von Ellenrieder Nicolás, Alrashid Mariam, Myers Kenneth, Osterman Bradley, Simard-Tremblay Elisabeth, Karamchandani Jason, Guiot Marie-Christine, Gotman Jean, Dudley Roy W R
Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.
Department of Neurosurgery, King Fahd Hospital of the University, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
Epilepsia. 2025 Sep;66(9):3168-3179. doi: 10.1111/epi.18459. Epub 2025 May 15.
Focal epilepsy is caused by focal brain pathologies sometimes with involvement of surrounding or distant tissue. However, within the epileptogenic zone (EZ), which can be resected to cure epilepsy, the contribution of histopathological cells to epileptogenicity remains unknown. We hypothesized that areas showing neurophysiological biomarkers of epileptogenicity would more often contain histopathological cells compared to areas without such biomarkers.
Pediatric epilepsy patients with nonlesional magnetic resonance imaging (MRI), or with lesions with unclear borders, underwent stereoelectroencephalographic (SEEG) exploration followed by resective surgery of the suspected EZ. Tissue specimens were taken from locations where the SEEG contacts had been, using intraoperative MRI-guided precise neuronavigation. Then, we explored the association between histopathology and rates of interictal epileptic discharges, ripples, and fast ripples (FRs), and the channels of the seizure onset zone (SOZ).
The association between histopathology and ictal/interictal activity was low and not statistically significant in 260 specimens from 20 surgeries. Rates of interictal events were slightly lower for pathological samples than in normal tissue (low effect size, Cliff |d| < .15, p > .1). The classification accuracy of tissue as normal or pathological based on interictal activity/SOZ was low (accuracy ≤ 54%). As a secondary outcome, SEEG events were excellent predictors of surgical outcome, FRs leading to perfect prediction (20/20).
Histopathological tissue initiates epileptogenicity in focal epilepsy. However, our findings suggest that the EZ is not strictly a histopathological entity but a hybrid of abnormal cells and normal-appearing cells. Thus, SEEG events are biomarkers of epileptogenicity and not histopathology. Resecting of electrophysiological biomarkers of epileptogenicity may be more important than resecting all histopathology.
局灶性癫痫由局灶性脑病变引起，有时会累及周围或远处组织。然而，在可通过切除治愈癫痫的致痫区（EZ）内，组织病理学细胞对致痫性的作用仍不清楚。我们假设，与没有此类生物标志物的区域相比，显示致痫性神经生理生物标志物的区域更常含有组织病理学细胞。
患有非病变性磁共振成像（MRI）或病变边界不清晰的小儿癫痫患者，接受立体定向脑电图（SEEG）探查，随后对疑似EZ进行切除手术。使用术中MRI引导的精确神经导航，从SEEG电极接触部位获取组织标本。然后，我们探讨了组织病理学与发作间期癫痫放电、涟漪和快速涟漪（FRs）发生率以及癫痫发作起始区（SOZ）通道之间的关联。
在来自20例手术的260个标本中，组织病理学与发作期/发作间期活动之间的关联较低，且无统计学意义。病理样本的发作间期事件发生率略低于正常组织（效应量低，Cliff |d| <.15，p >.1）。基于发作间期活动/SOZ将组织分类为正常或病理的准确率较低（准确率≤54%）。作为次要结果，SEEG事件是手术结果的优秀预测指标，FRs可实现完美预测（20/20）。
组织病理学组织引发局灶性癫痫的致痫性。然而，我们的研究结果表明，EZ并非严格意义上的组织病理学实体，而是异常细胞和外观正常细胞的混合体。因此，SEEG事件是致痫性的生物标志物，而非组织病理学标志物。切除致痫性的电生理生物标志物可能比切除所有组织病理学病变更为重要。
