Fiberoptic endoscopic examination of swallowing with simultaneous ice pack test in patient with myasthenia gravis: A case report

Abstract

Myasthenic crisis (MC) is a life-threatening complication of myasthenia gravis (MG), affecting 15–20% of patients with MG at least once. The rapid and accurate diagnosis of MG is mandatory but challenging because patients with MC require intubation and mechanical ventilation or noninvasive ventilation (NIV). We describe a case of an 81-year-old woman diagnosed with MG related dysphagia. Simultaneous fiberoptic endoscopic examination of swallowing (FEES) and ice-pack test (FEES-ice pack test) revealed a significant decrease in pharyngeal residue, suggesting MG. The day following the test, she experienced respiratory failure. FEES-ice pack test results and respiratory distress suggested MC. NIV followed by mechanical ventilation was started quickly, leading to improved respiratory condition. We show that the FEES-ice pack test led to prompt treatment for MC. Although further investigations are required for sensitivity, specificity, and positive criteria, the FEES-ice pack test could be a safe and easy method to diagnose MG.

Keywords:

• Myasthenia gravis
• fiberoptic endoscopic examination of swallowing
• ice pack test

Introduction

Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular junction with an annual incidence of 0.2–5 per 100,000 patients [1]. Most commonly patients with MG have elevated antibody levels directed toward the acetylcholine receptors (Ach R) present in the post-synaptic motor end plate. Patients with MG present with muscle weakness, diplopia, ptosis, dysarthria, and dysphagia. In 15% of cases, bulbar symptoms are the initial and sole presentation of MG, which makes diagnosing this disorder difficult for otolaryngologists [2].

Clinical examinations for MG include antibody assays (Ach R, muscle-specific receptor tyrosine kinase [MuSK], lipoprotein-related protein 4 [LRP4]), repetitive nerve stimulation single-fiber electromyography, Tensilon (edrophonium) test, and ice pack test.

Edrophonium is a short-acting acetylcholinesterase competitive inhibitor. Edrophonium increases the amount of Ach in neuromuscular junction synapses. In the Tensilon test, intravenous administration of edrophonium in increasing doses (e.g. 2 mg each, up to a total of 10 mg) improves MG-related symptoms such as muscle weakness and dysarthria. Improvement in symptoms is an indication that the patient has MG. The adverse effects of edrophonium include bronchospasm, bradycardia, atrioventricular block, and cardiac arrest. Although the adverse cardiac effects of edrophonium can be recovered by the administration of atropine, an anticholinergic drug, careful cardiac monitoring is necessary. Considering these serious adverse cardiac effects, the Tensilon test is difficult and dangerous to perform by otolaryngologists alone.

To assess swallowing and assist in the diagnosis of MG, fiberoptic endoscopic examination of swallowing (FEES) and videofluoroscopic swallowing study (VFSS) are performed.

Warnecke et al. proposed a fiberoptic endoscopic examination of swallowing (FEES) combined with simultaneous Tensilon application (FEES-Tensilon test) [2–4].

They performed the FEES-Tensilon test on four patients presenting with dysphagia, including three patients with MG and one with oculopharyngeal muscular dystrophy. The FEES-Tensilon test successfully detected MG-related dysphagia in all patients with MG. If the patient’s swallowing function improved after the test, it was rated as positive. Although they reported no severe side effects during the FEES-Tensilon test, physicians must pay attention to adverse effects.

The ice pack test was originally described as a cold test by Saavedra et al. Ice cubes (wrapped in cloth) were placed over the closed eyes of patients with MG for 5–10 min. In all the six patients tested, ptosis was improved by local cooling [5]. Sethi et al. gave the test the name ‘ice pack test’ which is now commonly used worldwide. In contrast to Saavedra et al.’s procedure, Sethi et al. place the ice cubes on patients’ closed eyes for 2 min only, or to the patient’s tolerance limit [6]. Unlike the Tensilon test, the ice-pack test has no cardiac side effects. Therefore, the ice pack test is a safe approach to diagnose MG.

