Professor Balyazin Viktor Alexandrovich, Honored Doctor Russian Federation, Professor, Doctor of Medical Sciences, Head of the Department of Nervous Diseases and Neurosurgery, Rostov State Medical University, Rostov-on-Don.

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Martirosyan Vazgen Vartanovich

Professor,Doctor of Medical Sciences,Assistant of the Department of Nervous Diseases of Rostov State Medical University since 1958,Doctor neurologist of the highest qualification category

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Fomina-Chertousova Neonila Anatolyevna, Candidate of Medical Sciences,Assistant of the Department of Nervous Diseases and Neurosurgery,Neurologist, epileptologist of the highest qualification category

HEREDITARY NEURO-MUSCULAR DISEASES

Progressive muscular dystrophies are hereditary degenerative diseases, which are based on damage to the muscle fiber and its autonomic innervation due to a violation of biochemical processes in muscle tissue.

The problem of progressive muscular dystrophies received comprehensive coverage in the works of S. N. Davidenkov (1932, 1952), who laid the foundation for the study of genetics.

Progressive muscular dystrophies are divided into primary, in which the muscle fiber is primarily affected, and secondary, in which the nervous regulation is primarily disturbed, and the damage to the muscle fiber is secondary.

primary forms

1. Shoulder-scapular-facial Landuzi-Dejerine.

2. Juvenile (youthful) Erba.

3. Pseudohypertrophic Duchenne.

4. Ophthalmoplegic Graefe.

5. Bulbar-paralytic Hoffmann

6. Distal Hoffmann-Navil.

7. Myosclerotic Sestana-Lezhonne.

8. Davidenkov's scapular-peroneal myopathy (transitional form)

Secondary Forms 1 Neural:

1) amyotrophy of Charcot - Marie - Toots;

2) chronic hypertrophic

polyneuritis Dejerine-Sotta;

3) polyneuritic atactic

Refsum degeneration;

4) Thevenard's acropathy.

2. Spinal:

1) Aran-Duchenne amyotrophy;

2) Werdnig-Hoffmann amyotrophy

Myopathies arising from diseases of the endocrine glands (endocrine), metabolic disorders (metabolic), intoxications, carcinomatous, neuromyopathies, myopathies with collagenoses (dermatomyositis, polymyositis) can be distinguished into a special group.

With primary myopathies, there are different forms, depending on the predominance of the lesion of various muscle groups. With the shoulder-scapular-facial form, the muscles of the face and shoulder girdle suffer, with the juvenile form, the muscles of the shoulder girdle, shoulder, pelvic girdle, with the bulbar-paralytic form, the muscles of the tongue, soft palate, larynx, chewing muscles, and with the ophthalmoplegic, the muscles of the eyes.

According to the onset of the disease, primary muscle atrophies can be distinguished as follows: at an early age (up to 5-8 years), the pseudo-hypertrophic form of Duchenne appears, from

10 to 20 years old - juvenile form of Erb, from 20 to 25 years old - shoulder-shoulder-linear form of Landuzi - Dejerine and scapular-peroneal amyotrophy; at the age of 25 - distal form of Hoffmann-Navil; at a later age - the bulbar-paralytic form of Hoffmann and the myosclerotic form of Sestan - Lezhonne. Secondary muscular atrophy: at the age of 1-2 years - amyotrophy of the Verdict-Hoffmann and at the age of 5-20 years - neural amyotrophy of Charcot-Marie.

According to the degree of progression, there are: slowly progressive forms (shoulo-scapular-facial Landuzi - Dejerine, Charcot's amyotrophy - Marie, Erb's juvenile myopathy) and rapidly progressive forms (pseudohypertrophic Duchenne, myosclerotic Sestana - Lezhonne).

The wide phenotypic polymorphism of hereditary neuromuscular diseases (presence of typical and atypical forms) depends on mutant gene variations and other genetic and environmental factors.

Etiology. Myopathy is inherited. Clinical and genetic studies have established a variety of forms of inheritance of neuromuscular diseases: dominant type (shoulo-scapular-facial form of Landuzi - Dejerine), autosomal recessive, recessive, sex-linked (pseudohypertrophic form of Duchenne). Myopathy is transmitted more often by a recessive type, often by a dominant one. Rudimentary forms of myopathy are inherited in an autosomal dominant manner. The genetics of myopathy is different depending on its forms. Since progressive muscular dystrophies sometimes begin many years after birth, it can be concluded that not only genetics matters, but also development, nutrition, lifestyle, various exogenous and endogenous factors that affect metabolism.

Pathogenesis. Violated biochemical indicators of protein metabolism. Hyperaminoaciduria is observed - an increase in urinary excretion of free amino acids (glycine, serine, alanine, glutamic acid, lysine, methionine, valine, leucine). The greatest increase in the excretion of amino acids in the urine is observed in patients with pseudohypertrophic form. In this case, the breakdown of specific muscle proteins is accompanied by their replacement with adipose and connective tissue. Hyperaminoaciduria depends on the intensity of the myodystrophic process: hyperaminoaciduria increases

with fast-flowing forms of myopathy and, apparently, has a muscular origin (accelerated breakdown of muscle proteins). The lag in the processes of muscle protein synthesis in muscular dystrophy compared with their faster decay leads to a progressive decrease in skeletal muscle tissue. There is a relationship between the form of myopathy and the content of DNA in the affected muscle. In the pseudohypertrophic form, the DNA content in the muscles decreases, while in the juvenile form, on the contrary, there is a tendency to increase the DNA content by N/g-2 times. Violation in the DNA structure of the nuclei of muscle cells leads to the inability of uscervical cells to synthesize fibrillar proteins. The study of the nucleotide composition of DNA established a defect mainly in guanine, cytosine, less adenine and thymine. The number of free nucleotides varies depending on the degree of nuclear DNA decay. The breakdown of striated muscle DNA, leading to a change in the amount of nuclear DNA, is accompanied by an increased release of low molecular weight compounds into the blood. The content of ATP (as the main nucleotide) in the dystrophic muscle is significantly reduced compared to the norm. The creatinine-creatine index is significantly lower in pseudohypertrophy (0.45), juvenile myopathy (0.72), and scapulo-facial myopathy (0.70). In the urine, the content of creatine decreases and the excretion of creatinine increases. Increased activity of aldolase in the blood serum. Changes in carbohydrate metabolism: fasting hypoglycemia, increased hyperglycemic coefficient and abnormal sugar curves after alimentary load (bimodal and delayed type), especially in severe myopathy. Reduced K/Ca ratio and sodium content. A muscle biopsy reveals an uneven diameter of the muscle fibers. Large edematous fibers predominate, in some places with a fine-grained and lumpy structure, the transverse striation is indistinct, disappearing. Among these fibers there are thin, atrophic. The muscle nuclei are pycnotic, in places they form "chains" of various lengths. Metachromasia in myopathies occurs within one bundle, with secondary muscle atrophy - bundle muscle atrophy. There is an abundant growth of connective tissue that penetrates between individual muscle fibers. The walls of the vessels are thickened due to the disintegration of the adventitia, swelling and proliferation of the endothelium. Among the fibers of the connective tissue and around the vessels, infiltrates are visible, consisting of round cells of the lymphoid type, leukocytes, plasma cells, histiocytes.

Symptoms. Leg fatigue when walking, difficulty running, climbing stairs. Muscle atrophy. Weight loss of the muscles that fix the scapula causes the scapula to lag behind the body (pterygoid scapulae). Shoulders hang down (drooped down and forward). The chest is flattened in the anterior-posterior direction, the costal edges protrude. Atrophy of the rectus and oblique abdominal muscles causes a "wasp waist". Characterized by lumbar lordosis due to atrophy of the muscles of the anterior abdominal wall and long muscles of the back, the abdomen protrudes forward, and the upper body bends back. Due to atrophy of the facial muscles, the face becomes like a mask: the forehead is smooth, devoid of skin folds, the lips are thick, turned out due to pseudohypertrophy of the circular muscle of the mouth (“tapir lips”). When laughing and smiling, the corners of the mouth do not pull up, but only move apart in a horizontal direction (“transverse smile”). The eyelids close tightly. Muscle tone is low. The range of passive movements is often limited due to muscular and tendon-ligamentous retractions, which lead to severe contractures. There are no fibrillar twitches in atrophying muscles. Tendon reflexes decrease in parallel with the degree of muscle atrophy and later disappear.

A decrease in the excitability of the sympathetic system in myopathy manifests itself in the form of hypo- or anhidrosis (dry skin), asymmetry of skin temperature in the proximal extremities. The hands and feet are usually cold and wet, and the pilomotor reflex is altered.

With myopathy, the excitability of muscles to galvanic and faradic current decreases, less often it is completely lost, sometimes the polarity is violated. EMG study (Fig. 15, A, B) helps to distinguish myopathy from neural muscle atrophy in the early stages of the disease. Muscle biocurrents in myopathy show low-wave (6-12 microvolts) dysrhythmic electrical activity, with active muscle contraction, biocurrents normal in frequency and amplitude are recorded, with significant muscle damage, the amplitude of bioelectric potentials decreases, and sometimes the frequency of their oscillations. On the EEG in patients with myopathy, the biopotentials of the brain are reduced, slow activity is visible, moderate diffuse changes (Fig. 152).

The course often depends on the type of hereditary transmission: malignant with X-chromosomal (sex-linked) transmission, benign - with dominant. There is a compensated stage of myopathy with muscle fatigue, awkwardness of movements, when patients walk and continue to work; subcompensated stage, when weakness and awkwardness of movements increase, gait and other motor acts become difficult; decompensated stage, when patients stop walking, are bedridden, stop serving themselves.

The shoulder-scapular-facial form of Landouzi - Dejerine usually begins between 10 and 15 years. Equally common in men and women. It is inherited in an autosomal dominant manner. Characterized by the fact that atrophy begins with the muscles of the face. The face acquires a characteristic appearance: a smooth forehead, no wrinkles, eyes that do not close or do not close completely. There is weakness of the orbicular muscle of the mouth, the lips are protruded, whistling is impossible, as well as puffing out the cheeks. Occasionally, the lips do not close completely, as a result of which speech becomes fuzzy, blurred. Atrophy of the muscles of the tongue and external muscles of the eye is not observed. Later, atrophy of the muscles of the shoulder girdle and shoulder, pelvic girdle and lower extremities develop. Sometimes the process is limited to the shoulder-scapular-facial localization, not ■ moving to the muscles of the lower extremities. Sometimes there are unsharply pronounced pseudohypertrophies. The disease can be limited only to weakness of the muscles of the face, for example, the patient sleeps "with open eyes", cannot whistle, "laughs strangely." Weakness and atrophy of the muscles of the shoulder girdle begin with damage to the trapezius muscle,. rhomboid, broad dorsal, pectoral muscles. Atrophy may be asymmetrical. The deltoid, supraspinous and infraspinatus muscles, the muscle that lifts the scapula, remain unaffected for a long time.

