Despite the clinical impact of dysphagia in myasthenia gravis (MG), a standard protocol for diagnosing dysphagia reliably has not yet been established. High-resolution manometry (HRM) provides precise information on pharyngeal pressure. We hypothesized that swallowing pressure assessment using HRM during the edrophonium chloride (EC) test could identify mild bulbar symptoms with no abnormalities on videoendoscopic (VE) and videofluorographic (VF) examination of swallowing, and we tested this hypothesis on a 72-year-old female patient diagnosed with ocular MG who developed slight pharyngeal discomfort over 3 months. The patient’s ocular symptoms were stable with pyridostigmine medication. VE and VF revealed no abnormalities. The swallowing pressure along the pharynx was measured using HRM during the EC test. HRM parameters, including velopharyngeal contractile integral and meso-hypopharyngeal contractile integral, were evaluated. These parameters were assessed for three swallows using 3 mL of water. After EC injection, the values of the velopharyngeal contractile integral (78.0 ± 5.4 vs. 134.7 ± 1.3 mm Hg cm·s) and the meso-hypopharyngeal contractile integral were both higher (130.6 ± 1.5 vs. 284.2 ± 11.9 mm Hg cm·s) than those observed before EC injection. Chest computed tomography revealed a thymoma that had not been observed in previous examinations. The patient was diagnosed with thymoma-associated MG. Intravenous immunoglobulin therapy improved the mild dysphagia. We concluded that swallowing pressure assessment during the EC test may be helpful in identifying mild bulbar symptoms in patients with MG.

© 2022 The Author(s). Published by S. Karger AG, Basel

Myasthenia gravis (MG) is an autoimmune disorder caused by antibodies against molecules expressed on the postsynaptic membrane at the neuromuscular junction [1]. Dysphagia may occasionally be the sole bulbar symptom of MG [2]. Delays in the diagnosis and treatment of myasthenic effects on swallowing-related muscles can lead to respiratory complications that require intensive care [3]. However, in spite of the clinical impact of dysphagia, there is no standardized protocol for the reliable diagnosis of dysphagia in MG.

Evaluation of swallowing using videoendoscopic (VE) examination and videofluoroscopic (VF) examination of swallowing is useful before and after intravenous edrophonium chloride (EC) injection to assess dysphagia due to MG [4, 5]. However, early or mild symptoms may not reveal abnormalities in these evaluations of swallowing.

Recently, high-resolution manometry (HRM) has been developed and used to evaluate pharyngeal dysphagia in various diseases, including neuromuscular diseases [5, 6]. HRM has 36 circumferential pressure sensors spaced 1 cm apart and provides precise pharyngeal pressure information. Pharyngeal findings of HRM have been clinically applied to identify pharyngeal weakness in MG [7]. However, changes in pharyngeal pressure during the EC test have not yet been evaluated with HRM. Herein, we present a case report that demonstrates changes in pharyngeal pressure before and after the EC injection using HRM in a patient with mild dysphagia due to MG.

A 72-year-old woman diagnosed with ocular MG 8 years previously developed slight pharyngeal discomfort for 3 months. The strength of the neck flexors evaluated by manual muscle testing was grade 4. Ocular symptoms and muscle weakness in the extremities were not observed. The patient’s condition was stable with pyridostigmine medication. The anti-acetylcholine receptor antibody level was increased (22.0 nmol/L). VE showed no pooling of saliva. VF was performed; however, no abnormal findings, such as pharyngeal residue or aspiration, were observed. The Myasthenia Gravis Foundation of America clinical classification was IIb.

The swallowing pressure along the pharynx and upper esophageal sphincter (UES) was measured using an HRM (Unisensor AG). HRM parameters including velopharyngeal contractile integral (VPCI), meso-hypopharyngeal contractile integral (MHPCI), UES relaxation duration, and UES nadir pressure were evaluated (shown in Fig. 1). The pharyngeal contractile integral (CI) (mm Hg·cm·s) is a parameter used to evaluate the pharyngeal swallowing pressure [8]. The CI was calculated as amplitude × duration × length of muscular contraction ≥20 mm Hg. This parameter is a measure of the “vigor” of pharyngeal contraction.

Pressure topography of the present case of a patient with dysphagia before (left) and after (right) the EC test. Spatiotemporal plots of liquid swallows. y-axis, catheter position; x-axis, time. Pressure is indicated by the color scale; black or red for high pressure and blue for low pressure. Velopharyngeal pressure and meso-hypopharyngeal pressure were measured at the velopharynx (a) and meso-hypopharynx (b), respectively. UES relaxation duration and UES nadir pressure were evaluated at (c, d).

