Treatment of severe forms of myasthenia gravis with high doses of prednisolone. Myasthenia - what is it? How is the disease determined?

Myasthenia gravis is a severe autoimmune disease that manifests itself as pathological muscle weakness and slowly progresses. Children suffer from it more often, but this pathology also occurs in adults.

A little about the reasons

Myasthenia gravis is a congenital hereditary disease. Its signs appear early childhood. The syndrome may develop with at different speeds and degree of severity. Due to genetic abnormalities, the connection between neurons and muscle fibers is disrupted. Due to the fact that the muscles actually turn off and do not function, their atrophy gradually develops.

Scientists have still not been able to fully identify the mechanism of the disease, but it is known for certain that the cause lies in a deficiency of the gene that is responsible for the functioning of myoneural connections. First of all, visual functions suffer, as the eye muscles atrophy. Then the process moves to the facial muscles, neck, muscles of the arms, legs, and swallowing muscles.

Often this congenital syndrome leads to serious consequences and even death of the patient, but when proper treatment recovery or temporary remission is possible. This pathology can be inherited from one of the parents or through a generation.

The following causes of disease among children are identified:

Failures of biochemical processes due to pathologies of the thymus and hypothalamus.
The thymus is attacked by its own immune cells, which causes less acetylcholine to be produced and broken down.

Please note that the condition of a sick child can be worsened by stressful situations, acute respiratory viral infections, and impaired immunity.

Symptoms

The symptoms of myasthenia gravis directly depend on its form. The main symptom is unusual weakness in the muscles. The patient gets tired quickly and is unable to cope with work or training. This is especially noticeable if you need to make a series of similar movements.

After rest, muscle function is restored. Waking up in the morning, patients feel cheerful, rested, and feel a surge of strength. After some time, characteristic symptoms begin to increase, the patient feels literally overwhelmed.

Myasthenia gravis

Myasthenia gravis can manifest itself in different ways, depending on the form. There are three of them:

bulbar;
ophthalmic;
generalized.

In the bulbar form, only one local muscle group is affected. They provide chewing and swallowing, so the patient’s voice begins to change. It becomes hoarse, quiet and even almost silent.

At ocular form myasthenia gravis affects the muscles that provide movement eyeballs. These are the muscles that raise the eyelid, the external circular muscle. A patient suffering from myasthenia gravis is easily recognized by drooping eyelids - he cannot lift them due to muscle damage.

If myasthenia gravis is generalized, the oculomotor, facial, and cervical muscles are gradually affected. Patients develop deep wrinkles on their faces, and their smile becomes unnatural and forced. Over time, it becomes difficult for a person to even hold his head up. This is a consequence of weakened neck muscles.

As the disease progresses, pathological process the muscles of the arms and legs are involved. Such patients practically lose the ability to walk and move, since the muscles do not experience normal stress, and over time they atrophy. It is the generalized form that occurs most often.

Myasthenia gravis may also be accompanied by characteristic crises. This is the most severe form of the disease. During a crisis, the pharyngeal and respiratory muscles are completely disabled. This is a direct threat to life, because movements stop completely chest, which results in oxygen starvation of the body.

Diagnostics

It is very important to carry out thorough examination to understand to what extent the disease progresses and what causes it to develop. For correct selection treatment regimens must go through all diagnostic stages. It includes:

Electromyography. It will help identify myasthenic reaction.
Proserine test. The patient is injected into the muscle with cholinesterase antagonist drugs.
Serology study. Its goal is to identify acetylcholine receptor antibodies in the patient.
CT. Helps identify possible tumors (for example, thymoma).

It is the proserine test that is the main diagnostic method that can definitively confirm myasthenia gravis.

Treatment

Myasthenia gravis is serious and life threatening pathology. When such a diagnosis is made, it is imperative to immediately begin treatment for myasthenia gravis. Often, ophthalmological treatment is also required, since the disease can provoke dysfunction of the eyes. You will also need to eat right.

The mechanism of therapy is based on the fact that new manifestations of myasthenia gravis are constantly taken into account and the dose of drugs is adjusted. It should not exceed that which provides a sustainable therapeutic effect. Sick children and young people respond more easily to therapy; in older people, remission occurs less frequently.

It is important for parents to remember that even a common cold can cause myasthenia gravis, so any infection. Such well-known infectious disease specialists as, for example, Academician Yuri Vladimirovich Lobzin insist on this. It is important to choose a good clinic that will provide everything modern methods treatment of this difficult disease.

Proper treatment can stop the progression of the disease, and in some cases, complete recovery can be achieved. Therapy must fully comply with modern standards, since in recent years the methods of treating myasthenia gravis have been significantly improved in medicine.

The symptoms of a particular patient must be taken into account. The disease can have quite different forms and severity. It all depends on the reason for its development. This can be not only a broken genetic code, but also an infectious lesion, head injury, snake bite, etc.

Treatment will be based on maintaining blood levels the required level anticholinesterase substances. These drugs are constantly introduced into the body. Sometimes it is difficult to immediately determine safe dose for a specific patient, therefore the administration of drugs begins with extremely small doses. Such patients require constant care and regular courses of treatment.

An overdose of these drugs can cause serious side effects and unpleasant phenomena from the liver, kidneys. It can even provoke cholinergic crisis, which manifests itself in the form of convulsions, miosis, bradycardia. They are accompanied by pain in the abdominal area. If such a crisis occurs, the patient is immediately given the required dose of atropine.

The essence of the treatment is that an acetylcholinesterase antagonist is selected for the patient. This selection is carried out strictly individually. It is important to take into account the patient’s age, weight, shape and severity of the disease. Oxazil, prozerin, galantamine or kalimine are also prescribed.

If pseudoparalytic myasthenia gravis is diagnosed, the patient is additionally administered spironolactone and potassium salts. They maintain the condition of the body. If the patient suffers from a severe form of the disease, glucocorticosteroids and cytostatics are prescribed. If thymoma is detected, the only treatment option is surgical removal of the tumor.

For cupping myasthenic crisis Prozerin, mechanical ventilation, plasmapheresis, and drugs based on human immunoglobulin are used. If it is gravis disease (a severe hereditary form), treatment will differ from treatment for other forms of the disease.

The most commonly prescribed drug is pyridostigmine bromide. The drug causes a number of side effects: diarrhea, abdominal pain, muscle fasciculations. An increased dose of the drug can cause a cholinergic crisis.

Immunomodulatory treatment

One of the areas of therapy is modulation of immunity. For this purpose, glucocorticoids are prescribed. They are effective, relatively safe and inexpensive. This is the secret of their worldwide popularity. Scientists have not yet fully figured out how these drugs work, but the fact is undeniable that they can significantly alleviate the patient’s condition and lead to long-term remission.

This group of medications has a number of side effects, but they directly depend on the dose. Therefore, the physician must prescribe the minimum effective dosage for a particular patient. The most popular drug in this group is Prednisolone.

It is prescribed with a minimum daily dose (10-25 mg) and then the dosage is slowly increased. Ideally daily dose should be 60-80 mg (one-time dose every other day). It can be replaced with Methylprednisolone.

If the patient suffers from a severe form of the disease, treatment is prescribed immediately with a high dose of corticosteroids. The drug is administered every day. At the same time, plasmapheresis is performed or immunoglobulin is administered intravenously. The goal of such enhanced therapy is to stabilize the patient’s condition. It will take from 4 to 16 weeks to achieve it. After improvement, the dose of corticosteroids is gradually reduced. They are brought to the level of maintenance therapy.

Azathioprine is a purine analogue that slows down the synthesis of nucleic acids. It affects lymphocytes. When using the drug, it is necessary to monitor liver function and blood condition. At first, a blood test is taken every day. If the drug is well tolerated by the patient, then after 1-2 weeks the dosage is increased. The maximum dose is 2-3 mg per kg of body weight (the average daily dose is 150-200 mg).

This drug is quite well tolerated, although it can sometimes cause nausea, lymphopenia, skin rashes, pancreatitis, and pancytopenia.

note that healing effect may not occur immediately. It often appears 4-12 months after the start of treatment. The maximum effect is usually observed after six months to a year.

Azathioprine is used as an addition to Prednisolone. It is prescribed to those patients who are taking long-term immunosuppressive therapy. Thanks to this combination, the dose of corticosteroids can not be increased without losing their effectiveness. This is the so-called sparring effect, when one drug enhances the healing effect of another.

