WBR0758

Author	[[PageAuthor::Rim Halaby, M.D. [1]]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pathophysiology
Sub Category	SubCategory::Musculoskeletal/Rheumatology
Prompt	[[Prompt::A 26 year old female patient, previously healthy, presents to the physician's office complaining of generalized weakness. Additionally, the patient explains that she has drooping of the eyelids with difficulty chewing and swallowing her foods. Additionally, she complains of having a "flat" smile that also started with her other symptoms. When asked, the patient denies any shortness of breath. Physical examination shows progressive weakness of her extremities upon repetitive movement. Which of the following factors does not necessarily correlate with a more severe disease in this patient's condition?]]
Answer A	AnswerA::Involvement of more organs beyond the eyes
Answer A Explanation	AnswerAExp::Grading of myasthenia gravis (MG) is based on clinical features. Mere ocular findings are considered grade I MG, whereas involvement of the diaphragm is considered myasthenia crisis or grade IV.
Answer B	AnswerB::Quantity of antibodies against target receptors
Answer B Explanation	[[AnswerBExp::The level of IgG antibodies that target acetylcholine receptors does not necessarily correlate with the severity of the disease. In contrast, the function of the antibodies is more important than their quantity. Their function and the acceleration of degradation of receptors is thus associated with severity of disease.]]
Answer C	AnswerC::Quantity of available receptors at the level of the muscle.
Answer C Explanation	AnswerCExp::Availability of acetylcholine receptors correlates directly with the severity of symptoms. As the number of receptors is reduced, MG becomes more severe.
Answer D	AnswerD::Difficulty of breathing
Answer D Explanation	AnswerDExp::Involvement of the diaphragm is the hallmark of severe myasthenia crisis.
Answer E	AnswerE::Female gender
Answer E Explanation	AnswerEExp::Females are more commonly affected by MG. However, female gender is not associated with more severe disease.
Right Answer	RightAnswer::B
Explanation	[[Explanation::The patient presents with signs and symptoms consistent with myasthenia gravis (MG). MG is characterized by a decrease in the numbers of the acetylcholine receptors at the neuromuscular junction. The quantity of receptor loss correlates with the severity of the disease and intensity of symptoms, manifested by muscle weakness. Physiologically, acetylcholine binds to its cationic receptor, causing the latter to open temporarily. 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 due to the abundance of available receptors. In the case of MG, the decreased available receptors will fail to produce sufficient electrical power to generate an action potential. 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 does not correlate with the severity of the disease. MG is also characterized by "neuromuscular fatigue", a condition whereby repeated contractions lead to progressive decrease of transmission of electric signals due to decreased amount of released acetylcholine following repetitive stimulation. This phenomenon is called "acetylcholine rundown", which is physiologically seen in normal individuals, but is usually clinically manifested in patients with MG to the baseline decreased numbers of receptors. Educational Objective: Myasthenia gravis (MG) is caused by autoimmune antibodies against the post-synpatic acetylcholine receptors at the neuromuscular junction. Quantity of antibodies in a patient's serum does not necessarily correlate with the severity of the disease. Reference: Drachman DB. Myasthenia gravis. N Engl J Med. 1994; 330:1797-1810. Educational Objective: References: ]]
Approved	Approved::No
Keyword	WBRKeyword::myasthenia, WBRKeyword::gravis, WBRKeyword::receptor, WBRKeyword::receptors, WBRKeyword::antibody, WBRKeyword::antibodies, WBRKeyword::IgG, WBRKeyword::acetylcholine, WBRKeyword::autoimmune, WBRKeyword::repetitive, WBRKeyword::muscle, WBRKeyword::weakness, WBRKeyword::fatigue, WBRKeyword::fatiguability, WBRKeyword::ocular, WBRKeyword::extraocular
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