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

Myasthenia gravis is a severe autoimmune disease that manifests itself as pathological weakness of the muscles and slowly progresses. Children are most often affected, but this pathology also occurs in adults.

A little about the reasons

Myasthenia is congenital hereditary disease. Its symptoms appear in the early childhood. The syndrome may develop different speed and degree of severity. Due to genetic abnormalities, the connection between neurons and muscle fibers is disrupted. Due to the fact that the muscles are actually switched off, do not function, their atrophy gradually develops.

Scientists have not yet been able to fully identify the mechanism of the onset of the disease, but it is known for certain that the reason lies in the deficiency of the gene that is responsible for the work of myoneural connections. First of all, visual functions suffer, as the muscles of the eyes atrophy. Then the process goes to the facial muscles, neck, muscles of the arms, legs, swallowing muscles.

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

There are such causes of the disease among children:

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

Please note that the condition of a sick child can be aggravated by stressful situations, SARS, impaired immunity.

Symptoms

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

After rest, the functions of the muscles are restored. Waking up in the morning, patients feel cheerful, rested, 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, it all depends on the form. They are distinguished by three:

bulbar;
eye;
generalized.

With the bulbar form, only one local muscle group suffers. They provide chewing, swallowing, because the patient's voice begins to change. It becomes hoarse, quiet and even almost silent.

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

If myasthenia gravis is generalized, the oculomotor, mimic, and cervical muscles are gradually affected. In patients, deep wrinkles appear on the face, and the smile becomes unnatural, strained. Over time, it becomes difficult for a person to even hold his head. This is a consequence of the weakening of the muscles of the neck.

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

Myasthenia can 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 completely stop. chest, resulting in oxygen starvation of the body.

Diagnostics

It is very important to carry out thorough examination to understand the extent to which the disease progresses, because of what it develops. For correct selection treatment regimen, it is necessary to go through all the stages of diagnosis. It includes:

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

It is the prozerin test that is the main diagnostic method that is able to confirm myasthenia definitively.

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, ophthalmic treatment is also required, since the disease can provoke eye dysfunction. 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. Therapies are easier for sick children and young people, in the elderly, remission occurs less frequently.

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

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

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

Treatment will be based on maintenance in the blood right level anticholinesterase substances. These funds are constantly introduced into the body. Sometimes it's hard to tell right away safe dose for a particular patient, therefore, the introduction of drugs begins with extremely small doses. Such patients need constant care and regular courses of treatment.

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

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

If pseudoparalytic myasthenia gravis is established, the patient is additionally administered spironolactone, potassium salts. They keep the body healthy. If the patient suffers from a severe form of the disease, he must be prescribed glucocorticosteroids, cytostatics. If thymoma is diagnosed, the only treatment is surgical removal of the tumor.

For cupping myasthenic crisis use prozerin, mechanical ventilation, plasmapheresis, preparations based on human immunoglobulin. If it is gravis disease (a severe hereditary form), therapy will be different from treatment for other forms of the disease.

The most commonly prescribed 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 directions of therapy is the 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 that they can significantly alleviate the patient's condition and lead to long-term remission is undeniable.

This group of medicines has a number of side effects, but they are directly dependent on the dose. Therefore, the physician should 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 slowly increase the dosage. Ideally daily dose should be 60-80 mg (single 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. In parallel, plasmapheresis is performed or immunoglobulin is administered intravenously. The purpose of such enhanced therapy is to stabilize the patient's condition. It will take from 4 to 16 weeks to achieve it. After improving the condition, gradually reduce the dose of corticosteroids. They are brought to the level of maintenance therapy.

Azathioprine is a purine analogue that slows down the synthesis of nucleic acids. It acts on lymphocytes. When using the drug, it is necessary to monitor the function of the liver, the state of the blood. Initially, 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 remedy is fairly well tolerated, although it can sometimes cause nausea, lymphopenia, skin rashes, pancreatitis, pancytopenia.

note that healing effect may not come immediately. Often it manifests itself 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 adjunct 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 therapeutic effect of another.

Cyclosporine is another drug that is prescribed for myasthenia gravis. It has a complex action that ultimately leads to slower T-cell activation. The drug may cause tremors, insomnia, kidney failure, high blood pressure, headache. These side effects depend on the dose used. If it is reduced, unpleasant manifestations can go away or are minimized.

Cyclosporine is prescribed quite rarely. It has much more pronounced side effects than other drugs, because this remedy apply if the others have shown low efficiency. If the medication is prescribed, it is important to control 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 are to be taken, their dose should be reduced as much as possible. Completely cancel Prednisolone will not work.

