A 62-year-old woman has double vision, especially when reading at bedtime. The problem first started several months ago and was intermittent but has worsened over the last 2 weeks and now bothers her constantly. The patient has also developed difficulty chewing and swallowing foods. She usually feels better in the mornings. She has no extremity weakness or sensory symptoms. The patient has no other medical problems and takes no medications. She does not use tobacco, alcohol, or illicit drugs. Vital signs are normal. BMI is 27 kg/m². Examination shows bilateral ptosis; there is weakness of adduction of the right eye and abduction of the left eye. Muscle strength is 4/5 in proximal muscles in the upper and lower extremities. Deep tendon reflexes are 2+ throughout. Which of the following changes involving the postsynaptic muscle cell most likely explains this patient's symptoms?

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Quizplus · Accepted Answer

11ec160b_3b0a_d6b8_9249_09605060bf3f_MD0001_00 This patient with progressive diplopia and weakness with mastication (both worse at night), along with ptosis and proximal muscle weakness on examination, likely has myasthenia gravis (MG). This disease is characterized by: MG is most commonly caused by autoantibodies against postsynaptic nicotinic acetylcholine receptors. Binding of antibody to these receptors results in blockade of the receptor's active site, receptor internalization and degradation, and damage to the motor end plate due to complement fixation. Overall, this leads to decreased numbers of functional acetylcholine receptors at the neuromuscular junction. The decrease in the number of available cation channels reduces the end plate potential following acetylcholine release. Because the threshold potential is not reached, the muscle cells do not depolarize. Synaptic concentrations of acetylcholine are unaffected, unlike in botulism or Lambert-Eaton syndrome. (Choice A) Excitation-contraction coupling refers to the process whereby an action potential within the muscle cell causes contraction of the muscle. In skeletal muscle, this process proceeds by the release of calcium into the cytoplasm, which subsequently binds troponin C and induces a conformational change allowing actin and myosin to bind. Impaired coupling implies that an action potential occurs but the skeletal muscle is unable to contract (eg, impaired actin and myosin binding), whereas MG is caused by a failure to achieve the threshold for an action potential to occur. (Choice B) The absolute refractory period for muscles in patients with MG is normal. (Choice C) The action potential amplitude of the postsynaptic muscle cell is determined by the properties of the cell membrane and is not affected by the quality of the stimulus at the muscle end plate. This is not the same as compound muscle action potential, which decreases with repeated excitation in patients with MG due to depolarization of fewer myofibers. (Choice D) Once the threshold voltage is exceeded at the neuromuscular end plate, an action potential propagates at a velocity determined by the particular properties of the muscle cell membrane. In MG, the muscle cell membrane is not affected outside of the neuromuscular junction. Educational objective: Myasthenia gravis is an autoimmune disease that causes a decrease in the number of functional acetylcholine receptors within the neuromuscular junction. This reduces the number of postsynaptic cation channels that can open in response to acetylcholine, which reduces the amplitude of motor end plate potential and prevents muscle fiber depolarization.

A 62-Year-Old Woman Has Double Vision, Especially When Reading at Bedtime