Cyclosporine is another drug prescribed for myasthenia gravis. It has a complex action that ultimately results in slower T cell activation. The drug may cause tremor, insomnia, renal failure, high blood pressure, headache. These side effects depend on the dose used. If it is reduced, unpleasant manifestations may go away or be minimized.

Cyclosporine is prescribed quite rarely. It has much more pronounced side effects than other drugs, because this remedy used if others have shown low efficiency. If a medication is prescribed, it is important to monitor the level of electrolytes in the blood, magnesium, and kidney function. Start with small doses, gradually increasing daily dosage to therapeutically effective.

If Cyclosporine is prescribed, diuretics (potassium-sparing) and NSAIDs should not be taken, and when corticosteroids must be taken, their dose should be reduced as much as possible. It is not possible to completely stop Prednisolone.

Mycophenolate myfetil - modern drug. Scientists have not yet fully studied how it works, but the results are encouraging. The substance slows down the replication of B and T cells. When using the drug, you need to take a blood test every month. Scientists agree that mycophenolate myfetil is as effective as Cyclosporn, but has fewer side effects.

Cyclophosphamide is an effective immunosuppressant, which is prescribed for severe forms of the disease, inhibiting T and B cells. It is rarely prescribed, only when other drugs have not shown their effectiveness. After just a couple of months, stable remission is observed in 50% of severe patients. If noticeable side effects occur, this remedy will have to be discontinued.

Methotrexate slows down cell division, but can provoke nausea, cystitis, mucositis, alopecia, and myelosuppression. Doctors consider it as a backup drug if first-line treatments are ineffective.

Rituximab is an antibody that has increased affinity for the CD20 cell antigen. It can cause fever, skin rashes, nausea, and sometimes bronchospasm. You can take a fairly long break between taking it - up to six months.

Short-term therapy

Along with medications, short-term treatment is prescribed: plasmapheresis, immunoglobulin is administered intravenously.

The mechanism of action of immunoglobulin is that it neutralizes activated complement, autoantibodies, modulates cytokines, etc. it can cause fever, headache, and skin rash.

The purpose of plasmapheresis is to remove autoantibodies and other components produced by the immune system from the blood. 4-5 sessions of plasmapheresis are performed. More often it is prescribed in the process of preparing for cooperation, a serious condition, when symptoms quickly increase. These two methods have approximately the same effectiveness.

DIAGNOSIS CRITERIA FOR MYASTHENIAS

Modern ideas about the pathogenesis of the disease allow us to distinguish 4 groups of main criteria for diagnosing myasthenia gravis:
clinical
pharmacological
electromyographic (EMG)
immunological diagnostic criteria

. Clinical criteria diagnostics

Detailed Study large number patients with myasthenia gravis showed that the most common clinical manifestations of the disease are:
dysfunction of extraocular and bulbar muscles,
weakness and fatigue of the muscles of the trunk and limbs.

Expressiveness clinical symptoms.
According to the results of observation of the Myasthenic Center, dysfunction of the extraocular muscles is observed in 75% of patients with myasthenia. Of them:

Minimum degree eye movement disorders, in the form of transient diplopia is observed in 31% of patients,
moderate, in the form of recurrent ophthalmoparesis and persistent diplopia - in 64%,
maximum, manifested by ophthalmoplegia - in 5% of patients.

Bulbar disorders have 54% of patients. Of them:
mild bulbar disorders, manifested by periodic disturbances in swallowing and speech, are detected in 57% of patients,
moderate, in the form of constant, but fluctuating in severity, dysphonia, nasal voice and periodic swallowing disorders - in 30%,
pronounced, manifested by aphonia and dysphagia - in 13% of patients.

Respiratory muscle dysfunction have 20% of patients. Of them:
respiratory disorders, which are regarded as mild, are manifested by periodic breathing disorders that occur after physical activity, are detected in 30% of patients, moderate, in the form of shortness of breath during the withdrawal of anticholinesterase drugs, or during the period of intercurrent infections, are also detected in 30% of patients, severe requiring mechanical ventilation - in 40% of patients.

Dysfunction of the muscles of the trunk and limbs have 60% of patients. It is assessed on a 6-point scale, where minimal decrease in function is assessed as 4 points (identified in 18% of patients), moderate – as 2-3 points (in 62%) and pronounced – less than 2 points (in 20% of patients).

Muscle atrophy is minimal and moderate degree severity are detected in 5% of patients. They arise, as a rule, against the background of pronounced disorders and are nutritional in nature (4% of patients).

Moderate amyotrophy observed in 1% of examined patients in whom myasthenia gravis was combined with thymoma.

Decreased tendon and periosteal reflexes detected in 7% of examined patients.

Vegetative-trophic disorders in the form of dry skin and mucous membranes, paresthesia, heart rhythm disturbances, intolerance to orthostatic stress, etc. - detected in 10% of patients with myasthenia gravis, among whom the majority (82%) had myasthenia gravis combined with thymoma.

(!!!) It must be emphasized that enlargement of the thymus gland according to CT or MRI is not a criterion for diagnosing myasthenia gravis.

. Pharmacological diagnostic criteria

For a pharmacological test, prozerin or kalimine forte are used.
A study of the effectiveness of a test with the introduction of proserin and kalimina forte showed that complete compensation of motor disorders is detected in 15% of patients with myasthenia gravis. It is necessary to note that full compensation involves restoration of muscle strength to 5 points, regardless of the degree of its initial decrease. In the majority of patients with myasthenia gravis (75%), the response to the administration of proserin was incomplete, i.e. was accompanied by an increase in muscle strength by 2-3 points, but did not reach 5 points. Partial compensation was characterized by an increase in strength by 1 point in individual muscles, while it was absent in other tested muscles.

(!!!) When conducting and evaluating a pharmacological test, the dose of the administered drug is of decisive importance, since only with the introduction of adequate doses of the drug is one or another assessment of the effectiveness of the test valid.

Kalimin-forte in a dose of 5 mg or prozerin 1.5 ml of 0.05% solution is administered subcutaneously when the patient weighs 50-60 kg; at a dose of 10 mg or 2.0 ml - with a weight of 60-80 kg, respectively; and 15 mg or 2.5 ml - for patient weights from 80 to 100 kg.
In children, the dose of the drugs is 5 mg or 1.0 ml, respectively.

If muscarinic effects of anticholinesterase drugs occur (hypersalivation, muscle twitching, increased rumbling in the abdomen), after assessing the effectiveness of the test, atropine is administered subcutaneously at a dose of 0.2–0.5 ml of a 0.1% solution. The test is assessed in the interval from 40 minutes to 1.5 hours after administration of the drug. The assessment is based on changes in the severity of clinical symptoms, as well as the absence or presence of side effects. With complete or incomplete compensation of motor disorders, the test is assessed as positive. If there is partial compensation, it is doubtful; if there is no compensation for motor disorders and there are side effects, it is negative.

. Electromyographic diagnostic criteria

The third criterion for diagnosing myasthenia gravis is the study of EMG indicators that reflect the state of neuromuscular transmission during the decrement test. Data obtained from indirect supramaximal stimulation of muscles of varying degrees clinical lesion show that in the muscles of patients with myasthenia, as a rule, M-responses of normal amplitude and area are recorded, but upon stimulation with frequencies of 3 and 40 impulses/s, a decrement in the amplitude of the M-response of varying degrees is detected. In 30% of the muscles studied, post-tetanic relief (PTF) of more than 120% was observed, in 85% of the muscles post-tetanic wasting (PTI) was detected. It must be emphasized that the magnitude of the decrement phenomenon of subsequent M-responses in a series, most typical for myasthenia gravis, when stimulated at a frequency of 3 impulses/s, is proportional to the degree of clinical damage to the muscle. It should be noted that EMG examination before and after the administration of anticholinesterase drugs (Kalimin-Forte, Proserin) allows us to objectify the effectiveness of the pharmacological test.

