National consensus on the diagnosis and treatment of myasthenia gravis

2025

Abstract

Myasthenia gravis is a neurological disease that is rare in general practice and this complicates its diagnosis and treatment. Although there is widespread agreement on the use of many drugs for the treatment of myasthenia gravis, there is no internationally accepted standard for this. As myasthenia gravis is a heterogeneous disease, there is no best therapeutic approach for all patients. The few randomized trials in these patients have limited generalization. Uncontrolled studies are of limited significance. This consensus is in line with international recommendations and guidelines, as well as our personal experience, and aims to guide clinicians on the approach to the diagnosis and treatment of myasthenia gravis.
Myasthenia gravis (MG) is an autoimmune disease caused by antibodies against acetylcholine receptors (AChR), muscle-specific tyrosine kinase (MuSK), and other AChR-associated proteins in the postsynaptic membrane. It is characterized by rapid fatigue of the striated muscles and muscle weakness due to impaired transmission of nerve impulses at the level of the neuromuscular synapse.
The prevalence is about 15-25/100,000, with an annual incidence of 1 per 100,000 population. The onset of the disease in the anti-AChR form is bimodal - with an early peak about the age of 30 and late - about the age of 70-80. In Europe, most patients start complaining after the age of 50. In myasthenia with an early onset, the ratio of women to men is 3:1, while in myasthenia with a late onset, men suffer more often. Environmental factors are still poorly investigated. MG with anti-MuSK antibodies has a geographical difference in Europe with a characteristic south-north gradient - most cases are observed in the Mediterranean, and the least in the Scandinavian countries.
The etiology is related to the influence of genetic and environmental factors. Evidence of this is the concordance of 35% in monozygotic and 5% in heterozygous twins for the development of MG. Numerous genes have been identified, including HLA genes, responsible for the increased risk of developing MG. While some of them lead to various autoimmune diseases, others are more specific to MG and certain types of MG. Sex hormones also play a role in the predisposition to MG. They may also explain the different sex distribution of early-onset and late-onset myasthenia gravis and the higher prevalence of the disease among young and postpartum women. The role of various viruses attacking the thymus has been suggested.
Some immunotherapies against tumors, as well as other autoimmune and rheumatic diseases, can induce myasthenia gravis.
The pathogenesis is autoimmune, involving the thymus gland. Disorder of neuromuscular transmission is associated with a significant reduction in the amount of acetylcholine receptors in the postsynaptic membrane of the neuromuscular synapse. The damage is due to an antibody-mediated and complement-dependent autoimmune response with antibody production. The latter can be divided into two major groups - antibodies to transmembrane or extracellular proteins and intracellular. The first group of antibodies directly pathological for MG (as anti-AChR antibodies) or indirectly (as anti-MuSK antibodies and anti-lipoprotein bound peptide 4 (LPR4) antibodies) affect the function of AChR in the neuromuscular synapse, leading to impaired ion transport through the muscle membrane and reduced muscle contraction. Antibodies to intracellular proteins (titin, ryanodine receptors, cortactin) are unlikely to be pathological for MG, but can be used as a clinical marker to determine disease severity, the presence of thymoma, or myopathy. Due to their high specificity, the latter are not present in clinical practice.