Myasthenia gravis in a child symptoms. Features of the treatment of myasthenia gravis in childhood

Myasthenia gravis is a serious autoimmune disease that manifests itself as pathological muscle fatigue. The disease occurs more often in young women, but can also manifest between the ages of four and twenty. By what signs can parents suspect something is wrong, how is the treatment of myasthenia gravis in the 21st century and what are the features of the treatment of the disease in children - these and many other questions will be answered by IllnessNews Daria Alexandrovna Vitarigova, pediatric neurologist at the Alfa Health Center clinic.

- Are there hidden forms of myasthenia gravis that are easily confused with ordinary fatigue? What should parents pay attention to, what should alert them - maybe it has become difficult for a child to raise his hands in order to comb his hair, for example? Or does the disease always begin acutely, with a crisis?

– Myasthenia gravis progresses gradually and the onset of the disease can be overlooked. Therefore, parents should pay attention to any inexplicable fatigue, lethargy of the child’s muscles, weakness that sharply increases with repeated movements. These conditions can be symptoms of myasthenia gravis, and it is necessary to consult a specialist to rule out this pathology. However, it is not necessary to sound the alarm because of any fatigue of the child. You need to understand what could lead to fatigue (outdoor games, the onset of SARS). Do not forget that the main indicator that you need to pay attention to is the absence of a cause of weakness and fatigue, increased fatigue with repeated movements, the regularity and persistence of this symptom.

So, what can a parent notice: a kind of “voice attenuation” during a conversation, chewing difficulties (the child may even refuse food), swallowing disorders, food getting into the nose, fatigue during stereotypical movements (this can be combing, climbing stairs, normal walking, the appearance of a shuffling gait), as well as drooping of the eyelids.

There are several simple ways, which will help parents to identify latent myasthenia gravis without resorting to the help of a doctor:

• Rapid opening and closing of the mouth. In a healthy child, this figure will be approximately 100 in 30 seconds, in myasthenic - less.
• In the position on the back, raising the head and holding it for about a minute, the eyes are directed to the stomach. Standing position with outstretched arms - three minutes.
• Rhythmic squeezing and unclenching of the brush - drooping of the eyelids often occurs.

However, the disease can also begin with a crisis. This will manifest itself as a sharp deterioration general condition, sudden muscle weakness up to their paralysis, respiratory failure up to apnea (cessation of breathing), vegetative manifestations. Of course, this condition requires immediate hospitalization of the child in a hospital for specialized treatment.

– What is most important in the diagnosis of myasthenia gravis? The presence of antibodies in the blood serum? Can myasthenia gravis occur without detecting antibodies in the blood?

- To date, there are 4 parameters by which the diagnosis of myasthenia gravis is made:

• clinical,
• pharmacological,
• EMG (electromyographic),
• immunological criteria.

We examined the clinical parameters: fatigue, lethargy, muscle weakness.

Pharmacological – this is the use of proserine samples.

Electromyographic – this is the study of electromyography, an assessment of the state of neuromuscular transmission.

And lastly, these are immunological parameters – the presence in the blood of antibodies against acetylcholine receptors. A concentration indicator of more than 0.40 nmol / l confirms the presence of pathology.

So, the presence of all 4 parameters confirms the diagnosis of myasthenia gravis, 3 criteria – the diagnosis is considered reliable, 2 – probable and finally 1 – dubious.

From this it follows that the diagnosis of myasthenia gravis can be made without the detection of antibodies.

– Does the onset of puberty affect the progression of myasthenia gravis? What are the most likely causes of the onset and progression of myasthenia gravis?

- Quite often, during the puberty, there is a regression of the symptoms of myasthenia gravis, and by the end of puberty, as a rule, persistent remissions are noted.

The onset of the disease can be provoked by severe stress, acute respiratory viral infections, excessive exposure to the sun. Naturally, these conditions are not the causes of myasthenia, because this is an autoimmune pathology, that is, this is a condition when one's own immunity begins to produce antibodies not against foreign proteins (for example, viruses), but against one's own cells.

- If a thymoma is visualized, does it need to be removed or can the selection of medicines be dispensed with?

- If a thymus tumor is detected, experts recommend its removal, because. this can achieve a lasting improvement in the well-being and general condition of the patient, or even remission.

The operation must be carried out as early as possible, because the longer the disease exists, the less effect comes after it.

- For any girl (and after all, autoimmune diseases affect the female sex more often?) A seam along the midline, which will remain for life, will be undesirable. Are more gentle and less traumatic methods of tumor removal possible?

- That's right, myasthenia gravis is more common in females.

To date, a more gentle method of removing thymoma is possible - thoracoscopy. This method has a number of advantages: low trauma, smoother rehabilitation period and a good cosmetic result, which is very important for girls and women. However, this technique can be applied only in the case of small tumor sizes (5-6 cm), with larger sizes, a median sternotomy is required.

– How available in Russia latest technique– robotic thymectomy?

– Robotic thymectomy – this is the latest technology. Robotic surgery is performed using the Da Vinci apparatus. In total, there are 25 of them in Russia and they are located in large cities such as St. Petersburg, Moscow, Yekaterinburg, Novosibirsk, Tyumen, Krasnodar, etc., however, the use of this device abroad is more common, mainly in the USA, Israel, Germany .

The advantages of using robotic technology cannot be underestimated, these are the reduction of complications, high precision of manipulations, shortening of hospital stay, and cosmetic effect.

– One operation will be enough or you will need chemo- or radiation therapy?

– If the tumor is localized, then surgical removal is sufficient, provided that adjacent tissues are not affected by the tumor.

Radiation therapy helps fight inoperable tumors. Radiotherapy can stop its development for many years.

Chemotherapy is used when the tumor has spread to other organs and tissues. The drugs help block the growth and development of abnormal cells.

Children are contraindicated in cytostatic therapy.

– Is it possible for the patient to make a choice of treatment for thymoma: surgery or, for example, radiation therapy.

- The tactics of managing a patient is determined only by the attending physician, after conducting a full examination and determining all the parameters of the pathology, therefore, in different situations treatment will be combined in different ways.

- Do you need the consent of relatives for surgical treatment if the girl is 15 years old, or is she already responsible for her own health? Does she have the right not to tell her parents about the operation?

- From the age of 15, a citizen of the Russian Federation can independently make decisions regarding his health, so tell your parents or not – This is a personal choice of a teenager.

How is myasthenia gravis treated without thymoma?

– Treatment of myasthenia gravis is determined by the doctor and depends on many factors.

In uncomplicated cases, it is sufficient to prescribe only anticholinesterase drugs and potassium preparations.

If there is significant muscle weakness and swallowing problems, glucocorticoids should be given.

If the effectiveness of prednisolone and thymectomy is low, immunosuppressive therapy is used.

In case of exacerbation, the use of plasmapheresis and the appointment of human immunoglobulin have a good effect.

Is the treatment lifelong?

Myasthenia gravis is a chronic, incurable disease. Myasthenia gravis drugs do not have a long-term effect and are effective only when taken regularly. The treatment is lifelong, however, it can improve the patient's condition. Doctors are trying to achieve a stable remission, which will be determined by the absence of disease progression and improvement in general well-being, maximum adaptation of the patient to everyday life.

- Are there any latest methods treatment for thymoma, possibly last years have invented (or are just researching) a completely new group of drugs against this disease?

– The most modern methods of surgical treatment are cyber-knife, brachytherapy (tumor removal using an X-ray beam). It is also used for the treatment of thymoma. photodynamic therapy(exposure to a laser beam that destroys tumor cells). This method used in cases of impossibility of surgical removal of the tumor.

Thanks a lot for the interesting information!

- Good luck to your readers!

