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Multiple sclerosis: correlation of gene expression and response to immunomodulatory therapy
Kleinová, Pavlína ; Kubala Havrdová, Eva (advisor) ; Taláb, Radomír (referee) ; Musil, Zdeněk (referee)
KLEINOVÁ, Pavlína. Roztroušená skleróza mozkomíšní: korelace genové exprese a odpovědi na imunomodulační léčbu [Multiple sclerosis: correlation of gene expression and response to immunomodulatory therapy]. Praha, 2023. 107 s., 3 přílohy. Disertační práce. 1. lékařská fakulta Univerzity Karlovy v Praze. Vedoucí práce Eva Kubala Havrdová. Abstract Multiple sclerosis is a chronic autoimmune disease of the central nervous system with a genetic component, modifiable with immunomodulatory therapy. It is assumed that genetic factors influence the course of the disease and the therapeutic response. The thesis presents the results of two studies investigating the genetic background of multiple sclerosis. In the first study, the influence of the (GT)n polymorphism of the promoter of the HMOX1 gene for heme oxygenase 1 affecting its expression was investigated in people with multiple sclerosis. No effect of this polymorphism on the course of the disease was observed. We confirmed the effect of immunomodulatory therapy on delaying disease progression. The second study, called the Genotype/Phenotype Project, is a multicentre international genome-wide association study aimed at detecting single nucleotide polymorphisms associated with severity of multiple sclerosis. It has been shown that common genetic variants with...
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Rehabilitation influence on quality of life in neurological patients
Kövári, Martina ; Kobesová, Alena (advisor) ; Kubala Havrdová, Eva (referee) ; Angerová, Yvona (referee)
Rehabilitation influence on quality of life in neurological patients Abstract: This work focuses on neurorehabilitation procedures that influence disability and improve the quality of life of neurological patients, especially those with multiple sclerosis (MS). We identified several positive effects of a complex physiotherapy program based on optimal postural stabilization training, intra-abdominal pressure regulation, and pelvic floor activation with biofeedback on anorectal dysfunction in MS patients. Fecal incontinence and subjective discomfort measured by St. Mark's Incontinence Score Questionnaire significantly decreased after the rehabilitation program with a physiotherapist. Changes in anorectal pressures after the rehabilitation program were not statistically significant, but a positive trend was found in the ability to activate the anal sphincter and pelvic floor muscles. The MS patients also regularly performed Pilates exercises. Significant improvements in gait speed and endurance, even during dual tasking situations, i.e. when walking and performing cognitive tasks were identified. Pilates exercise also significantly improved balance measured by the MiniBEST test and by the Falls Efficacy Scale International Questionnaire. The immediate effect of electrical stimulation according to Jantsch...
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Influence of corticosteroids and movement disorder on development of osteoporosis in patients with multiple sclerosis (MS)
Týblová, Michaela ; Kubala Havrdová, Eva (advisor) ; Vymazal, Josef (referee) ; Taláb, Radomír (referee)
Introduction: Multiple sclerosis (MS) is associated with impaired bone health in comparison to an equally healthy population, even already in patients at the onset of this disease. The main risk factors for development of osteoporosis in MS patients are known. The aim of the study was to find the relationship of the decrease in bone mineral density (BMD) to the administered cumulative dose of steroids and to other risk factors in MS, mainly to the degree of motor deficit. Further goal was to evaluate the occurence of the risk of low-trauma fractures in multiple sclerosis patients.. The BMD and muscle mass was compared in MS patients (women and men) and control subjects, to examine the effect of main ones - physical disability and long-term glucocorticoid (GC) therapy on BMD. Clinical values of bone remodeling markers were evaluated in assessment of rate of bone loss in patients with multiple sclerosis long term treated with low dose of GC. Patients and methods: We used dual -energy X-ray absorptiometry for a measurement of BMD in 591 MS patients (455 females and 136 males) in 2004 and in cross-sectional longitudinal study published in 2014 with 474 patients (353 women and 121 men). Out of the whole study group body composition was evaluated in 250 MS females, 104 males and 247 healthy controls (193...
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The detection of cognitive dysfunction in multiple sclerosis
Blahová-Dušánková, Jana ; Kubala Havrdová, Eva (advisor) ; Papežová, Hana (referee) ; Rektorová, Irena (referee)
Evaluation of cognitive impairment is often omitted in multiple sclerosis (MS), as the available instruments usually require considerable time and resources, and are not readily available in all countries. The aims of this study were to examine validity of the Czech translation of the MACFIMS (Minimal Assessment of Cognitive Function in MS), to validate the BICAMS (Brief International Cognitive Assessment for MS) and to compare outcomes of the MACFIMS and the BICAMS. We evaluated 367 MS patients and 134 healthy controls with the MACFIMS battery, which also comprises the 3 tests of the BICAMS (Symbol Digit Modalities Test, Brief Visuospatial Memory Test- Revised, California Verbal Learning Test, second edition). The most accurate BICAMS criterion of cognitive deficit was that of at least 1 of the overall 3 tests outside the normal range (sensitivity = 94%, specificity = 86%, p=10-28). Outcomes of the Czech translation of the MACFIMS were comparable to its original. The MACFIMS and the BICAMS identified cognitive deficit in 55% and 58% of the MS patients, respectively. Both the BICAMS and MACFIMS predicted patient vocational status. The BICAMS is highly sensitive and specific to cognitive impairment in MS as defined by the MACFIMS. This impairment is significantly associated with vocational status. Our work...