We performed fiberoptic endoscopic examination of swallowing (FEES) combined with a simultaneous ice pack test (FESS-ice pack test) as an alternative to the FEES-Tensilon test for patients with dysphagia. Although FEES and ice pack tests are the standard and common medical examinations per se, this is the first case report describing their simultaneous application on a patient.

Case presentation

An 81-year-old woman presented to our hospital with dysphagia. Her medical history included atrial fibrillation, cerebral aneurysms, bilateral ptosis, and thymoma. The patient had previously been examined by a neurologist and was diagnosed with age-related ptosis. Five months before admission, she complained of appetite loss and dysphagia. Thoracic computed tomography revealed thymoma, but surgery was not considered because we did not notice of the association between thymoma and dysphagia. At this moment, FEES was almost normal, except for marked regurgitation of colored water into the piriform sinus after swallowing. At that time, the patient was diagnosed with dysphagia associated with gastroesophageal reflux disease. One month prior to admission, her dysphagia deteriorated and was accompanied by generalized weakness. She was admitted to our hospital and MG was suspected. On the second day of hospitalization, FEES revealed remarkable saliva pooling in the vallecula and piriform sinus. Laryngeal elevation was weak, and the white-out time was short. The pharyngeal residue of the colored water was very large. Laryngeal invasion of colored water was also observed, but aspiration was not clear. As MG was strongly suspected, an ice-pack test was performed simultaneously with FEES. Ice cubes packed in plastic bags were placed over the patient’s anterior neck for two minutes. After cervical cooling, pooling of saliva, pharyngeal residue, and laryngeal elevation dramatically improved (Figure 1). The FEES-ice pack test was positive, and MG was strongly suggested. Although we, otolaryngologists strongly suspected MG based on the findings of FEES-ice pack test, neurologist in our hospital was skeptical to this diagnosis because he thought that dysphagia was the only neurological deficit at that time. Therefore, she was just observed and examined without any treatment of MG. VFSS was planned on day three of hospitalization. However, on hospital day 3, the patient was found to be in respiratory failure. Considering the result of the FEES ice pack test, she was immediately diagnosed with myasthenic crisis. Bag valve mask ventilation was initiated soon after, followed by noninvasive ventilation (NIV). Although NIV recovered her respiratory condition, sputum impaction led to cardiopulmonary arrest on the same day (hospital day 3). The patient was then resuscitated and intubated. Her respiratory condition improved soon after initiation of mechanical ventilation. On hospital day 5, she was treated with intravenous immunoglobulin (IVIg) and prednisone (20 mg/day = 0.5 mg/kg/day). On hospital day 9, tracheostomy was performed. After IVIg and prednisone administration, her respiratory condition and muscle weakness fully recovered. The tracheal stoma was closed on hospital day 50. The patient was discharged on hospital day 87. Serological tests returned positive for Ach R antibody and negative for Musk antibody (Table 1). The size of the thymoma decreased with prednisone treatment. Considering the risk of postoperative complication was high because of her age, thymectomy was postponed and the thymoma was kept on watchful waitingThe patient is currently being treated with prednisone (5 mg/day) and tacrolimus (3 mg/day). Clinical course is summarized in Figure 2.

Figure 1. Endoscopic findings of pre- (a) and post- (b) cervical cooling. Pooling of saliva and pharyngeal residue of colored water were dramatically decreased.

Figure 2. Clinical course.

Table 1. Laboratory findings.

Ach R antibody (nmol/L)	28.0 (< =0.2)
MuSK antibody (nmol/L)	<0.02 (<0.02)
Jo-1 antibody (IU/mL)	<1 (0.0–9.9)
CK (IU/L)	37 (43–165)

AchR: Achetylcholine receptor; MuSK: Muscle-specific receptor tyrosine kinase; CK: Creatine kinase.

