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Multiple sclerosis - clinical and paraclinical markers for monitoring disease activity and factors influencing its course
Šťastná, Dominika ; Horáková, Dana (advisor) ; Libertínová, Jana (referee) ; Taláb, Radomír (referee)
Multiple sclerosis (MS) is a chronic neurological disease that, without treatment, leads over years to decades to severe disability in most patients. We cannot cure the disease, but there is growing evidence that early initiation of anti-inflammatory therapy and management of associated comorbidities has a major impact on its course. Patient registries have an irreplaceable contribution to evaluating factors influencing the MS course and the monitoring of therapeutic agents in real clinical practice. First, this thesis evaluated therapy management trends between 2013 and 2021 based on data from the Czech National MS Registry (ReMuS). Subsequently, the paper responds to the onset of the covid-19 pandemic through registry data and addresses this issue in the context of MS. The proportion of patients in ReMuS treated with high-efficacy disease-modifying therapies (HE-DMT) increased from 16.2% to 37.1% between 2013 and 2021, and the proportion of treatment-naive patients initiating HE-DMT increased from 2.1% to 18.5%. Regarding covid-19 infection, we determined that higher body mass index, older age, recent high-dose glucocorticoid treatment, and anti-CD20 therapy were independent variables associated with pneumonia based on data from 958 MS patients with a history of covid-19. Further, we analyzed...
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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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Prognostic markers of disease course in early stages of multiple sclerosis
Petržalka, Marko ; Marusič, Petr (advisor) ; Taláb, Radomír (referee) ; Lízrová, Jana (referee)
Prognostic markers of disease course in early stages of multiple sclerosis ABSTRACT This thesis analyzes the biomarkers of unfavorable prognosis assessed at early stages of multiple sclerosis. Because specific biomarkers often providerather complex information,the theoretical part provides a summary of biomarkers used not only in prognosis assessment, but also in diagnostics and therapy monitoring. In the empirical part, we have investigatedthe prognostic value of intrathecal synthesis of class M immunoglobulins, serum and cerebrospinal fluid concentrations of interleukin 2, interleukin 6, interleukin 10, chitinase 3-like 2 protein and neurofilament heavy chains, assessed from samples acquired during diagnostic procedures. 58 patients early after the first manifestation of multiple sclerosis were included. All patients initiated therapy with glatiramer acetate, teriflunomide, or interferon beta. To assess the evolution of the disease, we followed the patients clinically and with MRI for two years. Interleukin 2 to interleukin 6 ratio of cerebrospinal fluidvalues ˂0.48 (p=0.0028), interleukin 2 in cerebrospinal fluid ≥1.23 (p=0.0260), chitinase 3-like 2 in cerebrospinal fluid ≥7900 (p=0.0330), age at clinical onset ˂22 years (p=0.0312) and baseline Expanded Disability Status Scale ≥1.5 (p=0.0481), proved to...
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Diagnostic markers in patients in early stage of multiple sclerosis
Hynčicová, Eva ; Laczó, Jan (advisor) ; Horáček, Jiří (referee) ; Taláb, Radomír (referee)
The aims of the thesis were to assess diagnostic markers for monitoring of the disease progression in patients with clinically isolated syndrome (CIS) and laboratory markers of efficacy of the interferon beta (IFNß) therapy. This thesis includes 4 studies. The first study was focused on evaluation of cognitive impairment and its structural correlates in patients with CIS. Using comprehensive neuropsychological testing and brain magnetic resonance imaging (MRI) with volumetric analyses we found cognitive impairment in 18-37 % of CIS patients in almost all cognitive domains. Brain volume was reduced predominantly in fronto- temporal regions and the thalamus. Next, visuo-spatial impairment was associated with lower white matter volume in patients with CIS. The two other studies evaluated neuropsychiatric symptoms, life satisfaction, health-related quality of life and their mutual relationships. In addition, one of these two studies evaluated structural correlates of neuropsychiatric symptoms on brain MRI. Using a battery of specific questionnaires, we demonstrated depressive symptoms and anxiety in patients with CIS, lower life satisfaction, lower health-related quality of life and close mutual relationships. The quality of life was associated more with cognitive functioning than with disability in...
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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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Multiple sclerosis: Clinical and paraclinical markers of disease activity.
Srpová, Barbora ; Horáková, Dana (advisor) ; Taláb, Radomír (referee) ; Bartoš, Aleš (referee)
Multiple sclerosis is chronic, autoimmune and neurodegenerative disorder of central nervous system. Currently, we have only limited markers of disease activity. From clinical markers, speech markers were analysed. Data from 141 patients and 70 healthy controls were evaluated. The most important results were detection of speech abnormalities in patients with minimal neurological disability (EDSS<2) and their correlations with global and regional brain atrophy. This work is predominantly concetrated on neurofilament light chain (NfL) as one of the most promising paraclinical biomarkers. NfL, especially level of serum NfL (sNfL), is considered to be a biomarker of future disease course, disease activity and effect of DMD (disease modifying drugs) therapy. The main aim was to clarify the position of NfL among others biomarkes and their potential benefit for routine clinical praxis. MRI data, clinical data and results of NfL measurements from 172 newly diagnosed patients with relaps-remiting MS (revised McDonald criteria 2017) from original SET cohort were analysed. Additionally, we compared levels of serum and CSF NfL with other biochemical parameters, such as lipidogram and markers of blood-brain permeability. We found sNfL as a marker of ongoing neuroinflammation and predictor of future brain atrophy...
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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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Diagnostic markers in patients in early stage of multiple sclerosis
Hynčicová, Eva ; Laczó, Jan (advisor) ; Horáček, Jiří (referee) ; Taláb, Radomír (referee)
The aims of the thesis were to assess diagnostic markers for monitoring of the disease progression in patients with clinically isolated syndrome (CIS) and laboratory markers of efficacy of the interferon beta (IFNß) therapy. This thesis includes 4 studies. The first study was focused on evaluation of cognitive impairment and its structural correlates in patients with CIS. Using comprehensive neuropsychological testing and brain magnetic resonance imaging (MRI) with volumetric analyses we found cognitive impairment in 18-37 % of CIS patients in almost all cognitive domains. Brain volume was reduced predominantly in fronto- temporal regions and the thalamus. Next, visuo-spatial impairment was associated with lower white matter volume in patients with CIS. The two other studies evaluated neuropsychiatric symptoms, life satisfaction, health-related quality of life and their mutual relationships. In addition, one of these two studies evaluated structural correlates of neuropsychiatric symptoms on brain MRI. Using a battery of specific questionnaires, we demonstrated depressive symptoms and anxiety in patients with CIS, lower life satisfaction, lower health-related quality of life and close mutual relationships. The quality of life was associated more with cognitive functioning than with disability in...
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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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