Neurophysiological mechanisms of gait disturbance in advanced Parkinson's disease patients
Neurophysiological mechanisms of gait disturbance in advanced Parkinson's disease patients
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DOI：
10.1111/ncn3.12683
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发表时间：
2022-11-23
影响因子：
0.4
通讯作者：
Chiba，Ryosuke
中科院分区：
文献类型：
--
作者：
Takakusaki，Kaoru;Takahashi，Mirai;Chiba，Ryosuke
本文综述了帕金森病（PD）姿势-步态障碍的病理生理机制。临床研究表明，姿势-步态障碍除了肌肉骨骼系统的功能障碍外，还可归因于整个神经轴的功能障碍。大脑皮层、基底神经节（BG）、小脑、脑干和脊髓在时间和空间上整合和协调多感觉反馈和运动命令的传出副本。因此，广泛的自主运动可以与预期的和反应性的姿势调整相结合，以提供支持和稳定目标导向的步态活动的框架。系统中的冗余允许通过分别通过BG和小脑途径实施的奖励导向和基于错误的学习过程进行适应和补偿。然而，PD中这些系统的损伤可能会大大损害适应能力，并导致适应不良的变化，损害姿势-步态控制。当这些损伤发生时，福尔斯的风险会显著增加，需要进行干预以降低发病率。多巴胺（DA）神经元的损伤是PD的主要原因。纹状体中DA供应不足干扰BG中固有网络的运作。这也在病理上增加了GABA能BG输出到大脑皮层和脑干，导致其他结构与BG的功能性断开。断开使PD患者无法实现习惯性获得的自动步态控制。此外，大多数脑区的路易体变性，特别是在胆碱能和其他易受神经变性影响的单胺能系统中，进一步干扰姿势-步态控制并改变PD的非运动症状。
This review considers pathophysiological mechanisms of posture‐gait disturbances in Parkinson's disease (PD). Clinical studies have shown that posture‐gait disturbance attributes to the dysfunction of the whole neuraxis in addition to the musculoskeletal system. The cerebral cortex, basal ganglia (BG), cerebellum, brainstem, and spinal cord temporally and spatially integrate and coordinate multisensory feedback and efferent copies of the motor command. Therefore, the extensive repertoire of voluntary movements can be coupled with anticipatory and reactive postural adjustments to provide the framework for supporting and stabilizing the goal‐directed gait activity. Redundancies in the system allow adaptation and compensation through reward‐oriented and error‐based learning processes implemented through the BG and cerebellar pathways, respectively. However, the impairment of these systems in PD may considerably compromise the capacity to adapt and lead to maladaptive changes impairing posture‐gait control. When these impairments occur, the risk of falls can significantly increase, and interventions are required to reduce morbidity. The damage in dopamine (DA) neurons is the primary cause of PD. Insufficient DA supply in the striatum disturbs the operation of intrinsic networks in the BG. This also pathologically increases GABAergic BG output to the cerebral cortex and brainstem, resulting in functional disconnection of other structures from the BG. The disconnection makes PD patients disable to achieve habitually acquired automatized gait control. Moreover, Lewy body degeneration in most brain areas, particularly in cholinergic and other monoaminergic systems vulnerable to neurodegeneration, further disturbs posture‐gait control and alters non‐motor symptoms of PD.