Academic literature on the topic 'Multiple Sclerosis (MS) sufferers'

Background: Pain is frequently reported by people with multiple sclerosis (MS). It has been associated with decreased quality of life, psychiatric morbidity, interference with day to day activities, and frequent healthcare attendance. It has been reported by people with multiple sclerosis to be one of their most important symptoms, and available treatments are limited in their effectiveness. Despite this, our understanding of the epidemiology and mechanisms of pain in people with MS are limited. Our understanding of the interactions of central nervous system mechanisms and pain states overall is growing. However, the application of this knowledge to MS is incomplete. Previous studies have shown that the descending pain modulatory system (DPMS) is an endogenous network of cortical and subcortical brain structures which act to limit, or accentuate, an individual’s perception of pain, via descending brainstem pathways. Associated clinical measures include depression, anxiety, and cognitive flexibility. Our understanding of the function or dysfunction of this system in MS is limited. We do not know if the MS disease process may adversely affect the structure or function of the DPMS. Hypothesis: In people with neuropathic limb pain in relapsing remitting MS (RRMS), compared to people with RRMS who do not have pain, there will be disruption of the endogenous descending pain modulatory system. This will manifest as impaired descending inhibition of pain. Aims and Methods Establishing the background using systematic reviews: The first aim of this thesis was to establish the prevalence, natural history and associations of pain (and pain syndromes) occurring in people with MS. The second aim was to explore existing knowledge of how the MS disease process may contribute to pain states, using a systematic review of neuroimaging studies. Prospective clinical study: A case-control study of 47 people with RRMS was then carried out. 31 of these had neuropathic pain in the limbs, and 16 did not have pain. Using targeted assessments, function of the descending pain modulatory system was assessed in the following ways: First: Detailed clinical, behavioural and neuropsychological assessment, focussing on cognitive, behavioural and affective features known to be closely related to the DPMS. Second: MRI imaging of brain structure, focussing on the volume and location of MS lesions, as well as the volume of key grey-matter structures involved in the DPMS. Third: Resting state functional MRI imaging of the brain, focussing on functional connectivity between the rostral anterior cingulate cortex and two other key DPMS structures (dorsolateral prefrontal cortex, and periaqueductal gray). Results: Systematic reviews: Meta-analysis of existing prospective studies confirmed that pain is very common in MS, affecting about 63% of people with MS on average (95%CI between 55 and 70%). Many different types of pain contribute to this overall estimate. No significant associations with disease course or stage emerged. Several neuroimaging studies have assessed people with MS-associated pain using MRI. These studies were often small, and with associated methodological issues. It is likely that location of MS lesions is implicated in aetiology of pain syndromes in some cases, though our overall knowledge is limited. Prospective study: In a prospective study, people with and without pain were matched for age and gender. Furthermore, groups were balanced for a range of other variables. The pain group more frequently received gabapentinoid medications. The presence of pain was significantly associated with increased scores for depression, fatigue and catastrophising, as well as with specific impairments at neuropsychological assessment, including cognitive flexibility. Many of these impairments are directly relevant to existing models of the DPMS. Overall volume of MS lesions was not different in people with pain, though lesions were more likely to occur in the brainstem. Some alterations of grey-matter volumes in people with pain which mirrored studies of pain disorders outside MS were found, but these did not involve structures key to the DPMS. Affected structures included trigeminothalamic nucleus (relative volume increase in pain group), posterior cingulate cortex and parahippocampal gyrus (volume decrease in pain group). Functional connectivity of the rostral anterior cingulate cortex to the periaqueductal grey matter, a key structure in the descending modulation of pain, was stronger in the group without pain. Conversely, functional connectivity to the dorsolateral prefrontal cortex, repeatedly implicated in the DPMS and thought to be involved in cognitive evaluation and flexibility, was stronger in the pain group. MS lesion volume appeared to account for some of this difference in a multivariate analysis. Limitations: Key limitations of this work include cross-sectional design, small sample size, and number of statistical comparisons carried out. Conclusions: Systematic reviews examined the prevalence, natural history and associations of pain in MS, as well as examining existing neuroimaging studies which investigated how the MS disease process could contribute to pain states. A prospective study found evidence of both emotional/affective and cognitive dysfunctions relevant to the hypothesis of dysfunction in the DPMS. Higher likelihood of MS lesions in the brainstem could be relevant to DPMS function. Separately, there were structural grey-matter volume alterations reflecting those found in many pain studies outside MS. Importantly, however, these did not affect key DPMS structures. Resting state functional MRI however demonstrated altered connectivity of core DPMS structures, which may be partly mediated by MS lesion volume. Functional connectivity findings could be consistent with the hypothesis of impaired descending pain inhibition, in people with relapsing remitting MS affected by neuropathic limb pain.

