Individuals with Multiple Sclerosis commonly use assistive mobility devices, such as rollators, to compensate for their mobility impairments. However, the effect of these devices on their foot placement during gait has not been explored in the community. The objective of experiment one was to develop and validate a tool that quantifies medio-lateral foot placement characteristics during rollator use. In this study, a technique was developed for an instrumented rollator (i.e. iWalker) and validated against a Vicon motion capture system in able-bodied young adults. The two systems were in strong agreement. The objective of experiment two was to apply this iWalker-based technique to individuals with Multiple Sclerosis to identify environment-related foot placement changes. This study revealed that step width variability, but not step width, can be influenced by certain outdoor environments. Therefore, environmental context is important to consider when investigating user-device interactions and factors responsible for safe mobility in this population.

T2 relaxation imaging can be used to measure signal from water trapped between myelin bilayers; the ratio of myelin water signal to total water is termed the myelin water fraction (MWF). First, results from multi-component T2 relaxation and diffusion tensor imaging (DTI) were compared for 19 multiple sclerosis (MS) subjects at 1.5 T to better understand how each measure is affected by pathology. In particular, it was determined that the detection of a long-T2 signal within an MS lesion may be indicative of a different underlying pathology than is present in lesions without long-T2 signal. Next, the single-slice T2 relaxation measurement was implemented, refined, and validated at 3.0 T. Scan parameters were varied for phantoms and in-vivo brain, and changes in multi-exponential fit residuals and T2 distribution-derived parameters such as MWF were monitored to determine which scan parameters minimized artifacts. Measurements were compared between 1.5 T and 3.0 T for 10 healthy volunteers. MWF maps were qualitatively similar between field strengths. MWFs were significantly higher at 3.0 T than at 1.5 T, but with a strong correlation between measurements at the different field strengths. Due to long acquisition times, multi-component T2 relaxation has thus far been clinically infeasible. The next study aimed to validate a new 3D multi-component T2 relaxation imaging technique against the 2D single-slice technique most commonly used. Ten healthy volunteers were scanned with both the 2D single-slice and 3D techniques. MWF maps were qualitatively similar between scans. MWF values were highly correlated between the acquisition methods. Although MWF values were generally lower using the 3D technique, they were only significantly so for peripheral brain structures, likely due to increased sensitivity of slab-selective refocusing pulses used for the 3D approach. The 3D T2 relaxation sequence was then applied to the study of MS to take advantage of the increased brain coverage. Thirteen MS subjects and 11 controls underwent T2 relaxation and DTI examinations to produce histograms of MWF and several DTI-derived metrics. MS MWF histograms differed considerably from those of controls, and differences in MS MWF histograms did not mirror differences in DTI histograms relative to matched controls.

The effects of multiple sclerosis (MS) on the central nervous system often manifest as abnormalities in gait kinematics. Clinically practical, valid, and reliable measures of gait kinematics are necessary to address research and clinical questions about MS. Wireless flexible electrogoniometry (EG) is a clinically practical measure of joint angles. The GAITRite walkway system is a clinically practical, valid and reliable measure of temporal and spatial gait characteristics. The overall objective of this two-study research project was to explore whether these clinically practical measures of gait kinematics can be used to accurately detect gait abnormalities in people with multiple sclerosis. Study 1 examined the reliability and validity of EG and Study 2 examined the gait kinematics of people with MS (PWMS) using EG and GAITRite. For Study 1, angle at initial contact and total joint excursion were measured by EG at both the knee and ankle while ten healthy adults walked at a self-selected comfortable speed. Measurements were repeated for two testers and two visits to assess reliability. The same variables were measured concurrently with three-dimensional motion analysis (3D) to assess validity. For all variables, reliability was good as indicated by low measurement error and validity was good as indicated by association and agreement of EG with 3D. For Study 2, the same joint angles, along with speed, cadence, step length, stride length, stance duration and double support duration were assessed for six PWMS and six controls without MS. PWMS showed significantly reduced speed, cadence, and ankle excursion and increased stance and double support duration as previously shown with 3D. Spasticity and/or instability may lead to these kinematic gait abnormalities in PWMS; however, reduced velocity may confound this interpretation by affecting the other observed gait abnormalities. Further research about the determinants of gait dysfunction in PWMS is required. EG and GAITRite are clinically practical, valid and reliable measures of gait kinematics and should be included in further clinic-based research to determine which kinematic gait abnormalities are causes and which are effects of the observed decrease in gait speed in PWMS.

