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Title: The effects of genes, antiepileptic drugs and risk of death on functional anatomy and cognitive networks in epilepsy
Author: Wandschneider, B.
ISNI:       0000 0004 7429 0223
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2016
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Epilepsy is one of the most common neurological disorders. Apart from seizures, patients are also affected by epilepsy comorbidities, such as cognitive impairment, side effects of antiepileptic drugs, and an increased risk of dying from sudden death. Within epilepsy research, recent efforts have been made to identify reliable biomarkers to advance the understanding of disease-mechanisms, to individualize and optimize treatment and side-effect profiles and to enhance prediction of treatment success and disease progression. Biomarkers are objective measures of a normal or pathological biological process and, in the context of this PhD, neuroimaging biomarkers ideally enable in vivo measurements of (i) disease activity, (ii) treatment effects and (iii) risk of comorbidities and mortality. Employing functional and structural neuroimaging techniques, we studied potential neuroimaging biomarkers in three different domains of epilepsy. In the first project, we explored fMRI endophenotypes in a prototype of a genetic generalised epilepsy syndrome, namely juvenile myoclonic epilepsy (JME). Endophenotypes are heritable traits, closer related to the genotype than the final phenotype and are found frequently in non-affected family members of patients. Our study revealed potential functional endophenotypes and support a genetically determined neurodevelopmental disease mechanism in JME. The second project investigated fMRI markers of antiepileptic drug effects on cognitive networks in patients with refractory epilepsy. In two retrospective studies employing fMRI cognitive tasks, we isolated task- and medication-specific effects on working memory and language networks for Levetiracetam (study 1) and Topiramate and Zonisamide (study 2). In the third project, we employed Voxel-Based-Morphometry in a retrospective analysis of structural imaging of patients who had died of sudden unexpected death in epilepsy (SUDEP) or were at high or low risk of SUDEP. We identified structural markers of high SUDEP risk, and discussed that these were at least partially specific, i.e. independent of disease progression and load.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available