Swallowing in PD

Alpha-Synuclein Pathology in Sensory Nerve Terminals of the Upper Aerodigestive Tract of Parkinson’s Disease Patients    https://pubmed.ncbi.nlm.nih.gov/26041249/


Dysphagia is common in Parkinson’s disease (PD) and causes significant morbidity and mortality. PD dysphagia has usually been explained as dysfunction of central motor control, much like other motor symptoms that are characteristic of the disease. However, PD dysphagia does not correlate with severity of motor symptoms nor does it respond to motor therapies. It is known that PD patients have sensory deficits in the pharynx, and that impaired sensation may contribute to dysphagia. However, the underlying cause of the pharyngeal sensory deficits in PD is not known. We hypothesized that PD dysphagia with sensory deficits may be due to degeneration of the sensory nerve terminals in the upper aerodigestive tract (UAT). We have previously shown that Lewy-type synucleinopathy (LTS) is present in the main pharyngeal sensory nerves of PD patients, but not in controls. In this study, the sensory terminals in UAT mucosa were studied to discern the presence and distribution of LTS. Whole-mount specimens (tongue-pharynx-larynx-upper esophagus) were obtained from 10 deceased human subjects with clinically diagnosed and neuropathologically confirmed PD (five with dysphagia and five without) and four age-matched healthy controls. Samples were taken from six sites and immunostained for phosphorylated α-synuclein (PAS). The results showed the presence of PAS-immunoreactive (PAS-ir) axons in all the PD subjects and in none of the controls. Notably, PD patients with dysphagia had more PAS-ir axons in the regions that are critical for initiating the swallowing reflex. These findings suggest that Lewy pathology affects mucosal sensory axons in specific regions of the UAT and may be related to PD dysphagia.

…………………………………………………………… ncbi.nlm.nih.gov/pmc/articl…

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.

Keywords: Alpha-synuclein aggregates, Dysphagia, Glossopharyngeal nerve, Immunohistochemistry, Internal superior laryngeal nerve, Lewy neurites, Nerve degeneration, Parkinson disease, Peripheral nervous system, Pharyngeal sensory nerves, Pharynx, Swallowing, Vagus nerve


Parkinson disease (PD) is a multiple system neurodegenerative disorder characterized by a large number of motor and non-motor features. In addition to the hallmark symptoms (resting tremor, bradykinesia, rigidity, and postural instability), PD patients frequently exhibit a number of secondary motor symptoms such as dysphagia, dysarthria, sialorrhoea, and non-motor symptoms including autonomic dysfunction and sensory abnormalities (). Among these, impaired swallowing and voice/speech represent a large clinical problem in PD as approximately 90% of patients with PD develop these disorders (). It is estimated that there are about 8 million or more people in the world each year that have or will have swallowing and speech disorders (). Unfortunately, treatment outcomes for these disorders have been disappointing. Although anti-PD drugs and deep brain stimulation have significant therapeutic effects on limb motor functions, their effects on swallowing in PD are less impressive, and in some cases, adverse (). Importantly, 25% to 50% of PD patients experience tracheal penetration/aspiration (). Aspiration pneumonia is the leading cause of death among PD patients with dysphagia (). As dysphagia is a challenging clinical issue, an urgent need exists to understand its pathophysiological mechanism for the development of effective therapies.

Despite the extremely high incidence of dysphagia in PD, the exact mechanism of this deficit remains unknown. Oropharyngeal swallowing involves a complex integration of motor and sensory modalities, many of which may be compromised in PD. Therefore, oropharyngeal dysphagia and associated aspiration can be caused by dysfunction of the motor and/or sensory nervous system controlling the upper aerodigestive tract. It is well known that the sensory branches of the glossopharyngeal nerve (cranial nerve IX) and vagus nerve (cranial nerve X) are major contributors to sensory innervation of the pharynx () and play important roles in reflex initiation and modulation of patterned motor behavior (). We hypothesized that oropharyngeal dysphagia may be associated, at least in part, with sensory dysfunction as a result of PD-induced nerve damage. An important aspect of understanding oropharyngeal dysphagia and aspiration is to determine whether the sensory nervous system of upper aerodigestive tract is affected in PD as peripheral sensory mediation of the pharynx and larynx is crucial for triggering swallowing and upper airway protective reflexes.

Author: suerosier

In May of 2018, I was diagnosed with Parkinson's. After researching, I believe the symptoms began to manifest themselves years prior to last year. The purpose for my blog is to share what I have learned (with an index) to save others time as they seek for answers about, symptoms, therapies [and alternative things to try], tools I use, Parkinsonisms, recipes, strategies, clinical studies, words of encouragement or just enjoy the photos or humor.

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