotics in the aetiology of the disease. Other aspects of the biological importance of selenium and manganese are described and some consideration is given to the DNA hypothesis of Bradley. This hypothesis is difficult to verify experimentally. A cytogenetic approach studying the sensitivity of lymphocytes obtained from control subjects and MND patients to mitomicin-C and ethyl methanesulphonate is described. This work did not yield any collateral evidence to support this hypothesis. In conclusion an attempt is made to bring the results of all this work together and consider how they might lead to a clearer understanding of the cause of this tragic and enigmatic disease.
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Ruddy, Deborah Marie. "Linkage studies in familiar motor neurone disease." Thesis, King's College London (University of London), 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.420083.
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Rafiq, Muhammad. "Mechanically assisted cough in motor neurone disease." Thesis, University of Sheffield, 2014. http://etheses.whiterose.ac.uk/6875/.
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Motor Neurone Disease (MND) is a disabling and inevitably fatal disease, usually with a life expectancy of 2-3 years from symptom onset. It is characterised by progressive wasting and weakness in bulbar, limb and respiratory muscles. There is no cure and treatment is mainly symptomatic. Neuromuscular respiratory failure, with or without a chest infection, is the commonest cause of death in MND patients. It has been shown that supporting respiratory function with non-invasive ventilation, improves survival and quality of life despite progression of the disease. The patients with respiratory muscle weakness may also have a weak cough and significant difficulty in clearing their airways of respiratory secretions. This causes much discomfort, predisposes to chest infections and adversely affects quality of life. Due to lack of evidence in this area, there is no clear consensus or guideline about how best to help such patients. This work aimed to establish the role of cough augmentation techniques in MND. A total of 40 eligible patients with MND were randomised to the breath-stacking technique (n=21) or Mechanical Insufflator-Exsufflator MI-E (n=19) and followed-up at 3 monthly intervals for at least 12 months or until death. All patients were diagnosed with respiratory failure and offered non-invasive ventilation (NIV). The primary outcome measure was the number of days with symptoms of chest infection, treated with antibiotics, in the community or in hospital. Survival and quality of life benefit, assessed by short form 36 mental component summary (MCS) and sleep apnoea quality of life index symptoms domain (sym), were the secondary outcome measures. There were 13 episodes of chest infection in the breath-stacking group and 19 episodes in MI-E group (p=0.87), requiring 90 and 95 days of antibiotics respectively (p=0.85). There were 6 episodes of hospitalisation in each group (p=0.87). The mean duration of symptoms per chest infection was 6.9 days in the breath-stacking group and 3.9 days in MI-E group (p=0.16). The chance of hospitalization, in the event of a chest infection was 0.46 in the breath-stacking group and 0.31 in MI-E group (p=0.47). Median survival in the breath-stacking group was 535 days and 266 days in the MI-E group. The MCS score was maintained above 75% of baseline for a median of 329 days in the breath-stacking group and 205 days in MI-E group (p=0.41). A non-significant improvement in quality of life, compared to baseline was observed in both interventional groups. In MND patients with respiratory failure, cough augmentation is likely to help maintain quality of life in the presence of the distressing symptom of weakened ability to cough. This study was not powered to assess the potential impact on life expectancy. There was no significant difference in terms of pulmonary morbidity between the two groups. A trend towards fewer chest infections was observed in the breath-stacking group, and a trend for reduced duration of antibiotic use and decreased chance of hospitalization in the event of a chest infection was observed in the MI-E group, though these changes did not reach statistical significance. These results are insufficient to draw firm conclusions, but support routine domiciliary use of a suitable cough augmentation technique in patients with ALS requiring respiratory support. The breath-stacking technique may be prescribed for domiciliary use with the onset of respiratory failure. MI-E may be useful in the event of a chest infection when it has the potential to reduce the duration of antibiotic use and chance of hospitalisation or when breath-stacking is no longer sufficient to maintain patient comfort. The results of this trial provide data useful for the power calculations required for a larger-scale multi-centre randomised trial.
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Chhetri, Suresh Kumar. "Outcomes of enteral feeding in motor neurone disease." Thesis, University of Central Lancashire, 2015. http://clok.uclan.ac.uk/12862/.
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Motor Neurone Disease (MND) is a fatal neurodegenerative disease of unknown aetiology characterised by the degeneration of motor neurones leading to progressive wasting and weakness of the bulbar, limb and respiratory muscles. Symptomatic treatment remains the cornerstone of management. Malnutrition is a common occurrence and an independent risk factor for worse prognosis. Clinical guidelines recommend enteral feeding when there is deterioration in nutritional status and/or dysphagia. However, it remains unclear whether enteral feeding offers any survival advantage. Moreover, the impact of enteral feeding on patients’ quality of life remains unknown. This study was undertaken to assess the impact of enteral feeding on survival and quality of life of patients with MND and describe the clinico-demographic characteristics of MND in Lancashire and South Cumbria in North West England. The study has both retrospective and prospective arms. The retrospective study was undertaken by reviewing the Preston MND database and case notes to examine the demographic, clinical and survival characteristics of MND in Lancashire and South Cumbria. The prospective study was undertaken over a period of three years to explore the perspectives of 21 patients with enteral feeding and its impact on their quality of life. The overall crude incidence of MND was 3.15 per 100,000. The mean age of onset was 67.28 (S.D. 11.06; range 22.78-93.06) years. Median overall illness duration was 1.98 (range 1.18-3.05) years. The presentation was limb onset in 62.1% cases and bulbar onset in 37.9% cases. A total of 91 (26.8%) patients received enteral feeding of which 67.0% were bulbar onset. Enteral feeding was not associated with a statistically significant survival advantage (χ2 (1) = 1.73, p = 0.19). iii Enteral feeding was associated with improved quality of life, despite the attendant inconveniences. Enteral feeding was perceived as being essential to survival by some participants while others reported a sense of relief and security that their nutritional needs were met. The body mass index stabilised following enteral feeding. A key finding, relevant for clinical practice, is that most study subjects acknowledged the importance of enteral feeding and a vast majority did not wish for the feeding tube to be removed, indicating a positive attitude towards enteral feeding. In conclusion, this study demonstrates a positive impact of enteral feeding on quality of life but not on survival. The lack of survival advantage should however, not dissuade clinicians from offering enteral feeding to patients with MND who manifest dysphagia and/or malnutrition. Even if enteral feeding does not add months to life, this study provides preliminary evidence that that it helps to add life to months.
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King, Susan Jane, and mikewood@deakin edu au. "Negotiating life choices: living with motor neurone disease." Deakin University. School of Nursing, 2005. http://tux.lib.deakin.edu.au./adt-VDU/public/adt-VDU20060719.144725.
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Motor neurone disease (MND) is an uncommon neurodegenerative disease that is terminal and has an insidious onset. With no known cause or cure, the disease triggers progressive death of motor neurones that causes increasing difficulties with mobility, communication, breathing and nutrition. Most research focuses on the disease process, but little is known of the illness experience from the perspective of those diagnosed with the disease. The aim of this study was to explore what it is like to live with MND and how people with the disease negotiate with others to exercise choice over the way they live.
A grounded theory methodology was used to explore the life world of people diagnosed and living with MND. Data were collected via in-depth interviews, their stories and photographs, poems and books participants identified as important and fieldnotes. The textual data were analysed using constant comparative analysis. The majority of participants experienced difficulty with verbal communication. Some invited a third person to interpret their speech and others used assistive technologies such as Lightwriters and computers.
Analysis revealed three constructs that, together, told the story of the MND illness experience. First, was the “diagnosis story” that described the devastating process of repeated tests had on the participants, shattering their trust in the competence of the health care system. The second construct revealed the process of living with MND as cyclical and repetitive requiring constant decision-making to adapt to the ongoing changes connected with the disease. The core theme and basic social process of “maintaining personal integrity” evolved as the third construct. This process underpinned and explained participants decision-making. Finally a substantive theory was conceptualised as the illness experience: “maintaining personal integrity in the face of ongoing change and adaptation”. This theory illustrates that the basic social process of maintaining personal integrity is central to decision and choice making while living with MND.
