Prospective neuroimaging and neuropsychological evaluation in adults with newly diagnosed focal epilepsy.

Objective: Few prospective studies exist on newly diagnosed focal epilepsy (NDFE), a critical period for understanding epilepsy's biology and identifying biomarkers and potential interventions. We report a prospective cohort study in patients with NDFE and age-, sex-, and education-matched healthy controls.

Methods: We recruited 104 patients with NDFE and 45 controls for research-grade 3 Tesla multi-modal magnetic resonance imaging (MRI), electroencephalography (EEG), comprehensive neuropsychological testing, and blood biomarker investigations. Baseline clinical, neuroradiological, MRI morphometric, and neuropsychological findings are reported in this article.

Results: Following neuroradiological reporting, MRI was unremarkable in 38% of patients, showed lesions associated with epilepsy in 12%, abnormalities of unknown significance in 49%, and incidental findings in 23%. For controls, these figures were 56%, 7%, 33%, and 16%, respectively. Patients had more white matter hyperintensities, classified as abnormalities of unknown significance, than controls. Reduced bihemispheric frontal lobe cortical thickness and thalamic volumes with moderate effect sizes were observed in patients. Compared to controls, patients scored lower on executive function, processing speed, and visual, delayed, and immediate memory tasks, and higher on depression and anxiety assessments. Cluster analysis identified four distinct patient cognitive profiles, two of which were associated with high levels of anxiety and depression and lower executive function and memory scores.

Significance: Adults with focal NDFE have more MRI-positive findings than previously reported. Subtle white matter lesions may have clinical significance and a pathophysiological basis in focal epilepsy. Morphometric and neuropsychological changes at epilepsy diagnosis suggest that brain and cognitive alterations are not solely due to chronic epilepsy.