Myasthenia gravis: Mechanisms, clinical syndromes, and diagnosis

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by muscle weakness and fatiguability. The pathogenesis of MG is mediated in most cases by autoantibodies directed against the nicotinic acetylcholine receptor at the neuromuscular junction, although less commonly autoantibodies may target muscle-specific kinase (MuSK) or low-density lipoprotein receptor-related protein 4 (LRP4). These autoantibodies disrupt cholinergic transmission at the neuromuscular junction through several mechanisms, including direct functional blocking, downregulation, destruction, or disruption of receptor clustering in the postsynaptic membrane. MG is characterized by fatigable muscle weakness in the ocular, bulbar, respiratory or limb muscles. Clinical manifestations can vary significantly among individuals depending on the type of autoantibody or presence of thymoma. Due to the variable presentation of symptoms, diagnosing MG can be challenging. A comprehensive approach that combines clinical assessment, serological testing, electrophysiological studies, and imaging is essential for accurate diagnosis.