V. Immunological diagnostic criteria

An important diagnostic criterion is the determination in the blood serum of antibodies against acetylcholine receptors of the postsynaptic membrane in patients with myasthenia gravis, and antibodies against the titin protein in patients with myasthenia gravis with the presence of thymoma.
To determine antibodies against acetylcholine receptors of the postsynaptic membrane, alpha-bungarotoxin (snake venom) labeled with radioactive iodine (125-I) is used. Antibodies are detected in the patient's blood serum using specific immunoassay kits. In blood serum healthy patients the concentration of antibodies to acetylcholine receptors does not exceed 0.152 nmol/l. In patients with various autoimmune diseases (autoimmune thyroiditis, Hashimoto's disease, rheumatoid arthritis) and other neuromuscular diseases, the antibody concentration does not exceed 0.25 nmol/l. Evidence of the presence of myasthenia gravis (generalized or ocular form) is the concentration of antibodies to acetylcholine receptors more than 0.4012 nmol/l.

Most patients with myasthenia gravis with the presence of thymoma develop autoantibodies against titin, a protein of striated muscle with a high molecular weight. Detection of antibodies to titin is a differential diagnostic criterion for distinguishing thymoma from thymic hyperplasia. Antibodies are determined in the patient's blood serum using immunological kits (DLD, Germany). The value characterizing high probability the presence of thymoma is a level of more than 1.0 conventional units.

(!!!) Thus, the diagnosis of myasthenia gravis is undoubted when it is confirmed by all 4 diagnostic criteria; reliable - with 3 criteria; probable - if there are 2 and doubtful - if there is 1 criterion.

TREATMENT OF MYASTHENIAS

The treatment of myasthenia gravis is based on the following principles:
1. Stages of treatment measures.
2. A combination of compensatory, pathogenetic and nonspecific therapy;
3. Treatment of chronic and acute (crises) phases of the disease.

The first stage is compensatory therapy.
Involves prescribing the following medications:
1) Anticholinesterase drugs (Kalimin 60N) are used orally in a maximum daily dose of 240-360 mg, and once - from 30 to 120 mg. The interval between doses of kalimine should be at least 4-6 hours.
2) Prescribing proserin for systematic treatment of myasthenia gravis is not advisable due to a shorter effect and greater severity of adverse cholinergic manifestations.
3) Potassium chloride is usually prescribed in powder, 1.0 g 3 times a day. The powder is dissolved in a glass of water or juice and taken with meals. Potassium-normine, calyposis, kalinor, potassium orotate are taken orally in a total dose of 3 g per day.
Products rich in potassium are cottage cheese, baked potatoes, raisins, dried apricots, bananas.

(!!!) It must be remembered that a contraindication for the use of large doses of potassium compounds is complete transverse blockade of the cardiac conduction system, a violation excretory function kidney

4) Veroshpiron (aldactone, spironolactone) is an antagonist of the mineralcorticoid hormone aldosterone, which is necessary for the regulation of electrolyte metabolism in the body. The ability of veroshpiron to retain potassium in cells serves as the basis for its widespread use in the treatment of myasthenia gravis. The drug is taken orally in a dose of 0.025 - 0.05 g 3-4 times a day.
Side effects: with long-term continuous use of the drug - in some cases, nausea, dizziness, drowsiness, skin rashes, mastopathy in women, a reversible form of gynecomastia.
Veroshpiron is relatively contraindicated in the first 3 months. pregnancy.

The second stage is thymectomy and treatment with glucocorticoid drugs.
Thymectomy is indicated if the drugs used at the first stage are well effective, but mild bulbar disorders persist despite daily withdrawal of kalimine.

Possible mechanisms the beneficial effect of thymectomy on the course of myasthenia gravis is associated with
1) removing the source of antigens in relation to acetylcholine receptors found in myoid cells of the thymus, which are capable of triggering the production of immune bodies;
2) removing the source of antibodies to acetylcholine receptors;
3) removal of the source of abnormal lymphocytes.

The effectiveness of thymectomy is currently 50-80%.

The result of the operation may be
1. Clinically complete recovery (the so-called effect A),
2. Persistent remission with a significant reduction in the dose of anticholinesterase drugs (effect B),
3. Significant improvement in condition against the background of the same amount of anticholinesterase drugs (effect C),
4. No improvement in condition (effect D).

Indications for thymectomy are:
presence of a tumor of the thymus gland (thymoma),
involvement of the craniobulbar muscles in the process,
progressive course of myasthenia.

In children, thymectomy is indicated for the generalized form of myasthenia gravis, poor compensation of impaired functions as a result drug treatment and as the disease progresses.
Thymectomy should be performed in thoracic surgery departments; the transsternal approach is currently most often used. If thymoma is present, thymthymomectomy is performed.

Contraindications to thymectomy are
Heavy somatic diseases patients
Acute phase of myasthenia gravis (severe, uncompensated bulbar disorders, as well as the patient being in crisis).

Thymectomy is not advisable in patients suffering from myasthenia for a long time with a stable course, as well as in the local ocular form of myasthenia.

Gamma therapy of the thymus region is used in those patients who, due to certain circumstances (elderly and senile age, as well as the presence of severe somatic pathology), cannot undergo thymectomy, and also as a method of complex therapy after removal of thymoma (especially in cases of tumor infiltration into nearby organs ). The total dose of a gamma irradiation course is selected individually in each specific case, averaging 40-60 Gray. Radiation therapy in a number of patients may be complicated by the development of radiation dermatitis, pneumonitis, and the development of fibrous changes in the tissue anterior mediastinum, which requires termination of procedures.

If the drugs used at the first stage are insufficiently effective, as well as to create a kind of safety margin in compensation for myasthenic disorders, so that possible deterioration of the condition after surgery does not lead to disruption of the functions of vital organs and the development of a crisis, a significant number of patients are prescribed treatment with glucocorticoid drugs.

(!!!) The effectiveness of glucocorticoid drugs in the treatment of myasthenia gravis reaches, according to some data, 80% of cases. Due to the relatively fast attack therapeutic action they are used as first-line treatment in patients with vital disorders, and are the drugs of choice when the disease begins with bulbar disorders, as well as in the ocular form of myasthenia gravis.

Currently, the most optimal therapy is to take glucocorticoids according to a schedule every other day, the entire dose at once, in the morning, washed down with milk or jelly. The dose of prednisolone (metipred) in patients with myasthenia gravis is based on an individual assessment of the severity of the patient's condition. On average, the dosage is determined at the rate of 1 mg per 1 kg of body weight, but should not be less than 50 mg. Considering the effect of glucocorticoid drugs on the autonomic nervous system(palpitations, tachycardia, sweating), the very first dose of the drug should be half the dose. Then, if well tolerated, switch to the full therapeutic dose. The effect of prednisolone is assessed after 6-8 doses of the drug.

(!!!) However, in the first few days, some patients may experience episodes of deterioration in the form of increasing muscle weakness and fatigue.
It is possible that these episodes are not random, but are associated with the direct effect of glucocorticoid drugs on the processes of release of the synaptic transmitter and contribute to the desensitization of receptors, thereby causing a deterioration in the condition of patients. This circumstance dictates the need for a possible reduction in the dose of anticholinesterase drugs for some time, as well as caution when prescribing prednisolone to patients with myasthenia gravis, i.e. It is advisable to begin therapy in a hospital setting. As the effect is achieved and the patients' condition improves, the dose of prednisolone is gradually reduced (1/4 tablet on each day of administration), and the patient gradually switches to maintenance doses of glucocorticoids (0.5 mg per 1 kg of body weight or less). While taking maintenance doses of prednisolone, patients can be in a state of drug remission for many years. When taking glucocorticoid drugs, it is necessary to follow a diet limiting sweets and starchy foods.

With long-term use of glucocorticoid drugs, some patients may develop side effects of varying severity.
The most common are weight gain, hirsutism, cataracts, impaired glucose tolerance with the development in isolated cases of steroid diabetes, arterial hypertension, and osteopenia. In rare cases, phenomena of hypercortisolism occur, up to the development of drug-induced Cushing's syndrome with all its manifestations, the occurrence of severe bacterial infections, gastric and intestinal bleeding, cardiac failure, osteoporosis with bone fractures (including the spine and head of the femur).

(!!!) In this regard, patients with myasthenia gravis, even with the active absence of complaints, should undergo an annual examination of their organs to exclude possible side effects of glucocorticoid drugs.

In cases of side effects, it is advisable to correct the identified violations and reduce the dose of the drug. It should be remembered that treatment with glucocorticoid drugs is determined, first of all, by the need to restore impaired vital functions of the body.
At the second stage of treatment, the medications prescribed in the first stage continue, although the doses of kalimine may vary depending on the effectiveness of the treatment measures in the second stage.