The juvenile form of Erb is characterized by onset in adolescence, on average at 17 years of age. Men get sick twice as often as women. The disease is inherited in an autosomal recessive manner. Atrophies begin with the mouse of the shoulder girdle and shoulder, or with the muscles of the pelvic girdle and lower extremities, or both. The muscles of the face are usually not affected, and if affected to some extent, then in the later stages of the disease,

Rice. 152. Electroencephalogram in myopathy: alpha-rhythm in the form of separateny groups of oscillations of low amplitude. Dominated by low-amplitude honeyslow activity and low-frequency beta rhythm. There are moderate differentialsfuzzy changes.

when there is a thinning of the circular muscle of the mouth ("tapir lips"). The muscles of the shoulder girdle (proximal arms), pectoral muscles, serratus anterior and rhomboid muscles (Fig. 153, A), muscles of the pelvic girdle and proximal legs are mainly affected. A manifestation of weakness of the muscles of the shoulder girdle is a symptom of loose shoulder girdle. Due to damage to the pectoral muscles, the chest acquires the type of "rook". The most characteristic symptoms are pterygoid scapulae (Fig. 153, B), due to atrophy of the anterior serratus and rhomboid muscles, and "wasp waist" - the result of atrophy of the muscles of the pelvic girdle. The gait of the patient due to the defeat of the same muscles becomes waddling (duck gait). The classic symptom of the transition from a horizontal to a vertical position is manifested in the form of a consistent emphasis with the hands when standing up as if on a ladder from the lower leg to the knees, from the hip to the waist, with a gradual straightening of the torso. Atrophies are distributed mainly in the muscles of the proximal limbs and in the muscles of the trunk. The muscles of the distal extremities are usually relatively preserved. Sensitivity often persists, pain and paresthesia in the back and limbs, mild hyp- and hyperesthesia of the distal limbs are sometimes noted. Tendon and periosteal reflexes gradually fade away. The disappearance of reflexes, as it were, precedes the “disappearance of muscles”: first, the reflexes on the hands disappear (from the tendon of the biceps muscle, triceps muscle, peri-

Rice. 153. Muscle atrophypatients with myopathy.

A - in the juvenile form of myopathy, there is atrophy of the muscles of the shoulder girdle, proximal arms, pectoral muscles, anterior and posterior serratus; B - with Erb's form of myopathy "pterygoid scapulae".

steel reflexes), then knee jerks. Achilles reflexes usually remain alive for a long time and disappear only in advanced cases. There is no rebirth reaction. Atypical symptoms include a hollow or flat foot, rare crampi-type cramps, mild ptosis and diplopia, and weakness of the masticatory muscles. In some patients, muscle fatigue comes to the fore, which sometimes leads to an erroneous diagnosis of myastomy

Here are the case histories of two brothers suffering from a juvenile form of myopathy (Fig. 154).

Yuri K., aged 25, and Viktor K., aged 28. Yuri has been ill since the age of 10, when weakness appeared in his right leg, it became difficult to climb stairs and walk quickly, he often fell and hardly got up. Weight loss of the leg and foot muscles was noted, followed by weakness in the left leg. At the age of 13, he noted weakness in the upper limbs and muscle weight loss. In 1952 and 1953 reconstructive orthopedic operations on the legs were performed. Weakness in the limbs, muscle atrophy increased, weakness in the muscles of the back joined, it became difficult to sit. The patient is sharply reduced nutrition. The skin is dry, flaky. The ankle joints and small joints of the foot are deformed. The chest is flattened, scaphoid, intercostal muscles are atrophied. The abdomen is drawn in. There are no wrinkles on the forehead. The face is symmetrical. The lips are thinned, the smile is "transverse". Eyes close. Speech and phonation are not disturbed. He walks independently, but his legs get tired quickly, it is difficult to move from a horizontal to a vertical position and vice versa. Significant diffuse atrophy of the muscles of the upper and lower extremities, torso. The shoulder blades lag behind the chest ("pterygoid shoulder blades"). Pronounced lumbar lordosis in a vertical position. "Waspen waist". Raises arms to a horizontal level, legs up to 30°, does not extend bent legs. Muscle strength was diffusely reduced, but more so in the proximal limbs. Tendon and periosteal reflexes on the upper and lower extremities are not caused. Abdominal reflexes are sharply reduced. Plantar reflexes are not elicited. Decreased skin temperature in the distal extremities. A quantitative decrease in the electrical excitability of muscles was found to varying degrees for both types of current. Contractions for the tolerable strength of both types of current cannot be obtained from the muscle that opposes the thumb, the first interosseous and the gluteus maximus muscles. Qualitative changes in electrical excitability are not observed, the nature of muscle contractions to the galvanic current is alive. A myasthenic reaction of a moderate degree is determined (weakening of contractions after 50-70 current circuits, disappearance after 90-100 circuits). Victor in early childhood was significantly inferior to his peers in running and physical exercises. From the age of 14, he began to notice weakness in his legs when walking. From the age of 18, atrophy of the muscles of the shoulder girdle, proximal arms, and then the muscles of the pelvic girdle appeared. The gait became swaying. Later, he had difficulty getting up from his chair. Sharply exhausted. The chest is navicular shaped. Significant atrophy of the muscles of the shoulder girdle. "Waspen waist". There is atrophy on the arms, more muscles in the proximal section, diffuse on the legs. Active movements of the limbs are limited in the ankle joints, where there are extensor contractures. Significantly reduced strength and muscle tone in all parts of the limbs, in the shoulder joints to the horizontal level. "Winged blades". Gait "duck".

Thus, both brothers fell ill at the age of 13-14 years and both had a picture of the juvenile form of progressive muscular dystrophy. A feature of myopathy in one of the brothers was a combination of myopathic and myasthenic reactions (according to electrical excitability). Both brothers had significant vegetative disturbances.

In the next observation, the combination of myopathic and myasthenic reactions, expressed clinically and in the study of muscle electrical excitability, is also of interest.

Patient P., 19 years old, was admitted to the clinic with complaints of increasing weakness in the legs, difficulty walking, especially when climbing stairs. In 1964, during a headache attack, high blood pressure (190/100 mm Hg) was discovered. Subsequently, there were periodic rises in blood pressure within 140/90 mm Hg. Art. In June 1965, an attack of weakness in the legs suddenly developed. She fell to her knees when she got off the bus, but immediately got up. A month later, while swimming in the river, she felt awkward in her legs. When I left the river, there was already a weakness that was growing. Then everything passed. Fell while climbing stairs. After 7-10 days all aslike it's gone. In January 1966, she again suddenly felt weakness, which was growing. 15/1 the patient fell down, they brought her into the house, then she got up and continued to walk. In the morning, after a long stay in bed, the strength in the limbs is almost completely preserved, but it is not possible to lower the legs and getting up is difficult.

Rice. 155. Different phases of the position of the torso and arms of a patient with myopathy when standing up, a - the patient leans her hands on her right knee, trying to stand up; b - the patient managed to stand on his left leg, she continues to lean on her hands; c - the patient managed to stand on both legs, while she tries to tear her hands off the support and straighten her torso; d - the patient managed to stand up, but the trunk was not fully extended; the patient stands with difficulty, spreading her arms for balance, her legs are widely spaced, the right leg is bent at the knee joint for greater stability.

but. After a muscular load (in bed she repeatedly flexed and extended her leg), the strength decreased sharply, the patient could not hold the raised yoga. After resting, she held her leg well again. The same phenomena in the upper limb, but less pronounced. On examination: the muscles of the back and lower leg are atrophic. With prolonged muscle tension, the face turns pale, general weakness appears. The gait is not grossly disturbed, but there are elements of a "duck" gait. When getting up from the floor, especially from squatting, several phases of the position of the torso and arms are noted. The patient holds on to the edge of the bed or to some other object (Fig. 155),but rises quickly. Injection of prozerin does not improve muscle weakness. Muscle tone is not changed. Tendon reflexes are increased, sometimes clonusoids of the feet are noted. There are no pathological reflexes. Electrical excitability from nerves and muscles is preserved for both types of current, but quantitatively reduced in the proximal lower extremities, more in the right. The nature of muscle contractions in response to galvanic current is alive. In the study of the myasthenic reaction of the muscles of the upper extremities, there is a weakening of contractions after 40-50 consecutive irritations and their disappearance after 80-90, i.e. there is a moderately pronounced myasthenic reaction characteristic of myopathy. It is not possible to study the myasthenic reaction in the legs due to poor current tolerance (due to a significant quantitative decrease in electrical excitability). The myasthenic reaction was detected on the biceps muscle, the common flexor of the fingers, the muscle that opposes the thumb. Urine creatinine 6.8 g, urine creatine 1.972 g. Total protein 8.06%, protein fractions: albumins 69.55%, a-globulins 10.15%, |3-globulins 8.7%, y-globulins 11, 6%, potassium 18.8 mg%, calcium 9.2 mg%.

Weakness in the proximal legs, "duck" gait, difficulty getting up from the floor give reason to think about the juvenile form of myopathy. Of interest are some paroxysmal attacks, elements of myasthenic nature, increased blood pressure, autonomic disorders.

There are rudimentary forms of Erb's myopathy that do not lead to further progression of the process. Rudimentary forms occur in families where Erb's myopathy is present in relatives of the proband, but these individuals usually consider themselves healthy. Rudimentary forms are characterized by slight atrophy of the muscles of the pelvic girdle and proximal legs, a decrease in knee reflexes, pseudohypertrophy of the calf muscles, and in some cases, a "duck" gait.

Sometimes there is kyphosis thoracic spine and smoothness of the lumbar lordosis.

The difference between the juvenile form of Erb and the shoulder-blade-facial form of Landouzi - Dejerine is sometimes very difficult. An essential sign for a differential diagnosis is damage to the muscles of the face: in the juvenile form of Erb, only in some cases atrophy passes to the muscles of the face. With the Landouzy-Dejerine form, the facial muscles are affected almost constantly. The genetics of both forms are different: the juvenile form of Erb belongs to the dominant type of hereditary transmission, significantly limited to the male sex. Shoulder-blade-facial form Landuzi - Dejerine belongs to the dominant type of inheritance, all carriers of the hereditary inclination fall ill. Light rudimentary forms in women are more common than in men.

