Myasthenia Gravis: Epidemiology, Pathophysiology and Clinical Manifestations

Abstract

Myasthenia gravis (MG) is an autoimmune neurological disorder characterized by defective transmission at the neuromuscular junction. The incidence of the disease is 4.1 to 30 cases per million person-years, and the prevalence rate ranges from 150 to 200 cases per million. MG is considered a classic example of antibody-mediated autoimmune disease. Most patients with MG have autoantibodies against the acetylcholine receptors (AChRs). Less commonly identified autoantibodies include those targeted to muscle-specific kinase (MuSK), low-density lipoprotein receptor-related protein 4 (Lrp4), and agrin. These autoantibodies disrupt cholinergic transmission between nerve terminals and muscle fibers by causing downregulation, destruction, functional blocking of AChRs, or disrupting the clustering of AChRs in the postsynaptic membrane. The core clinical manifestation of MG is fatigable muscle weakness, which may affect ocular, bulbar, respiratory and limb muscles. Clinical manifestations vary according to the type of autoantibody, and whether a thymoma is present.

Comorbid Autoimmune Diseases in Patients With Myasthenia Gravis: A Retrospective Cross-Sectional Study of a Chinese Cohort

“…The disorder is typically mediated by antibodies against acetylcholine receptor (AChR) or other proteins located at the neuromuscular junction, including muscle-specific tyrosine kinase (MuSK) and lipoprotein receptor-related protein 4 ( 2 ). The incidence of MG ranges from 0.3 to 2.8 per 100,000 worldwide, which varies with age, sex, and ethnic groups ( 3 , 4 ).…”

The Neuromuscular Junction: Roles in Aging and Neuromuscular Disease

“…Consistent with such destabilization, most patients with MG raise autoantibodies against the acetylcholine receptors (AChRs) and sometimes to MuSK, Lrp4 and agrin [ 112 , 113 ]. AChR antibodies are found in most MG patients (~80%), predominantly of the IgG1 and IgG3 subclasses [ 114 ].…”

“…There are some patients who do not have AChR or MuSK antibodies (double-seronegative MG) but likely have antibodies against yet unknown targets [ 116 ]. Lrp4 antibodies are present in some patients, often in females and with antibodies to agrin as well [ 112 ]. Structurally, changes to AChR density and localization result in reduced endplate size and complexity [ 100 , 117 ].…”

Factors affecting minimal manifestation status induction in myasthenia gravis

“…Pathogenic antibodies impair postsynaptic structures through complement activation, promoting anti-acetylcholine receptor (AChR) internalization, blocking AChR, or disturbing the agrin/low-density lipoprotein-receptor-related protein 4 (LRP4)/muscle-specific tyrosine-protein kinase receptor (MuSK)/Dok7/rapsyn pathway. 1 These processes impair neuromuscular junction transmission, characterized by fluctuating muscle weakness and fatigability. 2 , 3 With the development of intensive care and immunotherapy, the mortality of MG has significantly decreased, and many patients can achieve minimal manifestation status (MMS) or better status.…”