Mycophenolate mifetil - modern drug. Scientists have not yet fully understood how it works, but the results are encouraging. The substance slows down the replication of B-, T-cells. When using the drug, you need to take a blood test every month. Scientists agree that mycophenolate mifetil is as effective as Cyclosporne, but it 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. Already after a couple of months, a stable remission is observed in 50% of severe patients. If there are noticeable side effects, this remedy will have to be canceled.

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

Rituximab is an antibody that has an increased affinity for the CD20 cell antigen. It can cause fever, skin rashes, nausea, and sometimes bronchospasm. Between its reception, you can make a fairly large break - up to six months.

Short term therapy

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

The mechanism of action of immunoglobulin is that it neutralizes the activated compliment, autoantibodies, modulates cytokines, etc. it can cause fever, headache, 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 cooperation, a serious condition, when the symptoms are growing rapidly. These two methods have about the same efficiency.

DIAGNOSIS CRITERIA FOR MYASTENIA

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

. Clinical Criteria diagnostics

Detailed study a large number patients with myasthenia showed that the most common clinical manifestations of the disease are:
violations of the function of the extraocular and bulbar muscles,
weakness and fatigue of the muscles of the trunk and limbs.

expressiveness clinical symptoms.
Violations of the function of the extraocular muscles according to the results of observation of the Myasthenic Center are observed in 75% of patients with myasthenia gravis. 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 violations of 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%,
expressed, 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 respiratory disorders that occur after exercise, are detected in 30% of patients, moderate, in the form of shortness of breath against the background of discontinuation of anticholinesterase drugs, or during the period of intercurrent infections, are also detected in 30% of patients, expressed 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 the minimum decrease in function is estimated as 4 points (detected in 18% of patients), moderate - as 2-3 points (in 62%) and pronounced, less than 2 points (in 20% of patients).

Muscular atrophy minimal and moderate degree expressiveness found in 5% of patients. They occur, as a rule, against the background of severe tabular disorders and are alimentary in nature (4% of patients).

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

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

Vegetative-trophic disorders in the form of dry skin and mucous membranes, paresthesia, cardiac arrhythmias, intolerance to orthostatic loads, etc. - is detected in 10% of patients with myasthenia gravis, among which the majority (82%) had myasthenia combined with thymoma.

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

. Pharmacological criteria for diagnosis

For a pharmacological test, prozerin or kalimin-forte is used.
The study of the effectiveness of the test with the introduction of prozerin and kalimina-forte showed that complete compensation of motor disorders is detected in 15% of patients with myasthenia gravis. It should be noted that full compensation involves the restoration of muscle strength up to 5 points, regardless of the degree of its initial decrease. In the majority of patients with myasthenia gravis (75%), the reaction to the administration of prozerin 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, one or another assessment of the effectiveness of the sample is competent.

Kalimin-forte at a dose of 5 mg or prozerin 1.5 ml of a 0.05% solution is injected subcutaneously with a patient weighing 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 - with a patient weighing from 80 to 100 kg.
In children, the dose of 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 evaluating the effectiveness of the test, atropine is administered subcutaneously at a dose of 0.2–0.5 ml of a 0.1% solution. The evaluation of the test is carried out in the range from 40 minutes to 1.5 hours after the administration of the drug. The assessment is based on a change in the severity of clinical symptoms, as well as the absence or presence of side effects. With complete and incomplete compensation of motor disorders, the test is assessed as positive. With partial compensation - doubtful, in the absence of compensation for motor disorders and the presence of side effects - negative.

. Electromyographic diagnostic criteria

The third criterion for diagnosing myasthenia is the study of EMG indicators that reflect the state of neuromuscular transmission during the decrement test. Data obtained with indirect supramaximal stimulation of muscles of various degrees clinical lesion show that in the muscles of patients with myasthenia gravis, as a rule, M-responses of normal amplitude and area are recorded, but when stimulated with frequencies of 3 and 40 imp/s, a decrement of the M-response amplitude of various degrees is detected. In 30% of the muscles studied, post-tetanic facilitation (PTO) of more than 120% was noted, in 85% of the muscles post-tetanic exhaustion (PTI) was detected. It should be emphasized that the magnitude of the decrement of subsequent M-responses in the series, which is most typical for myasthenia gravis, with stimulation at a frequency of 3 pulses/s, is proportional to the degree of clinical muscle damage. It should be noted that the EMG examination before and after the administration of anticholinesterase drugs (kalimin-forte, prozerin) makes it possible 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 the 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.
Alpha-bungarotoxin (snake venom) labeled with radioactive iodine (125-I) is used to detect antibodies against acetylcholine receptors of the postsynaptic membrane. Antibodies are determined in the patient's blood serum using certain immunological kits. In the 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 concentration of antibodies does not exceed 0.25 nmol/l. Evidence for the presence of myasthenia gravis (generalized or ocular form) is the concentration of antibodies to acetylcholine receptors of more than 0.4012 nmol / l.

