Alterations in the hippocampal-thalamic pathway underlying secondarily generalized tonic-clonic seizures in mesial temporal lobe epilepsy: A diffusion tensor imaging study

Objective The epileptogenic network underlying secondarily generalized tonic-clonic seizures (sGTCS) in mesial temporal lobe epilepsy (mTLE) is not well understood. Here, we investigated alterations in the probabilistic hippocampal-thalamic pathway (pHTP) underlying sGTCS using diffusion tensor imaging and resting-state functional magnetic resonance imaging in a cohort of TLE patients with hippocampal sclerosis (HS). Methods We consecutively recruited 51 unilateral TLE-HS patients (26 with and 25 without sGTCS) and 22 healthy controls. Probabilistic tractography was used to track the pHTP. Raw fractional anisotropy (FA) and mean diffusivity (MD) of the pHTP were corrected by the FA/MD of the hemispheric white matter on the same side. The volume of the thalamic subregion connected to the hippocampus (TSCH) was investigated. Fractional amplitude of low-frequency fluctuations of the hippocampus, the TSCH, and the thalamic subregion unconnected to the hippocampus in resting-state functional magnetic resonance imaging were also calculated. Results After correction, the sGTCS group showed lower FA than the non-sGTCS group (P = 0.03), and lower FA as well as higher MD than controls in the ipsilateral pHTP. The non-sGTCS group only showed higher corrected MD in the ipsilateral pHTP relative to controls. Corrected FA or MD in the contralateral pHTP did not differ among groups. The TSCH was located in the mesial aspect of the thalamus, and it was atrophied in the sGTCS group compared to the non-sGTCS group and controls. The sGTCS group had lower fractional amplitude of low-frequency fluctuations in the ipsilateral hippocampus and TSCH compared to controls. Significance In TLE-HS, sGTCS was associated with impaired integrity of the pHTP as well as structural and functional abnormalities in the medial thalamus. The medial thalamus is important in seizure generalization in mTLE.

目的 内侧颞叶癫痫（mTLE）继发全面强直 - 阵挛发作（sGTCS）潜在的致痫网络尚未完全明确。在此，我们利用扩散张量成像和静息态功能磁共振成像对一组伴有海马硬化（HS）的颞叶癫痫患者进行研究，以探究sGTCS潜在的海马 - 丘脑概率通路（pHTP）的改变。 方法 我们连续招募了51例单侧颞叶癫痫 - 海马硬化患者（26例有sGTCS，25例无sGTCS）以及22例健康对照。采用概率纤维束成像技术追踪pHTP。pHTP的原始各向异性分数（FA）和平均扩散率（MD）通过同侧半球白质的FA/MD进行校正。对与海马相连的丘脑亚区（TSCH）的体积进行了研究。还计算了静息态功能磁共振成像中海马、TSCH以及与海马不相连的丘脑亚区的低频波动分数振幅。 结果 校正后，sGTCS组的FA低于非sGTCS组（P = 0.03），并且在同侧pHTP中，其FA低于对照组，MD高于对照组。非sGTCS组仅在同侧pHTP中校正后的MD高于对照组。对侧pHTP校正后的FA或MD在各组之间无差异。TSCH位于丘脑内侧，与非sGTCS组和对照组相比，sGTCS组的TSCH萎缩。与对照组相比，sGTCS组同侧海马和TSCH的低频波动分数振幅较低。 意义 在颞叶癫痫 - 海马硬化中，sGTCS与pHTP的完整性受损以及丘脑内侧的结构和功能异常有关。丘脑内侧在mTLE的癫痫发作泛化中具有重要作用。