Multiple sclerosis (MS) is a prevalent and progressive autoimmune inflammatory disease affecting both white and gray matter and resulting in lesions and atrophy within the central nervous system (CNS) (Bermel & Bakshi, 2006; Confavreux & Vukusic, 2006; Cree, 2012; Friese, Schattling, & Fugger, 2014). Fine motor impairment, including manual motor speed and fine motor dexterity deficits, is common in MS patients (e.g., Benedict et al., 2011; Chipchase, Lincoln, & Radford, 2003). However, impairment does not progress uniformly across patients (Confavreux, Vukusic, Moreau, & Adeleine, 2000; Filippi & Rocca, 2011; Scalfari, Neuhaus, Daumer, DeLuca, & Muraro, 2013) and the association between disease burden and physical disability is moderate at best (Bermel & Bakshi, 2006; Filippi et al., 2013). Though the brain reserve hypothesis has helped to explain the clinico-pathologic dissociation between cognitive functioning and disease burden in MS patients (Sumowski et al., 2013; Sumowski et al., 2014a), there is no published literature on brain reserve and motor functioning in MS. Instead, only preliminary data have been presented on brain reserve and general physical disability (Sumowski et al., 2014b). As such, the purpose of this dissertation was to examine the protective effect of brain reserve, estimated via intracranial volume (ICV), on fine motor functioning in relapse-onset MS patients. A sample of 178 relapse-onset, right-handed MS patients underwent neuropsychological testing along with neurological examination, including magnetic resonance imaging (MRI). As part of the evaluation, patients were administered the Nine Hole Peg Test (NHPT; a measure of fine motor speed and dexterity) and the Finger Tapping Test (FTT; a measure of manual motor speed), which served as this study’s outcomes (i.e., dependent variables). Predictors (i.e., independent variables) included demographic variables (age, sex), disease variables (disease duration and disease phenotype, including relapsing-remitting MS (RRMS) or secondary-progressive MS (SPMS)), MRI estimates of disease burden (T2 lesion volume [T2LV], normalized brain volumes as measures of cerebral atrophy), and MRI-derived measures of ICV as an estimate of brain reserve. Results revealed that phenotype (r = .56, p < .001) significantly predicted performance on the NHPT, such that patients with SPMS did worse than patients with RRMS. Regarding disease burden, T2LV (r = .24, p = .001) and normalized gray matter volume (r = -.18, p = .019) predicted NHPT, with less disease burden associated with better performance. Greater ICV (r = -.21, p =.006) was also significantly associated with better performance on the NHPT. Next, phenotype (r = -.45, p < .001) predicted FTT with SPMS patients again performing worse than RRMS patients. Sex (r = .40, p < .001) was a significant predictor of FTT with men outperforming women, on average. For FTT, normalized gray matter volume (r = .36, p < .001) was the only measure of disease burden that predicted performance, with greater volume (i.e., less atrophy) associated with better performance. Similarly, greater ICV (r = .31, p < .001) significantly predicted better performance on the FTT. For both NHPT and FTT, interactions between measures of disease burden and ICV were not significant. As such, some evidence from this study was not consistent with the reserve hypothesis; however, this finding may be due to differences in the way brain reserve impacts motor outcomes (relative to cognitive outcomes). Nonetheless, as ICV was associated with better performance for both outcome measures, these findings provide partial support for the brain reserve hypothesis in fine motor functioning in MS. Therefore, findings from this study have real-life applications with regard to improved understanding of fine motor disability in MS and identification of patients at risk for upper extremity dysfunction, leading to the possibility of early intervention. Findings also have implications for informing clinical research in MS. Future research should examine the protective effect of brain reserve on fine motor functioning within larger cross-sectional samples (i.e., RRMS vs. SPMS), within primary-progressive MS (PPMS) patients, and when using additional measures of upper extremity disability (e.g., Grip Strength Test). Longitudinal research would also help to determine whether there is a moderating effect of brain reserve on fine motor disability progression as well as allow patients to serve as their own baseline, which would control for individual differences in motor functioning. Next, examining reserve in patients experiencing lesions and atrophy in specific brain regions underlying motor function (e.g., cerebellum and precentral gyrus) may help explain why interactions between disease burden and ICV were not significant within the present study. Finally, by testing the brain reserve hypothesis as it relates to fine motor functioning in non-clinical, healthy controls, it would be possible to determine whether the protective effect of reserve is present premorbidly.

