Hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for multiple sclerosis (MS) with now more than 600 documented cases in the medical literature. Long-term remission can be achieved with this therapy, but when is it justified to claim that a patient is cured from MS? In attempt to answer this question, the outcome of the Swedish patients is described, mechanisms behind the therapeutic effect are discussed and new tools for demonstration of absence of disease have been developed. In Swedish patients treated with HSCT for aggressive MS, disease free survival was 68 % at five years, and no patient progressed after three years of stable disease. Presence of gadolinium enhancing lesions prior to HSCT was associated with a favorable outcome (disease free survival 79 % vs 46 %, p=0.028). There was no mortality and no patient required intensive care. The immune system of twelve of these patients was investigated further. In most respects HSCT-treated patients were similar to healthy controls, demonstrating normalization. In the presence of a potential antigen, leukocytes from HSCT-treated patients ceased producing pro-inflammatory IL-17 and increased production of the inhibitory cytokine TGF-β1 suggesting restoration of tolerance. Cytokine levels and biomarkers of tissue damage were investigated in cerebrospinal fluid from a cohort of MS patients. The levels were related to clinical and imaging findings. A cytokine signature of patients with relapsing-remitting MS could be identified, characterized by increased levels of CCL22, CXCL10, sCD40L, CXCL1 and CCL5 as well as down-regulation of CCL2. Further, we could demonstrate that active inflammation in relapsing-remitting MS is a tissue damaging process, with increased levels of myelin basic protein and neurofilament light. Importantly, relapsing-remitting MS patients in remission displayed no tissue damage. In secondary progressive MS, moderate tissue damage was present without signs of active inflammation. From a clinical vantage point, it seems that we confidently can claim cure of relapsing-remitting MS patients after five years absence of disease activity. The new tools for evaluation of disease can strengthen this assertion and may enable earlier prediction of outcome.

Using an institutional ethnographic approach, this research explores the everyday experiences of women living with Multiple Sclerosis and the work they do to understand and manage their illness. Starting with the women's own accounts of their everyday experiences with MS, this research analyzes and explicates the social relations that are involved in their everyday taken-for-granted lifework. An exploration of the ruling institutions coordinating with the everyday work of these women provides insight to some of the struggles and problems people with MS encounter. This project explicates and problematizes the disjuncture between the actual lived experience of having MS and the biomedical institution's authority over the illness. / Graduate

SAMMANFATTNING Bakgrund: Sexuell hälsa kan ses som en mänsklig rättighet, trots det kommer sexualitet och sexuell hälsa ofta i skymundan i den allmänna sjukvården. Sjuksköterskan har en viktig roll i att uppmärksamma och identifiera sexuell hälsa. Multipel skleros (MS) är en kronisk nervsjukdom som påverkar det centrala nervsystemet och personer med MS drabbas ofta av någon form av sexuell dysfunktion. Syfte: Syftet var att belysa hur personer med MS upplever att deras sexualitet påverkas av sjukdomen. Metod: Studien genomfördes som en litteraturöversikt. En textanalys genomfördes med induktiv ansats på tio kvalitativa vetenskapliga artiklar. Resultat: Resultatet visade att personer med MS upplevde att sjukdomen förändrade deras sexualitet genom att olika dimensioner av deras liv blev påverkade. Kroppens förändringar orsakade av sjukdomen påverkade identiteten, relationer och kommunikationen. Det framkom en skillnad mellan män och kvinnors upplevelse av hur kommunikationen fungerade. För många personer blev sexualiteten negativt påverkad på olika sätt medan några upplevde förbättrad sexualitet efter diagnosen. Slutsats: Sexualiteten var något som växelverkade med rollförändringar inom relationen som följde av sjukdomen. De var nära sammankopplade genom att förändringar i den ena sfären påverkade den andra och vice versa. Kommunikation blev en strategi för att hantera förändringar och kärleksfulla och stödjande relationer blev en resurs för personer med MS. Klinisk betydelse: Resultatet visar att sexualitet är viktigt för människors välbefinnande även om man är drabbad av långvarig sjukdom. Kunskapen kan användas i utveckling av sjuksköterskors omvårdnadsarbete för att synliggöra värdet av sexualitet för patienter med MS. / ABSTRACT Background: Sexual health can be seen as a human right. Despite that sexuality and sexual well-being are often neglected within the healthcare system, thus nurses have an important role to identify and enlighten the sexual health among patients. Multiple Sclerosis (MS) is a chronic disease that affects the central nervous system. Patients with MS often suffer from sexual dysfunctions in various forms. Objective: The purpose of this study was to illuminate how patients suffering from MS experience their sexuality. Method: The study was made as a literature review. Ten qualitative and scientific articles were included and analysed with an inductive approach. Result: The result of the study shows that patients suffering from MS experience that their sexuality has been affected by the disease since MS changes several aspects of their everyday lives. The physical changes caused by the disease affected the patient’s identity, relationships and communication. The result, however, also shows differences in the experience regarding communication between men and women and that not all patients found that their sexuality had been negatively affected by the disease. Conclusion: The sexuality was something that interacted with role changes related to the illness. Role changes in one life sphere affected the other and vice versa. Communication became a strategy to manage change, while loving and supportive relationships became a resource. Clinical implications: The result of the study shows that sexuality is an important part of people’s lives despite long-term illness. This knowledge can be used to develop nursing in order to enlighten the importance of sexuality among patients with MS.

