| Sumario: | Purpose: We aimed to analyze the characteristics of brain function and microstructure linked to epilepsy relapse after drug withdrawal in patients with focal epilepsy. Methods: 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. Results: 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). Conclusion: 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.
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