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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

ZEBRAFISH ASD DISCOVERY MODELS FOR EPILEPTIC MUTATIONS OF SCN2A AND SCN8A

Patrick Clement Milder (14216051), James A. Marrs (3074658) 03 February 2023 (has links)
<p>  </p> <p>Approximately 30% of patients with epilepsy do not achieve adequate seizure control through current anti-seizure drugs (ASD) and treatment methods. Therefore, a critical need exists to efficiently screen ASDs to enhance our ability to tailor treatment protocols and improve patient outcomes. The zebrafish pentylenetetrazol (PTZ) seizure model has become an increasingly popular screening paradigm for novel ASDs. Here, we present an optimized PTZ assay to improve reliability and reproducibility based on work in our laboratory. This optimized assay improves robustness in our screening of anti-seizure drugs (topiramate, lamotrigine, carbamazepine and GS967). These findings show that electroencephalogram (EEG) and calcium sensitive GFP from fusion protein (GCaMP) assays largely correlate with the behavioral findings, helping us connect physiological and behavioral responses to ASDs. Genetic epilepsy syndromes, like voltage gated sodium channel <em>SCN2A</em> and <em>SCN8A</em> pathogenic variants, are often poorly controlled by current medications. Our optimized assay relied on a fast and precise zebrafish seizure model using mRNA overexpression of h<em>SCN2A</em> and h<em>SCN8A</em> variants including: hSCN2A R1882Q and R853Q and hSCN8A R1872Q. All three pathogenic variants increased seizure activity, and the ASDs significantly decreased this seizure activity. This mRNA overexpression assay can be used to quickly evaluate seizure activity induced by pathogenic variants in voltage gated sodium channel genes and test ASDs to determine efficacy. In a separate study, we tested if the addition of the human <em>SCN2A </em>sodium channel could potentially rescue the loss of the zebrafish scn1Lab gene. Our GCaMP assay data indicates that this loss was successfully rescued. Cumulatively, these findings can be used to improve the screening of novel ASDs and treatments for patients with refractory epilepsy.</p>
2

Outcomes of Status Epilepticus in the Elderly

Towne, Alan R. 01 January 2007 (has links)
Background: Status epilepticus (SE) is a serious medical condition associated with significant morbidity and mortality. Few studies have addressed this condition in the elderly. The present study examines predictors of SE mortality in this growing population.Methods: SE patients visiting the Virginia Commonwealth University Medical Center from July 1, 1989, to June 30,2006 were included in the study. Data on demographic characteristics, SE type, etiology, time to treatment and mortality were collected. Logistic regression analysis was conducted to examine the determinants of mortality due to SE. Data was stratified by age to examine the characteristics of SE among the elderly population.Results: A total of 2,220 SE patients were included in this study. One-third of the patient population were elderly (>60 years). Mortality in the elderly group was significantly higher than in the young group (OR=3.54 CI 2.53-4.95). The logistic regression model showed that being white, female, having hypoxia, CNS acute, non-CNS acute and remote etiology groups were significant predictors for mortality in the elderly.Conclusions: SE is a serious medical condition, consisting of prolonged seizure activity, associated with a significant mortality. Elderly patients with SE represent a distinct population with unique characteristics.

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