The third stage is immunosuppressive therapy.
In cases of insufficient effectiveness, identification of side effects of glucocorticoid therapy, or the need to reduce the dose of prednisolone, it is advisable to prescribe cytostatic drugs.

Azathioprine (imuran) usually well tolerated and effective in 70-90% of myasthenia gravis patients. Compared to prednisolone, azathioprine acts more slowly, its clinical effect appears only after 2-3 months, but the drug has fewer side effects. Azathioprine can be used as monotherapy, as well as in combination with glucocorticoid drugs, when the effect of the latter is ineffective, or when the development of side effects requires a reduction in the dose of glucocorticoids. Azathioprine is prescribed orally daily at a dose of 50 mg per day, followed by an increase to 150-200 mg per day.
Sandimmune (cyclosporine) successfully used in the treatment severe forms myasthenia gravis, in cases of resistance to other types of immunocorrection. The effect of Sandimmune is practically independent of previous therapy; it is successfully used in the treatment of steroid-dependent patients, as well as in patients with myasthenia gravis with invasive thymomas. The advantages of Sandimmune lie in its more selective (compared to other immunosuppressants) effect on individual mechanisms of the immune response and the absence of suppression of the patient’s entire immune system. Sandimmune is administered orally, with an initial dose of 3 mg per 1 kg of body weight. Then, in the absence of toxic reactions, the dose of the drug can be increased to 5 mg per 1 kg of weight 2 times a day. Improvement is observed in most patients within 1-2 months from the start of therapy and reaches a maximum by 3-4 months. After achieving stable therapeutic effect the dose of sandimmune can be reduced to a minimum, and the effectiveness of treatment is monitored based on an assessment of the clinical status and concentration of the drug in plasma.
Cyclophosphamide is used in the treatment of patients with myasthenia gravis who do not respond to any type of immunocorrection, both as monotherapy and in combination with azathioprine in severe patients with myasthenia gravis who are resistant to other types of immunosuppression. At the same time, the effectiveness of the drug is observed in approximately 47% of patients. Cyclophosphamide is prescribed intramuscularly daily at a dose of 200 mg, or every other day at a dose of 400 mg, dissolving the powder in warm distilled water. The maximum total dose of the drug is 12-14 g, however positive effect can be assessed already with the introduction of 3 g of cyclophosphamide, and persistent improvement is evident at a dose of 6 g. Considering the lack of good tolerability of the drug in a number of patients, as well as the existing side effects, cyclophosphamide therapy must be started in a hospital setting, and only after making sure that it is well tolerated should it be transferred patients on outpatient treatment.

Among the side effects of azathioprine and cyclophosphanacytostatic drugs (occurring in approximately 40% of cases), anemia is often noted, which does not require a change in the dose of the drug. Reducing the dose of azathioprinacytostatic, up to its complete withdrawal, requires leukopenia (decrease in white blood cells below 3500 mm3), thrombocytopenia (decrease in platelets below 150), and/or serious violations liver function (signs of toxic hepatitis), as well as colds and inflammatory diseases. Other complications - allergic reactions, gastrointestinal disorders, alopecia, usually disappear as the dose of the drug is reduced. In order to prevent liver dysfunction, it is advisable for patients to be prescribed hepatoprotectors (Essentiale, Tykkeol, Karsil). Side effects of sandimmune are detected in less than 5% of patients and are characterized by impaired renal function, arterial hypertension, gout, tremor, gingival hyperplasia, hypertrichosis. However, it was noted that these adverse events decreased when the drug dose was reduced to the therapeutic dose.

At the third stage, to correct possible side effects of glucocorticoid and immunosuppressive therapy, immunomodulators obtained from the mammalian thymus gland can be used, which have hormonal activity, potentiate the production of antibodies, restore the sensitivity of antilymphocyte serum to azathioprine and affect neuromuscular transmission.

Immunomodulators are used to correct immunity in cases of frequent colds. Timagen, thymalin, T-activin are prescribed 1 ml intramuscularly for 10 days. Timoptin is administered subcutaneously at a dose of 500 mcg per course or once, after dissolving the contents of the bottle in saline solution. Injections are carried out at intervals of 3-4 days. Decaris is taken orally according to various regimens (50 mg 2 times a day for 2 weeks, or 150 mg 3 days with a break of 2 weeks and then 150 mg per week for 2 months and then 150 mg 1 time per month within 4 months). Decaris can sometimes cause nausea, then it is recommended to take the drug in smaller doses.
It should be remembered that immunomodulators in rare cases can cause exacerbation of myasthenia gravis, so it is better to use them when myasthenia gravis is stable.

TREATMENT OF ACUTE CONDITIONS IN MYASTHENIAS
During certain periods of myasthenia gravis, sudden disturbances in vital functions, called “crises,” may occur. These conditions are observed in 10-15% of patients with myasthenia gravis. There are myasthenic and cholinergic crises. The existing diagnostic difficulties in their differentiation are due to the fact that most often they develop in parallel in the form of a mixed crisis. Despite the similarity of the clinical picture of myasthenic and cholinergic crises, pathogenetic mechanisms their development is different and, accordingly, the treatment of these conditions requires different approaches.

Criteria for differentiating crises in myasthenia gravis
Differentiation of crises in myasthenia gravis is based on assessing the effectiveness of the test with the introduction of an adequate dose of Kalimina-Forte or Proserin.
In myasthenic crisis, the test is positive, and according to our data, complete compensation of the motor defect is observed in 12%, and incomplete compensation in 88% of patients.
During a cholinergic crisis, the test is negative, however, partial compensation may be observed in 13% of patients. Most often (in 80% of cases) partial compensation is observed with a mixed nature of the crisis, and in 20% of cases incomplete compensation is observed.

Myasthenic crisis
Myasthenic crisis is a suddenly developed critical condition in patients with myasthenia, which indicates not only a quantitative, but also a qualitative change in the nature of the process. The pathogenesis of the crisis is associated not only with a decrease in the density of cholinergic receptors of the postsynaptic membrane due to their complement-mediated destruction, but also with a change in the functional state of the remaining receptors and ion channels.

Severe generalized myasthenic crises are manifested by varying degrees of depression of consciousness, pronounced bulbar disorders, increasing respiratory failure, severe weakness of skeletal muscles. Breathing disorders progress steadily over hours, sometimes minutes. At first, breathing becomes frequent, shallow, with the inclusion of auxiliary muscles, then - rare, intermittent. Subsequently, the phenomenon of hypoxia develops with facial hyperemia, followed by cyanosis. Anxiety and excitement appear. Developing motor restlessness, then complete cessation of breathing, confusion and loss of consciousness. Impaired cardiovascular activity at the time of crisis is expressed by an increase in heart rate to 150-180 per minute and an increase in blood pressure to 200 mm. rt. Art. Subsequently, the pressure decreases, the pulse becomes tense at first, then arrhythmic, rare, thread-like. Intensifying autonomic symptoms– salivation, sweating. At extreme severity, loss of consciousness is accompanied by involuntary urination and defecation. In severe generalized myasthenic crises, hypoxic encephalopathy develops with the appearance of unstable pyramidal symptoms (symmetrical increase in tendon reflexes, the appearance of pathological foot signs). Pyramidal symptoms may persist long time after the crisis has subsided.

Cholinergic crisis
Cholinergic crisis is a condition that has a special development mechanism, caused by excessive activation of nicotinic and muscarinic cholinergic receptors due to an overdose of anticholinesterase drugs. With this type of crisis, along with the development of generalized muscle weakness, a whole complex of side cholinergic effects is formed. The basis of motor and autonomic disorders during a cholinergic crisis is hyperpolarization of the postsynaptic membrane and desensitization of cholinergic receptors, which is associated with a pronounced blockade of acetylcholinesterase and the resulting excess supply of acetylcholine to the cholinergic receptors of the postsynaptic membrane.
Cholinergic crises are quite rare (in 3% of patients) and (!!!) develop more slowly than myasthenic crises. In all cases, their occurrence is associated with an overdose of anticholinesterase drugs. Over the course of a day or several days, the patient’s condition worsens, weakness and fatigue increase, the patient cannot maintain the previous interval between doses of anticholinesterase drugs, individual signs cholinergic intoxication, then, after the next injection or enteral administration of anticholinesterase drugs (at the height of their action - usually after 30-40 minutes), a picture of a crisis develops, simulating myasthenic disorders. Complexity differential diagnosis cholinergic crisis is that in all its cases there is generalized muscle weakness with bulbar and respiratory disorders, which is also observed in myasthenic crisis. Diagnosis is aided by the presence of various cholinergic manifestations and signs of chronic cholinergic intoxication according to medical history. The diagnosis of cholinergic crisis is based on a paradoxical decrease in muscle strength (without previous provocation by physical effort) in response to the usual or increased dose of anticholinesterase drugs.

