Contraindications for myasthenia. Generalized myasthenia gravis: causes of increased muscle fatigue

Description:

Myasthenia gravis is an autoimmune disease that causes a violation of neuromuscular transmission and is manifested by weakness and pathological fatigue of skeletal (striated) muscles. Any muscle of the body can be involved in the process, but there is a tendency to predominantly affect the muscles of the face, lips, eyes, tongue, pharynx and neck.    Neonatal myasthenia gravis is a transient condition observed in infants born to mothers suffering from myasthenia gravis and is caused by the transfer of maternal antibodies to acetylcholine receptors through the placenta.

Symptoms:

Myasthenia gravis is manifested by muscle fatigue with concomitant weakness, especially ophthalmic and ocular muscles, innervated by bulbar nerves. Weakness of the ocular muscles leads to strabismus, unilateral or bilateral ptosis , most pronounced by the end of the day. Weakness of the facial and chewing muscles is often noted. Difficulties in speech and swallowing may be revealed after more or less prolonged talking and eating. Weakness and fatigue of the muscles of the tongue and a nasal tone of the voice are possible. Other striated muscles of the extremities and neck may also be affected, resulting in generalized weakness. Exhaustion of tendon reflexes is determined. With repeated electrical stimulation, pathological muscle fatigue and a pronounced ability to recover after a short rest are revealed. Characterized by lability, dynamism of symptoms with their intensification when reading, fixing the gaze, sometimes general physical activity. Myasthenia can be generalized and local (damage to the muscles of the eyes, pharynx, larynx, facial muscles or muscles of the body). The generalized form may be accompanied by respiratory disorders.
the disease is progressive. Myasthenic episodes (short-term myasthenic disorders and long-term spontaneous remissions) and myasthenic conditions (stable manifestations over a considerable period) are possible. In patients with myasthenia gravis, a sharp deterioration in the condition may occur in the form of a crisis with generalized muscle weakness, oculomotor and bulbar symptoms (aphonia,), respiratory disorders, psychomotor agitation, followed by lethargy, and autonomic disorders. At the same time, acute hypoxia of the brain with a disorder of consciousness develops. Possible death.

Causes of occurrence:

The disease is associated with the formation of antibodies against acetylcholine receptors located on the postsynaptic membrane of the neuromuscular junction. Long-term studies have proven the connection of myasthenia gravis with the thymus gland. Not the last role is played by hereditary factors.

Treatment:

For treatment appoint:

It is aimed at correcting the relative deficiency of acetylcholine and suppressing the autoimmune process. In order to compensate for neuromuscular transmission disorders, anticholinesterase agents are used: prozerin, oksazil, pyridostigmine bromide (mestinone, kalimin, amyridine). It is important to choose the optimal individually compensating dose, depending on the clinical form, severity of symptoms, comorbidities, response to the drug. In the pharyngeal-facial and ocular forms of myasthenia gravis, pyridostigmine bromide, prozerin and oxazil are more effective. Doses of drugs and intervals of administration are individual. Prescribe potassium chloride or orotate, veroshpiron, ephedrine. In severe cases, prozerin is administered parenterally. Taking large doses of anticholinesterase drugs can lead to a cholinergic crisis. The main methods of treatment for this crisis are the abolition of anticholinergics and the repeated administration of atropine.
In myasthenic crisis, resulting from an insufficient dose of anticholinesterase agents, prozerin is urgently administered intravenously and intramuscularly. Oksazil can be administered in suppositories. Apply also a solution of ephedrine subcutaneously, potassium preparations intravenously. Progressive and life-threatening weakness of the respiratory muscles may occur despite the administration of large amounts of proserin. Patients undergo intubation or tracheostomy, transferred to mechanical ventilation. Patients are fed through a nasogastric tube. It is necessary to maintain the balance of fluid and electrolytes, vitamins; carry out the correction of violations of the acid-base balance.
The main methods of pathogenetic treatment of patients with myasthenia gravis are thymectomy, radiotherapy and hormonal therapy. The surgical method (thymectomy) is indicated for all patients under the age of 60 suffering from myasthenia gravis, but in a satisfactory condition. It is absolutely indicated for tumors of the thymus gland. X-ray therapy on the area of ​​this gland is prescribed after an incomplete thymectomy, with an ocular form of myasthenia gravis, and also if there are contraindications to surgery in elderly patients with a generalized form of myasthenia gravis. In severe cases - with generalized myasthenia gravis - treatment with immunosuppressive drugs is indicated. Assign corticosteroids, the duration of the maximum dose of corticosteroids is limited to the onset of a significant improvement, which allows you to subsequently reduce the dose to maintenance.

Symptomatic treatment of myasthenia gravis - the use of anticholinesterase drugs

Anticholinesterase drugs (ACEPs) used for ophthalmic and generalized form of myasthenia gravis. This is the most commonly used class of drugs for this disease. Their mechanism of action is associated with the blockade of the cholinesterase enzyme in the synaptic cleft. As a result, there is a “prolongation” of the effect of the acetylcholine molecule on the cholinergic receptors of the postsynaptic membrane.

Pyridostigmine bromide is most widely used in the form of tablets of 60 mg. Treatment usually begins with 30-60 mg every 8 hours. The dose is increased in stages depending on the patient's condition. The maximum dose is 60-120 mg every 4 hours.

The most common side effects include gastrointestinal disorders: abdominal pain, diarrhea, muscle fasciculations. In high doses, it can provoke a cholinergic crisis.

Immunomodulatory therapy.

Glucocorticoids refer to the drugs of the first line of modulating agents for myasthenia gravis. Glucocorticoids are widely used in the world due to their high efficiency, relative cheapness, and relative safety. The mechanism of the immunomodulatory effect of this class of drugs is not completely clear.

The side effects of corticosteroids are well known and have a clear dose-dependent effect.

Therapy should be prescribed with 10-25 mg of prednisolone every other day, gradually increasing the dose (10 mg per week) until the target dose of 60-80 mg is reached (in one dose every other day). You can use methylprednisolone with the appropriate dose conversion: 5 mg prednisolone = 4 mg methylprednisolone.

If the patient's condition is severe, corticosteroids should be used immediately with high doses daily (along with short-term therapy - plasmapheresis or intravenous immunoglobulin) until the condition stabilizes. After achieving remission (usually after 4 - 16 weeks), the dose of corticosteroids is gradually reduced to maintenance.

Azathioprine- a purine analogue that inhibits the synthesis of nucleic acids (DNA and RNA). Primarily affects proliferating lymphocytes, induces T and B lymphopenia.