Etiology and pathogenesis of myasthenia gravis

Myasthenia Clinic

Diagnostics

Differential Diagnosis

Similar pathological processes

Treatment

Etiology and pathogenesis of myasthenia gravis

Myasthenia gravis (myasthenia; Greek mys - muscle + asthenia impotence; synonym; asthenic bulbar palsy; Erb-Goldflam disease - a severe systemic neuromuscular disease characterized by pathological fatigue and muscle weakness, which is based on the pathology of the synaptic apparatus of the muscles.

The etiology and pathogenesis of myasthenia are not fully understood. Currently, myasthenia gravis is regarded as an autoimmune disease. In the mechanism of pathological muscle fatigue, the main importance is attached to the blockade of postsynaptic acetylcholine receptors of neuromuscular junctions by autoantibodies. This leads to structural changes and death of some of the receptors. Apparently, acetylcholinesterase acquires pathological activity - it quickly destroys acetylcholine, which is necessary for muscle contraction. There is direct immunohistological evidence for the presence of antibodies and complement in the postsynaptic membrane in patients with myasthenia gravis. Evidence has been obtained in favor of a possible role for persistent thymus infection. In particular, an increase in the titer of complement-fixing antibodies to cytomegalovirus was found; in patients successfully treated with thymectomy or steroids, this sign was absent. The possibility of viral antigenic stimulation of the thymus, which induces the formation of antibodies to thymus acetylcholine receptors, which then cross-react with acetylcholine receptors of neuromuscular synapses, is assumed. Apparently, we are talking about a genetically determined or acquired defect in the immunological response, which is also supported by the predominance of the content of the HLA-B8 haptogen in patients with myasthenia gravis.

A frequent combination of myasthenia gravis with thymoma was noted, and mainly in patients aged 50-59 years. In these cases, the disease is characterized by an acute onset and a malignant course, and gives a huge lethality.

Myasthenia Clinic

Myasthenia gravis can occur at any age, but is more common between the ages of 16 and 40. Women get sick 3 times more often than men. The symptomatology of myasthenia gravis is characterized by a combination of muscle weakness and pathological muscle fatigue, leading to paresis or paralysis. The end plates of any muscle can be affected. The external and internal muscles of the eyes are early involved in the process. Appears ptosis of the upper eyelids, often asymmetric and fluctuating in intensity throughout the day. Ptosis intensifies in the evening, with re-closing - opening the eyes and fixing the gaze for a long time. There may be diplopia. Restriction of the movement of the eyeballs develops, which can reach complete external ophthalmoplegia. Less commonly, visual fatigue associated with weakness and fatigue of the muscles that carry out accommodation is detected. Sometimes there is myasthenic nystagmus, which increases after repeated movements of the eyeballs.

Weakness of facial muscles, temporal muscles, masticatory muscles is revealed, which leads to difficulty in chewing, impaired diction and change appearance(facial expression is not very expressive).

As a result of damage to the muscles of the soft palate, pharynx and upper muscles of the esophagus, bulbar syndrome develops - dysphagia, dysarthria, difficulty breathing. The appearance of bulbar symptoms is a poor prognostic sign.

The defeat of the diaphragm or intercostal muscles leads to a violation of breathing until it stops. Exhaustion of contractions of the heart muscle can be observed - from mild disturbances to cardiac arrest. Usually all or most of the striated muscles are affected, but there are also local forms of myasthenia gravis. Weakness of the muscles of the limbs and torso leads to difficulty in climbing stairs, walking, tilting the torso, carrying heavy loads.

When the neck muscles are affected, the symptom “head hanging on the chest” is observed. In 15-20% of patients, mild muscle weight loss is detected.

At severe forms myasthenia gravis, there is an exhaustion of tendon and periosteal reflexes, as well as taste, vision, hearing, and superficial sensitivity. Vegetative-endocrine and electrolyte changes are found. Cooling improves muscle function, warming worsens it.

Clinical classification of myasthenia gravis

I. Generalized forms:

1. neonatal myasthenia gravis

2. congenital myasthenia gravis

a) benign with ophthalmoparesis or ophthalmoplegia;

b) family nursery

3. juvenile myasthenia gravis

4. generalized myasthenia gravis in adults (mild, moderate, severe, late severe, with early development of atrophy)

II. Local forms:

1. eye

2. bulbar

3. cranial

By the nature of the flow:

1. myasthenic episodes

2. myasthenic condition

3. progressive form

4. malignant form

Neonatal myasthenia gravis is a transient condition that occurs in 10-20% of children born to mothers with myasthenia gravis.

Congenital myasthenia gravis is the rarest form.

With benign myasthenia gravis, there is a pronounced symmetrical lesion of the external eye muscles, often accompanied by complete ophthalmoplegia. To a lesser extent, the muscles of the face, limbs and trunk are affected, damage to the bulbar muscles is mild or moderate. The frequency of cases in the family is high, sometimes this form is diagnosed at the age of 30, does not pose a threat to the life of the patient.

In familial myasthenia gravis, there may be severe lesions of the bulbar and respiratory muscles. Ptosis is observed frequently, but the external eye muscles are not involved in the pathological process.

Juvenile myasthenia gravis. The disease begins at the age of more than 1 year, in 75% - older than 10 years. In some patients, the ocular and facial muscles are predominantly affected, while in others the bulbar muscles are affected, generalized muscle weakness is sometimes observed; 40% have respiratory disorders. The most common is eye muscle damage. There may be an acute fulminant course of the disease at the age of 2-10 years. Without timely diagnosis and careful treatment - the prognosis is poor.

Generalized myasthenia gravis in adults is divided into: mild (MGIIa), severe (MGII6), acute fulminant (MGIII), late severe (MGIV), myasthenia gravis with early muscle atrophy. IIa and IIb differ in the absence or presence of damage to the bulbar muscles. With MGIII, the patient rapidly develops severe muscle weakness, bulbar and respiratory disorders. The MGIV group includes patients whose condition deteriorated after staying for 2 years in groups I and IIa.

Myasthenia gravis (MGI) is a non-progressive form affecting only the muscles of the eyes and the muscles of the eyelids. The isolated ocular form does not pose a threat to life and leads to moderate disability. Subsequently, either the disease is limited to damage to the eye muscles, or a generalized form develops.

The bulbar form of myasthenia is characterized by dysphonia, dysphagia and dysarthria, i.e. symptoms associated with the involvement of the musculature of the pharynx, larynx and soft palate.

In the cranial form of myasthenia, masticatory and facial muscles are involved in the process, which leads to dysarthria, lethargy of facial expressions, chewing disorders, while a youthful face and a “growling” smile are characteristic (rises upper lip, the lower one remains stationary).

Myasthenic episodes are rapidly transient, the intervals between them can range from several months to 10 years or more.

The myasthenic state (stationary form) is characterized, as a rule, by the rapid (months) development of the disease and the subsequent long-term non-progressive course.

The progressive form, however, is combined with a relatively benign one, develops and progresses rather slowly, in some cases, progression may stop after some time.

The most severe is the malignant form - with the rapid involvement of more and more new muscles and the aggravation of the condition. Despite treatment, patients are often admitted to the hospital in an extremely serious condition, often requiring resuscitation due to respiratory disorders.

Diagnostics

For myasthenia gravis, the phenomenon of generalization of muscle fatigue is pathognomonic - fatigue of some muscle groups during repeated movements leads to an increase or the appearance of weakness in other muscle groups that were not subjected to direct physical activity. So, with repeated movements of the eyes horizontally, ptosis of the upper eyelids appears or rapidly increases. An early manifestation of myasthenia gravis is selective weakness and fatigue of the flexors and extensors of the IV and V fingers.

Application pharmacological tests is based on the high sensitivity of neuromuscular synapses, characteristic of myasthenia gravis, to the introduction of drugs that improve transmission in synapses (anticholinesterase drugs) or worsen it (curare-like drugs).

Tests with the introduction of anticholinesterase drugs facilitate the transmission of excitation from the nerve to the muscle, which is manifested by an increase in muscle strength and a decrease in muscle fatigue. For the test, 1-2 ml of a 0.05% solution of prozerin is injected subcutaneously or intramuscularly.