Most patients with myasthenia gravis with thymoma develop autoantibodies against titin, a protein of striated muscle with a high molecular weight. The 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 the level of more than 1.0 conventional units.

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

TREATMENT OF MYASTENIA

The treatment of myasthenia gravis is based on the following principles:
1. Stages of therapeutic measures.
2. Combination of compensatory, pathogenetic and non-specific therapy;
3. Treatment of chronic and acute (crises) phases of the course of the disease.

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

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

4) Veroshpiron (aldactone, spironolactone) is an antagonist of the mineralocorticoid hormone aldosterone, which is necessary for the regulation of electrolyte metabolism in the body. The ability of veroshpiron to retain potassium in cells is the basis for its widespread use in the treatment of myasthenia gravis. The drug is taken orally at a dose of 0.025 - 0.05 g 3-4 times a day.
Side effects: with prolonged 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 with good efficacy of the drugs used at the first stage, but with the preservation of mild bulbar disorders against the background of daily withdrawal of Kalimin.

Possible Mechanisms favorable effect of thymectomy on the course of myasthenia is associated with
1) removal of the source of antigens in relation to acetylcholine receptors found in thymic myoid cells, which are capable of provoking the production of immune bodies;
2) removal of 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. Stable remission with a significant reduction in the dose of anticholinesterase drugs (effect B),
3. Significant improvement in the condition against the background of the same amount of anticholinesterase drugs (effect C),
4. Lack of improvement in condition (effect D).

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

In children, thymectomy is indicated for the generalized form of myasthenia gravis, poor compensation for impaired functions as a result of drug treatment and as the disease progresses.
Thymectomy should be performed in thoracic surgery departments, with transsternal access being the most commonly used at present. In the presence of a thymoma, a thymthymectomy is performed.

Contraindications for thymectomy are
heavy somatic diseases patients
The acute phase of myasthenia gravis (pronounced, uncompensated bulbar disorders, as well as the patient being in a crisis).

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

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

With insufficient effectiveness of the drugs used at the first stage, as well as to create a kind of margin of safety, in compensating for myasthenic disorders so that a possible deterioration in the condition after surgery does not lead to dysfunction 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 reaches 80% of cases according to some data. Due to the relatively fast advancing therapeutic action they are used as a primary treatment in patients with vital disorders, they are the drugs of choice at the onset of the disease with bulbar disorders, as well as in the ocular form of myasthenia gravis.

Currently, the most optimal therapy is taking glucocorticoids according to the scheme every other day, at the same time the entire dose, in the morning, drinking 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. Given 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, in case of good tolerance, switch to the full therapeutic dose. The effect of prednisolone is evaluated 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 accidental, but are associated with the direct action of glucocorticoid drugs on the 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 desirable to start therapy in a hospital setting. As the effect is achieved and the condition of patients improves, the dose of prednisolone is gradually reduced (1/4 tablet per day of administration), and the patient gradually switches to maintenance doses of glucocorticoids (0.5 mg per 1 kg of body weight or less). Against the background of 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 with a restriction of sweet and starchy foods.

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

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

In cases of detection of side effects, it is advisable to correct the identified violations, reduce the dose of the drug. It should be remembered that treatment with glucocorticoid drugs is primarily due to the need to restore disturbed vital functions of the body.
At the second stage of treatment, the drugs prescribed at the first stage continue, although the doses of Kalimin may vary depending on the effectiveness of the second stage of treatment.

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

Azathioprine (Imuran) usually well tolerated and effective in 70-90% of patients with myasthenia gravis. 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 action of the latter is ineffective, or when, due to the development of side effects, a reduction in the dose of glucocorticoids is necessary. Azathioprine is administered orally daily at a dose of 50 mg per day, followed by an increase to 150-200 mg per day.
Sandimmun (cyclosporine) successfully used in the treatment severe forms myasthenia gravis, in cases of resistance to other types of immunocorrection. The effect of sandimmun 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 sandimmun are its more selective (compared to other immunosuppressants) effects on individual mechanisms of the immune response, the absence of suppression of the entire immune system of the patient. Sandimmun 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 body weight 2 times a day. Improvement is noted in most patients after 1-2 months from the start of therapy and reaches a maximum by 3-4 months. After reaching a stable therapeutic effect the dose of sandimmun can be reduced to a minimum, and monitoring of the effectiveness of treatment is carried out on the basis of an assessment of the clinical status and plasma concentration of the drug.
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 resistant to other types of immunosuppression. At the same time, the effectiveness of the drug is observed in approximately 47% of patients. Cyclophosphamide is administered 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 a stable improvement is manifested at a dose of 6 g. sick on outpatient treatment.

