The choice of drugs for myasthenia gravis depends on the degree of damage to muscle tissue and the magnitude of the disruption of synaptic conduction. Changes in ion exchange associated with potassium deficiency also require a special approach to the selection of drugs for therapy. Radical treatment methods are used - surgery or irradiation of the thymus gland.

Modern aspects of treatment

An autoimmune pathological process accompanied by paresis and paralysis. Modern drugs for myasthenia gravis allow patients to maintain their ability to work, avoid disability, and improve their quality of life. Electromyography data, a pharmacological test using anticholinesterase drugs, and blood serum testing for the presence of autoantibodies help prescribe effective treatment.

What painkillers are available for myasthenia gravis is determined by the doctor individually depending on the stage of the disease. The following drugs are prescribed for treatment:

• Fortalgin;
• Voltaren;
• Ibuprofen;
• Ketoprofen;
• Spasmalgon;
• Coldrex;
• Tempalgin.

Psychotropic substances - Aminazine, Amitriptyline - can aggravate the course of myasthenia gravis. Safe drugs are benzodiazepine derivatives and the drug Sonapax.

In patients with a generalized form of myasthenia, Chlorophyll is used to treat concomitant diseases of the nasopharynx. Antiseptic therapy ensures the saturation of infected tissues with oxygen. The patient's general condition is improved by Actovegin, which dilates the coronary vessels and improves the functioning of the nervous system. If the patient suffers from heart failure, medications are used to maintain the normal functioning of an important organ:

• Preductal;
• Mildronate.

Immunosuppressive therapy

Immunosuppressants are prescribed for:

• Cyclosporine;
• Prednisolone.

However, during therapy, the risk of infectious complications and the development of malignant tumors increases.

Azathioprine is the safest drug. It affects the absorption of glucocorticoids and can significantly reduce their dose. Side effects of the drug lead to its withdrawal. The patient complains of headache, chills, and fever. A person develops symptoms of liver dysfunction.

Methotrexate is a strong immunosuppressant, it is used in a small dose, because the drug has significant toxicity. The patient experiences discomfort in the epigastric region, nausea, and vomiting. Many people experience pain in the liver area, enzyme activity changes, and signs of cirrhosis appear.

Leucovorin, prescribed after Methotrexate therapy, reduces its toxicity. For a patient suffering from myasthenia gravis, treatment with antipsychotics and tranquilizers is contraindicated.

Medicines to reduce muscle tone

In some cases, non-depolarizing muscle relaxants are used for myasthenia gravis:

• Tracrium;
• Esmeron.

Considering the contraindications, the doctor tries not to prescribe muscle-relaxing drugs to treat patients, since many patients have increased sensitivity to their effects.

Non-depolarizing muscle relaxants are not used, since in many cases the patient develops an unpredictable reaction to their administration. The drug Succinylcholine causes a marked increase in the level of potassium in the blood serum and high temperature in the patient.

Patients suffering from periodic paralysis experience attacks accompanied by muscle weakness. During surgery to remove the thymus gland, the doctor does not use decompensated muscle relaxants. Sodium thiopental provides complete anesthesia.

The use of tablets for myasthenia gravis, which have a muscle relaxant effect, is prohibited for all categories of patients. Mydocalm, Sirdalud, Meprotan are especially dangerous to the patient’s health. The use of muscle relaxants in patients with the initial form of the disease causes respiratory arrest.

Glucocorticoid therapy

Prednisolone increases the number of cholinergic receptors. After taking it, muscle strength increases. To avoid certain risks in the early stages of the disease, therapy is carried out in a hospital setting. The patient is additionally prescribed anticholinesterase drugs. Treatment with glucocorticoids is long-term. The intermittent method is very popular, when the patient takes an increased dose of medication over several hours. Side effects may occur during treatment:

• increased blood pressure;
• stomach ulcer.

Azathioprine is used in patients with myasthenia gravis that is difficult to treat with Prednisolone. Dexamethasone is recommended by the doctor, taking into account the patient’s condition, since the drug is 10 times more active than other glucocorticoids. However, it is unsuitable for circadian therapy because it worsens the patient's condition.

Treatment with glucocorticoids involves taking alkalizing drugs: the patient is prescribed Phosphalugel or Ranitidine. To prevent the development of diabetes mellitus, the patient must follow a special diet. Limit consumption of foods containing large amounts of carbohydrates. Blood is drawn regularly to determine glucose levels.

Cholinesterase inhibitors

In mild cases of the disease, the patient is prescribed medications that prevent the decrease in acetylcholine in the area of ​​the neuromuscular nodes. The use of Proserin in the treatment of patients with myasthenia gravis provides active muscle stimulation, but large doses of the drug cause disruption of muscle conduction.

Diclofenac sodium is used for therapeutic blockade in case of nerve damage and intense pain. It is the drug of choice, since procedures using Novocaine and Lidocaine are prohibited in patients suffering from myasthenia gravis.

Axamon (Ipidacrine) is used for diseases of the peripheral nervous system. The medicine is well tolerated by patients. The drug has a double effect, while Proserin, Oksazil and Kalimin act only on the peripheral nervous system.

Patients are prescribed medications containing potassium. For therapy, KCL is used in powder form. Considering its side effect on the gastric mucosa, it is taken after meals with milk. Medicines Potassium-Normin and Kalipoz are intended for oral administration several times a day.

The following medications containing magnesium and potassium should not be prescribed to the patient:

• Panangin;
• Asparkam.

Pathogenetic impact

When treating myasthenia gravis, the doctor performs pulse therapy using Methylprednisolone and certain treatment regimens. Corticosteroids are prescribed in a therapeutic dose daily or every other day. The course of treatment lasts a week, and then the doctor reduces the dose of the drug.

