Systematic Assessment of Laryngopharyngeal Function in Patients With Neurodegenerative Diseases

Overview

This is a non-interventional observational study designed to systematically record the results of routine laryngeal examinations and specific characteristics of dysphagia in patients with neurodegenerative disorders. The results of a fiberoptic / flexible endoscopic evaluation of swallowing (FEES) while performing a structured task protocol will be recorded. If available, laryngeal electromyography (EMG) results will also be recorded. In addition to the examination results, demographic and disease-specific data are collected, and two questionnaires, the Swallowing Disturbance Questionnaire for Parkinson's Disease (SDQ-PD) and the swallowing specific Quality Of Life Questionnaire (SWALQOL), are administered.

Neurodegenerative disorders are associated with a high prevalence of neurogenic dysphagia. Depending on the underlying disease, the prevalence can affect up to 80% of patients. Dysphagia is associated with dehydration, malnutrition, facilitates aspiration pneumonia and thereby determines the prognosis of neurodegenerative diseases. For most of them, dysphagia-associated complications are the leading cause of death. Multiple system atrophy (MSA) is a sporadic progressive neurodegenerative disorder caused by oligodendroglial aggregation of α-synuclein affecting predominantly the nigrostriatal, olivo-ponto-cerebellar, and autonomic systems,resulting in a clinical presentation of dysautonomia combined with either predominantly parkinsonian (MSA-P) or cerebellar (MSA-C) symptoms of varying severity.In its early stage, the diagnosis of MSA according to the second consensus criteria can be challenging. Therefore, the Movement Disorders Society MSA study group recently addressed the importance of developing valuable diagnostic tools for securing an early diagnosis in patients with MSA not only to estimate disease prognosis but also to early initiate novel, potentially disease-modifying treatments in clinical trials. Despite laryngopharyngeal dysfunction being associated with decreased life expectancy and quality of life, systematic assessment of these functions in MSA is scarce. Previously, an easy-to-implement MSA-FEES task-protocol was suggested to systematically assess laryngopharyngeal function. A pilot study on 8 patients with MSA not only showed that the task protocol was feasible and well tolerated, but also that laryngopharyngeal symptoms where highly prevalent despite the lack of clinical presentation (Warnecke et. al 2019). Moreover, irregular arytenoid cartilages movements where present in all MSA-patients when performing this task protocol, suggesting this symptom could serve as a clinical marker to identify MSA-patients. Following this pilot study, an observational two center study assessed 57 MSA patients with this protocol and compared findings to an age-matched cohort of PD-patients (Gandor et al. 2020). While only 43.9% of MSA patients had clinical symptoms of laryngeal dysfunction, 93% showed laryngeal abnormalities during FEES performing the task-protocol. 91.2% of MSA-patients showed irregular arytenoid cartilages movements. In contrast, only one PD patient showed laryngeal abnormalities with vocal fold motion impairment, but not irregular arytenoid cartilages movements. This study suggests that irregular arytenoid cartilages movements allow differentiating MSA from PD with a sensitivity of 0.9 and a specificity of 1.0. 4repeat tauopathies (4RT) are caused by an intraneuronal accumulation of 4repeat tau. 4RT, also known as progressive supranuclear palsy (PSP) with all its clinical subtypes, is a rapidly progressive neurodegenerative disease that leads to increasing impairment of cortical and subcortical function in the affected person due to the accumulation of tau protein in the brain (Höglinger 2017). Due to the clinical variability of the presentation, early diagnostic certainty is desirable. Depending on the affected area in the central nervous system, different clinical phenotypes result. The most commonly described and researched entity is Progressive Supranuclear P, also known as Richardson Syndrome, or PSP-RS. Further clinical presentations include a Parkinsonian variant (PSP-P), corticobasal syndrome (PSP-CBS), pure akinesia with gait freezing (PSP-PAGF), speech/language dominant presentations (PSP-SL), frontotemproal dementia variants (PSP-FTD), and cerebellar presentations (PSP-C) (Höglinger 2017). 4RT is also associated with swallowing and speech problems, and aspiration pneumonia is one of the most common causes of death in this disease entity (Tilley 2016). In addition, dystonic dysinnervation of laryngeal muscles can lead to laryngeal motion abnormalities (Panegyres 2007). Equally, patients with motor neurone disease (MND) are affected by dysphagia early in the disease. In a FEES study by Steven B. Leder and colleagues (2004), which included 17 ALS patients subjectively complaining of dysphagia, fluid aspiration or an increased risk of fluid aspiration was found in almost 60% of cases, regardless of whether the disease initially mainly affected the bulbar musculature or the limb musculature. As the disease progressed, the depth of penetration of fluids into the hypopharynx prior to triggering the swallowing reflex increased, so these patients were advised to thicken fluids. Initially, residues of solid food consistencies were detected in the valleculae, piriform sinus and/or laryngeal inlet in three patients after swallowing. As a result of progressive paresis of the pharyngeal muscles, the residuals increased in the ALS patients examined during the course of the disease. If this disorder pattern was detected, it was advised to reduce the size of the food bolus and to clear the pharynx by swallowing water or reswallowing several times. In a further small case series (n = 11), the FEES showed that dysphagic ALS patients are particularly at risk of penetration/aspiration when swallowing liquids. Penetration and aspiration occur particularly frequently intradeglutitively (D'Ottaviano et al. 2013). A recent publication reports on FEES examinations in 202 ALS patients (w/m 95/107; bulbar/spinal onset 66/136; mean age 64.68 +/- 11.12 years). A close positive correlation with disease severity (measured using the ALSFRS-R) was found for all FEES parameters (leaking, aspiration, residuals), regardless of the three consistencies tested (liquid, semi-solid, solid) (Fattori et al. 2017). The aim of this FEEMSA trial is to continue recruitment of patients with neurodegenerative diseases and systematically assess laryngopharyngeal function in large cohorts, to categorise the dysphagia phenotypes and better correlate them with the disease subtypes (MSA Parkinson vs cerebellar; PSP variants, MND variants, etc). If available, laryngeal EMG will also be recorded.