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运动障碍的功能神经外科手术:历史视角

Functional neurosurgery for movement disorders: a historical perspective.

作者信息

Benabid Alim Louis, Chabardes Stephan, Torres Napoleon, Piallat Brigitte, Krack Paul, Fraix Valerie, Pollak Pierre

机构信息

CEA Minatec LETI and INSERM, Joseph Fourier University, Grenoble, France.

出版信息

Prog Brain Res. 2009;175:379-91. doi: 10.1016/S0079-6123(09)17525-8.

DOI:10.1016/S0079-6123(09)17525-8
PMID:19660668
Abstract

Since the 1960s, deep brain stimulation and spinal cord stimulation at low frequency (30 Hz) have been used to treat intractable pain of various origins. For this purpose, specific hardware have been designed, including deep brain electrodes, extensions, and implantable programmable generators (IPGs). In the meantime, movement disorders, and particularly parkinsonian and essential tremors, were treated by electrolytic or mechanic lesions in various targets of the basal ganglia, particularly in the thalamus and in the internal pallidum. The advent in the 1960s of levodopa, as well as the side effects and complications of ablative surgery (e.g., thalamotomy and pallidotomy), has sent functional neurosurgery of movement disorders to oblivion. In 1987, the serendipitous discovery of the effect of high-frequency stimulation (HFS), mimicking lesions, allowed the revival of the surgery of movement disorders by stimulation of the thalamus, which treated tremors with limited morbidity, and adaptable and reversible results. The stability along time of these effects allowed extending it to new targets suggested by basic research in monkeys. The HFS of the subthalamic nucleus (STN) has profoundly challenged the practice of functional surgery as the effect on the triad of dopaminergic symptoms was very significant, allowing to decrease the drug dosage and therefore a decrease of their complications, the levodopa-induced dyskinesias. In the meantime, based on the results of previous basic research in various fields, HFS has been progressively extended to potentially treat epilepsy and, more recently, psychiatric disorders, such as obsessive-compulsive disorders, Gilles de la Tourette tics, and severe depression. Similarly, suggested by the observation of changes in PET scan, applications have been extended to cluster headaches by stimulation of the posterior hypothalamus and even more recently, to obesity and drug addiction. In the field of movement disorders, it has become clear that STN stimulation is not efficient on the nondopaminergic symptoms such as freezing of gait. Based on experimental data obtained in MPTP-treated parkinsonian monkeys, the pedunculopontine nucleus has been used as a new target, and as suggested by the animal research results, its use indeed improves walking and stability when stimulation is performed at low frequency (25 Hz). The concept of simultaneous stimulation of multiple targets eventually at low or high frequency, and that of several electrodes in one target, is being accepted to increase the efficiency. This leads to and is being facilitated by the development of new hardware (multiple-channel IPGs, specific electrodes, rechargeable batteries). Still additional efforts are needed at the level of the stimulation paradigm and in the waveform. The recent development of nanotechnologies allows the design of totally new systems expanding the field of deep brain stimulation. These new techniques will make it possible to not only inhibit or excite deep brain structures to alleviate abnormal symptoms but also open the field for the use of recording cortical activities to drive neuroprostheses through brain-computer interfaces. The new field of compensation of deficits will then become part of the field of functional neurosurgery.

摘要

自20世纪60年代以来,深部脑刺激和低频(30Hz)脊髓刺激已被用于治疗各种原因引起的顽固性疼痛。为此,人们设计了特定的硬件,包括深部脑电极、延长线和植入式可编程发生器(IPG)。与此同时,运动障碍,尤其是帕金森病和特发性震颤,通过在基底神经节的各个靶点,特别是丘脑和苍白球内侧部进行电解或机械损伤来治疗。20世纪60年代左旋多巴的出现,以及毁损性手术(如丘脑切开术和苍白球切开术)的副作用和并发症,使运动障碍的功能性神经外科手术被遗忘。1987年,偶然发现高频刺激(HFS)具有类似损伤的效果,使得通过刺激丘脑来复兴运动障碍手术成为可能,该方法治疗震颤的发病率有限,且效果可调整和可逆。这些效果随时间的稳定性使得其能够扩展到猴子基础研究提出的新靶点。丘脑底核(STN)的高频刺激对功能性手术的实践产生了深远挑战,因为其对多巴胺能症状三联征的影响非常显著,能够减少药物剂量,从而减少其并发症——左旋多巴诱发的运动障碍。与此同时,基于之前各个领域的基础研究结果,高频刺激已逐渐扩展到潜在治疗癫痫,以及最近的精神疾病,如强迫症、抽动秽语综合征和重度抑郁症。同样,根据PET扫描变化的观察结果,高频刺激已扩展到通过刺激下丘脑后部治疗丛集性头痛,甚至最近还扩展到肥胖症和药物成瘾。在运动障碍领域,很明显丘脑底核刺激对非多巴胺能症状(如步态冻结)无效。基于在MPTP处理的帕金森病猴子中获得的实验数据,脚桥核已被用作一个新靶点,并且正如动物研究结果所表明的,当以低频(25Hz)进行刺激时,其使用确实改善了行走和稳定性。最终同时以低频或高频刺激多个靶点以及在一个靶点中使用多个电极的概念正在被接受,以提高效率。这导致并得益于新硬件(多通道IPG、特定电极、可充电电池)的发展。在刺激模式和波形方面仍需要进一步努力。纳米技术的最新发展使得设计全新的系统成为可能,从而扩展了深部脑刺激的领域。这些新技术不仅能够抑制或兴奋深部脑结构以缓解异常症状,还能为利用记录皮层活动通过脑机接口驱动神经假体开辟领域。缺陷补偿的新领域将成为功能性神经外科领域的一部分。

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