WBR0758

Author	[[PageAuthor::Yazan Daaboul, M.D. (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pathophysiology
Sub Category	SubCategory::Musculoskeletal/Rheumatology
Prompt	[[Prompt::A 26-year-old woman with no past medical history presents to the physician's office with complaints of generalized weakness for the past 4 weeks. The patient explains that she has recently noticed her eyelids have drooped down, and she has been having difficulty chewing and swallowing her foods. She also complains she has been having a "flat" smile that she never noticed in the past. When asked, the patient denies any shortness of breath or chest pain. Physical examination is remarkable for progressive bilateral weakness of the upper extremities upon repetitive movement. Which of the following factors is not associated with the severity of symptoms in this patient's condition?]]
Answer A	AnswerA::Involvement of more organs beyond the eyes
Answer A Explanation	AnswerAExp::Myasthenia gravis (MG) grading of severity is based on clinical features. While MG limited to ocular manifestations is grade I, whereas MG with myasthenic crisis or involvement of the diaphragm is grade IV.
Answer B	AnswerB::Greater quantity of antibodies against target receptors
Answer B Explanation	[[AnswerBExp::The concentration of IgG antibodies that target acetylcholine receptors is not associated with the severity of the disease. In contrast, the function of the antibodies is more important than their quantity. Antibody function, namely the acceleration of receptor degradation, is associated with disease severity.]]
Answer C	AnswerC::Fewer available receptors at the level of the muscle
Answer C Explanation	AnswerCExp::The availability of acetylcholine is inversely associated with the severity of symptoms.
Answer D	AnswerD::Difficulty of breathing
Answer D Explanation	AnswerDExp::Involvement of the diaphragm is the hallmark of severe myasthenia crisis.
Answer E	AnswerE::Need for plasma exchange
Answer E Explanation	AnswerEExp::Plasma exchange in MG is usually reserved for severe cases only.
Right Answer	RightAnswer::B
Explanation	[[Explanation::Myasthenia gravis (MG) is an autoimmune disorder characterized by a decrease in the numbers of the acetylcholine receptors at the neuromuscular junction. Physiologically, acetylcholine binds to its cationic receptor, which in turn, is stimulated to open temporarily, and an electrical potential is generated when the receptors open. The electrical potentials in the end-plate normally generate enough power to cause an action potential given the abundance of available receptors. In patients with MG, the decreased available receptors fail to produce sufficient electrical power to generate an action potential. MG manifests with symptoms of neuromuscular fatigue, whereby repeated contractions result in a progressive decrease of transmission of electric signals following repetitive stimulation ("acetylcholine rundown" phenomenon). The quantity of receptor loss is associated with a more severe disease and worse outcomes among patients with MG. The immunopathogenesis of MG is based on the presence of antibodies that target acetylcholine receptors at the post-synaptic neuromuscular junction. However, the amount of acetylcholine receptor antibodies is not associated with the severity of the disease or worse outcomes. Educational Objective: Myasthenia gravis (MG) is an autoimmune disorder characterized by a decrease in the numbers of the acetylcholine receptors at the neuromuscular junction. The concentration of IgG antibodies that target acetylcholine receptors is not associated with the severity of the disease. References: Drachman DB. Myasthenia gravis. N Engl J Med. 1994; 330:1797-1810. First Aid 2014 page 429]]
Approved	Approved::Yes
Keyword	WBRKeyword::Myasthenia gravis, WBRKeyword::Receptors, WBRKeyword::IgG antibodies, WBRKeyword::Autoimmune disorder, WBRKeyword::Acetylcholine receptor, WBRKeyword::Acetylcholine rundown
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