Neurodegenerative and Spinal Disorders

Question

1. A 32-year-old woman presents with complaints of “drooping eyelids,” difficulty chewing and swallowing, and weakness of her arms and legs that is less severe in the morning but becomes worse as the day progresses. She complains that climbing stairs and lifting objects are becoming increasingly difficult. Clinical examination confirms weakness of the eyelid and jaw muscles. She is told that she may have myasthenia gravis and is scheduled for testing using the short-acting acetylcholinesterase inhibitor edrophonium (Tensilon). 
2. Explain the pathogenesis of this woman’s symptoms as it relates to myasthenia gravis. 
3. Explain how information from the Tensilon administration can be used to assist in the diagnosis of the disorder.  

Answer 1

a. Myasthenia gravis is an autoimmune disorder that results from autoantibodies that bind with acetylcholine receptors on a motor endplate. Because of this, acetylcholine will not bind to the acetylcholine receptors to cause a depolarization of the membrane and eventually an end-plate potential. In addition, an action potential will not be generated in the sarcolemma. For a muscle to contract, the released acetylcholine from the presynaptic membrane has to bind to acetylcholine receptors in the postsynaptic membrane. In MG, the autoantibodies prevent the binding of acetylcholine to acetylcholine receptors and eventually an action potential for muscle contraction. Because of this, people with MG experience muscle weakness, drooping eyelids, difficulty chewing and swallowing, difficulty climbing and lifting, and weakness in the arms and legs that progress during the day and get better with rest.

b. The Tensilon test administers Tensilon or edrophonium which inhibits the enzyme acetylcholinesterase. This enzyme breaks down acetylcholine in the synaptic cleft. By inhibiting this enzyme, more acetylcholine can bind to acetylcholine receptors to cause muscle contraction. Therefore, a positive Tensilon test will show improved or better muscle strength after administration of Tensilon which indicates that a person has MG.

Porth's Pathophysiology 10th ed. by Norris (Review Exercise)