Mixed crisis
The mixed type of crisis is most often found in clinical practice. The difficulty of diagnosing it lies in the fact that it combines all the clinical features of myasthenic and cholinergic crises described above. This is the most severe type of vital disturbances in patients with myasthenia gravis. In the literature, a combined crisis is called “brittle” due to the opposite mechanisms of action that underlie it. On the one hand, the patient needs to immediately take anticholinesterase drugs, and on the other hand, he does not tolerate these drugs, and his condition worsens while taking them. A thorough analysis of the condition of patients in a mixed crisis showed that 25% of them had previously had myasthenic and cholinergic crises. Moreover, in half of these patients the nature of the crisis was myasthenic, and in the other half it was cholinergic.

The harbingers of mixed crises are hidden or obvious signs chronic cholinergic intoxication described above. IN clinical course Mixed crises are distinguished by the presence of two phases:
the first – myasthenic – is manifested by aggravation of bulbar and respiratory disorders, generalization of movement disorders and adequate response to taking anticholinesterase drugs;
the second – cholinergic – is characterized by clinical manifestations of cholinergic crisis.

The peculiarity of the distribution of movement disorders during a mixed crisis is that with complete functional failure of the cranio-bulbar and respiratory muscles, the strength of the muscles of the arms and legs can be slightly reduced. In addition, attention is drawn to the unequal reversibility of motor disorders in different muscle groups while taking anticholinesterase drugs. Thus, the introduction of kalimina forte or proserin can significantly reduce movement disorders trunk localization and practically do not affect the condition of the cranio-bulbar and respiratory muscles. Clinical experience suggests that cholinergic and mixed crises develop in patients with a predominantly craniobulbar form of myasthenia gravis, in whom the threshold between the therapeutic and toxic dose of anticholinesterase drugs is significantly reduced. The differential diagnosis of these conditions is based on a thorough clinical analysis, which allows us to identify the first phase of a mixed crisis, as well as clinical and electrophysiological assessment of the effectiveness of the administration of anticholinesterase drugs. It is this type of crisis that most often leads to fatal outcome in patients with myasthenia gravis.

Treatment of crises
According to modern concepts, the pathophysiological mechanisms of the development of crises in myasthenia gravis are associated with various options changes in the density and functional state of cholinergic receptors due to their autoimmune damage. In accordance with this, treatment of crises should be aimed at compensating for disorders of neuromuscular transmission and correcting immune disorders.
Artificial pulmonary ventilation (ALV).
The development of crises as a first step presupposes the need to ensure adequate breathing using forced ventilation.
In each specific case, the issue of transferring the patient to mechanical ventilation is decided on the basis of the clinical picture (impaired rhythm and depth of breathing, cyanosis, agitation, loss of consciousness, participation of auxiliary muscles in breathing, changes in the size of the pupils, lack of response to the administration of anticholinesterase drugs, etc.) , as well as objective indicators reflecting the gas composition of the blood, hemoglobin oxygen saturation, acid-base state (ABS), etc. (RR - over 40 per 1 min., VC less than 15 ml/kg, PaO2 below 60 mm Hg ., PaCO2 above 60 mm Hg, pH about 7.2, HbO2 below 70-80%).
One of the problems is the patient’s adaptation to the respirator, because a mismatch between the breathing cycles of the patient and the respirator can lead to a worsening of his condition. Certain actions are recommended to synchronize the patient’s spontaneous breathing and the respiratory cycles of the respirator or suppress the patient’s breathing if synchronization is impossible:
1) against the background of moderate hyperventilation at 120-150%, an individual selection of ventilation parameters is made: minimum inspiratory volume (MVV), tidal volume (TI), RR, optimal ratios of inhalation and exhalation durations, gas mixture injection rate, inhalation and exhalation pressure. Synchronization is considered achieved if the respiratory cycles of the patient and the device completely coincide;
2) drug suppression of activity respiratory center by intravenous administration of narcotic analgesics (morphine, etc.), as well as the administration of sodium hydroxybutyrate (40-50 mg/kg), which relaxes the transverse muscles.
Data available in the literature show that sometimes it is sufficient to perform mechanical ventilation and deprive the patient of anticholinesterase drugs for 16–24 hours to stop cholinergic and mixed crises. In this regard, mechanical ventilation can initially be carried out through an endotracheal tube, and only in case of prolonged breathing problems for 3 to 4 days or more, a tracheostomy is indicated due to the risk of developing a tracheal bedsore.

(!!!) During the period of artificial ventilation of the lungs, the administration of anticholinesterase drugs is completely excluded, intensive treatment of intercurrent diseases and pathogenetic treatment myasthenia gravis.

16 - 24 hours after the start of mechanical ventilation, provided that the clinical features of cholinergic or mixed crises are eliminated, a test should be carried out with the administration of Kalimina-Forte or Proserin. If the reaction to the administration of Kalimina-Forte or Proserin is positive, mechanical ventilation can be interrupted and, after making sure that adequate breathing is possible, the patient can be transferred to oral anticholinesterase drugs. In the absence of a positive reaction to the administration of anticholinesterase drugs, it is necessary to continue mechanical ventilation, repeating the test with the administration of Kalimina-Forte or Proserin every 24-36 hours.
Carrying out mechanical ventilation requires careful monitoring of the operation of respirators, special care for patients, timely application of measures to prevent possible complications.

The main requirements for performing mechanical ventilation are:
1) ensuring patency of the respiratory tract (monitoring the position of the endotracheal tube, timely aspiration of the contents of the tracheobronchial tree, inhalation of mucolytic, antibacterial drugs, vibration chest massage);
2) periodic monitoring of DO, peak inspiratory and expiratory pressures, MOV, CBS, gas composition blood. Of particular importance is monitoring control using devices that signal deviations from the specified parameters;
3) regular registration of the main indicators of circulatory function (blood pressure, central venous pressure, cardiac output, total peripheral resistance);
4) systematic monitoring of the uniformity of lung ventilation (auscultation, radiography), if necessary, “inflating” the lungs manually;
5) regular recording of body temperature, monitoring of diuresis and fluid balance;
6) for long-term mechanical ventilation - rational parenteral or tube nutrition, control of intestinal activity, prevention of infection urinary tract, bedsores;
7) prevention of complications associated with prolonged stay of an endotracheal or tracheostomy tube in respiratory tract(laryngitis, tracheobronchitis, bedsores, erosive bleeding);
8) timely transfer of the patient to spontaneous breathing with a careful assessment of the main indicators indicating the adequacy of spontaneous breathing (absence of cyanosis, tachypnea, tachycardia, preservation of muscle tone, sufficient DO - at least 300 ml - and MOV, PaO2 more than 80 mm Hg When breathing a mixture with 50% oxygen, the patient’s ability to create an inspiratory vacuum of at least 20 cm of water column, complete restoration of consciousness).

Plasmapheresis
An effective treatment measure for the development of myasthenic and cholinergic crises is exchange plasmapheresis. The plasmapheresis method is based on collecting blood from the ulnar or one of the central veins, followed by centrifugation and separation shaped elements and replacing plasma with either donor or artificial plasma. This procedure leads to rapid - sometimes within a few hours - improvement in the condition of patients. It is possible to extract plasma again over several days or every other day.

The patient's examination should include:
1) assessment of the state of vital functions
2) complete clinical blood test (including platelets, hematocrit)
3) determination of blood group and Rh factor
4) RV, HIV carriage, Australian antigen;
5) total protein, protein fractions;
6) main indicators of peripheral and venous blood coagulation;
7) clinical urine analysis.

