|
|
Genotype and fenotype characterization in patients with ALS and ALS-FTD in Czech and Slovak Republic
Navrátilová, Nela ; Šlachtová, Lenka (advisor) ; Šípek, Antonín (referee)
Amyotrophic lateral sclerosis (ALS) is a rare and fatal neurodegenerative disease characterized by the degeneration of upper and lower motor neurons in the brain and spinal cord. It manifests itself with gradual muscle weakness and atrophy, and patients commonly succumb to respiratory failure within 2-4 years of disease onset. Frontotemporal dementia (FTD) is one of the three most prevalent early-onset dementias, characterized by the degeneration of frontal and temporal brain lobes leading to progressive deterioration of cognitive functions, behavior, and language abilities. These two clinical entities intersect within the ALS-FTD spectrum, histopathologically characterized by the presence of hyperphosphorylated TDP-43 and other proteinopathies. The aim of this thesis was to characterize the demographic and genetic background, phenotypic manifestations of ALS and ALS-FTD, and the potential occurrence of other neurodegenerative diseases in the family history of ALS patients. The demographic profile and analysis of phenotypic manifestations were conducted based on patient clinical records and questionnaire surveys. A total of 184 patients were examined, 146 were genetically analyzed, and 78 questionnaires were processed. Regarding the genetic background characterization, the study focused on...
|
|
|
Case Study of a Physiotherapy Treatment of a Patient with Amyotrophic Lateral Sclerosis
Pešková, Laura ; Novotná, Irena (advisor) ; Hamouzová, Dita (referee)
v Abstract Author: Laura Pešková Supervisor: Mgr. Irena Novotná Title: Case study of a physiotherapy treatment of a patient with amyotrophic lateral sclerosis Objectives: The aim of this bachelor thesis is to summarize the theoretical knowledge about the diagnosis of amyotrophic lateral sclerosis, about the possibilities of therapy and to elaborate a case study of physiotherapy treatment of a patient with this diagnosis. Methods: The thesis is divided into two parts - a general part and a special part. The general part is focused on the summary of theoretical knowledge about amyotrophic lateral sclerosis. This part includes chapters of neuroanatomy, general characteristics and clinical picture of the disease, possibilities of diagnostic and therapeutic procedures. The special part includes initial kinesiological examination, design of short-term and long-term physiotherapy plan, description of therapeutic units, output kinesiological examination and evaluation of the effect of therapy. Results: Positive outcomes of the physiotherapy intervention include increased range of motion, improved gait stability and training in independent verticalization. The therapy failed to affect muscle tone and spasticity. All results of the work are presented in the chapter on the effect of therapy. Conclusion: The above case...
|
|
|
Study of mechanisms influencing inflammatory and neurodegenerative processes and their subsequent treatment in ALS and spinal cord injury
Vargová, Ingrid ; Jendelová, Pavla (advisor) ; Jiruška, Přemysl (referee) ; Balaštík, Martin (referee)
Study of mechanisms influencing inflammatory and neurodegenerative processes and their subsequent treatment in models of ALS and spinal cord injury The mechanisms of neurodegeneration during spinal cord injury (SCI) and amyotrophic lateral sclerosis (ALS) are complex and poorly understood, which is why it's troublesome to counteract them with effective therapies. This thesis explores the pathways of autophagy, endoplasmic reticulum (ER) stress, and the mammalian target of rapamycin (mTOR) pathway that regulates these mechanisms in models of both SCI and ALS. Upregulation of autophagy and the mTOR pathway in an in vivo contusion SCI injury model was confirmed. The mTOR inhibition led to upregulation of autophagy, reduction of inflammation, and recovery in acute SCI. Upregulated autophagy was discovered in the SOD1G93A rat model of ALS. By treating the ALS rats with human mesenchymal stem cells, prolonged survival of the animals and preservation of motor neurons (MNs) possibly occurred through modulation of autophagy. The involvement of the mTOR pathway in the degeneration of MNs was further explored in the context of astrocytes. Pleckstrin homology like domain family A member 3 (PHLDA3), a newly discovered repressor of the mTOR pathway, was found to lead to ER stress if overexpressed in astrocytes...
