Laryngeal Movement Disorders in Multiple System Atrophy: A Diagnostic Biomarker?

Abstract

A BS TRACT: Background: Multiple system atrophy (MSA) is a rare neurodegenerative disorder, and its parkinsonian variant can be difficult to delineate from Parkinson's disease (PD). Despite laryngeal dysfunction being associated with decreased life expectancy and quality of life, systematic assessments of laryngeal dysfunction in large cohorts are missing. Objectives: The objective of this study was to systematically assess laryngeal dysfunction in MSA and PD and identify laryngeal symptoms that allow for differentiating MSA from PD. Methods: Patients with probable or possible MSA underwent flexible endoscopic evaluation of swallowing performing a systematic task protocol. Findings were compared with an age-matched PD cohort. Results: A total of 57 patients with MSA (64 [59-71] years; 35 women) were included, and task assessments during endoscopic examination compared with 57 patients with PD (67 [60-73]; 28 women). Patients with MSA had a shorter disease duration (4 [3-5] years vs 7 [5-10]; P < 0.0001) and higher disease severity (Hoehn & Yahr stage 4 [3-4] vs 3 [2-4]; P < 0.0001). Of the patients with MSA, 43.9% showed clinically overt laryngeal dysfunction with inspiratory stridor. During endoscopic task assessment, however, 93% of patients with MSA demonstrated laryngeal dysfunction in contrast with only 1.8% of patients with PD (P < 0.0001). Irregular arytenoid cartilages movements were present in 91.2% of patients with MSA, but in no patients with PD (P < 0.0001). Further findings included vocal fold motion impairment (75.4%), paradoxical vocal fold motion (33.3%), and vocal fold fixation (19.3%). One patient with PD showed vocal fold motion impairment. Conclusion: Laryngeal movement disorders are highly prevalent in patients with MSA when assessed by a specific task protocol despite the lack of overt clinical symptoms. Our data suggest that irregular arytenoid cartilage movements could be used as a clinical marker to delineate MSA from PD with a specificity of 1.0 and sensitivity 0.9.

Endoscopic Characteristics of Dysphagia in Multiple System Atrophy Compared to Parkinson's Disease

“…22 In brief, we compared a cohort of patients with MSA (median, 64 [interquartile range (IQR): 59-71] years) with an age-matched cohort of patients with PD (median, 67 [IQR: 60-73] years; P = 0.06). Patients with MSA had a shorter disease duration (median, 4 [IQR: 3-5] vs. 7 [5][6][7][8][9][10] years; P < 0.0001), a higher disease severity (H&Y stage 4 [IQR: 3-4] vs. 3 [2][3][4]; P < 0.0001), and were physically more impaired (Unified Parkinson's Disease Rating Scale-motor, Part III: 35.5 [IQR: 29.8-41.8] vs. 28 [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36]; P < 0.01; Table 1). Cerebral MRI scans of 49 patients with MSA were available for analysis to support the clinical diagnosis.…”

“…In brief, this protocol is divided into an examination of laryngeal function at rest and during specific task performances followed by a detailed evaluation of swallowing. For the laryngeal assessment, please refer to the previous publications 21,22 . Swallowing was assessed as follows: during FEES, participants received 11 consecutive standardized test boluses in the following order: (1) 3 teaspoons of applesauce (approximately 3 mL each), (2) 1 teaspoon of blue‐dyed liquid (approximately 3 mL) to test oral control of a liquid bolus (task to hold a liquid bolus in the oral cavity until told to swallow), (3) 2 teaspoons of blue‐dyed water (approximately 3 mL), (4) one sip of blue‐dyed water from a glass or straw, (5) three pieces of buttered soft white bread (about 3‐cm square), and (6) one swallow of a placebo tablet (10‐mm diameter) ingested with either blue‐dyed water or applesauce.…”

“…A pilot study showed that the task protocol was feasible and well tolerated 21 . Furthermore, we recently showed that patients with MSA present with MSA‐specific laryngeal motion abnormalities when using this task protocol, allowing for a highly sensitive and specific delineation from patients with PD 22 …”

Pharyngolaryngeal semiology and prognostic factors in multiple system atrophy

“…For Warnecke et al [ 22 ], arytenoid fluttering or flapping and abduction defects are pathognomonic signs of MSA. This fact was corroborated by Gandor et al [ 23 ], who explained that arytenoid fluttering could serve as a biomarker to differentiate between MSA and PD. These studies also confirm the importance of stridor, already identified as a factor for a poor prognosis in Krim and Yekhlef’s study (RR = 3.64; p = 0.006) [ 24 ].…”

Phoniatricians and otorhinolaryngologists approaching oropharyngeal dysphagia: an update on FEES

“…In all the cases with an undiagnosed underlying disease, detailed information on the anatomical, sensory-motor findings, and effects of compensatory strategies must be obtained and discussed with the physician or medical team in charge of the patient. In some cases, this information is pathognomonic for the underlying disease, such as the sign of the rising tide in case of a Zenker diverticulum [ 50 ], while in other cases, additional clinical information is necessary to determine the underlying diagnosis, such as a vocal fold movement disorder in multiple system atrophy [ 51 , 52 ].…”