The findings have implications for people with MND, their carers, health professionals and service providers. Recommendations include improved counselling services for people at the time of diagnosis; the introduction of nurse specialists to support health professionals, people diagnosed with the disease and their families; open, accessible, realistic health and funding policies.
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Lloyd, Catherine Margaret. "Aspects of cortical function in motor neurone disease." Thesis, Imperial College London, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243835.
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Rewaj, Phillipa Jane. "Nature of language impairment in motor neurone disease." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/9744.
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Background: Language impairment associated with Motor Neurone Disease (MND) has been documented since the late 19th century, yet little is understood about the pervasiveness or nature of these deficits. The common clinical view among healthcare professionals is that communication difficulties can be attributed solely to the motor speech disorder dysarthria. Recent literature raises the possibility of more central processing deficits. Impairments in naming ability and comprehension of complex grammatical constructs have been frequently reported in some patients with MND. However, there is now growing evidence of spelling impairment, which could suggest the contribution of a more phonologically based deficit. In addition, the close relationship between MND and frontotemporal dementia (FTD) raises questions about the connection between the language impairments seen in MND patients and those documented in patients with the primary progressive aphasia (PPA) syndromes associated with FTD. Aims: This thesis examines the nature of speech and language deficits in people with MND and the extent to which expressive communication impairment can occur above and beyond dysarthria. In particular, the study explores: i) to what extent these language impairments can be attributed to deficits in working memory, executive functioning and/or disease severity; ii) what spelling errors can reveal about the integrity of lexical, phonological and orthographic processing; iii) whether similar patterns of impairment can be seen in PPA syndromes; iv) the relationship between language impairment and bulbar onset; and v) the impact these findings have on clinical management of MND patients. Methods: MND patients from across Scotland with changes in speech and/or language were tested using a neuropsychological battery of experimental and standardised tests of naming, spelling, syntactic comprehension, prosody and phonological and orthographical awareness. Patients were also screened for levels of dysarthria, executive functioning and working memory deficits, and results compared to those of matched controls. Findings: As a group, MND participants performed significantly worse than matched controls on measures of naming, spelling, orthographical awareness, grammatical comprehension, affective prosody and verbal fluency, but not working memory. However, based on patterns of individual impairment, of which spelling impairment formed a distinctive marker, the patient group divided into dichotomous subgroups, with 44% of participants categorised as ‘linguistically impaired’, while the remainder displayed little to no impairment. Those participants identified as linguistically impaired did not differ significantly from other MND participants on measures of disease severity, disease duration or dysarthria severity, although significantly more bulbar onset than limb onset participants were linguistically impaired. Spelling error patterns were suggestive of deficits at both a lexical and sublexical level, and were comparable to those reported in PPA literature. These findings suggest that dysarthria may be masking linguistic deficits in almost half of dysarthric MND patients, and highlight the importance of multidimensional assessment of language for effective clinical management.
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Bansal, Jacqueline A. "Quality of life issues in motor neurone disease." Thesis, Queensland University of Technology, 1998. https://eprints.qut.edu.au/36747/1/36747_Digitised%20Thesis.pdf.
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Motor Neurone Disease (MND) is caused by the degeneration and death of motor neurones. It is universally fatal and causes wasting and weakness of the somatic musculature. The disease usually affects those aged between 40 and 70, with 50% of people with MND dying within 3 years and 90 percent within 6 years. Only 10 percent survive 10 years or more
While the incidence of MND is much lower than that of Multiple Sclerosis, twice as many people die of MND as die from Multiple Sclerosis and Muscular Dystrophy combined. Once diagnosis is confirmed it appears that the health care service has little to offer in the way of care or a cure. The majority of people with MND are cared for in their home by family members which places enormous stress on both the individual and other family members.
The purpose of this study is to examine the factors which influence quality of life (QOL) in people with MND. This remains sadly under-investigated with only one significant report in the last three decades. The present study utilised a self-rated questionnaire, sent to individuals with neurologically confirmed MND, volunteering their participation via requests for help published in the MND Association newsletters throughout Australia. The questionnaire comprised standard measures which allowed the assessment of general well being (Rand 36-item Health Survey), depression (Beck Depression Inventory), coping strategies (Jalowiec Coping Scale), levels of hope (Herth Hope Scale), social support network (Norbeck Social Support Scale). Additional questions were constructed to assess illness-related knowledge, use of alternative therapies, the importance of spirituality and satisfaction with the way the diagnosis was delivered.
Demographically the individuals involved with the study differed little from other reports on MND. Psychologically, low mood was evident in over three quarters of the subjects. However, only 10 percent could be described as depressed. Coping strategies most frequently used was a problem solving approach and a dependency mechanism least frequently. Fifty three of the 74 in the study group held favourable levels of hope.
For such a terrible diagnosis it was most disturbing that 45 percent of those with MND thought that the information made available at diagnosis was inadequate. Of even greater concern was the fact that three quarters said that the diagnosis was disclosed in a brutal manner, with 61 % saying the manner was officious and factual.
Many individuals with MND had a poor knowledge about the disease with 40 percent believing that MND was a disorder of the muscles and one third did not know the median survival in this condition. Twenty three of the 74 admitted to using at least one alternative therapy at some stage. Expectedly, MND had a significant adverse effect on the life style, financial situation, social life, physical disability , psychological state and overall quality of life of many involved in the study. Only family relationships appeared to show little change following the diagnosis of MND. Despite great strains on marital harmony spouses remained the main carers in over half of the individuals with MND.
People with MND suffer greatly from the moment that the diagnosis is communicated through the depression of relentless muscle weakness and finally death from aspiration or respiratory failure. This study has highlighted that in general the care available to those suffering from MND is rather a hit or miss affair. Several measures to meet the specific needs of those diagnosed with MND are discussed. Most important of all is the need to better anticipate the rapidly changing needs of such individuals and for the medical and nursing professionals to be aware of the great harm they cause by removing all hope by well meaning frankness and the good they can do by offering support at all stages of the disease.
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Vance, Caroline. "Genetic linkage and association studies in motor neurone disease." Thesis, King's College London (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.435086.
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Kwok, Alice. "Unfolded protein responses in models of Motor Neuron Disease." Thesis, University of Oxford, 2010. http://ora.ox.ac.uk/objects/uuid:2f3efba7-dce1-4521-bda6-4db8ee81094d.
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Motor neuron disorders are a heterogeneous group of diseases characterized by the selective degeneration of motor neurons leading to muscle wasting and atrophy. Amyotrophic Lateral Sclerosis (ALS) is the most common amongst these disorders and is characterized by the selective loss of both upper and lower motor neurons in the brain and spinal cord. 20% of familial cases of ALS are caused by mutations in the Cu, Zn-superoxide dismutase gene (SOD1), a ubiquitously expressed enzyme responsible for scavenging superoxide radicals. The exact mechanisms underlying mutant SOD1-mediated neurotoxicity are unknown. Misfolded mutant SOD1 accumulates in the cytosol and mitochondrial intermembrane space (IMS) indicating the involvement of unfolded protein responses in ALS pathogenesis. Unfolded protein responses (UPRs) are complex signal transduction cascades which detect perturbations in protein folding and couple them to the expression of protein quality control machinery thereby allowing individual compartments to adapt to stress. In the cytosol, this study has shown that HspB8 was upregulated by SOD1 mutants, where it induced the clearance of aggregates by macroautophagy. This is a protective mechanism, as overexpression of HspB8 suppressed mutant-SOD1 mediated toxicity. In contrast, HspB8 mutants were impaired in macroautophagy and are toxic to NSC-34 cells. The mechanisms for the IMS-UPR have not been previously identified. To address this issue, a model for the accumulation of misfolded mutant SOD1 within the IMS was created and candidate proteins involved in protein quality control within the IMS were explored at the transcriptional level and at the level of protein expression. Preliminary results revealed some possible candidates that may have a role in the adaptation to mitochondrial stress. Interestingly, increased mitophagy was also found in IMS-G93A expressing cells, advocating the central role of macroautophagy in eliminating protein aggregates and damaged mitochondria in SOD1-FALS.
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Bäumer, Dirk. "Functional genetic analysis of motor neuron disease." Thesis, University of Oxford, 2010. http://ora.ox.ac.uk/objects/uuid:859016f8-5eff-4a8e-bfda-48afb8695646.
