A 61-year-old woman comes to the clinic due to vision problems for the last 6 months. The patient says her eyes get tired easily, especially in the late afternoon and evening. She has smoked a pack of cigarettes daily for the past 35 years and does not use alcohol or illicit drugs. On physical examination, there is weakness of the extraocular muscles. Pupillary reflex, deep tendon reflexes, and sensation are normal. A contrast-enhanced CT scan of the chest is shown in the exhibit. Which of the following is the most likely mechanism underlying this patient's symptoms?

Question

A 61-year-old woman comes to the clinic due to vision problems for the last 6 months.  The patient says her eyes get tired easily, especially in the late afternoon and evening.  She has smoked a pack of cigarettes daily for the past 35 years and does not use alcohol or illicit drugs.  On physical examination, there is weakness of the extraocular muscles.  Pupillary reflex, deep tendon reflexes, and sensation are normal.  A contrast-enhanced CT scan of the chest is shown in the exhibit.  Which of the following is the most likely mechanism underlying this patient's symptoms?

Quizplus · Accepted Answer

11ec160b_39d3_1974_9249_eba05e365f67_MD0001_00 This patient's presentation is consistent with myasthenia gravis (MG), an autoimmune disease caused by autoantibodies directed against nicotinic acetylcholine receptors on the postsynaptic membrane of the neuromuscular junction. Acetylcholine binding normally opens these ligand-gated sodium channels, and the subsequent influx of sodium ions raises endplate potential. To produce a self-propagating muscle action potential, there must be enough activated acetylcholine receptors to allow the endplate potential to reach threshold. In MG, antibody binding leads to receptor degradation and complement-mediated damage of the postsynaptic membrane, preventing action potentials from being triggered. Patients commonly have fluctuating weakness that worsens throughout the day and most often involves the extraocular (eg, ptosis, diplopia) and bulbar (eg, fatigable chewing, dysphagia) muscles. Ptosis can increase when the patient sustains an upward gaze, and electrophysiologic studies may demonstrate decreasing force of muscle contraction with repetitive stimulation. Most patients have thymic abnormalities (eg, thymoma, thymic hyperplasia) that may appear as an anterior mediastinal mass on chest imaging. (Choice B) Lambert-Eaton syndrome is caused by autoantibodies directed against the presynaptic calcium channel, which causes reduced acetylcholine release. Patients usually have proximal extremity weakness that improves with muscle use, as opposed to the fatigable weakness of extraocular and bulbar muscles common in MG. In addition, hyporeflexia (vs normal reflexes) is typically present. (Choice C) Guillain-Barré syndrome is caused by segmental demyelination of peripheral nerves by infiltrating T lymphocytes (CD8⁺) and autoantibody formation. Patients with this acute inflammatory polyneuropathy can have ocular muscle weakness; however, symmetric ascending muscle weakness is classic, and symptoms typically progress rapidly over hours to days (vs months). (Choice D) Polymyositis is an autoimmune disease that occurs due to CD8⁺ lymphocyte-mediated skeletal muscle damage. It usually presents with symmetric proximal muscle weakness (eg, hip flexors) rather than extraocular muscle weakness. (Choice E) Vascular deposition of circulating immune complexes-as may occur in connective tissue disorders such as systemic lupus erythematosus and rheumatoid arthritis-can cause inflammation of blood vessel walls (vasculitis) and a wide range of symptoms. Muscle weakness can occur but is unlikely to be isolated to extraocular muscles or fluctuate over the course of the day. Educational objective: Myasthenia gravis is caused by circulating antibodies directed against acetylcholine receptors of the neuromuscular junction. Autoantibody binding leads to receptor degradation, producing fluctuating weakness that worsens throughout the day and most commonly affects the extraocular muscles (eg, ptosis, diplopia). Most patients have thymic abnormalities (eg, thymoma). __________ References: Myasthenia gravis: a review. (http://www.ncbi.nlm.nih.gov/pubmed/23193443)

A 61-Year-Old Woman Comes to the Clinic Due to Vision