If the patient's condition worsens, a stepwise therapy regimen is used, based on increasing the single dose until the maximum allowable amount of medication is reached at one time. Metypred is a drug with high mineralocorticoid activity, therefore it is more often used for treatment and stabilizes the patient’s condition.

Use of immunoglobulins

For treatment (MG), infusions of immunoglobulins (IVIG) obtained from donor blood are prescribed. The purpose of the method is to increase the patient’s body’s defenses. Functional changes in patients with MG reach significant values. Immunoglobulin administered to the patient does not cause serious side effects. The following drugs are used in the treatment of patients:

• Gamimun-N;
• Pentaglobin;
• Octagam 10%;
• Intraglobin.

During a crisis, immunoglobulins are prescribed only after emergency resuscitation measures. Human specific protein prevents the development of severe complications. It is administered every other day at the dose prescribed by the doctor.

Often, patients with myasthenia gravis complain of nausea and headache after infusion. The doctor evaluates the functioning of the patient’s immune system and notes the number of T cells. During the study, defects in immune particles are detected, and in the serum - increased activity of thymic humoral factors.

The concentration of immunoglobulins reflects the state of internal organs that affect the body's defenses. Normal human protein containing a special fraction, administered in a standard dose for the first time, causes the appearance of flu-like symptoms:

• heartbeat;
• drowsiness;
• convulsions;
• high temperature.

There is another serious problem - it is necessary to constantly monitor the patient’s condition, in case of collapse and increased blood pressure, discontinue treatment, administer intravenous plasma solution and antihistamines.

In the treatment of myasthenia gravis, cytostatics are used:

• Cyclophosphamide;
• Cyclosporine;
• Cyclophosphamide;

Often, after achieving the effect, the dose of the medicine is reduced. Taking Cyclophosphamide causes side effects:

• leukopenia;
• hepatitis A;
• inflammation of the pancreas;
• septicemia;
• intestinal disorders;
• dizziness,
• visual impairment.

Harmful drugs

The following drugs are contraindicated for patients with myasthenia gravis:

• anticonvulsants;
• antibiotics (aminoglycosides);
• B-blockers;
• Lithium carbonate;
• Procainamide hydrochloride;
• Trihexyphenidyl hydrochloride;
• antimalarial and antirheumatic drugs;
• eye drops;
• hypoglycemic drugs.

Illicit drugs contribute to the development of myasthenic symptoms and increase skeletal muscle weakness. Antibacterial medications worsen the symptoms of the disease. The following drugs are not recommended for use:

• Ampicillin;
• Imipenem;
• Erythromycin.

Sleeping pills are contraindicated for myasthenia gravis. Treatment with benzodiazepine derivatives and barbiturates is unacceptable. Medicines containing magnesium significantly worsen the patient's condition. You should not take diuretics that affect the conduction of neuromuscular impulses.

The patient must take the medications prescribed by the doctor in courses, monitor his well-being and lead a healthy lifestyle.

Various methods of treating myasthenia gravis (medical and surgical) remain relevant. Each of the methods pursues specific goals and is most appropriate at one or another stage of the development of the disease.

Non-drug treatment

Non-drug treatment includes methods of extracorporeal immunocorrection (hemosorption and plasmapheresis - see "Treatment of crises"). Non-drug treatment methods include gamma therapy for the thymus region. This method is used in patients who, due to certain circumstances, 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 gamma irradiation is selected individually (on average 40-60 Gray).

Drug treatment

The strategy for drug therapy for myasthenia gravis is based on the following principles.

Stages of treatment measures.
Combinations of compensatory, pathogenetic and nonspecific therapy.
Taking into account the phase of the disease [chronic or acute (crises)].

First stage

Compensatory therapy involves prescribing the following drugs.

Anticholinesterase drugs: pyridostigmine bromide orally in a maximum daily dose of 240-360 mg (30-120 mg per dose). Acetylcholine secretion is improved by neuromidin at a dose of 120-160 mg/day orally, 45 mg/day parenterally.
Potassium preparations (for example, potassium chloride powder 1.0 g 3 times a day; the powder is dissolved in a glass of water or juice and taken with meals). Contraindications for the use of large doses of potassium are complete transverse blockade of the cardiac conduction system, impaired renal excretory function.
Potassium-sparing diuretics. In particular, spironolactone is used orally at a dose of 0.025-0.05 g 3-4 times a day.

Second phase

If the drugs used at the first stage are insufficiently effective, as well as to create a kind of safety margin in compensating for myasthenic disorders, treatment with glucocorticoids is prescribed before preparing for surgery (thymectomy).

The effectiveness of glucocorticoids in the treatment of myasthenia gravis reaches, according to some data, 80%. Due to the relatively rapid onset of the effect, they are considered the drugs of choice in patients with vital disorders, as well as at the onset of the disease with bulbar disorders and in the ocular form of myasthenia.

Currently, taking glucocorticoids according to a schedule every other day is considered the most optimal. The dose of prednisolone (methylprednisolone) is selected individually, focusing on the severity of the patient’s condition. On average it is 1 mg (kg x day), but not less than 50 mg. The drug is taken once a day in the morning. It is advisable to begin treatment in a hospital setting. The effect is assessed after 6-8 doses. In the first few days, some patients may experience episodes of deterioration in the form of increasing muscle weakness and fatigue. Perhaps these episodes are associated with the direct effect of glucocorticoids on the processes of synaptic transmitter release and receptor desensitization. This circumstance necessitates a temporary reduction in the dose of anticholinesterase drugs. As the effect is achieved and the patients' condition improves, the dose of prednisolone is gradually reduced to maintenance.

With long-term use of glucocorticoids, some patients may develop side effects of varying severity. The most common symptoms include weight gain, hirsutism, cataracts, impaired glucose tolerance, arterial hypertension, and osteopenia. If side effects develop, in addition to symptomatic therapy, it is advisable to reduce the dose of the drug.