It is necessary to start with a dose of 50 mg / day, orally under the control of a clinical analysis of blood and liver function (at the beginning of therapy, these tests should be taken weekly). In the event that the patient tolerates the drug well and there are no negative test results, then after 7-14 days the dosage is increased by 50 mg every 7-14 days until a maximum dose of 2-3 mg / kg of body weight per day is reached (on average - about 150 - 200 mg / day).

The drug is well tolerated and has minor side effects (nausea, skin rashes, lymphopenia, pancytopenia, pancreatitis, etc.).

It should be remembered that the onset of the therapeutic effect can be delayed up to 4-12 months, and the maximum therapeutic effect usually develops after 6-24 months.

Azathioprine should be used as an adjunct to prednisone in patients who are on long-term immunosuppressive therapy. This allows not to increase the dose of corticosteroids and maintain their effectiveness ("sparring effect").

Cyclosporine- a drug with a complex mechanism of action, the end result is the inhibition of activation and proliferation of T-cells.

The development of adverse reactions (headache, arterial hypertension, renal failure, insomnia, tremor, etc.) is dose-dependent.

Cyclosporine is rarely used. Given the spectrum and nature of adverse reactions, it is prescribed only to patients who are insensitive to azathioprine (in combination with glucocorticoids).

At the beginning of therapy, it is prescribed at a dose of 3-5 mg / kg of body weight per day, in two divided doses. The level of cyclosporine in the blood should be measured once a month. Target level is 200-300mcg/mL. At the same time, the concentration of electrolytes in the blood plasma, magnesium and kidneys should be monitored (the amount of creatinine in the blood serum should not exceed more than 1.5 times at the start of treatment).

When treating with cyclosporine, NSAIDs and potassium-sparing diuretics should be avoided. If the patient simultaneously takes corticosteroids with cyclosporine, then their dosage can be reduced, but the complete abolition of prednisolone is often impossible.

Mycophenolate mofetil- a modern drug, the main mechanism of action is the inhibition of B- and T-cell replication. The main side effects include: diarrhea, headache, skin reactions, etc. Studies of the effectiveness of this drug in myasthenia gravis are ongoing.

According to a retrospective analysis, the effectiveness of the drug in standard doses of 2000-3000 mg/day in two divided doses is shown (the initial dose is 500 mg twice a day, the dose is increased to 1000 mg twice a day after 7-14 days from the start of therapy).

When using Mycophenolate mofetil, a clinical blood test is performed monthly. It is believed that the range of side effects of this drug is less than that of cyclosporine, and their effectiveness is comparable.

Cyclophosphamide used as an immunosuppressant in severe immunological diseases. The mechanism of action is based on the inhibition of T and B cells (as well as other actively dividing cells of the body).

Cyclophosphamide is rarely used - with the ineffectiveness of the combined use of corticosteroids and azathioprine or methotrexate, or cyclosporine.

Assign at a dose of 150-200 mg orally (3-5 mg / kg of body weight per day) or 250 mg / day for intravenous administration (with a further switch to tablets).

Approximately 50% of patients experience improvement in 1-2 months after the start of therapeutic therapy.

The use of the drug should be discontinued if severe adverse reactions occur.

Methotrexate inhibits the process of division of actively dividing cells (including T and B cells). Side effects: myelosuppression, mucositis, nausea, alopecia, cystitis, nausea, etc.

Methotrexate should be used as a reserve drug (with the ineffectiveness of first-line therapy - glucocorticoids and azathioprine).

The drug is used in / m at 0.02 - 0.08 mg twice a week for 2 - 4 weeks or / in 25 - 50 mg twice a week.

Rituximab is a monoclonal antibody with high affinity for antigens of CD20 cells. The main side effects include fever, skin rashes, nausea, rarely - bronchospasm, etc. There are reports of the effectiveness of rituximab at a dose of 375 mg / m2 in the form of infusions once a week for 4 weeks, the interval between courses of treatment is 6 months. multicenter studies on the efficacy of rituximab in myasthenia gravis are ongoing.

Short-term therapy - plasmapheresis and intravenous immunoglobulin.

The mechanism of action of intravenous administration of immunoglobulin is based on the neutralization of activated complement, autoantibodies, modulation of pro-inflammatory cytokines, etc. Side effects include: erythematous skin rashes, headache, myalgia, fever, etc.

Immunoglobulin is used at a dose of 2 g / kg of body weight for 3-5 days (usually a dose of 0.4 g / kg of body weight is used 1 time per day for 5 days).

As a result of plasmapheresis, autoantibodies, immune complexes, and inflammatory mediators are removed from the blood plasma of patients.

Plasmapheresis in myasthenia gravis is carried out in a short course (4-5 sessions): in severe forms of the disease, in preparation for surgical treatment, with a rapid increase in symptoms.

Immunoglobulin intravenously for myasthenia gravis is used for the same indications as plasmapheresis. It is believed that the effectiveness of THESE methods is the same.

Surgical treatment - thymectomy

thymectomy- one of the most commonly used methods in the treatment of myasthenia gravis.

Thymectomy is usually performed in the presence of proven thymoma, as well as in patients under the age of 50 - 60 years with generalized myasthenia gravis (without thymoma) when AchR-Ab is detected in them. In the generalized form of myasthenia gravis, patients who do not have AchR-Ab in their blood, but have MuSK-Ab, do not perform thymectomy.

The clinical effect after thymectomy occurs after 6-12 months.

Thus, in recent years, a lot of data has been obtained regarding the pathogenesis of myasthenia gravis.

Modern methods of research allow not only to diagnose, but also to predict the nature of the course of the disease.

Understanding the essence of the disease, the main links of its pathogenesis, knowledge of the arsenal of modern therapeutic agents and algorithms for their use can improve the quality of care for patients with myasthenia gravis.

The list of references is in the editorial

V. M. SHKOLNIK, A. I. KALBUS,
A. N. BARANENKO, A. V. POGORELOV
State Institution "Dnepropetrovsk Medical Academy of the Ministry of Health of Ukraine"

Myasthenia gravis is a chronic neuromuscular disease that manifests itself as a relapsing 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 pronounced paresis of the muscles affected by the pathological process.

Causes

There is no single point of view about the causes of this disease. At different times, hereditary, infectious, autoimmune theories were expressed. There is also a clearly defined relationship 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 getting myasthenia gravis increases significantly with the existing family history. However, in sick people in the same family, the manifestations of myasthenia often vary from minimal (ocular form of myasthenia gravis) to maximally possible (myasthenia gravis).

The disease is quite common, the incidence of myasthenia gravis varies from 5 to 10 people per 100,000 population. Women get sick more often (in a ratio of 2 to 1), the age of the onset of the disease mainly falls on 15-45 years. Cases are described when the disease occurs in children. More often there is early muscle weakness, which resolves within 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 the endocrine organs, systemic diseases of the connective tissue, etc.