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Amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) are the commonest motor neuron diseases of adult- and childhood onset. Alterations of the RNA binding protein TDP-43 are associated with most cases of ALS, while SMA is caused by deletion of the Survival Motor Neuron (SMN1) gene. SMN has been well characterised in its role in the assembly of the cellular machinery that carries out splicing of pre-mRNA, but is thought to have other functions in RNA metabolism unrelated to pre-mRNA splicing. It is conceivable that specific aspects of RNA handling are disrupted in both SMA and ALS. A variety of genetic, molecular and neuropathological approaches were applied to investigate a potential common pathway in these diseases. The spectrum of genetic mutations underlying motor neuron disorders were explored by screening patient DNA. Cell culture and mouse models were used to test the hypothesis that altered pre-mRNA splicing causes motor neuron death. Human neuropathological specimens were examined for changes in proteins involved in RNA metabolism. The results indicate that altered pre-mRNA splicing is a late occurrence in disease and more likely to be a consequence rather than the cause of motor neuron degeneration. However, the notion that RNA metabolism is highly relevant to motor neuron diseases was strengthened by the discovery of mutations in another RNA binding protein, FUS, in cases of ALS without TDP-43 pathology. Overall the findings highlight the need to consider disruption of mRNA transport and regulation of mRNA translation in future motor neuron disease research.
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Cikurel, Katia. "Threshold electrotonus and ion channel dysfunction in motor neurone disease." Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.248415.
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Bourke, Stephen C. "Sleep, breathing and non-invasive ventilation in motor neurone disease." Thesis, University of Newcastle Upon Tyne, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.433126.
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Broom, Lucy Jane. "Ubiquitinated proteins in a mouse model of motor neurone disease." Thesis, King's College London (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.434369.
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Cox, Laura Elizabeth. "The contribution of ANG and CHMP2B to motor neurone disease pathogenesis." Thesis, University of Sheffield, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.555879.
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Motor neurone disease (MND) is the third most common adult-onset neurodegenerative disorder. It is relentlessly progressive and universally fatal, usually as a result of respiratory failure. In 3-5% of MND cases overt dementia is present, however, subtle impairment to cognitive function is present in up to 50% of sufferers. In approximately 10% of MND cases there is a clear pattern of inheritance, however, genetic causes are believed to make a substantial contribution to apparently 'sporadic' disease. Mutations in ANG were first identified in a large cohort of MND cases from several diverse geographical regions, four of the patients suffered from familial disease, whereas the remaining 11 had no family history of MND. A mutation in CHMP2B was originally identified in a Danish pedigree with autosomal dominant FTD, which was subsequently followed by the identification of missense mutations in two, unrelated, patients with familial MND, one of whom also showed features ofFTD. The initial aim of the present study was to determine whether mutations in ANG and CHMP2B contribute to MND pathogenesis by mutation screening a large cohort of MND patients for whom serial clinical details were available. Neuropathological tissue was available for a proportion of these cases. Sequencing of ANG revealed a mutation in one case diagnosed with an early-onset, classical amyotrophic lateral sclerosis (ALS) phenotype, who showed rapid deterioration and characteristic ALS neuropathology. Four cases carrying 3 missense mutations in CHlvfP2B, including one novel mutation, p. Thrl04Asn, \vere identified. Only 1 case had a family history of MND, the remaining 3 were affected by apparently sporadic disease. In all 4 cases analysis of clinical and neuropathological data was consistent \vith a diagnosis of the progressive muscular atrophy (PMA) variant of MND. To analyse the affect of mutant CHMP2B on the transcriptional response, gene expression profiling was performed on RNA extracted from motor neurones (MNs) from CHMP2B cases and controls. Significant changes in the expression of genes from multiple pathways were identified, including: axon guidance; actin cytoskeleton regulation and SNARE interactions in vesicular transport; cell cycle; apoptosis; mTOR signalling and autophagy regulation; MAPK signalling; calcium signalling and Wnt signalling. The alterations to these pathways were predicted to result in: disassembly of cell structure; increased calcium concentration in the ER lumen; decrease in the availability of A TP; downregulation of the classical and p38 MAPK signalling pathways; reduction in autophagy initiation and a global repression of translation. Finally, to determine the effect of CHMP2B mutations on cellular phenotypes, HEK- 293 cells were transiently-transfected. This demonstrated that mutant CHMP2B expression resulted in the formation of large cytoplasmic vacuoles and aberrant lysosomal localisation.
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Beaujeux, Timothy Paul. "Protein aggregation in a mouse model of familial motor neurone disease." Thesis, University of Sheffield, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.427349.
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Clarke, Janice Barbara. "Values of lay and professional care : an interpretive enquiry." Thesis, University of Southampton, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.324774.
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Waterfall, Alan H. "The development of in vivo methods to measure the neuropeptide thyrotrophin releasing hormone in the central nervous system." Thesis, University of Nottingham, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.358269.
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Gibbons, Christopher Julian. "Towards a psychosocial model of quality of life in motor neurone disease." Thesis, University of Liverpool, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.570230.
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Background Quality of life (QoL) in motor neurone disease is a complex issue, and is known to be associated with a number of factors. Previous research has suggested that QoL may be more closely related to psychosocial features of the disease than high levels of functional impairment frequently witnessed in the disease. However, the accuracy of research into patient QoL is potentially mitigated by reliance on generic questionnaire measures that may not be sensitive to the unique experience of living with MND. Fatigue is a salient issue for patients with MND although no previous study has attempted to explore the symptom of fatigue from the perspective of the MND patient and create a disease-specific measurement tool for fatigue. The current study seeks to create an accurate questionnaire measure for fatigue in this population, as well as validating existing measures of anxiety and depression. These measures will be employed to determine the direct and indirect effects between important features of the disease, and their relationship with patient quality of life. The central hypothesis is that quality of life is closely related to fatigue and psychosocial aspects of the disease, including depression and social withdrawal, but is not associated with functional impairment. Methods Initial qualitative interviews with ten MND patients were carried out using an Interpretative Phenomenological Analysis approach to explore the experience of fatigue and validate a 52-item fatigue set for use in this population. Two hundred and ninety eight patients recruited from five MND care centres in Liverpool, Oxford, Preston, Salford and Sheffield completed the Phase One questionnaire suite containing the nascent Neurological Fatigue Index - MND (NFI-MND), The Hospital Anxiety and Depression Scale (HADS), the MND Social Withdrawal Scale and the MND Coping Scale. Psychometric and Rasch analyses are presented for the NFI-MND and the HADS. A subsample of 78 patients recompleted the Phase One questionnaire suite after four to six weeks to assess test-retest validity. Contemporaneous functional status information was taken from the hospital notes of 139 patients from the Phase One cohort. After six months, 107 participants were reconsented to complete the Phase Two questionnaire suite which contained validated versions of the measures included in the Phase One questionnaire pack, in addition to the World Health Organisation Quality of Life Brief Scale (WHOQoL-BREF) and the Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R). Preliminary correlation and regression analyses were used to assess relationships within the dataset before entering study variables assessing the relationship between study variables using structural equation mode ling. Results Based on interpretative analysis of interview transcripts, fatigue was defined as reversible motor weakness and whole-body tiredness that was predominantly brought on by muscular exertion and was partially relieved by rest. This bi-partite definition was supported by factor analysis of the 52-item fatigue set. Rasch analysis led to the validation of 'Reversible Motor Weakness' and 'Lack of Energy' scales that closely reflected the patient experience of fatigue. A higher order measure of fatigue was supported by the Rasch model, and consisted to items from both subscales. The original HADS did not satisfy the requirements of the Rasch model, with both sub scales containing misfitting items. Following removal of misfitting items, both the HADS-D and the HADS-A were shown to fit the Rasch model. A higher order measure of psychological distress was confirmed as being valid and suitable for research use. Structural equation modeling revealed that depression and fatigue are key variables in the determination of patient QoL, although fatigue did not exhibit a significant direct effect of QoL. Coping was found to be a strong modifier of both depression and anxiety, and have a strong indirect effect on patient QoL. Conclusion These analyses provided support for the experimental hypothesis that quality of life is strongly associated with fatigue, depression, anxiety, coping and social withdrawal but is not significantly associated with functional status. The objectives of this thesis were met and in doing so many questions regarding fatigue, psychological issues and QoL in MND were answered, providing a strong base upon which future research may be conducted.