Third stage

If glucocorticoids are insufficiently effective or severe side effects develop, it is advisable to prescribe cytostatic drugs.

Azathioprine (Imuran) is generally 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. Azathioprine can be used as monotherapy or in combination with glucocorticoids if they are not sufficiently effective or if side effects require a dose reduction. Azathioprine is prescribed orally daily at 50 mg/day, followed by increasing the dose to 150-200 mg/day.

Mycophenolate mofetil is well tolerated and effective in 60-70% of patients. Compared to azathioprine, it acts faster (the clinical effect appears after 3-4 weeks) and has fewer side effects. As monotherapy, the drug is not effective enough, so it is prescribed in addition to glucocorticoids in cases where it is necessary to reduce their dose. Mycophenolate mofetil is prescribed orally daily at 2 g/day with subsequent dose adjustment depending on the effectiveness of treatment.

Cyclosporine is successfully used in the treatment of severe forms of myasthenia gravis in cases of resistance to other drugs. The effect is practically independent of previous therapy. The advantage of cyclosporine is its more selective (compared to other immunosuppressants) effect on individual mechanisms of the immune response. The drug is prescribed orally at a dose of 3 mg/kg. In the absence of toxic reactions, the dose can be increased to 5 mg/kg 2 times a day. Improvement in most patients is noted after 1-2 months from the start of therapy, it reaches a maximum after 3-4 months. After achieving a stable therapeutic effect, the dose of cyclosporine can be reduced to the minimum maintenance level.

Cyclophosphamide is used in the absence of effect from other immunosuppressants, both as monotherapy and in combination with azathioprine. The drug is administered intramuscularly daily at a dose of 200 mg or every other day at a dose of 400 mg. Therapy begins in a hospital setting, and only after ensuring that the drug is well tolerated can patients be transferred to outpatient treatment.

At the third stage, to correct possible side effects of glucocorticoid and immunosuppressive therapy, immunomodulators obtained from the thymus gland (thymus extract, thymalin, etc.) can be used. It should be remembered that these drugs in rare cases can cause exacerbation of myasthenia gravis.

Treatment of crises

According to modern concepts, the pathophysiological mechanisms of the development of crises in myasthenia gravis are associated with various variants of 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 ventilation

When crises develop, it is first necessary to ensure adequate breathing, in particular with the help of mechanical ventilation. In each specific case, the issue of transferring a patient to mechanical ventilation is decided on the basis of the clinical picture (impaired rhythm and depth of breathing, cyanosis, agitation, loss of consciousness), as well as objective indicators reflecting the gas composition of the blood, hemoglobin oxygen saturation, acid-base state ( RR >40/min, vital capacity<15 мл/кг, P a O 2 <60 мм рт.ст., Р а СО 2 >60 mm Hg, pH about 7.2, S a O 2<70-80%). в ряде случаев достаточно про ведения ИВЛ и отмены антихолинэстеразных препаратов на 16-24 ч для купирования холинергического и смешанного кризов. В связи с этим ИВЛ вначале можно про водить через интубационную трубку, и только при затянувшихся нарушениях дыхания в течение 3-4 дней и более показано наложение трахеостомы. В период проведения ИВЛ полностью исключают введение антихолинэстеразных препаратов, про водят интенсивное лечение интеркуррентных заболеваний и патогенетическое лечение миастении. Через 16-24 ч после начала ИВЛ, при условии ликвидации клинических проявлений холинергического или смешанного кризов, следует провести пробу с введением антихолинэстеразных препаратов. При положительной реакции можно прервать ИВЛ и, убедившись в возможности адекватного дыхания, перевести больного на приём пероральных антихолинэстеразных препаратов. При отсутствии положительной реакции на введение антихолинэстеразных препаратов необходимо продолжить ИВЛ и повторять пробу каждые 24-36 ч.

When performing mechanical ventilation, the following measures are necessary.

Ensuring airway patency (monitoring the position of the endotracheal tube, timely aspiration of the contents of the tracheobronchial tree, inhalation of mucolytic, antibacterial drugs, vibration massage of the chest).

Periodic monitoring of tidal volume, peak inspiratory and expiratory pressures, indicators of acid-base balance and blood gas composition, as well as indicators of circulatory function (BP, central venous pressure, cardiac output, total peripheral resistance).

Systematic monitoring of the uniformity of lung ventilation (auscultation, radiography), if necessary, “inflating” the lungs manually.

Regular monitoring of body temperature, diuresis and fluid balance.

Rational parenteral or tube nutrition (with long-term mechanical ventilation), control of intestinal activity, prevention of urinary tract infections, bedsores.

Prevention of complications associated with prolonged stay of an endotracheal or tracheostomy tube in the respiratory tract (laryngitis, tracheobronchitis, bedsores, erosive bleeding).

The patient is transferred to spontaneous breathing after a thorough assessment of the main indicators indicating the adequacy of spontaneous breathing - absence of cyanosis, tachypnea, tachycardia, preservation of muscle tone, sufficient tidal volume (>300 ml), p.Oz 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

The most effective treatment for myasthenic and cholinergic crises is plasmapheresis. The plasmapheresis method is based on collecting blood from the ulnar or one of the central veins, followed by centrifugation, separation of the formed elements and replacement of the plasma either with donor or artificial one. This procedure leads to rapid (sometimes within several hours) improvement in the condition of patients. It is possible to extract plasma again over several days or every other day.

Examination of the patient before plasmapheresis includes:

Assessment of vital functions;
complete clinical blood test (including platelets, hematocrit);
determination of blood group and Rh factor;
serological tests for syphilis, HIV, hepatitis B virus;
determination of the concentration of total protein, protein fractions;
determination of the main indicators of blood clotting;
clinical urine analysis.

