In the present study the characteristics of dysphagia in patients with MSA were analyzed using FEES. The dysphagia phenotypes have been analyzed for the first time. In addition, the laryngeal motility, as well as the associations among unsafe and not-efficient swallow and laryngeal motility impairment were evaluated.

The large majority of patients with MSA demonstrated a swallowing impairment and in 80% of them 2 or more dysphagia phenotypes were detected. The more common were the Delayed pharyngeal phase with all the tested consistencies, followed by Posterior oral incontinence mainly visible with Liquids and Propulsion deficit with Semisolids and Solids. These data are in line with those of Warnecke et al. [20] who performed a systematic literature review in order to analyze the characteristics of neurogenic dysphagia using FEES. The authors reported that patients with atypical parkinsonian syndromes more commonly present pharyngolaryngeal movement disorders, premature bolus spillage and impaired swallowing reflex. Higo et al. [13] analyzed a total of 29 patients with MSA (22 MSA-C and 7 MSA-P) using VFS and found a delayed bolus transport in 73% of patients and impaired oral bolus control in 49%. The same author a couple of years later [14] analyzed the swallowing function in a group of 21 patients with MSA-C and found that swallowing function in the oral phase became gradually disturbed with the progression of the disease affecting both the bolus transport and bolus holding. Finally, Park et al. [15] who studied the swallowing outcomes following speech therapy in 7 patients with MSA-C using VFS found that patients suffered mainly from pharyngeal phase disturbances and premature bolus loss.

In our sample no differences between patients with MSA-C and MSA-P were demonstrated. This finding agrees with the results of Vogel et al. [12] who evaluated the endoscopic characteristics of dysphagia using FEES in 57 PD, 12 MSA-C and 45 MSA-P patients and found no differences in dysphagia pattern between MSA-C and MSA-P patients. In addition, Fernagut et al. [39] did not find any significant differences in the severity of dysphagia between patients with MSA-P and MSA-C. Lee et al. [18] analyzed the swallowing functions in a group of 31 patients with MSA-P and 21 with MSA-C using VFS. The authors did not find any significant differences in the oral and pharyngeal transit time, triggering of pharyngeal swallow, and premature bolus loss between the two groups. Moreover, Higo et al. [13, 14] demonstrated oral and pharyngeal dysfunction in both patients with MSA-P and MSA-C. The authors suggested that dysphagia in patients with MSA-P is a result of Parkinsonism which manifests with bradykinesia and rigidity of the tongue with consequent delayed bolus transport from the oral cavity to the pharynx and disturbance of bolus holding in the oral cavity, while in patients with MSA-C it is the disturbed coordination of tongue movement by cerebellar dysfunction, rather than Parkinsonism, which determines swallowing dysfunction in the oral phase at the early stage even if parkinsonism is also involved at the late stage [13, 14]. It is possible that in patients with MSA, both Parkinsonism and cerebellar dysfunction may distinctly contribute to dysphagia and consequently the absence of statistically significant differences between patients with MSA-P and MSA-C found in the present study might be related to the low number of enrolled patients. On the other hand, it is also possible that no difference exists in the dysphagia phenotypes in MSA-P and MSA-C. Further studies are needed to test these hypotheses.

Aspiration (bolus below the true vocal folds) occurred only with Liquid and was found in the 20% of the sample, while penetration (bolus enters the airway but not below the true vocal folds) was far more frequent (68%), in particular with Liquid, followed by Semisolid. Accordingly, safety of swallow was lower with Liquid with a compromised airway protection occurring both “during” and “before” the swallow in the majority of patients. These data suggest that the viscosity of the ingested food significantly affect the swallowing safety in patients with MSA. This finding agrees with Clavé et al. [40] who found that in patients with neurogenic dysphagia, increasing viscosity brought about a dramatic improvement on safety by minimizing penetration and aspiration during swallow.

As far as the high percentage of patients who demonstrated penetration and/or aspiration found in the present paper is concerned, the results here reported are in accordance with those of Lee et al. [18] who found that penetration or aspiration occurred in 67.8% of patients with MSA. Several previous studies evaluated the prevalence of dysphagia among patients with MSA but no information regarding the PAS score were provided. For example, Vogel et al. [12] by analyzing through FEES the swallowing abilities in a group of 57 patients with MSA found that penetration and aspiration occurred in 21% and 7% of the sample respectively.

The Fisher test did not demonstrate any significant differences in the distribution of PAS categories and safety of swallow between patients with MAS-P and MSA-C with the only exception for the Semisolid. In particular, penetration occurred significantly more frequently in patients with MSA-C. A possible explanation is related to a delayed pharyngeal phase which is particularly common even in early stages in patients with MSA-C as reported by Higo et al. [14]. However, no differences in the safety of swallow between the two groups was demonstrated thus suggesting that the severity of dysphagia is similar in both phenotypes. This finding agrees with those of Do et al. [17] who did not find any significant differences in the incidence of aspiration pneumonia between patients with MSA-P and MSA-C.