Amyotrofisk lateralskleros och multipel skleros är båda neurologiska sjukdomar som orsakar fysiska begränsningar och påverkar vardagslivet. Syftet med studien var att undersöka hur vardagslivet gestaltar sig för dessa patienter. Studien baseras på en kvalitativ metod utifrån sex självbiografier och en biografi, vilket ger en insyn i patienternas egna upplevelser av hur det är att leva med ALS eller MS. Resultatet består av fyra huvudteman; Relationer, Begränsningar, Psykisk hälsa och Tankar. I samband med sjukdomen blir relationer mer betydelsefulla samtidigt som den för med sig påfrestningar i förhållandet. Begränsningarna kan leda till att den sjuke får allt svårare att klara av sin vardag vad det gäller hemmet, fritiden samt arbete. Den psykiska hälsan kan yttra sig som depression och det blir en daglig kamp där de söker mening med livet och försöker ta kontroll över situationen. Tankarna handlar om nya värderingar i livet och deras ovisshet om framtiden samt att acceptera situationen. Denna studie kan öka sjuksköterskans kunskap och förståelse för patientens situation, samt vara till hjälp vid individanpassningen av omvårdnaden för dessa patienter. Den kan även vara till hjälp för andra personer som vårdar dessa patienter, som till exempel anhöriga och annan ansvarig vårdpersonal. / Amyotrophic lateral sclerosis and multiple sclerosis are both neurological diseases that cause physical limitations and have consequences on daily life. The aim of this study was to clarify how this daily life appears for these patients. The study is based on a qualitative method with six autobiographies and one biography, which gives an insight of their own, lived experiences on how it is to live with ALS or MS. The result contains four main subjects; Relations, Limitations, Psychical health and Thoughts. In sickness relations becomes more of value, but it also cause stress within a relationship. The limitations make life more difficult in different aspects, such as home environment, leisure activities and work. The mental health can develop into a depression and it becomes a daily fight where they seek a meaning with life and try to take control over the situation. Thoughts are about new values in life, an uncertainty about the future and to accept the situation. The findings of this study can give nurses more knowledge and understanding and be helpful when adjusting nursing care for each of these individuals. It can also be a help to other people who take care of these patients, such as family members and other involved care staff.

Purpose: The purpose of this project was to look at the costs of individuals with Alzheimer’s disease and related dementias (ADRD), ALS, and MS in long stay home care in Ontario, Canada. The specific goals were to produce estimates of costs for these individuals, as well as identify clinical and personal characteristics associated with these costs. This project also tested the effectiveness of the Resource Utilization Group for home care case-mix system for use in these special populations. Methods: This project was conducted using a secondary analysis of assessment data from the Canadian Staff Time Resource Intensity Verification Project, a 13-week study of home care costs (N=435 141). The project was guided by the Andersen and Newman (1973) framework for healthcare resource utilization. Descriptive characteristics and mean costs were produced using bivariate frequency and means procedures for each of three conditions. Predictors of costs were identified for each of the three neurological conditions through multivariate regression analysis conducted separately for each condition. In total 41 independent variables were included into the bivariate and multivariate analyses. The dependent variable was the total weekly formal and informal home care costs across all multivariate analyses. Results: In total, ADRD, ALS, or MS diagnoses were present in 16% of the assessments. The mean costs for the three conditions combined were $594.81. The mean costs for ADRD, ALS, and MS were $593.32, $898.41, and $574.92, respectively. Characteristics that were predictive of cost across all conditions included the Resource Utilization Group for home care case-mix system, ADL functionality, IADL functionality, cognitive performance, unsteady gait, stair use, difficulty swallowing, respiratory challenges, and bowel incontinence. The Resource Utilization Group for home care case-mix system had the highest level of explained variance of any single item tested in this project across all conditions. However, other clinical characteristics also contributed substantial levels of explained variance to the models for each of the three conditions. Conclusions: The findings from this project suggest that although diagnosis of ADRD, ALS, and/or MS can describe cost, clinical characteristics are the most important predictors of costs for individuals with these conditions. In addition, the Resource Utilization Group for home care case-mix system can adequately predict costs of individuals with these conditions. The addition of some clinical characteristics would likely improve the predictive abilities of the Resource Utilization Group for home care case-mix system.