Of the side effects of azathioprine and cyclophosphanacytostatic agents (occurring in approximately 40% of cases), the appearance of anemia is often noted, which does not require a change in the dose of the drug. Reducing the dose of azathioprine cytostatic, up to its complete withdrawal, requires leukopenia (decrease in leukocytes 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 on the background of a decrease in the dose of the drug. In order to prevent liver dysfunction, it is advisable for patients to prescribe hepatoprotectors (Essentiale, tykveol, carsil). Side effects of sandimmun 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 with a decrease in the dose of the drug to therapeutic.

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

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 injected under the skin at a dose of 500 mcg per course or once, after dissolving the contents of the vial in saline. Injections are carried out with an interval 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 taking the drug in smaller doses is recommended.
It should be remembered that immunomodulators in rare cases can cause an exacerbation of myasthenia gravis, so it is better to use them with a stable course of myasthenia gravis.

TREATMENT OF ACUTE CONDITIONS WITH MYASTENIA
In certain periods of the course of myasthenia gravis, sudden violations of 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, pathogenic 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 the evaluation of the effectiveness of the test with the introduction of an adequate dose of calimina-forte or prozerin.
In myasthenic crisis, the test is positive, and according to our data, complete compensation of the motor defect is observed in 12%, and incomplete - in 88% of patients.
With a cholinergic crisis, the test is negative, however, in 13% of patients, partial compensation may be observed. 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 noted.

myasthenic crisis
Myasthenic crisis is a suddenly developed critical condition in patients with myasthenia gravis, 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 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, severe bulbar disorders, increasing respiratory failure, a sharp weakness of skeletal muscles. Respiratory disorders progress steadily over hours, sometimes minutes. At first, breathing becomes frequent, shallow, with the inclusion of auxiliary muscles, then rare, intermittent. In the future, the phenomenon of hypoxia develops with flushing of the face, followed by cyanosis. There is anxiety, excitement. Developing restlessness, then complete cessation of breathing, confusion and loss of consciousness. Violation of cardiovascular activity at the time of the crisis is expressed by an increase in heart rate up to 150-180 per minute and an increase in blood pressure up to 200 mm. rt. Art. In the future, the pressure decreases, the pulse becomes tense at first, then arrhythmic, rare, thready. Are getting stronger autonomic symptoms- salivation, sweating. At extreme severity loss of consciousness is accompanied by involuntary urination and defecation. In severe generalized myasthenic crises, the phenomena of hypoxic encephalopathy develop with the appearance of intermittent 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
A cholinergic crisis is a condition that has a special development mechanism due to excessive activation of nicotinic and muscarinic cholinergic receptors due to an overdose of anticholinesterase drugs. In this type of crisis, along with the development of generalized muscle weakness, the whole complex of side cholinergic effects is formed. At the heart of motor and autonomic disorders in 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 flow 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. Within a day or several days, the condition of patients worsens, weakness and fatigue increase, the patient cannot withstand the previous interval between taking anticholinesterase drugs, appear individual signs cholinergic intoxication, then, after another 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. Assistance in the diagnosis is provided by the presence of various cholinergic manifestations, signs of chronic cholinergic intoxication according to the anamnesis. The diagnosis of a cholinergic crisis is based on a paradoxical decrease in muscle strength (without prior exercise provocation) in response to a normal or increased dose of anticholinesterase drugs.

mixed crisis
The mixed type of crisis is the most common in clinical practice. The difficulty of its diagnosis lies in the fact that it combines all the clinical features of myasthenic and cholinergic crises described above. This is the most severe variant of vital disorders in patients with myasthenia gravis. In the literature, a combined crisis is called “brittle” due to the opposite of the mechanisms of action underlying 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 - cholinergic.

Harbingers of mixed crises are hidden or clear signs chronic cholinergic intoxication described above. AT clinical course mixed crises distinguish the presence of two phases:
the first - myasthenic - is manifested by the aggravation of the bulbar and respiratory disorders, generalization of movement disorders and an adequate response to taking anticholinesterase drugs;
the second - cholinergic - is characterized by clinical manifestations of a cholinergic crisis.

