Resolution of Severe Obstructive Sleep Apnea after Treatment of Anti-Muscle Kinase Receptor-Positive Myasthenia Gravis Despite 60-Pound Weight Gain

Abstract

Obstructive sleep apnea (OSA) in patients with myasthenia gravis (MG) may be caused by reduced pharyngeal dilator muscle activity. We report a patient with anti-muscle kinase receptor MG with severe OSA and hypoventilation that resolved upon successful treatment of MG despite a 60-lb weight gain. Keywords: myasthenia gravis, obstructive sleep apnea, antimusk antibody, hypoventilation Citation: Morgenstern M, Singas E, Zleik B, Greenberg H. Resolution of severe obstructive sleep apnea after treatment of anti-muscle kinase receptor-positive myasthenia gravis despite 60-pound weight gain. J Clin Sleep Med 2014;10(7):813-814.http://dx.doi.org/10.5664/jcsm.3884 C A S E R E P O R T SM yasthenia gravis (MG) may contribute to development of obstructive sleep apnea (OSA) by inducing pharyngeal dilator muscle weakness, although not all studies have demonstrated this association.1-3 MG is often caused by acetylcholine receptor antibodies (AchR-Abs) blocking neuromuscular transmission. However, approximately 40% of MG patients who do not have AchR-Abs have anti-muscle kinase receptor antibodies (anti-MuSKR-Ab). This likely alters clustering of acetylcholine receptors during neuromuscular junction formation.4 MG has a variable clinical course that may be exacerbated by stress including infection, exertion or various drugs that may lead to "myasthenic crisis" with respiratory compromise. REPORT OF CASEA 45-year-old female with 6 months of headaches, weakness, dysarthria, dysphagia, and 60-pound weight loss (BMI 26 kg/m 2 ) was admitted for hypercapnic respiratory failure (ABGsupplemental O 2 : pH 7.27 / PCO 2 60 mm Hg / PO 2 99 mm Hg / HCO3 -28 mmol/L). Neurological evaluation showed fatigable diplopia, ptosis, and bi-facial and genioglossus weakness. Neck fl exor and extensor and proximal extremity muscles were spared. Formal swallowing evaluation confi rmed dysphagia. However, AchR-Abs were negative. Electromyography, nerve conduction studies and repetitive nerve stimulation (no decremental response) were not consistent with MG. No defi nitive neurological diagnosis was made. The patient was discharged on nocturnal bilevel positive airway pressure for treatment of persistent hypercapnia (ABG after 2 weeks: pH 7. -27 mm Hg), fatigue, dyspnea, and weakness persisted. Subsequent serology revealed antiMuSKR-Abs prompting treatment with plasma exchange, maintenance mycophenolate mofetil and prednisone, which normalized her neurological exam and muscle weakness. After 3 months, despite a 60-lb weight increase (BMI 35 kg/m 2 ), repeat diagnostic PSG showed resolution of OSA and nocturnal hypoventilation (AHI = 1/h; T90% = 0) with normal serum HCO3-(25 mmol/L). DISCUSSIONBoth insuffi cient neural drive to upper airway dilator muscles and anatomic factors that compromise the upper airway contribute to the pathophysiology of OSA. In MG, muscular strength varies based on muscle exertion, fl uctuating levels of autoantibodies that affect neuromuscular junction transmission, and other factors. The impact of MG may not be uniformly distr...

Sleep-disordered Breathing in Neuromuscular Disease

“…Although those events were considered to be obstructive in nature and unrelated to diaphragm weakness, an earlier study that used esophageal pressure monitoring to determine the nature of the events emphasized that the sleepdisordered breathing events in myasthenia gravis were predominantly REM related rather than obstructive (18). Medical or surgical treatment of myasthenia can normalize severe sleep-disordered breathing (48,50).…”

Sleep Related Conditions with Myasthenia Gravis: Evidence, Causes and Implications

“…In some patients with MG, sleep related conditions do not improve despite of improvement of muscle weakness, thus resolution of SDB, nocturnal hypoventilation, disturbance of REM sleep and daytime symptoms have to be considered among the treatment approaches for patients with MG [10,46,79]. Treatment must be adjusted to the severity of the problem during sleep.…”

“…The current treatment for MG due to nAChR Abs include AChE-Is (as pyridostigmine) [36], immunopharmacologic drugs [37,38] and thymectomy [39] while for anti-MuSKR-Ab MG, the therapeutic response is better with plasma exchange and immunosuppressive therapy but not with AChE-Is [10].…”

“…Studies reported that the majority of patients with MG experience sleep-related breathing disorder or sleep-disordered breathing (SDB) even if well controlled on medical treatment [5][6][7][8][9][10]. SDB include central sleep apnea (CSA), obstructive sleep apnea (OSA), mixed apneas (OSA and CSA), hypopneas and hypoventilation or hypoxemic syndromes.…”

“…Also sleep related disorders are among the clinical manifestations of MG which include sleep disordered breathing (SDB) [i.e. central sleep apnea (CSA), obstructive sleep apnea (OSA), mixed apnea (OSA and CSA), sleep-related hypoventilation or hypoxemic syndromes] [5][6][7][8][9][10], poor sleep quality, reduced sleep efficiency, reduced sleep and awakening quality, increased number of nocturnal awakenings, excessive daytime sleepiness, reduced rapid eye movement sleep (REM sleep) and altered sleep perception and dreaming [6,8,[11][12][13] and excessive limb movements during sleep [e.g. restless leg syndrome (RLS)] [14].…”