The pseudohypertrophic form of Duchenne begins more often at the age of 3 years, is inherited recessively through the maternal X chromosome. In female carriers, microsymptoms are sometimes found (damage to the muscles of the lumbosacral region, etc.). The disease is characterized by atrophy of the muscles of the pelvis and thighs, as a result of which the gait is disturbed, later the muscles of the shoulder girdle and arms are affected, first of the proximal section, as a result of which patients cannot raise their shoulders, then the distal one.

Ophthalmoplegic myopathy (progressive dystrophy of the external eye muscles) has a family character with an autosomal dominant and autosomal recessive type of inheritance, characterized by a predominance of other symptoms of ptosis and ophthalmoplegia with atrophy of the muscles of the upper eyelids, circular muscles of the eyes. In some cases, weakness and atrophy of the chewing muscles, the circular muscles of the mouth are noted. The muscles innervated by the V, VII, IX, X, XII nerves, the muscles of the shoulder girdle and, in rare cases, the pelvic girdle and limbs, may be involved in the process, as a result of which the gait is disturbed.

Rice. 156. Pseudohypertrophy of gastrocnemiusmuscles in a child with myopathy (a, b).

Patient M., 38 years old, was admitted to the clinic with complaints of lowering of the upper eyelids, especially on the right, double vision when looking in front of him and to the left, breaking pain in the right eye, aggravated by trying to raise the eyelid, periodic headaches. These phenomena are aggravated by the end of the day and with physical exertion. He considers himself ill since the spring of 1953, when the right eyelid began to droop in the afternoon. The patient was very tired at this time. In 1954-1955. ptosis of the right eyelid, growing towards evening, persisted, in 1956-1957. as if passed. In the spring of 1958, a recurrence of ptosis on the right and a slight pain in the right eye of a bursting nature. These phenomena, as before, increased in the second half of the day. In 1962, double vision joined in the spring when looking in front of him, in September - ptosis on the left. Then there was an indefinite weakness in the hands. Bilateral, varying in its severity ptosis, more on the right. Weakness of the external rectus muscle of the eye on the right and slight weakness on the left. Weakness of the internal rectus muscle of the eye on the left. Convergence is broken. Slight restriction of upward gaze. Diplopia when looking in front of you and to the left (in the horizontal plane). General flabbiness of the muscles of the body with severe diffuse atrophy of the muscles of the left shoulder and, to a lesser extent, the right. Atrophy of the extensor muscle group of the forearms, more to the left. Progressively increasing fatigue of the extensor muscles of the forearm and shoulder girdle. The triceps reflex is not elicited on both sides. Blood potassium 24.6 mg%, calcium 11 mg%.

In a patient against the background of a progressive course of the disease with remission, a clinic of damage to the muscles that lift the eyelid is determined, more on the right, and a symmetrical lesion of the muscles of the extensor group of the proximal upper limbs with their atrophy and loss of the reflex from the triceps muscle on both sides. Based on the clinical picture, an ophthalmoplegic variant of myopathy can be assumed.

The bulbar-paralytic form of Hoffman is characterized by damage to the bulbar muscles, often combined with external ophthalmoplegia. This form is never passed on from parents to children, and thus does not follow a dominant pattern of inheritance. In addition to the bulbar muscles, the muscles of the trunk and extremities can be involved in the process.

Patient P., 23 years old, was admitted with complaints of weakness in all limbs, more in the legs, general weakness, moves independently with difficulty, cannot pick up an object from the floor, get up from a chair, "closes her eyes" when taking liquid food, sometimes it is difficult to chew solid food - "jaws get tired and do not clench." Sick for about 3 years. There was weakness in the legs and arms (almost simultaneously): she fell on the street, could not climb the stairs, take the child in her arms, wring out the laundry. Weakness in the extremities increased, weakness of the eyelids appeared (“drooping eyelids”), weakness of the masticatory muscles, sometimes doubling in the horizontal plane, choking when swallowing liquid food. The left palpebral fissure is narrower than the right one. Ptosis of both upper eyelids. Limited movement of the eyeballs up, more on the right. At times, slightly does not bring the left eyeball outwards. Diplopia in the horizontal plane when looking to the right and left. Slight weakness of the temporal muscles on both sides. Smoothed right nasolabial fold. Puffy face. Lips are wide. Horizontal nystagmoid on both sides. Phonation is not broken. Occasionally chokes on liquid food. The pharyngeal reflexes are not elicited. Atrophy and weakness of the muscles of the shoulder and pelvic girdle, proximal limbs, more in the legs. Raises arms to horizontal level. In a horizontal position, he can raise his legs by 5-10 °, he cannot hold his raised leg. She can only get up and sit down with her hands. When you try to kneel on a chair, bend down falls. Gait "duck". Muscle tone is reduced. The triceps reflex is not elicited on both sides. The Achilles reflex is lowered on the right. Electrical excitability of muscles: a quantitative decrease in both types of current, most pronounced in the muscles of the proximal section. Aldolase 6 units (6/1II) and 4.8 units (11/IV). Blood potassium 20.1 mg%, blood calcium 8.4 mg%. The combination of myopathy with muscle damageoculomotor, masticatory, soft palate and pharynx allows diagnosing combined bulbar-paralytic and ocular forms of myopathy.

Distal muscular dystrophy has an autosomal dominant pattern of inheritance. According to our observations, people at the age of 30 get sick more often, less often from 5 to 15 years, the muscles of the distal extremities are affected, first the lower ones, and then the upper ones. After 5-15 years, with the slow progression of the disease, the proximal limbs are also affected. Differentiate with Charcot-Marie amyotrophy. It is distinguished by the absence of sensitivity disorders, the greater prevalence of the process, the absence of fibrillar twitches and the reaction of degeneration.

Myosclerotic myopathy of Sestan-Lezhon is characterized by the occurrence of fibrous (muscle-tendon-ligamentous) retractions, leading to various deformities. Submits to the dominant type of hereditary transmission, limited to the male sex. It can be difficult for the patient to straighten the legs and hips and have to stand in the position of a sitting person, leaning on short crutches fixed in the armpits. Moving in this way, the patient resembles a quadruped. The deformities can spread to the muscles of the neck, resulting in rotation of the head. The myosclerotic process in some cases is combined with trembling, ptosis, nystagmus, and divergent strabismus.

Myosclerotic myopathy of Sestan-Lejeune is characterized by a proximal distribution of atrophy in the upper limbs (as in myopathy) and a distal distribution in the lower (as in neural amyotrophy). The disease has a family character, usually begins at the age of 23-24 years, slowly progresses. The extensor and abductor muscles of the foot (anterior-outer muscle group of the lower leg) are especially affected, the extension and abduction of both feet, and the extension of the fingers are sharply weakened. The gait is broken (“steppage”). Achilles reflexes fade early. There are no pseudohypertrophies. Sometimes the muscles of the face, abdominals and extensors of the spine are involved in the process. The interscapular space is expanded, the patient cannot bring the shoulder blades to the midline. The pectoral muscles, supra- and infraspinatus, trapezius muscles atrophy. Sensitivity disorders are noted on all limbs, intensifying towards the distal section, with damage to the facial muscles - perioral hypesthesia. The reaction of muscle degeneration is expressed unsharply. Vegetative disturbances in this form are insignificant.

Neural muscular atrophy of Charcot-Marie-Tooths is characterized by the development of atrophy of the muscles of the feet, then the hands. The disease is hereditary-familial in nature with an autosomal dominant, recessive, sex-linked and autosomal recessive type of inheritance. Men are more commonly affected than women (3:1). The disease usually begins at the age of 19-20 years. Changes in the foot are characteristic: a hollow foot with a high arch (such as Friedreich's foot). Sometimes atrophy extends to the muscles of the thighs.

Only a few years later, atrophy captures the muscles of the hand. Tendon and periosteal reflexes are absent. The gait takes on a peculiar look (“steppage”). Patients often complain of pain in the lower extremities, paresthesia, aggravated by muscle fatigue, in cold and damp weather. S. N. Davidenkov described a symptom of cold paresis, which consists in increased weakness in the hands during cooling, so in winter patients feel worse than in spring and summer. Fibrillar twitches in atrophied muscles are frequent. Changes in electrical excitability, the reaction of degeneration are revealed. On EMG, monotonous, dysrhythmic, low amplitude currents of action without differentiation into currents of large and small amplitude. Quite often, on resting EMG, a perverted reaction is high-amplitude "spikes", grouped into regular, clear rhythms of the order of 6-12 Hz. Such electrical activity in the form of "palisade rhythms" is observed in the muscles of the distal extremities. At maximum voluntary contractions, a decrease in the rhythm of oscillations and a decrease in their amplitude are determined (Fig. 157). Sometimes, when examining individual muscles during tonic reactions against the background of a decrease in potentials, a sharp increase in amplitude (above 50 microvolts) and oscillation frequency is detected, which indicates spasticity.

Patient S., 32 years old, notes increasing weakness in the legs during long walking, sometimes aching pain in the calf muscles after a long walk. About 4 years ago, after giving birth, there were pains in the shoulder girdle on both sides, but then they disappeared. A year later, after giving birth, pain and increasing weakness in the legs appeared again. It became difficult to walk, especially on the street, where she fell at the slightest bump. Slight weakness in the extensors of the hand. When raising the arms up, the anterior belly of the deltoid muscle is noticeably reduced. Slight restriction of dorsiflexion of the feet, more on the left. These muscles have reduced strength. Atrophy of the calf muscles of the left leg. The drumstick is bottle shaped. The Achilles reflex is low on the right, absent on the left. Loss of sensitivity is very indistinct on the outer surface of the left leg. When walking, a small "steppage". Stands steady on toes, cannot stand on heels.

Progressive atrophy of the muscles in the legs with the extinction of Achilles reflexes, moderate pain in the radicular type of the upper and lower extremities, and fuzzy sensory disturbances in the peripheral type made it possible to diagnose Charcot-Marie's neural amyotrophy.

Dejerine-Sott hypertrophic neuritis is a subspecies of neural muscular atrophy. It is characterized by thickening of the nerve trunks. It has a hereditary-family character. The disease begins in childhood. The nerve trunks are dense to the touch, painless, their electrical excitability is reduced. Shooting pains are sometimes noted, the reaction of rebirth is revealed. Violation of sensitivity by polyneuritic type. Tendon reflexes are absent. There are also nystagmus, miosis, uneven pupils with a sluggish reaction to light, kyphoscoliosis, dysarthria, ataxia. Neural muscular atrophy differs from hypertrophic interstitial neuritis only in hypertrophy of the nerve trunks. The course of the disease is slow. There may be rudimentary (non-progressive) forms of the disease, which are characterized by deformities of the feet, kyphosis or kyphoscoliosis, hypertrophy or thickening of peripheral nerves, slight paresis of the extensors of the feet or fingers, a slight decrease in superficial or deep sensitivity in the distal legs. Often there are no knee and Achilles reflexes.

