Parkinson Disease Affects Peripheral Sensory Nerves in the Pharynx

Abstract

Dysphagia is very common in patients with Parkinson’s disease (PD) and often leads to aspiration pneumonia, the most common cause of death in PD. Unfortunately, current therapies are largely ineffective for dysphagia. As pharyngeal sensation normally triggers the swallowing reflex, we examined pharyngeal sensory nerves in PD 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 (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 potential 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 significantly greater in PD subjects with documented dysphagia compared to those without dysphagia. In addition, α-synuclein-immunoreactive nerve fibers in the ISLN were much more abundant than those in the IX and PSBX. These findings suggest that pharyngeal sensory nerves are directly affected by the pathologic process of PD. This anatomic pathology may decrease pharyngeal sensation impairing swallowing and airway protective reflexes, thereby contributing to dysphagia and aspiration.

Dysphagia in Parkinson’s disease: Prevalence, Impact and Management Challenges

“…A reduction of sensitivity can be present in the pharynx [35] as describe by Mu et al [35]. The pharynx has an important role in the bolus conduction, and also, in triggering the swallowing reflex.…”

“…The pharynx has an important role in the bolus conduction, and also, in triggering the swallowing reflex. Mu et al [35] found a large number of muscular fibers atrophied in the pharynx, an additionally alteration in sensorial nerves, such as: glossopharyngeal nerve, pharyngeal sensory branch of the vagus nerve and the internal superior laryngeal nerve. This sensorial alteration leads to an insufficient auto-perception of swallowing problems and several of PD patients do not complaint about dysphagia.…”

Peripheral nervous system involvement in Parkinson's disease: Evidence and controversies

“…a-synuclein aggregates have been detected in the pharyngeal motor and sensory branch of vagus nerve, in the glossopharyngeal nerve and in the internal superior laryngeal nerve in PD patients with dysphagia [8,9]. Lewy bodies have also been found in the dorsal vagus ganglion and parasympathetic sacral nuclei, as well as in the enteric nervous system, and cardiac and pelvic plexus, even in early disease stages [10e14].…”

Emergence of Deglutology: A Transdisciplinary Field

“…Recent comprehensive postmortem neuropathologic studies of PD patients have indicated that brain pathology (Lewy neurites and Lewy bodies) in PD originates in the olfactory bulb and visceromotor projections of dorsal nucleus of the glossopharyngeal and vagal nerves in medulla oblongata years prior to involvement of nigrostriatal pathway and onset of somatomotor dysfunction 7 . Furthermore, these histopathologic observations have shown atrophic and denervated pharyngeal constrictors and cricopharyngeus myofibers 8 ; axonal degenerative changes in vagal and sympathetic motoneurons innervating pharyngeal constrictors and cricopharyngeus 9 , along with degenerative changes of predominantly sensory internal superior laryngeal branch of the vagus nerve 10 . Collectively these central and peripheral autonomic sensorimotor impairments in dysphagic PD patients may explain compromised cough reflex 11 , delayed swallow reflex 3, 12 , pharyngeal peristaltic incoordination 3, 13 and incomplete UES relaxation 3, 14 .…”