A test with the introduction of curare-like drugs is used in unclear cases against the background of the abolition of anticholinesterase drugs. The cuff from the sphygmomanometer is applied at shoulder level and air is injected into it until the pressure rises by 20 mm Hg. above normal systolic. Then, 0.2 mg of D-tubocurarine dissolved in 20 ml of saline is injected into a vein on the hand. Wait 5 minutes, then remove the cuff. The initial strength measured by the dynamometer is compared with the strength of the muscles of the hand 10 and 20 minutes after cuff removal. The test is considered positive if the muscle decreases by more than 2 times.

As a result, pathological fatigue and weakness of the skeletal muscles develop, mutations in the proteins of the neuromuscular junctions can lead to the development of congenital myasthenic syndromes.

What it is?

Myasthenia gravis is a fairly rare autoimmune disease characterized by muscle weakness and lethargy. With myasthenia, there is a violation of the connection between the nerve and muscle tissues.

The official scientific name of this disease is myasthenia gravis pseudoparalitica, which translates into Russian as asthenic bulbar paralysis. In Russian medical terminology, the concept of “myasthenia gravis” is widely used.

Causes of myasthenia gravis

To date, experts do not have clear information about what exactly provokes the onset of symptoms of myasthenia gravis in a person. Myasthenia gravis is an autoimmune disease, because multiple autoantibodies are found in the serum of patients. Doctors record a certain number of family cases of myasthenia gravis, but there is no evidence of the influence of a hereditary factor on the manifestation of the disease.

Quite often, myasthenia manifests itself in parallel with hyperplasia or a tumor of the thymus gland. Also, myasthenic syndrome can occur in patients who complain of organic diseases of the nervous system, polydermatomyositis, and oncological diseases.

More often females suffer from myasthenia gravis. As a rule, the disease manifests itself in people aged 20-30 years. In general, the disease is diagnosed in patients aged 3 to 80 years. In recent years, specialists have shown significant interest in this disease due to the high incidence of myasthenia gravis in children and young people, which leads to subsequent disability. First this disease was described over a century ago.

Pathogenesis

Autoimmune processes play a role in the mechanism of myasthenia development, antibodies have been found in muscle tissue and thymus. The muscles of the eyelids are often affected, ptosis appears, which varies in severity during the day; chewing muscles are affected, swallowing is disturbed, gait changes. It is harmful for patients to be nervous, as it causes chest pain and shortness of breath.

A provoking factor may be stress, acute respiratory viral infections, dysfunction immune system The organism leads to the formation of antibodies against the body's own cells - against the acetylcholine receptors of the postsynaptic membrane of the neuromuscular junctions (synapses). Autoimmune myasthenia gravis is not inherited.

Most often, the disease manifests itself during transitional age in girls (11-13 years old), less common in boys at the same age. Increasingly, the disease is detected in preschool children (5-7 years).

Classification

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 omission upper eyelid usually 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.

Symptoms

Unfortunately, most often myasthenia gravis is diagnosed already in those cases when the disease has been going on for several years in a row and goes into a neglected form. For this reason, any inexplicable fatigue, muscle flaccidity, weakness that increases sharply with repetitive movements must be regarded as a possible symptom of myasthenia gravis until this diagnosis is completely refuted.

Early symptoms include:

• swallowing disorder,
• difficulty chewing solid food up to refusal to eat,
• when talking - "attenuation of the voice",
• fatigue when combing, climbing stairs, normal walking,
• the appearance of a shuffling gait,
• drooping eyelids.

The most commonly affected are the oculomotor, facial, chewing muscles, as well as the muscles of the larynx and pharynx. The following tests help identify latent myasthenia gravis:

• If the patient is asked to quickly open and close his mouth within 30 seconds, then healthy man will make about 100 movements, and those suffering from myasthenia gravis - less.
• Lie on your back, raise your head and hold it in this position for 1 minute, while looking at your stomach.
• Stretch your arms and stand like this for 3 minutes.
• Do 15-20 deep squats.
• Quickly squeeze and unclench the hands - in a patient with myasthenia gravis, this often causes drooping of the eyelids.

The local form of myasthenia gravis is characterized by the manifestation of muscle weakness of a certain group of muscles, and in the generalized form, the muscles of the trunk or limbs are involved in the process.

myasthenic crisis

As shows clinical practice, myasthenia gravis is a progressive disease, which means that under the influence of certain factors of paralysis (external environment or endogenous causes), the degree and severity of symptomatic manifestations of the disease may increase. And even in patients with mild form myasthenia gravis, a myasthenic crisis can occur.

This condition may be caused by:

• trauma;
• stressful conditions:
• any acute infections;
• reception medical preparations with neuroleptic or tranquilizing effect;
• surgical interventions in the body, etc.

Symptoms are manifested by the fact that at first double vision appears. Then the patient feels a suddenly increasing attack of muscle weakness, the motor activity of the muscles of the larynx decreases, which leads to disruption of the processes:

• voice formation;
• breathing and swallowing;
• increased salivation and increased heart rate;
• pupils may dilate, tachycardia may occur, and complete paralysis may occur without loss of sensation.

Development acute insufficiency oxygen supply to the brain can lead to a direct threat to life, so resuscitation is urgently needed.

Diagnostics

In order to make a correct diagnosis, the patient is prescribed a comprehensive study, since the clinical picture of myasthenia gravis may be similar to other diseases. The main diagnostic methods are:

1. Detailed biochemical blood tests for the detection of antibodies;
2. Electromyography is a study during which it is possible to assess the potential of muscle fibers when they are excited;
3. Genetic screening, which is carried out to identify the congenital form of myasthenia gravis;
4. Electroneurography is a study that allows you to evaluate the speed of transmission of nerve impulses to muscle fibers;
5. MRI - using this study you can notice even the most insignificant signs of thymus hyperplasia;
6. Test for muscle fatigue - the patient is asked to quickly open and close his mouth several times, wave his arms and legs, squeeze and unclench his hands, squat. The main syndrome of myasthenia gravis is the appearance of increasing muscle weakness with the repetition of these movements.
7. Prozerin test - the patient is injected subcutaneously with prozerin, after which they wait up to half an hour, and then evaluate the result. A patient with myasthenia gravis feels a significant improvement in his condition, and after a few hours clinical symptoms resumed with the same strength.

How to treat myasthenia gravis?

In severe myasthenia gravis, removal of the thymus gland during surgery is indicated. The most effective medicines that are successfully used to relieve the symptoms of the disease include prozerin and kalinin. Along with them, they use medicines that increase immunity, and a number of other medicines that improve the patient's well-being. It is important to remember that the earlier treatment is started, the more effective it will be.

At the first stage of the disease, anticholinesterase drugs, cytostatics, glucocorticoids and immunoglobulins are used as symptomatic therapy. If the cause of myasthenia is a tumor, then an operation is performed to remove it. In cases where the symptoms of myasthenia are rapidly progressing, extracorporeal hemocorrection is indicated, which makes it possible to purify the blood from antibodies. Already after the first procedure, the patient notes an improvement in the condition, for a more lasting effect, the treatment is carried out for several days.

To the new effective methods treatment includes cryophoresis - blood purification from harmful substances under the influence of low temperatures. The procedure is carried out in a course (5-7 days). The advantages of cryophoresis over plasmaphoresis are obvious: in the plasma that is returned to the patient after cleaning, all useful material unchanged, which helps to avoid allergic reactions and viral infection.

Also, new methods of hemocorrection used in the treatment of myasthenia gravis include cascade plasma filtration, in which purified blood, after passing through nanofilters, returns to the patient. Already after the first minutes of the procedure, the patient notes an improvement in well-being, a full course of treatment for myasthenia gravis requires five to seven days.

