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Translation potential of current preclinical techniques for gene therapy of neurological diseases in clinic. A critical review.
Žideková, Paulína ; Novák, Ondřej (advisor) ; Jendelová, Pavla (referee)
Research in the field of gene therapy has potential to become a revolutionary way to the existing treatment for a wide spectrum of neurological diseases. To treat these disorders causally, by specific substituting, deleting, silencing or editing faulty genes could be a privilege of gene therapy. The concept of translational medicine is to facilitate the transfer of working principles in preclinical research into treatment in humans. Its key issue is to overcome limitations associated with the gap between the tremendous variety molecular biology tools of preclinical research and the lack of simple corresponding options in humans. Clinical implementation of most of the preclinical approaches is still considered to be limited. The main focus of this thesis is to summarize latest advancements of molecular and genetic engineering tools that themselves or in combination have the potential to promote most preclinical gene therapy of neurological diseases to clinical use. Based on that, this study aims to suggest perspective methods of treatment for selected neurological diseases.
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The role of parvalbumin interneurons in seizure initiation, propagation and termination in a mouse model of focal cortical dysplasia of type II
Populová, Jana ; Řehořová, Monika (advisor) ; Kirdajová, Denisa (referee)
Focal cortical dysplasia is a structural and functional malformation of cortical development caused by mutations in mTOR signalling cascade that can result in pharmacoresistant epilepsy. Parvalbumin interneurons are probably the most important inhibition force in the brain that can help to stop epileptic seizures and it is possible that there are changes in function of these interneurons that are dependent on focal cortical dysplasia. This thesis had the aim to create a murine model of focal cortical dysplasia type II with labeled parvalbumin interneurons. This model was created by injecting plasmid with mutated mTOR gene during in utero electroporation. Cranial window implantation was then performed over created lesion together with calcium indicator injection for measuring neuronal activity under two-photon microscope. Our results confirm the same morphological characteristics as other studies has shown and also occurence of spontaneous seizures. We have shown statistically significant differences in size of pyramidal neurons depending on lesional or non-lesional position. For parvalbumin interneurons there was no such difference. Counting these two types of neurons in lesion and outside of lesion shown a trend towards reduced numbers in lesion, however it was not significant. Data from...
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Sleep dynamics analysis using electrophysiological features
Lampert, Frederik ; Janoušek, Oto (referee) ; Mívalt, Filip (advisor)
Táto práca sa zaoberá metódami detekcie spánku pomocou elektrofiziologických príznakov, bez dostupnosti anotácií v podobe hypnogramov. Vyhodnocovanie spánku pomocou polysomnografických (PSG) dát je časovo apersonálne náročný proces, ktorý sa odohráva zväčša vnemocničnom prostredí. Moderné implantabilné zariadenia schopné kontinuálneho snímania azdieľania dát otvárajú možnosť dlhodobého akontinuálneho monitorovania spánkovej aktivity upacientov snurologickými chorobami v domácom prostredí. Súčasné metódy na spánkovú detekciu využívajú intrakraniálne elektroencefalografické (iEEG) spánkové klasifikátory, ktoré sú tvorené a validované na štandardných polysomnografických dátach. Tie však nie sú vždy kdispozícii čo vedie kpotrebe vyvinutia metódy spánkového hodnotenia, ktorá by bola schopná analyzovať spánok pomocou elektrofyziologických príznakov aj bez dostupnosti anotácií v podobe hypnogramov ato obecne z malého počtu zvodov. Za týmto účelom bola navrhnutá metóda spánkového hodnotenia, ktorá vyhodnocuje spánok na základe výkonu elektroencefalografické (EEG) signálu v spektrálnej oblasti pomocou metrík zvaných Power in Band (PIB) metriky. V tejto práci bol analyzovaný výkon vdelta pásme (0,5-4 Hz), keďže EEG signál má vňom najvyššiu amplitúdu azároveň je jeho aktivita najviac výrazná počas N2 aN3 spánkových cyklov, ktoré sú najviac zastúpené vspánku počas noci, takže poskytujú najlepšiu informáciu orozložení spánku počas noci. Scieľom validácie PIB metrík boli taktiež predstavené štandardné metriky založené na hypnogramoch. Tieto metriky boli následne implementované do programovacieho prostredia Python a aplikované na dva voľne dostupné datasety, Dreem Open Dataset-Healthy (DOD-H) a Dreem Open Dataset-Obstructive (DOD-O) obsahujúce polysomnografické merania 25 zdravých jedincov (DOD-H dataset) a56 jedincov so syndrómom spánkového apnoe (OSA)(DOD-O dataset). Výsledky analýz boli vyhodnotené pomocou vizuálnej analýzy vo forme boxplotov, korelačných matíc a štatistických testov. Z výsledkov analýz vyplýva, že navrhnuté PIB metriky majú schopnosť rozlišovať medzi fyziologickým a patofyziologickým spánkom, avšak ich schopnosť rozlišovať niektoré aspekty spánku sa líši od štandardných metrík založených na hypnogramoch. Ztoho vyplýva, že PIB metriky nenahrádzajú štandardné metriky, ale skôr ponúkajú inú perspektívu na analýzu spánku.