Symptoms

Symptoms have a variety of severity, localization, but they can be characterized by one phrase - muscle weakness. Depending on the localization of the process and the severity of the manifestations, several forms of myasthenia gravis are distinguished:

• Eye form.
• Bulbar form.
• Generalized form (myasthenia gravis, Erb-Goldflam disease).
• Malignant fulminant myasthenia gravis.
• myasthenic crisis.

Myasthenia gravis 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 falls in the late afternoon, after visual stress. Double vision and other transient visual disturbances are often noted. If two years after 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 gravis is characterized by the development of weakness of the muscles of the soft palate, tongue, and pharynx. The patient suffers from speech disorders, violations of the act of swallowing. At the same time, the changes dynamically change during the day, with different loads, which distinguishes this form of the disease from the true bulbar syndrome.

The generalized form is a 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 passes to other muscle groups, paresis of the muscles of the limbs begins to appear. The patient's gait is disturbed, facial expressions are distorted. There is a noticeable improvement in the morning, after daytime sleep, after a long rest. The slightest physical exertion sometimes leads to severe weakness.

A malignant type of the course of the disease is present only in the presence of a thymus tumor, often malignant. The disease debuts from the age of about 50 years and within a short period of time (months, and sometimes even weeks), leads to complete disability. At the 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, psychoemotional overstrain, fever, or other causes. Insufficient dosage of drugs in the treatment of the disease can also lead to the development of complications. During a crisis, a pronounced weakness of all muscles, including respiratory ones, develops. The duration of the crisis varies widely and can last as several tens of minutes or hours, as well as weeks, and in some cases even months.

Difference between myasthenic crisis and cholinergic crisis.

Diagnostics

As a rule, the diagnosis of the disease is not difficult, because all the 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:

Eyelid drooping test - there is a characteristic look from under the lowered eyelids, a person can rarely look with his eyes open, the eyelids drop quickly.
Cooling test. It is carried out more often for centuries. A piece of ice is placed on one eyelid, after cooling, an improvement in the work of the eyelid is noted.
Prozerin test. (Then there will be a section in symptoms-syndromes, and check the request) The patient is injected subcutaneously with 2-3 ml of prozerin 0.05% solution. With myasthenia, the function of the affected muscles is practically restored after half an hour. This state sometimes comes to the original not earlier than 2-3 hours.
allows you to identify the characteristic myasthenic reaction of neuromuscular transmission, to identify rapid muscle fatigue during their repeated stimulation.

Treatment

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

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

Treatment of myasthenic crisis should begin with the maintenance of vital functions, gradually moving to a course of plasmapheresis, hormone therapy, clarifying the presence of a thymus 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 an improvement in their condition.

Also, myasthenia therapy should include pure potassium preparations (in no case panangin, because magnesium can lead to worsening of symptoms!), the appointment of potassium-sparing diuretics (veroshpiron), metabolic drugs (riboxin, B vitamins). Reasonable appointment of physiotherapy, special exercise therapy, massage.

List of drugs that can not be used for myasthenia gravis

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

What if pregnancy?

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

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.

Causes

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

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

The main reason for the development of myasthenia gravis is an autoimmune reaction of the body to its own tissues. Such a process can be started:

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 a violation in the contractile function of the muscles. The second form is often a consequence of a thymus tumor. Myasthenia can affect the muscle fibers of any part of the body. The ophthalmic form of the disease is more common. Children rarely suffer from this disease. They account for less than 3% of the total number of patients.

Clinical picture

Whichever muscle group is affected by the disease, patients will notice common symptoms in the affected area:

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

The pathological focus causes discomfort to a person. This defective part does not cope with the tasks assigned to it. Muscles of any part of the body can suffer. But especially often the eyes are involved in the process. This brings the patient a lot of inconvenience. However, rest for the muscles, relieving tension from them, brings relief. But it is short lived.

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:

Diagnostics

In order to fix the fact of the disease, the doctor alone symptoms are not enough. Any study of the 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 appoints him 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;
• proserin test;
• Biochemical blood test;
• Immunograms;

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

• Needle electromyography;
• Study of the conductive functions of nerve fibers;
• Electromyography of certain muscles - jitter.

Treatment

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

• Forms of the disease;
• The patient's condition;
• Associated pathologies;
• The prevalence of the process.

Medical treatment is standard. However, in some cases, surgery is recommended. Autoimmune processes in the thymus can cause thymectomy surgery. Among effective medicines, Prozerin, Kalinin and preparations with a high content of potassium are known. They also prescribe medications that stimulate the immune system.

Symptomatic treatment that alleviates the patient's condition includes the following drugs:

• Anticholinesterase - "Ipigrix";
• Cytostatics;
• Glucocorticoids - "Prednisolone", "Metipred";
• Immunoglobulins.

In the case of rapidly progressive changes, extracorporeal hemocorrection is prescribed - a method that helps to purify the patient's blood from antibodies against its own tissues. Even the first treatment gives people a chance to feel the 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, influencing with the help of low temperature. Such treatment is carried out in a course for 5-7 days in a row. The method of cascade plasma filtration is widely used. This procedure is carried out with the help of nano cleaners. They purify the blood and then return it to the patient.

Another modern method of treating myasthenia is extracorporeal immunopharmacotherapy. It involves the extraction of lymphocytes from the patient, their drug treatment and subsequent shipment to the blood system. Using this technique, it was possible to cause a stable remission in patients during the year. It is especially important to follow the recommendations of the doctor, since with myasthenia gravis there are 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 her that the process of myasthenia begins, and then spreads to other organs. The main symptoms that patients note:

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

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

bulbar form

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

• Dysphonia - a disorder of the voice function;
• Dysphagia - a violation of swallowing;
• Dysarthria - disorganization in the work of the muscular apparatus of the pharynx, larynx, and also the soft palate.

The described symptomatic manifestations entail dangerous consequences. Dysphagia may progress to complete inability to swallow. The list of foodstuffs for such patients is extremely poor. Food is prescribed by a doctor. Patients have to be fed through a tube, they lose weight and weaken. This means that their general condition worsens, which does not contribute to recovery.

Disorder of voice formation reduces the social sphere of life of patients. And dysatria can be fatal due to respiratory disorders caused by paresis of the vocal cords that close 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 invariably causes up to 1% of deaths among patients with this pathological process. The generalized form captures a large number of muscles, including respiratory ones - this can cause failure and death if no help is 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 not uncommon in patients, they, as a rule, arise and end abruptly. Therefore, myasthenic episodes and conditions are distinguished.

