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Thesis Format

Monograph

Degree

Master of Science

Program

Neuroscience

Supervisor

Khan, Ali

2nd Supervisor

Mirsattari, Seyed

Co-Supervisor

Abstract

Accurate epilepsy diagnosis after a First-Time Unprovoked Seizure (FTUS) remains challenging as the epileptogenic abnormalities and epileptiform EEG abnormalities used for such diagnoses infrequently occur and are often missed or misinterpreted. Expanding the scope of diagnostic abnormalities to include cortical thickness changes could enhance diagnostic efficacy. This is because cortical thickness changes are a significantly prevalent pathophysiological change that occurs in cases of epilepsy progressively, independent of seizure frequency, drug load and age. These changes are theorised to be a product of epileptogenesis, the process in which brain networks undergo disruptions becoming epileptic. This study aims to investigate whether these changes can be used for epilepsy diagnosis by determining if epileptogenic brain network changes and cortical thickness changes are present as early as the FTUS of epilepsy. In this study, 16 healthy controls and 16 FTUS patients were recruited and underwent 7T structural Magnetic Resonance Imaging (MRI) scans; of the 16 FTUS patients, six were confirmed to be epileptic (CE). The participants' MRI scans were parcellated using the 17-network Schaefer 200 and 100 parcellation maps. Within these maps, the average cortical thicknesses per region were measured for each participant group and used for between-group comparisons. These comparisons contrasted the cortical thicknesses of the FTUS patients with their age- and sex-matched healthy controls (HC) and the cortical thicknesses of solely the CE patients with their age- and sex-matched HC. Each between-group comparison included both mixed-sex and sex-based comparisons. The cortical thickness measures were used for structural covariance analysis, with the calculated nodal and global measures undergoing the same set of between-group comparisons conducted for the cortical thickness measures. No statistically significant differences in cortical thickness were observed in any of the comparisons. At both parcellation levels, the CE patients displayed sex-dependent statistically significant differences in their structural covariance nodal measures. These differences indicate that brain network changes are present as early as the FTUS and support the theory that the cortical thickness changes observed in people with epilepsy are a byproduct of the network disruptions observed in epilepsy. Indicating that cortical thickness changes are not an ideal diagnostic symptom for epilepsy.

Summary for Lay Audience

When an individual experiences a seizure for the first time in their life, there is no guarantee that the seizure occurred due to epilepsy. As a result, individuals who have experienced a seizure undergo a series of medical exams and neuroimaging scans to determine if such seizures are due to epilepsy. However, accurate and prompt epilepsy diagnosis is still an ongoing issue as the current definitive indicators of epilepsy are not universal; as such, there is a need for additional epilepsy indicators that can be noticed as early as the first-time unprovoked seizure (FTUS). One such indicator could be cortical thickness changes, as past research on people with epilepsy (PWE) has shown it to occur progressively in PWE regardless of age and seizure frequency. This research study aims to investigate whether cortical thickness changes can be used as an observable epilepsy symptom for diagnosis by evaluating the cortical thicknesses of individuals who have experienced a first-time seizure. Additional research looking into the brain networks of the participants will be conducted as past research has indicated that the cortical thickness changes occurring in PWE are a product of brain network changes. The cortical thicknesses of individuals who have experienced a first-time seizure were measured via 7T MRI scans, the strongest human MRI scan available, and compared with healthy participants of the same age and sex as the patients. These comparisons were conducted once for all of the FTUS patients and then once again for the FTUS patients who were confirmed to have epilepsy. These cortical thickness measures were then used for structural covariance analysis, which uses the biological phenomenon of brain morphological features, like cortical thickness, reflecting brain networks to quantify and evaluate brain networks. This study's results indicated no cortical thickness changes could be detected at the FTUS stage. Still, the data did suggest that there were observable brain network changes in the FTUS patients who were confirmed to have epilepsy.

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