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The classification of epileptogenic tissue after electrical stimulation using machine learning
Formánková, Zuzana ; Mívalt, Filip (referee) ; Cimbálník, Jan (advisor)
This thesis addresses electrophysiological biomarkers of epileptic activity after direct electrical stimulation in the classification of epileptogenic tissue. Suitable biomarkers included high-frequency oscillations, interictal spikes, changes in connectivity and signal power across frequency bands. Biomarkers were detected in iEEG recordings and their response to direct electrical stimulation was analyzed by statistical tests. Biomarker analysis demonstrated the effect of direct electrical stimulation on electrophysiological biomarkers of epileptic activity. Relevant biomarkers were selected by selection methods as signal power in the frequency band 80-250 Hz, relative entropy in the frequency band 250-600 Hz and linear correlation. Machine learning models, namely logistic regression, support vector machines and decision forest, were implemented for epileptogenic tissue classification. The support vector machines method showed the highest sensitivity (70,5 %) among the models, but the overall results were insufficient (PPV 38,5 %, F1 score 42,9 %). Despite the limitations in the performance of the classification models, this work highlights the potential of electrophysiological biomarkers in identifying epileptogenic foci and establishes a foundation for further research in the field.
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Optimizing neural network architecture for EEG processing using evolutionary algorithms
Pijáčková, Kristýna ; Maršálek, Roman (referee) ; Götthans, Tomáš (advisor)
Tato práce se zabývá optimalizací hyperparametrů neuronových sítí pro zpracování EEG signálu pomocí evolučních algoritmů. Využití evolučních optimalizace může snížit závislost na lidské intuici a empirických znalostech při návrhu neuronové sítě a může tak zefektivnit návrh neuronové sítě. V této práci byl navržen genetický algoritmus, který je vhodný pro optimalizaci hyperparametrů i pro hledání neuronové architektury. Tyto metody byly porovnány s referenčním modelem navrženým inženýrem s expertýzou v této oblasti. Data použitá v této práci jsou rozdělena do čtyř kategorií a pocházejí z Fakultní nemocnice svaté Anny v Brně (SAUH) a Mayo kliniky (MAYO) a obsahují iEEG záznamy u pacienta s epilepsií rezistentní na léky, který podstupuje předoperační vyšetření. Metoda hledání neuronové architektury dosáhla výsledků srovnatelných s referenčním modelem. Optimalizovaný model zlepšil F1 skóre oproti originálnímu, empiricky navrženému modelu z 0.9076 na 0.9673 pro data z SAUH a 0.9222 na 0.9400 pro data z Mayo kliniky. Ke zvýšenému skóre přispěla hlavně zvýšená přesnost klasifikace patologických událostí a šumu, která může mít dále pozitivní vliv v aplikacích tohoto modelu v detektoru záchvatů a šumu.
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The effect of selected cannabinoids on quantitative EEG, behaviour, and their therapeutic potential
Uttl, Libor
Cannabinoids and especially CBD are these days a highly discussed topic with a huge overlap in the media space. Their ability to interact not only with cannabinoid receptors, but also with other pathways, in combination with a huge "hype", leads, despite the not very strong evidence of their effects in clinical practice, to the testing of cannabinoids in a broad spectrum of indications. Nowadays, we have more than 150 isolated cannabinoids, but the research is focused only on the main cannabinoids like for example THC, CBD, cannabigerol, cannabichromen or hexahydrocannabinol. For our research, we have chosen the two most well- known cannabinoids THC and CBD, and our key question was not only what is the role of these cannabinoids individually, but, also, how do they interact when administered together, how do they influence behaviour and how do they interact in dependence on the method of administration. All these questions were addressed within our rat experiments. Somewhat surprisingly, we did not observe the typical cannabinoid tetrad (decreased sensitivity to painful stimuli, hypothermia, catalepsy, and overall decrease in motor activity) after the THC administration, so we wondered what would happen if we used more potent and selective synthetic cannabinoids JWH- 073, JWH-210, instead of THC....
