Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA.
Medical College of Georgia, Augusta, Georgia, USA.
Epilepsia. 2022 Sep;63(9):2192-2213. doi: 10.1111/epi.17326. Epub 2022 Jun 29.
Electrical brain stimulation has become an essential treatment option for more than one third of epilepsy patients who are resistant to pharmacological therapy and are not candidates for surgical resection. However, currently approved stimulation paradigms achieve only moderate success, on average providing approximately 75% reduction in seizure frequency and extended periods of seizure freedom in nearly 20% of patients. Outcomes from electrical stimulation may be improved through the identification of novel anatomical targets, particularly those with significant anatomical and functional connectivity to the epileptogenic zone. Multiple studies have investigated the medial septal nucleus (i.e., medial septum) as such a target for the treatment of mesial temporal lobe epilepsy. The medial septum is a small midline nucleus that provides a critical functional role in modulating the hippocampal theta rhythm, a 4-7-Hz electrophysiological oscillation mechanistically associated with memory and higher order cognition in both rodents and humans. Elevated theta oscillations are thought to represent a seizure-resistant network activity state, suggesting that electrical neuromodulation of the medial septum and restoration of theta-rhythmic physiology may not only reduce seizure frequency, but also restore cognitive comorbidities associated with mesial temporal lobe epilepsy. Here, we review the anatomical and physiological function of the septohippocampal network, evidence for seizure-resistant effects of the theta rhythm, and the results of stimulation experiments across both rodent and human studies, to argue that deep brain stimulation of the medial septum holds potential to provide an effective neuromodulation treatment for mesial temporal lobe epilepsy. We conclude by discussing the considerations necessary for further evaluating this treatment paradigm with a clinical trial.
电脑刺激已成为三分之一以上对药物治疗有抗药性且不适合手术切除的癫痫患者的重要治疗选择。然而，目前批准的刺激模式平均仅取得中等成功率，大约有 75%的患者癫痫发作频率降低，20%的患者癫痫发作持续时间延长。通过确定新的解剖学靶点（特别是与致痫区具有显著解剖和功能连接的靶点），可以改善电刺激的效果。多项研究已将内侧隔核（即内侧隔核）作为治疗内侧颞叶癫痫的目标进行了研究。内侧隔核是一个小的中线核，在调节海马θ节律方面发挥着关键的功能作用，θ节律是一种 4-7-Hz 的电生理振荡，在啮齿动物和人类中与记忆和更高阶认知有关。升高的θ振荡被认为代表了一种抗癫痫发作的网络活动状态，这表明电神经调节内侧隔核并恢复θ节律生理学不仅可以降低癫痫发作频率，还可以恢复与内侧颞叶癫痫相关的认知并发症。在这里，我们回顾了隔海马网络的解剖和生理功能、θ节律的抗癫痫发作作用的证据，以及啮齿动物和人类研究中刺激实验的结果，以论证内侧隔核深部脑刺激有可能为内侧颞叶癫痫提供有效的神经调节治疗。最后，我们讨论了进一步通过临床试验评估这种治疗模式的必要性。
