Neuromuscular junction disorders: Pathology review

While doing your rounds, you see Kira, a 23-year-old female who presents with a series of recurrent symptoms that get worse as the day progresses. These include slurring of speech, difficulty swallowing, and double vision. She also mentions that her head feels heavy and is hard to hold up. She also complained that her arms are so weak she can’t even brush her hair. Additionally, she reports severe fatigue and shortness of breath. On examination, sensation and reflexes are normal. Next, you see a 62-year-old man named Jonathan, who presents with a history of leg muscle weakness that prevents him from doing simple things like climbing stairs or standing up, which gets better the more he uses his legs. He also reports shortness of breath, fatigue, dry mouth, impotence, and unintentional weight loss. Examination reveals a severely underweight man with dilated pupils. Reflexes are initially absent, although these are obtainable after a brief period of exercise. Blood tests were obtained, detecting anti-acetylcholine receptor antibodies in Kira and anti-voltage-gated calcium channels antibodies in Jonathan.

Now, both seem to have some type of neuromuscular junction disease. But first, a bit of physiology. In normal neuromuscular function, a nerve impulse is carried down the axon from the spinal cord, to the nerve endings, in the neuromuscular junction, where the impulse is transferred to the muscle cell. Here, the nerve impulse leads to the opening of voltage-gated calcium channels, causing an influx of calcium ions into the nerve terminal, which triggers synaptic vesicle fusion with plasma membrane. These synaptic vesicles contain a neurotransmitter called acetylcholine, which is released into the synaptic cleft. The neurotransmitter then binds to nicotinic acetylcholine receptors on muscle cell membranes and activates a chain reaction in the muscles that ultimately results in their contraction.