High‐Resolution Pharyngeal Manometry Assessment of Swallowing in Asymptomatic Myotonic Dystrophy

Abstract

ABSTRACT

Objectives

Myotonic dystrophy (MyD) adversely affects swallowing function from an early stage. However, the swallowing characteristics of patients with MyD, who rarely seek medical attention owing to a lack of subjective symptoms, remain unclear. We aimed to analyze multifaceted swallowing function tests, including high‐resolution manometry (HRM), in patients with asymptomatic MyD and evaluate the swallowing pathophysiology in these patients.

Methods

We included patients who underwent HRM and swallowing function tests, including videofluoroscopic swallow study (VFSS), at our hospital. We analyzed the results along with the clinical and demographic profiles of the patients, comparing them to those in a non‐MyD control group of patients with mild dysphagia.

Results

The MyD group demonstrated significantly decreased swallowing motility on VFSS and reduced pharyngeal contraction force at all stages from the pharynx to the upper esophageal sphincter (UES) on HRM. In the non‐MyD control group, a weak negative correlation was observed between maximum pharyngeal contraction force and minimum UES pressure during swallowing. Conversely, in the MyD group, the minimum UES pressure remained consistently low, regardless of weak pharyngeal contraction force.

Conclusion

Our study confirmed that patients with MyD exhibited significant motor disorders of swallowing‐related muscles even when unaware of their dysphagia. While constant UES relaxation may help maintain swallowing, particularly for liquids, it hinders patients' ability to recognize their swallowing problems and can lead to sudden choking episodes. Early risk management and intervention are, thus, necessary for patients with MyD, even those unaware of their dysphagia.

Level of Evidence

IV.

Introduction

Myotonic dystrophy (MyD) is an autosomal dominant inherited genetic muscular disorder characterized by progressive muscle weakness, myotonia, and multiorgan involvement [1, 2]. MyD is caused by an expansion of cytosine–thymine–guanine (CTG) of trinucleotide repeats in the 3′ untranslated region (3′ UTR) of the dystrophia myotonica protein kinase (DMPK) gene located on chromosome 19q13.3 [3, 4]. As the disease progresses, weakness and myotonia in the distal muscles increase, causing stiffness and debilitating pain, which collectively reduce motor function and quality of life [5]. One of the common and potentially severe complications of MyD is dysphagia, which affects approximately 55%–80% of patients [6]. Dysphagia in these patients can lead to severe complications such as aspiration pneumonia, malnutrition, and even sudden death due to choking [7–9].

While the prevalence and risks of dysphagia in MyD are well-documented, the specific swallowing characteristics and pathophysiology in patients with MyD, especially those unaware of their swallowing difficulties, remain incompletely understood. Previous studies have shown impairments at various stages of swallowing in patients with MyD, from the oral preparatory phase to the esophageal phase [10–12]. However, conflicting findings have been reported regarding upper esophageal sphincter (UES) function [9–14]. Some studies have noted decreased resting pressure, while others found normal function [15] or delayed UES opening [16].

The challenge with studying dysphagia in MyD is compounded by the fact that many patients have few subjective symptoms owing to emotional deficits and lack of interest, making it difficult to identify swallowing problems using conventional screening tests [17, 18]. This lack of symptom awareness can delay diagnosis and intervention, potentially increasing the risk of serious complications. Early management is crucial; however, personality disorders, intellectual and cognitive impairments, lack of interest in the disease [18], or sleepiness can result in poor awareness of declining swallowing function among patients with MyD [19].

To address these knowledge gaps, we conducted a cross-sectional study involving multifaceted swallowing function tests, including high-resolution manometry (HRM), in patients with MyD with little to no subjective symptoms of dysphagia. Participants were divided into two groups: Those with and without myotonic dystrophy (MyD and non-MyD, respectively), both exhibiting only mild or no apparent symptoms of swallowing difficulty. By comparing these results, we sought to determine whether patients with MyD exhibit more severe swallowing dysfunction than non-MyD patients despite similar levels of subjective complaints, and to characterize the swallowing pathophysiology specific to MyD.