The HRM parameters were assessed for three swallows with 3 mL of water. These evaluations were repeated before and after the intravenous injection of normal saline, 2 mg EC, and 8 mg EC (Table 1). The VPCI and MHPCI did not increase after normal saline injection, and the mean values of these parameters increased after EC injection. After 8 mg EC injection, the VPCI (78.0 ± 5.4 vs. 134.7 ± 1.3 mm Hg cm·s) and MHPCI (130.6 ± 1.5 vs. 284.2 ± 11.9 mm Hg cm·s) values were both higher than before EC injection. The UES relaxation time and UES nadir pressure did not change after the EC injection.

Manometric study before and after the intravenous EC injection

Computed tomography of the chest revealed a thymoma that had not been observed during previous examinations. We diagnosed a transformation from ocular MG to generalized MG caused by thymoma-associated MG. Intravenous immunoglobulin therapy improved the mild dysphagia and cervical muscle weakness, and thymectomy was performed. The pathological examination of the lesion revealed a type B2 thymoma (size: 4.0 × 1.4 × 3.5 cm).

This is the first report of MG with mild bulbar symptoms identified based on increased pharyngeal pressure during the EC test using HRM. The diagnosis of bulbar MG is clinically challenging [3], and some patients could be misdiagnosed using standard assessment methods [2]. Evaluation of swallowing pressure during EC test with HRM may be useful for identifying mild pharyngeal weakness, which is difficult to evaluate using conventional standard assessments, including VE and VF.

In the present case, the only bulbar symptom was a very slight feeling of discomfort in the pharynx. MG patients with dysphagia present decreased pharyngeal clearance [3, 7, 9], but VE revealed no abnormalities, such as pooling of the saliva. Although pharyngeal residues have been reported in MG-related dysphagia [2, 7, 9, 10], VF revealed no pharyngeal residues or penetration/aspiration in our patient. Interestingly, we could identify mild bulbar symptoms that were undetectable by evaluation of swallowing function using VE or VF.

The strength of this evaluation is that the increase in pharyngeal contraction during the EC test was quantitatively evaluated. The increased VPCI and MHPCI reflect improved soft palate closure and pharyngeal contraction, respectively. The evaluation of swallowing pressure using HRM provides objective values for the increase in soft palate closure and pharyngeal contractility during the EC test. A manometric study during the EC test is highly reliable, without variation in measurement results between clinicians.

One of the mechanisms of MG-related dysphagia is the weakness of the posterior pharyngeal muscles [3]. Furthermore, weakness of the suprahyoid muscles leads to impaired opening of the UES. In the present case, HRM revealed weakness of the pharyngeal muscles; however, the UES function was preserved. Some patients with MG-related dysphagia present with UES dysfunction [11]. Submental and laryngeal elevators associated with UES opening are clinically involved in MG [12]. Thus, HRM could be used to evaluate weakness of the pharyngeal muscle and/or suprahyoid muscles before and after intravenous EC injection in diagnosing MG patients. The strength of evaluation by HRM might be that it is able to assess slight muscle weakness in swallowing-related muscles for early diagnosis or identification of recurrence, before serious complications develop. In summary, swallowing pressure assessment during the EC test may facilitate identification of very mild bulbar symptoms in patients with MG.

This case report did not require the Ethics Review Committee of the Gifu University Graduate School of Medicine in accordance with local or national guidelines. Written informed consent was obtained from the patient for publication of the details of the medical case and any accompanying images.

The authors have no conflicts of interest to declare.

This work was supported by JSPS KAKENHI, grant no. 21K17471.

Kenjiro Kunieda, Yuichi Hayashi, and Nobuaki Yoshikura: determined the diagnosis and treated the patient. Kenjiro Kunieda and Yuichi Hayashi: drafted the manuscript. Tomohisa Ohno: performed the statistical analysis. Kenjiro Kunieda, Yuichi Hayashi, Akio Kimura, Ichiro Fujishima, and Takayoshi Shimohata revised the manuscript. Kenjiro Kunieda, Yuichi Hayashi, Nobuaki Yoshikura, Tomohisa Ohno, Akio Kimura, and Takayoshi Shimohata read and approved the final version of the manuscript.

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.

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