Myasthenia gravis (MG) can result in weakness of the respiratory muscles in 30% of patients. A life-threatening exacerbation, MG crisis can cause respiratory insufficiency requiring mechanical ventilation. Sleep disordered breathing (SDB) is seen in 40% to 60% of stable MG patients. Factors associated with SDB include age, male sex, obesity, and steroid use. Continuous positive airway pressure (CPAP) can reverse paradoxical weakness in MG patients with obstructive sleep apnea (OSA), but whether SDB can contribute to respiratory failure in MG and whether CPAP works in such patients remain unclear. This report presents a 54-year-old woman with MG with a history of 7 episodes of respiratory failure requiring mechanical ventilation. For each episode, she was treated for MG crisis using plasmapheresis and high-dose steroids. Later, OSA and obesity hypoventilation syndrome were confirmed by polysomnography with transcutaneous CO2 monitoring. Thereafter, the patient had no further recurrence of MG crisis for 5 years, using pyridostigmine and CPAP only.
Lai YC, Chen JY, Wu HD, Yang CC, Lin CH, Lee PL. Sleep disordered breathing mimicking myasthenia crisis in a patient with myasthenia gravis. J Clin Sleep Med 2016;12(5):767–769.
Myasthenia gravis (MG) is an autoimmune disorder affecting the neuromuscular junction of skeletal muscle. It can result in weakness of respiratory muscles in 30% of patients.1 A life-threatening exacerbation, MG crisis causes respiratory insufficiency, requiring mechanical ventilation (MV) with plasmapheresis, intravenous immunoglobulin, and high-dose steroids. Sleep disordered breathing (SDB) is common in MG, with obstructive sleep apnea (OSA) found in 36% to 41% of myasthenics.1,2 Factors associated with SDB in MG include age, male sex, obesity, and steroid use.1,3 Continuous positive airway pressure (CPAP) has been demonstrated to reverse paradoxical weakness in MG patients with OSA.4,5 However, whether SDB can contribute to respiratory insufficiency in MG, especially in MG crisis, and whether CPAP works in such critical patients remain unclear.
Here is a case of a woman with MG with a history of 7 episodes of respiratory failure requiring MV. She was treated for MG crisis with plasmapheresis and high-dose steroids. Her OSA and obesity hypoventilation syndrome (OHS) were confirmed by polysomnography (PSG) with transcutaneous CO2 (PtcCO2) monitoring. Thereafter, she remained well for 5 years using CPAP.
REPORT OF CASE
A 54-year-old woman was diagnosed with seronegative MG without thymoma in August 2007. Her height and weight were 144.4 cm and 77.4 kg. Her symptoms included progressive weakness, nasal speech, dysarthria, dysphagia, and ptosis. Arterial blood gas (ABG) showed hypoxemia and hypercapnia (pH 7.31, PaCO2 56.1 mm Hg, PaO2 57.1 mm Hg, HCO3- 27.5 mEq/L, at room air). She was intubated, and plasmapheresis, pyridostigmine (480 mg/day), and methylprednisolone were started for suspicion of MG crisis. The muscle power of her limbs fully recovered, while her vital capacity (VC) was 1.5 L and maximal inspiratory (Pimax) and expiratory (Pemax) pressures were −50 mm Hg and 52 mm Hg, respectively. The patient was extubated 9 days later.
After extubation, the patient suffered from wheeze and persistent hypercapnia (pH 7.41, PaCO2 50.4 mm Hg, HCO3- 31.5 mEq/L). Spirometry demonstrated mild obstructive ventilatory defect (Table 1), while bronchoscopy revealed intact vocal cords. Asthma was considered, and she was given inhaled fluticasone/salmeterol and oral bambuterol.
Serial measurements of pulmonary function and body mass index.
Serial measurements of pulmonary function and body mass index.
