A Prospective Advanced Magnetic Resonance Imaging Study of Newly Diagnosed Epilepsy

Abstract

According to the World Health Organization (WHO), approximately 50 million people in the world have active epilepsy. Epilepsy is the most common neurological disorder after migraine, stroke and Alzheimer’s disease. Epilepsy disorder affects men and women of all ages, races and social classes. There is an extensive neuroimaging literature describing patients with chronic epilepsy. However, few studies have investigated brain structural changes in patients with newly diagnosed epilepsy (NDE) using quantitative magnetic resonance imaging (MRI). The main goal of this thesis was to determine the nature and extent of brain structural and functional differences in patients with NDE using different MRI techniques compared with healthy controls. The first study was to determine the morphometric changes in patients with NDE compared to healthy controls using quantitative MRI analysis. The second study was to identify functional connectivity differences (in the whole brain and regions of interest) in patients with NDE and healthy controls using resting state functional magnetic resonance imaging (RS-fMRI). All study participants were recruited from the Walton Centre NHS Foundation Trust, Liverpool. All had been diagnosed with focal epilepsy by a consultant neurologist and recruited for MRI scanning within 12 months of diagnosis. Twenty-seven patients with NDE were recruited (14 male, 13 female, with mean age (M)=33.2) and 32 healthy matched controls (14 male, 18 female, M=33.07).Control and NDE study participants were matched for age, handedness and gender. All participants were scanned using a Siemens 3T Trio whole-body scanner (Siemens, Erlangen, Germany) with eight-channel radiofrequency (RF) head coil together with foam padding to comfortably restrict head motion at the Magnetic Resonance and Image Analysis Research Centre (MARIARC), University of Liverpool. Various MRI sequences were conducted including: 3D MPRAGE T1-weighted anatomical data, and RS-fMRI In the first study, shape, surface based, and voxel based morphometry analysis were applied, and the results suggested differences to the morphology of the brain stem and both the right and left thalami in patients with NDE. The independent component analysis of RS-fMRI showed abnormal different functional connectivity in visual and attention networks in patients with NDE relative to healthy controls while ROI-ROI demonstrated increased functional connectivity between the subcallosal cortex and both thalami in NDE patients. This is the first extensive programme of research to employ various analysis techniques and advanced MRI sequences to study structural and functional differences in patients with NDE compared to healthy controls. The results of this thesis show that structural and functional differences occur in both thalami in patients with NDE. These findings suggest that the thalamus plays a very important role in epilepsy pathophysiology. The results of this thesis offer further understanding regarding the role of structural and functional differences in NDE. They highlight the need for future quantitative MRI analysis studies of NDE to help patients avoid the chronic stage of the disorder and improve their quality of life.