Witzig V, Pjontek R, Tan S K H, Schulz J B, Holtbernd F
Department of Neurology, RWTH Aachen University, Aachen, Germany.
Department of Neurosurgery, RWTH Aachen University, Aachen, Germany.
J Neurochem. 2025 Feb;169(2):e16264. doi: 10.1111/jnc.16264. Epub 2024 Nov 18.
Parkinson's disease (PD) is the second-fastest growing neurodegenerative disease in the world. The major clinical symptoms rigor, tremor, and bradykinesia derive from the degeneration of the nigrostriatal pathway. However, PD is a multi-system disease, and neurodegeneration extends beyond the degradation of the dopaminergic pathway. Symptoms such as postural instability, freezing of gait, falls, and cognitive decline are predominantly caused by alterations of transmitter systems outside the classical dopaminergic axis. While levodopa and deep brain stimulation (DBS) of the subthalamic nucleus or globus pallidus internus effectively address PD primary motor symptoms, they often fall short in mitigating axial symptoms and cognitive impairment. Along these lines, the cholinergic system is increasingly recognized to play a crucial role in governing locomotion, postural stability, and cognitive function. Thus, there is a growing interest in bolstering the cholinergic tone by DBS of cholinergic targets such as the pedunculopontine nucleus (PPN) and nucleus basalis of Meynert (NBM), aiming to alleviate these debilitating symptoms resistant to traditional treatment strategies targeting the dopaminergic network. This review offers a comprehensive overview of the role of cholinergic dysfunction in PD. We discuss the impact of PPN and NBM DBS on the management of symptoms not readily accessible to established DBS targets and pharmacotherapy in PD and seek to provide guidance on patient selection, surgical approach, and stimulation paradigms.
帕金森病（PD）是全球增长第二快的神经退行性疾病。主要临床症状僵硬、震颤和运动迟缓源于黑质纹状体通路的退化。然而，PD是一种多系统疾病，神经退行性变不仅限于多巴胺能通路的退化。姿势不稳、步态冻结、跌倒和认知衰退等症状主要是由经典多巴胺能轴以外的递质系统改变引起的。虽然左旋多巴以及丘脑底核或苍白球内侧部的深部脑刺激（DBS）能有效缓解PD的主要运动症状，但在减轻轴性症状和认知障碍方面往往效果不佳。因此，胆碱能系统在调节运动、姿势稳定性和认知功能中的关键作用日益受到认可。于是，通过对胆碱能靶点如脚桥核（PPN）和梅纳特基底核（NBM）进行DBS来增强胆碱能张力的兴趣与日俱增，旨在缓解这些对针对多巴胺能网络的传统治疗策略有抗性的衰弱症状。本综述全面概述了胆碱能功能障碍在PD中的作用。我们讨论了PPN和NBM DBS对PD中既定DBS靶点和药物治疗难以触及的症状管理的影响，并试图为患者选择、手术方法和刺激模式提供指导。