A feature 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 movement disorders in different muscle groups while taking anticholinesterase drugs. So, the introduction of kalimina-forte or prozerin can significantly reduce movement disorders trunk localization and practically does not affect the state 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 which the threshold between the therapeutic and toxic doses of anticholinesterase drugs is significantly reduced. The differential diagnosis of these conditions is based on a thorough clinical analysis, which allows to identify the first phase of a mixed crisis, as well as a clinical and electrophysiological assessment of the effectiveness of the administration of anticholinesterase drugs. It is this type of crisis that most often leads to lethal outcome in patients with myasthenia gravis.

Crisis treatment
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, the treatment of crises should be aimed at compensating for neuromuscular transmission disorders and correcting immune disorders.
Artificial lung ventilation (ALV).
The development of crises as a first measure suggests the need to ensure adequate breathing with the help of forced ventilation.
In each case, the issue of transferring the patient to mechanical ventilation is decided on the basis of the clinical picture (disturbance of the rhythm and depth of breathing, cyanosis, agitation, loss of consciousness, participation in breathing of auxiliary muscles, changes in the size of the pupils, lack of response to the introduction of anticholinesterase drugs, etc.) , as well as objective indicators reflecting the gas composition of the blood, oxygen saturation of hemoglobin, acid-base state (CBS), etc. ., PaCO2 above 60 mm Hg, pH about 7.2, HbO2 below 70-80%).
One of the problems is the adaptation of the patient to the respirator, because. mismatch between the respiratory cycles of the patient and the respirator can lead to a deterioration in his condition. Certain actions are recommended to synchronize the spontaneous breathing of the patient and the respiratory cycles of the respirator, or to suppress the patient's breathing if synchronization is not possible:
1) against the background of moderate hyperventilation at 120-150%, an individual selection of ventilation parameters is made: minimum inspiratory volume (MOV), tidal volume (TO), respiratory rate, optimal ratios of inhalation and exhalation duration, gas mixture injection rate, inspiratory and expiratory pressure. Synchronization is considered to be achieved if the respiratory cycles of the patient and the apparatus coincide completely;
2) drug suppression of activity respiratory center by intravenous administration of narcotic analgesics (morphine, etc.), as well as the introduction of sodium oxybutyrate (40-50 mg / kg), which relaxes the transverse muscles.
The data available in the literature show that sometimes it is sufficient to carry out mechanical ventilation and deprive the patient of anticholinesterase drugs for 16–24 hours to stop the cholinergic and mixed crises. In this regard, mechanical ventilation can first be carried out through an endotracheal tube, and only with prolonged respiratory disorders for 3-4 days or more is the imposition of a tracheostomy due to the risk of developing a pressure sore of the trachea.

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

16 - 24 hours after the start of mechanical ventilation, subject to the elimination of the clinical features of cholinergic or mixed crises, a test should be performed with the introduction of kalimina-forte or prozerin. With a positive reaction to the introduction of kalimina-forte or prozerin, you can interrupt the mechanical ventilation and, after making sure that adequate breathing is possible, transfer the patient to oral anticholinesterase drugs. In the absence of a positive reaction to the introduction of anticholinesterase drugs, it is necessary to continue mechanical ventilation, repeating the test with the introduction of kalimin-forte or prozerin every 24-36 hours.
Ventilation requires careful monitoring of the work of respirators, special care for patients, timely application of measures to prevent possible complications.

The main requirements for carrying out IVL are:
1) ensuring the patency of the respiratory tract (control of 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, KOS, 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 (BP, central venous pressure, cardiac output, total peripheral resistance);
4) systematic control of the uniformity of ventilation of the lungs (auscultation, radiography), if necessary - “inflating” the lungs manually;
5) regular registration of body temperature, control of diuresis and fluid balance;
6) with prolonged mechanical ventilation - rational parenteral or tube nutrition, control of intestinal activity, infection prevention urinary tract, bedsores;
7) prevention of complications associated with prolonged stay of the endotracheal or tracheostomy tube in respiratory tract(laryngitis, tracheobronchitis, bedsores, erosive bleeding);
8) timely transfer of the patient to spontaneous breathing with a thorough 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 with a mixture of 50% oxygen, the patient's ability to create an inspiratory depression of at least 20 cm of water, full recovery of consciousness).

Plasmapheresis
An effective therapeutic measure in the development of myasthenic and cholinergic crises is the exchange plasmapheresis. The plasmapheresis method is based on taking blood from the ulnar or one of the central veins, followed by its centrifugation, separation shaped elements and replacement of plasma with either donor or artificial plasma. This procedure leads to a rapid - sometimes within a few hours - improvement in the condition of patients. Re-extraction of plasma within a few days or every other day is possible.

