A 35-year-old woman comes to the emergency department with progressively worsening exertional dyspnea and generalized weakness. She also complains of cough, especially during and after meals. Over the past 3 weeks she has had episodes of blurry vision and difficulty raising her arms above her head and walking up and down stairs. She has no hemoptysis, muscles aches, slurred speech, headaches, numbness, or paresthesias. Her medical history is significant for hypothyroidism and hypertension. There is no family history of malignancy. She is an active smoker with a 20-pack-year history.
Vital signs are within normal limits. The patient has subjective fatigable horizontal binocular diplopia. Her neck flexors and proximal muscles of the upper and lower extremities are 4/5 in strength. Sensory examination and reflex testing are unremarkable.
Vital capacity obtained at the bedside is 0.5 L (

Question

A 35-year-old woman comes to the emergency department with progressively worsening exertional dyspnea and generalized weakness.  She also complains of cough, especially during and after meals.  Over the past 3 weeks she has had episodes of blurry vision and difficulty raising her arms above her head and walking up and down stairs.  She has no hemoptysis, muscles aches, slurred speech, headaches, numbness, or paresthesias.  Her medical history is significant for hypothyroidism and hypertension.  There is no family history of malignancy.  She is an active smoker with a 20-pack-year history.
Vital signs are within normal limits.  The patient has subjective fatigable horizontal binocular diplopia.  Her neck flexors and proximal muscles of the upper and lower extremities are 4/5 in strength.  Sensory examination and reflex testing are unremarkable.
Vital capacity obtained at the bedside is 0.5 L (< 50% of predicted).
Complete blood count, comprehensive metabolic panel, thyroid-stimulating hormone, and chest x-ray are normal.  Noncontrast computed tomography scan of the chest shows mild centrilobular emphysema and a 2.6-cm mediastinal mass.  There is no regional lymphadenopathy.
Which of the following is the best next step in management of this patient?

Quizplus · Accepted Answer

This patient's presentation suggests generalized myasthenia gravis (MG). MG is due to autoantibodies blocking acetylcholine receptors. Ocular MG presents with eyelid and ocular muscle weakness. Generalized MG affects ocular muscles with variable involvement of bulbar (eg, dysarthria, dysphagia, fatigable chewing), limb, or respiratory muscles. These symptoms can fluctuate throughout the day but are usually worse later in the day. Weakness and fatigue worsen with exercise, stress, or infection and improve with rest. Diagnosis of MG is confirmed with serology. Acetylcholine receptor (AchR) antibody is present in up to 85% of MG patients. Muscle-specific tyrosine kinase receptor (MuSK) antibodies are present in up to 50% of AchR-antibody-negative patients. MG is also commonly associated with thymic hyperplasia, thymoma, and autoimmune thyroid disease. All MG patients should have thyroid-stimulating hormone measured to evaluate for thyroiditis and chest computed tomography to look for mediastinal mass (thymoma). Once the diagnosis of MG is confirmed via serology or electrophysiology, patients can be treated with symptomatic (eg, pyridostigmine) and/or immune (eg, corticosteroids, intravenous immunoglobulin) therapies. Diagnosis of MG (Choice A) Lumbar puncture can help diagnose multiple sclerosis, Guillain-Barré syndrome, or central nervous system tumor. Multiple sclerosis usually presents with relapsing-remitting episodes of neurologic dysfunction disseminated in space and time. Guillain-Barré syndrome typically presents with ascending weakness, absent deep-tendon reflexes, and mild sensory symptoms after a recent viral illness. Central nervous system tumors (lymphomatous or carcinomatous meningitis) have other symptoms, including headache, nausea, vomiting, mental status changes, focal weakness, radicular pain, or cranial nerve palsies. (Choice B) Brain magnetic resonance imaging is recommended in MG patients who have bulbar symptoms to rule out other pathology. However, cervical spine imaging does not explain this patient's ocular findings. (Choice C) Muscle biopsy can diagnose a myopathy, which can cause symmetrical muscle weakness but not ocular symptoms. (Choice E) Lambert-Eaton myasthenic syndrome (LEMS) is a paraneoplastic syndrome most commonly associated with small-cell lung cancer. LEMS presentation can be similar to myasthenia gravis. Both can have ocular symptoms and muscle weakness. In LEMS, deep-tendon reflexes are decreased or absent. However, deep-tendon reflexes and weakness improve with repetitive muscle activation. Voltage-gated calcium channel antibodies confirm the diagnosis. Given this patient's young age and mediastinal (rather than lung) mass, MG is more likely. Educational objective: Diagnosis of myasthenia gravis consists of serologies (acetylcholine receptor and muscle-specific tyrosine kinase receptor antibodies) and nerve conduction studies in a stepwise manner. Thyroid-stimulating hormone and chest computed tomography (to look for thymoma) should be ordered in all patients diagnosed with myasthenia gravis. __________ References: Misdiagnosis of myasthenia gravis and subsequent clinical implication: A case report and review of literature. (http://www.ncbi.nlm.nih.gov/pubmed/22375266) Muscle autoantibodies in myasthenia gravis: beyond diagnosis?. (http://www.ncbi.nlm.nih.gov/pubmed/22882218)

A 35-Year-Old Woman Comes to the Emergency Department with Progressively