Brain functional and structural characteristics of patients with seizure recurrence following drug withdrawal

We aimed to analyze the characteristics of brain function and microstructure linked to epilepsy relapse after drug withdrawal in patients with focal epilepsy.

Resting-state functional magnetic resonance imaging and high-resolution T1-weighted images were acquired within 1 month prior to drug withdrawal from 15 patients who did not have epilepsy relapse (PER - group) and 16 patients who subsequently had epilepsy relapse (PER + group). Additionally, 23 healthy participants undergoing the same scanning protocol were included as controls. Fractional amplitude of low-frequency fluctuation (fALFF) and gray matter density (GMD) were compared among groups. Subgroup and correlation analyses were also performed.

There were no significant differences in fALFF between patient groups, but the PER + group showed lower GMD in the bilateral calcarine, left precuneus, and right superior temporal gyrus than the PER - group (Gaussian random field correction, voxel-level P < 0.001 and cluster-level P < 0.05). Both increased seizure number and polytherapy were associated with lower GMD; also, patients using other antiseizure medications showed lower GMD than those using only levetiracetam (Gaussian random field correction, voxel-level P < 0.001, and cluster-level P < 0.05). The active period and disease duration showed both positive and negative correlations with GMD, while the seizure-free period mainly showed positive correlations with GMD (uncorrected, P < 0.001).

Gray matter microstructure, but not local functional activity, showed distinct characteristics between patients with and without epilepsy relapse and may serve as a potential biomarker for predicting seizure recurrence upon drug withdrawal.