Myasthenia gravis

Myasthenia gravis (MG, Latin: "grave muscle weakness") is a neuromuscular disease leading to fluctuating weakness and fatiguability. It is one of the best known autoimmune disorders and the antigens and disease mechanisms have well been identified. Weakness is caused by circulating antibodies that block acetylcholine receptors at the post-synaptic neuromuscular junction, inhibiting the stimulative effect of the neurotransmitter acetylcholine. Myasthenia is treated with immunosuppression and cholinesterase inhibitors.

Pathophysiology

Myasthenia gravis is an autoimmune disease: it features antibodies directed against the body's own proteins. While in various similar diseases the disease has been linked to a cross-reaction with an infective agent, there is no known causative pathogen that could account for myasthenia. There is a slight genetic predisposition: particular HLA types seem to predispose for MG (B8 and DR3 with DR1 more specific for ocular myasthenia). Up to 25% have a concurrent thymoma, a tumor (either benign or malignant) of the thymus. There are various theories that explain why thymoma may predispose to MG; the disease process often improves after resection of the tumor.

Related Topics:
Autoimmune disease - Pathogen - HLA - Thymoma - Thymus

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In MG, the autoantibodies are directed against the acetylcholine receptor (nicotinic type), the receptor in the motor end plate for the neurotransmitter acetylcholine that stimulates muscular contraction. Some forms of the antibody impair the ability of acetylcholine to bind to receptors. Others lead to the destruction of receptors, either by complement fixation or by inducing the muscle cell to eliminate the receptors through endocytosis.

Related Topics:
Acetylcholine receptor - Nicotinic type - Receptor - Motor end plate - Neurotransmitter - Acetylcholine - Complement - Endocytosis

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In normal muscle contraction, cumulative activation of the ACh receptor leads to influx of sodium and calcium. Only when the levels of these electrolytes inside the muscle cell is high enough will it contract. Decreased numbers of functioning receptors therefore impairs muscular contraction.

Related Topics:
Muscle contraction - Sodium - Calcium

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