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何子雅 and Tsz-nga Ho. "The role of free radicals and antioxidants in motor neurone degenerative disease." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1998. http://hub.hku.hk/bib/B31215294.
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Ho, Tsz-nga. "The role of free radicals and antioxidants in motor neurone degenerative disease /." Hong Kong : University of Hong Kong, 1998. http://sunzi.lib.hku.hk/hkuto/record.jsp?B19737786.
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Forrest, Vanessa Ann. "Aspects of serotonergic and glutamatergic neurotransmission in the human motor system and in motor neurone disease." Thesis, University of Newcastle Upon Tyne, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.336814.
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Fitzmaurice, P. S. "The involvement of free radicals in the causal mechanism of motor neurone disease." Thesis, University of Central Lancashire, 1996. http://clok.uclan.ac.uk/20546/.
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The detoxification of free radicals at a cellular level is crucial for maintaining cell viability. The progressive loss of motor neurones associated with motor neurone disease (MND) may be due to acute or chronic free radical damage causing irreversible cell lesions. Perturbation in the mechanisms involved in the cell's protection against the deleterious effects of free radicals could therefore initiate, or indeed propagate, this damage. Measurement of the free radical detoxif'ing enzymes superoxide dismutases (copper/zinc superoxide dismutase (SOD I), manganese superoxide dismutase (SOD2), glutathione peroxidase (GSHPx) and catalase (CAT) at the site of motor neurone loss (i.e. the anterior horn in the spinal cord) showed a significant increase in the percentage of SOD2, in MND patients than controls, at the thoracic level. GSHPX activity was approximately 10-fold higher in the white matter of the spinal cord compared to that in the gray matter, whilst CAT activity was approximately 100-fold higher than GSHPX and equally distributed between the white and gray matter of the spinal cord. The activity of CAT within the central nervous system (CNS) is compartmentalised in microperoxisomes, it is therefore likely that removal of peroxides from the cytoplasm and other cellular organelles is reliant on GSHPx activity, which has a significantly lower activity in the anterior horn of the spinal cord than in other cells. Xanthine oxidase (XO) activity is a potential source of superoxide (07) (metabolism of xanthine to uric acid by XO produces 07) its subcellular location in the perikatyon of the spinal cord was shown to be associated with mitochondria. Thus the normal generation of 07 accompanied by alteration in superoxide dismutation may lead to increased free radical damage of the mitochondria which might initiate the process of cell death. 8-Hydroxylation of guanosine (indicative of oxidative damage) within the spinal cord from MIND patients was 10-fold higher than that in controls, showing that the nerve perikaiyon in MIND are subject to increased oxidative damage. It is clear therefore that free radical mechanisms play an important role in MIND.
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Piggin, Lucy Helen. "The experience of non-invasive ventilation in motor neurone disease : a qualitative exploration." Thesis, University of Liverpool, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.569269.
Full textAbstract:
Motor neurone disease (MND) is a fatal neuromuscular illness defined by progressive muscle weakness and wastage. Death typically occurs within 2-3 years from symptom onset and is most often attributable to respiratory complications. Weakness in the respiratory muscles increases the risk of mortality and is also a significant predictor of quality of life in MND, which makes management of respiratory aspects of the condition a vital component of care. The first signs of respiratory insufficiency are typically related to the onset of nocturnal hypoventilation, which can disturb sleep and lead to waking headaches, somnolence, fatigue, impaired concentration, cognitive impairment, reduced appetite, and low mood. The primary means of managing these symptoms is through the use of non-invasive ventilation (NIV). There is a vast quantitative research base charting the impact of NIV. It is known to decrease the number of arousals from sleep, reduce somnolence/fatigue, eliminate waking-headaches, improve cognitive functioning, and may also exert a positive impact on emotional/social functioning in some patients. NIV can also benefit daytime respiratory performance, improving self-rated dyspnoea and slowing the rate of respiratory decline as the illness progresses. Crucially, NIV also affords selected MND patients a significant survival advantage. Existing research offers limited insight into the lived experience of respiratory impairment and NIV use; it is unknown how patients themselves feel about using a ventilator or how they receive the positive clinical outcomes associated with the treatment. This thesis presents a body of qualitative research using interpretative phenomenological analysis (IPA) to explore MND patients' experiences of respiratory impairment and NIV use. The first study, a small cross- sectional enquiry (11=5), reports the experiences of patients already established on the ventilator. This study found complex emotional •and psychological responses to NIV, including reluctance to initiate, fear of dependence and threats to control. Respiratory masks were also found to have a significant negative impact on identity and self-esteem. However, patients felt that the positive physical effects of NIV made this experience acceptable. This cross-sectional study was a preparative step for a subsequent longitudinal study, recruiting patients (11=26) and carers (n=26) prior to ventilation and interviewing them over time as they started using NIV. Two data sets are reported: 'pre-ventilation' and 'post-ventilation' analysis. Pre-ventilation analysis also explored the lived experience of respiratory impairment and treatment decision-making. This longitudinal study found that referral into a respiratory service was an emotionally stressful event for patients; most had been unaware of the prospect of respiratory impairment and were vulnerable to anxiety. Patients seemed to lack insight into their own respiratory status, which appeared to be attributable to both a lack of understanding of respiratory aspects of the condition and difficulties in making sense of respiratory changes within the wider physical context of the illness. Most patients responded negatively to the idea of ventilation, seeing it both as a 'defeat' and as an ominous sign of illness progression, yet they were also comforted by the idea that there was 'help' available to prevent suffering. Patients typically elected not to think about NIV ahead of time, which appeared to be part of a wider 'one day at a time' approach to MND. Patients who went on to trial NIV (11= 12) reported markedly different responses to initiation and variable degrees of involvement in treatment decision-making. Many patients did not feel that intervention was needed. Positive physiological! clinical outcomes did not necessary lead to positive psychological and emotional responses to the treatment and did not ensure that the experience of using a ventilator was a positive one. There were a number of practical and psychological challenges that determined tolerance and compliance with the treatment; however, the same challenges were often perceived differently by different patients. It was not possible to predict 'success' on NIV based on clinical or demographic variables alone. Patients' experiences of NIV were best understood in the individual context of each patient and in light of their personal illness experiences. These findings make a significant contribution to the established research base, providing an alternative perspective to substantiate the quantitative evidence. It is intended that the research presented in this thesis will be of direct practical utility, helping clinicians who are supporting MND patients to ensure that patients' experiences of respiratory care and NIV use are as positive as they can be.
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Wicks, Paul Jon Andrew. "The profile of cognitive, behehavioural and emotional change within MND [motor neurone disease]." Thesis, King's College London (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.430936.
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Lyall, Rebecca Ann. "Respiratory muscle function and non-invasive positive pressure ventilation in motor neurone disease." Thesis, King's College London (University of London), 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.417858.
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Newbold, Sarah Georgina. "Susceptibility factors to Parkinson's Disease and motor neurone disease : cyctochromes P450 1A2, 2D6, 2E1 and flavin monooxygenase." Thesis, University of Sheffield, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.425191.
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Radakovic, Ratko. "Multidimensional apathy in neurodegenerative disease." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/25959.