The first one starts and ends quickly. The second is a continuous 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 curariform;
• Antipsychotics, tranquilizers and drugs that enhance their action - "Gidazepam", "Corvalcaps";
• Diuretics, with the exception of Veroshpiron and Spironolactones;
• The use of some antibiotics by the type of aminoglycosides - "Gentamicin" and "Streptomycin", fluoroquinolones - "Enoxacin" and "Ciprofloxacin";
• Vaccinations.

Contraindicated drugs for myasthenia gravis should not be ignored. There are tables and lists of medicines that answer the question "What antibiotics can be used for myasthenia gravis?". You should avoid drugs that have this disease on the list of complications. These drugs include "Glutalit". So the use of these tablets is a contraindication. Compliance with the doctor's prescriptions is the key to a favorable course of the disease.

umozg.ru

Principles of treatment of bronchopulmonary infection in patients with myasthenia gravis

Myasthenia is a classic autoimmune disease, which is based on an autoimmune process directed against the acetylcholine receptor on 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 localization. At present, great progress has been made in the study of 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 the complete cure of this disease. The outcome of the development 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 non-excitability 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, is expressed by varying degrees of respiratory failure. These changes lead to a violation of the ventilation function of the lungs, causing congestion, which are "favorable" for the development of an infectious-inflammatory process. In a study conducted at the Johns Hopkins University Hospital from 1990-1998, it was shown that 46% of patients experiencing some kind of respiratory disturbance on the background of myasthenia gravis develop 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, the treatment of myasthenia gravis is aimed at suppressing the activity of the autoimmune process, which is carried out by suppressing the overall immune response of the body. The methods of treatment of myasthenia gravis include the use of pulse therapy with glucocorticosteroids, the use of cytotoxic immunosuppressants (azathioprine, cyclophosphamide), thymectomy. The listed methods of treatment in connection with suppression of immunity create an additional background for the development of bacterial complications. It is important to note that for some drugs, such as Cyclophosphamide, a direct toxic effect on lung tissue has been noted. Thus, the role of infection in myasthenia gravis is clear.

The urgency of the problem of the development of bronchopulmonary diseases is also associated with the complexity of the treatment of 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 due to their inhibitory effect on neuromuscular conduction. The drugs that are absolutely contraindicated in myasthenia gravis also include some antibiotics: aminoglycosides, macrolides, fluoroquinolones. This imposes certain restrictions in these patients on the treatment of infectious complications (AI), as noted earlier, which are so often manifested by the respiratory system.

Thus, due to the complexity of the treatment of IO in patients with myasthenia gravis, it becomes necessary to search for new approaches in the treatment of this group of patients. Unfortunately, during the preparation of the materials, no English-language literature on this problem was found.

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

Materials and methods of research

The study group consisted of 19 patients with a generalized form of myasthenia gravis (6 men, 13 women; the age of the patients ranged from 22 to 81 years); of these, 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 an exacerbation of the infectious process were as follows: cough with mucopurulent sputum, an increase in its production, shortness of breath, fatigue, some patients had subfebrile condition. Before the start of treatment, a conventional clinical and laboratory study was performed, the study of the bacteriological composition of sputum, secretion from the trachea (or tracheostomy), studies of respiratory function (EPF), X-ray 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 seeded on standard nutrient media. Sputum samples were considered acceptable if the leukocyte count was greater than 25 and the epithelial cell count was less than 10 per field of view. When sowing isolated pathogens, species identification was performed (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 iatrogenesis. Thus, one patient had tracheal stenosis, which developed as a result of prolonged artificial ventilation of the lungs, carried out in connection with a myasthenic crisis. Another patient had cancer of the tongue, in connection with which the patient underwent an open tracheostomy. In these cases, the situation is aggravated: immunological protection is reduced, tracheobronchial secretion evacuation is disrupted, which contributes to colonization by 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 increased sputum production up to 300 ml/day. In this regard, the patient was forced to stop taking the drug and independently conduct positional morning drainage.

The auscultatory picture was poor: 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.

Examination of respiratory function revealed ventilation disorders. The decrease in FEV1 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 r / day) through a nebulizer or per os.

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

We consider it important to describe the clinical case in this study. A 74-year-old patient was diagnosed with generalized myasthenia gravis since December 2010. According to the severity of the condition, he took 80 and 40 mg of methylprednisolone according to an alternating daily regimen. He applied in August 2012 with complaints of severe weakness, fatigue, increasing shortness of breath with little physical effort. An objective examination of the patient noted a state of moderate severity, skin without visible pathology, peripheral lymph nodes are not enlarged, the feet are pasty. During percussion of the chest, a box sound was determined, 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 wheezing, 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. In the presented CT images of the chest organs on the left in the projection of segments S1–2, an irregularly shaped cavity formation with uneven, somewhat infiltrated contours against the background of limited pneumofibrosis is determined (Fig. 1). On the left, in the projection of the S9 segment, there is a large infiltrate of an inhomogeneous structure (Fig. 2). A diagnostic bronchoscopy was performed: the bronchi are patent, the mucosa is pale pink, atrophic. Conclusion: chronic atrophic tracheobronchitis II st.

So, a patient against the background of myasthenia gravis developed pneumonia with destruction of lung tissue. The etiological factor could not be identified 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. IVIG was administered at the same time, the course dose was 15.0 g. The therapy with the inclusion of IVIG allowed to achieve a faster remission of the infectious and inflammatory process, confirmed by clinical and laboratory data and the results of repeated CT scans of the lungs, where a positive dynamics of the pathological process was noted (Table 1) : an increase in platelet levels - up to 131 × 109/l, a decrease in leukocytosis to 15.0 × 109/l, a decrease in the level of C-reactive protein - up to 5.0 mg/l.

The patient was consulted by an endocrinologist: there are complaints of back pain when walking and physical exertion, a decrease in height by 4 cm over 3 years, a feeling of fatigue in the back while sitting; on examination, thoracic kyphosis is determined, the results of a 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 an increase in the intake of foods rich in calcium and vitamin D, maintaining adequate physical activity and exercising with a load corresponding to the state of health; alfacalcidol (Alpha D3-Teva) 0.75 mcg daily, ibandronic acid (Bonviva) 3.0 ml bolus once every 3 months.