No description available.

An acute demyelinating syndrome (ADS) in a child may be a monophasic illness or may represent the incident attack of multiple sclerosis (MS) – an inflammatory demyelinating neurodegenerative disorder affecting the brain, spinal cord and optic nerves. The central objective of this dissertation was to identify MRI parameters present at ADS that predict MS diagnosis. A scoring tool was first created containing 14 parameters identified from the literature and demonstrating substantial inter-rater agreement (Cohen’s kappa values ≥0.6). Children aged <16 years were enrolled at incident ADS and are currently followed for five years at 23 Canadian centers. Standardized MRI scans were acquired at onset and serially. MS was defined based on the occurrence of a second demyelinating attack or MRI evidence of new lesions in accordance with McDonald criteria for dissemination in time. Multivariable Cox proportional hazards regression models were used to identify MRI parameters that predicted MS diagnosis. Over 1100 MRI scans in 284 children with ADS were evaluated. To date, 57(20%) children have been diagnosed with MS. For those that developed MS, the median (IQR) time from incident attack to diagnosis was 6.2 (4.7-11.1) months. The presence of ≥1 T1-hypointense lesion (HR 20.6, 95% CI 5.5-78.0) and ≥1 T2 periventricular lesion (3.3, 1.3-8.8) were associated with an increased likelihood for MS diagnosis (sensitivity 84%, specificity 93%, PPV 76%, NPV 96%). The predictive parameters were validated in an independent Dutch cohort of 45 children with ADS (n=15, 33% MS): sensitivity 93%, specificity 87%, PPV 78%, NPV 96%. Finally, it was determined that the 2010 McDonald criteria are applicable for diagnosis of pediatric-onset MS diagnosis in older children with non-ADEM presentations. The work embodied herein emphasizes the value of MRI in predicting MS diagnosis in children with incident ADS. Early identification of children with MS is important for planning clinical care and will be valuable in future pediatric MS treatment trials.

Brain atrophy has been used as a marker for disease progression in Multiple Sclerosis (MS). SIENA, an automated tool for measuring brain volume change, was tested to see whether MRI slice thickness and gap presence affect longitudinal atrophy measures. Isotropic global scan-rescan images were used to simulate 3 mm and 5 mm axial slice thicknesses with 1 and 2mm gaps, respectively. SIENA remained accurate and precise with increasing slice thickness and gap presence. Furthermore, symmetric pre-registration was crucial for scans with larger slice-thickness and gaps. / SIENA was used to observe atrophy in children who have experienced a Clinically Isolated Syndrome (CIS) of the type leading to MS (CIS-MS). Brain atrophy was present within the first three months after a CIS event, and then subsided over the rest of the year. If the first acute episode was excluded, there was no significant difference in atrophy rates between the CIS-MS group and the CIS group, and no significant difference between those with T2-weighted brain lesions versus those who had none.

Multiple Sclerosis (MS) is an autoimmune disease of central nervous system. It may result in a variety of symptoms from blurred vision to severe muscle weakness and degradation, depending on the affected regions in brain. To better understand this disease and to quantify its evolution, magnetic resonance imaging (MRI) is increasingly used nowadays. Manual delineation of MS lesions in MR images by human expert is time-consuming, subjective, and prone to inter-expert variability. Therefore, automatic segmentation is needed as an alternative to manual segmentation. However, the progression of the MS lesions shows considerable variability and MS lesions present temporal changes in shape, location, and area between patients and even for the same patient, which renders the automatic segmentation of MS lesions a challenging problem. In this dissertation, a set of segmentation pipelines are proposed for automatic segmentation of multiple sclerosis (MS) lesions from brain magnetic resonance imaging (MRI) data. These techniques use a trained support vector machine (SVM) to discriminate between the blocks in regions of MS lesions and the blocks in non-MS lesion regions mainly based on the textural features with aid of the other features. The main contribution of this set of frameworks is the use of textural features to detect MS lesions in a fully automated approach that does not rely on manually delineating the MS lesions. In addition, the technique introduces the concept of the multi-sectional views segmentation to produce verified segmentation. The multi-sectional views pipeline is customized to provide better segmentation performance and to benefit from the properties and the nature of MS lesion in MRI. These customization and enhancement leads to development of the customized MV-T-SVM. The MRI datasets that were used in the evaluation of the proposed pipelines are simulated MRI datasets (3 subjects) generated using the McGill University BrainWeb MRI Simulator, real datasets (51 subjects) publicly available at the workshop of MS Lesion Segmentation Challenge 2008 and real MRI datasets (10 subjects) for MS subjects acquired at the University of Miami. The obtained results indicate that the proposed method would be viable for use in clinical practice for the detection of MS lesions in MRI.