Extracorporeal immunopharmacotherapy also belongs to modern methods of treating myasthenia gravis. As part of the procedure, lymphocytes are isolated from the patient's blood, which are treated with medicines and sent back to the patient's bloodstream. This procedure in the treatment of myasthenia gravis is considered the most effective. It allows you to reduce the activity of the immune system, reducing the production of lymphocytes and antibodies. This technique gives a stable remission within a year.

Prevention of myasthenia gravis and its complications

It is impossible to prevent the disease, but you can do everything possible to live fully with such a diagnosis.

1. First, the control of the doctor. These patients are treated by neurologists. In addition to the prescribed treatment regimen and systematic visits to a neurologist, it is necessary to monitor the general condition (blood sugar, pressure, etc.) in order to prevent the development of other diseases during the treatment of myasthenia gravis.
2. Secondly, it is worth avoiding excessive stress - physical and emotional. Stress, hard physical work, overly active sports worsen the condition of patients. Moderate physical exercises, walks are even useful.
3. Thirdly, it is necessary to exclude exposure to the sun.
4. Fourthly, it is necessary to know the contraindications for patients with myasthenia gravis and strictly observe them.
5. Fifth, strictly follow the treatment regimen prescribed by the doctor, do not skip taking medications and do not take more medicines than prescribed by the attending physician.

The doctor is obliged to issue a list of medications that are contraindicated for such a patient. It includes magnesium preparations, muscle relaxants, tranquilizers, some antibiotics, diuretics, with the exception of veroshpiron, which, on the contrary, is indicated.

Do not get carried away with immunomodulatory drugs and any sedatives, even those that seem safe (for example, valerian or peony tincture).

Forecast

Previously, myasthenia gravis was a serious disease with a high mortality rate of 30-40%. However, with modern methods of diagnosis and treatment, mortality has become minimal - less than 1%, about 80% against the background of proper treatment achieve full recovery or remission. The disease is chronic, but requires careful monitoring and treatment.

Catad_tema Diseases of the nervous system in children - articles

ICD 10: G70

Year of approval (revision frequency): 2016 (review every 3 years)

ID: KR366

Professional associations:

• Union of Pediatricians of Russia

Approved

Union of Pediatricians of Russia

Agreed

Scientific Council of the Ministry of Health Russian Federation __ __________201_

GCS - glucocorticosteroids

Terms and Definitions

New and narrowly focused professional terms are not used in these clinical guidelines.

1. Brief information

1.1 Definition

Myasthenia gravis is an autoimmune disease characterized by impaired neuromuscular transmission and manifested by weakness and pathological fatigue of skeletal (striated) muscles.

1.2 Etiology and pathogenesis

According to modern concepts, the basis of the pathogenesis of myasthenia gravis is an autoimmune reaction caused by the binding of antibodies to acetylcholine receptors (AChR) of postsynaptic membranes of striated muscles. The number of these receptors is significantly reduced under the influence of these autoantibodies. In some cases, with autoimmune myasthenia gravis (MG), antibodies (AT) to AChR are not detected, and this form is called seronegative myasthenia gravis (SN-MG). The term "seronegative" is inaccurate in relation to a group of patients, including children, who have IgG antibodies to muscle specific receptor tyrosine kinase (MyCK). This form is called MuSK-MG. Although convincing evidence of the pathogenicity of AChR AT has been obtained, the pathogenetic role of MSC AT remains unclear. Other antibodies, the role of which has not been established, may also be detected, including those against titin, ryanodine receptors, and the intracellular AChR-associated protein rapsin.

The mechanism that triggers the production of AT remains unknown. The role of the thymus is indicated by the combination of AChR and lymphoid hyperplasia of thymus tumors, as well as the effectiveness of thymectomy. With MuSC-MG, if they are detected, then only small histological changes in the thymus. The presence of a genetic predisposition is indicated by the relatively common clinical and electromyographic (EMG) symptoms in the patient's relatives and the frequent individual groups of antigens of the human major tissue compatibility complex (HLA).

There is a combination with other autoimmune disorders, especially with pathology thyroid gland(hyper- or hypothyroidism), rheumatoid arthritis, lupus erythematosus and diabetes. According to some researchers, malignant tumors were observed in 5% of children.

1.3 Epidemiology

Myasthenia gravis is a relatively rare disease, although there are good reasons to believe that it is observed much more often than previously thought. Persons with the HLA-B3, HLA-B8, HLA-DW3 phenotype are most predisposed to the disease. The prevalence of myasthenia gravis is 0.5-5 cases per 100 thousand of the population, however, at present there is a tendency to increase the number of patients and is 10-24 cases per 100 thousand of the population. Myasthenia gravis can debut at any age, from early childhood (more often in girls and in adolescence) and ending with old age. Children and adolescents under 17 years of age account for 9-15% of patients with myasthenia gravis. AT childhood the juvenile form of myasthenia is more common. Approximately 5-20% of infants (according to various sources) born to mothers with myasthenia gravis develop transient neonatal myasthenia gravis (TNM), caused by the transfer of antibodies to acetylcholine receptors (AChR) from the mother through the placental barrier. The highest incidence is noted in 2 age categories: 20-40 years (during this period, women are more likely to get sick) and 65-75 years (during this period, men and women are affected equally often). The average age of onset of the disease in women is 26 years, in men - 31 years.

1.4 ICD-10 coding

G70 Myasthenia gravis and other neuromuscular junction disorders Excl.: botulism (A05.1), transient neonatal Myasthenia gravis (P94.0)

G70.0 Myasthenia gravis

G70.1 - Toxic disorders of the neuromuscular junction

G70.2 - Congenital or acquired myasthenia gravis

G70.8 - Other disorders of neuromuscular junction

G70.9 Disorder of neuromuscular junction, unspecified

1.5 Examples of diagnoses

• Myasthenia gravis, generalized form, progressive course, moderate severity, sufficient compensation against the background of ACEP.
• Myasthenia gravis, local (ocular) form, stationary course, mild severity, good compensation on ACEP.
• Myasthenia gravis, a generalized form with respiratory disorders, a progressive severe course with insufficient compensation for ACEP.

1.6 Classification

There are several classifications of myasthenia gravis. The Osserman classification is the most common in the world (adopted as international in 1959 in Los Angeles, modified in 1971 by Osserman and Jenkin).

Generalized myasthenia gravis:

• Myasthenia gravis in newborns
• Congenital myasthenia gravis
• Benign with ophthalmoparesis or ophthalmoplegia
• family nursery
• Juvenile myasthenia gravis

Ocular myasthenia gravis:

• Youthful
• adult

V.S. Lobzin in 1960. proposed classification of myasthenia gravis according to the course of the pathological process:

1 - acute onset with rapid development of the symptom complex and further slow progression,

2 - acute onset, longer (from 3 months to 1 year) development of the syndrome, course with remissions, but steady progression,

3 - gradual onset, slow development over several years and then a slowly progressive course,

4 - start with a limited muscle group and slow progression.

In 1965 A.G. Panov, L.V. Dovgel and V.S. Lobzin developed a classification of myasthenia according to the localization of the pathological process, taking into account the violation of vital functions (impaired breathing and cardiac activity):

1 - generalized:

a) without violation of vital functions, b) with violation of respiration and cardiac activity;

2 - local:

a) facial form (ophthalmic, pharyngeal-facial), b) musculoskeletal form: without respiratory failure and with respiratory failure.

The classification proposed in 1965 by B.M. Gecht. It takes into account the nature of the course of the disease, the degree of generalization of the myasthenic process, the severity of movement disorders and the degree of their compensation against the background of acetylcholinesterase (AChE) inhibitors, which helps to formulate the diagnosis quite fully and accurately.

By the nature of the flow:

1. Myasthenic episodes (single or relapsing course) - transient motor disorders with complete regression (10-12%).

2. Myasthenic conditions (i.e. stationary course) - stationary non-progressive form for many years (13%).

3. Progressive course - steady progression of the disease (50-48%).

4. Malignant form - acute onset and rapid increase in muscle dysfunction (25%).

Forms are merged into each other.