Results and discussion

We studied 24 samples of sputum and bronchial secretions isolated from patients with bronchopulmonary diseases. The main clinically significant microorganisms were: S. pneumoniae (33.4%), S. aureus (20.8%), S. pyogenes (12.5%) (Fig. 3). Among the non-fermenting gram-negative bacteria were strains of P. aeruginosa (12.5%). In four biomaterial samples, the growth of microbial association was observed: P. aeruginosa and Candida albicans fungi, 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) did the antibiotic show 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. Gram-positive pathogens such as S. pneumoniae, S. aureus, S. pyogenes were the leading pathogens (which accounted for 66.7%). Cefoperazone/sulbactam showed high activity against these strains of microorganisms. At the same time, the growth of gram-negative pathogens P. aeruginosa and Kl. pneumoniae (12.5% ​​each, respectively), which were sensitive to cefoperazone/sulbactam. Some Gram-negative microorganisms were associations of P. aeruginosa with fungi 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 was torpid, despite adequate antimicrobial therapy. It is known that in myasthenia there is a general depression of the immune system due to the inhibition of both specific and nonspecific defense factors, which requires the correction of immune "breakdowns".

It is important to note the main properties of the used antibiotic. Cefoperazone/sulbactam has shown 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 in relation to sensitive strains of microorganisms decreases up to 4 times). Of great importance is the good tolerability of the drug by patients, 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 capable of inactivating a wide range of antigens. Immunoglobulins are a factor in acquired immunity that opsonize infectious foci, promote rapid elimination of the bacterial agent and its metabolites, activating a whole cascade of immune responses.

Conclusion

Many years of experience allows IVIG to be used in the complex therapy of bacterial infections of the respiratory tract. The course of the disease is significantly improved, the terms of treatment of patients are 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.

Literature

1. Sanadze A. G. Myasthenia gravis and myasthenic syndromes. 2012, p. 252.
2. Shcherbakova N. I. Pathogenetic rationale for the strategy and tactics of treating myasthenia gravis (Abstract of a doctoral dissertation). 2007, p. 3–50.
3. Varelas P. N., Chua H. C., Natterman J., Barmadia L., Zimmerman P., Yahia A., Ulatowski J., Bhardwaj A., Williams M. A., Hanley D. F. Ventilatory care in myasthenia gravis crisis: assessing the baseline adverse event rate // Crit Care Med. Dec 2002; 30(12): 2663–2668.
4. Sulkowski S., Sulkowska M. Alveolar cells in cyclophosphamide-induced lung injury. II. Pathogenesis of experimental endogenous lipid pneumonia // Histol Histopathol. 1999, Oct; 14(4): 1145–1152.
5. Sanadze A. G., Sokolova V. I., Shcherbakova N. I., Nikiforuk N. M. Efficiency of using minimal doses of immunoglobulin in the treatment of severe myasthenia gravis complicated by abscessing pneumonia // Topical issues of clinical transport medicine. 2001, v. 6: p. 280–286.
6. Skeie G. O. et al. Guidelines for treatment of autoimmune neuromuscular transmission disorders // Journal of Neurology. 2010, 17: 893–902.
7. Serrano M. C., Rabinstein A. A. Causes and outcomes of acute neuromuscular respiratory failure. Arch Neurol. Sep. 2010 Vol. 67 (No. 9): 1089–1092.
8. Latysheva E. A., Latysheva T. V. The use of intravenous immunoglobulins in intensive care // General Reanimatology. 2012, VIII; 3:45–49.

V. I. Sokolova, Candidate of Medical Sciences A. G. Sanadze, Doctor of Medical Sciences, Professor D. A. Sychev1, Doctor of Medical Sciences, Professor M. B. Babarina, Candidate of Medical Sciences D. A. Zaikov

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

www.lvrach.ru

Generalized myasthenia gravis: causes of increased muscle fatigue

Myasthenia gravis is a severe autoimmune pathology accompanied by progressive muscle weakness. In this case, only striated muscle fibers are affected. Cardiac and smooth muscles remain normal. When identifying the first symptoms of such a disease, you should immediately contact a specialist.

Severe weakness is the main symptom of myasthenia

Reasons for development

This disease was first described by the British physician Thomas Willis in the second half of the 17th century. At present, the exact reasons for its development are already known. Myasthenia gravis is formed when the body's immune system begins to produce antibodies to its own acetylcholine receptors in the postsyoptic membrane of the neuromuscular junctions. It is thanks to such synapses that the transmission of nerve impulses to the striated muscles occurs.

With myasthenia, the activity of synapses that transmit nerve impulses to striated muscles is disrupted.

Any infectious disease of the upper respiratory tract, severe stress, as well as disruption of the nervous system can become a triggering factor in the development of an autoimmune reaction.

Another cause of this disease can be biochemical changes in the work of neuromuscular synapses. This can occur against the background of a violation of the activity of the hypothalamus and thymus gland.

All the reasons described above contribute to insufficient production or excessively rapid destruction of acetylcholine, due to which the transmission of a nerve impulse to a striated muscle cell is carried out.

Thymus dysfunction can lead to the development of myasthenia gravis

Note. Striated muscle fibers differ from smooth and cardiac muscles in that a person controls their activity independently.

To date, it has been established that myasthenia gravis is not inherited. It is more often formed in young women (20-40 years). The prevalence of this pathology is approximately 5 cases per 100,000 people.

Clinical picture

Currently, there are several types of this disease. Each of them manifests itself with its own symptoms. The main forms of pathology are:

• bulbar myasthenia gravis;
• myasthenia gravis;
• generalized myasthenia gravis.

The most mild is the ocular form of the disease. It is characterized by the following clinical manifestations:

1. Omission of the eyelid on one side (this is the initial sign, which is later also characteristic of the second century).
2. With active blinking, the eyelid begins to fall even lower.
3. As a result of the "hanging" of one of the eyelids, double vision occurs.

This course of the disease is quite rare. More frequent is the bulbar form of myasthenia gravis. It will be characterized by the following clinical picture:

1. The patient gets tired quickly when eating for a long time.
2. At the same time, his voice becomes hoarse, nasal. In the future, it becomes difficult for him to pronounce the letters "s", "p" and "sh".
3. If food intake is not stopped in a timely manner, then a person loses the ability to swallow, and his speech can become almost silent.

With the bulbar and generalized form of myasthenia gravis, the patient has a number of characteristic external signs

Note. Patients with bulbar disorders in myasthenia tend to eat at the peak of drug action.

The most common is the generalized form of myasthenia gravis. This pathology implies the presence of the following symptoms:

1. The disease initially affects the oculomotor muscles and only then the striated muscle fibers of other localizations are involved in the pathological process.
2. The patient becomes amicable.
3. He has a hard time keeping his head straight.
4. There is salivation from the mouth.
5. In the future, the patient becomes difficult to walk for a long time. Over time, this symptom gets worse. It becomes difficult for a person to even get up and serve himself.
6. Over time, muscle hypotrophy occurs, which is especially pronounced in the limbs.
7. Decreased tendon reflexes.