Polyneuritic atactic degeneration of Refsum is characterized by the development of chronic polyneuritis syndrome with distal peripheral paresis, a gross violation of deep sensitivity. Has a hereditary-family character. Begins / begins at the age of 4 to 30 years. The course is progressive with / outbreaks. Cerebellar and posterior columnar ataxia, concentric narrowing of the visual field, anosmia, hearing loss, miosis, atypical retinitis pigmentosa, cataracts, Friedreich's foot, kyphoscoliosis and congenital anomalies of the skeleton, protein-cell dissociation in the cerebrospinal fluid (1-6% 0) are noted. find interstitial hypertrophic polyneuritis, degeneration of the posterior columns, atrophy of the cells of the anterior horns, atrophy of the inferior olives and degeneration of the olivo-ponto-cerebellar system. Spino-cerebral and spinal forms of amyotrophy are characterized by a combination of muscular dystrophy with a clinic of anterior horn lesions of the spinal cord (poliomyelitis syndrome). These include the following diseases.

Aran-Duchenne amyotrophy begins imperceptibly, develops and progresses very slowly. Men aged 40-60 get sick more often. Characterized by damage to the distal upper extremities. Due to atrophy and dysfunction of the muscle that opposes the thumb, short flexor, abductor, adductor thumb and interosseous muscles of the first interdigital space, and later atrophy of all interosseous muscles, the hand successively takes the form of a "monkey's paw" and "clawed brush". Later, atrophy spreads to the muscles of the forearm and then the shoulder (“skeleton arm”), sometimes to the neck muscles (the head hangs down), the muscles of the trunk and abdominal wall. Much later, the muscles of the lower extremities are affected (primarily the flexors of the foot and hip). Tendon reflexes gradually disappear. In the study of electrical excitability, the reaction of muscle degeneration is determined. The most characteristic symptom of the disease are fibrillar and fascicular muscle twitches. Pathological anatomical examination reveals atrophic changes in the ganglion cells of the anterior horns (loss of nuclei, processes, pigment accumulations), degeneration of the fibers of the anterior roots and growth of connective tissue in them. Degenerative changes in the endings of nerve fibers in the muscles are especially pronounced. Muscles are also changed (atrophy of groups of muscle fibers).

Spinal amyotrophy of Werdnig-Hoffman is familial, begins more often in the second half of the first year of a child's life, sometimes congenital. Werdnig and Hoffman noted that the disease is characterized by a malignant course and ends fatally in the first 2-4 years of a child's life. It is characterized by an autosomal recessive mode of inheritance.

Symptoms. At first, the child's movements are limited in the legs, then in the trunk, and later the paresis covers the muscles of the shoulder girdle, upper limbs, and neck. The “frog posture” is characteristic (legs are divorced and rotated outwards). Due to muscle hypotension, a sharp hyperextension develops. There is no mechanical excitability of the muscles. In atrophied muscles, the reaction of rebirth is determined. The transition of the process to the nuclei of the bulbar cranial nerves is characterized by the addition of a picture of bulbar paralysis. Tendon and periosteal reflexes are reduced or not evoked. Atrophy of the interosseous muscles often leads to respiratory failure. Fibrillar twitches are sometimes noted. Vegetative disorders are often expressed: cold snap and cyanosis of the extremities, obesity.

Patients die from pneumonia, atelectasis of the lungs, resulting from paresis of the intercostal muscles and diaphragm. Histopathological examination shows a decrease in the number of motor cells in the anterior horns of the spinal cord and brain stem, demyelination of the anterior roots and spinal nerves. With a muscle biopsy: a decrease in the size of individual muscle fibers with the preservation of their structure.

Cases of the onset of the disease at a later age, with an autosomal recessive type of inheritance, are described. Recent literature reports on the appearance of spinal amyotrophy in primary school and adolescence. The following forms are distinguished: 1) congenital, in which spinal amyotrophy develops in the prenatal period; 2) early childhood; 3) late forms. Late forms include youthful, in which spinal amyotrophy appears for the first time in children 5-13 years old. In the youthful form, the course of the disease is slower, the defeat of the muscles of the proximal section predominates.

Myotonic dystrophy (Steinert-Batten disease) is characterized by a combination of myotonic syndrome with muscle atrophy. The course of the disease is progressive. It occurs in many family members, equally common in men and women, inherited in an autosomal dominant manner with incomplete penetrance. It is more severe in men. The selectivity of muscle atrophy is characteristic. The disease begins with atrophy and weakness of the muscles of the forearm, then the small muscles of the feet, later the muscles of the face and neck ("swan neck"), nasopharynx, tendon reflexes disappear and with active muscle contractions myotonic reactions are determined. Myotonic reactions can also be obtained with mechanical and electrical stimulation of the muscles, especially the tongue, thenar muscles. Speech becomes slurred, with a nasal tint (myototic lesion of the tongue, weakness of the muscles of the pharynx by the type of myasthenic reactions). A “myotonic face” is characteristic (glossy forehead, enophthalmos, unilateral or bilateral ptosis). The creatine-creatinine index is often disturbed. The following vegetative disorders are determined: acrocyanosis, cold extremities, Chvostek's symptom, motor insufficiency of the esophagus with dysphagia, dyskinesia of the gastrointestinal tract, early baldness, general exhaustion. Very often, patients have cataracts, testicular atrophy, loss of libido and potency, dysmenorrhea, mental disorders. Myotonic reactions are determined on EMG: bioelectric potentials that arise when muscles are stimulated by current continue for some time also after the cessation of irritation, forming a plateau. In striated muscles, the size of the nuclei is increased. They are arranged in chains; myofibrils in a state of decay. In the late stage, fatty and connective tissue degeneration of muscles is noted.

Patient N., 59 years old, was admitted with complaints of weakness and weight loss of the arms and legs, stiffness in the hands and feet, a short-term feeling of twitching in various parts of the limbs and trunk, and wandering pains in the limbs, in the area of ​​the shoulder girdle with irradiation to the neck. In 1956, she discovered that during exercise she could not quickly unclench her fisted hands. Later, she discovered weight loss in the left calf muscle. In the future, the weight loss of other muscles of the limbs slowly progressed. The right foot began to "twist" when walking. For several years she noted twitches and pains in various muscle groups of the trunk and limbs. In 1960, the thyroid gland was removed. After a slight improvement, the stiffness of movements soon began to progressively increase again. Last year walks with a stick. Suffering from Achilles gastritis. Menstruation ended many years ago. There were two pregnancies, one birth. There were no such diseases in relatives.

Slight pastosity of the legs. Wrinkles the eyebrows badly, the strength of the circular muscle of the eyes on both sides is reduced. Gross atrophy of the temporal muscles, shoulder girdle, interosseous, deltoid, "pterygoid scapula". Restriction of active movements in the area of ​​the shoulder girdle, in the extensors of the left foot, extensors of the fingers. Cannot raise outstretched arms to horizontal. Muscle strength is reduced within 4 points. In the terminal joints of the fingers, the range of motion and muscle strength are normal. Decreased muscle strength in the wrist joints (more in the extensors and fingers) and in the lower extremities (more in the extensors of the left foot). Muscle tone in the limbs is low. "Duck" gait. From tola rises according to the "myopathic" type. Hands clenched into a fist cannot quickly unclench. All tendon reflexes are not elicited.

The combination of muscle atrophy with myopathic and myotonic reaction made it possible to diagnose myotonic dystrophy (Steinert-Batten disease).

Endocrine-metabolic myopathies are observed in violation of the functions of the endocrine glands and metabolism. There are climacteric myopathies in menopause, myopathies in myxedema, thyrotoxic chronic and acute flowing, accompanied by exophthalmos, it must be differentiated from myasthenia gravis, periodic paralysis, adrenal lesions. With hyperparathyroidism, symmetrical muscle atrophy, weakness, pain and increased reflexes in the limbs, creatinuria and hypercalcemia, and sometimes scleroderma are noted. When the parathyroid glands are removed, the condition of the patients improves. In Addison's disease, atrophy is accompanied by shortening of the fascia and tendons with contractures, pain, convulsions, and myotonic phenomena. AK.TG and cortisone therapy give a significant improvement. Senile muscular atrophy is characterized by progressive weakness of the muscles of the proximal limbs with atrophy and areflexia. The use of ACTH and vitamin E is effective. In Cushing's syndrome, atrophy of the muscles of the proximal limbs and muscles of the trunk is observed, apparently due to glucocorticoid and mineralocorticoid disorders. These muscle atrophies are distinguished by the lack of progression. With dysfunction of the pituitary gland, myopathies are observed, accompanied initially by an increase in the volume and strength of the muscles and later by weakness and atrophy of the muscles, which are usually combined with acromegaly. Growth hormone deficiency leads to impaired creatine metabolism and the development of muscle atrophy and weakness. Skeletal muscle glycogenesis due to acid maltase deficiency with deposition of glycogen in the muscles is also accompanied by the development of myopathy syndrome. Electron microscopy reveals vacuoles filled with glycogen and osmiophilic lipids in muscle fibers. Myopathy syndrome develops in acute and chronic alcohol intoxication. Acute alcohol intoxication can lead to edema and muscle necrosis. Flaccid muscle paralysis is accompanied by sharp pains and hyperesthesia. AT severe cases hyperkalemia is observed. With chronic alcohol intoxication, flaccid paralysis, pain in the muscles of the pelvic and, less often, the shoulder girdle develop. Pathological examination reveals degeneration of muscle fibers, sometimes focal muscle necrosis, and fatty degeneration. In milder cases, degenerative changes are not found. Zenker's hyaline degeneration occurs after infectious diseases and is nonspecific.

Carcinomatous neuromyopathies are characterized by neurogenic, myogenic and myasthenic symptoms, EMG changes, they are observed mainly in bronchogenic cancer, cancer of thepancreas and gastrointestinal tract. Surgical removal of the tumor leads to regression of the myopathic syndrome. In each case, for the correct diagnosis and treatment of myopathy, a neurological, therapeutic, endocrinological, biochemical and neurophysiological examination of the patient is necessary.