Our findings could provide valuable insights into the early detection and management of dysphagia in patients with MyD, potentially improving clinical outcomes and quality of life in this patient population.

Materials and Methods

Ethics

This study was approved by the Institutional Review Board of Ehime University Medical Hospital (Approval no. 2108030). Written informed consent was obtained from all participants enrolled in this study. No stipends were provided for participation.

Participants

To assess the degree of swallowing function deterioration in patients with MyD with few subjective symptoms, this study employed a control group comprising individuals who maintained independent oral intake despite mild awareness of swallowing difficulties, such as throat discomfort after swallowing. The exclusion criteria were: (1) unstable vital signs, (2) poor level of consciousness, (3) history of cerebrovascular disease, other neuromuscular diseases, or head and neck tumors or related surgical procedures, and (4) patients who had undergone a tracheostomy or had vocal cord paralysis.

MyD Group

Of the 21 patients with MyD referred by neurologists for evaluation of swallowing function between September 2014 and April 2023, seventeen who reported little or no dysphagia were enrolled (eight males, nine females; median age 42.0 years [interquartile range, IQR 27.0, 50.0]; range, 21–63 years). All patients were diagnosed with MyD by a neurologist based on clinical, genetic, and electromyographic findings. Sixteen patients with MyD were genetically diagnosed, and the phenotype was classical adult [20]. One patient with MyD was diagnosed clinically, and the phenotype was mild/late-onset adult. Disease duration since symptom onset ranged from 0 to > 40 years, and the number of repeats ranged from 160 to 2000. No patient had a history of aspiration pneumonia.

Non-MyD Control Group

For this group, 293 consecutive patients who underwent HRM and fiberoptic endoscopic evaluation of swallowing or videofluoroscopic swallow study (VFSS) for evaluation of swallowing function at our hospital between November 2016 and April 2023 were recruited. From this pool, 22 patients were selected as age-matched controls to the MyD group. These individuals reported mild swallowing-related symptoms, such as throat discomfort after swallowing, but maintained independent oral intake (13 males, 9 females; median age 48.5 years [IQR, 46.0, 53.0]; range, 29–58 years).

Study Design and Procedures

Clinical and demographic data, nutritional assessment, body mass index (BMI), prognostic nutritional index (PNI), HRM, and VFSS with modified barium swallow impairment profile (MBSImP) scoring in a subset of participants were collected and compared between the MyD and non-MyD control groups.

PNI is an index that predicts the incidence of postoperative complications after surgical procedures [21].$$$ PNI=\left[10\times serum\ albumin\ \left(g/ dl\right)\right]+\left[0.005\times total\ lymphocyte\ count\ \left(/ mm3\right)\right] $$$

PNI ≤ 40 indicates moderately malnourished patients and is a contraindication for resection.

There were no missing HRM data in either group. The non-MyD control group was selected by age matching; however, some participants had randomly missing clinical or VFSS data. Therefore, BMI, PNI, and albumin were compared between 16 patients with MyD and 19 non-MyD control patients, while VFSS was compared between 17 patients with MyD and 14 non-MyD control patients.

HRM

A solid-state manometric assembly with 36 circumferential sensors spaced at 1-cm intervals with a 4.2-mm external diameter (ManoScan 360; Medtronic, Minneapolis, MN) was used. Manometric analyses were performed as reported previously [22]. Patients were examined at least 2 h postprandially seated in an upright position. The walls of the nasal cavity were anesthetized for 5 min using a gauze soaked in a topical solution containing xylocaine and adrenaline. Subsequently, a pressure sensor catheter was inserted up to the cervical esophagus, approximately 40 cm from the nostril, and fixed by taping it to the patient's nose. Testing commenced 5 min after catheter insertion to allow acclimation. Pressures were recorded while swallowing 2 mL of saline water approximately four times at 30-s intervals. Although the 2021 guidelines by the High-Resolution Pharyngeal Manometry International Working Group recommend 5- or 10-mL boluses, we used 2-mL boluses following our institutional protocol, which has been in place since 2016. A previous report also demonstrated the utility of 2-mL swallows in assessing dysphagia severity [22]. Manometric data were analyzed using ManoView software (Medtronic, Minneapolis, MN, USA).