|
|
|
Huntington's disease modeling and stem cell therapy in spinal cord disorders and injury
Hruška-Plocháň, Marián ; Motlík, Jan (advisor) ; Bjarkam, Carsten (referee) ; Roth, Jan (referee)
Neurological disorders affect more than 14% of the population worldwide and together with traumatic brain and spinal cord injuries represent major health, public and economic burden of the society. Incidence of inherited and idiopathic neurodegenerative disorders and acute CNS injuries is growing globally while neuroscience society is being challenged by numerous unanswered questions. Therefore, research of the CNS disorders is essential. Since animal models of the CNS diseases and injuries represent the key step in the conversion of the basic research to the clinics, we focused our work on generation of new animal models and on their use in pre-clinical research. We generated and characterized transgenic minipig model of Huntington's disease (HD) which represents the only successful establishment of a transgenic model of HD in minipig which should be valuable for testing of long term safety of HD therapeutics. Next, we crossed the well characterized R6/2 mouse HD model with the gad mouse model which lacks the expression of UCHL1 which led to results that support the theory of "protective" role of mutant huntingtin aggregates and suggest that UCHL1 function(s) may be affected in HD disturbing certain branches of Ubiquitin Proteasome System. Traumatic spinal cord injury and Amyotrophic Lateral...
|
|
|
Physiotherapy in patients with amyotrophic lateral sclerosis
Dobešová, Petra ; Šebek, Milan (advisor) ; Šebková, Natálie (referee)
BACHELOR THESIS ABSTRACT Title: Physiotherapy in patients with amyotrophic lateral sclerosis Abstract: This bachelor thesis is consisting of a theoretical part and a practical part. The theoretical part is consisting of the basics of neuroanatomy needed to understand the disease, pathophysiology of amyotrophic lateral sclerosis (ALS) and clarify the term motor neuron disease. Then is the ALS described in more details, talks about its history, epidemiology, aetiology, diagnosis, clinical manifestation, classification, treatment and palliative care in patients with ALS. In terms of physiotherapy is first described the course of physiotherapy in the 6 stages of ALS. Subsequently, specific physiotherapeutic techniques are described, which are used in therapy with a justification of what we can influence with their help. The described techniques are respiratory physiotherapy, active exercise, dynamic neuromuscular stabilization, passive exercise and the possibility of influencing pain through physiotherapy. The practical part is consisting of an information brochure for patients with ALS in the 1st and 2nd stage of the disease and a case report of a patient in the late phase of ALS. The brochure is containing basic information about the disease and the possibilities of movement and exercise with the...
|
|
|
Occupational Therapy in Patients with Amyotrophic Lateral Sclerosis
Stříhavková, Jana ; Sýkorová, Jitka (advisor) ; Rejtarová, Anna (referee)
BACHELOR THESIS ABSTRACT Name, Surname: Jana Stříhavková Supervisor: Mgr. Bc. Jitka Sýkorová Title: Occupational Therapy in Pacient with Amyotrophic Lateral Sclerosis Abstract: Amyotrophic lateral sclerosis (ALS) is a progressive, neurodegenerative and untreatable illness, which causes slow weakening of muscles leading to their atrophy. Condition of the patient is slowly deteriorating and it can lead from lowering self-sufficiency to complete dependency on personal care. Terminal stage of this disease leads most commonly to insufficiency of breathing muscles causing death of patient. For patients suffering from ALS is complex rehabilitation care is extremely important. This bachelor thesis shows the important role of an occupational therapist during care for the patients with ALS. It describes possibilities of occupational therapy interventions and their differences considering, in which stage of the illness the patient is situated. This thesis is also specializing on the possibilities of using applicable assistive technologies and strategies in areas of activities of daily living, in a job or during leisure time activities. During the examination was used an evaluative scale ALSFRS-R, which evaluates functional condition of patients with ALS. Key words: amyotrophic lateral sclerosis, occupational therapy,...
|
|
|
Modelovanie ochorenia a štúdium regeneračných procesov v Huntingtonovej chorobe a ALS in vivo
Hruška-Plocháň, Marián
Neurological disorders affect more than 14% of the population worldwide and together with traumatic brain and spinal cord injuries represent major health, public and economic burden of the society. Incidence of inherited and idiopathic neurodegenerative disorders and acute CNS injuries is growing globally while neuroscience society is being challenged by numerous unanswered questions. Therefore, research of the CNS disorders is essential. Since animal models of the CNS diseases and injuries represent the key step in the conversion of the basic research to the clinics, we focused our work on generation of new animal models and on their use in pre-clinical research. We generated and characterized transgenic minipig model of Huntington's disease (HD) which represents the only successful establishment of a transgenic model of HD in minipig which should be valuable for testing of long term safety of HD therapeutics. Next, we crossed the well characterized R6/2 mouse HD model with the gad mouse model which lacks the expression of UCHL1 which led to results that support the theory of "protective" role of mutant huntingtin aggregates and suggest that UCHL1 function(s) may be affected in HD disturbing certain branches of Ubiquitin Proteasome System. Traumatic spinal cord injury and Amyotrophic Lateral...
