5.17:
Myasthenia Gravis: Overview and Treatment
Myasthenia gravis is an autoimmune disorder involving the thymus gland that produces anti-receptor antibodies against the α1 subunit of nicotinic receptors.
It prevents acetylcholine interaction with the receptor at the neuromuscular junction, inhibiting impulse transmission. This leads to chronic, progressive weakness of skeletal muscles.
The antibodies can act by blocking the acetylcholine binding site, or cross-link the receptors to stimulate their internalization or induce postsynaptic membrane lysis to reduce the receptor functioning.
Patients with myasthenia initially display ptosis and diplopia. Later, they experience dysarthria that progresses to dysphagia. Eventually, the limbs and respiratory muscles are also affected.
Administration of anticholinesterases allows acetylcholine accumulation and muscle depolarization, leading to muscle strength improvement.
Alternative treatments include plasmapheresis to remove the circulating antibodies and administration of corticosteroids or immunosuppressants to limit the production of antibodies.
As the disorder is often accompanied by a thymus gland tumor, thymectomy shows gradual improvement of motor symptoms.
5.17:
Myasthenia Gravis: Overview and Treatment
Myasthenia gravis is a neuromuscular transmission disorder characterized by weakness and increased fatigability of skeletal muscles. It is an autoimmune disease affecting approximately one in 2000 people, where antibodies against the α1 subunit of nicotinic acetylcholine receptors are produced.
These antibodies interfere with the function of the nicotinic receptors in three ways: by binding to the receptor and disrupting acetylcholine binding; by causing cross-linking of receptors which leads to their internalization and degradation; and by inducing the breakdown of the postsynaptic muscle membrane. This results in impaired neurotransmission, leading to drooping eyelids, double vision, difficulty swallowing (dysphagia), and speech difficulties (dysarthria). In severe cases, respiratory and limb muscles may also be affected.
The primary drugs used to manage the symptoms of myasthenia gravis are acetylcholinesterase (AChE) inhibitors. These include neostigmine, pyridostigmine, and ambenonium. These medications help increase the accumulation of acetylcholine in the synaptic cleft, which assists in depolarizing the endplate and improving muscle function. Thymectomy, the surgical removal of the thymus gland, is often recommended due to its potential role in the disease's development and the frequent presence of thymus gland tumors. Thymectomy can gradually improve motor symptoms and sometimes lead to complete remission. In severe cases, plasmapheresis may be necessary to remove circulating antibodies. Immunosuppressant medications such as azathioprine, cyclosporine, and glucocorticoids are used to target T-cells and reduce the production of anti-receptor antibodies, providing clinical benefits.