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Apathy is characterised by a lack of motivation towards goal directed behaviour and is a symptom of various neurodegenerative diseases. There are various tools that can be used to assess apathy but a caveat of these is that they usually assess it as a unidimensional concept. Apathy has been recognised to have a multidimensional substructure. The Dimensional Apathy Scale is the only comprehensive measure designed to quantify neurobiologically-based subtypes, called Executive, Emotional and Initiation apathy. The first aim of this study was to explore multidimensional apathy, and its associations with demographic variables, in healthy, community dwelling adults. Secondly, multidimensional apathy was explored in neurodegenerative diseases, specifically Amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD) and Alzheimer’s disease (AD). For each disease group, the validity and reliability of both the self rated and carer rated DAS were also determined. Finally, the association between specific apathy subtype impairments and executive dysfunction was explored in ALS patients. Four hundred healthy community dwelling adults, eighty-three ALS patients (seventy-five carers), thirty-four PD patients (thirty carers) and forty-nine AD patients (eighty-nine carers) were recruited for the questionnaire study. In the healthy community dwelling adults, Executive apathy decreased with age, whereas Emotional increased with age. Gender differences were also shown with higher apathy in males on Emotional apathy. There were also employment differences, in that Executive apathy was higher in unemployed individuals compared to those who were employed. Emotional apathy showed difference in type of employment, where full time employed individuals were significantly more apathetic than those employed part time. These findings were taken into account in selecting the appropriate control samples to match our patient groups. In the patient groups, ALS patients were found to be significantly more impaired on the Initiation subscale when compared to controls. Furthermore, Initiation apathy was found to be the most frequent impairment above abnormality cut-off on the carer rated DAS. PD patients were significantly more impaired on Executive and Initiation apathy when compared to controls. These two subscales were most frequently above abnormality cut-off in the carer rated DAS. Finally, AD patients were significantly more impaired on all subscales when compared to controls and, on the carer rated DAS, global impairment over all subscales was most often reported as above abnormality cut-off. Additionally in AD, there was a significant disparity between carer and patient ratings on Executive and Initiation apathy, indicating patients’ impaired awareness. When comparing patient groups, there was a significant difference between carer rated apathy subtype impairments for each patient group. Validity and reliability of the DAS was found to be robust when compared to standard measures of apathy and depression. In the experimental study, a sample of ALS patients (and their carers) and healthy controls (and their informants) were recruited to complete a battery of neuropsychological tests, the DAS, other apathy and depression measures. ALS patients were impaired on tasks of executive functioning when compared to controls. Furthermore, apathy subtype deficits were associated with executive dysfunction in ALS. In conclusion, apathy is a multidimensional concept that manifests in different subtype profiles dependent on neurodegenerative disease. This has further implications for understanding and assessment of cognitive dysfunction and neuropsychiatric symptoms, such as apathy, in ALS and other neurodegenerative disease patient groups.
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Bibbings, Kate. "The utility of b-mode ultrasound for the diagnosis of motor neurone disease : automated detection and analysis of muscle twitches in ultrasound images of motor neurone disease affected participants and healthy controls." Thesis, Manchester Metropolitan University, 2017. http://e-space.mmu.ac.uk/619950/.
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Motor Neurone Disease (MND) is a progressive, neurodegenerative disease, for which there is no known cure. Electromyography (EMG) is the standard technique for the detection of diagnostic indicators, such as fasciculations (twitches). Ultrasound (US) imaging may provide a more sensitive alternative to EMG for detection of fasciculations. However, only one computational technique has previously been applied to image sequences to provide an objective measure of fasciculation occurrence. The work presented here therefore describes the development and evaluation of a new computational approach, based on foreground detection using a mixture of Gaussians (GMM). In addition, the only other computational analysis approach available, which is based on feature tracking and mutual information analysis (KLT/MI) was further evaluated. Two data sets were used to evaluate the computational approaches. The first data set had previously been collected and comprised US images from medial gastrocnemius (MG) and biceps brachii (BB) from healthy (n = 20) and MND affected (n = 5) participants. The second data set comprised simultaneously recorded US images and intramuscular EMG from five muscles (medial gastrocnemius (MG), biceps brachii (BB), rectus femoris (RF), trapezius (TRAP), rectus abdominis (RA) and thoracic paraspinal (TP)) of healthy (n = 20) and MND affected (n = 20) participants. Accuracy of the approaches for fasciculation detection was evaluated against two measures of ground-truth: i) manual identification; ii) intramuscular EMG. Accuracy was defined as the area under the receiver operator curve and comparisons made between the performance of GMM and KLT/MI. Initial analysis was completed on the large limb muscles, MG and BB. The GMM had better accuracy than the KLT/MI when compared against operator identifications as the ground truth signal (88 – 94 % vs. 82 – 90 %). When EMG was used as the ground truth the GMM again had higher accuracy (81 – 88 % vs. 70 – 79 This thesis has shown a GMM computational analysis can detect fasciculations across a wide range of muscles and also can be used for the characterisation of fasciculations as they appear in ultrasound images, with significant differences being found between the healthy and MND affected participant groups. It has provided a foundation from which to build, with suggestions for future work being collecting images of stimulated twitches in a wide range of muscles for further characterisation and also a larger scale study prior to an official diagnosis being made to determine sensitivity and specificity values for this method as a diagnostic test.
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Dharmasaroja, Permphan. "The role of eEF1A2 in the pathogenesis of motor neurone disease in wasted mice." Thesis, University of Edinburgh, 2007. http://hdl.handle.net/1842/24522.
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Mice with autosomal recessive gene wasted (wsf) develop a set of neurological features that include progressive muscle wasting, weight loss, progressive paralysis, and degeneration of motor neurones in spinal cord and brainstem. The wasted mutation is caused by a 15.8-kilobase deletion that completely abolishes the detectable expression of eukaryotic elongation factor 1A2 (eEF1A2), a tissue specific protein that expresses only in nervous system, heart and skeletal muscle. In this PhD thesis I describe the characterisation of neuromuscular abnormalities of wasted mice and study expression of nerve-regulated genes using real-time RT-PCR. Muscle of wasted mice showed evidence of denervation atrophy, and the patterns of gene expression were characteristic for the type of denervation. I have constructed an epitope-tagged eEF1A2 plasmid and studied colocalisation of eEF1A2 and spinal motor neurone (SMN) protein in HeLa cells, using quantitative immunocolocalisation analysis. I have shown that a proportion of cytoplasmic eEF1A2 colocalises with SMN. To study the role of eEF1A2 I have constructed a muscle-specific transgene and generated transgenic homozygous wasted mice that specifically express human eEF1A2 in skeletal muscle, but not in neurones. Transgenic wasted mice showed the same phenotype as spontaneous mutant wasted mice. Muscle pathology and the patterns of gene expression were compatible with denervation. These findings suggest that the loss of eEF1A2 in motor neurone, but not muscle, leads to muscle atrophy in wasted mice.
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Mistry, Kriten. "Exploring the psychological experiences of people living with a diagnosis of motor neurone disease." Thesis, Lancaster University, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.587077.
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One of the aims of this study was to explore the psychological experiences of people diagnosed and living with motor neurone disease (MND). As qualitative research within this area is currently limited a literature review of other similar chronic conditions such as Parkinson's disease (PD), multiple sclerosis (MS) and Huntington's disease (HD), as well as MND, were evaluated using an meta-ethnographical approach. This approach was used as it allows for multiple cases, accounts, narratives or studies to be assimilated and interpreted so as to develop new understandings in areas where research may be limited. The review found that people living with one of the four conditions experienced similar difficulties and could be conceptualised under three main concepts. The second aim of this study was to explore the psychological experiences of people with a recent diagnosis of MND and the transitional process they experienced to accept their diagnosis and to make adjustments in their lives. An interpretative phenomenological approach (IPA) was used and three themes were constructed from the analysis of the data collected. The first described the sense of devastation people experienced when they realised they had been diagnosed with a life limiting condition. The second theme describes the processes of accepting and adjusting to the diagnosis. The third theme describes the progressive losses that were experienced as symptoms affected functional abilities and how this impacted on their lives. Ideas for future research were also discussed as well reflections on some of the difficulties that were experienced whilst completing the study.
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Hamdalla, Hisham Hamdalla Mohamed. "Transcranial magnetic stimulation in normal human adult subjects and patients with motor neurone disease." Thesis, University of Newcastle upon Tyne, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.407642.
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Dodd, R. S. "Emotional distress in Motor Neurone Disease : the role of metacognitive beliefs and repetitive negative thinking." Thesis, University of Liverpool, 2017. http://livrepository.liverpool.ac.uk/3009717/.
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Stephenson, Jodie. "Beyond SOD1 : detailed characterisation of a TDP-43 transgenic mouse model of motor neurone disease." Thesis, University of Sheffield, 2017. http://etheses.whiterose.ac.uk/16694/.
