WBR0766

Author	[[PageAuthor::Rim Halaby, M.D. [1]]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Pathology
Sub Category	SubCategory::Musculoskeletal/Rheumatology
Prompt	[[Prompt::A 58-year-old man with a past medical history significant for small cell lung cancer (SCLC), presents to the physician's office complaining of proximal muscle weakness and eyelid ptosis. He explains that his lower extremities were first affected, but then his upper extremities became involved. Physical examination is remarkable for tendinous areflexia. Electromyographic repetitive nerve stimulation using high-frequency stimulation shows an increment in compound muscle action potential amplitude. Which of the following is the most likely pathophysiology of the patient's condition?]]
Answer A	AnswerA::Antibodies against the pre-synaptic sodium (Na) channels
Answer A Explanation	AnswerAExp::Lambert-Eaton myasthenic syndrome (LEMS) is not due to formation of antibodies against the pre-synaptic sodium (Na) channels.
Answer B	AnswerB::Antibodies against the post-synaptic acetylcholine receptors
Answer B Explanation	AnswerBExp::Myasthenia gravis is due to formation of auto-antibodies against the post-synaptic acetylcholine receptors.
Answer C	AnswerC::Antibodies against the post-synaptic calcium (Ca) channels
Answer C Explanation	AnswerCExp::LEMS is not due to antibodies against the post-synaptic Ca channels.
Answer D	AnswerD::Antibodies against post-synaptic acetylcholine receptors
Answer D Explanation	AnswerDExp::LEMS is not due to antibodies against post-synaptic acetylcholine receptors.
Answer E	AnswerE::Antibodies against pre-synaptic Ca channels
Answer E Explanation	AnswerEExp::LEMS is due to formation of auto-antibodies against the presynaptic calcium (Ca) channels.
Right Answer	RightAnswer::E
Explanation	[[Explanation::Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune neuromuscular disorder that may present in approximately half of the patients as a paraneoplastic syndrome in patients who have SCLC. LEMS is characterized by the presence of autoimmune antibodies against voltage-gated calcium channels (VGCC) that are located on the presynaptic nerve terminal. LEMS, similar to myasthenia gravis (MG), is also a neuromuscular junction disease. Unlike MG, LEMS is characterized by incremental improvement of the junction following repetitive stimulation. In contrast, MG is characterized by junctional fatigue; loss of action potential generation is seen following repetitive stimulation. The most common presentation of patients with LEMS is proximal muscle weakness, which often starts in the lower extremities and progresses to involve the upper extremities. Ocular involvement, similar to patients with MG, is also frequently implicated in LEMS. On physical examination, muscle weakness and tendinous areflexia are common findings. Educational Objective: Lambert-Eaton myasthenic syndrome (LEMS) is characterized by formation of autoantibodies that target voltage-gated calcium channels (VGCC) in the pre-synaptic terminal of the neuromuscular junction. References: Titulaer MJ, Lang B, Verschuuren J. Lambert-Eaton myasthenic syndrome: from clinical characteristics to therapeutic strategies. Lancet Neurol. 2011; 10:1098-107.]]
Approved	Approved::No
Keyword	WBRKeyword::LEMS, WBRKeyword::Lambert-eaton, WBRKeyword::Myasthenia, WBRKeyword::Myasthenic, WBRKeyword::Myasthenia gravis, WBRKeyword::Lambert, WBRKeyword::Eaton, WBRKeyword::Presynaptic, WBRKeyword::pre-synaptic, WBRKeyword::VGCC, WBRKeyword::voltage, WBRKeyword::gated, WBRKeyword::calcium, WBRKeyword::channel, WBRKeyword::channels, WBRKeyword::autoimmune, WBRKeyword::autoantibody, WBRKeyword::autoantibodies, WBRKeyword::auto-antibody, WBRKeyword::auto-antibodies, WBRKeyword::small, WBRKeyword::cell, WBRKeyword::lung, WBRKeyword::cancer, WBRKeyword::carcinoma, WBRKeyword::paraneoplastic, WBRKeyword::acetylcholine, WBRKeyword::receptor, WBRKeyword::receptors, WBRKeyword::antibody, WBRKeyword::antibodies
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