Mu Liancai, Chen Jingming, Li Jing, Nyirenda Themba, Hegland Karen Wheeler, Beach Thomas G
Upper Airway Reserch Laboratory, Center for Discovery and Innovation, Hackensack Meridian Health, 111 Ideation Way, Nutley, NJ, 07110, USA.
Center for Discovery and Innovation, Hackensack Meridian Health, 111 Ideation Way, Nutley, NJ, 07110, USA.
Dysphagia. 2024 Dec;39(6):1001-1012. doi: 10.1007/s00455-024-10693-3. Epub 2024 Mar 18.
The majority of patients with Parkinson's disease (PD) develop swallowing, speech, and voice (SSV) disorders. Importantly, swallowing difficulty or dysphagia and related aspiration are life-threatening conditions for PD patients. Although PD treatments have significant therapeutic effects on limb motor function, their effects on SSV disorders are less impressive. A large gap in our knowledge is that the mechanisms of SSV disorders in PD are poorly understood. PD was long considered to be a central nervous system disorder caused by the death of dopaminergic neurons in the basal ganglia. Aggregates of phosphorylated α-synuclein (PAS) underlie PD pathology. SSV disorders were thought to be caused by the same dopaminergic problem as those causing impaired limb movement; however, there is little evidence to support this. The pharynx, larynx, and tongue play a critical role in performing upper airway (UA) motor tasks and their dysfunction results in disordered SSV. This review aims to provide an overview on the neuromuscular organization patterns, functions of the UA structures, clinical features of SSV disorders, and gaps in knowledge regarding the pathophysiology underlying SSV disorders in PD, and evidence supporting the hypothesis that SSV disorders in PD could be associated, at least in part, with PAS damage to the peripheral nervous system controlling the UA structures. Determining the presence and distribution of PAS lesions in the pharynx, larynx, and tongue will facilitate the identification of peripheral therapeutic targets and set a foundation for the development of new therapies to treat SSV disorders in PD.
大多数帕金森病（PD）患者会出现吞咽、言语和嗓音（SSV）障碍。重要的是，吞咽困难或吞咽障碍以及相关的误吸对PD患者来说是危及生命的情况。尽管PD治疗对肢体运动功能有显著疗效，但它们对SSV障碍的效果却不那么显著。我们在认知上的一个巨大差距在于，对PD中SSV障碍的机制了解甚少。长期以来，PD被认为是一种由基底神经节中多巴胺能神经元死亡引起的中枢神经系统疾病。磷酸化α-突触核蛋白（PAS）聚集体是PD病理的基础。SSV障碍被认为是由与导致肢体运动受损相同的多巴胺能问题引起的；然而，几乎没有证据支持这一点。咽、喉和舌在执行上呼吸道（UA）运动任务中起关键作用，它们的功能障碍会导致SSV紊乱。本综述旨在概述神经肌肉组织模式、UA结构的功能、SSV障碍的临床特征，以及关于PD中SSV障碍病理生理学的知识空白，以及支持以下假设的证据：PD中的SSV障碍可能至少部分与PAS对控制UA结构的外周神经系统的损害有关。确定PAS病变在咽、喉和舌中的存在和分布将有助于确定外周治疗靶点，并为开发治疗PD中SSV障碍的新疗法奠定基础。