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Background: Motor neurone disease (MND) is a fatal, progressive, neurodegenerative disease causing muscle weakness, spasticity and paralysis. No small molecule drugs have translated from MND mouse models to MND patients, possibly because of MND mouse models being based on SOD1 mutations, representing only a small proportion of patients. Nearly all non-SOD1 patients have TDP-43 pathology, whereas SOD1 patients do not, suggesting a mechanistic difference between non-SOD1 and SOD1-related MND. A TDP-43 model may be more representative of the patient population and lead to better translation of treatments. There is also a need for translational biomarkers in MND to further improve translation. Methods: A colony of mice transgenic for mutant human TDP-43 (TDP-43Q331K) was established, alongside a control line (TDP-43WT). The mice were characterised for motor function including rotarod, gait analysis, and neuroscoring. Immunohistochemical, mRNA and protein level studies were also carried out. Increased weight was noted in the TDP-43Q331K mice, leading to a study of voluntary activity and food intake. A further study investigated electrophysiological parameters, apathy, and riluzole treatment. Preclinical 31P-MRS imaging was carried out in SOD1G93A mice in an attempt to find a translational biomarker. Results: TDP-43Q331K mice developed a progressive phenotype, whilst TDP-43WT mice showed none. TDP-43Q331K mice showed signs of motor dysfunction, increased TDP-43 in the nucleus and cytoplasm of motor neurons (supported by increased mRNA and protein levels), astrogliosis, and microgliosis in the spinal cord, apathy, overeating and electrophysiological findings suggestive of denervation. Riluzole may have had a mild treatment effect in TDP-43Q331K mice, measured by electrophysiology. No conclusions could be drawn from the preclinical 31P-MRS due to animal welfare issues. Conclusions: TDP-43Q331K mice have a progressive motor phenotype of low variability with reliable motor, pathological and cognitive readouts of disease and may provide a useful model for evaluating potential neuroprotective therapies.
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Jones, Ross Alexander. "Comparative anatomy of the human neuromuscular junction." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/29629.
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The neuromuscular junction (NMJ), the synapse formed between lower motor neuron and skeletal muscle fibre, is known to be a target in a number of neurodegenerative conditions, including motor neuron disease (MND). Located in an accessible part of the peripheral nervous system, the NMJ can be used as a ‘model synapse’ in the context of ‘connectomics’ – the study of synaptic connectivity throughout the nervous system as a whole. Although the NMJ has been studied in a number of species, relatively little is known about its structure in humans, complicating the translation of animal models of disease to the human condition. Described here is the first detailed cellular and molecular characterization of the human NMJ. A standardized methodology for comparative morphometric analysis of NMJs was developed and validated (‘NMJ-morph’). NMJ-morph was used to generate baseline data for 2160 NMJs from a single litter of wild type mice, representing 9 distinct muscles across 3 body regions. Principal components analysis (PCA) revealed synaptic size and fragmentation to be the key determinants of synaptic variability. Correlation data revealed the pre-synaptic cell (motor neuron) to be a stronger predictor of synaptic morphology than the post-synaptic cell (muscle fibre). Other factors influencing synaptic variability were in a clear hierarchy: muscle identity accounted for more variation in synaptic form than animal identity, with side having no effect. Human tissue was obtained from 20 patients (aged 34 to 92 years) undergoing lower limb amputation, primarily for the complications of peripheral vascular disease (PVD). Muscle samples were harvested from non-pathological regions of the surgical discard tissue. 2860 human NMJs were analyzed from 4 distinct muscles (extensor digitorum longus, soleus, peroneus longus and peroneus brevis), and compared with equivalent NMJs from wild type mice. Human NMJs displayed unique morphological characteristics, including small size, thin axons, rudimentary nerve terminals and distinctive ‘nummular’ endplates, all of which distinguished them from equivalent mouse NMJs. The previous notion of partial occupancy in human NMJs was disproved. As in mice, the pre-synaptic cell was shown to correlate more strongly with NMJ morphology; in contrast to mice, the human NMJ was found to be relatively stable throughout its 90+ year lifespan. In support of the tissue harvesting procedure, patient co-morbidities (diabetes mellitus and vascular disease) did not significantly impact NMJ morphology. Super-resolution imaging of the NMJ revealed significant differences in the functional architecture of human and mouse active zones. Despite the smaller synaptic size in humans, the total quantity of active zone material was conserved between the species, suggesting a homeostatic mechanism to preserve effective neurotransmission. Parallel proteomic profiling demonstrated further species-specific differences in the broader molecular composition of the NMJ. The cellular and molecular anatomy of the human NMJ is fundamentally different to that of other mammalian species. These differences must be taken into account when translating animal models of disease to the human condition.
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Zeman, Sara-Sophia. "Molecular biology and neurochemistry of the cortical lesion in motor neurone disease : human post mortem study." Thesis, King's College London (University of London), 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.294787.
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Hobson, Esther V. "Facilitating access to specialist care for patients and carers living with motor neurone disease using telehealth." Thesis, University of Sheffield, 2017. http://etheses.whiterose.ac.uk/18376/.
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Care of patients with motor neurone disease (MND) is best provided by a specialist, multidisciplinary team but access to this care is not universal. Technology-enabled care has the potential to improve access to specialist care in MND. A telehealth system (TiM: Telehealth in Motor neurone disease) was developed to allow patients and carers to share information about their condition using the internet with a specialist MND nurse. An 18-month, mixed methods, randomised, controlled pilot and feasibility study was conducted and a process evaluation explored the use, feasibility, acceptability and potential impact of the TiM system. Clinical outcomes (such as quality of life) were collected and semi-structured interviews with participants and clinicians were conducted. 40 patients and 37 carers were recruited and randomised to receive usual care or usual care plus the TiM system. Participants and clinicians felt that the TiM system was an acceptable and feasible way of improving access to specialist care and thought it could have the potential to improve their care. Formal comparisons of the two treatment groups were not aims of the trial but only modest differences were observed. The study identified further necessary improvements to the TiM, particularly focusing on the way clinicians act upon the information received and interact with patients and carers. The trial methods appeared to be feasible. The main challenge posed by a definitive trial appeared to be how to effectively measure impacts of the TiM on participants and the clinical service. This thesis recommends that the next step of TiM development should include further iterative improvements to TiM system in parallel with research that explores how the system would be used best in different MND services. If these evaluations also suggest the TiM system offers value, a definitive randomised controlled trial may be feasible. However, this thesis identifies better ways to further evaluate this complex intervention.
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Sakellariou, Dikaios. ""As you can see, we plod along" : narratives of living with motor neurone disease in Wales." Thesis, Cardiff University, 2014. http://orca.cf.ac.uk/62506/.
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This dissertation is the outcome of a 25-month long narrative inquiry-based study on experiences of living with motor neurone disease (MND). MND is an adult onset, incurable, neurodegenerative condition that is characterised by loss of voluntary muscle movement as a result of destruction of motor neurones, leading gradually to partial or complete paralysis and eventually to death. The aim of this study was to explore the experiences of people living with MND. Following a narrative inquiry methodology the focus of the study was to explore how specific people live in their local contexts. Data were collected through the use of multiple semi-structured interviews with people with MND and some of their partners. The findings illustrate the unique ways in which people with MND experience the disease and make sense of their life. The seven people who participated in this study were trying to construct a notion of normality in their everyday life, in the midst of what were sometimes perceived as difficult or even abnormal circumstances. Through seeking and trying out different solutions to the challenges they were facing, participants were trying to create a life they could describe as good. The findings highlight the intersubjective nature of illness experiences. For the three couples who participated in the study the experience of being in a long-term relationship was a vital part of who they were, and how they experienced MND. The findings also underline the importance of exploring the experiential knowledge that people living with MND develop through managing the disease and incorporating it in various ways in their daily life. This knowledge can help create a kind of life that people living with MND feel is worth living.
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Donaghy, Colette Geraldine. "A clinical epidemiological study of motor neurone disease in Northern Ireland with special reference to eye movements." Thesis, Queen's University Belfast, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.492150.
