Dr. Christian Homedes /Dr. Carlos Casasnovas.
Neuromuscular Diseases Unit. HUB.
BACKGROUND:
Myasthenia Gravis (MG) is an autoimmune disease of the neuromuscular junction in the postsynaptic site. It has a prevalence of 20 cases per 100,000 inhabitants and an incidence of 21 new cases per 1,000,000. The incidence of this disease has double top-hill located between the second and fourth decade of life and a second high incidente in the fifth decade. In the first peak there is a clear predominance of women and is often associated with thymic hyperplasia. In the second peak, however, there is a clear predominance in men, also having a higher incidence of thymoma. In most patients the disease is mediated by anti-nicotinic acetylcholine receptor (AChRs), antibodies and less frequently by anti-Muscle-Specific-tyrosine kinase (MuSK) i against the low density lipoprotein receptor-related 4 (Lrp4). The anti-AChR antibodies are predominantly IgG1 and IgG3 immunoglobulins that activate complement. These antibodies disrupt neuromuscular transmission through three mechanisms: (1) complement-mediated activating the membrane attack complex and destroying the postsynaptic membrane; (2) crosslinking of AChRs, leading to degradation through receptor internalization by endocytosis; and (3) direct blockade in the binding site between acetylcholine and its receptor.
The anti-MuSK antibodies are predominantly IgG4 and do not activate complement, but MuSK inhibit the function of the grouping of AChR in the postsynaptic membrane. Some patients with MG have negative detection of antibodies in serum, either by the presence of antibodies against unknown antigens (seronegative MG) or by the presence of anti-AChR antibodies of low affinity not detectable in conventional tests. 15% of patients with thymoma and MG are often released antibodies against antigens as Titina striated muscle myosin and the ryanodine receptor, which are considered markers of severe MG. The anti-Kv1.4 anticuerpor is frequent in Japanese patients with thymoma and myocarditis and / or myositis, and recently described in a cohort of Caucasian patients with predominantly ocular MG. Recently described antibody against cortactin and agrin.
CLINICAL SYNDROMES.
The main clinical manifestation of MG is the fluctuating muscle fatigue is often accompanied by muscle weakness. The signs and symptoms of myasthenia dependent on the muscles involved:
1) Diplopia and ptosis,
2) Weakness of the facial muscles,
3) Fatigability of the cervical muscles and masseterus , with jaw claudication,
4) Bulbar musculature impairment produces dysphagia, dysphonia, dysarthria and dyspnea.
5) Weakness and fatigability of muscles of the upper and lower extremities proximally above have been described although early disease exclusively weakness of the distal muscles.
Most patients have isolated ocular symptoms, and if this is isolated is called ocular MG. Although ocular symptoms are usually the first to appear, many patients end up generalizing their symptoms, and only 15% remain with isolated ocular MG. In most patients the generalization of symptoms occurs in the first year to be in 80% of cases in the second year. After two years of onset of ocular MG, patients who are still isolated eye clinic is probably not generalize later. Between 40% -70% of patients with ocular myasthenia have positive anti-AChR. For the patient with generalized MG 85% had anti-AChR antibodies and that are negative, 20-50% have anti-MuSK antibodies and lesser anti-Lrp4. The spontaneous remission of symptoms is rare but long term stability has been reported in up to 10-20% of cases.
Press here to check video first use (1935) of prostigmine in MG⇐