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

Premedication is prescribed according to indications and includes analgesics, antihistamines.
Depending on the indications, centrifugal plasmapheresis (manual or hardware), filtration (hardware), plasmapheresis in combination with plasmasorption are used.
The operation is carried out in an operating room or intensive care unit, equipped and equipped in accordance with the requirements for the management of patients in critical condition, the availability of monitoring and medical equipment, appropriate medications and infusion media, the possibility of cardiopulmonary resuscitation.
With discrete plasmapheresis, blood sampling and plasma separation are carried out separately, for which blood is taken into a large bag "Gemacon 500/300" and after immediate centrifugation in a centrifuge for 15 minutes. With a manual plasma extractor, the plasma is transferred into a small bag of “Gemacon”. The cell mass remaining in the large bag is resuspended in an isotonic blood substitute and reinfused to the patient. After reinfusion of the cell suspension, blood is taken again into a new “Gemacon 500/300” and a new dose of blood is centrifugally processed with plasma separation and erythrocyte reinfusion. The total dose of plasma removed from a patient by this method is 500-1500 ml. The multiplicity and 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. The preparation and conduct of an extracorporeal operation is carried out in accordance with the instructions for this type of apparatus.
In severe myasthenic, cholinergic crises, in patients with severe bulbar disorders and other disorders, it is effective to carry out plasma exchanges. A high volume of plasma exfusion during plasma exchange should be compensated during the operation (or immediately after its completion) by infusion therapy, the program of which may include not only crystalloids, colloids, but also native donated plasma, albumin solutions. As an alternative to intensive plasmapheresis and plasma exchange for donor plasma, cryoprecipitation is used in the treatment of myasthenia gravis. With its use, 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 the previous operation for plasma exchange. This increases the selectivity of extracorporeal surgery, and most of the plasma components are returned to the patient.
In cases of violation of protein metabolism and deficiency of infusion media containing donor proteins, a sorption column is included in the extracorporeal circuit for plasmapheresis and a plasma sorption operation is performed.
As a rule, plasmapheresis is carried out in a course of 1-2 weeks with a frequency of 2-5 operations. Intermittent plasmapheresis leads to improvement after 3-4 sessions. The efficiency of continuous plasmapheresis, despite the great possibilities in terms of the volume of plasma to be replaced, does not differ significantly from intermittent one. 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 regimen of therapy is short (five-day courses) of 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 the end of the course. After 3-4 months. repeated course of immunoglobulin therapy is possible

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

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

(!!!) The introduction of anticholinesterase drugs as a diagnostic test is indicated for any form of crisis. Evaluation of the test with the introduction of kalimina-forte or prozerin after a period of withdrawal of anticholinesterase drugs allows you to determine the effectiveness of the therapeutic measures and the possibility of transferring the patient to spontaneous breathing.

PREGNANCY AND BIRTH
Pregnant patients with myasthenia need to be monitored during pregnancy. In the absence of obstetric indications for caesarean section, delivery is carried out through natural birth canal. If a caesarean section is necessary, epidural anesthesia is desirable.

With the appearance of weakening in childbirth labor activity- injections of prozerin 1.5 ml parenterally in 3-4 hours.

If the condition worsens after childbirth with the appearance of bulbar disorders - the appointment of prednisolone at a dose of 1 mg per 1 kg of body weight every other day, orally, in the morning the entire dose.
kalimin 1/2 - 1 t 2-3 r / day (if necessary)
potassium chloride 1-2 g 3 r / day (constantly with meals)

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

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

CONTRAINDICATED IN MYASTENIA:
Contraindicated in myasthenia gravis: excessive exercise, magnesium preparations (magnesia, panangin, asparkam), curare-like muscle relaxants, neuroleptics and tranquilizers (except grandaxin), GHB, diuretics (except veroshpiron 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, fluorine-containing corticosteroids, quinine derivatives, D-penicillamine.

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

One of the most unpleasant diseases that women are susceptible to, 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 greatly affect the muscular and nervous systems.

Forms of myasthenia gravis

Myasthenia manifests itself in generalized and local forms. When flowing in the first form, respiratory processes are disturbed. In the local form, there is a division into ophthalmic, pharyngeal-facial and musculoskeletal. Most widespread among patients, myasthenia gravis has an ocular form, therefore its treatment causes the most questions and disputes.

