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Neurological manifestations of Fabry disease
Reková, Petra ; Kemlink, David (advisor) ; Karetová, Debora (referee) ; Kešnerová, Petra (referee)
Neurological manifestations of Fabry disease Abstract The presented thesis deals with cerebrovascular manifestations of a rare X-linked disease, Fabry disease (FD). Screening programs can detect unrecognized disease and increase awareness of the disease with the goal of early diagnosis and initiation of therapy before developing an irreversible organ damage. Identifying vascular abnormalities and the influence of comorbidities on the cerebrovascular phenotype of FD patients may help to promote the knowledge of the pathophysiology of cerebrovascular involvement. The main objectives of the studies underlying this thesis were to determine the prevalence of FD and to evaluate the relevance of FD diagnosis in an at-risk group of patients with acute ischemic stroke, to analyse the cerebrovascular phenotype of patients with FD using ultrasound, and to identify predictors of significant cerebrovascular involvement. In this thesis we showed a relatively high prevalence of FD in adult patients with acute stroke, proposed to reclassify the G325S variant, and identified a novel R30K variant. We noted that the combination of aseptic meningitis with lacunar stroke in a young person should lead to suspicion of FD. We further demonstrated multiple differences in neurosonological parameters between patients with FD and a...
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The elucidation of the causes of neurogenetic diseases by the MPS data analysis using advanced algorithms
Staněk, David ; Laššuthová, Petra (advisor) ; Halbhuber, Zbyněk (referee) ; Kemlink, David (referee)
8 Summary The thesis "The elucidation of the causes of neurogenetic diseases by the MPS data analysis using advanced algorithms" is focused on processing the massively parallel sequencing (MPS) data from a gene panel, whole-exome sequencing (WES) and whole-genome sequencing (WGS). The aim of the study was to develop a suitable pipeline to evaluate at least 250 MPS gene panel data, 150 WES data and 20 WGS data in order to improve molecular genetic testing of rare neurogenetic disorders. Associated data management and database implementation is also described. Targeted gene panel sequencing A custom-designed gene panel consisting of ge- nes previously associated with the disease was used. In the Epileptic Encephalopathy (EE) panel, two prerequisites need to be met for inclusion into the panel: the gene has to have been published in at least two independent publications OR at least in one publication but in multiple independent families. In the case of the EE panel, 112 genes were included. The targeted gene panel sequencing was then performed on 257 patients with EE. Pathogenic or likely pathogenic (according to ACMG criteria) variants have been found in 28% of patients (72 out of 257). Further analysis of the pathogenic or likely pathogenic variants was performed (76 in total); the variants were grouped by...
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Ischemic strokes in vertebrobasilar region, caused by lesions of magistral arteries
Škoda, Ondřej ; Kalvach, Pavel (advisor) ; Šonka, Karel (referee) ; Kemlink, David (referee)
Vertebrobasilar ischemic strokes, caused by lesions of magistral arteries. Background and Purpose Progress in modern non-invasive or minimally invasive diagnostic methods has improved detection and evaluation of pathological changes in the vertebral arterial system. Ischemia in vertebrobasilar circulation, often caused by stenotic processes of vertebral arteries, is considered a severe form of stroke, with a mortality of 20 - 30%. Stenoses of these arteries may be responsible for up to one half of ischemic events in their nutritive region. Although there is no general consensus on treatment of the VA stenoses so far, recent recommendations consider interventions in secondary stroke prevention, when optimal conservative treatment did not prevent recurrent clinical symptoms. With the increasing number of centers providing diagnostics and possible interventional treatment, the objective assessment of these lesions should be available. However, due to a relatively small part of patients, who are indicated to vertebral angioplasty, the diagnostic procedures should be as noninvasive and safe, as possible. The aim of this study was to create the accurate, noninvasive an safe diagnostic algorithm for the detection and evaluation of the VA stenoses and to test its reliability on our own patients group....
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Genetic and clinical aspects of the restless legs syndrome
Pavlíčková, Jana ; Kemlink, David (advisor) ; Seeman, Pavel (referee) ; Martásek, Pavel (referee)
Introduction: The Restless Legs Syndrome (RLS) is a frequent neurological disorder with a prevalence ranging from 5 - 10%. RLS is characterized by an urge to move the lower extremities during the night, thus RLS causes sleep disturbance. It presents as both idiopathic and secondary form. Idiopathic RLS is associated with common genetic variants in MEIS1, BTBD9, PTPRD and MAP2K5/SCOR1. Recently, multiple sclerosis (MS) was identified as a common cause for secondary RLS, the prevalence of RLS in patients with MS ranges from 13.3 to 37.5%. The aim of our study was to analyse the clinical and genetic aspects of this disorder, especially in patients with multiple sclerosis. In the clinical part, we evaluated the prevalence of RLS among Czech patients with MS and we compared the extent of brain damage between patients with and without RLS using magnetic resonance imaging (MRI). In the genetic part, we further analysed the impact of known genetic variants (MEIS1, BTBD9, MAP2K5/SCOR1, PTPRD) for RLS in other European populations and in patients with MS. Methods: Clinical part: Each patient with MS underwent a semi-structured interview. A patient was considered to be affected by RLS if he/she met all four standard criteria at life- long interval. Lesion load (LL - T2), brain atrophy - T1 and brain...
