Mu Liancai, Chen Jingming, Nyirenda Themba, Li Jing, Hegland Karen Wheeler, Adler Charles H, Caviness John N, Shill Holly A, Serrano Geidy E, Beach Thomas G
Upper Airway Research Laboratory, Center for Discovery and Innovation, Hackensack Meridian Health, 111 Ideation Way, Nutley, NJ, 07110, USA.
Upper Airway Dysfunction Laboratory, Department of Speech, Language and Hearing Sciences, College of Public Health and Health Professions, University of Florida, 1225 Center Dr., Gainesville, FL, 32611, USA.
Dysphagia. 2025 Aug 23. doi: 10.1007/s00455-025-10870-y.
Swallowing, speech and voice (SSV) disorders are very common in Parkinson's disease (PD). The aim of the present studies was to test our hypothesis that PD pathology affects the peripheral nervous system (PNS) of the larynx, thus possibly contributing to SSV deficits. Twenty-eight adult human larynges obtained from autopsied subjects with clinically diagnosed and neuropathologically confirmed PD (n = 20) and age-matched healthy controls (n = 8) were studied. Three laryngeal nerves (i.e., recurrent laryngeal nerve, RLN; external and internal superior laryngeal nerves, ESLN and ISLN), three muscles (i.e., thyroarytenoid, TA; posterior cricoarytenoid, PCA; and cricothyroid, CT), and three mucosa samples overlying the larynx and laryngopharynx (i.e., true vocal fold, TVF; laryngeal surface of the epiglottis, LSE; and aryepiglottic fold, AEF) were examined to detect phosphorylated α-synuclein (PAS) aggregates, the pathological hallmark of PD. The severity of the PAS lesions in the examined tissues was quantified by using a total PNS pathology score we newly developed. The results showed that the larynx was affected by PAS pathology in PD subjects but in none of the controls. The relative contributions of the PNS and brain pathologies to SSV disorders were analyzed. In this series, SSV severity levels in a substantial percentage (45%) of PD patients were more consistent with PNS than brain pathology severity levels. These findings suggest that in addition to brain pathology, PAS lesions in the PNS of the larynx also play an important role in the development of SSV disorders in PD.
吞咽、言语和嗓音（SSV）障碍在帕金森病（PD）中非常常见。本研究的目的是验证我们的假设，即PD病理改变会影响喉部的周围神经系统（PNS），从而可能导致SSV功能缺陷。我们研究了28个从尸检受试者获取的成人喉部，这些受试者临床诊断为PD且经神经病理学确诊（n = 20），以及年龄匹配的健康对照（n = 8）。检查了三条喉神经（即喉返神经，RLN；喉上神经外支和内支，ESLN和ISLN）、三块肌肉（即甲杓肌，TA；环杓后肌，PCA；和环甲肌，CT），以及覆盖喉部和喉咽部的三个黏膜样本（即真声带，TVF；会厌喉面，LSE；和杓会厌襞，AEF），以检测磷酸化α-突触核蛋白（PAS）聚集体，这是PD的病理标志。通过使用我们新开发的总PNS病理评分对所检查组织中PAS病变的严重程度进行量化。结果显示，PD受试者的喉部受到PAS病理影响，而对照组均未受影响。分析了PNS和脑部病理对SSV障碍的相对影响。在这一系列研究中，相当比例（45%）的PD患者的SSV严重程度水平与PNS病理严重程度水平比与脑部病理严重程度水平更一致。这些发现表明，除了脑部病理外，喉部PNS中的PAS病变在PD患者SSV障碍的发生发展中也起重要作用。