Premedication is prescribed according to indications and includes analgesics and antihistamines.
Depending on the indications, centrifugal plasmapheresis (manual or hardware), filtration (hardware), plasmapheresis in combination with plasma sorption are used.
The operation is carried out in an operating room or intensive care ward, equipped and equipped in accordance with the requirements for the management of patients in critical condition, the presence of monitoring and treatment equipment, appropriate medications and infusion media, and the ability to perform cardiopulmonary resuscitation.
With discrete plasmapheresis, blood sampling and plasma separation are carried out separately, for which the blood is taken into a large “Gemacon 500/300” bag and after immediate centrifugation in a centrifuge for 15 minutes. Using a manual plasma extractor, the plasma is transferred into a small “Gemakon” bag. The cell mass remaining in the large sac is resuspended in an isotonic blood substitute and reinfused into the patient. After reinfusion of the cell suspension, blood is taken again into a new “Gemakon 500/300” and a new dose of blood is centrifuged with separation of plasma and reinfusion of erythrocytes. The total dose of plasma removed from a patient using this method is 500-1500 ml. The frequency of operations is determined by the characteristics of the patient's condition.
Hardware plasmapheresis is carried out on continuous blood fractionators with a system of disposable lines. Preparation and performance of extracorporeal surgery is carried out in accordance with the instructions for this type of device.
In severe myasthenic and cholinergic crises, in patients with severe bulbar disorders and other disorders, it is effective to carry out plasma exchanges. The high volume of plasma exfusion during plasma exchange must be compensated during the operation (or immediately upon its completion) by infusion therapy, the program of which may include not only crystalloids, colloids, but also native donor plasma, albumin solutions. Cryoprecipitation is used as an alternative to intensive plasmapheresis and plasma exchange for donor plasma in the treatment of myasthenia gravis. Using it, the ideology of plasma exchange for autoplasma (POAP) has been developed. Its essence lies in the use of specifically processed (cryosorption, cryoprecipitation) autoplasma of the patient, obtained during a previous operation, for plasma exchange. At the same time, the selectivity of the extracorporeal operation increases, and most of the plasma components are returned to the patient.
In cases of protein metabolism disturbances and a deficiency of infusion media containing donor proteins, a sorption column is included in the extracorporeal circuit for plasmapheresis and a plasmasorption operation is performed.
As a rule, plasmapheresis is carried out over a course of 1-2 weeks with a frequency of 2-5 operations. Intermittent plasmapheresis leads to improvement after 3–4 sessions. The effectiveness of continuous plasmapheresis, despite the large capacity for the volume of replaced plasma, does not differ significantly from intermittent plasmapheresis. The duration of improvement in the condition of patients after exchange plasmapheresis ranges from 2 weeks to 2 - 3 months. A contraindication to the use of plasmapheresis is the presence of pneumonia or other inflammatory processes.

Immunoglobulins G(HUMAGLOBIN, OCTAGAM, BIAVEN, VIGAM, INTRAGLOBIN human immunoglobulin for intravenous administration NIZHFARM) can cause a rapid temporary improvement in the course of myasthenia gravis. Human immunoglobulin is an immunoactive protein. The use of high doses of immunoglobulins has the ability to suppress immune processes. The generally accepted treatment regimen is short (five-day courses) intravenous administration of the drug at a dose of 400 mg per 1 kg of body weight daily. On average, the clinical effect occurred on the 4th day from the start of treatment and lasted for 50-100 days after completion of the course. In 3-4 months. a repeat course of immunoglobulin therapy is possible

During myasthenic crises, potassium chloride is administered intravenously by drip, adding 70 ml of a 4% solution, or 30 ml of a 10% solution in 400 ml of a 5% glucose solution or saline solution slowly (at a rate of 20-30 drops per minute) with the introduction of 4 - 7 units. insulin short acting at the end of the drip.

Antioxidants
The antioxidant properties of lipoic acid preparations (thioctacid, berlition) provide grounds for their use in patients with myasthenia gravis. Lipoic acid preparations promote the activation of mitochondrial synthesis. In addition, they reduce the severity of oxidative stress in patients in a state of myasthenic and cholinergic crises by reducing blood levels free radicals, contributing to damage to cellular and mitochondrial membranes during ischemia. Treatment should begin with intravenous drip administration in the amount of 600 - 900 mg/day with further transition to oral administration in the same dosage.

(!!!) The administration of anticholinesterase drugs as a diagnostic test is indicated for any form of crisis. Evaluation of a test with the administration of Kalimina-Forte or Proserin after a period of withdrawal of anticholinesterase drugs allows us to determine the effectiveness of the treatment measures taken and the possibility of transferring the patient to independent breathing.

PREGNANCY AND CHILDREN
Pregnant patients with myasthenia gravis require monitoring during pregnancy. In the absence of obstetric indications for cesarean section, delivery is carried out through natural birth canal. If a caesarean section is necessary, epidural anesthesia is recommended.

When weakness appears during labor labor activity- injections of proserin 1.5 ml parenterally after 3-4 hours.

If the condition worsens after childbirth with the appearance of bulbar disorders, prescribe prednisolone at a dose of 1 mg per 1 kg of body weight every other day, orally, the entire dose in the morning.
Kalimin 1/2 - 1 t 2-3 times a day (as needed)
potassium chloride 1 -2 g 3 times a day (continuously during meals)

In the presence of neonatal myasthenia in a newborn ( general lethargy, weak cry, difficulty swallowing and breathing, improving after the administration of anticholinesterase drugs) - before each feeding, injections of proserin 0.1 - 0.2 ml depending on the weight of the child and 30 mg of prednisolone in the morning by injection - until the symptoms of myasthenia gravis are completely compensated (usually last from 1 week to 1 month).

Breastfeeding is contraindicated for patients with myasthenia gravis - only artificial feeding is possible.

CONTRAINDICATED IN MYASTHENIAS:
Contraindicated in myasthenia gravis: excessive physical activity, magnesium preparations (magnesium, panangin, asparkam), curare-like muscle relaxants, neuroleptics and tranquilizers (except grandaxin), GHB, diuretics (except veroshpirone and other spironolactones), aminoglycoside antibiotics (gentamicin, streptomycin, neomycin, kanamycin , monomycin, tobramycin, sisomycin, amikacin, dideoxykanamycin-B, netilmicin), fluoroquinolones (enoxacin, norfloxacin, ciprofloxacin, ofloxacin, fleroxacin, lomefloxacin, sparfloxacin), and tetracycline - under medical supervision, fluorinated corticosteroids, quinine derivatives, D- penicillamine.

Summarizing the above, it should be emphasized that correct diagnosis and timely prescription of adequate treatment methods leads to compensation of movement disorders in more than 80% of patients with myasthenia gravis.

One of the most unpleasant diseases that affects women, especially between the ages of 20 and 40, is myasthenia gravis. Moreover, the number of sick women is three times higher than the number of sick men. This disease can severely affect the muscular and nervous systems.

Forms of myasthenia

Myasthenia gravis manifests itself in generalized and local forms. When occurring in the first form, respiratory processes are disrupted. In the local form there is a division into ocular, pharyngofacial and musculoskeletal. Most widespread among patients has myasthenia gravis of the ocular form, therefore its treatment raises the most questions and controversy.

Symptoms of myasthenia gravis

The disease first appears on the face, then on the neck and spreads further down the body. The first symptoms of the disease that patients notice are, as a rule, double vision and involuntary drooping of the eyelids. Some people experience general fatigue.

If at first these symptoms disappear after a short rest, then later the disease progresses so much that even long rest and sleep are not able to get rid of all the symptoms. Further symptoms include:

speech disorder;
difficulty moving the tongue and chewing food;
labored breathing;
general muscle weakness;
voice change.

To make a final diagnosis, electromyography and electroneurography are performed. Muscle tissue and blood composition are also analyzed. If there is a possibility that myasthenia gravis is inherited, then a genetic analysis is done.

Causes of myasthenia gravis

Among the possible causes of the occurrence and development of the disease, experts identify the following:

thymus tumor;
genetic mutations squirrel (heredity);
transferred ;
severe viral diseases;
significant disturbances in the functioning of the immune system.

Treatment of myasthenia gravis

If the disease is not treated, it will eventually lead to death. Therefore, at the first manifestations of the disease, it is worth thinking about how to treat myasthenia gravis. Even though doctors don't recommend it self-treatment myasthenia gravis folk remedies, but still there are several very effective traditional methods of treatment:

Take steamed oats with a spoon of honey 30 minutes before each meal.
A mixture of garlic, lemon, linseed oil and honey should also be taken 30 minutes before meals.
Prepare a mixture of onion and sugar, take three times a day.