Important! A feature of myasthenia gravis is the fact that after a sufficiently long rest or sleep, all these symptoms become less pronounced and the person feels much better.

During sleep and rest, the stores of acetylcholine in the synapses are restored and the patient feels better.

Features of diagnostics

In the event that characteristic manifestations of myasthenia gravis occur, it is necessary to consult a neurologist for a consultation. This doctor knows exactly what kind of disease it is and how to confirm or deny its presence. Diagnosis of myasthenia gravis includes the following steps:

1. Questioning the patient (not only the main complaints are clarified, but also all the circumstances that preceded the development of the pathology).
2. Clinical examination.
3. Carrying out functional tests to clarify the presence of rapid muscle fatigue (for example, the patient is asked to blink quickly).
4. Electromyographic study.
5. Carrying out a proserine test.
6. Repeated electromyographic study (performed in order to clarify how muscle activity was affected by the proserine test).
7. Repeated clinical examination (it is carried out in order to determine the degree of influence of the prozerin test on muscle activity).
8. Blood test for the presence of antibodies to acetylcholine receptors and titin.
9. Computed tomography of the thymus.

Diagnosis of myasthenia involves the use of modern advances in medicine

After carrying out all these diagnostic measures, the doctor either establishes a diagnosis or refutes it.

Note. In some cases, fewer diagnostic measures are performed, especially when there is a pronounced clinical picture of myasthenia gravis.

Treatment

If the diagnosis of myasthenia gravis has confirmed the presence of this serious disease, then its therapy should be started as early as possible. From the speed of initiation of treatment of myasthenia gravis will depend on its further course and the degree of limitation of physical capabilities.

eye shape

In mild cases, when there is an ocular form of the disease, the use of the following drugs is required:

• kalimin or prozerin;
• potassium chloride.

Important! The selection of the dosage of these drugs is most often carried out in stationary conditions. This is due to the fact that severe complications can develop in case of an overdose. At their initial manifestations, it is necessary to administer an antidote (in this case, atropine).

After selecting the necessary doses of kalimina or prozerin, as well as potassium chloride, the patient is discharged from the hospital. Further treatment and prognosis will have a clear relationship. The more accurately the patient follows the recommendations of a specialist, the higher his quality of life and the lower the risk of developing major complications.

With myasthenia gravis, the patient has to take a large number of drugs

bulbar form

With the bulbar form, the treatment of myasthenia gravis has to be supplemented with glucocorticosteroids. These drugs have their own side effects in the form of increased blood pressure and glucose metabolism disorders, but often they are the only ones that save a person from severe muscle weakness.

Most often, the tablet drug "Prednisolone" or "Methylprednisolone" is used. Take them every other day in the morning. The dose of such drugs is selected at the rate of 1 mg / 1 kg of human weight.

Note. The minimum dose of prednisolone that can have a therapeutic effect is 50 mg every other day. As a result, patients have to use at least 10 tablets at the same time, which, of course, often causes some difficulties.

Take glucocorticosteroids in such dosages should be for at least 1-2 months. In the future, there is a gradual decrease in the dose of prednisolone. It cannot be completely cancelled. For a normal state, patients have to take 10-20 mg of such a drug every other day. At the same time, it is imperative to control those negative effects that occur with the systematic use of such drugs. The local general practitioner will prescribe additional drugs to the patient for these purposes.

Advice! With the development of side effects while taking glucocorticosteroids, you should not independently adjust their dose. Only a doctor can do this correctly.

If taking glucocorticosteroids is contraindicated (for example, in old age), then the patient is recommended to use cytostatic drugs. Usually the initial remedy here is the medicine "Azathioprine". If its effectiveness is insufficient, then stronger cytostatics are prescribed.

With a generalized form of the disease, it is important to remove the thymus gland in a timely manner

Generalized form

The causes and symptoms of myasthenia gravis of a generalized form require more serious therapeutic measures. Within 1-2 years after the diagnosis is established, the patient undergoes a surgical operation to remove the thymus gland. Most often, the clinical effect of such manipulation appears after 1-12 months. After 1 year, the doctors conduct a second full examination of the patient and clarify how great the benefit of the surgical intervention turned out to be.

In the future, the same drug therapy is carried out as with the ophthalmic and bulbar form.

With a sharp increase in muscle weakness, the patient is prescribed the drug "Immunoglobulin" and plasmapheresis.

What can not be done with myasthenia gravis?

Currently, some contraindications for myasthenia gravis are known. The main ones among them are the following:

1. Serious physical activity.
2. Taking medications containing magnesium.
3. Prolonged exposure to direct sunlight.
4. Taking curare-like muscle relaxants.
5. The use of diuretics (with the exception of Spironolactone).
6. The use of neuroleptics.
7. The use of tranquilizers (with the exception of Grandaxin drugs).
8. Taking most antibiotics from the group of fluoroquinolones and aminoglycosides.
9. The use of drugs that are derivatives of quinine.
10. Use of corticosteroids that contain fluoride.
11. Taking the drug "D-penicillamine".

In addition, the patient will have to follow a certain diet. Proper nutrition with myasthenia gravis practically excludes foods rich in magnesium (flounder, sea bass, shrimp, perch, cod, mackerel, dairy products, white beans, spinach, whole grains, broccoli, blackberries, sesame seeds, raspberries, dried apricots and others).

Myasthenia gravis is not a contraindication to pregnancy

Myasthenia gravis and pregnancy are not mutually exclusive. Modern advances in medicine allow a woman with this disease to bear a full-fledged baby without harming her own health. If there are no obstetric indications, then in such patients delivery is carried out naturally. If present, a caesarean section is performed. In this case, anesthesia for myasthenia gravis in a pregnant woman should be epidural. Such anesthesia will be safer. General anesthesia in patients with myasthenia is tried to be used only when the thymus gland is removed. Breastfeeding is contraindicated in patients with myasthenia gravis.

Important! Neglect of these contraindications can lead to aggravation of the course of the disease.

Myasthenia gravis requires constant monitoring by specialists and the strict implementation of all their recommendations. Only such an approach will allow the patient to make his life as full as possible.

pozhelezam.ru

Myasthenia gravis - what is this disease?

Myasthenia gravis is one of the autoimmune chronic diseases. It is characterized by a decrease in muscle tone and rapid fatigue. The ICD 10 code for this disease is G70, it is in the same group with various disorders of the neuromuscular fibers.

For the first time, this condition was described back in the 17th century, and recently the number of people who have encountered it has been growing. Myasthenia gravis, as this disease is fully called, is more common in women, and develops at the age of 20-30 years, it is very rare in children. If the disease is not treated, it gradually progresses, which over time can lead to the death of the patient.