By localization:

– local (limited) processes: ocular, bulbar, facial, cranial, trunk;

- generalized processes: generalized without bulbar disorders, generalized and generalized with respiratory failure.

According to the severity of movement disorders:

Medium

heavy

According to the degree of compensation of motor disorders against the background of acetylcholinesterase (AChE) inhibitors:

Sufficient

Insufficient (bad).

2. Diagnostics

2.1 Complaints and medical history

When collecting anamnesis and complaints, attention is paid to the variability of symptoms during the day, their relationship with exercise, the presence of partial or complete remissions, the reversibility of symptoms while taking AChE inhibitors (for the duration of their action) and against the background of adequate immunosuppressive therapy.

2.2 Physical examination

The clinical examination should include a study of the general neurological status, as well as a check of the strength of the voluntary muscles of the face, neck, trunk and limbs before and after the load (strength assessment in points, where 0 is no strength, 5 is the strength of this muscle group of a healthy person). One of the most important clinical tests for diagnosing myasthenia gravis is the presence of pathological muscle fatigue syndrome: an increase in symptoms after exercise. For example, an increase in ptosis, oculomotor disorders during fixation of the gaze, after squinting; decrease in strength in certain muscle groups after repeated active movements in the limb under study, squats or walking; the appearance or increase of speech disorders when counting, reading aloud, etc. It does not show any symptoms organic damage nervous and neuromuscular system (in the absence of concomitant diseases): there are no disturbances in the reflex and coordinating sphere, sensitivity is preserved, in typical cases there are no muscle atrophies, muscle tone is preserved.

Juvenile autoimmune myasthenia gravis (JMG)

Symptoms of the disease can develop at any age over one year, but are most common in girls during adolescence. The onset of the disease may be gradual or sudden.

The clinical picture is characterized by:

• damage to the oculomotor muscles with diplopia, ophthalmoplegia and ptosis (may be symmetrical, asymmetric or unilateral),
• weakness of the muscles of the face (especially the circular muscle of the eye),
• weakness of the proximal limbs,
• damage to the respiratory and oropharyngeal muscles,
• deep tendon reflexes are preserved.

When examining children with developed respiratory failure in the absence of pulmonary pathology, the possibility of JMG should be considered, even if there are no other symptoms of this disease.

Initially, muscle strength may be normal or near normal, and therefore muscle strength should be assessed before and after exercise.

The incidence of cases in which the involvement is limited to the oculomotor muscles only (myasthenia gravis) varies considerably between publications, but is probably 20-50%, and up to 80% in young children in China. MySC-MG is more common in women, the clinical picture is dominated by weakness of the oculomotor muscles and muscles of the skull, frequent respiratory crises are noted. The differences between MuSK-MG and AHR-MG have yet to be clarified.

Transient neonatal form (myasthenia gravis in newborns) s)

Clinical manifestations include:

• general muscle hypotonia,
• weak cry,
• difficulty breathing and sucking
• possible development of ptosis,
• amimia, oculomotor disorders,
• swallowing disorders, decreased deep reflexes.

Congenital myasthenic syndromes are presented in more detail in Appendix D1.

Transient myasthenic syndrome, which manifests itself in such children in the first days of life and lasts for 1-1.5 months, is due to the transfer of antibodies to AChR from the mother through the placental barrier.

• comorbidities, and are a hallmark of the condition now referred to as IUD with episodic sleep apnea).

Thus, the difference between all the symptoms of myasthenia gravis is dynamism during the day, intensification after exercise, reversibility or a decrease in their severity after rest.

myasthenic crisis , at which different reasons there is a sharp deterioration in the state with a violation of vital functions. The molecular basis of the myasthenic crisis is probably a sharp decrease in the number of functioning AChRs due to a massive attack by their autoantibodies. Often a myasthenic crisis is provoked by a bronchopulmonary infection, and in some cases pneumonia develops against the background of a crisis, and then respiratory disorders can be mixed.

It is possible to differentiate a myasthenic crisis from other severe conditions accompanied by respiratory disorders by the presence of:

• bulbar syndrome,
• hypomimia,
• ptosis,
• asymmetric external ophthalmoparesis,
• weakness and fatigue of the muscles of the limbs and neck (decreasing in response to the introduction of AChE inhibitors).

Myasthenic crisis should be distinguished from cholinergic crisis (Appendix D2), which develops with an excessive dose of AChE inhibitors. Common symptoms of crises are pronounced weakness of voluntary muscles with respiratory failure and bulbar syndrome, psychomotor agitation and impaired consciousness (stupor, coma).

Mixed (myasthenic + cholinergic) crises occur in patients with myasthenia gravis with incorrect intake and / or initially a narrow range of therapeutic doses of AChE inhibitors, as well as against the background of conditions that cause general or muscle weakness various genesis(intercurrent infections, somatic, hormonal disorders, taking drugs that affect the contractile function of voluntary muscles, etc.).

2.3 Laboratory diagnostics

• Determination of anticholinesterase antibodies is recommended.

Comments: Antibodies to AChR are detected in children in the range of 60-80%. In prepubertal age, the test is positive in about 50% of children. Antibody titer decreases in successfully treated patients. Of those seronegative for antibodies to AChR, about 40-50% are seronegative for antibodies to MySC. The higher frequency of these antibodies in children has not been clearly established, but they may be present at the onset of the disease in early childhood.

2.4 Instrumental diagnostics

• Iterative nerve stimulation (ISN) is recommended to detect electrical neuromuscular blockade.

Comments: This test is stressful, especially in young children, and should therefore be performed sparingly. Technical difficulties in young children are also a problem, and therefore, before declaring a test positive, one must be completely sure that the decrease in amplitude is of the myasthenic type. The total action potentials of the muscle are recorded from surface electrodes, preferably over a weak muscle; nerve stimulation frequency 3Hz and 5Hz. A decrease in amplitude of more than 10% between the third and fifth potentials is considered a positive result. Single-fiber EMG, which makes it possible to detect increased “trembling” during contraction of pairs of fibers, is more sensitive than the classical ISN, but difficult to perform in children. A normal HF does not exclude the diagnosis of JMG.

• It is recommended in diagnostically difficult cases to conduct a morphological study of the muscle biopsy (light, electron microscopy, histochemical, immunohistochemical, immunofluorescent and other types of visual study of the neuromuscular junction and its surrounding tissues).

Comments: The main qualitative and quantitative changes in myasthenia gravis are found in the postsynaptic membrane, which contains AChR, and in the stage of expanded clinical picture the number of AChRs decreases to 10-30% of normal values, their density decreases.

2.5 Other diagnostics

• The use of anticholinesterase drugs is recommended - a test with AChE inhibitors: neostigmine methyl sulfate (ATC code: N07AA01), pyridostigmine hydrochloride (ATC code: N07AA02). After the introduction of one of these drugs, the effect is observed in one or more weakened muscles. The most common test is with neostigmine methyl sulfate. The dose is selected individually at the rate of 0.125 mg / kg of body weight (approximately: 1.5 ml of a 0.05% solution - with a body weight of up to 70 kg and 2 ml - with a body weight of more than 70 kg or with severe generalized limb muscle weakness without taking into account body weight). You can choose any parenteral route of administration of the drug, but usually done by subcutaneous injection. The effect of the drug is evaluated after 30-40 minutes .

Comments:A positive complete test is considered when muscle strength is restored up to 5 points with compensation for bulbar and oculomotor disorders, a positive incomplete test is considered when strength increases by 1-2 points, but without its complete restoration and (or) preservation of a reduced bulbar or oculomotor defect. Partial compensation consists in the selective action of AChE inhibitors on individual muscle groups, as a rule, with an increase in the strength of voluntary muscles by 1 point. A dubious proserin test is isolated when there is some positive dynamics in relation to individual symptoms (a decrease in ptosis by 1-2 mm, a slight increase in the range of motion eyeballs, a slightly more sonorous voice, the impression of a certain increase in the strength of the muscles of the limbs, etc.

