Systematic Assessment of Laryngopharyngeal Function in Patients With MSA, PD, and 4repeat Tauopathies

Study Overview
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Brief Summary
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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 multiple system atrophy (MSA), Parkinson's disease (PD) and progressive supranuclear palsy (PSP) and related 4repeat tauopathies. 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.

Detailed Description
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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. The aim of this FEEMSA trial is to continue recruitment of patients with MSA and PD and systematically assess laryngopharyngeal function in an even larger cohort. Moreover, patients with PSP and related 4repeat tauopathies will also be recruited at eligible sites to compare results from this cohort to results in MSA and PD. If available, laryngeal EMG will also be recorded.

Official Title
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Prospective Observational Study for the Systematic Assessment of Laryngopharyngeal Function in Patients With Multiple System Atrophy, Parkinson's Disease and 4repeat Tauopathies

Conditions
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Multiple System Atrophy, Parkinson Disease, Progressive Supranuclear Palsy

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis of probable or possible multiple system atrophy according to current consensus criteria (Gilman et al. 2008) or diagnosis of probable or possible PSP according to the the Movement Disorders Society (MDS) diagnostic criteria (Höglinger et al. 2017) or diagnosis of Parkinson's disease according to the MDS diagnostic criteria (Postuma et al 2015) Hoehn and Yahr Stage within the range of I-V Exclusion Criteria: Patients who do not sign the consent form Patients who have contraindications for performing fiber endoscopic laryngoscopy and swallowing examination. Pregnancy in female patients

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Multiple System Atrophy<br>Patients diagnosed will probable or possible MSA according to the 2nd criteria for the diagnosis of MSA (Gilman 2008) that received laryngopharyngeal assessment according to the systematic task protocol during FEES (Warnecke et al. 2019). | |
| progressive supranuclear palsy<br>Patients diagnosed will probable or possible Progressive Supranuclear Palsy or (PSP) related 4repeat tauopathies according to the Movement Disorders Society diagnostic criteria (Höglinger 2017) that received laryngopharyngeal assessment according to the systematic task protocol during FEES (Warnecke et al. 2019). | |
| Parkinson Disease<br>Patients diagnosed will Parkinson's disease according to the Movement Disorders Society diagnostic criteria (Postuma 2015) that received laryngopharyngeal assessment according to the systematic task protocol during FEES (Warnecke et al. 2019). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| laryngeal movement disorders | occurrence of vocal fold motion impairment, paradoxical vocal fold motion, vocal fold fixation or involuntary irregular arytenoid cartilages movements when assessed with the task-protocol | 1 day | 
| dysphagia | occurrence of dysphagic symptoms when assessed with the task-protocol | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple System Atrophy, Progressive Supranuclear Palsy, Parkinson's disease, clinical biomarker, FEES, laryngeal EMG, irregular arytenoid cartilages movements, dysphagia