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.

Depending on the indications, centrifugal plasmapheresis (manual or hardware), filtration (hardware) or in combination with plasma sorption is used.

Immunoglobulin therapy

Intravenous administration of normal human immunoglobulin (Gamunex, Gamimun N, Octagam, Intraglobin, etc.) can cause a rapid temporary improvement in the course of myasthenia gravis. The administration of high doses of immunoglobulins suppresses immune processes. The generally accepted treatment regimen is short (5-day) courses of intravenous administration of the drug at a dose of 400 mg/kg daily. On average, the clinical effect occurs on the 4th day from the start of treatment and persists for 50-100 days after completion of the course. After 3-4 months, a second course of immunoglobulin therapy is possible. Side effects manifest themselves in the form of increased body temperature (4%), nausea (1.5%), headache (1.5% of cases). Most of these events resolve after reducing the rate of drug administration or after temporarily stopping the infusion.

Surgery

If the first-stage drugs are well effective, but mild bulbar disorders persist after discontinuation of pyridostigmine bromide, thymectomy is indicated. Possible mechanisms for the beneficial effect of thymectomy on the course of myasthenia gravis are associated with the removal of the source of antigens that induce the synthesis of antibodies to acetylcholine receptors; decreased production of autoantibodies; removing the source of abnormal lymphocytes. The effectiveness of thymectomy is currently 50-80%. The result of the operation can be complete clinical recovery (effect A), stable remission with a significant reduction in the dose of anticholinesterase drugs (effect B), significant improvement in condition while maintaining the need for anticholinesterase drugs (effect C), and no improvement (effect D). Indications for thymectomy are a tumor of the thymus gland (thymoma), involvement of the craniobulbar muscles in the process, as well as the progressive course of myasthenia gravis. In children, thymectomy is indicated for a generalized form of myasthenia gravis, poor compensation of impaired functions as a result of drug treatment, and with progression of the disease.

Contraindications to thymectomy are severe somatic diseases, as well as the 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.

In myasthenia gravis, excessive physical activity, insolation, magnesium preparations, curare-like muscle relaxants, neuroleptics and tranquilizers (except tofisopam), diuretics (except spironolactones), aminoglycosides (gentamicin, streptomycin, kanamycin, tobramycin, sisomycin, amikacin, etc.), fluoroquinolones (norfloxacin) are contraindicated , ciprofloxacin, ofloxacin, etc.), fluorinated corticosteroids, quinine derivatives, penicillamine.

FORECAST

Correct diagnosis and timely prescription of adequate treatment methods lead to compensation of movement disorders in more than 80% of patients with myasthenia gravis.

Myasthenia gravis is a chronic neuromuscular disease manifested by a recurrent or gradually progressive type of course. People with myasthenia gravis suffer from increased muscle fatigue, which at the end of the day sometimes leads to severe paresis of the muscles affected by the pathological process.

Causes

There is no consensus on the causes of this disease. At different times, hereditary, infectious, and autoimmune theories were expressed. There is also a clear connection between the development of this condition and a tumor of the thymus gland, although the latter is not always present, and its removal does not always lead to an improvement in the condition.

It should be said that the risk of developing myasthenia gravis increases significantly with an existing family history. However, among sick people in the same family, very often the manifestations of myasthenia gravis vary from minimal (ocular form of myasthenia) to the maximum possible (myasthenia gravis).

The disease is quite common, the incidence of myasthenia gravis varies from 5 to 10 people per 100,000 population. Women are more often affected (in a ratio of 2 to 1); the age of onset of the disease is mainly between 15 and 45 years. Cases have been described when the disease occurs in children. More often there is early muscle weakness, which resolves during the first month of life.

It should be noted the possibility of developing myasthenic syndrome against the background of existing chronic diseases: dermatomyositis, tumors of endocrine organs, systemic connective tissue diseases, etc.

Symptoms

The symptoms vary in severity and localization, but they can be characterized by one phrase - muscle weakness. Depending on the localization of the process and the severity of manifestations, several forms of myasthenia are distinguished:

• Eye shape.
• Bulbar form.
• Generalized form (myasthenia gravis, Erb-Goldflam disease).
• Malignant myasthenia fulminans.
• Myasthenic crisis.

Ocular myasthenia is manifested primarily by the development of eyelid weakness, often on one side or unevenly on both sides. At the same time, at the beginning of the disease, the eyelid droops in the evening, after visual stress. Double vision and other transient visual disturbances are often observed. If within two years from the onset of the disease the process has not moved to other anatomical zones, then further generalization becomes unlikely. Localized myasthenia gravis (ocular form) is not life-threatening.

The bulbar form of myasthenia is characterized by the development of weakness of the muscles of the soft palate, tongue, and pharynx. The patient suffers from speech disorders and swallowing disorders. Moreover, the changes change dynamically throughout the day, with different loads, which distinguishes this form of the disease from true bulbar syndrome.

The generalized form is widespread muscle weakness. It all starts, as a rule, with the muscles of the neck; it becomes difficult for a sick person to hold his head, gradually the disease spreads to other muscle groups, and paresis of the muscles of the limbs begins to appear. The patient's gait is disturbed and facial expressions are distorted. There is a noticeable improvement in the condition in the morning, after a nap, and after a long rest. The slightest physical activity sometimes leads to severe weakness.

The malignant type of the disease occurs only in the presence of a thymus tumor, often malignant. The disease debuts at the age of about 50 years and within a short period of time (months, and sometimes even weeks), leads to complete disability. At extreme stages, the skeletal respiratory muscles are affected with the likelihood of developing life-threatening conditions.