• The introduction of intramuscular or subcutaneous neostigmine methyl sulfate is recommended for suspected transient neonatal form (myasthenia gravis of the newborn).

Comments: Clinical symptoms allow a correct diagnosis if the mother is known to have myasthenia gravis, but the mother's disease may be undiagnosed or asymptomatic. The diagnosis is confirmed by intramuscular or subcutaneous administration of Neostigmine methyl sulfate (ATC code: N07AA01); ISN can also be performed to confirm the diagnosis, but its implementation at this age is technically difficult and painful. Neostigmine methyl sulfate (ATC code: N07AA01, Prozerin) is preferable for diagnosis and then for treatment, especially before feeding, as its effect lasts longer, allowing more time for examination (for example, a single dose of 0.1 mg before feeding and additional doses as needed).

If the diagnosis of myasthenia is in doubt, dynamic monitoring is required, a trial course of AChE inhibitors (pyridostigmine hydrochloride in combination with potassium preparations - only strictly avoiding cholinergic reactions), repeated clinical and electromyographic (EMG) examinations.

The anticholinesterase test and ISN do not have high sensitivity and specificity, while the presence of antibodies to AChR is specific for myasthenia gravis.

2.6 Differential diagnosis.

The diagnosis of myasthenia gravis is made on the basis of a combination of clinical data, the results of instrumental examinations. The main difference between myasthenia gravis and other forms of pathology is the dynamism of symptoms and positive reaction for the administration of anticholinesterase drugs.

It is necessary to exclude the following diseases:

- endocrine ophthalmopathy;

- oculopharyngeal muscular dystrophy;

- multiple sclerosis;

- Fisher's syndrome;

- botulism;

- Tolosa-Hunt syndrome;

- mitochondrial cytopathies;

- congenital myasthenic syndromes, etc.

Bulbar manifestations of myasthenia gravis should be differentiated from vascular and tumor lesions of the brain, which are characterized by severe cerebral symptoms, as well as the lack of dynamics of disorders and the lack of response to the administration of anticholinesterase drugs.

Sometimes significant difficulties arise when differential diagnosis myasthenia gravis and amyotrophic lateral sclerosis (ALS), in which in some cases not only the clinical symptoms of myasthenia gravis are possible, but also neuromuscular transmission disorders and reactions to the administration of anticholinesterase drugs. In such cases, the correct diagnosis can only be made after an EMG, which reveals signs of denervation and reinnervation, as well as the presence of a large number fasciculation potentials characteristic of ALS. Respiratory disorders and crises in myasthenia gravis should be differentiated from Guillain-Barré syndrome (GBS), which is characterized by areflexia, impaired composition of the cerebrospinal fluid, absence of neuromuscular transmission disorders and response to the administration of anticholinesterase drugs.

Weakness of the muscles of the trunk and limbs in patients with myasthenia is differentiated from various forms congenital and acquired myopathies.

The myopathic process, as a rule, is characterized by a distribution of movement disorders that is different from myasthenia gravis: the absence (with rare exceptions) of signs of damage to the extraocular and bulbar muscles, respiratory disorders; often accompanied by a decrease or absence of tendon reflexes, varying degrees expression of muscle atrophy.

Clinical symptoms resembling myasthenia are also possible in other forms of neuromuscular transmission disorders, such as Lambert-Eaton syndrome and botulism. And if extraocular, bulbar and respiratory disorders are not typical for the Lambert-Eaton syndrome, then they are the main clinical core of botulism. Weakness and fatigue of the muscles of the trunk and extremities, characteristic of the Lambert-Eaton syndrome, are relatively rare in botulism. Both forms are characterized by hypo- or areflexia.

The effect of the introduction of anticholinesterase drugs in Lambert-Eaton syndrome is minimal, and is absent in botulism. Neuromuscular transmission disorders are characterized by a decrease in the initial amplitude of the M-response and its significant increase during high-frequency stimulation (increment) or after maximum voluntary effort.

3. Treatment

3.1 Conservative treatment

• The use of cholinesterase blockers is recommended.

Comments: These drugs increase the half-life of acetylcholine (ACh) released into the synaptic cleft by inhibiting its hydrolysis by acetylcholinesterase, thus increasing the likelihood that ACh molecules will reach the reduced number of receptors.

• Pyridostigmine bromide g, vk (code ATX: N07AA02) at a dose of up to 7 mg/kg/day is prescribed in 3-5 doses.
• Neostigmine methyl sulfate f, vk (ATC code: N07AA01) the initial dose is 0.2-0.5 mg / kg every four hours in children under 5 years of age and 0.25 mg / kg in older children, the maximum single dose is 15 mg.

• The use of corticosteroids is recommended.

Comments:GCS cause remission in most children with JMG. Prednisolone f, uc (ATC code: H02AB06) is prescribed at a dose of 1-2 mg/kg/day until a stable effect is achieved, after which the drug is gradually withdrawn.

• The use of other types of long-term immunotherapy is recommended.

Comments:

• Azathioprine w/vk (ATC code: L04AX01) can be used in combination with steroids or alone. An initial dose of 50 mg/day and up to 100-200 mg/day along with a maintenance dose of prednisolone.
• Cyclosporine g (ATC code: L04AD01) can be prescribed for intolerance to Azathioprine.
• Cyclophosphamide g, vk (ATC code: L01AA01) is used for very severe disease.
• High-dose pulse therapy Methylprednisolone f.v.c. (H02AB04) is used in children with refractory disease.

• The use of plasma replacement is recommended.

Comments:Plasmapheresis is used for the treatment of myasthenic crises, as well as for pre- and postoperative support. Held intravenous administration class G immunoglobulins - normal human immunoglobulin (ATC code: J06BA02, normal human immunoglobulin) The effect is observed after 3-4 days and lasts up to 3 months.

3.2 Surgical treatment

• Thymectomy is recommended.

Comments: applied as the main method long-term treatment, especially in children at high risk of developing complications of treatment with ChE blockers or corticosteroids, or other types of immunotherapy.

Indications for surgical treatment are:

a) malignant forms;

b) progressive form;

c) myasthenic state, depending on the severity of the defect.

With local forms, surgical treatment is selective.

Contraindications for thymectomy:

• severe decompensated somatic diseases;

Before surgical treatment, preoperative preparation is required:

• restorative therapy;
• therapeutic plasmapheresis;
• if necessary - a course of glucocorticosteroid therapy.

4. Rehabilitation

Not required

5. Prevention and follow-up

5.1 Prevention

Prevention has not been developed.

5.2 Case management

Management of patients with myasthenia gravis in an outpatient setting should include:

• ECG for all children 1 time in 3 months.
• ?Ultrasound abdominal cavity, heart, kidney - 1 time in 6 months.
• ?X-ray examination chest, joints, if necessary, the spine, sacroiliac joints - 1 time in 6 months.
• esophagogastroduodenoscopy with biopsy for Helicobacter pylori and morphological diagnostics- 1 time in 6 months to exclude erosive, ulcerative processes and gastropathy.
• in case of exacerbation - ultrasound internal organs and chest X-ray, ECG and other necessary instrumental methods examinations (CT, MRI) according to indications:
• in patients with myasthenia gravis, the Mantoux reaction is performed, the examination for tuberculosis is carried out under the supervision of a phthisiatrician
• when positive tuberculin samples(papule> 5 mm) referral for a consultation with a phthisiatrician to resolve the issue of conducting a Diaskin test or tuberculin tests with dilution and conducting specific therapy

Management of a patient receiving immunosuppressive therapy

• examination by a neurologist - 1 time per month;
• ?clinical analysis blood (hemoglobin concentration, number of erythrocytes, platelets, leukocytes, leukocyte formula, ESR) - 1 time in 2 weeks;
• ?with a decrease in the number leukocytes, erythrocytes, platelets below normal - cancel immunosuppressants for 5-7 days. After a control blood test with normalization of indicators - resume taking the drug;
• urea, creatinine, bilirubin, potassium, sodium, ionized calcium, transaminases, alkaline phosphatase) - 1 time in 2 weeks:
• with an increase in the level of urea, creatinine, transaminases, bilirubin above normal - cancel immunosuppressants for 5-7 days. Resume medication after recovery biochemical indicators;
• - analysis of immunological parameters (concentration of Ig A, M, G; CRP, RF, ANF) - once every 3 months.