Many individuals with multiple sclerosis (MS) are classified as having relapsing-remitting MS (RRMS), a form of the illness that requires constant symptom management for suffers to achieve optimum outcomes. There are only a few community-based educational programs that exist to help RRMS sufferers cope with their illness; the effectiveness of those that have been fielded has not yet been adequately assessed. The research questions of this study were to determine if an online training development module would increase the coping skills of those affected by RRMS and if the online educational module would be more effective at improving the coping skills of mild RRMS sufferers versus severe RRMS sufferers. The theoretical foundation was based on a stress-coping model commonly utilized for chronic disease management. The research design employed 2 groups, nonrandom selection, and use of a pretest/posttest applied to the target population from the Georgia MS Chapter. SPSS was used to perform statistical analysis as well as to perform the Mann-Whitney test on study data/results. According to findings from this quantitative study, the application of the online education development module to RRMS sufferers does provide a mechanism of significantly improving their coping skills. This positive social change improvement of coping strategies helps the patients as well as family, friends, and coworkers, and this module would serve as the complement to augment coping strategy improvement efforts for RRMS suffers. This study supports improvement of RRMS sufferer coping skills in the short term, and a future area of research focus would address the long-term improvements in coping skills for RRMS sufferers from the application of this online module.

This qualitative study explored the psychosocial experiences of children and adolescents with early-onset multiple sclerosis. In particular, an emphasis was placed on examing peer relationships and social behaviours in relation to these experiences. MS is a chronic neurological disease primarily affecting young adults. However, a proportion of MS patients have onset during childhood and adolescence. Very little is know about the psychosocial impact of MS on these children and adolescents. In particular, youth with MS may be at risk for negative peer experiences due to their chronic illness. Previous research suggested that negative peer experiences increase the risk of poor psychosocial development. In addition, research suggested that the social behaviours of these youth also impact the nature of their experiences with peers. Ultimately, this research aimed to provide insight into the psychoscial experiences of youth with MS and the role of their peer relationships. Six linked parent-youth pairs, from the MS Clinic in Calgary, AB, participated in semi-structured interviews to identify the issues that are pertinent to the participants' own experiences. Constant comparison analysis was then used to summarize the rante of psychosocial experiences in the adolescent participants. Data analysis was derived from grounded theory, which provided a framework for examining and categorizing interview data into themes. The categories were then constructed logically and systematically into a theoretical model which represented the data. Through this innovative grounded theory, a theoretical paradigm for understanding the psychosocial experiences of adolescents with MS was developed. The theory was comprised of two core categories: "the grief experience" and "dynamic relationships', each with several sub-categories. There were two primary conclusions drawn from the theory. The first reflected the significance of grief in understanding psychosocial experiences in adolescents with MS. The second identified that peer relationships play a variety of roles in this grief process. The second identified that peer relationships play a variety of roles in this grief process. The results of this study have many implications for the role of counsellors in the treatments of adolescents with MS. This model can act as a foundation for guiding therapeutic treatment of adolescents with MS. This model can act as a foundation for guiding therapeutic treatment and promoting future research in the area of psychosocial development in children and adolescents with early-onset MS.<br>xiv, 181 leaves ; 28 cm.