Multiple Sclerosis (MS) is the most common demyelinating disease affecting the central nervous system. Over 80% of MS patients are in the relapsing remitting stage. Symptoms range from fever, fatigue, emotional distress, tingling, numbness, optic neuritis, spasticity, muscle weakness, impaired coordination, to other abnormal neurological problems. Expression of symptoms is known as a relapse or exacerbation. The cause of relapses is unknown, but multiple factors seem to play a significant role. Possible factors that may influence MS onset and relapse consist of a genetic association, viruses, disruption of the blood-brain barrier, and stress. Stress has shown to have negative implications and may stimulate relapses. Thus, this study examined a possible stress intervention that most people already had available to them, companion animals. Companion animals have been shown to lower blood pressure, decrease heart rate, provide social support, and reduce stress. The main hypothesis was to evaluate whether or not pet ownership and/or attachment influenced the perceived stress level and number of negative life events experienced by MS patients in the relapsing remitting stage. Participants were given a questionnaire that consisted of 7 surveys. The questionnaire accessed quality of life, disease severity, number of negative life events, perceived stress level, level of depression, social support, and pet ownership and attachment level. Our sample population consisted of MS patients seen at the University of Texas Southwestern Neurology clinic from February 23rd to May 21st, 2004. One hundred and forty seven relapsing remitting MS patients were included in the study. Multiple linear regression was used to compare the relationship of stress and number of negative life events to pet ownership and attachment. Results revealed that pet ownership and attachment levels did not affect the stress level and number of negative life events of MS patients. No confounders were identified. Interaction terms with disease severity as the dependent variable, pet ownership and perceived stress level or negative life events as the independent variables were not significant. The type of pet owned did not influence the attachment level of the MS patient. In conclusion, the results of this study did not support the hypothesis.

Stressful life events have been associated with the onset and/or exacerbation of multiple sclerosis (MS). To investigate the effects of stress on the pathogenesis of MS, we employed restraint stress (RST) in the Theiler’s virus-induced demyelination (TVID) model, an animal model for human MS. Intracerebral inoculation of susceptible strain of mice with Theiler’s murine encephalomyelitis virus (TMEV) results in a biphasic disease – an acute encephalomyelitis and chronic demyelination. The establishment of persistent viral infection is critical in inducing immune-mediated demyelination during the chronic disease. The exposure of mice to RST prior to viral infection produced a stress response as evidenced by elevated circulating corticosterone (CORT). To further study the effect of stress on the immune response to TMEV infection and demyelination, we first examined the cytokine and chemokine response during the acute TMEV infection. We demonstrated that RST down-regulated the virus-induced expression of chemokines, Ltn, IP-10, RANTES, and pro-inflammatory cytokines, TNF, IFN and LT in both the brain and spleen during early infection. Histologically, a decreased pattern of inflammation was observed in the brain of restrained mice as compared to non-restrained mice. The increased viral titer was noted in the CNS of restrained mice and was correlated with the decreased production of pro-inflammatory cytokine, suggesting an impaired immune response by RST. Secondly, the duration of stress on the late demyelination was investigated. Repeated and chronically stressed SJL/J mice developed an early onset of clinical signs and a delayed onset was observed in acutely stressed mice. Both acute and chronic RST suppressed the antibody response to TMEV and stressed displayed a higher incidence of demyelination than non-restrained mice. Axonal loss was also noted in chronic stressed mice. Additionally, RST caused an increased systemic viral infection in extraneural organs during the acute infection and cardiotropic TMEV was isolated from the heart of stressed mice. Taken together, stress resulted in profound immunsuppression during acute infection, which may consequently increase the incidence of demyelination. The present study may be generalized in human MS which is potentially triggered by viral infection.

Thesis (Ph. D.)--Ohio State University, 2009. / Title from first page of PDF file. Includes vita. Includes bibliographical references (p. 119-139).

No description available.