Myasthenic crisis is a special manifestation of the generalized form of this pathology. The exact causes of the crisis have not been identified; it develops more often against the background of menstruation, psycho-emotional stress, fever or other reasons. Insufficient dosage of drugs in the treatment of the disease can also lead to the development of complications. During a crisis, pronounced weakness of all muscles, including the respiratory ones, develops. The duration of the crisis varies very widely and can last from several tens of minutes to hours, to weeks, and in some cases, months.

Difference between myasthenic crisis and cholinergic crisis.

Diagnostics

As a rule, diagnosing the disease is not difficult, because all manifestations of myasthenia gravis are expressed quite characteristically. Also, even with a standard neurological examination, rapid muscle fatigue, myasthenic reaction of tendon reflexes and gradual exhaustion can be detected. Special tests and additional research methods are also used:

Test of drooping eyelids - there is a characteristic look from under drooping eyelids, a person can rarely look with his eyes open, the eyelids quickly droop.
Cooling test. It is performed more often on the eyelids. A piece of ice is placed on one eyelid; after cooling, an improvement in the functioning of the eyelid is noted.
Proserine test. (there will be a section in symptoms-syndromes later, and check the request) The patient is injected subcutaneously with 2-3 ml of proserine 0.05% solution. With myasthenia gravis, the function of the affected muscles is practically restored after half an hour. This state sometimes returns to its original state no earlier than 2-3 hours.
makes it possible to identify a characteristic myasthenic reaction of neuromuscular transmission and to identify rapid muscle fatigue upon repeated stimulation.

Treatment

Treating myasthenia gravis is not an easy task. The patient should be immediately set up for constant or very long-term use of anticholinesterase drugs that act on the pathogenesis of the disease. Kalimin drugs, and the less commonly used proserin, should be carefully dosed, taking into account body weight, severity of symptoms, age and other factors.

Hormone therapy is often resorted to, especially with acute development of symptoms and their rapid progression. Most often, pulse therapy is carried out in high doses, with a further transition to minimal dosages. It is also advisable to conduct sessions of plasmapheresis (purification of blood from circulating autoimmune complexes) while using pulse therapy with hormones (metipred, dexamethasone, etc.).

Treatment of myasthenic crisis should begin with maintaining vital functions, gradually moving to a course of plasmapheresis, hormonal therapy, and clarifying the presence of a thymic tumor. The presence of thymoma (especially growing) in combination with frequent myasthenic crises is an indication for surgical removal of thymoma. Unfortunately, only about 50% of patients report improvement.

Also, therapy for myasthenia gravis should include pure potassium preparations (in no case Panangin, because magnesium can lead to worsening of symptoms!), the prescription of potassium-sparing diuretics (veroshpiron), metabolic drugs (riboxin, B vitamins). The prescription of physiotherapy, special physical therapy exercises, and massage is justified.

List of drugs that cannot be used for myasthenia gravis

You should also strictly adhere to specific approaches to the treatment of other diseases. There is a list of drugs that cannot be used for myasthenia gravis:

What if pregnancy?..

It should be noted that pregnancy is not a contraindication to the prescription of the main drugs for the treatment of myasthenia gravis. During pregnancy, you should avoid hormone therapy, plasmapheresis sessions, and the use of large doses of potassium-containing drugs.

A neuromuscular disease with an autoimmune nature of development is myasthenia gravis - from the Latin Myasthenia Gravis. Ten people out of 100,000 suffer from this disease. More than 50% of patients achieve remission.

Some are predisposed to the occurrence of myasthenia gravis - a risk group. It includes:

• Young people aged 20 - 40 years;
• Female gender - according to statistics, women get sick 3 times more often than men, but in adulthood these figures become equal.

The main reason for the development of myasthenia gravis is the body’s autoimmune reaction to its own tissues. This process can be started:

• Genes;
• Stress;
• ARVI.

Depending on the provoking factor, myasthenia gravis is divided into 2 large classes:

• Congenital;
• Acquired.

The first type is the outcome of a genetic mutation. Failure leads to disruption of muscle contractile function. The second form is often a consequence of a thymus tumor. Myasthenia gravis can affect muscle fibers in any part of the body. The ocular form of the disease is more common. Children rarely suffer from this disease. They make up less than 3% of the total number of patients.

Clinical picture

Regardless of which muscle group the disease affects, patients will notice general symptoms in the affected area:

• Excessive fatigue;
• Increased weakness;
• Decreased performance and functionality.

The pathological focus causes discomfort to a person. This defective part cannot cope with the tasks assigned to it. Muscles in any part of the body can suffer. But the eyes are especially often involved in the process. This brings a lot of inconvenience to the patient. However, resting the muscles, relieving tension from them, brings relief. But it doesn't last long.

Over time, even prolonged relaxation will not reduce the severity of the patient’s symptoms. Progress in the field of pharmacology allows patients to fight the disease. In clinical practice, the following forms of myasthenia are distinguished:

• Lightweight;
• Heavy.

Diagnostics

In order to record the fact of the disease, symptoms alone are not enough for a doctor. Any study of a pathological process is not limited to instrumental methods. The doctor examines the patient, finds out the clinical signs of the disease. Reviews the patient's medical history. And then he prescribes laboratory and instrumental diagnostics. The standard set of tests to detect myasthenia gravis consists of the following:

• Functional tests aimed at detecting pathological muscle fatigue;
• Electromyographic study, which indicates activity in the affected areas;
• Decrement test, which allows you to identify the blockade of the neuromuscular signal, and at the same time the severity of the process;
• Proserine test;
• Biochemical blood test;
• Immunograms;

If it is difficult to make a diagnosis, a differential study may be prescribed by:

• Needle electromyography;
• Studying the conductive functions of nerve fibers;
• Electromyography of certain muscles – jitter.

Treatment

The choice of therapy for myasthenia gravis depends on many factors:

• Forms of the disease;
• Patient's condition;
• Associated pathologies;
• Prevalence of the process.