Management of a patient with myasthenia gravis receiving anticholinesterase drugs

• examination by a neurologist once a month;
• ? clinical blood test (hemoglobin concentration, number of erythrocytes, platelets, leukocytes, leukocyte formula, ESR) - 1 time in 2 weeks;
• ?analysis of biochemical parameters (total protein, protein fractions, concentration urea, creatinine, bilirubin, potassium, sodium, ionized calcium, transaminases, alkaline phosphatase) - 1 time in 2 weeks;
• ? analysis of immunological parameters (concentration of Ig A, M, G; CRP, RF, ANF) - once every 3 months;
• planned hospitalization 2 times a year for a complete examination and, if necessary, correction of therapy.

Patients with myasthenia gravis are shown the status of "disabled child". During periods of exacerbation of the disease, it is necessary to provide training at home. In the stage of remission of the disease, exercise therapy with a specialist familiar with the characteristics of the pathology is recommended. When visiting school? physical education classes in the general group are not shown. Patients with myasthenia gravis are contraindicated for prophylactic vaccinations, introduction? globulin.

Patients with a diagnosis of myasthenia gravis should be under constant dispensary supervision of a pediatrician and a neurologist. Children with this pathology are shown a comprehensive examination in a specialized round-the-clock / day hospital, average duration hospitalization - 21 days. It is advisable to conduct courses of rehabilitation therapy for a period of at least 21-28 days 2-3 times a year under the supervision of a neuropathologist, physiotherapist and exercise therapy specialist.

6. Additional information affecting the course and outcome of the disease

6.1 Outcomes and prognosis

The most severe course of myasthenia gravis is observed in children with multiple stigmas of dysembryogenesis (musculoskeletal dysplasia, anomalies in the development of the central nervous system), neuroendocrine disorders (diencephalotemporal paroxysmal conditions, growth retardation and puberty against the background of hypopituitarism syndrome, acquired hirsutism and others), immaturity lymphoid system of the nasopharynx (adenoids, tonsillitis, pharyngitis), broncho-obstructive syndrome and other comorbidities. Boys with the onset of the disease in the prepubertal period and regression of myasthenia gravis by the end of puberty, as a rule, have persistent remissions.

Choosing the right treatment tactics allows you to achieve a positive effect (persistent complete or partial remission against the background of taking medications or without them) in 80% of patients with myasthenia gravis. However, to date, there are no methods for predicting the course of the disease and specific pathogenetic methods for the treatment of myasthenia gravis.

Criteria for assessing the quality of medical care

Table 1 - Organizational and technical conditions for the provision of medical care.

Table 2 - Criteria for the quality of medical care

Bibliography

1. Autoimmune diseases of the neuromuscular transmission. In: Brief reference book of a neurologist. - M.: "ABV-press", 2015. - S. 129-139.
2. Guzeva V.I., Chukhlovina M.L. Clinical guidelines for the diagnosis and treatment of myasthenia gravis in children. In the book: Children's neurology. Issue 1: clinical guidelines / ed. IN AND. Guzeva. - M.: LLC "MK", ​​2014. - S. 101-127.
3. Sanadze A.G. Myasthenia. In: Autoimmune diseases in neurology. Under. ed. Zavalishina I.A., Piradova M.A., Boyko A.N., Nikitina S.S., Spirina N.N., Peresedova A.V. Clinical guide. - V.2. - M.: ROOI "Human Health", 2014. - S. 101-128.
4. Aicardi J. Diseases of the nervous system in children. - T.2. – M.: Binom, 2013. – S. 940-949.
5. Sanadze A.G. Myasthenia and myasthenic syndromes. M.: Litterra, 2012. - 256 p.
6. Suponeva N.A., Piradov M.A. Myasthenia gravis. In: Intravenous immunotherapy in neurology. M: Hotline-Telecom, 2013. - S. 165-191.
7. Kaminski H.J. Myasthenia gravis. In book: Neuromuscular disorders in clinical practice (Eds. Katirji B., Kaminski H.J., Ruff R.L.). - New York: Springer, 2014. - P. 1075-1088.
8. Parr J., Jayawant S., Buckley C., Vincent A. Childhood autoimmune myasthenia. In book: Inflammatory and autoimmune disorders of the nervous system in children (Eds. Dale R.C., Vincent A.). London: Mac Keith Press, 2010. - P. 388-405.

Annex A1. Composition of the working group

Baranov A.A., acad. RAS, Professor, MD, Chairman of the Executive Committee of the Union of Pediatricians of Russia.

Namazova-Baranova L.S., acad. RAS, Professor, Doctor of Medical Sciences, Deputy Chairman of the Executive Committee of the Union of Pediatricians of Russia.

Kurenkov A.L.,

Kuzenkova L.M., professor, MD, member of the Union of Pediatricians of Russia

Goltsova N.V.,

Mamedyarov A.M., Candidate of Medical Sciences, Member of the Union of Pediatricians of Russia

Bursagova B.I., Candidate of Medical Sciences, Member of the Union of Pediatricians of Russia

Vishneva E.A., Candidate of Medical Sciences, Member of the Union of Pediatricians of Russia

1. pediatricians, neurologists;
2. orthopedic doctors;
3. Physical therapy doctors, physiotherapists,
4. Doctors general practice(family doctors);
5. Medical students;
6. Students in residency and internship.

Methods used to collect/select evidence: searches in electronic databases.

Description of the methods used to assess the quality and strength of the evidence: The evidence base for recommendations are publications included in the Cochrane Library, the EMBASE, MEDLINE and PubMed databases. Search depth - 5 years.

Methods used to assess the quality and strength of evidence:

• expert consensus;
• assessment of significance in accordance with the rating scheme.

Methods used to analyze the evidence:

• reviews of published meta-analyses;
• systematic reviews with tables of evidence.

Description of the methods used to analyze the evidence

When selecting publications as potential sources of evidence, the methodology used in each study is reviewed to ensure its validity. The outcome of the study affects the level of evidence assigned to the publication, which in turn affects the strength of the recommendation.

To minimize potential errors, each study was evaluated independently. Any differences in the estimates were discussed by the whole group of authors in full. If it was impossible to reach a consensus, an independent expert was involved.

Evidence tables: filled in by the authors clinical guidelines.

Methods used to formulate recommendations: expert consensus.

Economic analysis

Cost analysis was not performed and publications on pharmacoeconomics were not analyzed.

• External peer review.
• Internal peer review.

These draft guidelines have been peer-reviewed by peer reviewers, who were primarily asked to comment on the ease of understanding of the interpretation of the evidence underlying the recommendations.

Comments were received from primary care physicians regarding the intelligibility of the presentation of these recommendations, as well as their assessment of the importance of the proposed recommendations as a tool for daily practice.

All comments received from the experts were carefully systematized and discussed by the members of the working group (the authors of the recommendations). Each item was discussed separately.

Consultation and expert assessment

Working group

For the final revision and quality control, the recommendations were re-analyzed by the members of the working group, who came to the conclusion that all the comments and comments of the experts were taken into account, the risk of systematic errors in the development of recommendations was minimized.

Table P1 - Scheme for assessing the level of recommendations

*in the table digital value corresponds to the strength of recommendations, letters - corresponds to the level of evidence

These clinical guidelines will be updated at least once every three years. The decision to update will be made on the basis of proposals submitted by medical professional non-profit organizations, taking into account the results of a comprehensive assessment. medicines, medical devices, as well as the results of clinical testing.

