Kundishora Adam J, Gummadavelli Abhijeet, Ma Chanthia, Liu Mengran, McCafferty Cian, Schiff Nicholas D, Willie Jon T, Gross Robert E, Gerrard Jason, Blumenfeld Hal
Department of Neurology.
Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06520, USA.
Cereb Cortex. 2017 Mar 1;27(3):1964-1975. doi: 10.1093/cercor/bhw035.
Impaired consciousness occurs suddenly and unpredictably in people with epilepsy, markedly worsening quality of life and increasing risk of mortality. Focal seizures with impaired consciousness are the most common form of epilepsy and are refractory to all current medical and surgical therapies in about one-sixth of cases. Restoring consciousness during and following seizures would be potentially transformative for these individuals. Here, we investigate deep brain stimulation to improve level of conscious arousal in a rat model of focal limbic seizures. We found that dual-site stimulation of the central lateral nucleus of the intralaminar thalamus (CL) and the pontine nucleus oralis (PnO) bilaterally during focal limbic seizures restored normal-appearing cortical electrophysiology and markedly improved behavioral arousal. In contrast, single-site bilateral stimulation of CL or PnO alone was insufficient to achieve the same result. These findings support the "network inhibition hypothesis" that focal limbic seizures impair consciousness through widespread inhibition of subcortical arousal. Driving subcortical arousal function would be a novel therapeutic approach to some forms of refractory epilepsy and may be compatible with devices already in use for responsive neurostimulation. Multisite deep brain stimulation of subcortical arousal structures may benefit not only patients with epilepsy but also those with other disorders of consciousness.
意识障碍在癫痫患者中突然且不可预测地发生,显著恶化生活质量并增加死亡风险。伴有意识障碍的局灶性癫痫发作是最常见的癫痫形式,约六分之一的病例对目前所有的药物和手术治疗均无效。在癫痫发作期间及发作后恢复意识可能会给这些患者带来变革性的影响。在此,我们研究了深部脑刺激对改善局灶性边缘叶癫痫大鼠模型中意识觉醒水平的作用。我们发现,在局灶性边缘叶癫痫发作期间,双侧对丘脑板内核中央外侧核(CL)和脑桥嘴侧核(PnO)进行双位点刺激可恢复看似正常的皮质电生理,并显著改善行为觉醒。相比之下,单独对CL或PnO进行双侧单位点刺激不足以达到相同效果。这些发现支持了“网络抑制假说”,即局灶性边缘叶癫痫发作通过广泛抑制皮质下觉醒而损害意识。驱动皮质下觉醒功能可能是治疗某些形式的难治性癫痫的一种新方法,并且可能与已用于反应性神经刺激的设备兼容。对皮质下觉醒结构进行多部位深部脑刺激可能不仅有益于癫痫患者,也有益于其他意识障碍患者。