Symptoms of myasthenia gravis

First of all, the disease manifests itself on the face, then on the neck and spreads down the body. The first symptoms of the disease that patients notice in themselves 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 in the future the disease progresses so much that even a long rest and sleep are not able to get rid of all the symptoms. Subsequent symptoms include:

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

For the 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 onset and development of the disease, experts distinguish the following:

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

Treatment of myasthenia gravis

If the disease is not treated, then, in the end, it leads to death. Therefore, at the first manifestations of the disease, it is worth thinking about how to treat myasthenia gravis. Although doctors do not recommend self-treatment myasthenia gravis folk remedies, but still there are several very effective alternative methods of treatment:

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

These three folk methods of treating myasthenia gravis can be combined for best effect. It is recommended to take all three mixtures throughout the year, alternating every two to three months. In addition, potassium-rich foods such as bananas, raisins and

Myasthenia gravis is a neuromuscular disease characterized by weakness and pathological muscle 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 disorders of the immune system. This is also associated with damage to skeletal muscles such as polymyositis. In 70-90% of patients, pathology of the thymus gland (hyperplasia, thymitis, thymoma) is found.

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

Treatment. Anticholinesterase drugs (ACEPs) 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, use of corticosteroid drugs, immunosuppressants, plasmapheresis and hemosorption.

AHEPs differ in duration of action (Table 26), effectiveness in different forms of the disease (kalimin is more effective in ocular, and oxazil in bulbar and trunk forms), and in the degree of toxicity (increases in the series; kalimin, galantamine, oxazil, prozerin). The choice of AHEP 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 the drug in each patient. The drug should be taken again 30-60 minutes before the expected cessation of action. previous dose. When replacing drugs, it should be borne in mind that in terms of the effectiveness of 1 table. proserin, kalimina or oxazil corresponds to 1 ml of a 0.05% solution of proserin. Individual adequate daily dose averages 3-9 tab. This dose in some cases has to be increased to 20 tablets. In any case, prescribing without prior testing of high doses or a combination of ACE inhibitors should be avoided due to the risk of a cholinergic crisis.

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

Potassium preparations improve the synthesis of acetylcholine and synaptic transmission, prolong the action of AHEP. They are shown at all stages of treatment. In patients with local forms of the disease and with stable long-term remission, they are used as monotherapy, in other cases - as part of combined treatment. Assign potassium orotate (dioron, oronur) in tablets of 0.5 g 3 times a day; potassium chloride in powder or tablets of 0.5-1 g or 1 g or 50 ml of a 4% solution (10 ml of a 10% solution) orally 2-3 times a day: spironolactone (veroshpiron, aldactone) in tablets of 25 mg 3-4 times a day. Veroshpiron is contraindicated in mastopathy, gynecomastia, pregnancy, atrioventricular blockade 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 now given a crucial role 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 general strengthening therapy, treatment concomitant diseases, sometimes thymus irradiation, 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 frequency of improvement and remission after thymectomy reaches 70-90%, and improvement can occur within 5 years after surgery. It is inappropriate to use thymectomy in stationary mild forms, as well as in the local ocular form of myasthenia gravis. Contraindications to thymectomy are severe decompensated somatic diseases. Mortality due to thymectomy decreased to 0.8%.

Gamma or X-ray irradiation of the thymus gives a less stable than thymectomy positive effect in 30-50% of cases. Radiation therapy is performed 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 in children and patients in 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 appointment is the lack of effectiveness of the combined treatment of myasthenia gravis by other means, as well as the period of preparation of patients for thymectomy. In severe forms of myasthenia, prednisolone is prescribed daily, and when it comes significant improvement, every other day with the intake of the entire daily dose on an empty stomach in the morning. If it is not possible to quickly switch to taking the drug every other day, unequal doses can be prescribed: for example, 100 mg on even numbers, 50 mg on odd numbers. 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 given for several years. Taking prednisolone every other day avoids 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 doses of AHEP before prescribing prednisolone in order to avoid a cholinergic crisis. In some cases, at the beginning of treatment with prednisolone, a deterioration in the condition may occur, so hormonal therapy should be started in a hospital setting.

Side effects noted during prolonged therapy with prednisolone: viril obesity, hirsutism, menstrual irregularities, Itsenko-Cushing's syndrome, mental disorders. Possible mucosal ulceration 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 preparations 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 lack of effectiveness of therapy for progressive myasthenia gravis by other means. Azathioprine (Gshuran) at the beginning of treatment is prescribed in small doses (50 mg per day). 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. Usually, azathioprine is prescribed along with a maintenance dose of prednisone. Side effects: thrombo-, leukopenia, hepatitis, pancreatitis, the addition of a 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 1 time in 3 days. With a decrease in the number of leukocytes in the peripheral blood to 3-3.5 * 109 / l, azathioprine is canceled.

Cyclophosphamide in 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 cytostatic is reduced. Side effects: dyspeptic and dysuric disorders, leukopenia, alopecia, dizziness, blurred vision. Cyclosporine inhibits the activity of T-helpers and T-killers. Assign him to average dose 3-5 mg per day. The tactics of changing the dose is the same as in the treatment of 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 in 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 1-1.5 months.