One of the main symptoms in a disease of the neuromuscular system is pathological muscle fatigue, weakness - myasthenic syndrome. Pathological fatigue can occur when there is a violation of the transmission of impulses through synapses (weakness appears in the muscles when acetylcholine is destroyed by excessively formed cholinesterase), with damage to the peripheral motoneuron, with metabolic disorders and diseases of the endocrine glands: with a violation of mineral metabolism (hypokalemia, hyperkalemia), carbohydrate metabolism (hypoglycemia, impaired activity of the muscle phosphorylase enzyme), with hyperthyroidism or hypothyroidism, with hyperfunction of the adrenal cortex (adrenogenital syndrome, Itsenko-Cushing's syndrome) or adrenal insufficiency (Addison's disease), with diseases of the thymus gland (thymectomy in many cases gives a positive result), diseases of the pancreas (in diabetes mellitus, weakness occurs as a result of a violation of carbohydrate metabolism, potassium metabolism, a disorder in the process of phosphorylation and depletion of muscle glycogen), and diseases of the pituitary gland. Myasthenic syndrome occurs after emotional stress, Unlike localized myasthenic syndrome, manifested by weakness in the limbs (in the proximal section), generalized myasthenic syndrome in the form of muscle fatigue and weakness occurs with lesions of the central nervous system (after encephalitis, brain injury), and the main value has damage to the hypothalamus. In such cases, myasthenic syndrome is combined with metabolic, trophic and vegetative disorders. EMG reveals the myasthenic type - a progressive decrease in biopotentials after muscle stimulation.

Differential diagnosis between myositis, myopathies and neuromuscular diseases is based on the clinic, type of inheritance, EMG and biopsy. In primary and secondary forms of progressive muscle atrophy, the electrical excitability of muscles is different. For myopathy, a quantitative change in electrical excitability is characteristic, and for secondary muscle atrophy, a reaction of degeneration. Electromyography in myopathy is dysrhythmic, with secondary muscle atrophies, peaks and “adhesions” are observed. A test with ACTH in primary muscular dystrophy leads to an increase in creatine release, in contrast to a decrease in its release in myositis. Differential diagnosis between neural and primary muscle lesions is aided by enzymatic activity studies (aldolase, transaminase, and especially creatine phosphokinase). Plasma enzyme activity

significantly increased in Duchenne myopathy, especially in the acute phase, and slightly increased in neural amyotrophies. In 2/3 carriers of Duchenne myopathy, the level of creatine phosphokinase is elevated even in the absence of clinical manifestations illness.

Treatment of patients with myopathy should be complex and combined. Apply adenosine triphosphoric acid (ATP) 1-2 ml intramuscularly (for a course of 30-40 injections), vitamin E 30-40 drops 3 times a day, a-tocopherol or erevit 1-2 ml (for a course of 15 injections), insulin 4-8 units with glucose or sugar (20 injections per course), ACTH. Anticholinesterase drugs are recommended: prozerin (0.05% solution, 1 ml), mestinone (0.06 g 3 times a day), galantamine (1% solution, 1 ml), nivalin (0.5% solution), dibazol (1% solution, 1 ml), securinin (0.2% solution, 1 ml). Repeated (5-7 times) fractional transfusions of donor blood (150-200 ml), protein hydrolyzate or hydrolysin 150-250 ml subcutaneously (for a course of 4-6 transfusions), autohemotherapy, B vitamins (Bb B2, B6, B12) ), nicotinic and ascorbic acid, nerobol, lecithin, glutamic acid, phytin. Dosed physiotherapy exercises and massage, a rational diet and proper employment of patients are important.

Prevention of hereditary diseases, including myopathies, is based on early recognition of the disease, detection of early diagnostic signs of muscle damage and early biochemical disorders in these patients. In prevention, intensive systematic treatment, dispensary observation, organization of the life of patients with myopathy, rational physical activity at school and adolescence, and the development of correct indications for the choice of professions in some forms of myopathy are important. It is important to conduct an examination of children, taking into account the possibility of their genetic history (the presence in the family or family of indications of the pathology of the muscular system). Special biochemical and electromyographic studies reveal the disease at the subclinical stage, when the neurological picture is not expressed. Of great importance for prevention is the organization of medical genetic consultations, which make it possible to give correct recommendations regarding the prevention of the birth of patients in a family where there are diseases of myopathy.

Neuromuscular diseases are a conditionally distinguished group of diseases that are characterized by dysfunction of the muscles, primarily by their weakness. Neuromuscular diseases include muscle disease, peripheral nerve disease, neuromuscular junction disease, and motor neuron disease. The same symptom of muscle weakness can be a manifestation of diseases that are very different in mechanism. This determines a completely different prognosis and methods of treatment.

Muscle diseases

Acquired myopathies:

inflammatory myopathies: (polymyositis, dermatomyositis, myositis with inclusions, sarcoid myopathy;

drug and toxic myopathies (corticosteroid myopathy, myopathy when using drugs to lower cholesterol, alcoholic myopathy, myopathy in critical conditions).

Secondary metabolic and endocrine myopathies:

hypokalemia myopathy;

hypophosphatemic myopathy;

myopathy in chronic renal failure;

myopathy in diabetes;

myopathy in hypothyroidism;

myopathy in hyperthyroidism;

myopathy in hyperparathyroidism;

Cushing's disease.

Primary metabolic myopathies:

myoglobinuria;

channelopathy;

hereditary myopathies;

muscular dystrophies.

Diseases of the peripheral nerves

Diseases of the neuromuscular junction

myasthenia gravis

Lambert-Eaton syndrome

Botulism

tick paralysis

Motor neuron diseases

amyotrophic lateral sclerosis

Diseases of the lower motor neuron

spinal muscular atrophy

monomelic amyotrophic lateral sclerosis

Kennedy disease

Diseases of the upper motor neuron

hereditary spastic paraparesis

primary lateral sclerosis

Diseases of the neuromuscular junction

Neuromuscular junction or neuromuscular junction- this is the connection of the nerve ending and the muscle fiber with the formation of the so-called synaptic cleft, in which the impulse is transmitted from the nerve to the muscle membrane. The impulse is transmitted using the neurotransmitter acetylcholine, which is secreted by the end of the nerve and then attached to the muscle membrane. In some diseases, there is a violation of neuromuscular transmission due to insufficient release of acetylcholine from the nerve ending or due to a violation of its attachment to the membrane of the muscle fiber.

Myasthenia Gravis

The Greek term myasthenia is translated as "muscle weakness" and gravis as "serious". Myasthenia gravis is a disease characterized by severe muscle weakness and fatigue. With myasthenia gravis, there is a violation of the transmission of impulse from the nerve fiber to the muscle. The disease is based on the production of autoantibodies that block the attachment of the neurotransmitter acetylcholine to the muscle membrane at the neuromuscular junction.

Symptoms

Muscle weakness changes during the day, is usually less pronounced in the morning and increases in the afternoon and evening. Early signs of the disease are (ptosis), double vision, weakness of the facial muscles, impaired swallowing, chewing, decreased strength in the arms and legs. The disease affects both men and women, and in women the diagnosis is more often made before the age of 40 years, and in men after 60 years.

How is the diagnosis made?

The diagnosis of myasthenia gravis is made by a doctor based on a blood test and electroneuromyography. If necessary, computed tomography of the chest is prescribed to assess the size and condition of the thymus gland as a search for a possible cause of the disease (production of autoantibodies).

Treatment

In the treatment of myasthenia gravis, anticholinesterase drugs (Pyridostigmine or Kalimin) and drugs that suppress the immune system (prednisolone and others) are used. Removal of the thymus gland (thymectomy) is performed when drug therapy is ineffective. Plasmapheresis and immunoglobulins can also be used in the treatment.

Lambert-Eaton syndrome

Lambert-Eaton syndrome is a syndrome of muscle weakness and fatigue that develops due to an autoimmune process. Usually the cause of the syndrome is a malignant oncological process, most often lung cancer. Therefore, when making a diagnosis of Lambert-Eaton syndrome, the patient is always shown an additional examination for the purpose of oncosearch.

Symptoms

Symptoms of the disease are most often associated with weakness of the muscles of the shoulders, hips, neck, swallowing, respiratory muscles, as well as the muscles of the larynx and muscles associated with speech articulation. Early signs of Lambert-Eaton syndrome are usually difficulty walking up stairs, getting up from a sitting position, raising your arms above your head. Sometimes vegetative functions are disturbed, manifested by dry mouth, impotence.

Why does Lambert-Eaton syndrome occur?

The cause is antibodies produced by the body itself (a similar autoimmune conflict is observed in myasthenia gravis). In particular, antibodies destroy nerve endings, thereby disrupting the regulation of the amount of neurotransmitter released. When the amount of the neurotransmitter is insufficient, the muscles cannot contract. The disease is not hereditary, predominantly young people under 40 suffer. The prevalence of the disease is 1 per 1,000,000 people. In 40% of patients with Lambert-Eaton syndrome, cancer is found.

How is Lambert-Eaton syndrome diagnosed?

Diagnosis includes a blood test for antibodies, test administration of an anticholinesterase drug, electroneuromyography.

Treatment

The most effective measure is the removal of a malignant tumor found in the body. Symptomatic therapy includes drugs that increase the release or amount of the neurotransmitter acetylcholine, which acts in the synaptic cleft (kalimin, 3,4-diaminopyridine). Drugs that suppress the immune system (prednisolone, etc.), plasmapheresis and immunoglobulins are also used.

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CLASSIFICATION OF NEURO-MUSCULAR DISORDERS
Sensory and motor disorders of the peripheral nervous system are commonly referred to as neuromuscular diseases. They are typically involved in the process of one element of the spinal reflex arc or more: cells of the anterior horns of the spinal cord, motor nerve fibers, neuromuscular synapses, muscles and sensory nerve fibers innervating muscles and tendons (Fig. 21-1). Damage to the elements of this reflex arc leads to the suppression of tendon reflexes, which is characteristic of all neuromuscular diseases. In addition, muscle weakness and atrophy are usually noted.
Classification

1. Damage to the cells of the anterior horns of the spinal cord Werdnig-Hoffmann disease

Polio
Other viral infections

1. Polyneuropathies

Post-infectious polyneuritis (Guillain-Barré syndrome)
Diphtheria polyneuritis
Toxic neuropathies (heavy metal poisoning), drug-induced neuropathies, metabolic polyneuropathy (see Table 21-2) Hypertrophic interstitial neuritis (Dejerine-Sott disease) Charcot-Marie-Tooth disease (peroneal muscular atrophy) Congenital sensory neuropathy Congenital absence of pain sensitivity

1. Mononeuropathies Congenital ptosis

Paralysis of the oculomotor nerve (Tholosa-Hunt syndrome)
Paralysis of the VI pair of cranial nerves (Duane's syndrome)
Facial palsy (Bell's palsy)
Erb's palsy Peroneal palsy Sciatic nerve injury

1. Diseases of neuromuscular synapses Myastenia gravis

Botulism

1. Muscular diseases Inflammatory processes Polymyositis

Myositis ossificans Endocrine or metabolic myopathies Myopathy in hyperthyroidism

Rice. 21-1. Schematic representation of the structures that make up the neuromuscular system.
1 - cell of the anterior horn; 2 - motor nerve fiber; 3 - motor nerve ending in the muscle; 4 - muscle; 5 - sensory receptor in the muscle (muscle spindle) - 6 - sensory nerve fiber.
Myopathy in hypothyroidism
Myopathy due to corticosteroid treatment
Muscle carnitine deficiency
General carnitine deficiency
Congenital muscle defects
Lack of muscle
Congenital torticollis
Congenital myopathies (central core disease and non-crimson myopathy)
Mitochondrial myopathy
Myotonia congenita (Thomsen's disease)
Periodic paralysis
Hyperkalemic form (adynamia episodica hereditaria) Hypokalemic form Paroxysmal myoglobinuria Carnitine palmityltransferase deficiency McArdle disease Muscular dystrophy
Pseudohypertrophic form (Duchenne)
Congenital muscular dystrophy

DAMAGE TO THE CELLS OF THE ANTERIOR HORNS OF THE SPINAL CORD

Selective damage to the cells of the anterior horns of the spinal cord occurs in polio and sometimes in other viral infections, including those caused by Coxsackie and ECHO viruses. Their hereditary degeneration manifests itself mainly in infancy.

