Prospective Observational Study for the Systematic Assessment of Laryngopharyngeal Function in Patients With Neurodegenerative Diseases

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).