From October 1, 2007, to April 20, 2009, the patient had another 5 episodes of hypercapnic respiratory failure despite maintenance medications of prednisolone (20–30 mg/ day), pyridostigmine (480 mg/day), azathioprine (50 mg/day), fluticasone/salmeterol, and bambuterol. For each episode of respiratory failure, she was treated with plasmapheresis and methylprednisolone for suspicion of MG crisis. Her body mass index (BMI) increased to 43.8 kg/m2 in November 2008 and to 45.9 kg/m2 in January 2009. The patient also complained of dyspnea, tiredness, sleepiness, non-refreshing sleep, and frequent sleep awakening. Finally, she was put on BPAP (bilevel positive airway pressure) spontaneous/time (S/T) mode, with inspiratory and expiratory positive airway pressure (IPAP/EPAP) at 16/6, rate 12/min, Ti 0.9 sec, and O2 3L/min, which was empirically adjusted by respiratory therapist in intensive care unit (ICU). With these settings, the morning ABG was PH 7.37, PaCO2 65.7 mm Hg, PaO2 67.5 mm Hg, and HCO3- 37.2 mEq/L. The patient continued using BPAP at the same settings after discharge.
She then had a 7th episode of hypercapnic respiratory failure on June 15, 2009, when her BMI was 44.2kg/m2. An MG crisis was thought not to be likely because of her preserved VC (1.66 L; Table 1). Consultation with a sleep specialist disclosed that the patient used BPAP while awake, not during sleep. Overnight PSG with PtcCO2 monitoring showed apnea-hypopnea index (AHI) of 64/h, lowest oxygen saturation 51%, and percentage of total sleep time with SpO2 < 90% of 96%, with the percentage of total sleep time with transcutaneous CO2 > 50 mm Hg as 79.4%. The final diagnosis was severe OSA and OHS. The setting of BPAP was adjusted as guided by the PSG-PtcCO2 monitoring where IPAP/EPAP 25/13 was the optimal pressure. Maintenance prednisolone was tapered to no more than 10 mg/day and was discontinued since March 2010.
Since then, the patient has had no further episodes of MG crisis following initiation of BPAP with maintenance of pyridostigmine (180 mg/day) and inhaled fluticasone/salmeterol. Sixteen months later, the patient had weight loss (BMI 36.4 kg/m2) and complained that the air blowing of BPAP was too strong. Repeated titration revealed CPAP 16 cm H2O as the optimal pressure with AHI of 0 and lowest SpO2 of 98%. The BPAP was then shifted to CPAP. Sixty months later, the patient was still compliant with CPAP at BMI 39 kg/m2.
This report is of a woman with MG and repeated hypercapnic respiratory failure treated as MG crisis using plasmapheresis and high-dose steroids. Eventually, severe OSA and OHS were confirmed by PSG-PtcCO2, which resulted in discontinuation of steroid.
Even though 40% to 60% of MG patients have SDB, the prevalence of OHS has never been studied, possibly because MG-related respiratory insufficiency must first be excluded before counting obesity as the cause of awake hypoventilation.6,7 Although this patient had full muscle power and intact vocal cords, she still had repeated hypercapnic respiratory failure. Also, the patient had no more MG crisis after weight reduction and BPAP initiation despite tapering off steroids. The clinical course is compatible with the diagnosis of OHS.7
Respiratory insufficiency related to unrecognized SDB may lead to unnecessary and increased steroid use, causing central obesity and weight gain which further compromised the upper airway and worsened SDB during sleep. In this patient, the changes in body weight were highly concordant with the dose of steroid exposure; this is compatible with findings in the literature.2,4,5 An early diagnosis of SDB with PSG-PtcCO2 could have led to early BPAP use and prevented unnecessary steroid use and weight gain.2,4,5
This was not an industry supported study. The study was supported by grants from the National Taiwan University Hospital (Project Number 104-N2931) and National Science Council of Taiwan (NSC 102-2314-B-002-099). The authors have indicated no financial conflicts of interest.
arterial blood gas
body mass index
bilevel positive airway pressure
continuous positive airway pressure
expiratory positive airway pressure
intensive care unit
inspiratory positive airway pressure
obesity hypoventilation syndrome
obstructive sleep apnea
maximal expiratory pressures
maximal inspiratory pressures
sleep disordered breathing
The study was supported by grants from the National Taiwan University Hospital (Project Number 104-N2931) and National Science Council of Taiwan (NSC 102-2314-B-002-099). Author contributions: YC Lai, JY Chen, and PL Lee did the study design, data analysis, and manuscript writing. HD Wu, CC Yang, and CH Lin did the data analysis. All of the authors read and approved the manuscript.
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