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Laryngeal Movement Disorders as a Clinical Biomarker in Multiple System Atrophy: Results from the LaPD Study
31 Pages Posted: 26 Jun 2020
More...Abstract
Background: Multiple system atrophy (MSA) is a rare neurodegenerative disorder that can be difficult to delineate from idiopathic Parkinson's disease (PD) in early stages. Despite laryngeal dysfunction being associated with decreased life expectancy and quality of life in MSA, a systematic evaluation of laryngeal movement disorders in a large cohort has not been performed so far. The present study systematically assessed laryngeal dysfunction in MSA and PD and identified potential clinical laryngeal biomarkers that allow for differentiating MSA from PD.
Methods: At two specialised centres in Germany, eligible participants with probable or possible MSA underwent flexible endoscopic evaluation of swallowing (FEES) performing a systematic MSA-FEES task-protocol. Findings were compared to an age-matched cohort of PD-patients.
Findings: Between September 2017 and January 2020, 57 consecutive MSA-patients (median age 64 [IQR 59-71] years, 35 women) were included and MSA-FEES task-assessments compared to 57 PD-patients (age 67 [60-73] years; 28 women). MSA-patients had a shorter disease duration (4 [3-5] years vs. 7 [5-10] years; p<0·0001) and higher disease severity expressed by Hoehn&Yahr stage (4 [3-4] vs. 3 [2-4]; p<0·0001). 43·9% of MSA-patients showed clinically overt laryngeal dysfunction with inspiratory stridor. During the MSA-FEES task-assessment however, 93% of MSA-patients demonstrated laryngeal dysfunction in contrast to only 1·8% PD-patients (p<0·0001). Irregular arytenoid cartilages movements (iACM) were present in 91·2% MSA-patients but in no PD-patient (p<0·0001), resulting in a specificity of 1·0 and a sensitivity of 0·9. Further findings included vocal fold motion impairment (VFMI) (75·4%), paradoxical vocal fold motion (33·3%) and vocal fold fixation (19·3%). One PD-patient showed VFMI.
Interpretation: Laryngeal movement disorders are highly prevalent in MSA-patients when assessed by a specific MSA-FEES task-protocol despite the lack of overt clinical symptoms. Our data suggest that iACM could be used as a clinical biomarker to delineate MSA from PD with high specificity and sensitivity.
Funding: This study was not funded
Declaration of Interest: Florin Gandorreports personal fees from AbbVie Pharma, personal fees from Merz Pharma, personal fees from BIAL Pharma, outside the submitted work.Annemarie Vogelreports no conflicts of interest. Inga Clausreports personal fees from AbbVie Pharma, outside the submitted work.Sigrid Ahringreports no conflicts of interest.Doreen Gruberreportspersonal fees from Licher Pharma, personal fees from Medtronic, personal fees from UCB Pharma, outside the submitted work. Hans-Jochen Heinzereportsno conflicts of interest. Rainer Dziewasreports personal fees from Bayer AG, personal fees from Boehringer Ingelheim Pharma, personal fees from Daiichi-Sankyo GmbH, personal fees from Nestlé S.A., personal fees from Olympus, personal fees from Pfizer Pharma, personal fees from Sanofi-Aventis GmbH, outside the submitted work. Georg Ebersbachreports personal fees from AbbVie Pharma, personal fees from BIAL Pharma, personal fees from Britannia Pharma, personal fees from Desitin Pharma, personal fees from Licher Pharma, personal fees from UCB Pharma, personal fees from Zambon Pharma, personal fees from STADA Pharma, personal fees from Neuroderm Inc, personal fees from Kohlhammer Verlag, personal fees from Thieme Verlag, outside the submitted work. Tobias Warneckereports personal feesfrom AbbVie Pharma, personal fees from BIAL Pharma, personal fees from Desitin Pharma, personal fees from Licher Pharma, personal fees from Zambon Pharma, personal fees from Biogen GmbH, personal fees from Pfizer Pharma, personal fees from Phagenesis Ltd., grants from AbbVie Pharma, outside the submitted work.
Ethical Approval: This prospective observational study was approved by the Ethics Committee of the Brandenburg Medical Board (S21(a)/2017) and the Ethics Committee of the University of Münster (2017-585-b-S) and is registered in the Fox Trial Finder of the Michael J. Fox Foundation (www.foxtrialfinder.michaeljfox.org, trial number 005066). Participants:All participants provided written informed consent. Included participants were either diagnosed with possible or probable MSA of the predominant Parkinsonian (MSA-P) or cerebellar (MSA-C) variant according to the second consensus criteria4or met the diagnosis of idiopathic Parkinson's disease (PD) according to the Movement Disorders Society criteria. Participants were recruited at two German study centres specialized in the diagnosis and treatment of movement disorders
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