Drug treatment is usually prescribed. However, in some cases, surgery is recommended. Autoimmune processes in the thymus can cause thymectomy surgery. Among the effective medicines, “Proserin”, “Kalinin” and drugs with a high potassium content are known. They also prescribe medications that stimulate the immune system.

Symptomatic treatment that alleviates the patient’s condition includes the following medications:

• Anticholinesterase - "Ipigrix";
• Cytostatics;
• Glucocorticoids – “Prednisolone”, “Metypred”;
• Immunoglobulins.

In case of rapidly progressing changes, extracorporeal hemocorrection is prescribed - a method that helps cleanse the patient’s blood of antibodies against his own tissues. Even the first procedure gives people a chance to feel improvement. Further therapy helps to achieve a lasting effect.

An effective method is cryophoresis. This procedure allows you to cleanse the blood of harmful substances, exerting an effect through lowered temperature. This treatment is carried out over a course of 5–7 days in a row. The method of cascade plasma filtration has become widespread. This procedure is carried out using nano cleaners. They purify the blood and then return it to the patient.

Another modern method of treating myasthenia gravis can be considered extracorporeal immunopharmacotherapy. It involves the extraction of lymphocytes from the patient, their drug treatment and subsequent release into the blood system. Using a similar technique, it was possible to induce stable remission in patients for a year. It is especially important to follow the doctor’s recommendations, since myasthenia gravis has contraindicated drugs, the use of which is fraught with dangerous consequences.

Eye shape

One of the most common types of disease is orbital. Often, it is from here that the process of myasthenia gravis begins, and then spreads to other organs. The main symptoms noted by patients:

• Diplopia, that is, double vision. Patients see more than one holistic image;
• Decreased visual acuity and clarity;
• Impairment in the rotational and motor functions of the orbits;
• Ptosis, that is, drooping eyelids. As a result, the palpebral fissure is unable to open and close normally.

All the described signs can apply to either one or both orbits. Usually, by closing their eyes for a short time, patients experience relief. However, mild tension associated with reading or watching TV causes discomfort.

Bulbar form

This type of myasthenia gravis can become life-threatening for the patient. It entails:

• Dysphonia is a disorder of voice function;
• Dysphagia – difficulty swallowing;
• Dysarthria is disorganization in the functioning of the muscular system of the pharynx, larynx, and soft palate.

The described symptomatic manifestations entail dangerous consequences. Dysphagia may progress to complete inability to swallow. The list of food products for such patients is extremely scarce. The doctor prescribes the food. Patients have to be fed through a tube, they lose weight and become weaker. This means that their general condition worsens, which does not contribute to recovery.

Voice disorder reduces the social sphere of patients’ lives. And dysatria can cause death due to respiratory problems caused by paresis of the vocal cords that cover the larynx. This is fraught with asphyxia - suffocation.

Generalized form

The most unfavorable type of disease is systemic, that is, widespread. This dangerous type of myasthenia gravis invariably causes up to 1% of deaths among patients with this pathological process. The generalized form involves a large number of muscles, including the respiratory ones - this can cause failure and death if help is not provided.

This disease is often accompanied by the prevalence of the process. Over time, the limited form progresses to the systemic form. And although remissions are common in patients, they usually arise and end suddenly. Therefore, myasthenic episodes and conditions are distinguished.

The first ones start and end quickly. The latter represent a long-term ongoing process, up to several years. However, this myasthenic condition is not prone to progression.

Contraindications

Patients suffering from this disease are forced to have some restrictions. These include:

• Excessive physical activity;
• Insolation, that is, exposure to direct sunlight;
• Medicines with magnesium - “Magnesia” and “Panangin”, “Asparkam”;
• Muscle relaxants are curare-like;
• Neuroleptics, tranquilizers and drugs that enhance their effect - “Gidazepam”, “Corvalcaps”;
• Diuretics, with the exception of Veroshpiron and Spironolactones;
• The use of certain antibiotics such as aminoglycosides - Gentamicin and Streptomycin, fluoroquinolones - Enoxacin and Ciprofloxacin;
• Vaccinations.

Contraindicated drugs for myasthenia gravis should not be ignored. There are tables and lists of medications that answer the question “What antibiotics can be used for myasthenia gravis?” You should avoid drugs that have this disease in the list of complications. Such drugs include “Glutalit”. This means that the use of these tablets is a contraindication. Compliance with the doctor’s instructions is the key to a favorable course of the disease.

Myasthenia gravis is a classic autoimmune disease, which is based on an autoimmune process directed against the acetylcholine receptor of the postsynaptic muscle membrane. The leading link in the development of myasthenia gravis is a violation of neuromuscular conduction, which is clinically expressed in the development of increasing muscle weakness of various localizations. Currently, great strides have been made in studying the pathogenesis of the disease, in diagnosis, in approaches to the management and treatment of various groups of patients with myasthenia gravis. However, despite pathogenetic therapy, there are no specific approaches to completely cure this disease. The outcome of the disease depends on the effectiveness of the selected therapy and the rate of progression of increasing muscle weakness, which can lead to complete inexcitability of certain muscle groups.

The most clinically significant in patients with myasthenia gravis is the involvement of the main and auxiliary respiratory muscles in the pathological process, which ultimately results in varying degrees of respiratory failure. These changes lead to disruption of the ventilation function of the lungs, causing congestion, which are “favorable” for the development of the infectious-inflammatory process. In a study conducted at Johns Hopkins University Hospital from 1990-1998, it was shown that 46% of patients experiencing some type of respiratory distress due to myasthenia gravis developed pneumonia.