Much of this thesis describes the use of immunohistochemical methods on salivary glands from patients with Sjogren's syndrome (SS) to quantify the position, nature and proliferative activity of the inflammatory cell infiltrate, deposition of cell matrix proteins and glandular expression of TGFp. Studies are also undertaken on glands from an experimental animal model and from patients with two associated conditions, benign lymphoepithelial lesion (BLEL) and systemic sclerosis (SSc). Initially a rat model of SS was examined and changes in salivary glands quantified at different stages after autoimmunisation. Immunohistochemically there were similarities to SS, in that class II antigen was expressed by glandular epithelium and the early lesions contained T lymphocytes. However, B lymphocytes were rare, the cell infiltrate contained large populations of macrophages and neutrophils, and there was evidence of increased elaboration of fibrous connective tissue. These results indicate that this animal model is of doubtful use for the study of Sjogren's syndrome. Studies on human tissue showed that the lymphocyte infiltrate in BLEL patients was more extensive than SS and that T cells predominated in small foci, whereas B cells were the dominant lymphocyte type in larger foci. In areas of extensive lymphocyte infiltration, B cells were closely associated with ducts or present in germinal centre-like structures with T cells being found elsewhere. A previously unreported feature of BLEL was the presence of intra-epithelial (and intra-lumenal) B cells, many of which were proliferating. The remaining duct walls in BLEL appeared to be under pressure due to this population of B lymphocytes and "holes" were observed both in the basement membrane and at the lumenal surface that may facilitate migration of lymphocytes from glandular stroma into duct lumens. There was significantly more tenascin and fibronectin in BLEL glands (p<0.01) compared to normal parotid controls which contained minimal amounts of these proteins. By contrast, both proteins were expressed in normal labial glands with no significant increase in glands from SS and SSc patients. As both tenascin and fibronectin are important in cell migration, increased levels may be a factor facilitating lymphoid infiltration in BLEL. Absorbance measurements demonstrated that ductal expression of TGFI differed between control, SS and BLEL salivary glands. SS glands showed an increase in expression of all isoforms of TGFß with the increase for TGFP2 and TGFP3 being significant (p=0.02 & p<0.002). By contrast, ductal expression of all isoforms of TGFI in BLEL was reduced in both confluent (p<0.0001) and minimally infiltrated (p<0.005) areas of gland. Thus reduced glandular expression of TGFJ may be important in allowing the high levels of lymphocyte and epithelial cell proliferation detected in BLEL which are rarely seen in SS. Salivary glands from SSc and Raynaud's phenomenon (RP) patients contained small, predominately T cell foci with few proliferating B cells and a significantly increased mast cell population (p<0.005). Fibrosis within the glands was variable and not associated with increased deposition of fibronectin or tenascin. Subjectively, the most obvious difference in TGFI expression in SSc compared to controls was exhibited by fibroblasts. Cell counts revealed no differences in fibroblast expression of TGFßI or TGFß receptors. However, the percentage of TGFß2-positive fibroblasts was significantly higher in SSc glands compared to controls (p<0.004). RP glands showed an intermediate level of expression. By contrast, a lower percentage of RP fibroblasts expressed TGF(33 compared to controls, with SSc glands showing an intermediate level of expression. The results indicate that both SSc and RP are associated with an increased salivary gland mast cell population and changes in expression of TGFß2 and ß3 isoforms by glandular fibroblasts. The final section of this thesis describes an investigation of antioxidant levels in saliva from healthy individuals and patients with SS or periodontal disease. The results demonstrated that in SS there was an increase in the concentration of antioxidants in unstimulated saliva but a reduced rate of production. This diminished output of salivary gland antioxidants may be of significance to the oral health of these patients. In periodontal disease there was a reduction in antioxidant levels in stimulated saliva that may have been the result of local depletion by reactive oxygen species, produced by chronic inflammation within the gingival tissues. Alternatively, these patients may have intrinsically reduced levels of antioxidants and therefore be more susceptible to periodontal disease.

published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

The purpose of this secondary analysis was to test a multivariate model of disability separately in women with two different conditions, multiple sclerosis (MS) and fibromyalgia syndrome (FMS), and to compare respective models across groups. Guided by the Disablement Process Model, this study examined the influences of functional limitations, depressive symptoms, economic adequacy, and social support on disability by use of two-group structural equation modeling (SEM). Nonprobability samples of women with MS (N = 118) and women with FMS (N = 197) were recruited for separate health promotion intervention studies. Baseline data collection occurred between 1997 and 1998 for women with MS enrolled in the Wellness Intervention and between 2004 and 2006 for women with FMS enrolled in the Lifestyle Counts Intervention. Participants in both samples were largely married, well-educated, middle-age, and Caucasian. Descriptive statistics, bivariate correlations, and SEM were conducted with the Statistical Package for the Social Sciences 15.0 and Amos 7.0 software programs. Mean scores of the major study variables indicated poorer physical and mental health for the sample of women with FMS compared to that with MS. Controlling for age, duration of illness, and education, greater functional limitations predicted greater SFdisability and Role Physical (RP)-disability in both groups. The influence of Functional Limitations on both SF-disability and RP-disability was greater for women with FMS than MS. The effect of Depressive Symptoms on SF-disability was equivalent across groups. Feeling depressed significantly impacted RP-disability, although these effects were not equal across groups. Depressive Symptoms played a larger role than did Functional Limitations in explaining SF- and RP-disability in women with MS. Social Support affected Depressive Symptoms equally for both groups. For women with MS, compared to women with FMS, Economic Adequacy had greater detrimental effects on Depressive Symptoms and both measures of disability. Social Support and Depressive Symptoms mediated the effect of Functional Limitations on disability. Adjustment to life with a chronic illness depends on, at the very least, individual physical, social, and psychological capacities. Practitioners should be sensitive to depressive symptoms and availability of social support in women with MS or FMS. / text