Causes of the disease

Myasthenia gravis is a poorly understood disease. It is believed that it has a genetic nature. The work of the gene responsible for the work of neuromuscular fibers is disrupted. Normally, these connections, called synapses, transmit impulses from the nerves to the muscles, causing them to contract. This process is regulated by various biochemical reactions involving the mediator acetylcholine and the enzyme chilinesterase.

The pathogenesis of the disease is complex: in some cases, the work of the thymus and hypothalamus, which are responsible for the synthesis of these substances, is disrupted. If too little acetylcholine or too much cholinesterase is produced, nerve impulses are blocked and the muscle cannot perform its functions.

The causes of such a violation are malfunctions of the immune system, when the body produces antibodies to its own cells, destroying acetylcholine. This can happen after a cold or infectious disease, severe stress, hormonal failure or weakening of the body due to overwork.

Signs of the disease

The main symptom of the disease is increased muscle fatigue. In the process of physical work, especially with repetitive movements, muscle weakness gradually increases, which over time can lead to their paresis or paralysis. But after rest, these symptoms of myasthenia gravis disappear, and in the morning, patients feel quite well for several hours. At various stages and forms of the disease, the following symptoms appear:

• double vision;
• ptosis - drooping of the upper eyelid;
• salivation;
• voice change;
• chewing dysfunction, fatigue when eating solid food;
• choking when eating;
• difficulty breathing;
• poor facial expression;
• change in gait;
• weakness of the muscles of the limbs and neck;
• dry skin.

One of the first signs of myasthenia gravis is ptosis - drooping of the upper eyelid.

Forms of myasthenia gravis

This disease develops differently for everyone. Most often, myasthenia gravis begins with weakness of the eye and facial muscles, then this violation passes to the muscles of the neck and trunk. But some people have only some of the symptoms of the disease. Accordingly, there are several types of myasthenia gravis.

1. The ocular form is characterized by damage to the cranial nerves. The first sign of this is the drooping of the upper eyelid, most often on one side first. The patient complains of double vision, difficulty in moving the eyeballs.
2. The bulbar form of myasthenia gravis is a lesion of the chewing and swallowing muscles. In addition to the violation of these functions, the patient's speech changes, the voice becomes quiet, nasal, there are difficulties in pronouncing some sounds, for example, "r" or "b".
3. But most often there is a generalized form of the disease, in which the muscles of the eyes are first affected, then the process spreads to the neck, upper and lower limbs. The hips and muscles of the arms are especially often affected, it is difficult for the patient to climb stairs, to hold objects. The danger of this form of the disease is that weakness extends to the respiratory muscles.

It is very important to make the correct diagnosis in time to start treatment.

How the disease is defined

In addition to patient complaints and history taking, the diagnosis of myasthenia gravis includes various tests, hardware examinations and analyzes.

Electromyography helps to determine muscle response to exercise, while CT or MRI reveals the absence of diseases that could cause similar symptoms. After all, myasthenic syndrome is observed with encephalitis, meningitis, cancer, botulism, thyrotoxicosis. But the difference in this case from myasthenia gravis is that the facial muscles are rarely affected, and during electromyography, there is not a slowdown, but an increase in muscle potential upon repeated stimulation.

It should also be time to distinguish myasthenia gravis from Duchenne muscular dystrophy, although their symptoms are different. Muscular dystrophy occurs mainly in boys and begins in childhood.

Most often, to make a diagnosis, an immunological test is done to determine antibodies to acetylcholine and a proserine test is performed. Its meaning is that after intramuscular injection of 1 ml of Prozerin, the patient's condition improves significantly after 30 minutes, and after 2-3 hours the symptoms return.

A very important method for diagnosing myasthenia gravis are various tests that allow you to identify the degree of muscle weakness, as well as which of them are more affected. Since fatigue increases with repetitive movements, the following tests may be effective:

• if you ask the patient to look to the side or up for at least 30 seconds, ptosis and double vision appear;
• to provoke dysarthria and a decrease in the strength of the voice, you need to ask the patient to read something aloud;
• it is possible to detect weakness of the neck muscles if the patient lies on his back and raises his head, he will not be able to keep it on weight for more than a minute;
• sometimes, with myasthenia gravis, the phenomenon of M. Volker manifests itself - repeatedly squeezing and unclenching the hands causes an increase in ptosis.

Electromyography helps determine muscle response to exercise

Crises in illness

Myasthenia is a chronic disease, it is constantly progressing. If the patient does not receive proper treatment, his condition worsens. A severe form of the disease may be accompanied by the onset of a myasthenic crisis. It is characterized by the fact that the patient experiences a sharp weakness of the muscles responsible for swallowing and the movement of the diaphragm. Because of this, his breathing is difficult, his heartbeat quickens, salivation is often observed. Due to paralysis of the respiratory muscles, the death of the patient may occur.

With an overdose of anticholinesterase drugs, a cholinergic crisis may occur. It is expressed in a slowing of the heartbeat, salivation, convulsions, increased intestinal motility. This condition also threatens the patient's life, so he needs medical help. The anticholinesterase drug must be canceled, and its antitode, the Atropine solution, should be injected intramuscularly.

How to treat the disease

Myasthenia gravis is a serious disease that requires constant medical supervision and treatment. Often it leads to disability of the patient. But the correct treatment of myasthenia gravis helps to achieve long-term remission. The main direction of therapy is the use of drugs that block cholinesterase. The most effective for myasthenia are "Kalimin", "Oksazil", "Proserin", "Galantamine", "Ambenonium". They need to be used for a long time, alternating different means.

Potassium preparations enhance the effect of these drugs and improve muscle contractility, so they are also prescribed, for example, Potassium Normin or Potassium Chloride. The diuretic "Veroshpiron" also helps to enhance the effect of anticholinesterase drugs.

Generalized myasthenia requires more serious treatment. In severe cases, hormonal agents are used. Most often it is "Prednisolone" or a drug based on it "Metipred". Usually prescribed 12-16 tablets per day in the morning every other day. If a stable remission is observed after a couple of months, the dose is gradually reduced.

Recently, myasthenia gravis has also been treated with pulse therapy. This method consists in the fact that high doses of Metipred are administered within 3-5 days. If it was possible to achieve remission, the drug is gradually canceled. But sometimes you have to take it for a long time, often for several years, at 60 mg every other day.

With myasthenia gravis, it is very important to constantly take the drugs prescribed by the doctor.