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Study of polymorphisms in candidate genes in the population of ADHD children
Kopečková, Marta ; Goetz, Petr (advisor) ; Šantavý, Jiří (referee) ; Kemlink, David (referee) ; Zvolský, Petr (referee)
The research of tbc way of participatioo of each Iransmitte ystem in pathology of ADHD cao be of belp. in tbe future, in tbe seleetion of the approprisle drug ss substances witb different mechanisms of functioniog are used to Ireat UlC byperklnctic syndrome. For our resear h the genes of dopominergic (DR02, DRD3 a DATl ). noradrenergic (OBH) and serotoninergic (5-HTT) systems were selected. ln these geoes I1 polymorphisms were analysed by molecular-genetic metbods based on sssociation slrategy "case-conlrol". Tbe presence of risk allcles was compared betweeo tbe sarople of 100 ADHD childreo BOd a coolrol group of 100 subjects, in whom tbc ADHD symptoms were excluded by Coooers' test. Tbc results of our research suggest tbc an association of thc gcnes witb ADI·ID. Specifically, after multiple testlng correction, sex correction, and power analysis, it could be coocJuded: I) tbe risk of ADHD is sigolficantJy lncreased in tbc presence oť one risk allele in genes DRD2 (7,5-fold), 5-HTT (2,7-fold) and DATl (l ,6-fold) 2) tbe risk of ADHD is significaotJy increased at homozygotes for risk alleles in genes DRD2 (54-fold), 5-HTT (6,7-fold) BOd DATl (6,6-fold) For polymorphisms G444A and Cl603T in DBH, which were detected by univariant analysis, baplotype artaIysis was performed and resultedln conclusion...
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Circadian system in peripheral clock in neurodegenerative disorder and affective disorder and their synchronization in constant light condition
Weissová, Kamila ; Kopřivová, Jana (advisor) ; Kemlink, David (referee) ; Svoboda, Jan (referee)
Summary: The circadian system plays an important role in human physiology and pathophysiology. It controls all processes that repeat in our body within a 24-hour period. It is a complex system that works from the behavioral level to the molecular level. This system is controlled from the central brain structure located in the hypothalamus, but its rhythmic manifestations can also be observed in almost any individual body cells. Disruption of this system in humans is often associated with the development of affective disorders or neurodegenerative diseases. The affective disorder has often been associated with a phase shift in some of the circadian driven outputs, as for example, rhythm in their physical activity. The patients with neurodegenerative disorders are seen to have circadian amplitude damping in a series of circadian rhythms. Therapeutic approaches which aim to stabilize and strengthen the circadian rhythms have also a positive long term effect on the course of these diseases. Interestingly, in the genetic studies of these diseases, a couple of specific polymorphisms have been identified in areas related to the molecular mechanism of the internal clock. In this thesis, I tried to look at the human circadian rhythms from several different angles. In the first part of this thesis I tried to identify...
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Effect of peroneal nerve functional electrical stimulation on gait in patients with stroke
Jeníček, Jakub ; Petr, Miroslav (advisor) ; Jeřábek, Jaroslav (referee) ; Kemlink, David (referee)
The Abstract The Title: Effect of Peroneal Nerve Functional Electrical Stimulation on Gait in Post-stroke Patients The Goal: The aim of this work was to compare two different ways of applying functional electrical stimulation of the peroneal nerve as to their impacts on the gait speed and performance and the spastic paresis of lower leg in adult patients suffering from chronic stages of stroke accompanied by foot drop. The Method: An open, randomized, controlled clinical pilot study combining elements of both controlled and pragmatic experiments in comparing two different clinical approaches to peroneal nerve functional electrical stimulation. With the first group of patients (group A, consisting of 14 subjects), the intervention was carried out as an outpatient, strictly controlled and intense training of gait with electrical stimulation over the period of four weeks, five times a week; the B-group patients (13 subjects) were all provided with their own stimulator which they applied continuously throughout all their daily routines at their homes and community over the equal period of time. The Results: The four-week intervention turned out to cause no statistically significant difference in our two groups in terms of its impact on any of the monitored parameters of the gait speed and performance as well as...
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Ischemic strokes in vertebrobasilar region, caused by lesions of magistral arteries
Škoda, Ondřej ; Kalvach, Pavel (advisor) ; Šonka, Karel (referee) ; Kemlink, David (referee)
Vertebrobasilar ischemic strokes, caused by lesions of magistral arteries. Background and Purpose Progress in modern non-invasive or minimally invasive diagnostic methods has improved detection and evaluation of pathological changes in the vertebral arterial system. Ischemia in vertebrobasilar circulation, often caused by stenotic processes of vertebral arteries, is considered a severe form of stroke, with a mortality of 20 - 30%. Stenoses of these arteries may be responsible for up to one half of ischemic events in their nutritive region. Although there is no general consensus on treatment of the VA stenoses so far, recent recommendations consider interventions in secondary stroke prevention, when optimal conservative treatment did not prevent recurrent clinical symptoms. With the increasing number of centers providing diagnostics and possible interventional treatment, the objective assessment of these lesions should be available. However, due to a relatively small part of patients, who are indicated to vertebral angioplasty, the diagnostic procedures should be as noninvasive and safe, as possible. The aim of this study was to create the accurate, noninvasive an safe diagnostic algorithm for the detection and evaluation of the VA stenoses and to test its reliability on our own patients group....
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