Key parameters measured included maximum swallowing pressures at multiple pharyngeal locations (velopharynx, mesopharynx, hypopharynx, and postdeglutitive UES), UES relaxation metrics (minimum UES pressure and UES relaxation time), and UES pressure and width at rest (Figure 1).

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VFSS

Generally, all patients were positioned upright; however, one patient had difficulty holding her neck; therefore, she underwent VFSS in a semi-upright position at approximately 60°. Subsequently, each patient swallowed 5 mL of iopamidol. An X-ray TV system was employed in the lateral and anteroposterior views at 15 frames per second (ZEXIRA DREX-ZX80; Canon, Tokyo, Japan). Approximately 3–5 swallowing events were recorded in each patient and digitized as video clips.

The VFSS data were analyzed using the MBSImP, an ordinal rating system designed to evaluate multiple physiological components observed on videofluoroscopy. We selected 10 of the 17 MBSImP components corresponding to the pharyngeal stage (Table 1). Each scale ranged from 0 to 3 or 4 points [23]. The total score ranged from 0 to 29, with higher scores indicating more severe impairment. Two otolaryngologists with more than 20 years and 7 years of experience interpreted each swallowing image.

TABLE 1 MBSImp corresponding to the pharyngeal stage.

Pharyngeal phase	Scale
Soft palate elevation	0–4
Laryngeal elevation	0–3
Anterior hyoid excursion	0–2
Epiglottic movement	0–2
Laryngeal vestibular closure	0–2
Pharyngeal stripping wave	0–2
Pharyngeal contraction	0–3
Pharyngoesophageal segment opening	0–3
Tongue base retraction	0–4
Pharyngeal residue	0–4

Statistical Analyses

All data are expressed as median values ± IQR. The metrics between the two groups were compared using the Chi-square or Wilcoxon rank-sum tests. The correlation between the manometric parameters was computed using Spearman's rank correlation coefficient. Correlation coefficients were calculated between the minimum UES pressure and each contraction pressure. Statistical significance was set at p < 0.05 for all tests. The inter- and intraexaminer agreements for the MBSImP score were evaluated using the kappa (κ) statistic. All statistical analyses were performed using the JMP software for Macintosh (SAS Institute Inc., Cary, NC, USA).

Results

Clinical Characteristics and Demographic Data of Patients With MyD

The clinical features of all the patients are summarized in Table 2. Table 3 presents the characteristics of the study population. Sex, age, BMI, PNI, and albumin levels were not significantly different between the MyD and non-MyD groups (p > 0.05).

TABLE 2 Clinical features of patients with myotonic dystrophy.

No	Age (y)	Sex	Phenotype (CTG repetition > age of onset)	Disease duration (y)	Number of repetitions
1	21	M	Classical adult	8	650
2	50	M	Classical adult	6	1000
3	29	M	Classical adult	14	730
4	22	F	Classical adult	5	300
5	24	M	Classical adult	11	800
6	63	F	Mild/late onset adult	7	Unknown
7	42	F	Classical adult	1	1000
8	47	M	Classical adult	6	600
9	30	F	Classical adult	7	440–600
10	33	F	Classical adult	0	1700
11	25	F	Classical adult	8	300
12	53	F	Classical adult	10	1350–2000
13	53	M	Classical adult	7	160
14	27	M	Classical adult	14	550–800
15	56	F	Classical adult	40	Unknown
16	46	F	Classical adult	> 20	1800
17	49	M	Classical adult	8	600

TABLE 3 Characteristics of the study participants.

	n (%) or median [IQR]	p a
MyD (n = 17)	Non-MyD (n = 22)
Sex (male)	8 (47.1)	13 (59.1)	0.45
Age (years)	42.0 [27.0, 50.0]	48.5 [46.0, 53.0]	0.07
BMI (kg/m2)	18.1 [17.0, 24.0]	20.2 [17.8, 22.8]	0.75
(n = 16)	(n = 19)
PNI	50.2 [47.1, 54.0]	50.7 [44.5, 53.2]	0.92
(n = 16)	(n = 19)
Albumin (g/dL)	4.3 [3.7, 4.3]	4.3 [4.0, 4.5]	0.35
(n = 16)	(n = 19)