Rice. 21-2. Fascicular atrophy of muscle tissue (a), pallor of the anterior roots (b) and degeneration of motor neurons (c) in Werdnig-Hoffmann disease.

Spinal muscular atrophy of early age. Werdnig-Hoffmann disease is inherited in a recessive manner. The primary pathological sign is atrophy of the cells of the anterior horns of the spinal cord and the motor nuclei of the brain stem (Fig. 21-2), followed by atrophy of the roots of the motor nerves and muscle tissue.

Rice. 21-3. Typical posture of a newborn with Werdnig-Hoffmann disease.
The onset of the disease occurs before the age of 2 years, but most often in the prenatal period. There are reports of quite rare cases of a similar disease in older children. Its early manifestations include weakness and hypotension of the muscles of the proximal and distal parts of the arms and legs, intercostal, innervated by cranial nerves. The child's legs are in a typical frog position: they are separated at the hip and bent at the knee joints (Fig. 21-3). The diaphragm suffers relatively rarely. Dysfunction of breathing due to weakness of the intercostal muscles is expressed in its paradoxicality with retraction of the chest during inspiration. External eye muscles are not involved in the process. Fibrillar twitches of the muscles of the tongue are usually noticeable. Tendon reflexes are almost always absent. The mental development of children remains within the normal range, and a meaningful facial expression and normal appearance the patient is in sharp contrast with the lack of motor activity. In the initial stages of the disease, there is a tendency to be overweight; in the later stages, patients cannot perform swallowing movements. Death can occur as a result of cessation of breathing and aspiration of food. If the onset of the disease is in utero, children usually die before the age of 2 years.

With a later onset, life expectancy is several years; sometimes the patient lives to adulthood.
Diagnosis of Werdnig-Hoffmann disease is largely based on clinical signs. Electromyography data (fibrillations and fascicular twitches) indicate muscle denervation. A biopsy of muscle tissue reveals groups of cells in different stages of degeneration: each group of muscle fibers contains cells innervated by one motor neuron. In the study of CSF, nerve conduction and activity of enzymes in the blood serum, no pathology is detected.
Differentiate the disease from a large number of less typical conditions in which the infant has weakness and hypotension. In this case, it is called sluggish (Table 21-1).
Table 21-1. Diseases accompanied by persistent muscle hypotension
Diseases

CNS dysfunction accompanied by muscle hypotension can be differentiated from peripheral neuromuscular disease based on such signs as reduced response to visual stimuli and preservation of tendon reflexes. Werdnig-Hoffmann disease from diseases of peripheral nerves and muscles in some cases can be distinguished only after special diagnostic methods, such as CSF examination, determination of the speed of the impulse along the peripheral nerves and the activity of serum enzymes, muscle tissue biopsy. However, it must be borne in mind that some manifestations of hypotonic disorders in children do not belong to the diseases listed in Table. 21-1. Under such conditions, muscle excitability remains, tendon reflexes are depressed, but usually do not completely fade away. Laboratory studies, including a biopsy of muscle tissue, do not reveal pathology. In most children with these symptoms, hypotension and weakness gradually disappear. To characterize them, terms such as "benign congenital hypotension" and "congenital amyotonia" are usually used. However, it is doubtful that such symptoms are signs of a homogeneous group of diseases.

Degenerative diseases with a primary lesion of peripheral nerves and muscles make up a significant proportion of human hereditary pathology. Diagnosis of neuromuscular diseases is based on molecular genetic and electrophysiological (EMG) studies.

Electroneuromyography allows you to confirm the diagnosis and monitor the dynamics of the disease. With neurogenic muscular pathology, signs of denervation can be detected: fibrillation potentials, positive sharp waves, a decrease in the amplitude of the interference potential, polyphasic potentials. In primary muscle pathology, the EMG picture is nonspecific and variable; the most characteristic is a decrease in the amplitude of the potentials. Indicators of impulse conduction velocity (SPI) with axonopathy are slightly reduced or are at the lower limit of the norm. In demyelinating neuropathies, SPI is significantly reduced. By changing the SPI and the amplitude of action potentials (by sensory or mixed nerves), one can diagnose tunnel neuropathies, as well as differentiate axonopathy and myelinopathy. An increase in the latent period of late responses is observed in neuropathies and radicular syndrome.

A significant role in the diagnosis is played by morphological, immunohistochemical and electron microscopic methods for studying biopsy specimens. The state of muscle fibers in light biomicroscopy helps to differentiate primary myogenic atrophy from secondary denervation (neurogenic or myelogenous) amyotrophy. Histochemical analysis of biopsy specimens is necessary to detect specific metabolic defects in muscle tissue. Electron microscopy has opened a whole class of diseases that are united by the concept of "structural myopathy".

Treatment.For many diseases of muscles, neuromuscular synapses, peripheral nerves and motor neurons, etiological and pathogenetic treatment has been developed. In other cases, therapy is aimed at slowing the progression of the disease, prolonging the period of remission and improving the patient's quality of life. The treatment of neuromuscular diseases requires the joint efforts of neurologists and rehabilitation specialists. Treatment tactics depend on the severity and rate of progression of the disease.

Rice. 6.1.Appearance of a 13-year-old child who received long-term hormonal therapy. Cushingoid

Principles of long-term corticosteroid therapy

Complications depend on the dose and duration of treatment (Fig. 6.1). The main complications: Cushing's syndrome, diabetes mellitus, osteoporosis, activation of tuberculosis, arterial hypertension, psychosis, susceptibility to infections, peptic ulcer.

With the abolition of corticosteroids, 3 types of complications are possible. 1. Complications associated with suppression of adrenal function

cov. It develops with fractional intake of prednisolone at a dose exceeding 20-30 mg / day for more than one week. Full recovery takes up to one year. At doses close to physiological, adrenal function usually remains intact if the duration of treatment does not exceed 1 month. Replacement therapy is not required after normal doses of corticosteroids.

2. General withdrawal symptoms (anorexia, nausea, vomiting, drowsiness, headache, fever, myalgia and arthralgia, weight loss) are more likely after long-term therapy. Treatment is symptomatic, with small doses of cortisone (10 mg/day) for several weeks.

3. Exacerbation of the underlying disease. This is one of the most dangerous complications of corticosteroid withdrawal. Its risk decreases with gradual dose reduction. In neuromuscular diseases, prednisolone is most often used - a short-acting drug for oral administration. It can be administered daily (in divided doses or once in the morning) or every other day (once in the morning). With a short course (less than a month), the regimen is not essential. With long-term treatment, fractional daily intake contributes to the development of Cushing's syndrome, suppression of adrenal function and reduces resistance to infections. With a long course, a single morning dose of a daily dose of a short-acting drug is less likely to cause suppression of

kidneys (although it does not prevent the occurrence of Cushing's syndrome). When taken every other day, twice the daily dose develops less adrenal suppression, Cushing's syndrome and a decrease in resistance to infections. This scheme is effective in most neuromuscular diseases.

6.1. progressive muscular dystrophies

The term "muscular dystrophies" refers to a group of clinically polymorphic genetically determined diseases, which are based on primary progressive degenerative changes in muscle fibers. Various forms of myodystrophies differ from each other in their genetic nature, type of inheritance, onset time, topographical peculiarity of the distribution of muscle atrophies. A characteristic clinical marker of myodystrophy is a "duck" gait associated with weakness of the gluteal muscles that fix the pelvis relative to the femur. As a result, during walking, there is a tilt of the pelvis towards the non-supporting leg (Trendelenburg phenomenon) and a compensatory tilt of the torso in the opposite direction (Duchenne phenomenon). In addition, patients can observe walking on their fingers, frequent falls, slow motor development and specific restrictions when raising their hands up, climbing stairs, getting up from the floor.

Duchenne and Becker myodystrophy. The Duchenne form is widespread in the world and occurs with a frequency of 1 in 3500 newborn boys, while the Becker form is observed about 3-5 times less often.

Etiology and pathogenesis. Duchenne and Becker myodystrophy are allelic variants, are inherited in a recessive X-linked type and are caused either by a complete lack of synthesis or by the synthesis of a defective high-molecular cytoskeletal protein-dystrophin. Due to the lack of dystrophin, myofibrils lose their resistance to cyclic acts of contraction-relaxation and break. Sarcoplasmic membranes become unstable, the work of ion channels is disturbed, as a result, the concentration of free intracellular ionized calcium increases, which has a necrotizing effect on muscle fibers, causing their lysis (Fig. 6.2).

clinical picture. The first clinical symptoms in most boys with Duchenne muscular dystrophy occur before the age of 3-5 years: gait is disturbed, children often begin to fall, lose

Rice. 6.2.Molecular organization of dystrophin

Rice. 6.3.Patients depicted by G. Duchenne

mobility. Developing pseudohypertrophy of the calf muscles creates a misleading impression of muscle strength (Fig. 6.3). Pseudohypertrophy can also develop in the gluteal, deltoid, abdominal and tongue muscles. Finally, muscle weakness becomes so pronounced that the child hardly gets up from the floor, walks with a "duck" gait, uses myopathic techniques: "climbing on one's own", "climbing with a ladder" (Govers's symptoms).

