A 70-year-old woman presents to the primary care clinic reporting increasing fatigue over the past 6 months that is more severe in the evenings. Along with fatigue, the patient reports fluctuating bilateral ptosis with vertical binocular diplopia that began 4 months before the visit.
Episodes of bilateral ptosis and binocular diplopia lasting 1 to 4 weeks alternate with symptom-free intervals of 3 to 4 weeks. Ptosis is asymmetric and more severe in the left eye. The patient denies muscle weakness (other than ocular weakness), weight loss, fevers, vision loss, dysarthria, headaches, dyspnea, dysphagia, dizziness, and gait disturbances. Her medical history includes macular degeneration, managed with antioxidants and zinc, and hypertension, controlled with metoprolol and losartan. She denies drug allergies and alcohol or drug use.
On physical examination, the patient’s vital signs are within normal limits. Extraocular movements show bilateral superior and medial rectus weakness. A sustained upward gaze increases the ptosis bilaterally. Pupils appear equal and reactive to light. Neurologic exam, evaluating cranial nerves, sensation, and reflexes, shows no abnormalities.
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The patient’s fluctuating bilateral ptosis, binocular diplopia, fatigue, and an absence of pupillary abnormalities raises the clinical index of suspicion for myasthenia gravis (MG). Serologic testing for acetylcholine receptor (AChR) antibodies is positive. A computed tomography (CT) scan of the brain rules out intracranial neoplasm.
Myasthenia Gravis
Myasthenia gravis is an autoimmune disease that causes postsynaptic neuromuscular junction dysfunction via an antibodymediated, T-cell–dependent process. Autoantibodies attack and reduce the number of functioning AChRs and muscle-specific receptor tyrosine kinase (MuSK) receptors.1
Myasthenia gravis is an uncommon disorder with a worldwide prevalence of 70 to 320 per million people. The age of disease onset has a bimodal distribution, with the first peak in the second and third decade, primarily in women, and the later peak between the sixth and eighth decade, primarily in men. Although rare, MG is the most common neuromuscular transmission disorder.2,3
The cardinal feature of MG is fluctuating skeletal muscle weakness that often presents with true muscle fatigue. The fatigue is a declining contractile muscle force specified to particular muscle groups.2 Symptoms of ocular weakness include ptosis and diplopia.4 A sustained upward gaze increases ptosis, in what is called “the curtain sign.” Binocular diplopia is caused by extraocular muscle weakness. Double vision can occur horizontally or vertically, and the pupil always is spared.
Bulbar symptoms of MG include dysarthria, dysphagia, and fatigable chewing. Weakened oropharyngeal muscles may prevent the ability of the patient to hold the jaw in a closed position. Changes in speech include a nasal tone or decreased volume. Dysphagia, linked with solids and liquids, increases the risk for aspiration, dehydration, and malnutrition.5
Facial, neck, and limb muscles frequently are affected in patients with MG. Facial muscle weakness can cause patients to appear expressionless. Neck flexor and extensor muscles can weaken, causing a “dropped head.”6 Both upper and lower extremities are affected proximally, with the greatest weakness typically in the upper extremities. Weakness in wrist and finger extensors and foot dorsiflexors also can be present.6
The most serious complications of MG occur in later stages of the disease, with increasing respiratory muscle weakness. Dyspnea and shortness of breath can present spontaneously during the active disease phase or when aggravated by physical activity, illness, infection, surgery, medications, or immunosuppressive tapering. Respiratory insufficiency and impending respiratory failure signal a myasthenic crisis. Crises can be precipitated by events that exacerbate symptoms, such as infection, surgery, or pregnancy.7
Weakness in respiratory and oropharyngeal muscles results in dyspnea, which causes a suffocating or drowning sensation, and dysphagia. Other signs include hypophonia, accessory muscle breathing, and paradoxical abdominal breathing. The patient will have a low vital capacity and need intubation.7
Preventing myasthenic crisis is vital to avoid mechanical ventilation; once it becomes necessary, it often is challenging to wean the patient off the ventilator. In addition, MG crises increase the risk for various infections, such as pneumonia, bronchitis, urinary tract infection, Clostridioides difficile colitis, bacteremia, and sepsis. Vascular complications such as deep vein thrombosis, heart failure, acute myocardial infarction, and cardiac arrest can result.7
Muscle weakness worsens with muscle use and improves with rest. Sensations and reflexes throughout the body remain unaffected. As the disease progresses, symptoms become increasingly severe, widespread, and frequent. Symptom progression peaks within a few years of symptom onset.8