Appendix B. Information for Patients

Myasthenia gravis is a severe autoimmune neuromuscular disease with a progressive course, clinically manifested by pathological muscle fatigue leading to paresis and paralysis. Immunological disorders in myasthenia are genetically determined.

Myasthenia gravis affects both males and females. The debut of the disease can occur at any age: from the first days of life to (myasthenia gravis of newborns) to old age.

The disease has a progressive character, quickly leads to disability and social maladjustment.

Appendix D

Annex G1. Congenital myasthenic syndromes

AChR-acetylcholine receptor; AChE blocker - acetylcholinesterase blocker; SPDM is the total muscle action potential; 3,4-DAP - 3,4-diaminopyridine; ISN, iterative nerve stimulation; MG - myasthenia gravis.

Annex D2. Distinctive symptoms of myasthenic and cholinergic crises

Annex G3. Deciphering notes.

… and - medicine included in the List of Essential and Essential Medicines for medical use for 2016 (Decree of the Government of the Russian Federation of December 26, 2015 N 2724-r)

… VC - medicinal product included in the List of medicinal products for medical use, including medicinal products for medical use prescribed by decision medical commissions medical organizations(Decree of the Government of the Russian Federation of December 26, 2015 N 2724-r)

Half-closed eyelids, inability to raise a hand or take the next step, speech disorders, periodic nasal voice - are these symptoms characterized by myasthenia gravis? And if so, how can you recognize a formidable disease at the very beginning?

What is myasthenia gravis

According to the medical encyclopedia, myasthenia gravis is a special disease, the leading symptom of which is muscle weakness of the striated muscles. Moreover, this weakness increases sharply when performing any movements and decreases after have a nice rest, sleep.
The main cause of myasthenia is a disorder in the transmission of impulses between nerve endings and muscles due to a violation of the formation, release and attachment of acetylcholine to the corresponding receptors. It is believed that this disease is autoimmune, so it responds well enough to treatment. hormonal drugs such as prednisolone.

Myasthenia gravis: symptoms that often go unrecognized

Unfortunately, most often myasthenia gravis is diagnosed already in those cases when the disease has been going on for several years in a row and goes into a neglected form. For this reason, weakness that sharply increases with repetitive movements must be regarded as a possible symptom of myasthenia gravis until this diagnosis is completely refuted.

Early symptoms include:

• when talking - "attenuation of the voice",
• difficulty chewing solid food up to refusal to eat,
• swallowing disorder,
• fatigue when combing, climbing stairs, normal walking,
• the appearance of a shuffling gait,
• drooping eyelids.

The most commonly affected are the oculomotor, facial, chewing muscles, as well as the muscles of the larynx and pharynx. The following tests help identify latent myasthenia gravis:

• If the patient is asked to quickly open and close his mouth within 30 seconds, then a healthy person will make about 100 movements, and a person suffering from myasthenia gravis - less.
• Lie on your back, raise your head and hold it in this position for 1 minute, while looking at your stomach.
• Stretch your arms and stand like this for 3 minutes.
• Do 15-20 deep squats.
• Quickly squeeze and unclench the hands - in a patient with myasthenia gravis, this often causes drooping of the eyelids.

The local form of myasthenia gravis is characterized by the manifestation of muscle weakness of a certain group of muscles, and in the generalized form, the muscles of the trunk or limbs are involved in the process.

Symptoms of myasthenia gravis in children

A special place is occupied by myasthenia gravis in children, the early symptoms of which have some of their own characteristics:

• Congenital myasthenia gravis. Rapid fatigue of the muscular system can be suspected even in utero during an ultrasound scan. With myasthenia, fetal movements are less active, or even completely absent. After birth, the symptoms of this myasthenia gravis are similar to neonatal myasthenia gravis. Death occurs due to a violation of spontaneous breathing.
• Myasthenia gravis in newborns. It occurs in those children whose mothers themselves suffer from myasthenia gravis. It starts already from the first days of life and can last about 2 months. Its main symptoms can be the following:

1. the baby is more lethargic than other newborns,
2. breathes superficially,
3. periodically chokes,
4. his cry is weak, more like a squeak,
5. he also sucks badly at the breast and gets tired quickly,
6. his mouth is open,
7. the gaze is almost fixed,
8. in some cases, swallowing may also be difficult.

The child often dies from suffocation.

• Early childhood myasthenia gravis. According to experts, it occurs at the age of up to 2 years, when, against the background of complete health, vision problems begin to appear: the eyelids involuntarily droop, gaze paralysis develops, and strabismus develops. In some cases, the baby may refuse to walk, run, it is difficult for him to go up or down the stairs, often asking for his arms. Refusal to eat can occur if the masticatory muscles are involved in the process.
• Juvenile and children's myasthenia gravis. It develops from 2 to 10 years or in adolescence, mainly in girls. Among early signs it is necessary to pay attention to the child's complaints about sudden fatigue, visual impairment, difficulties with jogging, walking long distances, squats, and doing physical work around the house.

Myasthenia gravis: symptoms of a local form

• Eye myasthenia. It is characterized by: drooping of the eyelid (ptosis), doubling of the image (diplopia), limitation of eye movement.
• Bulbar form. It is manifested by weakness of the muscles of the pharynx, larynx and soft palate. As a result, the following symptoms are observed:

1. dysphonia - the voice becomes weak, as if subsiding as the conversation continues, turns to a whisper, or nasality appears;
2. dysphagia - the process of swallowing first solid and then liquid food is disrupted, to the point that the patient has to be fed through a tube;
3. dysarthria - speech can become slurred, the pronunciation of individual sounds is distorted.

• cranial form. Damage to the masticatory and facial muscles joins the bulbar form. With this form of myasthenia gravis, facial expressions are poor, the face takes on a youthful appearance due to the smoothing of wrinkles, with a smile only the upper lip moves, and the lower one continues to remain motionless (the person, as it were, growls). It is difficult for the patient to chew food, in severe cases - his mouth is ajar, and lower jaw sags. Due to the defeat of the circular muscle of the mouth, the pronunciation of labial sounds is disturbed.

With bulbar and cranial, as well as generalized forms of myasthenia gravis, immobilization of the muscles of the vocal cords can occur, which leads to asphyxia.

Symptoms of myasthenic crisis

A myasthenic crisis is a sharp deterioration in the general condition of the body associated with a sharp weakness of the muscles up to their paralysis. Most characteristic symptoms crises are as follows:

1. Breathing: at first it is frequent, superficial, with the involvement of the intercostal muscles in the act of breathing, and then rare and intermittent. The face at the same time becomes red, subsequently acquires a bluish, cyanotic hue. The patient is agitated and anxious. After a complete cessation of breathing, loss of consciousness occurs, and without timely assistance, clinical death occurs very quickly.
2. Cardiovascular system: pulse quickens up to 180 beats per minute, arterial pressure reaches 200 mm Hg. Art. Then the pulse slows down, becomes threadlike, weak.
3. Autonomic nervous system: profuse salivation,.

If timely assistance is not provided, then brain damage occurs due to oxygen starvation.

Treatment

Treatment of myasthenia gravis is carried out by the appointment of hormonal agents, as well as anticholinesterase drugs. In severe cases, cytostatic agents may be prescribed. During a cholinergic crisis, the patient is ventilated until his condition stabilizes.

Conclusion

Myasthenia gravis is a serious disease that in many cases begins insidiously. It is possible to suspect myasthenia gravis and consult a doctor in a timely manner only if you know the early symptoms of the disease, and do not write off weakness and fatigue as a simple unwillingness to do something.

Which doctor to contact

When inexplicable muscle weakness appears, it is necessary to contact a neurologist, show the child to a pediatrician, and then to a pediatric neurologist. Additionally, you will need an examination by a rheumatologist to exclude systemic diseases of the connective tissue, an ENT doctor, an immunologist.