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

Immunoglobulin with repeated intravenous drip infusions improves the condition 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, with 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 halve the dose of corticosteroid drugs. 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 extremities. In 20-25% of cases, as with the start of treatment with prednisone, there is a transient increase in muscle weakness.

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

Hemosorption - extracting blood from a vein, passing it through an adsorbent and infusing it into cubital vein. Usually spend 1 session, in which 6-10 liters of blood is passed through the adsorbent. Subsequent sessions are ineffective.

Enterosorption is carried out by prescribing for oral fibrous salt adsorbent vaulen at a dose of 50-60 mg/kg of body weight 3 times a day (2 hours after meals and not earlier than 2 hours before the next meal) for 20 days.

In recent years, other methods of influencing immune status a patient with myasthenia gravis: the use of antilymphocytic 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 killed in a matter of years. Thanks to the development of medicine and pharmacology, today we can hope for a tangible extension of the life of the victim of this disease. It is important that a lot is in the hands of the patient himself, who is able to keep himself within a safe framework, protecting him from the risks of exacerbation and progress of a serious illness.

Features of treatment

Modern treatment of myasthenia gravis involves a clear phasing of therapeutic measures, ranging from more point impact specifically on neuromuscular transmission, and ending complex therapy aimed at modifying immune interactions. The volume 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 neuromuscular junctions increases, which helps to improve impulse transmission. Of the drugs, prozerin, pyridostigmine, oxazil, etc. are used.

For patients with myasthenia gravis, an adequate intake of B vitamins is very important.

As a rule, anticholinesterase drugs at the first stages of treatment of myasthenia gravis are quite effective. They are also essential first aid in crises, and therefore every patient with myasthenia gravis should have these medicines in a quick access area.

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

Therefore, in no case should one neglect the prescriptions of doctors, which, it would seem, are not very important. For patients with myasthenia gravis, normal potassium metabolism and sufficient intake 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 a more aggressive medical tactics. Immunosuppressive hormones enter the arena, which are the means of choice for any processes associated with immunity failures towards an inadequate increase. These drugs are hard on the body, but given the choice between a life of side effects and a quick inevitable death, the feasibility of their use is obvious.

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

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

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

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

Strict adherence to the doctor's instructions is prerequisite prolonging the life of a patient with myasthenia gravis. In addition, it is in the power of the patient himself to save 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 time.

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

Prevention of recurrence of myasthenia gravis

Constant monitoring by the attending neurologist is necessary

The first thing that a patient with myasthenia needs to learn is the constant supervision of the attending neurologist. You can not arbitrarily move the date of the inspection. In the event of new symptoms or any other option for worsening the condition, contact the doctor unscheduled. If, due to a change of residence or any other factors, it is necessary to change the attending physician, then it is necessary to contribute to the most complete transfer of information about the patient's condition and anamnesis of his illness to a new specialist.

You should radically revise your lifestyle, adapting it to the requirements dictated by the state of health.

The work of a patient with myasthenia should in no case be physical. Optimal is mental work or a position of an organizational nature. If possible, long routes to the place of work should be avoided. Moving from the center to the periphery is shown - a slower rhythm of life and the absence of a stressful life background of 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 SARS is contraindicated. Absolutely any infection is a stress for the body that can cause additional failures of the immune response. There are frequent cases of myasthenic crises against the background of transferred 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 relaxing effect, most sedatives and hypnotics, as well as atypical neuroleptics, are contraindicated.

If it is necessary to select an antibiotic or sedative, a thorough consultation is necessary at least with the attending neurologist, and best of all in the form of a consultation of various specialists. In addition, any new drug should be checked by the patient for contraindications. In this day and age of the Internet, such verification is not difficult.

You need to change the way you eat. 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.

You can't rush while walking. When arranging a home, make sure that the interior is thought out according to the requirements of the disease - in any place there should be something that makes it possible to grab onto oneself in case of a sudden attack of weakness. This way you can avoid unnecessary injury.

If suddenly weakness rolls in a crowded place, then do not be shy to ask for help. This will help decide current situation, and will contribute to the rapid provision of urgent therapeutic measures in the event of an increase in symptoms.

It must be remembered that panic aggravates the clinical picture. It is necessary to develop a calm attitude towards the disease and a willingness to act soberly in the event of a myasthenic crisis. The coldness of the mind is the key to a happy resolution of sudden exacerbations of myasthenia gravis.

It is strictly contraindicated to stay in direct sunlight - this enhances the immune response and provokes new attacks on acetylcholine receptors. In addition to the "shadow" way of life, myasthenics are shown wearing sunglasses when in open space.