HRM Findings

HRM data measures are shown in Table 4. Pharyngeal contractility significantly decreased in the MyD group at all phases (velopharynx, mesopharynx, hypopharynx, and postdeglutition UES). UES relaxation time was significantly longer in the MyD group than in the non-MyD control group. UES pressure and width at rest were markedly decreased. A weak negative correlation (correlation coefficient = −0.25) was observed between mesopharyngeal contraction pressure and minimum UES pressure in the non-MyD control group (p = 0.27). That is, the stronger the pharyngeal contractility, the lower the minimum UES pressure. A weak positive correlation (correlation coefficient = 0.25) between mesopharyngeal contraction pressure and minimum UES pressure was observed in the MyD group (p = 0.33), which was not statistically significant. Figure 2 shows the HRM topography of two representative cases in patients with MyD. In both cases, a significant reduction in pharyngeal contraction force is observed. Furthermore, the UES region, which normally forms a positive pressure zone at rest, is poorly visualized owing to the reduced pressure.

TABLE 4 HRM data.

	Median [IQR]	p a
MyD (n = 17)	Non-MyD (n = 22)
Velopharynx (mmHg)	43.9 [24.5, 54.9]	127.3 [88.3, 181.3]	< 0.001
Mesopharynx (mmHg)	50.4 [26.4, 60.8]	104.6 [72.8, 153.9]	0.001
Hypopharynx (mmHg)	41.4 [30.1, 61.8]	146.6 [98.3, 212.2]	0.001
Postdeglutitive UES (mmHg)	70.5 [59.5, 89.4]	201.7 [146.6, 344.0]	< 0.001
UES pressure at rest (mmHg)	13.0 [3.8, 14.9]	39.9 [29.6, 55.3]	< 0.001
UES width at rest (cm)	1.1 [0.0, 1.9]	3.5 [2.8, 4.8]	< 0.001
Minimum UES pressure (mmHg)	−5.0 [−9.7, −3.4]	−6.2 [−8.0, −2.9]	0.58
UES relaxation time (s)	0.40 [0.40, 0.60]	0.35 [0.26, 0.40]	0.02

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Modified Barium Swallow Impairment Profile Findings

Table 5 shows the MBSImP scores. The total pharyngeal stage score was 15.0 [IQR 14.0, 18.0] in the MyD and 6.5 [IQR, 2.0, 11.0] in the non-MyD control group (p < 0.001). In VFSS, patients with MyD had significantly more severe dysphagia than those in the non-MyD control group. The interrater reliability with intraclass coefficients (κ statistic) for the MBSImP score was 0.98. Figure 3 shows the VFSS findings. In the patient with MyD, when the swallowing reflex is triggered, the laryngeal cavity remains partially open due to weak laryngeal elevation and reduced pharyngeal contraction. However, the UES remains open, allowing the contrast medium to pass into the esophagus (Figure 3b). Postswallow, the contrast medium continues to flow from the pharynx into the esophagus, indicating insufficient closure of the UES (Figure 3c).

TABLE 5 MBSImP scores.

	Median [IQR]	p a
MyD (n = 17)	Non-MyD (n = 14)
MBSImP total	15.0 [14.0, 18.0]	6.5 [2.0, 11.0]	< 0.001

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Discussion

In this study, we investigated the swallowing function in patients with MyD with few subjective swallowing symptoms, examining the degree of dysphagia and associated pathological characteristics. HRM swallowing pressures at multiple pharyngeal locations revealed that patients with MyD exhibited a marked decline in pharyngeal swallowing motor function, even without subjective symptoms. Furthermore, we observed that the constant relaxation of the UES allowed liquids to pass into the esophagus gradually by gravity despite the decline in pharyngeal swallowing motor function, which appears to be characteristic of this disease. While the decrease in pharyngeal contraction force and UES pressure in patients with MyD observed in our study aligns with similar results in previous reports [12, 24], our study is the first to elucidate how these physiological changes affect swallowing dynamics in these patients. It is well established that patients with MyD often lack awareness of their swallowing function decline owing to cognitive impairment and indifference to their condition. However, this study suggests that the constant relaxation of the UES in MyD may have an advantage in swallowing and may also contribute to patients' reduced awareness of their swallowing difficulties. This lack of awareness directly correlates with severe, life-threatening complications such as sudden aspiration pneumonia and choking. Consequently, to mitigate the risk of aspiration and choking in patients with MyD, evaluating their swallowing function early and regularly is crucial, as it guides the selection of appropriate food types and postures tailored to their condition.