Cytostatic immunosuppressants are also used to treat such patients. "Azathioprine" is needed to block immunoglobulins and reduce the concentration of antibodies to acetylcholine. "Cyclophosphamide" and "Methotrexate" inhibit their activity. Such therapy is indicated for patients for whom glucocorticoids are contraindicated. But sometimes these drugs alternate.

As adjuvant therapy, agents to improve metabolism in muscle tissue can be used. These are calcium preparations, "Ephedrine", "Methionine", glutamic acid, tocopherol acetate, vitamins of group B. Treatment with folk remedies is not used, since many herbal preparations are contraindicated for patients. Tonic plants are acceptable: ginseng, lemongrass and others on the recommendation of a doctor.

Myasthenic crisis necessarily requires the placement of the patient in a hospital in the department of neurology. There, he undergoes plasmapheresis to cleanse the blood of antibodies and artificial ventilation of the lungs. For a more rapid improvement in the condition, "Prozerin", "Ephedrine" and immunoglobulins are introduced.

In the absence of the effect of conservative therapy and the progressive course of the disease, surgical treatment is used. Thymectomy is the removal of the thymus gland. In 70% of patients after surgery, there is an improvement in the condition. But the difficulty is that anesthesia in this disease has features.

Many drugs are contraindicated in such patients, especially muscle relaxants and tranquilizers, as well as morphine and benzodiazepines. Therefore, the operation is performed in a serious condition of the patient and only in patients younger than 70 years.

It is very important for patients with myasthenia gravis to be careful about the drugs they take, since many of them are contraindicated for them.

Rules of conduct for myasthenia gravis

If the diagnosis is made on time, and the patient fulfills all the doctor's prescriptions, his working capacity and lifestyle hardly change. The treatment of myasthenia gravis consists in the constant use of special drugs and the observance of certain rules.

It is forbidden for such patients to sunbathe, perform heavy physical work and drink medications without a doctor's recommendation. Patients must be aware of the contraindications for myasthenia gravis for taking medications. Many drugs can cause a complication of the course of the disease or the development of a myasthenic crisis. These are such medicines:

• all preparations of magnesium and lithium;
• muscle relaxants, especially curare-like;
• tranquilizers, neuroleptics, barbiturates and benzodiazepines;
• many antibiotics, for example, "Neomycin", "Gentamicin", "Norfloxacin", "Penicillin", "Tetracycline" and others;
• all diuretic drugs, except "Veroshpiron";
• "Lidocaine", "Quinine", oral contraceptives, antacids, some hormones.

Can myasthenia gravis be cured?

Previously, this disease was considered incurable, 30% of cases ended in death. Now the prognosis for myasthenia is more favorable. With the right approach to therapy, more than 80% of patients experience a stable remission. They can continue a normal life and even remain functional. Permanent disability or even death of the patient can occur if the patient does not see a doctor in time or if the prescribed treatment is not followed.

Many people have not even heard of such a disease as myasthenia gravis. Therefore, they do not always seek medical help on time. This is dangerous as it can cause complications. But proper treatment and compliance with all doctor's recommendations will help the patient lead a normal life.

moyaspina.ru

Lactofiltrum while taking antibiotics

The choice of drugs for myasthenia gravis depends on the degree of damage to muscle tissue and the magnitude of the violation of synaptic conduction. The change in ion exchange associated with a lack of potassium also requires a special approach to the selection of drugs for therapy. Apply radical methods of treatment - surgery or irradiation of the thymus gland.

Modern aspects of treatment

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

What painkillers can be used for myasthenia gravis, the doctor determines individually, depending on the stage of the disease. The following drugs are prescribed for treatment:

• Fortalgin;
• Voltaren;
• ibuprofen;
• Ketoprofen;
• Spazmalgon;
• Coldrex;
• Tempalgin.

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

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

• Preductal;
• Mildronate.

Immunosuppressive therapy

For prescribe immunosuppressants:

• 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, fever. A person has 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, vomiting. Many people experience pain in the liver, enzyme activity changes, and signs of cirrhosis appear.

Leucovorin given after Methotrexate therapy reduces its toxicity. A patient suffering from myasthenia is contraindicated in treatment with antipsychotics and tranquilizers.

Medications to reduce muscle tone

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

• Trakrium;
• Esmeron.

Given the contraindications, the doctor tries not to prescribe muscle-relaxing drugs for the treatment of patients, since many patients have increased sensitivity to their action.

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 pronounced increase in the level of potassium in the blood serum and high temperature in the patient.

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

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

Therapy with glucocorticoids

Prednisolone increases the number of cholinergic receptors. After taking it, muscle strength increases. In order to avoid a certain risk 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 carried out for a long time. The intermittent method is very popular, when the patient takes an increased dose of the drug for 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 prednisone. 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, as 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, the patient must follow a special diet. Limit the intake of food containing a large amount of carbohydrates. Regular blood sampling is carried out to determine the level of glucose.

Cholinesterase inhibitors

In a mild form of the disease, the patient is prescribed medicinal substances that prevent the decrease in acetylcholine in the region of the neuromuscular nodes. The use of Prozerin in the treatment of patients with myasthenia gravis provides active muscle stimulation, but large doses of the drug cause impaired 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 drug is well tolerated by patients. The drug has a dual effect, while Prozerin, Oksazil and Kalimin act only on the peripheral nervous system.

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

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

• Panangin;
• Asparkam.

Pathogenetic impact

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

In case of deterioration of the patient's condition, a stepwise scheme of therapy is used, based on increasing the single dose until the maximum allowable amount of the drug is reached at one time. Metipred is a drug with high mineralocorticoid activity, therefore it is more often used for treatment, it stabilizes the patient's condition.

The 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 protective forces of the patient's body. Functional changes in patients with MG reach a significant value. Immunoglobulin administered to the patient does not cause serious side effects. In the treatment of patients, drugs are used:

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

In a crisis, immunoglobulins are prescribed only after urgent resuscitation. 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 work of the patient's immune system, notes the number of T-cells. In the course of the study, defects in immune particles are detected, and in the serum - an increased activity of thymic humoral factors.

The concentration of immunoglobulins reflects the state of internal organs that affect the body's defenses. A normal human protein containing a specific fraction, given in a standard dose for the first time, causes 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 an increase in blood pressure, stop treatment, inject intravenous plasma solution and antihistamines.

In the treatment of myasthenia gravis, cytostatics are used:

• Cyclophosphamide;
• Cyclosporine;
• Cyclophosphamide;

Often, after the effect is achieved, the dose of the drug 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 a patient 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 drugs exacerbate the symptoms of the disease. The following drugs are not recommended for taking:

• Ampicillin;
• Imipenem;
• Erythromycin.

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

Medicines prescribed by a doctor, the patient must take courses, control his well-being and lead a healthy lifestyle.