MYASTENIA - an autoimmune disease that causes a violation of neuromuscular transmission and is manifested by weakness and pathological fatigue of skeletal (striated) muscles. The disease is associated with the formation of antibodies against acetylcholine receptors located on the postsynaptic membrane of the neuromuscular synapse. Neonatal myasthenia gravis is a transient condition observed in infants born to mothers suffering from myasthenia gravis and due to the passage through the placenta of maternal antibodies to acetylcholine receptors.
Myasthenia gravis can occur at any age, but the peak incidence occurs in 20-40 and 65 - 75 years. In the vast majority of cases, the disease primarily involves the eye muscles, so at first patients complain of drooping eyelids and double vision. Over the next 1-2 years, in most patients, a generalization of the process occurs with the addition of weakness of the facial and bulbar muscles, muscles of the neck, limbs and trunk. But in some patients, the disease does not extend further than the external muscles of the eye (ocular form). Pronounced fluctuations in symptoms during the day are characteristic, in connection with this, the disease is often mistaken for hysteria. The phenomenon of pathological muscle fatigue is manifested by an increase in symptoms against the background of physical exertion (for example, increased dysphagia during meals, and dysphonia during a conversation). Characteristic is the absence of autonomic disorders (disorders of the innervation of the pupil or pelvic disorders), and sensitivity disorders. A neurological examination reveals a decrease in strength, increasing with the repetition of movements. To enhance ptosis, the patient is asked to fix his gaze, looking up or ask to raise his hands up for 30 - 60 s. To detect muscle weakness in the larynx, the patient is asked to count aloud to 100. Reflexes are usually normal. Often there is a selective involvement of muscles (for example, the flexors of the neck are weaker than the extensors), this allows us to distinguish myasthenia gravis from asthenia or hysteria. Symptoms of myasthenia gravis can aggravate a number of drugs that can be prescribed to the patient only if absolutely necessary, provided that they are stable. This group consists of antibiotics (streptomycin, gentamicin and other aminoglycosides, polymyxin B, colistin, tetracycline , ampicillin , erythromycin , ciprofloxacin , clindamycin), sulfonamides, cardiovascular (beta-blockers, quinidine, lidocaine , novocainamide , antagonists, antagonists, antagonists, antagonists, antagonists, antagonists (Trimethadione, phenytoin, carbamazepine, barbiturates), and lithium preparations chlorpromazine, diazepam (relanium) mioplegicheskie agents, quinine, corticosteroids, thyroid hormone, magnesium salts containing iodine rentgenokontra tnye substances.
In patients with generalized myasthenia gravis, sometimes a rapid deterioration occurs with the development of respiratory failure associated with weakness of the respiratory muscles or bulbar muscles (myasthenic crisis). Crisis can occur due to infection or taking medications that disrupt neuromuscular transmission. The development of the crisis may be preceded by pronounced fluctuations in muscle weakness, a decrease in the Mars of the body, restriction of motor activity, increased drooping of the head, increasing dysarthria, shortness of breath . Less commonly, an increase in muscle weakness and respiratory failure is caused by an overdose of anticholinergics (cholinergic crisis). Generalized fasciculations and krampi, hypersalivation, increased peristalsis, diarrhea, vomiting , and bradycardia testify in favor of this variant of the crisis.
The diagnosis . To confirm the diagnosis, a proserin test is performed with 2 ml of a 0.5% solution of proserin, which is administered subcutaneously and the effect is monitored for 40 minutes. The test should be carried out only when the weakness of certain muscles is detected. To exclude the placebo effect, it is previously recommended to introduce saline. To correct the possible side effects of proserin (bradycardia, bronchospasm, arterial hypotension), you should also have a syringe with 0.5-1 mg of atropine and Ambu bag ready. With the introduction of proserin, other undesirable effects are also possible - hypersalivation, lacrimation, fasciculations, diarrhea, intestinal colic , nausea , urinary and fecal incontinence. The diagnosis is also confirmed by determining the content of antibodies to acetylcholine receptors. In adults with a confirmed diagnosis of myasthenia gravis, pneumomediastinography or computed tomography of the chest is indicated to exclude thymoma. To exclude thyrotoxicosis, which is often combined with myasthenia, investigate the content of thyroid hormones or conduct other tests that determine the functional activity of the gland. To exclude other autoimmune diseases, studies of rheumatoid factor, antinuclear antibodies are shown.
Treatment . Anticholinesterase drugs inhibit the breakdown of acetylcholine in the synapse and increase muscle strength. More often used pyridostigmine (Kalimin). When taken orally, its action begins after 10-30 minutes, reaches a peak after 2 hours, and then gradually weakens over 2 hours. Treatment begins with 30 mg 3 times a day, then the dose is increased to 60-120 mg every 4-6 hours. Although pyridostigmine is effective in most patients, only a small fraction of them completely regress their symptoms. Common side effects include abdominal pain, nausea , diarrhea, and hypersalivation. The drug is contraindicated in chronic obstructive pulmonary diseases and bronchial asthma. Corticosteroids are prescribed with insufficient effectiveness of anticholinesterase drugs. They cause improvement in 70 - 90% of patients, but in the first 3 weeks, especially if treatment is started with a high dose, muscle weakness (including bulbar and respiratory) can increase. When a lasting effect is achieved, they begin to slowly reduce the dose. In a significant part of cases, patients are forced to take a maintenance dose of the drug for many years.
Immunosuppressants (azathioprine, less commonly cyclosporine and cyclophosphamide) are prescribed in generalized or boulevard form with poor tolerance to corticosteroids. Timectomy is indicated in young patients (up to 60 years old) with a generalized form of the disease, as well as in patients with thymomas. When signs of myasthenic crisis appear, the patient should be urgently hospitalized in the intensive care unit. It is advisable to place the patient in a half-sitting position, give oxygen through a mask or nasal catheter. Introduce intravenously 1 ml of a 0.05% solution of proserin and proceed with a slow intravenous infusion of proserin (8-12 mg of the drug should be administered per day). If infusion is temporarily impossible, the drug can also be administered intramuscularly at a dose of 1-2 mg). Atropine is administered simultaneously (0.5 mg subcutaneously 3-5 times a day) to eliminate side effects. Prescribe corticosteroids (100 mg / day), however, they can temporarily increase weakness; carry out plasmapheresis. It is important to monitor airway and lung capacity. With the development of respiratory failure, they are intubated and begin mechanical ventilation. With signs of infection, antibiotics are prescribed (cyclosporins are preferred). In case of a cholinergic crisis, anticholinesterase drugs are temporarily discontinued, airway patency is restored, atropine (0.5-1 mg every 2 hours) is administered subcutaneously until dry mouth appears, cholinesterase reagents are prescribed (dipyroxime 150-300 mg intravenously or intramuscularly), if necessary, resort to intubation and mechanical ventilation.