Department of Neurology, Farber Institute for Neuroscience, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Department of Psychology, University of Science and Technology of China, Hefei, Anhui, China.
Epilepsia. 2024 Jun;65(6):1756-1767. doi: 10.1111/epi.17960. Epub 2024 Mar 22.
Focal to bilateral tonic-clonic seizures (FBTCS) represent a challenging subtype of focal temporal lobe epilepsy (TLE) in terms of both severity and treatment response. Most studies have focused on regional brain analysis that is agnostic to the distribution of white matter (WM) pathways associated with a node. We implemented a more selective, edge-wise approach that allowed for identification of the individual connections unique to FBTCS.
T1-weighted and diffusion-weighted images were obtained from 22 patients with solely focal seizures (FS), 43 FBTCS patients, and 65 age/sex-matched healthy participants (HPs), yielding streamline (STR) connectome matrices. We used diffusion tensor-derived STRs in an edge-wise approach to determine specific structural connectivity changes associated with seizure generalization in FBTCS compared to matched FS and HPs. Graph theory metrics were computed on both node- and edge-based connectivity matrices.
Edge-wise analyses demonstrated that all significantly abnormal cross-hemispheric connections belonged to the FBTCS group. Abnormal connections associated with FBTCS were mostly housed in the contralateral hemisphere, with graph metric values generally decreased compared to HPs. In FBTCS, the contralateral amygdala showed selective decreases in the structural connection pathways to the contralateral frontal lobe. Abnormal connections in TLE involved the amygdala, with the ipsilateral side showing increases and the contralateral decreases. All the FS findings indicated higher graph metrics for connections involving the ipsilateral amygdala. Data also showed that some FBTCS connectivity effects are moderated by aging, recent seizure frequency, and longer illness duration.
Data showed that not all STR pathways are equally affected by the seizure propagation of FBTCS. We demonstrated two key biases, one indicating a large role for the amygdala in the propagation of seizures, the other pointing to the prominent role of cross-hemispheric and contralateral hemisphere connections in FBTCS. We demonstrated topographic reorganization in FBTCS, pointing to the specific WM tracts involved.
局灶至双侧强直阵挛发作（FBTCS）在严重程度和治疗反应方面代表了局灶性颞叶癫痫（TLE）的一种具有挑战性的亚型。大多数研究都集中在区域脑分析上，而忽略了与节点相关的白质（WM）通路的分布。我们实施了一种更具选择性的、边缘导向的方法，该方法允许识别出与 FBTCS 特有的个体连接。
从仅局灶性发作（FS）的 22 名患者、43 名 FBTCS 患者和 65 名年龄/性别匹配的健康对照者（HPs）中获得 T1 加权和弥散加权图像，生成束流（STR）连接组矩阵。我们使用基于扩散张量的 STR 进行边缘导向分析，以确定与 FBTCS 相比，FS 和 HPs 中与发作泛化相关的特定结构连接变化。在基于节点和基于边缘的连接矩阵上计算了图论度量。
边缘分析表明，所有明显异常的对侧半球连接均属于 FBTCS 组。与 FBTCS 相关的异常连接主要位于对侧半球，与 HPs 相比，图论度量值普遍降低。在 FBTCS 中，对侧杏仁核的结构连接途径到对侧额叶选择性减少。TLE 的异常连接涉及杏仁核，同侧侧增加，对侧减少。所有 FS 发现都表明涉及同侧杏仁核的连接具有更高的图论度量。数据还表明，一些 FBTCS 连接效应受年龄、近期发作频率和更长疾病持续时间的调节。
数据表明，并非所有 STR 通路都受到 FBTCS 发作传播的同等影响。我们证明了两个关键的偏差，一个表明杏仁核在发作传播中起着重要作用，另一个表明在 FBTCS 中对侧和对侧半球连接起着重要作用。我们在 FBTCS 中证明了拓扑重排，指出了涉及的特定 WM 束。