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This thesis describes the epidemiology of Motor Neurone Disease (MND) in Northern Ireland. A study of eye movements in MND is then described which had the aim of developing a biomarker for disease. The incidence of MND in Northern Ireland was found to be 2 per 100,000 person-years and, using capture-recapture analysis, was found to be an underestimate. The prevalence of MND in Northern Ireland was 4.9 per 100,000 population and remained unchanged due to the finding of 0.7 missing cases using capture-recapture analysis. The results of the epidemiological study described in this thesis added to current literature highlighting the likely level secular trend of MND. Incidence increased with age in males without peaking, a trend not observed since work performed in the Mayo Clinic, USA, in the 1980's. 'Timeliness of diagnosis' in MND was then examined revealing that the longest time period in the diagnostic process for patients with MND was that time spent with a physician before appropriate referral was made to a neurologist. It was felt that one of the reasons for this was that GPs were likely to be disillusioned with long waiting times for neurological outpatient referrals. Practical solutions are presented. A study of eye movements in MND was undertaken. The primary hypothesis stated that fixation would be abnormal in MND, particularly bulbar-onset disease. Fixation was indeed found to be abnormal in MND but did not relate to bulbar dysfunction. Instead fixation was found to correlate with the sub-clinical frontal lobe dysfunction that has been uncovered in patients with MND recently. To the authors knowledge this is the first study to examine fixation formally in a disease population. Furthermore, little is known of the neural substrate of fixation and this work helps in defining it.
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Mockford, Carole. "Motor Neurone Disease: Assessment of Carer Burden and Experiences of Service Provision - The Development of a Questionnaire." Thesis, University of Oxford, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.490114.
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Motor Neurone Disease (MND) is a life threatening, neurodegenerative disease for which there is no known cure. As the patient becomes increasingly disabled and subsequently dependent on others, responsibility often falls to close friends and relatives to care for them at home. The health of the carer is often at risk due to long hours of caring and the nature of the work involved.
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Smith, Hayley-Jane. "The personal experience of carers of individuals with Motor Neurone Disease (MND) and their experiences of services." Thesis, University of Birmingham, 2009. http://etheses.bham.ac.uk//id/eprint/1221/.
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This thesis consists of research and clinical components and is submitted as partial fulfilment of a doctorate degree in Clinical Psychology. Volume 1, the research component, comprises of a literature review, an empirical paper and a public domain paper. The systematic literature review looks at evidence linking attachment and caregiving in adult couples. The empirical paper explores the experiences of individuals with a partners diagnosed with Motor Neurone Disease (MND). Lastly, a public domain provides a summary of the empirical paper. Volume II, the clinical component, contains clinical practice reports conducted within placements from adult, child, learning disability older adult specialities. The first report contains a behavioural and systemic formulation of a 3 year-old who was referred as her mother was having difficulties managing her behaviour. The second report describes an evaluation of the Experiences of practitioners interpreting and delivering Triple P (Positive Parenting Programme) groups in South Asian Community languages. The third report presents a single case experimental design concerning a behavioural approach to challenging behaviour displayed by a 7-year old boy with learning disabilities and autism. The fourth report is a case study of a Cognitive Behavioural approach used with a man diagnosed with Persistent Paranoid Delusional Disorder. Finally, the fifth report is an abstract of an oral case presentation of a small-scale service related project around a multiple family therapy group for adolescents with anorexia nervosa.
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Pancani, Silvia. "Assessing residual neck mobility when wearing a cervical orthosis : an application in patients with motor neurone disease." Thesis, University of Sheffield, 2016. http://etheses.whiterose.ac.uk/16179/.
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Severe weakness of the neck extensor muscles has been observed in neuromuscular pathologies, such as motor neurone disease (MND). This condition reduces the ability to perform daily activities and communicate, leading to the adoption of a cervical orthosis. However, commercially available devices are designed to immobilize the neck, which makes them uncomfortable and strenuous to wear for a long time. The lack of a device specifically designed for those patients led to the development of the Sheffield Support Snood (SSS) which enables to adjust the support given to the head, according to the task performed and to the disease progression. The following step toward the SSS commercialisation and adoption was an objective evaluation of its performance and the assessment with the end users, which was the aim of this thesis. To this purpose, an experimental protocol designed to quantitatively assess neck mobility when wearing cervical orthoses, has been developed. This protocol and the associated signal processing techniques proved to be suitable for the assessment of neck mobility through the measurement of head movements, both in laboratory and clinical settings. After having quantitatively assessed head movement limitation in MND patients, filling an existing gap in the current literature, the effects of the SSS were tested. Compared to controls, patients presented an overall impaired ability to perform head movements in terms of reduced velocity (mean values between 27% and 41% lower in movements performed reaching the maximum range of motion and between 34% and 48% lower in movements performed reaching the maximum angular velocity), reduced smoothness (mean values between 21% and 44% lower in movements performed reaching the maximum range of motion) and increased presence of coupled movements (mean values between 37% and 58% higher in movements performed reaching the maximum range of motion and between 44% and 53% in movements performed reaching the maximum angular velocity). The SSS was effective in facilitating the head movements in MND patients. Among those 9 individuals that were fitted with anterior or anterior plus lateral supports 5 of them had a reduced presence on coupled movements in at least one of the movements performed. However, a proper fitting of the orthosis appeared crucial and in the future it should be based on a quantitative approach similar to the one developed in this thesis. This study paved the way for improvements in the SSS design and for future quantitative assessment of the characteristics of motor control and movement strategies in MND patients and of how these change when using a device aiming at compensating for functional impairments.
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Daude, Amina. "A review of cases of motor neurone disease seen at Groote Schuur Hospital from 2005 to 2010." Master's thesis, University of Cape Town, 2014. http://hdl.handle.net/11427/12643.
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Includes bibliographical references.Motor neurone disease (MND) is a rare progressive neurodegenerative disorder in which selective degeneration of the motor neurones of the brain and spinal cord occurs. Progressive weakness of limb, bulbar and respiratory muscles eventually results in death. Most descriptive and epidemiological studies of MND have been performed in the industrialized countries of Europe and North America. We know very little about the incidence or prevalence of MND in Africa in general and South Africa in particular. However, anecdotal evidence based on observations by clinicians in the neurology and geriatric medical clinics at Groote Schuur Hospital suggest that the condition is not uncommonly seen, even in younger patients. Furthermore, many cases appear to originate from the West Coast area of the Western Cape. The proposed study aimed at describing the demographic and clinical characteristics of MND seen at Groote Schuur Hospital between 2005 and 2010. I hypothesized that disease duration, measured from age of onset of first symptoms to death, would be shorter in patients with bulbar-onset disease, in younger-onset disease, and in patients with higher CSF protein and blood creatine kinase levels at baseline. Furthermore, age of onset of the disease would be younger in familial compared with sporadic MND. I also hypothesized that smoking and certain occupational exposures might be risk factors for MND, that there would be a male preponderance of the disease, and that a disproportionate number of cases would come from the West Coast region. This was a retrospective study. I reviewed the clinical notes of cases of motor neurone disease and collected data relevant to the aims and hypotheses described above. I applied the El Escorial diagnostic criteria for MND to check the validity of the diagnoses. Mortality data were obtained through the Burden of Diseases Research Unit at the South African Medical Research Council. Forty eight patients were identified who met El Escorial criteria for the diagnosis of probable or definite MND. The median age of onset of the disease was 54 (IQR 47-63) and the mean duration of the disease from earliest symptoms to death was 2 years (IQR 1-3). These did not differ significantly between bulbar and limb-onset disease sub-types. There was a male preponderance of the disease (60%) and the majority of patients (60%) were smokers. African patients tended to have a younger age of onset. Occupations involving potential exposure to chemicals were disproportionately represented in the MND patients compared with the general population of the Western Cape. People from the West Coast region were not disproportionately represented in the patient population. Baseline CSF protein and serum creatine kinase levels were not associated with disease duration. The characteristics of MND cases seen at Groote Schuur Hospital between 2005 and 2010 are similar to those described in the world literature. Smoking and chemical exposure may be risk factors for the disease. There was no evidence of clustering of cases. This study will serve as the basis for future larger prospective studies on MND prevalence and aetiology in South Africa.
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James, Owain Thomas. "Electrophysiological characterization of human stem cell-derived neurones and glia in models of neurodevelopmental and neurodegenerative diseases." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/28975.