These three traditional methods of treating myasthenia gravis can be combined to better effect. It is recommended to take all three mixtures for a year, alternating every two to three months. In addition, your diet should include foods rich in potassium, such as bananas, raisins and

Myasthenia gravis is a neuromuscular disease characterized by muscle weakness and pathological fatigue. Its development is based on a violation of neuromuscular transmission due to the blockade and lysis of acetylcholine receptors of the postsynaptic membrane by polyclonal autoantibodies. The production of antibodies is due to a genetic predisposition to immune system disorders. Damage to skeletal muscles such as polymyositis is also associated with this. In 70-90% of patients, pathology of the thymus gland (hyperplasia, thymitis, thymoma) is detected.

There are localized (ocular, bulbar, skeletal or trunk) and generalized forms of the disease. When making a diagnosis, take into account the increase in muscle weakness in the evening or after physical activity, as well as a significant decrease or complete disappearance of symptoms after administration of 2 ml of a 0.05% solution of proserin. EMG (using the rhythmic stimulation method) reveals the myasthenic exhaustion reaction.

Treatment. Anticholinesterase drugs (AChED) are prescribed, which increase the content of acetylcholine in the neuromuscular junction, and a number of measures are taken that affect the immune state - thymectomy, radiation exposure to the thymus gland, corticosteroid drugs, immunosuppressants, plasmapheresis and hemosorption are used.

ACEPs differ in duration of action (Table 26), effectiveness in different forms of the disease (kalimin is more effective in the ocular form, and oxazil in the bulbar and trunk forms), and in the degree of toxicity (increases in the series; kalimin, galantamine, oxazil, proserin). The choice of ACEP depends on the individual sensitivity of patients.

Table 26. Dynamics of the clinical effect of anticholinesterase drugs

The intervals between doses are determined by the duration of action of the drug in each patient. Medicines should be re-taken 30-60 minutes before the expected cessation of action previous dose. When replacing drugs, it should be taken into account that according to the effectiveness of 1 table. proserin, kalimine or oxazil corresponds to 1 ml of a 0.05% solution of proserin. The individual adequate daily dose averages 3-9 tablets. In some cases this dose has to be increased to 20 tablets. In any case, large doses or combinations of ACEP should be avoided without prior testing due to the risk of cholinergic crisis.

Sensitivity to ACEP can vary significantly. This happens during pregnancy, during the menstrual period, with various concomitant infections, after thymectomy, the start of hormonal therapy, and during remission. Therefore, single and daily doses require constant adjustment. In case of an overdose of ACEP, miosis, hypersapivation, nausea, diarrhea, frequent urination. Muscle weakness increases, fasciculations appear, first in the muscles of the face, throat of the neck, then in the muscles of the shoulder girdle, external eye muscles and muscles of the pelvic girdle. Relative contraindications for prescribing ACEP: bronchial asthma, angina pectoris, severe atherosclerosis, epilepsy. In case of an overdose of ACEP, anticholinergics are used, most often a 0.1% solution of atropine sulfate, 1 ml subcutaneously.

Potassium preparations improve acetylcholine synthesis and synaptic transmission, prolong the action of ACEP. They are indicated at all stages of treatment. In patients with local forms of the disease and in stable long-term remission, they are used as monotherapy, in other cases - as part of combination treatment. Prescribe potassium orotate (Dioron, Oronur) in tablets of 0.5 g 3 times a day; potassium chloride in powder or tablets 0.5-1 g or 1 g or 50 ml of 4% solution (10 ml of 10% solution) orally 2-3 times a day: spironolactone (veroshpiron, aldactone) in tablets 25 mg 3-4 times a day. Veroshpiron is contraindicated in mastopathy, gynecomastia, pregnancy, atrioventricular block and renal failure.

Thymectomy improves the course of myasthenia gravis, since the operation removes the source of formation of antibodies to acetylcholine receptors and pathologically activated lymphocytes. Thymectomy is currently considered crucial in the treatment of myasthenia gravis. The indication for thymectomy is the steady progression of the disease, especially in the case of a generalized form with impaired swallowing, speech and breathing. Preparation for surgery includes restorative therapy, treatment concomitant diseases, sometimes irradiation of the thymus gland, corticosteroid drugs, plasmapheresis.

It is preferable to use short-acting barbiturates (hexenal, sodium thiopental or sodium hydroxybutyrate) as induction anesthesia, and nitrous oxide as the main anesthetic. The rate of improvement and remission after thymectomy reaches 70-90%, and improvement can occur within 5 years after surgery. It is not advisable to use thymectomy in hospital during mild forms, as well as in the local ocular form of myasthenia. Contraindications to thymectomy are severe decompensated somatic diseases. The mortality rate for thymectomy was reduced to 0.8%.

Gamma or X-ray irradiation of the thymus produces a less lasting positive effect than thymectomy in 30-50% of cases. Radiation therapy is carried out in cases where thymectomy is contraindicated (senile age, incurable somatic diseases), with tolerance to drug therapy, before and after thymectomy to stabilize the condition of patients (usually 1-2 courses). This method is contraindicated for children and patients during puberty.

Corticosteroid drugs reduce the level of antibodies to acetylcholine receptors, reduce the manifestations of polymyositis and, apparently, improve neuromuscular conduction. The indication for their use is the lack of effectiveness of combined treatment of myasthenia gravis with other drugs, as well as the period of preparation of patients for thymectomy. For severe forms of myasthenia gravis, prednisolone is prescribed daily, and when it occurs significant improvement, every other day, taking the entire daily dose on an empty stomach in the morning. If you cannot quickly switch to taking the drug every other day, you can prescribe unequal doses: for example, 100 mg on even days, 50 mg on odd days. The initial dose (60-150 mg per day) is gradually reduced as the condition improves (by 5 mg every week).

A maintenance dose (50 mg per day) can be prescribed for several years. Taking prednisolone every other day allows you to avoid side effects even with long-term treatment. Since when taking prednisolone, the content of antibodies to acetylcholine receptors decreases and the release of acetylcholine increases, it is advisable to slightly reduce the dose of ACEP before prescribing prednisolone in order to avoid a cholinergic crisis. In some cases, when starting treatment with prednisone, the condition may worsen, so hormonal therapy should be started in a hospital setting.

Side effects observed with prolonged therapy with prednisolone: virile obesity, hirsutism, menstrual irregularities, Itsenko-Cushing syndrome, mental disorders. Possible ulceration of the mucous membrane digestive tract, perforation of an unrecognized ulcer, disturbances in water and electrolyte balance. To prevent the side effects of corticosteroids, antacids (Almagel), a diet low in sodium, salt, carbohydrates, and potassium supplements are prescribed.

Immunosuppressants reduce the level of antibodies to acetylcholine receptors, correct the reactions of cellular and humoral immunity. The indication for such treatment is the insufficient effectiveness of therapy for progressive myasthenia gravis by other means. Azathioprine (Gshuran) is prescribed in small doses (50 mg per day) at the beginning of treatment. Every week the dose is increased by 50 mg. The maximum daily dose is 2-3 mg/kg or an average of 100-200 mg per day. The effect is usually observed within 2-3 months in 79-80% of patients.

When the effect is achieved, the dose of the cytostatic is gradually reduced. Azathioprine is usually prescribed along with a maintenance dose of prednisolone. Side effects: thrombo-, leukopenia, hepatitis, pancreatitis, secondary infection (especially when azathioprine is combined with prednisolone), septicemia, etc. In the first weeks of azathioprine therapy, it is necessary to examine peripheral blood at least once every 3 days. When the number of leukocytes in the peripheral blood decreases to 3-3.5 * 109/L, azathioprine is discontinued.

Cyclophosphorus for myasthenia gravis is prescribed at a dose of 1 mg/kg per day, then the dose is gradually increased to 2-3 mg/kg per day. until clinical improvement, after which the dose of the cytostatic is reduced. Side effects: dyspeptic and dysuric disorders, leukopenia, alopecia, dizziness, blurred vision. Cyclosporine inhibits the activity of T-helper and T-killer cells. He is appointed to average dose 3-5 mg per day. The tactics for changing the dose are the same as for treatment with other cytostatics.

Clinical improvement occurs earlier than with azathioprine, but the incidence of side effects is 2 times higher than with azathioprine. Methotrexate is a highly toxic cytostatic. It is used only for severe forms of myasthenia gravis, if the combination of azathioprine with prednisolone is ineffective. The initial dose is 20 mg intramuscularly or intravenously 2 times a week, then the dose is increased to 40 mg 2 times a week. Course duration is 1-1.5 months.