Rice. 6.4.1.5 year old child with Duchenne

Rice. 6.5.The same child at age 5. Muscle pseudohypertrophy, lordosis

Motor functions stabilize relatively between 3 and 6 years of age. In most cases, the ability to walk and climb stairs lasts until the age of 8. From 3 to 8 years, further shortening of the Achilles tendons occurs and fixed flexion contractures are formed in the ankle joints, compensatory lumbar hyperlordosis, kyphoscoliosis of the thoracic spine develop, atrophy of the muscles of the thigh, pelvic, and then the shoulder girdle, back and proximal arms. Attention is drawn to the presence of "loose shoulder girdle", "pterygoid shoulder blades", "wasp waist". Often, muscle atrophy is masked by a well-developed subcutaneous fat layer. Often develop deformities of the chest and feet, diffuse osteoporosis. Patellar, flexion, and extensor elbow reflexes disappear first, while Achilles reflexes may persist for quite a long time. At the age of 9, some children already move around with the help of a wheelchair, but for the majority, the ability to move independently until the age of 12, and the ability to stand until the age of 16. Weakness of the respiratory muscles and diaphragm causes a decrease in the vital capacity of the lungs to 20% of the norm, which leads to episodes of nocturnal hypoventilation (Fig. 6.4-6.6).

Some patients show various signs of endocrinopathy: adiposogenital syndrome, short stature. Due

Rice. 6.6.Same kid at 14. Expressed spinal deformity, flexion contractures, muscle atrophy

Rice. 6.7.Pseudohypertrophy of the leg muscles in Becker's disease

with a deficiency of cerebral isoforms of dystrophin - apodystrophins, some patients with Duchenne muscular dystrophy have mental retardation of varying degrees. The severity of mental disorders in children does not correlate with the severity of the muscle defect and the stage of the myodystrophic process. An obligate sign of the advanced stage of Duchenne myodystrophy is hypertrophic, or dilated, cardiomyopathy, which is accompanied by cardiac arrhythmias, expansion of its boundaries, and symptoms of heart failure. Cardiomyopathy is the most common cause of death in Duchenne myodystrophy. Respiratory failure, which is provoked by intercurrent infections or aspiration, also leads to lethality. Patients die in the 2-3rd decade of life.

Becker's myodystrophy (Fig. 6.7) can develop after 15-

20 years, flows much softer. Patients with this form of myodystrophy survive to adulthood. Intellectual impairment is uncharacteristic for her, tendon retractions and contractures are less pronounced than in Duchenne, cardiomyopathy may be absent. However, in some patients, cardiac dysfunction comes to the fore and is often a symptom of the disease. In addition, fertility is preserved in some patients with Becker's myodystrophy, so adult patients can transmit the disease to their grandchildren through their daughter ("grandfather effect").

Diagnostics.Duchenne myodystrophy is characterized by a significant increase in the level of enzymes already in the early stages of myodystrophy.

physical process. In patients under 5 years of age, the level of creatine phosphokinase (CPK) can exceed the upper limit of normal by tens and even hundreds of times. The enzyme concentration then decreases by approximately 20% per year. Serum levels of aldolase, lactate dehydrogenase, and transaminases are also elevated. High activity of CK is practically an obligate sign of the disease and, in addition to Duchenne myodystrophy, can occur with Becker's myodystrophy (usually not exceeding 5000 IU / l), polymyositis, dermatomyositis, hypothyroidism, alcoholic myopathy and paroxysmal myoglobinuria. EMG reveals signs of primary muscle damage (low-voltage curve with an abundance of polyphasic potentials, shortening of action potentials of motor units).

Currently, the generally accepted "gold standard" for the diagnosis of Duchenne and Becker myodystrophy, the detection of gene carriers and prenatal diagnosis is mutational analysis. An immunohistochemical reaction for dystrophin is used in the analysis of the percentage of dystrophin in muscles and distinguishes the Duchenne and Becker forms (at the first it is absent). In heterozygous carriers (mothers and sisters of patients), in approximately 70% of cases, subclinical signs of skeletal muscle pathology are detected: an increase in CPK, primary muscle changes on EMG and in the study of muscle biopsy specimens. Occasionally, carriers have noted compaction and an increase in the volume of the calf muscles, increased muscle fatigue during exercise, muscle spasms after exercise (crampy).

X-ray of the bones helps to identify atrophy of the diaphysis of long bones, thinning of the cortical layer, narrowing of the osteoarticular canal, diffuse osteoporosis.

Damage to the cardiovascular system (cardiomyopathy) develops in 73% of sick children. Dystrophin deficiency in cardiomyocytes leads to progressive atrophy of cardiomyocytes and their replacement with fibrous tissue. Cardiomyopathy is first diagnosed at the age of 6-7 years, by the age of 20 it is present in 95% of patients. There are also tachycardia, arrhythmia, lability of the pulse and blood pressure, muffled tones, expansion of the boundaries of the heart. The ECG shows cardiac arrhythmias, ventricular extrasystoles, signs of left ventricular hypertrophy (27%): deep prong Q in leads II-III aVF and V 6 ; high R in lead V 1 , signs of myocardial ischemia (5%). Echo-CG can reveal hypertrophic (55%) or dilated

(25%) cardiomyopathy, atrial septal defect, mitral valve prolapse, left ventricular myxoma.

A biopsy of the heart muscle reveals atrophy of muscle fibers, interstitial fibrosis, fatty infiltration.

Differential diagnosis of Duchenne and Becker myodystrophy is carried out with congenital hip dysplasia, vitamin D-resistant rickets, proximal types of spinal amyotrophies, polymyositis and dermatomyositis, metabolic and endocrine myopathies.

In the presence of the clinical phenotype of Duchenne myodystrophy in girls, the presence of X-autosomal translocations or other chromosomal aberrations with the interest of the X-chromosome, as well as some other rare genetic variants, should first be excluded. In addition, Shereshevsky-Turner syndrome (X-monosomy) must be excluded. For this purpose, a cytogenetic study of the karyotype is carried out.

Emery-Dreyfus myodystrophy is a slowly progressive form of myodystrophy with an X-linked recessive type of inheritance, which is caused by a mutation in the gene of the cytoskeletal muscle protein - emerin, which is produced mainly in skeletal, smooth muscles and cardiomyocytes.

Clinical picture (Fig. 6.8). The disease begins between 5 and 15 years of age. The earliest and most typical symptoms are progressive flexion contractures in the elbow joints and extensors of the hands, retraction of the Achilles tendons. As a rule, at the age of 12, patients already have significant contractures in the knee, ankle and elbow joints. Then there is weakness and atrophy of the biceps and triceps muscles of the shoulder, later - the deltoid and other muscles of the shoulder girdle. In some cases, walking on the toes and outer edges of the feet is noted as the first symptom, which occurs at about 5 years of age. Up to this point, the motor development of children is usually not disturbed. Muscle weakness occurs imperceptibly and slowly progresses. Approximately at the age of 20, relative stabilization occurs. The ability to walk and climb stairs is preserved. The facial muscles are not affected. Muscle weakness is present in the arms (scapulohumeral) and in the legs (peroneal). Govers maneuvers and pseudohypertrophy of the calf muscles may be absent. Tendon reflexes are not elicited. The posterior cervical muscles are often shortened, there is a limitation

Rice. 6.8.A 12-year-old patient with Emery-Dreyfus muscular dystrophy

movements in the cervical spine (stiff spine syndrome). Frequent and prognostically important symptoms of the disease are cardiac conduction disorders and developing dilated or hypertrophic cardiomyopathy. Cardiomyopathy may be complicated by the development of atrial palsy due to fibrosis of the pacemakers of the sinus node. In these cases, urgent implantation of an artificial pacemaker is indicated.

Syncope and bradycardia attacks in some cases may precede the onset of muscle weakness, but most often occur in the 3rd decade of life. Changes in the conduction system of the heart are not always detected by a standard ECG study, but monitoring can reveal atrioventricular blockades and Samoilov-Wenckebach periods. An arrhythmia that cannot be corrected by the implantation of an artificial pacemaker can lead to a stroke and death of the patient. The vital prognosis for Emery-Dreyfus myodystrophy depends entirely on the degree of heart damage.

Diagnostics.The activity of CPK is increased moderately, lactate dehydrogenase and aldolase - to a lesser extent. In favor of Emery-Dreyfus muscular dystrophy is evidenced by the absence of an immunofluorescent reaction to emerin with 12 monoclonal antibodies in biomicroscopy of leukocytes, muscle and skin biopsies. The disease is characterized by combined EMG signs of primary muscular and neurogenic lesions with a large representation of spontaneous denervation activity.

Facial-shoulder-shoulder myodystrophy (Landuzi-Dejerine type). The disease is inherited in an autosomal dominant manner with high penetrance and variable expressivity. It occurs with a frequency of 2.9 per 100,000 population. The genetic heterogeneity of facial-shoulder-shoulder myodystrophy was established. Most cases are associated with a mutation in the long arm of chromosome 4.

clinical picture. The disease usually begins in the 2nd decade of life. Initially, atrophy is observed in the shoulder girdle, later spreading to the face. In patients, facial expressions are depleted; speech becomes slurred. At the height of the disease, the circular muscles of the mouth and eyes, the pectoralis major, anterior serratus and lower sections of the trapezius muscle, the latissimus dorsi, the biceps and triceps muscles of the shoulder are affected. There are characteristic symptoms in the form of a "transverse smile" ("Gioconda's smile"), protrusion of the upper lip ("tapir lips"). The chest is flattened in the anteroposterior direction, the shoulder joints are rotated inward, the shoulder blades acquire a pterygoid shape. Atrophies spread in a downward direction. When the leg muscles are involved in the process, weakness is most noticeable in the peroneal muscle group - “hanging foot”. Asymmetric atrophy is characteristic. Muscle pseudohypertrophy may be observed. Contractures and retractions of the tendons are moderately expressed. Cardiomyopathy is rare. Anomalies of retinal vessels in angioretinography are considered as one of the phenotypic manifestations of the disease. Severe ocular symptoms are accompanied by telangiectasia, edema, and retinal detachment. Hearing loss may occur. Telangiectasias are eliminated by coagulation, which prevents the development of blindness. The course of the disease is relatively favorable. Physical overload, intense sports activities and irrationally conducted physiotherapy exercises can contribute to a more severe course of the disease. Many sick

remain functional and their quality of life does not deteriorate. Other patients with the disease are confined to a wheelchair in adulthood.

Diagnostics.The level of CPK can increase 5 times. EMG records both myopathic motor units and denervation potentials. In many limb muscles, histological changes are minimal; in the suprascapular muscles, progressive degeneration and marginal denervation are found. It is necessary to exclude myasthenia gravis and tumor of the brain stem.

Limb-girdle myodystrophy (CPMD) - cases of proximal muscle weakness that begins to develop in the 2nd or 3rd decade of life, slowly progresses and leads to deep disability only after 15-20 years.