This study described the play experiences of daughters who were caregivers to their mothers with multiple sclerosis (MS). The experiences of four Canadian-Caucasian women aged 19-26 were captured using phenomenological methods of individual and focus group interviews, field notes, and artefacts. Three themes with supporting sub-themes emerged: (a) being a good daughter, (b) blurred relationship boundaries, and (c) encumbered play. Caregiving for their mothers was part of being a good daughter. Excessive caring duties changed their roles from being daughters to caregivers and contributed to feelings of maturity over peers. Their mother-daughter relationship boundaries were blurred and the participants wished to spend more time as daughters. Play, although sometimes limited, was highly valued and provided an escape from caregiving. Using family systems theory to interpret the findings, it was concluded that support for families living with MS would release children from caregiving duties so rounded childhood play could be experienced.

The project described in this thesis began with a broad analysis of the changes to amino acid and biogenic amine concentrations in the central nervous system (CNS) during experimental autoimmune encephalomyelitis (EAE) in mice, an animal model of Multiple Sclerosis (MS). That study identified deficits in specific neurotransmitters during EAE that I targeted pharmacologically using the antidepressant drug phenelzine. Phenelzine administration substantially influenced the concentrations of amino acids and biogenic amines in EAE mice in a manner likely to be therapeutic. In the final experiment, I treated EAE mice chronically with phenelzine; This treatment was associated with significant improvements in motor abilities compared to vehicle treated animals. In an open field, improvements were also observed in behavioural indices of depression, physical sickness and anxiety. The results of this thesis may offer new insights into the pathogenesis of EAE and MS and indicate the disease-modifying potential of phenelzine treatment in MS.

This thesis was concerned with determining the scope, nature and impact of pain on quality of life (QOL) among a community-based sample of people with multiple sclerosis (MS). An analysis of the research literature on pain in MS reveals that pain is a significant problem which has historically been underinvestigated and is currently poorly understood. The vast majority of the published literature consists of prevalence studies, descriptive research and clinical reports. Where available, empirical data are often limited by methodological and analytical problems such that substantive conclusions about the scope and nature of MS-related pain remain unclear. Among the most fundamental issues is the extent to which pain is problematic in a population which is already impaired by other physical disabilities. Little is known about how pain contributes to MS-related disability, distress and QOL. Moreover, research examining the psychosocial aspects of MS-related pain is noticeably absent. It is clear that there are substantial gaps in the literature and that many basic questions about the scope, nature and impact of pain problems among individuals with MS remain unanswered. Thus the primary aim of this study was to begin to fill some of these gaps by systematically investigating the following research questions: (1) What is the prevalence and nature of pain experienced by people with MS? (2) What is the impact of pain on the QOL of people with MS, over and above the impact of disability itself? (3) To what extent do physical and psychosocial factors influence adjustment to chronic pain in people with MS? (4) What meaning is given to the pain experience by people with MS? The present study utilised a multimethod research design involving cross-sectional postal survey, structured in-person pain interviews and focus groups. Survey respondents were a 219-person sample recruited from the Queensland MS Society membership database via systematic random sampling. All participants completed a piloted questionnaire containing questions about their demographic and clinical characteristics, validated measures of QOL and MS-related disability, and a question on whether or not they had experienced clinically significant pain in the previous two weeks. Respondents who reported pain then completed face-to-face structured pain interviews assessing pain characteristics (viz. intensity, quality, location, extent and duration), pain-related beliefs and coping strategies, and pain management techniques used. Four focus groups were also conducted that included 32 people with MS living in the community. Study participants were a purposive sample drawn from four MS support groups located in the South-East Queensland region. Pain was found to be common with some 67.1% of the sample reporting pain during the two weeks preceding the study. Comprehensive pain assessment revealed that a substantial subset of these individuals experience chronic pain conditions characterised by moderate-to-severe pain intensity. Pain prevalence and intensity were found to be strongly correlated with QOL: physical health, psychological health, level of independence and global QOL were more likely to be impaired among people with MS when pain was present, and the extent of impairment was associated with the intensity of pain. Moreover, these relationships remained significant even after statistically controlling for multiple demographic and clinical covariates associated with self-reported QOL. Pain-related beliefs and coping strategies were also associated with and explained a significant proportion of the variance in adjustment to pain among people with MS, over and above that accomplished by demographic and MS-related variables and pain intensity. Finally, qualitative data analysis revealed four broad conceptualisations of the experience of chronic MS-related pain including: pain is pervasive, nobody understands, I'm fine, and always a factor in the equation. These findings suggest that for people with MS, pain is an important source of distress and disability over and above that caused by neurological impairments. These data also lead to the hypothesis that recognition and effective treatment of pain would improve the QOL of people with MS, irrespective of their level of neurologic disability. Although correlational, the findings provide support for a biopsychosocial model of pain and adjustment to pain in people with MS.