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Characteristics of gait impairment and possible therapeutic interventions in people with multiple sclerosis.
Novotná, Klára ; Kubala Havrdová, Eva (advisor) ; Čakrt, Ondřej (referee) ; Taláb, Radomír (referee)
Walking disorders are one of the most visible symptoms of multiple sclerosis (MS). Multiple sclerosis (MS) is a chronic autoimmune neurodegenerative disease of the central nervous system that is the most common cause of disability of young adults. Walking disorders are one of the most common motor problems that accompany this disease, which patients themselves perceive as the most limiting. Walking disorders can be caused by many symptoms of MS such as: muscle weakness, spasticity, sensory disturbances, visual disturbances, sphincter problems, cognitive dysfunction, fatigue and thermosensitivity. Measuring of various gait parameters (most often speed and endurance) also helps to monitor the effects of treatment and to evaluate the progression of the disease. Even in patients with minimal neurological symptoms it is possible to detect deterioration of gait parameters. Realized studies have shown that subjectively perceived improvement in gait after treatment with natalizumab can be objectified with the aid of assessment of walking parameteres. Similarly, a functional gait test can be used to assess the therapeutic response (and thus evaluate the cost effectiveness of treatment) to symptomatic treatment with fampridine. As a physiotherapist, I was also interested in the possibility of influencing...
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Optical coherence tomography in multiple sclerosis.
Lízrová-Preiningerová, Jana ; Kubala Havrdová, Eva (advisor) ; Vymazal, Josef (referee) ; Taláb, Radomír (referee)
Spectral domain optical coherence tomography (SD-OCT), a non-invasive imaging method, is based on an analysis of a near-infrared light deflected from tisssue layers, that provides detailed images of retinal structures. Nerve cells of the retina, that originate from neuroectoderm, reflect neurodegeneration of the central nervous system (CNS), as well as acute damage of nerve structures caused by optic neuritis. The dissertation first presents established imaging protocol and quality standards for SD-OCT imaging in multiple sclerosis (MS). In the following section we introduce SD-OCT as a biomarker in MS. In a multicentric cross-sectional study, we had shown, that a single time measurement of peripapillary retinal nerve fiber layer thickness (RNFL) has a predictive value for a risk of disease progression in the next five years. Patients with a thickness of RNFL in the lowest tercile of the studied population had a relative risk of disease progression 2x higher than patients in the highest tercile. The second presented study tests whether the history of optic neuritis (ON) in MS is a risk factor for neurodegeneration of RNFL in later years. The study confirmed that long term changes of RNFL thickness in eyes post-ON and in eyes with no history of ON are not different. Therefore, we conclude that both,...
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Immunosuppression in active multiple sclerosis: combination treatment with interferon beta and azathioprine and fingolimod monotherapy
Tichá, Veronika ; Kubala Havrdová, Eva (advisor) ; Vymazal, Josef (referee) ; Laczó, Jan (referee)
Introduction: Addition of a second drug used to be a strategy to achieve clinical stabilization of multiple sclerosis in many patients with on-going activity despite monotherapy. Modern immunosuppressive drugs used in monotherapy exert more specific mode of action. Methods: This retrospective observational study evaluated 5-year data from 85 patients with active multiple sclerosis despite monotherapy with either interferon beta or azathioprine, who received add-on azathioprine or interferon beta, respectively. In a subgroup of 23 patients 10- year data were analysed. In a second part of the study, a group of 126 patients switched either from interferon beta or glatiramer acetate to fingolimod was followed-up for one after the change of their treatment and a in a subgroup of 53 patients the 2-year data were assessed. Clinical (relapse frequency, disability) parameters were compared preceding and following the addition of second drug or the switch of treatment. Laboratory results and potential serious adverse events were evaluated in a group of patients with combination therapy. Results: The add-on treatment triggered a drop in annualised relapse rate by approximately 1.5 points sustained over 5 and 10 years. No effect on disability was observed. Simultaneously, white blood cell and lymphocyte counts...
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Influence of corticosteroids and movement disorder on development of osteoporosis in patients with multiple sclerosis (MS)
Týblová, Michaela ; Kubala Havrdová, Eva (advisor) ; Vymazal, Josef (referee) ; Taláb, Radomír (referee)
Introduction: Multiple sclerosis (MS) is associated with impaired bone health in comparison to an equally healthy population, even already in patients at the onset of this disease. The main risk factors for development of osteoporosis in MS patients are known. The aim of the study was to find the relationship of the decrease in bone mineral density (BMD) to the administered cumulative dose of steroids and to other risk factors in MS, mainly to the degree of motor deficit. Further goal was to evaluate the occurence of the risk of low-trauma fractures in multiple sclerosis patients.. The BMD and muscle mass was compared in MS patients (women and men) and control subjects, to examine the effect of main ones - physical disability and long-term glucocorticoid (GC) therapy on BMD. Clinical values of bone remodeling markers were evaluated in assessment of rate of bone loss in patients with multiple sclerosis long term treated with low dose of GC. Patients and methods: We used dual -energy X-ray absorptiometry for a measurement of BMD in 591 MS patients (455 females and 136 males) in 2004 and in cross-sectional longitudinal study published in 2014 with 474 patients (353 women and 121 men). Out of the whole study group body composition was evaluated in 250 MS females, 104 males and 247 healthy controls (193...
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