Department of Bioengineering, University of Pennsylvania, Philadelphia PA 19104, USA.
Center for Neuroengineering and Therapeutics, University of Pennsylvania, Philadelphia PA 19104, USA.
Brain. 2019 Dec 1;142(12):3892-3905. doi: 10.1093/brain/awz303.
Patients with drug-resistant epilepsy often require surgery to become seizure-free. While laser ablation and implantable stimulation devices have lowered the morbidity of these procedures, seizure-free rates have not dramatically improved, particularly for patients without focal lesions. This is in part because it is often unclear where to intervene in these cases. To address this clinical need, several research groups have published methods to map epileptic networks but applying them to improve patient care remains a challenge. In this study we advance clinical translation of these methods by: (i) presenting and sharing a robust pipeline to rigorously quantify the boundaries of the resection zone and determining which intracranial EEG electrodes lie within it; (ii) validating a brain network model on a retrospective cohort of 28 patients with drug-resistant epilepsy implanted with intracranial electrodes prior to surgical resection; and (iii) sharing all neuroimaging, annotated electrophysiology, and clinical metadata to facilitate future collaboration. Our network methods accurately forecast whether patients are likely to benefit from surgical intervention based on synchronizability of intracranial EEG (area under the receiver operating characteristic curve of 0.89) and provide novel information that traditional electrographic features do not. We further report that removing synchronizing brain regions is associated with improved clinical outcome, and postulate that sparing desynchronizing regions may further be beneficial. Our findings suggest that data-driven network-based methods can identify patients likely to benefit from resective or ablative therapy, and perhaps prevent invasive interventions in those unlikely to do so.
患有耐药性癫痫的患者通常需要手术才能实现无癫痫发作。虽然激光消融和可植入式刺激设备降低了这些手术的发病率,但无癫痫发作率并未显著提高,尤其是对于没有局灶性病变的患者。部分原因是因为在这些情况下,通常不清楚在哪里进行干预。为了满足这一临床需求,一些研究小组已经公布了对癫痫网络进行绘图的方法,但将其应用于改善患者护理仍然是一个挑战。在这项研究中,我们通过以下方法推进了这些方法的临床转化:(i)提出并共享一种稳健的流水线,以严格量化切除区域的边界,并确定颅内 EEG 电极位于其中的位置;(ii)在 28 名接受颅内电极植入术以进行手术切除的耐药性癫痫患者的回顾性队列中验证脑网络模型;(iii)共享所有神经影像学、注释电生理学和临床元数据,以促进未来的合作。我们的网络方法能够根据颅内 EEG 的同步性(接受者操作特征曲线下面积为 0.89)准确预测患者是否可能从手术干预中受益,并提供传统电生理特征所不提供的新信息。我们进一步报告称,去除同步化的脑区与改善临床结果相关,并推测保留去同步化的脑区可能会进一步获益。我们的研究结果表明,基于数据驱动的网络方法可以识别出可能从切除性或消融性治疗中受益的患者,并且可能避免对那些不太可能受益的患者进行有创干预。