Thesis (M.S.)--West Virginia University, 2002. / Title from document title page. Document formatted into pages; contains ix, 67 p. : ill. Includes abstract. Includes bibliographical references (p. 63-67).

Multiple Sclerosis (MS) is a chronic neurological condition, which affects around 2.5 million people worldwide. At a time when there is yet no recognised cure, it is imperative that MS patients learn to cope and adjust well to living with the illness. However, research has found high rates of psychological distress associated with MS (Minden &amp; Schiffer, 1991). This highlights the need for research to investigate the psychological factors, which make MS patients vulnerable to psychological distress. One popular social cognition model called the Self-Regulation Model (Leventhal et al., 1980) has been found to successfully predict adjustment in a range of chronic illnesses. However, previous research applying the SRM to understand adjustment to MS has been limited. The current research therefore represented the first attempt to successfully apply the full SRM to an MS population prospectively. The present thesis is comprised of three studies and employed a mixed quantitative and qualitative research design method. Studies 1 (N=103) and 3 (N=150) were both quantitative studies, which applied an extended SRM model to clinical samples of MS patients and assessed indices of psychological distress over time. Study 2 (N=15) however was a qualitative study, designed to investigate MS patients experiences of living with the condition. By combining both quantitative and qualitative methods, the findings provided a fuller understanding of the psychological factors underlying successful adjustment to MS. Overall the findings provided some support for the utility of the extended SRM in predicting adjustment to MS and highlighted the importance of positive mind states and acceptance for successful adjustment to the condition. The findings also had a number of clinical implications, which are also discussed.

Purpose: The purpose of this project was to look at the costs of individuals with Alzheimer’s disease and related dementias (ADRD), ALS, and MS in long stay home care in Ontario, Canada. The specific goals were to produce estimates of costs for these individuals, as well as identify clinical and personal characteristics associated with these costs. This project also tested the effectiveness of the Resource Utilization Group for home care case-mix system for use in these special populations. Methods: This project was conducted using a secondary analysis of assessment data from the Canadian Staff Time Resource Intensity Verification Project, a 13-week study of home care costs (N=435 141). The project was guided by the Andersen and Newman (1973) framework for healthcare resource utilization. Descriptive characteristics and mean costs were produced using bivariate frequency and means procedures for each of three conditions. Predictors of costs were identified for each of the three neurological conditions through multivariate regression analysis conducted separately for each condition. In total 41 independent variables were included into the bivariate and multivariate analyses. The dependent variable was the total weekly formal and informal home care costs across all multivariate analyses. Results: In total, ADRD, ALS, or MS diagnoses were present in 16% of the assessments. The mean costs for the three conditions combined were $594.81. The mean costs for ADRD, ALS, and MS were $593.32, $898.41, and $574.92, respectively. Characteristics that were predictive of cost across all conditions included the Resource Utilization Group for home care case-mix system, ADL functionality, IADL functionality, cognitive performance, unsteady gait, stair use, difficulty swallowing, respiratory challenges, and bowel incontinence. The Resource Utilization Group for home care case-mix system had the highest level of explained variance of any single item tested in this project across all conditions. However, other clinical characteristics also contributed substantial levels of explained variance to the models for each of the three conditions. Conclusions: The findings from this project suggest that although diagnosis of ADRD, ALS, and/or MS can describe cost, clinical characteristics are the most important predictors of costs for individuals with these conditions. In addition, the Resource Utilization Group for home care case-mix system can adequately predict costs of individuals with these conditions. The addition of some clinical characteristics would likely improve the predictive abilities of the Resource Utilization Group for home care case-mix system.