The importance of the development of the infectious process is associated with the treatment carried out in patients with various forms of myasthenia gravis. In addition to the main therapy with anticholinesterase drugs, treatment of myasthenia gravis is aimed at suppressing the activity of the autoimmune process, which is carried out by suppressing the general immune response of the body. Treatment methods for myasthenia gravis include the use of pulse therapy with glucocorticosteroids, the use of cytotoxic immunosuppressants (azathioprine, cyclophosphamide), and thymectomy. The listed treatment methods in connection with immune suppression create an additional background for the development of bacterial complications. It is important to note that some drugs, such as Cyclophosphamide, have a direct toxic effect on lung tissue. Thus, the role of infection in myasthenia gravis is obvious.

The relevance of the problem of the development of bronchopulmonary diseases is also associated with the complexity of treating such complications in patients with myasthenia gravis. Some drugs that are used in standard practice in the treatment of concomitant diseases (curare-like drugs, D-penicillamine, interferon-alpha, magnesium salts, beta blockers, calcium channel blockers, etc.) are contraindicated in myasthenia gravis due to their inhibitory effects on neuromuscular conduction. Drugs that are absolutely contraindicated for myasthenia gravis also include some antibiotics: aminoglycosides, macrolides, fluoroquinolones. This imposes certain restrictions in these patients on the treatment of infectious complications (IO), as noted earlier, so often manifested in the respiratory system.

Thus, due to the complexity of treating IO in patients with myasthenia gravis, there is a need to search for new approaches in the treatment of this group of patients. Unfortunately, when preparing the materials, no English-language literature on this issue was found.

The purpose of this study was to study the microbiological landscape of sputum, tracheobronchial secretions and evaluate the clinical effectiveness of antibiotic and immunotherapy in patients with infectious and inflammatory diseases associated with myasthenia gravis.

Materials and research methods

The study group consisted of 19 patients with a generalized form of myasthenia (6 men, 13 women; patient age ranged from 22 to 81 years); of which 3 men, 7 women - with exacerbation of chronic tracheobronchitis, 3 men, 1 woman - with residual signs of hospital-acquired pneumonia; 2 women - with chronic obstructive bronchitis; 1 woman - with Lambert-Eaton syndrome; 2 women with bacterial focal pneumonia (one of them had a history of thymectomy). Clinical signs of exacerbation of the infectious process were as follows: cough with mucopurulent sputum, increased production, shortness of breath, fatigue, and some patients had low-grade fever. Before starting treatment, a standard clinical and laboratory study was carried out, a study of the bacteriological composition of sputum, secretions from the trachea (or tracheostomy), studies of external respiratory function (RPF), radiography or computed tomography (CT) of the chest.

Samples obtained from patients were delivered within 2 hours to the bacteriological laboratory, where smear microscopy was performed to assess the quality of the biomaterial and cultured on standard nutrient media. Sputum samples were considered acceptable if the white blood cell count was greater than 25 and the epithelial cell count was less than 10 per field of view. When inoculating the isolated pathogens, species identification was carried out (BBL Crystal test systems). The antibiotic sensitivity of microorganisms was determined by the agar diffusion method.

The severity of the condition and the difficulty of treating patients are due to immunodeficiency and iatrogenicity. Thus, one patient had tracheal stenosis, which developed as a result of prolonged artificial ventilation performed in connection with myasthenic crisis. Another patient had tongue cancer, and therefore the patient underwent an open tracheostomy. In these cases, the situation worsens: immunological protection is reduced, the evacuation of tracheobronchial secretions is disrupted, which contributes to the colonization of nosocomial resistant strains of microorganisms and the development of purulent-infectious complications. And in another patient, the severity of the condition was aggravated directly by taking the anticholinesterase drug pyridostigmine (Kalimin), prescribed for myasthenia gravis. While taking pyridostigmine, the patient's sputum production increased to 300 ml/day. In this regard, the patient was forced to stop taking the drug and independently carry out positional morning drainage.

The auscultatory picture was scanty: vesicular breathing, weakened in the lower lateral parts of the lungs, local wet and scattered dry rales, respiratory rate at rest 18-20 per minute.

When examining the respiratory function, ventilation disorders were revealed. The decrease in FEV 1 averaged from 60% to 49%.

As antibiotic therapy, all patients received cefoperazone/sulbactam intravenously or intramuscularly at a dose of 1.0 g 2 times a day. The duration of therapy was 7-10 days (depending on the degree of activity of the infectious process). In order to improve the rheological properties of sputum, all patients were prescribed mucolytics (acetylcysteine ​​(Fluimucil) 300 mg 2 times a day) through a nebulizer or per os.

Human intravenous immunoglobulin G (IVIG: Octagam, Biaven V.I., Octaglobin) was included in the immunoreplacement treatment program. Treatment was carried out against the background of basic basic therapy, including methylprednisolone, pyridostigmine and potassium chloride.

It seems important to us to describe the clinical case in this study. A 74-year-old patient was diagnosed with “generalized myasthenia gravis” since December 2010. Depending on the severity of the condition, he took 80 and 40 mg of methylprednisolone on an alternating daily regimen. He came in in August 2012 with complaints of severe weakness, fatigue, and increasing shortness of breath with little physical effort. An objective examination of the patient revealed a moderate condition, the skin was without visible pathology, the peripheral lymph nodes were not enlarged, and the feet were pasty. When percussing the chest, a box sound was detected, the excursion on both sides was 3 cm (1.5 + 1.5). On auscultation, breathing in the projection of segments S4-5, S9 on the right was sharply weakened, there were no wheezes, the number of respiratory movements while sitting was 18 per minute. Heart rate - 85 per minute, blood pressure - 130/85 mm Hg. Art., temperature 36.8 °C. Palpation of the abdomen is painless, the abdominal organs are not enlarged. The results of laboratory research are presented in table. 1. On the presented CT images of the chest organs, on the left in the projection of segments S1-2, a cavity formation of irregular shape with uneven, somewhat infiltrated contours is determined against the background of limited pneumofibrosis (Fig. 1). On the left in the projection of segment S9 there is a large infiltrate of a heterogeneous structure (Fig. 2). A diagnostic bronchoscopy was performed: the bronchi were patent, the mucous membrane was pale pink and atrophic. Conclusion: chronic atrophic tracheobronchitis stage II.