Improvement in condition is observed in 50% of patients. Once the effect is achieved, it is advisable to switch to the less toxic azathioprine. Side effects: nausea, diarrhea, stomatitis, alopecia, ulcerative intestinal lesions, thrombocytopenia with hemorrhagic complications, toxic hepatitis, kidney damage.

Immunoglobulin with repeated intravenous drip infusions causes improvement in 70-90% of patients. It occurs on the 2-6th day after the start of treatment and lasts from 3 weeks to 3 months. This allows, during an exacerbation of myasthenia gravis, to gain the time necessary for the onset of the effect of other drugs. The degree of improvement is sometimes such that it is possible to reduce the dose of corticosteroid drugs by half. Immunoglobulin preparations are administered intravenously daily for 5 days or 3 times a week for 2-3 weeks. Side effects are rare: transient headache, swelling of the distal limbs. In 20-25% of cases, as with the beginning of treatment with prednisolone, a transient increase in muscle weakness is observed.

Plasmapheresis ensures the washout of toxic circulating immune complexes, eliminates excess AChE during cholinergic crisis, reduces cholinesterase levels. Indications for plasmapheresis: exacerbation of myasthenia gravis, ineffectiveness of corticosteroid and immunosuppressive therapy, myasthenic or cholinergic crisis, preparation for thymectomy in myasthenia gravis, deterioration of condition after thymectomy. 3-5 sessions of plasmapheresis are performed, first every other day, and then once a week, with replacement of 1-2 liters of plasma per session depending on tolerance (up to 5-10 liters per course). The clinical effect appears after a few days, it is usually unstable and lasts several months. A complication of plasmapheresis is venous thrombosis.

Hemosorption - extraction of blood from a vein, passing it through an adsorbent and infusion into ulnar vein. Usually, 1 session is carried out, in which 6-10 liters of blood are passed through the adsorbent. Subsequent sessions are ineffective.

Enterosorption is carried out by prescribing the fibrous salt adsorbent vaulene for oral administration at a dose of 50-60 mg/kg body weight 3 times a day (2 hours after meals and no earlier than 2 hours before the next meal) for 20 days.

In recent years, other methods of influencing immune status patient with myasthenia gravis: the use of antilymphocyte and antithymic globulin, interferon, splenectomy, X-ray irradiation of the spleen, drainage of the thoracic duct.

Until recently, myasthenia gravis was an incurable disease that could kill in a matter of years. Thanks to the development of medicine and pharmacology, today we can hope for a significant extension of the life of those who have fallen victim to this disease. The important thing is that much is in the hands of the patient himself, who is able, through volitional efforts, to keep himself within a safe framework that protects him from the risks of exacerbation and progression of a serious illness.

Features of treatment

Modern treatment of myasthenia gravis involves a clear phasing of treatment measures, ranging from more point impact specifically on neuromuscular transmission, and ending complex therapy, aimed at modifying immune interactions. The scope of medical intervention depends on the severity of myasthenic symptoms and the body’s response to the treatment.

First of all, scientists proposed cholinesterase inhibitors, as a result of which the concentration of acetylcholine in the neuromuscular junctions increases, which helps improve impulse transmission. The drugs used are prozerin, pyridostigmine, oxazil, etc.

For patients with myasthenia gravis, a sufficient intake of B vitamins is very important.

As a rule, anticholinesterase drugs in the first stages of treatment of myasthenia gravis are quite effective. They are also essential first aid during crises, and therefore every myasthenia gravis patient should have these medications readily available.

Along with strengthening neuromuscular impulse transmission, competent correction of the body’s water and electrolyte balance is necessary to ensure the efficiency of metabolism in muscles working in conditions of neurological insufficiency.

Therefore, in no case should you neglect the instructions of doctors, which, it would seem, are not very important. For patients with myasthenia gravis, normal potassium metabolism and a sufficient supply of B vitamins are very important, which is invariably reflected in the prescription sheet.

Honey, legumes, potatoes, cabbage, bananas, nuts, carrots are rich in potassium. Oysters, peas, eggs, nuts, seeds, yeast and fish are rich in B vitamins.

With the progression of the disease and the insufficiency of the above measures, there is a sad need for the use of more aggressive therapeutic tactics. Immunosuppressive hormones are entering the arena and are the means of choice for any processes associated with immune failure towards an inadequate increase. These drugs are difficult for the body, but in conditions of choice between life with side effects and quick, inevitable death, the advisability of their use is obvious.

Very often, myasthenia gravis is associated with tumors that produce immune cells in excessive quantities. If the tumor is clearly localized, for example, in the thymus gland, then radical solution in the form of its removal or radioactive irradiation brings stable remission in most cases.

If the tumor cannot be seen, but there are suspicions of its presence due to a number of specific symptoms, then it is rational to use cytostatics - drugs used in standard chemotherapy for tumors. This type of treatment is difficult, but sometimes necessary - it is impossible to eliminate invisible tumors in any other way.

In recent years, in the treatment of myasthenia gravis, extracorporeal detoxification methods have been used (plasmapheresis, hemosorption, cryoplasmapheresis, etc.), when the blood is purified outside the body using various technologies and returned back. The results are positive and allow for a reduction in more aggressive therapeutic interventions.

Also promising is the use of human immunoglobulins that modify the distorted immune response.

Strict adherence to doctor's instructions is prerequisite prolonging the life of a patient with myasthenia gravis. In addition, the patient himself has the opportunity to preserve himself longer at a certain stage of treatment, without creating the need to move on to more massive and painful measures. This requires strict adherence to the preventive regimen throughout the entire period.

By taking medications and knowing what not to do, you can stop the further development of the disease.

Prevention of relapses of myasthenia gravis

Constant supervision of the attending neurologist is necessary

The first thing a patient with myasthenia gravis needs to learn is that constant supervision by the attending neurologist is necessary. You cannot change the inspection date without permission. If new symptoms occur or any other way the condition worsens, contact your doctor unscheduled. If, due to a change of place of residence or any other factors, it is necessary to change the attending physician, then it is necessary to facilitate the most complete transfer of information about the patient’s condition and medical history to the new specialist.

You should radically reconsider your lifestyle, adapting it to the requirements dictated by your health.

The work of a patient with myasthenia gravis should in no case be physical. Optimal is mental work or an organizational position. Long journeys to work sites should be avoided whenever possible. A move from the center to the periphery is shown - a slower pace of life and the absence of a stressful life background in a metropolis always have a beneficial effect on the status of the immune system.

Hypothermia or being in places with an increased risk of contracting ARVI are contraindicated. Absolutely any infection is stressful for the body and can cause additional disruptions in the immune response. There are frequent cases of myasthenic crises due to viral infections.

The following medications are strictly contraindicated: aminoglycoside antibiotics, beta-blockers, calcium antagonists, magnesium salts, hormones thyroid gland, muscle relaxants, tranquilizers, quinine derivatives, morphine and its analogues, barbiturates and typical antipsychotics. Due to respiratory depression and relaxant effects, most sedatives and hypnotics, as well as atypical antipsychotics, are contraindicated.

If it is necessary to select an antibiotic or sedative, a thorough consultation is required, at least with the treating neurologist, and best of all, in a consultation of various specialists. In addition, any new drug should be checked by the patient himself for contraindications. In our time of widespread access to the Internet, such verification is not difficult.

It is necessary to change the order of eating. With myasthenia gravis, it is advisable to eat more often, in small portions, so that the swallowing muscles do not have time to deplete their reserves. The food itself should be as liquid or soft as possible, not requiring significant chewing effort.

Don't rush while walking. When arranging your home, make sure that the interior is designed according to the requirements of the illness - in any place there should be something that makes it possible to grab hold of yourself during an attack of sudden weakness. This way you can avoid unnecessary injuries.

If you suddenly feel weak in a crowded place, then don’t be shy to ask for help. This will help you decide current situation, and will facilitate the rapid provision of emergency treatment measures in the event of an increase in symptoms.

We must remember that panic aggravates the clinical picture. You should develop a calm attitude towards the disease and a willingness to act soberly in the event of a myasthenic crisis. Coolness of mind is the key to a happy resolution of sudden exacerbations of myasthenia gravis.

Staying in direct sunlight is strictly contraindicated - this enhances the immune response and provokes new attacks on acetylcholine receptors. In addition to the “shadow” way of life, myasthenic patients are advised to wear sunglasses when in open space.