Abstracts

Rationale: Focal to bilateral tonic-clonic seizures (FBTCS) is one of the severest forms of epilepsy that is associated with a higher risk of epilepsy-related injury, sudden unexpected death in epilepsy, and unfavorable prognosis after epilepsy surgery. This study aims to establish a link between metabolic phenotypes and transcriptional signatures in patients with temporal lobe epilepsy (TLE), aiming to enhance our comprehension of the mechanisms underlying potential epileptic discharge propagation and biological changes in TLE-FBTCS.

Methods: The study included three cohorts. The 2-[¹⁸F]-fluoro-2-deoxy-D-glucose ([¹⁸F]FDG) positron emission tomography (PET) cohort comprised 128 TLE patients treated at Xiangya Hospital, followed for at least one year after surgery. The transcriptome dataset consisted of hippocampal dentate gyrus tissue samples from six TLE patients who underwent standard anterior temporal lobectomy at the Department of Neurosurgery in Xiangya Hospital and a publically available transcriptomic dataset. Metabolic factors and corresponding loading coefficients for each participant were evaluated using non-negative matrix factorization applied to [¹⁸F]FDG PET images. The association between metabolic factors and TLE-related gene expression was modeled using partial least squares regression (PLS), and cell-type enrichment of PLS-derived genes was performed using Cell-type Specific Expression Analysis.

Results: This study included 85 TLE-FBTCS patients, 43 TLE patients with focal seizures (FS), and 80 healthy controls. TLE-FBTCS patients showed overloading of metabolic factors characterized by hypometabolism in the ipsilateral hippocampus and temporal lobe, and hypermetabolism in the bilateral cerebellum and thalamus. Metabolic factors were significantly correlated with the linear combination of TLE-related gene expression (R₂₇₂=0.559, P_permutation< 0.0001; R₂₇₂=0.883, P_permutation< 0.0001), and cerebellum weighted most in the PLS component. PLS-derived genes were significantly enriched in cerebellar astrocytes (P_FDR< 0.01).