Full textAbstract:
Human pluripotent stem cell (hPSC)-derived neuronal and glial material presents a relatively new opportunity to model human neurophysiology in both health, and disease. Validation of regionally-defined hPSC-derived neurones and glia cultures thus represents the founding blocks of technology that aims to complement existing models. Principally, the relevance of in vitro hPSC-derived material is determined by how representative it is of native material, yet at present the physiology of these cells remains underexplored. Here, electrophysiology and pharmacology are used to functionally assess hPSC-derived excitatory cortical neurones (hECNs), motorneurones (MNs) and oligodendrocyte-lineage cells in the context of regional-specific properties and maturation. These properties are then examined in material derived from hPSCs generated from patients with neurological disorders. This thesis examines of the properties of GABAARs and strychnine-sensitive glycine receptors (GlyRs) in hECNs by assessing their subunit composition, and compares these with studies which have made comparable investigations of rodent tissue where maturation is associated with a shift in GABAA and GlyR compositions. Using pharmacology and RNAseq analysis, GABAAR and GlyRs in hECNs were found to possess receptor populations typical of those reported in the immature cortex. hECNs generated from patients harbouring a mutation to the Disrupted-in-schizophrenia-gene 1 (DISC1), a candidate schizophrenia gene, were then examined. Imbalances in the excitation/inhibition balance are suspected in schizophrenia and, in this regard, the intrinsic excitability properties alongside expression and composition of major neurotransmitter receptors and intracellular chloride concentration were assessed. No obvious differences in excitability or functional expression of AMPARs, GABAARs or NMDARs were observed between case and control derived neurones. Receptor composition and intracellular chloride concentrations were found to be predominantly immature-like, however, AMPAR composition and intracellular chloride concentration were found to be like that of adult cortical neurones. These data are discussed in the context of modelling DISC1-associated pathologies. Thirdly, MNs from hPSCs generated from ALS patients harbouring mutations on the C9ORF72 gene were examined. The hypothesis that increased glutamate-mediated excitoxicity could, in part, be explained by increased expression of Ca2+- permeable AMPARs was examined. The estimated mean single-channel conductance of AMPARs was found to be high in MNs derived from ALS patients, reminiscent of Ca2+-permeable AMPARs and was reversed by gene-editing of the C9ORF72 mutation. Finally, oligodendrocytes generated from ALS patients harbouring TARDBP mutations were examined. Distinctive electrophysiological shifts in oligodendrocytes-lineage cell development are reported. A similar AMPAR phenotype of elevated Ca2+-permeable AMPAR expression was observed in oligodendrocytes derived from two patient hPSC lines and was rescued in an isogenic, gene-edited line, raising the intriguing possibility of convergence in pathophysiologies in the nature of the overlap between cell-type, AMPAR pathology and excitotoxicity in ALS disease progression mechanisms.
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Clabburn, Oliver. "Investigating the use of digital legacies with people affected by Motor Neurone Disease (MND) : an Interpretative Phenomenological Analysis." Thesis, Edge Hill University, 2018. http://repository.edgehill.ac.uk/10255/.
Full textAbstract:
Background: A video-based 'digital legacy' is a selection of videos which document a person's life, memories, achievements, or special family events. The videos are copied to a digital source to be specifically given to a child or young person to use in the future. A video-based digital legacy may either be purposefully recorded by the person living with MND (plwMND), or, compiled later by bereaved family members. To date, there is little published research about how children and young people are affected when a family member has MND and subsequently dies. As such, there is a dearth of literature on how to best support these young people. Objective: This research is investigating the views, perceptions and experiences of digital legacies with people affected by MND. Methods: The study is underpinned by Interpretative Phenomenological Analysis (IPA) meaning a small homogeneous sample was required using purposive methods of recruitment. Interviews were conducted and audio recorded with four plwMND regarding their experiences of creating a purposeful digital legacy for a child or young person in their family. Interviews were also conducted with three bereaved young people regarding their experiences of using a video legacy of a parent who had died from MND. Also, a sample of twenty healthcare professionals, specialists and experts were interviewed from across the United Kingdom regarding their perceptions on the use of digital legacies with plwMND, and, young people who are bereaved. Ethics: Ethical approvals were obtained from a Faculty of Research Ethics Committee at Edge Hill University (FREC), the Health Research Authority (HRA), and the National Research Service for Scotland. Discussion: 'The Model of Reciprocal Bonds Formation' and coining of the term 'autobiographical chapter' has been developed from this study. Creating a digital legacy provides a number of mutual challenges and benefits for both plwMND, and bereaved young people. Recommendations are provided regarding i) optimal 'windows of opportunity' in which the digital legacy is recorded/used; ii) actionable solutions for current policy/practice; iii) future directions for research.
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Mutihac, Ruxandra. "In vitro transgenic models to elucidate the molecular mechanisms of TDP-43 pathology in amyotrophic lateral sclerosis." Thesis, University of Oxford, 2013. http://ora.ox.ac.uk/objects/uuid:1d8aa081-342f-4994-ac74-12c6ebdc30c6.
Full textAbstract:
Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disorder characterized by loss of upper and lower motor neurons. TDP-43 was identified as a major protein component of the characteristic neuronal inclusions and it has been detected in 90% of ALS cases. Furthermore, pathogenic mutations in the gene encoding TDP-43, TARDBP, were found in both sporadic and familial ALS cases. The aim of this study is to investigate the molecular mechanisms of cellular dysfunction and ultimately death caused by TDP-43 mutations in human cells using established cell lines and human motor neurons derived from induced pluripotent stem cells (iPSCs). We generated a novel in vitro cellular model using a fluorescently tagged human genomic TARDBP locus carrying three ALS-specific mutations, A382T, M337V or Y374X. In site specific bacterial artificial chromosome (BAC) human stable cell lines, TDP M337V mislocalized to the cytoplasm more frequently than wild-type TDP-43 (TDP Ypet) and TDP-A382T, an effect potentiated by oxidative stress. Cytoplasmic mislocalization was significantly higher in TDP M337V cells compared to TDP-Ypet and correlated with cell death. Cells expressing the mislocalized TDP M337V mutant spontaneously developed cytoplasmic punctae, while for TDP-A382T punctae were only revealed after endoplasmic reticulum (ER) stress induced by the calcium-modifying drug thapsigargin (TG). Lowering Ca2+ concentration in the ER of TDP-Ypet cells partially recapitulated the effect of pathogenic mutations by increasing TDP-43 cytoplasmic mislocalization, suggesting Ca2+ dysregulation as a potential mediator of pathology. Ca2+ signaling from the ER was impaired in cells carrying TDP-43 mutations, with a 50% reduction in the levels of luminal ER Ca2+ stores content and delayed Ca2+ release induced by carbachol compared to TDP-Ypet cells. The deficits in Ca2+ release correlated with upregulation of Bcl-2 and siRNA-mediated knockdown of Bcl-2 restored amplitude of Ca2+ oscillations in TDP-M337V cells. These results suggest that TDP-43 pathogenic mutations elicit cytoplasmic mislocalization of TDP-43 through Bcl-2 regulation of ER Ca2+ signalling. Preliminary work in iPSC-derived motor neurons transduced with genomic DNA expression TDP-43 vectors using Herpes Simplex Virus type 1 (HSV-1) amplicons showed cytoplasmic redistribution of TDP-43 under high oxidative stress, without significant differences between mutations and wild-type. TDP-43 mutations delivered by HSV-1 amplicons also did not affect survival of iPSC-derived motor neurons. In ALS patient-derived motor neurons carrying C9orf72 expansions, TDP-43 pathology was not detected. However, preliminary data indicate that C9orf72 MNs present ER Ca2+ dysregulation with significantly high intracellular Ca2+ concentration, which correlates with high protein levels of ER stress markers and low levels of Bcl 2. This work highlights a potentially pathogenic role for TDP-43 mutations in the dysregulation of Ca2+ homeostasis and explores the use of iPS technology to investigate the effects of ALS-associated mutations in healthy and patient-derived motor neurons.
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Virgo, Lisa. "A study of neurotransmitter function in motor neurone disease : using the techniques of in situ hybridisation and receptor autoradiography." Thesis, Imperial College London, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.336581.
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