Prabhu S, Chabardès S, Sherdil A, Devergnas A, Michallat S, Bhattacharjee M, Mathieu H, David O, Piallat B
Univ Grenoble Alpes, GIN, F-38000 Grenoble, France; INSERM, U836, F-38000 Grenoble, France.
Univ Grenoble Alpes, GIN, F-38000 Grenoble, France; INSERM, U836, F-38000 Grenoble, France; CHU de Grenoble, Hôpital Michallon F-38000 Grenoble, France.
Brain Stimul. 2015 Mar-Apr;8(2):177-84. doi: 10.1016/j.brs.2014.10.017. Epub 2014 Nov 4.
Drug-resistant motor epilepsies are particularly incapacitating for the patients. In a primate model of focal motor seizures induced by intracortical injection of penicillin, we recently showed that seizures propagated from the motor cortex towards the basal ganglia.
Using the same animal model here, we hypothesized that disruption of subthalamic nucleus (STN) activity by chronic high frequency stimulation (HFS) could modify pathological excessive cortical synchronisation occurring during focal motor seizures, and therefore could reduce seizure activity.
Two monkeys were chronically implanted with one electrode positioned into the STN. In each experiment, seizures were induced during 6 hours by injecting penicillin into the motor cortex. During stimulation sessions, HFS-STN was applied at the beginning of penicillin injection.
Our results indicate that HFS-STN improved focal motor seizures by delaying the occurrence of the first seizure, by decreasing the number of seizures by 47% and therefore the total time spent seizing by 53% compared to control. These results argue for a therapeutic use of HFS-STN in motor seizures because they were obtained in a very severe primate model of motor status similar to that seen in human. Furthermore, HFS-STN was much more efficient than direct cortical HFS of the epileptic focus, which we already tested in the same primate model.
The present study suggests that HFS-STN could be used as an experimental therapy when other therapeutic strategies are not possible or have failed in humans suffering from motor epilepsy but the present study still warrants controlled studies in humans.
耐药性运动性癫痫对患者的影响尤为严重。在通过皮层内注射青霉素诱导局灶性运动性癫痫发作的灵长类动物模型中，我们最近发现癫痫发作从运动皮层向基底神经节传播。
在此使用相同的动物模型，我们假设通过慢性高频刺激（HFS）破坏丘脑底核（STN）的活动可以改变局灶性运动性癫痫发作期间发生的病理性过度皮层同步，从而可以减少癫痫发作活动。
对两只猴子长期植入一个电极置于丘脑底核。在每个实验中，通过向运动皮层注射青霉素诱导癫痫发作6小时。在刺激阶段，在注射青霉素开始时施加丘脑底核高频刺激（HFS-STN）。
我们的结果表明，与对照组相比，丘脑底核高频刺激（HFS-STN）通过延迟首次癫痫发作的发生、减少47%的癫痫发作次数以及因此减少53%的总发作时间，改善了局灶性运动性癫痫发作。这些结果支持在运动性癫痫中使用丘脑底核高频刺激（HFS-STN）进行治疗，因为它们是在一个与人类所见非常严重的运动状态灵长类动物模型中获得的。此外，丘脑底核高频刺激（HFS-STN）比我们已经在相同灵长类动物模型中测试过的癫痫病灶直接皮层高频刺激效率更高。
本研究表明，当其他治疗策略对患有运动性癫痫的人类不可行或失败时，丘脑底核高频刺激（HFS-STN）可作为一种实验性治疗方法，但本研究仍需要在人类中进行对照研究。
