Pathophysiology
Clinical meaning
Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disease in which antibodies attack acetylcholine receptors at the neuromuscular junction, preventing normal nerve-to-muscle signal transmission. Understanding this mechanism explains the characteristic pattern of muscle weakness that worsens with activity and improves with rest. Normal neuromuscular transmission requires acetylcholine (ACh) to be released from the motor nerve terminal, cross the synaptic cleft, and bind to ACh receptors on the muscle fiber (motor end plate). This triggers muscle contraction. In MG, the immune system produces antibodies (primarily IgG anti-AChR antibodies in 85% of patients) that attack these receptors through three mechanisms: blocking ACh from binding, accelerating receptor degradation through complement-mediated destruction, and triggering internalization and destruction of receptors. The result is a reduced number of functional ACh receptors, meaning fewer muscle fibers are recruited with each nerve impulse. The thymus gland plays a central role in MG pathology. Approximately 15% of MG patients have a thymoma (thymic tumor), and 65% have thymic hyperplasia. The thymus is believed to be the site where autoreactive T-cells that drive the anti-AChR antibody response are generated. Thymectomy...