Parkinson disease affects peripheral sensory nerves in the pharynx

Abstract

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.

Figure 1

Images from adult human pharynges showing sampling sites of the pharyngeal sensory nerves. A Posterior view of a normal human pharynx processed with Sihler’s stain, a whole mount nerve staining technique. (Adapted and reproduced in part with permission from Mu and Sanders [20].) B Posterolateral view of a fresh pharynx and larynx from a patient with PD. The sampling site for each nerve studied is outlined (enclosed region). The arrow indicates the entry point of the internal superior laryngeal nerve (ISLN) into the pharynx and larynx through the cricothyroid membrane. CA, carotid artery; CP, cricopharyngeus; H, greater cornu of hyoid bone; IPC, inferior pharyngeal constrictor; IX, glossopharyngeal nerve; MPC, middle pharyngeal constrictor; N, nodose ganglion of X nerve; PSB-X, pharyngeal sensory branch of the X nerve; RLN, recurrent laryngeal nerve; SPC, superior pharyngeal constrictor; T, superior cornu of thyroid cartilage; X, vagus nerve.

Figure 2

Photomicrographs of the longitudinal sections of the pharyngeal sensory nerves from PD patients with dysphagia A–C and nondysphagia D–F immunostained with monoclonal antiphosphorylated α-synuclein antibody (psyn#64), showing phosphorylated α-synuclein-immunoreactive neurites (threads and dots). A–C Stained sections of the ISLN A, IX B, and PSB-X C from a PD patient with dysphagia (PD 6, 81-year-old man with disease duration of 11 years, Hoehn & Yahr 4, and motor UPDRS 43). Note that α-synuclein aggregates (darkly stained threads and dots) were more abundant in the ISLN (lesion severity: severe, +++) than in the IX (lesion severity: moderate, ++) and PSB-X (lesion severity: moderate, ++). D–F Stained sections of the ISLN, IX, and PSB-X from a PD subject without dysphagia (PD 5, 80-year-old man with disease duration of 11 years, Hoehn & Yahr 4, and motor UPDRS 53). Note that the severity of axonal α-synuclein aggregates in the ISLN (lesion severity: moderate, ++), IX (lesion severity: mild, +), and PSB-X (lesion severity: mild, +) in this case without dysphagia was lower than that observed in the PD subject with dysphagia. Original magnification: A–F 200x.