Discussion

In the ice pack test, local cooling decreased the activity of muscle-AChE. Subsequently, decreased decomposition of acetylcholine improves neuromuscular transmission [7]. Other than the decreased enzyme activity, possible alternative mechanisms may include changes in the properties of the motor end-plate [8], increased sensitivity of the acetylcholine receptor [7], increased facilitation of neurotransmitter release in the motor end-plate [9] and reduction in the rate of removal of calcium ions from the nerve terminal following stimulation [10]. However, the precise physiological mechanism of the ice pack test remains unclear.

Chatzistefanou et al. reported that the sensitivity of the ice pack test by five minutes application of ice pack was 76.9% and 92.3% for detecting myasthenic diplopia and blepharoptosis respectively. Specificity was 98.3%, indicating an acceptable level of sensitivity and high specificity of the test [11].

Recently, Warnecke et al. reported that the sensitivity and specificity of the FEES-Tensilon test are 88.2% and 95.9%, respectively. (The authors also changed the name of FEES-Tensilon test into flexible endoscopic evaluation of swallowing-Tensilon test (FTT)) [12]. Although sensitivity and specificity of FEES-Tensilon test are very high and reliable, sensitivity and specificity of FEES-ice pack test are unknown. Moreover, it is easier to make a judgement in our case because the improvement was clear, but the positive criteria used for of FEES-ice pack test were not established.

A recent literature review mentioned that the Tensilon test should be performed by an expert. Although the serious side effects occur only in <0.2% of patients, heart rate and blood pressure should be monitored to tackle serious side effects, such as bradycardia, cardiac arrest, bronchospasm, seizures, and transient ischemic attack (TIA) [13]. On the other hand, Sethi et al. reported that there are no side effects except for mild local discomfort in ten patients with MG who underwent an ice pack test [6]. Furthermore, as of 2018, the Food and Drug Administration (FDA) discontinued edrophonium in the United States because of its high rate of false-positive test results and the development of serological antibody detection. Compared to the FEES-Tensilon test, the FEES-ice pack test is an easier and safer way to diagnose MG. Moreover, serological studies require a few days or weeks to provide the results. In our case, it took 13 days to obtain the Ach R antibody test results. However, in the FEES-ice pack test, results can be obtained immediately. Approximately 15–20% of MG patients experience myasthenic crisis at least once in their lives [14]. Thus, for a presenting with a complaint of dysphagia, it is important for a clinician to know whether the diagnosis of MG is likely or not. Respiratory failure along with dysphagia in an MG patient is indicative of patient being in myasthenic crisis, therefore a rapid MG diagnosis helps doctors and medical staff to start appropriate treatment immediately. In this case, patient was misdiagnosed during first FEES (when no ice pack test was used), highlighting it could be challenging for the otolaryngologists. However, with the ice pack test, a positive result led to prompt and proper diagnosis and treatment of the myasthenic crisis. In this patient, we managed to recover from the respiratory failure soon after starting NIV, but it resulted in sputum impaction later. Although neurologist in our hospital recommended the patient to be intubated, she strongly rejected. Though NIV needs no sedation and NIV is less invasive to patients, from the hindsight, we should have intubated her immediately after the respiratory failure.

Although further investigations are required for sensitivity, specificity, and positive criteria, the FEES-ice pack test could be an alternative to the FEES-Tensilon test, especially for otolaryngologists and in areas where edrophonium is not available.

Conclusion

FEES-ice pack test could be a safe and easy method to diagnose MG. Further investigations are required for sensitivity, specificity, and positive criteria.

Ethical statement

The authors have obtained informed consent from the patient.

Informed consent

Authors confirm that consent was obtained from the patients for this study.

Acknowledgments

The authors would like to thank Editage (www.editage.com) for English language editing.

Disclosure statement

No potential conflict of interest was reported by the author(s).