|
|
|
Immunomodulatory properties of mesenchymal stem cells from patients with amyotrophic lateral sclerosis and healthy donors
Matějčková, Nicole
Mesenchymal stem cells (MSC) possess a multilineage differentiation potential and have the ability to regulate reactivity of the immune system. They are usually isolated and expanded from the bone marrow, adipose tissue or umbilical cord. MSC represent promising cell population for the treatment of some severe diseases, such as amyotrofic lateral sclerosis (ALS), due to the combination of regenerative and immunomodulatory properties. The aim of this study is to compare MSC from ALS patients and healthy donors in their phenotype, proliferative activity and mainly their immunomodulatory properties. The assessment of impact of the disease on the properties of MSC is important for their autologous use in clinical trials. In this study we used MSC isolated from bone marrow of 14 ALS patients and 15 patients undergoing mostly orthopedic surgery as control group. We also used MSC stimulated for 24 hours by poinflammatory cytokines. Cells were compared in terms of immunophenotype, differentiation in adipocytes and osteoblasts, metabolic activity, expression of selected genes for immunomodulatory molecules and for inhibition of lymphocyte proliferation. Further experiments were focused on evaluation of immunomodulatory properties of MSC. The effect of MSC on peripheral blood mononuclear cells stimulated...
|
|
|
Mmultidisciplinary care with the focus on speech and swallowing disorders provided to patients with amyotrophic lateral sclerosis
Černá, Adéla ; Klenková, Jiřina (advisor) ; Horynová, Jana (referee)
The diploma thesis is focused on the issue of acquired dysarthric and swallowing disorders in amyotrophic lateral sclerosis and on multidisciplinary care provided to patients with this disease. Theoretical part of the thesis is divided into three chapters. The introductory chapter presents a summary of current knowledge about amyotrophic lateral sclerosis (ALS). The following two chapters are dedicated to dysarthria and dysphagia and their specifics in ALS. The practical part of the diploma thesis is represented by the fourth chapter which incorporates a research survey focused on multidisciplinary care provided to patients with ALS. The primary aim of the research is to evaluate the multidisciplinary care provided to two selected patients with ALS with a focus on speech and swallowing disorders. The secondary objectives of the research relate to the evaluation of the extent of acquired dysarthric and swallowing disorders of these patients, providing a comprehensive overview of the course and content of the provided care and gathering information to create information brochure for patients with ALS and caregivers. The research approach to achieve the determined objectives of the research survey is creation of case studies using qualitative methods of data collection, which is a structured interview...
|
|
|
Identification of changes in membrane properties of astrocytes in a mouse model of amyotrophic lateral sclerosis
Vaňátko, Ondřej ; Turečková, Jana (advisor) ; Vlachová, Viktorie (referee)
Amyotrophic lateral sclerosis (ALS) is a progressive neurological disorder of the central nervous system characterized by loss of motor neurons and voluntary muscle degeneration. Astrocytes play a major role in regulation of the disease onset and progression due to their intimate association with neurons. Regulation of ionic homeostasis is one of their key functions and its failure has been linked to several neurological diseases. The aim of this thesis was to explore differences in membrane properties of astrocytes in ALS. To fulfill this aim, a double transgenic mouse strain with ALS-like phenotype and a specific expression of enhanced green fluorescent protein in astrocytes was generated. To phenotype this strain, two sensorimotor tests, wire grid hang test and rotarod test, were conducted. Immunohistochemistry was used to characterize the strain on a cellular level and to explore changes of specific ion channels. Functional properties of astrocytes were explored using the patch clamp technique. The double transgenic strain has the characteristic ALS-like phenotype and is comparable to the original strain with differences in symptom onset and progression between models and sexes. On the cellular level, there are characteristic ALS features, specifically loss of motor neurons and astrogliosis....
|
guest ::