So, the patient developed pneumonia with destruction of lung tissue against the background of myasthenia gravis. It was not possible to identify the etiological factor due to the lack of sputum. It is important to note that, against the background of long-term use of high doses of methylprednisolone, the patient developed signs of thrombocytopenia, manifested by skin bruises on the body, and a course of complex antibiotic and immunotherapy was started. Cefoperazone/sulbactam was administered intravenously for 10 days. At the same time, IVIG was administered, the course dose was 15.0 g. The therapy with the inclusion of IVIG allowed us to achieve a faster remission of the infectious-inflammatory process, confirmed by clinical and laboratory data and the results of repeated CT studies of the lungs, where positive dynamics of the pathological process were noted (Table 1) : increase in platelet level - up to 131 × 10 9 / l, decrease in leukocytosis to 15.0 × 10 9 / l, decrease in the level of C-reactive protein - up to 5.0 mg/l.

The patient was consulted by an endocrinologist: there were complaints of back pain when walking and physical activity, a decrease in height by 4 cm over 3 years, a feeling of fatigue in the back while sitting; Upon examination, thoracic kyphosis is determined, the results of laboratory examination are presented in table. 2.

X-ray of the spine in the lateral projection revealed compression fractures of the 1st and 2nd lumbar vertebrae. Dual-energy X-ray absorptiometry: bone mineral density according to the T-criterion in the lumbar spine - 3.0 SD, bone mineral density according to the T-criterion in the femoral neck - 2.0 SD.

Diagnosis: drug-induced (glucocorticoid) osteoporosis with compression fractures of the vertebral bodies. Recommended: a balanced diet with increased consumption of foods rich in calcium and vitamin D, maintaining adequate physical activity and performing exercises with a load corresponding to the state of health; alfacalcidol (Alfa D3-Teva) 0.75 mcg daily, ibandronic acid (Bonviva) 3.0 ml bolus once every 3 months.

Results and discussion

24 samples of sputum and bronchial secretions isolated from patients with bronchopulmonary diseases were studied. The main clinically significant microorganisms were: S. pneumoniae (33,4%), S. aureus (20,8%), S. pyogenes(12.5%) (Fig. 3). Among the non-fermentative gram-negative bacteria there were strains P. aeruginosa(12.5%). An increase in microbial association was observed in four biomaterial samples: P. aeruginosa and mushrooms Candida albicans and in another sample Kl. pneumoniae + S. pneumoniae. Of great interest is the study of the sensitivity of isolated pathogens to cefperazone/sulbactam. It was noted that all strains of microorganisms were included in the antimicrobial spectrum of action of cefoperazone/sulbactam; and only in one sample ( P. aeruginosa + Candida albicans) the antibiotic showed weak activity against the isolated pathogen.

So, a clinical study of sputum in patients with exacerbation of chronic bronchitis and pneumonia against the background of myasthenia gravis revealed the heterogeneity of the microbiological landscape. The leading pathogens were gram-positive pathogens such as S. pneumoniae, S. aureus, S. pyogenes(which amounted to 66.7%). Cefoperazone/sulbactam showed high activity against these strains of microorganisms. At the same time, there was an increase in gram-negative pathogens P. aeruginosa and Kl. pneumoniae(12.5% ​​each, respectively) who were sensitive to cefoperazone/sulbactam. Some gram-negative microorganisms presented associations P. aeruginosa with mushrooms of the genus Candida(4,2%),Kl. pneumoniae with S. pneumoniae(16.7%); in such cases, fungicidal therapy with fluconazole (Diflucan) was prescribed, which significantly improved the course of the disease.

The infectious process of the respiratory tract in this group of patients proceeded torpidly, despite adequate antimicrobial therapy. It is known that with myasthenia gravis there is a general depression of the immune system due to the inhibition of both specific and nonspecific protective factors, which requires correction of immune “breakdowns”.

It is important to note the basic properties of the antibiotic used. Cefoperazone/sulbactam showed activity against both gram-positive and gram-negative microorganisms, including P. aeruginosa. In addition, the antibiotic is stable to the action of beta-lactamases, thanks to an irreversible inhibitor - sulbactam, which synergistically increases the effectiveness of the antibiotic used (the minimum inhibitory concentration of cefoperazone against strains of microorganisms sensitive to it is reduced by up to 4 times). Good tolerance of the drug by patients is of great importance, i.e. the antibiotic does not affect neuromuscular conduction.

So, in addition to detoxification, antibacterial and other types of therapy, IVIG is currently widely used for various localizations of the infectious and inflammatory process. IVIG (Octagam, Biaven V.I., Pentaglobin, etc.) contain a repertoire of antibodies that can inactivate a wide range of antigens. Immunoglobulins are a factor of acquired immunity, which opsonizes infectious foci, contributes to the rapid elimination of the bacterial agent and its metabolites, activating a whole cascade of immune reactions.

Conclusion

Many years of experience allow the use of IVIG in the complex treatment of bacterial infections of the respiratory tract. The course of the disease is significantly improved, the recovery time for patients is accelerated, and most importantly, the risk of colonization by resistant strains of microorganisms and, accordingly, the risk of a repeated episode of infection is reduced.

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V. I. Sokolova,Candidate of Medical Sciences
A. G. Sanadze,
D. A. Sychev 1,Doctor of Medical Sciences, Professor
M. B. Babarina, Candidate of Medical Sciences
D. A. Zaikov

GBOU DPO RMAPO Ministry of Health of the Russian Federation, Moscow