The glycosylation features of CSF oligoclonal IgG, and possible changes in N-glycans of CSF IgG in multiple sclerosis (MS) were studied. After isoelectric focusing (IEF) of CSF, bands were detected using biotinylated lectins and avidin-horseradish peroxidase. Concanavalin A (Con A) binding showed that mannose exists throughout the pH range of oligoclonal IgG. Sambucus nigra antigen (SNA) bound acidic and neutral oligoclonal IgG only, suggesting that alkaline oligoclonal IgG is deficient in sialic acid. Deglycosylation of CSF IgG using peptide-N-glycosidase F suggested that the range of isoelectric points of oligoclonal IgG bands is not due to carbohydrate differences alone. Lectin immunoassays, whereby protein A purified IgG was captured by anti-IgG coated tubes and probed using a range of biotinylated lectins, were used to compare 13 CSF samples from MS patients with 14 control samples. With Con A binding, a significantly higher mean and larger variance was found for the MS group (t-test: P < 0.05). Con A binding correlated with CSF [IgG]/[total protein]% (r=0.390; P=0.0443). Using HPLC to separate oligosaccharides released from IgG by hydrazinolysis and labelled with 2-aminobenzamide, glycans were determined in 7 CSF samples with oligoclonal IgG, and 6 CSF samples without. The ratio of the peak for biantennary fucosylated agalactosyl glycans to total monogalactosylated glycan peaks was lower for the oligoclonal IgG samples (t-test: P=0.0141). The overall results suggested that glycosylation changes occur in CSF IgG in MS, and that oligoclonal IgG contains less sialic acid but more galactose than polyclonal IgG.

The glutathione S-transferase (GST) supergene family encodes isoenzymes that appear to be critical in protection against oxidative stress. Certain GST loci are polymorphic, demonstrating alleles that are null (GSTMI/GSTT1), encode low activity variants (GSTPI), or are associated with variable inducibility (GSTM3). Interleukin-1 (IL- 1) alpha and beta are cytokines involved in recruitment of inflammatory cells, the process of inflammation, and blood-brain barrier breakdown and nerve regeneration. Polymorphisms of both GST and of a complementary interleukin-1 receptor antagonist have been associated with severity and susceptibility to other inflammatory conditions. This thesis examines the influence of the GST and IL-1 genes on both the susceptibility to Multiple Sclerosis (MS), and the course of disease progression. The population examined consisted of four hundred patients with clinically definite MS. Disease severity was measured using the Kurtzke Expanded Disability Status Scale (EDSS), a robust established ranking scale. PCR-based genotyping was performed using DNA extracted from lymphocytes. Significant associations between genotypes and clinical outcome were corrected for known demographic factors influencing prognosis, these being; gender, onset age, and disease duration using the statistical method of logistic regression. Significant associations, withstanding multiple testing corrections, with certain IL-I genotypes and disease severity were found. There was also a significant trend with the GST isoenzymeM 3 that is expressedin nervous tissue. No robust findings suggest that these genes influence susceptibility to MS, but the results suggest that long-term prognosis is genetically influenced by the modulation of inflammatory cytokines and also by the ability to remove the toxic products of oxidative stress.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by inflammation and demyelination. In addition to these hallmark features, MS also presents with axonal pathology, which is likely responsible for the signs and symptoms of the disease. Although prominent in MS, axonal pathology is frequently considered a consequence of demyelination and not a primary event. This conclusion is consistent with demyelination inducing the loss of specific axonal domains, known as the nodes of Ranvier that are responsible for the propagation of action potentials along the axon. In contrast, we propose that axonal pathology associated with MS is a primary pathological event, independent of demyelination, and not a product of it. In support of our hypothesis, we have analyzed a different axonal domain known as the axon initial segment. Whereas a single axon has numerous nodes of Ranvier uniformly distributed along the axon, each axon contains only a single axon initial segment that is positioned immediately distal to the neuronal cell body. The axon initial segment is responsible for action potential generation and modulation, and hence is essential for normal neuronal function. Background studies conducted by our lab, employing a murine model of demyelination/remyelination, revealed no correlation between axon initial segment stability and myelin integrity. Here we investigate the fate of the axon initial segment in human multiple sclerosis. While not statistically significant, we provide data demonstrating an apparent 40% reduction in AIS numbers in MS. We further provide qualitative evidence that AIS integrity in MS is not dependent on myelination suggestive that axonal pathology may be a primary event in MS, independent of demyelination. Our current findings are intriguing, but unfortunately this study is underpowered, and more samples will be required to determine whether this apparent reduction is statistically significant.