**1. Myasthenia gravis: overview**

Myasthenia gravis (MG) is a neuromuscular autoimmune disease characterized by the production of autoantibodies directed against molecules involved in neuromuscular transmission (NMT): the α1 subunit of the nicotinic postsynaptic acetylcholine receptors (AChR) and muscle-specific tyrosine kinase (MuSK) [1–3].

MG occurs more frequently in women than men; the age of onset in women is in their second and third decade of life, while in men, it is in the fourth [1, 4]. Moreover, there is a second peak of incidence in the sixth and seventh decades, with men being more affected. Epidemiologically, it was found that men tend to experience more severe symptoms [4, 5].

Clinically, MG is defined by a painless, fluctuant muscle weakness that progressively increases with repetitive muscle action but decreases with rest [1–3]. The degree of weakness is dependent on the exertion of the skeletal muscle group involved, but in some cases, it may change over longer periods without any evident cause [6].

Even though all types of voluntary muscle can be involved during the disease course, MG characteristically begins with a few isolated signs and spreads to other muscles within a variable period of time (weeks, months, or even years) [6].

In about 15–20% of the patients, myasthenic symptoms remain confined to the ocular muscles; however, with disease progression and usually within 2 years, the rest of them develop bulbar symptoms (i.e., dysphagia, dysarthria) and facial, axial, and limb weakness [1, 2, 6, 7].

The maximum severity of MG manifestations is usually reported during the first year in two-thirds of patients [1]. Additionally, it has become evident that, in general, the illness tends to stabilize, improve (57%), or even resolve (13%) after several years [3, 6].

It is important to emphasize that in MG, symptoms may worsen in certain conditions including stress, systemic illness (especially upper respiratory infections), hypo−/hyperthyroidism, pregnancy, menstrual cycle, exposure to heat, operative procedures, drugs affecting NMT, and fever [1, 5, 8]. However, in the majority of cases, no precipitating factor can be found [3, 5]. A severe exacerbation requiring endotracheal intubation with mechanical ventilation is defined as myasthenic crisis (Class V myasthenia by MG Foundation of America) [5].

The treatment used in MG includes symptomatic treatment (acetylcholinesterase inhibitors), rapid short-term immunomodulating therapies (plasmapheresis and intravenous immunoglobulin), chronic long-term immunomodulating treatment (glucocorticoids and/or other immunosuppressive agents), and, in selected patients, surgical treatment (thymectomy). In all cases, MG management should be individualized according to patient characteristics and the severity of the disease [3].

Currently, the mortality of MG is extremely low, considering that only among the 19% of the patients with severe generalized MG also need endotracheal intubation; the mortality can reach 8% despite ventilation [5, 6, 9].
