Upper Airway Research Laboratory, Department of Research, Hackensack University Medical Center, Hackensack, New Jersey 07601, USA.
J Neuropathol Exp Neurol. 2013 Jul;72(7):614-23. doi: 10.1097/NEN.0b013e3182965886.
Dysphagia is very common in patients with Parkinson disease (PD) and often leads to aspiration pneumonia, the most common cause of death in PD. Current therapies are largely ineffective for dysphagia. Because pharyngeal sensation normally triggers the swallowing reflex, we examined pharyngeal sensory nerves in PD patients for Lewy pathology.Sensory nerves supplying the pharynx were excised from autopsied pharynges obtained from patients with clinically diagnosed and neuropathologically confirmed PD (n = 10) and healthy age-matched controls (n = 4). We examined the glossopharyngeal nerve (cranial nerve IX), the pharyngeal sensory branch of the vagus nerve (PSB-X), and the internal superior laryngeal nerve (ISLN) innervating the laryngopharynx. Immunohistochemistry for phosphorylated α-synuclein was used to detect Lewy pathology. Axonal α-synuclein aggregates in the pharyngeal sensory nerves were identified in all of the PD subjects but not in the controls. The density of α-synuclein-positive lesions was greater in PD patients with dysphagia versus those without dysphagia. In addition, α-synuclein-immunoreactive nerve fibers in the ISLN were much more abundant than those in cranial nerve IX and PSB-X. These findings suggest that pharyngeal sensory nerves are directly affected by pathologic processes in PD. These abnormalities may decrease pharyngeal sensation, thereby impairing swallowing and airway protective reflexes and contributing to dysphagia and aspiration.
吞咽困难在帕金森病(PD)患者中非常常见,常导致吸入性肺炎,这是 PD 患者最常见的死亡原因。目前的治疗方法对吞咽困难的疗效大多不佳。由于咽感觉通常会引发吞咽反射,我们研究了 PD 患者的咽感觉神经中的路易体病理。我们从临床诊断和神经病理学证实的 PD 患者(n=10)和年龄匹配的健康对照组(n=4)的尸检咽中切除供应咽的感觉神经。我们检查了舌咽神经(颅神经 IX)、迷走神经的咽感觉分支(PSB-X)和支配喉咽的内上喉神经(ISLN)。用磷酸化α-突触核蛋白免疫组化检测路易体病理。在所有 PD 患者中都发现了咽感觉神经中的α-突触核蛋白聚集物,但在对照组中没有。与无吞咽困难的 PD 患者相比,有吞咽困难的 PD 患者的α-突触核蛋白阳性病变密度更大。此外,ISLN 中的α-突触核蛋白免疫反应性神经纤维比颅神经 IX 和 PSB-X 中的更丰富。这些发现表明,PD 中的病理过程直接影响咽感觉神经。这些异常可能会降低咽感觉,从而损害吞咽和气道保护反射,导致吞咽困难和吸入。