Division of Child Neurology, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA; Neurology Care Line, Michael E. DeBakey VA Medical Center, Houston, TX 77030, USA.
Epilepsy Behav. 2024 Nov;160:110067. doi: 10.1016/j.yebeh.2024.110067. Epub 2024 Oct 10.
Developmental and epileptic encephalopathies (DEEs) are a group of childhood-onset epilepsy syndromes characterized by frequent seizures, severe cognitive and behavioral impairments, and poor long-term outcomes. These conditions are typically refractory to currently available medical therapies, prompting recent exploration of neuromodulation treatments such as deep brain stimulation (DBS) and responsive neurostimulation (RNS), which aim to modulate epileptic networks spanning cortical and subcortical regions. These advances have occurred alongside an improved understanding of syndrome-specific and interictal epileptiform discharge/seizure-specific brain networks. By targeting key nodes within these networks, DBS and RNS hold promise for influencing seizures and associated cognitive and behavioral comorbidities. Initial experiences with centromedian (CM) thalamic DBS for Lennox-Gastaut syndrome (LGS) have shown modest efficacy across multiple seizure types. Reports also indicate the application of DBS and RNS across various genetic and structural etiologies commonly associated with DEEs, with mixed success. Although DBS and RNS are increasingly used in LGS and other DEEs, their mixed efficacy highlights a knowledge gap in understanding why some patients with LGS do not respond and which neuromodulation approach is most effective for other DEEs. To address these issues, this review first discusses recent neuroimaging studies showing similarities and differences in the epileptic brain networks underlying various DEEs, revealing the common involvement of the thalamus and the default-mode network (DMN) across multiple DEEs. We then examine thalamic DBS for LGS to illustrate how such network insights may be used to optimize neuromodulation. Although network-based neuromodulation is still in its infancy, the LGS model may serve as a framework for other DEEs, where optimal treatment necessitates consideration of the underlying epileptic networks. Lastly, the review suggests future research directions, including individualized connectivity assessment and biomarker identification through collaborative efforts, which may enhance the therapeutic potential of neuromodulation for individuals living with DEEs.
发育性和癫痫性脑病（DEEs）是一组儿童期起病的癫痫综合征，其特征为频繁发作、严重认知和行为障碍以及预后不良。这些病症通常对现有的医学治疗方法具有抗性，因此最近探索了神经调节治疗方法，如深部脑刺激（DBS）和反应性神经刺激（RNS），这些方法旨在调节跨越皮质和皮质下区域的癫痫网络。这些进展伴随着对综合征特异性和发作间癫痫样放电/发作特异性脑网络的更好理解。通过针对这些网络中的关键节点，DBS 和 RNS 有望影响癫痫发作以及相关的认知和行为共病。在 Lennox-Gastaut 综合征（LGS）中使用中央中脑（CM）丘脑 DBS 的初步经验表明，多种癫痫类型的疗效均较为适度。报告还表明，DBS 和 RNS 在与 DEEs 相关的各种遗传和结构病因中得到了应用，但效果不一。尽管 DBS 和 RNS 在 LGS 和其他 DEEs 中的应用越来越广泛，但它们的疗效不一突显了一个知识缺口，即为什么一些 LGS 患者没有反应，以及哪种神经调节方法对其他 DEEs最有效。为了解决这些问题，本综述首先讨论了最近的神经影像学研究，这些研究显示了各种 DEEs 下癫痫脑网络的相似性和差异性，揭示了丘脑和默认模式网络（DMN）在多个 DEEs 中的共同参与。然后，我们研究了 LGS 的丘脑 DBS，以说明如何利用这些网络见解来优化神经调节。尽管基于网络的神经调节仍处于起步阶段，但 LGS 模型可能成为其他 DEEs 的框架，在这些模型中，优化治疗需要考虑潜在的癫痫网络。最后，该综述提出了未来的研究方向，包括通过合作努力进行个体化连接评估和生物标志物识别，这可能会增强神经调节对患有 DEEs 的个体的治疗潜力。
