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

Abstract

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.

Keywords: neuroimaging; neuropsychology; newly diagnosed focal epilepsy.

FIGURE 1

Patient outcome over time. The proportion of patients with NDFE that have persistent seizures (PS) and those that are seizure‐free (SF) for 0 (time of testing), 6‐, 12‐, 18‐, and 24‐month follow‐ups (left). Individual‐level outcomes over time (right). Gray indicates data missing or not yet acquired. NA, data not yet available.

FIGURE 2

Exemplar MRI‐positive cases across the three lesional categories. Known relevance to epilepsy: Nodular heterotopia of the left supra‐trigonal periventricular region (left) and arachnoid cyst overlying anterior aspect of the right sylvian fissure, abutting the inferior frontal gyrus superiorly and the temporal pole inferiorly (right). Unknown relevance to epilepsy: Multiple focal white matter hypointensities (T1w) and hyperintensities (T2‐FLAIR) (left) and amygdala asymmetry (right; note additional ventricular asymmetry). Incidental: Asymmetric lateral ventricles, including frontal and temporal horns (left) and pineal cyst (right).

FIGURE 3

Quantitative MRI and neuropsychological differences between patients and controls. (A) MRI brain morphometrics. Differences displayed as Cohen's d in regional cortical thickness (top) and subcortical volumes (bottom) in patients with NDFE compared to healthy controls. Blue indicates larger values in controls, red indicates larger values in patients. (B) Neuropsychology radar plot indicating the percentage of patients with NDFE with z‐scores greater than 2 SD for each neuropsychological feature (blue) compared to healthy controls (black) (top left). Optimal number of clusters using the Elbow method and within‐cluster sum of squares (WCSS) and cluster overlap using PCA (bottom left). Patient Profiles 1–4 of neuropsychological z‐scores (right).