Patients with MyD are reportedly prone to poor swallowing function [25]. However, most of these studies are case series [11, 14–16, 26–29], with only nine case–control studies [12, 13, 15, 16, 30–33] and one cross-sectional study [34] reported [2]. These studies also had small sample sizes, heterogeneous study designs, and no standardized swallowing evaluation methods; hence, the swallowing pathophysiology in these patients remains unclear [2]. MyD affects a wide range of functions, from the oral preparatory stage to the esophageal stage of swallowing [10–12, 25]. With few subjective symptoms and varying degrees of progression, it is difficult to elucidate which parts of swallowing are affected and how they interact. Our study specifically focused on pharyngeal swallowing in patients with few subjective symptoms, conducting a detailed evaluation and analysis. To date, only two studies have specifically examined patients with MyD with few subjective symptoms: Six cases by Swaic et al. [10] and 11 by Guerrero et al. [35]. Swaic et al. reported decreased pharyngeal peristalsis amplitude, decreased UES resting pressure, and normal UES relaxation in asymptomatic patients with MyD using VFSS and manometry [10]; our findings were consistent with these results. In this study, patients with MyD showed significantly lower pharyngeal contraction force than non-MyD control patients with mild subjective symptoms of dysphagia, confirming that a significant decrease in pharyngeal swallowing motor function, even if unconscious, is a characteristic of this disease.

In this study, the VFSS, which evaluated the motility of the pharyngeal phase of swallowing, including the tongue base, larynx, and pharyngeal peristalsis, confirmed a significant decrease in motility in the MyD group compared to the non-MyD control group. The HRM test also revealed that the pharyngeal phase contractile force of the MyD group significantly decreased from the velopharynx to the UES level. A recent HRM study on patients with swallowing disorders reported that when the maximum contractile pressure at the velopharynx level was < 105 mmHg, oral intake became difficult, and the risk of aspiration pneumonia increased [36]. However, although the pharyngeal contractile force at the same level in the MyD group significantly decreased to 45.6 mmHg, the minimum UES pressure during swallowing was reduced to −5.0 mmHg, similar to that in healthy individuals [37, 38], suggesting that the UES was sufficiently relaxed. Generally, the cricopharyngeal muscle, that constitutes the UES, contracts at rest, relaxes only at the moment of swallowing, and then contracts again [39]. The UES opening, controlled by the central pattern generator located in the medulla oblongata, is influenced not only by cricopharyngeal-muscle relaxation but also by laryngeal elevation and intrabolus pressure [40]. In the non-MyD control group, a negative correlation was observed between the maximum oropharyngeal contraction pressure and the minimum UES pressure, suggesting that a weak contraction force makes it difficult for the UES to open. In contrast, the MyD group showed a weak positive correlation between these parameters, opposite to that of the non-MyD control group. This finding suggests that the UES in patients with MyD remains consistently relaxed despite a marked decrease in pharyngeal swallowing movement. The low correlation coefficient observed in the control group in this study is likely attributable to the inclusion of patients with mild symptoms who were able to maintain oral intake. Future research should aim to increase the sample size and conduct a more detailed examination of the relationship between maximum pharyngeal contraction and UES opening.