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The effect of selected cannabinoids on quantitative EEG, behaviour, and their therapeutic potential
Uttl, Libor ; Páleníček, Tomáš (advisor) ; Šlamberová, Romana (referee) ; Šustková, Magdaléna (referee)
Cannabinoids and especially CBD are these days a highly discussed topic with a huge overlap in the media space. Their ability to interact not only with cannabinoid receptors, but also with other pathways, in combination with a huge "hype", leads, despite the not very strong evidence of their effects in clinical practice, to the testing of cannabinoids in a broad spectrum of indications. Nowadays, we have more than 150 isolated cannabinoids, but the research is focused only on the main cannabinoids like for example THC, CBD, cannabigerol, cannabichromen or hexahydrocannabinol. For our research, we have chosen the two most well- known cannabinoids THC and CBD, and our key question was not only what is the role of these cannabinoids individually, but, also, how do they interact when administered together, how do they influence behaviour and how do they interact in dependence on the method of administration. All these questions were addressed within our rat experiments. Somewhat surprisingly, we did not observe the typical cannabinoid tetrad (decreased sensitivity to painful stimuli, hypothermia, catalepsy, and overall decrease in motor activity) after the THC administration, so we wondered what would happen if we used more potent and selective synthetic cannabinoids JWH- 073, JWH-210, instead of THC....
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Influence of Religiosity on Quality of Life of patients with Epilepsy
Kolská, Marta ; Javůrková, Alena (advisor) ; Nikodemová, Hana (referee)
Objectives: The aim of this thesis is to investigate how the variables Locus of Control, God Locus of Health Control and religiosity predict the quality of life of patients with epilepsy and whether these variables differ in prevalence in a healthy control group. Methods: The research group consisted of 275 patients with epilepsy examined within the neuropsychological Centre for the Treatment of Epilepsy of the Department of Neurology, 2nd Medical Faculty and Motol University Hospital. The comparison group consisted of a group of 182 healthy respondents. Respondents were interviewed using WAIS-III, EPQ R abbreviated version, BDI-II, VAS, QOLIE-89 (version 1.0) and GLHC. The t-test and the Mann-Whitney test were used to determine differences between groups. Contingency tables were used for discrete quantities. The relationship between the variables was demonstrated by Spearman's correlation coefficient and multiple linear regression. The research was approved by the Ethics Committee of the Motol University Hospital. Results: The resulting model of stepwise linear regression prediction of the Mean score showed that by including the variables Neuroticism HS and GLHC˃6 in the overall model, these significant variables can explain 21.44 % variability of Locus of control (R2=0.2144). It was also found...
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Rehabilitation care for children with epilepsy in the Czech Republic and in the world
Chrásková, Anežka ; Carbajo, Anna (advisor) ; Nováková, Pavlína (referee)
The goal of this bachelor thesis is to summarize rehabilitation procedures for children with epilepsy used in the Czech Republic and worldwide. The first part focuses on the general characteristics of children epilepsy from the neurological point of view, its aetiology, patho- physiology, clinical manifestation, diagnosis and treatment specific for paediatric patients. The second part deals with rehabilitation care for children with epilepsy provided in our country and other countries. In the discussion, these rehabilitation procedures are compared and evaluated. Several chapters are devoted to physical activity and cognitive rehabilitation in relation to children epilepsy, which play an essential role in rehabilitation and their importance should not be underestimated. The practical part is a case study of a paediatric patient with epilepsy, in whom we observe the changes and the effect of rehabilitation after neurosurgical removal of the epileptiform lesion. We use the Barthel Index to assess the patient's self-sufficiency, the Gross Motor Fuction Measure (GMFM) to assess his motor function, and the Box and Block test and the Nine-Hole Peg Test (9HPT) to post-assess manual dexterity. The practical part also includes a questionnaire survey on rehabilitation care of paediatric patients with...
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Quality of life and pain in patient with epilepsy
Došlová, Dana ; Javůrková, Alena (advisor) ; Nikodemová, Hana (referee)
Bacground: The bachelor thesis deals with the subjective and objective evaluation of the relationship between pain and quality of life in patients with epilepsy based on the questionnaire survey Quality of Life in Epilepsy Inventory (QOLIE-89), Visual Analogue Scale (VAS). Objectives: The aim of this qualitative study is to assess the relationship between pain and quality of life in patients with epilepsy based on scoring in the scale Pain in the questionnaire QOLIE-89 and examination of pain intensity using VAS, validation of results in the examined patient sample, assessment of pain presence and intensity and others. cognitive, affective and functional variables depending on sociodemographic and clinical variables., determining whether pain is a variable that significantly predicts quality of life in patients with epilepsy. Early understanding of the relationship between pain and quality of life helps to set up appropriate nursing care and to ensure a better quality of life for patients with epilepsy. Methods: The study population comprised 150 patients from the Center for Epilepsy Treatment of the Neurological Department 2nd Medical Faculty Charles University and the Motol University Hospital, who met inclusive and exclusive criteria. All patients were examined neurologically and...
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