Multiple sclerosis is a progressive autoimmune disease where myelin is gradually stripped from axons. Axon degeneration inevitably follows protracted myelin loss ultimately leading to irreversible neurological decline. To better understand the cellular mechanisms associated with the axon loss phase of the disease, spinal cord axons from the experimental autoimmune encephalomyelitis (EAE) animal model of multiple sclerosis were examined using correlated in vivo time-lapse microscopy and serial section transmission electron microscopic (ssTEM) reconstruction. A novel technique, termed near infrared burning (NIRB), was developed that took advantage of a femtosecond-pulsed mode locked laser’s ability to create photoconvertable fiducial markers for routine identification of previously imaged axons for ssTEM reconstruction. This combination of imaging techniques revealed the subcellular milieu that underlies axon degeneration at both the light and electron microscopic level. In particular, paranodal regions of axons in EAE animals contained a significantly higher population of mitochondria with large rounded, electron lucid, vesiculated mitochondria with unorganized cristae compared to controls. This effect was largely restricted to the paranodal region and was not always associated with direct immune cell interaction or myelin loss. Together, these results suggest a novel mechanism for axon degeneration that is not only focal in nature, but decoupled with myelin loss in the EAE animal model of multiple sclerosis. / Department of Biology

The purpose of this investigation was to examine the effects of Multiple Sclerosis (MS) on the structural and functional characteristics of skeletal muscle. More specifically, we analyzed the myosin heavy chain (MHC) and fiber type distribution of the vastus lateralis, measured single fiber cross sectional area (CSA), and determined the isokinetic and isotonic strength of the knee extensor muscles. Six sedentary subjects with MS (age: 44 ± 2 yrs) and six sedentary gender-matched controls (age: 46 ± 4) were evaluated. EachMS subject was rated on the Kurtzke's Expanded Disability Status Scale (EDSS) and performed an 8-meter walk test to determine gait speed. Furthermore, the spasticity of the knee extensors was evaluated in each MS subject and weekly energy expenditure was estimated using the Yale Physical Activity Survey. Concentric and eccentric isokinetic strength of the right knee extensors (left in one MS subject) was determined at 60 and 180°/sec and a bilateral isotonic one-repetition maximum (1-RM) was evaluated in eachsubject. Muscle biopsies were taken from the right vastus lateralis (left in one MS subject) and individual fibers were dissected from these samples. Fibers were submitted to SDSPAGE with silver staining to determine MHC expression. Densitometry was performed on MHC hybrid fibers to determine the degree of co-expression. An additional section ofthe biopsy was stained for mATPase activity and further analyzed for single fiber CSA and fiber type. The mean EDSS score for the MS subjects was 5.4 ± 0.6 (range 3.5-6.5) and MS patients were slower than controls (p < 0.05) on the walk-test. AshworthSpasticity Scores ranged from 0 - 2. No differences were noted in weekly energy expenditure. The controls were 45 and 56% stronger than the MS group at isokinetic concentric velocities of 60 and 180°/sec (p < 0.05), respectively. The isotonic 1-RM andthe eccentric isokinetic contractions were not different between the two groups. There were no differences noted in any of the MHC isoforms or percentage of hybrid fibers. Furthermore, mATPase fiber type distribution and single fiber CSA were not different between the groups. There was a greater proportion of MHC IIx dominant MHC IIa/IIx fibers in the MS groups (p < 0.05). Multiple Sclerosis appears to result in large strengthdeficits, when compared to healthy individuals. Based on our findings, these strength differences cannot be explained by alterations in MHC/fiber type expression or decreases in fiber CSA. / School of Physical Education

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.

Diss. (sammanfattning) Umeå : Univ., 2007. / Härtill 4 uppsatser.