In healthy participants, the UES pressure at rest varies approximately between 35 and 100 mmHg, and the width is 3–4.7 cm [41, 42]. In contrast, patients with MyD exhibited a significant decrease in UES resting contraction force, with the UES pressure and width at rest being 13 mmHg and 1.1 cm, respectively. Thus, the UES in patients with MyD appeared to be constantly relaxed and remained open despite the marked reduction in laryngeal elevation and intrabolus pressure, allowing liquids to pass into the esophagus gradually by gravity. Since UES dysfunction is directly related to pharyngeal residue and aspiration [22], constant relaxation of the UES may be advantageous for swallowing in patients with MyD. This allows liquids to pass into the esophagus without aspiration with the aid of gravity, although potential complications such as reflux remain a concern. These support previous findings showing that patients with MyD tend to experience more pronounced dysphagia with solids than with liquids [19]. In contrast, this may be one of the factors delaying the recognition of impaired swallowing function. It is important to keep in mind that the risk of sudden choking increases when masticatory disorders caused by cognitive decline, reduced tongue pressure, and poor oral function become evident [34]. Since patients with MyD are prone to sudden choking episodes, the importance of early evaluation and management, including dietary advice, is emphasized, even in the absence of significant subjective symptoms.

A lengthy debate has been initiated by the question of whether the UES should be tonic or flaccid. Previous studies have reported delayed UES opening [16] and demonstrated the effectiveness of phenytoin and balloon dilation in relaxing the UES [25, 43]. Meanwhile, Ertekin et al. revealed that electromyography of the CP muscles in patients with asymptomatic MyD showed regular UES relaxation; however, abnormal CP muscle activity was detected in 40% of patients [15]. Furthermore, many recent manometry studies have shown reduced resting UES pressure and regular UES relaxation in MyD, and the results of this study are consistent with those findings. Further studies on the CP muscles of patients with MyD, including histopathological investigations, are needed to determine whether CP myotomy and botulinum toxin therapy, which are among the main treatments for swallowing disorders, are effective for this disease.

Early management is crucial for patients with MyD; however, personality disorders, intellectual and cognitive impairments, lack of interest in the disease [18], or sleepiness can result in poor awareness of declining swallowing function [19]. Additionally, many patients lack interest in their health, are reluctant to seek treatment, and may not visit a medical institution despite having swallowing difficulties [44]. Furthermore, there are currently no clear clinical guidelines for managing MyD. Although Conravey and Santana-Gould (2010) presented a comprehensive approach to managing patients with MyD, they did not provide specific recommendations for evaluating and treating swallowing disorders [45]. The Eating Assessment Tool, validated in the literature [46], is a valuable screening method for swallowing disorders. Nevertheless, it may not be effective for patients with MyD, necessitating caution.

Further research is required to develop disease-specific assessment tools. In cases involving family members, obtaining a detailed history of coughing during meals, frequent choking, and worrying choking episodes is essential. Educating family members and caregivers to engage them in the evaluation and management process is also important [44]. Evaluation of swallowing function is recommended at the time of MyD diagnosis. Given the risk of choking associated with impaired swallowing, routine screening assessments should be conducted every 6–12 months, depending on the severity of the dysfunction. Nutrition should also be addressed, including objective weight assessment and BMI calculations. Although a correlation between the number of CTG repeats and the severity of dysphagia-related muscle abnormalities on videofluoroscopy has been reported [26], this study suggests that dysphagia can occur even with a small number of repeats, underscoring the need for vigilance from the early stages of the disease.

This study was limited by its cross-sectional design and relatively small sample size. Longitudinal studies are needed to better understand the progression of swallowing dysfunction in MyD and evaluate the long-term efficacy of early interventions. Additionally, future research should explore the development of MyD-specific swallowing assessment tools, as standard screening methods may not be effective in this patient population.

Conclusions

Our study demonstrates that patients with MyD exhibit a marked decline in pharyngeal swallowing motor function, even without subjective symptoms, and highlights the importance of comprehensive, multidimensional swallowing assessments in this population. Early detection and management of dysphagia in patients with MyD, even in those without subjective symptoms, may help prevent complications and improve their quality of life.

Acknowledgments

We want to thank Editage () for English language editing.

Ethics Statement

We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. This study was approved by the Institutional Review Board of Ehime University Medical Hospital (Approval no. 2108030).

Consent

Written informed consent was obtained from all the participants enrolled in this study. All the patients agreed to publish their data.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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