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Considerable discrepancy found between overt clinical symptoms of laryngeal pathology and abnormalities observed during a task protocol.
New research shows laryngeal movement disorders could serve as a diagnostic biomarker for multiple system atrophy (MSA), which could help distinguish the disease from Parkinson disease following systematic assessments of laryngeal dysfunction identifying it as highly prevalent in this patient population.
Conducted by a group including Georg Ebersbach, MD, chief physician, Parkinson Clinic, Movement Disorders Hospital, Kliniken Beelitz GmbH, the study found that with flexible endoscopic evaluation of swallowing (FEES), 93% of patients (n = 53) with MSA demonstrated laryngeal dysfunction compared with only 1.8% of patients (n = 1) in the matched Parkinson cohort (P <.0001).
In total, the study included 57 patients with MSA and 57 patients with Parkinson disease. In the MSA group 43 patients presented with more than 1 laryngeal symptom on FEES.
“FEES is becoming increasingly available in neurology departments worldwide, and we therefore suggest that whenever MSA is suspected, patients should undergo a systematic and standardized endoscopic MSA‐FEES task protocol assessment of laryngeal function to improve diagnostic certainty of MSA and delineation from Parkinson, taking other clinical signs into account,” Ebersbach and colleagues concluded. “Furthermore, we suggest that endoscopic laryngeal findings, above all the occurrence of irregular arytenoid cartilages movements, should be implemented into the next revised diagnostic criteria for MSA.”
Of those with MSA, 43.9% (n = 25) showed clinically overt laryngeal dysfunction with inspiratory stridor, compared to none of the patients with Parkinson.
The investigators noted there was “considerable discrepancy” between overt clinical symptoms of laryngeal pathology and the abnormalities observed during the task protocol, which has been somewhat identified by prior literature in 2019 showing the difficultly in diagnosing inspiratory stridor in MSA.
Additionally, they pointed to the work of Ozawa et al. in 2010, showing that irregular arytenoid cartilages movements (iACM)—which investigators observed in 91.2% (n = 52) of those with MSA compared to 0% of the Parkinson cohort (sensitivity, 0.9; specificity, 1.0; P <.0001)—are likely to precede the clinical onset of inspiratory stridor, which might explain their observations of its occurrence of iACM without inspiratory stridor.
Ebersbach and colleagues observed that iACM were present at rest in 80.7% (n = 46) of the MSA group, and could be provoked in an additional 10.5% (n = 6) patients during a newly designed positioning task.
“Therefore, laryngeal function should be assessed as early as possible, even without clinical evidence of laryngeal motion abnormalities, when MSA is suspected,” Ebersbach and colleagues wrote. “To further support this recommendation, we performed a subgroup analysis and showed that laryngeal motion abnormalities are present as early as 1 year after disease onset.
The aforementioned analysis revealed that the frequency of laryngeal findings was independent of MSA phenotype (χ2 = 3.96; P = 0.41; Cramér's V = 0.15) and a diagnostic level of certainty (χ2 = 8.87; P = 0.06; Cramér's V = 0.22).
The MSA cohort did have some significant differences from the matched Parkinson cohort, coming with shorter disease duration (MSA: 4 years [interquartile range (IQR), 3–5]; Parkinson: 7 years [IQR, 5–10]; P <.0001), higher disease severity (MSA: Hoehn and Yahr stage, 4 [IQR, 3–4]; Parkinson: stage, 3 [IQR, 2–4]; P <.0001), and more physical impairment (MSA: Unified Parkinson's Disease Rating Scale motor score, 35.5 [IQR, 29.8–41.8]; Parkinson: motor score, 28 [IQR, 19–36]; P <.01).
Additional analysis showed that patients with MSA had higher rates of vocal fold motion impairment (75.4%; n = 43; At rest: 66.7% [n = 38]), paradoxical vocal fold motion (33.3%; n = 19), and vocal fold fixation (19.3%; n = 11). In comparison, 1 patient with Parkinson showed vocal fold motion impairment.
The investigators identified a number of unknowns that require further study, including if laryngeal abnormalities allow for delineation of MSA from 4R‐tauopathies, as well as in the debate around the underlying pathology of laryngeal symptoms in MSA.
“An international multicenter study under guidance of the Movement Disorders Society MSA study group is under way to collect longitudinal data on laryngopharyngeal findings in patients with MSA using the MSA‐FEES task protocol,” they wrote. “In addition, systematic laryngeal assessment with the FEES task protocol will also be performed in patients with 4R‐tauopathies and the results compared with patients with MSA and Parkinson.”