Residues of ingested food were demonstrated both in the pyriform sinus and in the vallecula with all the three consistencies. In addition, inefficient swallow was found in a high percentage of patients regardless of the consistency of the ingested food and of the phenotype of MSA, thus suggesting an impairment in the bolus propelling from the oropharynx to the esophagus. This finding is in accordance with the results of Higo et al. [13] who analyzed the manometric data of oropharyngeal and hypopharyngeal swallowing pressure in patients with MSA and found a decreased swallowing pressure compared to control subjects. In addition, the authors demonstrated bolus stasis at the pyriform sinuses in the 27.2% of patients with MSA. Similarly, Lee et al. [18] reported that the most common finding at VFS in patients with MSA was vallecular and pyriform sinus residues (89.8% and 63.2% respectively). Vogel et al. [12] found relevant pharyngeal residues in 50.9% of patients with MSA. Additionally, Ueha et al. [41] found abnormal hypertensive proximal esophageal contraction during swallowing, deficient upper esophageal sphincter (UES) relaxation and impaired UES relaxation in the 56%, 32% and 12% of patients with MSA.

FEES examination revealed that most patients with MSA demonstrated at least one laryngeal movement alteration. IACM and VFMI were the conditions most frequently encountered; in addition, more than half of the enrolled patients demonstrated more than 2 laryngeal movement alterations. These results are in line to those previously reported even if the percentages of patients affected by laryngeal movement alterations appear lower than those reported by Gandor et al. [1] and by Warnecke et al. [20]. In the former study, the authors analyzed laryngeal movement in a group of 57 patients with MSA and found that iACM was the most prevalent laryngeal findings (91.2% of the sample) followed by VFMI (75.4%) [1]. In the latter, the authors found irregular arytenoid cartilages movements and vocal fold abduction restriction in all patients with MSA [20]. It is possible that the lower percentages found in our study might be related to differences in the severity of MSA among the patients enrolled in the different studies. In our sample 9 patients scored 1 or 2 at GD-UMSARS, in the study of Gandor et al. [1] the median Hoehn and Yahr stage was 4 while in the study of Warnecke et al. [20] the mean Hoehn and Yahr stage was 3.75. On the other hand, other authors reported a lower prevalence of laryngeal movement disorders in patients with MSA. Higo et al. [19] performed laryngoscopy on 38 MSA patients to assess laryngeal function and found VFMI in 17 of them. Simpson et al. [42] reported “flickering movements of the vocal folds” in 3 of 6 MSA patients during laryngoscopy. Irregular tremulous movement of the arytenoid cartilages was detected also by Shimohata et al. [43]. As suggested by Gandor et al. [1], the systematic assessment of laryngeal function using task provoking maximum VF movement (which allowed an easier identification of motion abnormalities) might explain the higher prevalence of laryngeal movement disorders found in this study.

The underlying pathology of laryngeal symptoms in MSA still remains under debate [1]. Nonetheless, iACM seems to predict the occurrence of glottic area reduction [44] and has been suggested as a valuable clinical marker for MSA allowing for delineation from Parkinson disease [1, 20]. Therefore, as proposed by Gandor et al. [1], an early evaluation of laryngeal function should be performed when MSA is suspected.

No significant differences in the safety of swallow and presence of laryngeal movement alterations on one side and the different dysphagia phenotypes on the other were demonstrated at Fisher’s exact test. This finding is difficult to compare since in none of the previous study the association among these elements was analyzed. On the other hand, patients with Propulsion deficit demonstrated a significantly lower swallow efficiency than patients without Propulsion deficit. This result agrees with those reported by Steele et al. [45]. In their systematic review the authors concluded that patients affected by poor pharyngeal contraction and tongue-base retraction experience more residues as the effort required for swallowing increases with thicker and harder foods.

There are several limitations in this study. First, the number of enrolled patients is quite small, even if in line with previous studies. Because of the rarity of the disease, it was difficult to collect a large number of patients. For this reason, the results here reported should be considered with caution. For example, even if there is no statistically significant difference between MSA-P and MSA-C for GD-UMSARS, it doesn't seem that the two groups are homogenous populations. In fact, according to a power calculation a difference of about 40% in the percentage of patients with GD-UMSARS less than 4, will have a power of 80% with alpha equal to 5% with 32 and 16 patients in MSA-P and MSA-C groups, respectively (hypothesizing a 2 to 1 ratio). This further stress the need to take with extreme caution the results of the comparison between patients with MSA-P and MSA-C. In addition, a larger number of enrolled patients would have allowed to perform subgroup analysis on the basis of the severity of the disease. Dysphagia phenotypes were judged as present or absent, according to the classification proposed by Desuter [31], whose psychometric properties still need to be analyzed.

In conclusion even in MSA patients under full oral nutrition with more than one consistency unsafe and inefficient swallow are quite frequent. The most common dysphagia phenotypes are delayed pharyngeal phase and posterior oral incontinence. Propulsion deficit is associated with lower swallow efficiency. Swallowing function and abnormal laryngeal movements seems to be similar in patients with MSA-C and patients with MSA-P.