Etiology and pathogenesis. CMDD is not genetically homogeneous; To date, about 10 different genetic defects have been identified.

clinical picture. The muscles of the shoulder and pelvic girdle are the first to be affected. In advanced stages, the muscles of the back and abdomen are significantly affected, and lumbar hyperlordosis is formed. The muscles of the face are usually not affected. Patients show a typical "duck" gait, myopathic techniques. Contractures and pseudohypertrophy of muscles are uncharacteristic. Cardiomyopathy does not develop; intelligence is preserved. Men and women are equally affected. Fatal outcome may result from pulmonary complications.

Diagnostics.The content of CPK is moderately increased. EMG shows signs of a primary muscle lesion. CMMD must be distinguished from Becker myopathy, juvenile spinal amyotrophy, glycogen storage myopathy, endocrine, toxic, drug-induced myopathies, polymyositis, and myositis.

6.2. Congenital structural myopathies

Congenital structural myopathies (SCM) are a genetically heterogeneous group of slowly progressive skeletal muscle diseases. Clinical symptoms of various SCM are nonspecific. The main clinical symptom is diffuse muscular hypotension, which can occur even in utero and determine the rare fetal movement. SCM belongs to a significant proportion among the causes of the so-called sluggish child syndrome. Hypotension prevails in the muscles of the pelvic girdle and proc-

simal parts of the legs. The muscles of the shoulder girdle and arms are affected to a lesser extent. Often, congenital dislocation of the hip, dolichocephalic head shape, gothic palate, horse foot, kyphoscoliosis, muscle hypoplasia are detected. A delay in motor development is characteristic: children begin to hold their heads up, sit, get up, walk late, often fall when walking, and are unable to run. In the future, they cannot perform the simplest gymnastic exercises, participate in outdoor games. Tendon reflexes in patients may be normal, reduced or absent. An extremely important criterion for SCM is the absence of progression or a very slow increase in muscle weakness. In some forms, motor functions may improve somewhat with age.

Diagnostics.CPK activity is normal or slightly increased. EMG records low-amplitude polyphasic myopathic potentials of motor units. The speed of impulse conduction along the motor and sensory fibers is normal. The diagnosis is reliably established only by performing a muscle biopsy using light and electron microscopy, which reveals the specific structure of the muscle fiber. Examination of muscle biopsy specimens from sick children can reveal unique histological features that have determined a number of names: central rod disease, myotubular myopathy, non-crimson myopathy, three-lamellar myopathy, type I fiber lysis myopathy, spherical body myopathy, myopathy with the accumulation of bodies in the form of "prints fingers", myopathy with cytoplasmic inclusions in the form of reduced bodies, myopathy with tubule aggregation, etc.

Treatment of muscular dystrophies. Therapeutic options for myodystrophy are significantly limited. Etiological and pathogenetic treatment practically does not exist. Symptomatic treatment is aimed at maintaining the existing muscle strength for as long as possible, reducing the rate of atrophy and preventing the formation of contractures. The main task is to extend the period of activity for the maximum possible period.

Comprehensive treatment consists of drug therapy, physiotherapy, therapeutic exercises and massage, orthopedic correction and diet. An important role is played by psychological support, continuing education, and proper professional orientation.

Physiotherapeutic procedures include electrophoresis of prozerin, calcium chloride, sinusoidally modulated or diadynamic currents of various penetrating abilities, electromyostimulation, ozocerite, paraffin and mud applications, baths (radon, coniferous, sulfuric, hydrogen sulfide). Oxybarotherapy is recommended, since oxygen inhibits the processes of fibrosis and collagen formation. Orthopedic correction of a conservative (special splints and styling) and operational nature (Achilleotomy, myotomy) is aimed at combating contractures and emerging pathological limbs and also aims to preserve the patient's ability to move independently. In each case, it is necessary to individually weigh the expected benefits and possible harm from surgery. With developing contractures after thermal procedures, it is recommended to carefully stretch the muscles up to 20-30 times a day, followed by splinting during sleep.

The patient is recommended a diet enriched with protein, with a restriction of fats (especially of animal origin) and carbohydrates with an optimal and balanced content of vitamins and microelements. It is necessary to avoid salty, fried, spices, marinades, strong meat broths, coffee, chocolate, cocoa, cakes, pastry.

Drug therapy aims to compensate for the energy deficit in muscle tissue, improve tissue metabolism and blood circulation, and stabilize the membranes of muscle fibers. Apply nicotinic acid, vitamins B 6 , B 12 , A and E (aevit). Amino acid preparations (cerebrolysin, glycine, methionine, glutamic, folic acids) are used to improve protein-synthetic processes. Non-steroidal anabolic agents (potassium orotate), macroergic drugs (phosphaden), cardiotrophics (riboxin, carnitine chloride, solcoseryl), peripheral circulation improvers (trental, halidor, teonicol, oxybral) and nootropics [pantogam, piracetam (nootropil)] are prescribed. To improve the energy processes occurring in the mitochondrial respiratory chain system, coenzyme Q10 (ubiquinone), lymantar, intravenous infusions of cytochrome-C are used. The effects of detoxification and improvement of the rheological properties of blood, relief of slide syndrome are achieved by infusions of vasoactive drugs, rheopolyglucin, and plasmapheresis courses. Relative stabilization of cell membranes is facilitated by small doses of prednisolone. For correction

cardiomyopathy use cardiotrophics (except for patients with hypertrophic cardiomyopathy); in heart failure - cardiac glycosides, diuretics, captopril. With cardiac arrhythmias, quinidine, β-blockers, calcium antagonists are prescribed. With the development of a complete atrioventricular blockade, the question of the advisability of implanting an artificial pacemaker becomes relevant.

Prospects for the development of genetic therapy methods for some myodystrophies (Duchenne and Becker diseases) are associated with the improvement of genetic technologies. Goes active search genetic carriers (vectors) capable of inserting the dystrophin gene or mini-genes into the muscle cells of a sick recipient. Exceptional importance is attached to medical genetic counseling of the family, prenatal diagnostics with the study of fetal DNA.

6.3. Spinal muscle amyotrophies

Spinal muscle amyotrophies (SMA) is a heterogeneous group of hereditary disorders of the peripheral nervous system. The pathogenesis is associated with the progressive degeneration of the motor neurons of the anterior horns of the spinal cord (in some cases, the motor nuclei of the brain stem). The reason for this is a genetic defect that causes programmed cell death - cell apoptosis. The loss of motor neurons leads to the development of flaccid paralysis and denervation atrophy of the striated muscles. In most cases, there is a symmetrical lesion of the proximal muscles of the limbs; distal amyotrophy, damage to the bulb

bar muscles and asymmetry of the lesion develop less frequently. The central motor neuron is usually intact. There are no sensory disturbances.

Different variants of SMA differ in the age of onset, the nature of the course, the topography of the lesion of the skeletal muscles and the type of inheritance (Fig. 6.9). Most forms are inherited in an autosomal recessive manner. Several forms are characterized

Rice. 6.9.Flaccid baby syndrome in SMA

autosomal dominant and X-linked recessive inheritance patterns. Histological examination of muscle biopsy reveals that muscle fibers of small size, bundles of hypertrophic and atrophic muscle fibers are adjacent to groups of fibers of normal size.

If the EMG shows undeniable symptoms of SMA, a muscle biopsy is not necessary. The principles of treatment and rehabilitation of SMA are the same as for myodystrophy. Etiotropic and pathogenetic treatment has not yet been developed.

Proximal spinal amyotrophies of childhood are inherited in an autosomal recessive manner. There are three phenotypically different variants that differ in the age of clinical manifestation, course and prognosis:

Type I, or acute malignant infantile SMA of Werdnig-Hoffmann;

Type II, or chronic infantile SMA (intermediate type);

Type III, or juvenile Kugelberg-Welander SMA.

They are based on a single genetic mutation - a deletion of the gene for the viability of a motor neuron located on the long arm of chromosome 5. The search for a mutation is carried out during DNA diagnostics, including in the fetus during prenatal diagnosis, which helps to avoid the birth of a sick child.

Acute malignant infantile spinal amyotrophy (Werdnig-Hoffmann disease, or SMA type I) occurs with a frequency of 1 in 25,500 newborns. Clinical symptoms are noted already at birth or appear before 6 months of life. Still in utero, sluggish stirring is noted, indicating a decrease in the motor activity of the fetus. A sick child is found to have generalized weakness, mainly in the proximal muscle groups, hypotension and areflexia. In the position on the back, a "frog pose" is observed with breeding and external rotation of the hips. The facial muscles are relatively intact, the oculomotor muscles are not involved. Respiratory function is initially adequate. Atrophy and fasciculations in the tongue, fascicular tremor of the hands are revealed. With the development of the bulbar syndrome, the pharyngeal reflex disappears, feeding becomes much more difficult, which can lead to aspiration pneumonia. Chest deformity is often formed (Fig. 6.10). If muscle weakness

Rice. 6.10.Child, 6 months old, with Werdnig-Hoffmann disease

is detected immediately after birth, then death occurs at about 6 months of age, while when the first symptoms appear after 3 months of life, the survival period can be about 2 years. The main cause of death is respiratory failure against the background of intercurrent respiratory diseases (Fig. 6.11, 6.12).

For diagnosis, a gene mutation is detected by molecular genetic analysis. The concentration of CPK is usually normal, but in children with rapidly progressive weakness, it may be slightly increased. EMG detects fibrillation and fasciculation potentials at rest and an increase in the average amplitude of motor unit potentials. The speed of conduction along the motor axons of peripheral nerves, as a rule, corresponds to the norm. Type I SMA must be differentiated from other conditions that cause flaccid baby syndrome. These include congenital myodystrophy and neuropathy, structural myopathies, congenital or neonatal myasthenia gravis, metabolic myopathies, intrauterine poliomyelitis, botulism, chromosomal pathology, atonic form of cerebral palsy, Marfan's syndrome.

Chronic infantile spinal amyotrophy (SMA type II). Muscle weakness usually appears between the 6th and 24th months of life. The earlier the symptoms debut, the more malignant the course. The initial manifestations of weakness are usually symmetrical and are observed in the proximal muscle groups of the limbs. Weakness of the thigh muscles is the most noticeable symptom. In the early period, distal muscle weakness is minimal or absent. Tendon reflexes from the affected muscles are sharply reduced. All patients are able to sit, most are able to stand on their own, and some can even walk (Fig. 6.13). Mimic muscles

Rice. 6.11.Boy, 5 years old, with Werdnig-Hoffmann disease

Rice. 6.12.Boy, 3 years old, with Werdnig-Hoffmann disease

Rice. 6.13.Girl, 9 years old, with Kugelberg-Welander disease

and external muscles of the eye in the early stages of the disease are not affected. Muscle weakness progresses slowly. In some cases, it remains stable for many years, and then the progression resumes. It is assumed that patients will survive until adulthood, but even during the period of relative stabilization, EMG reveals

fibrillation and fasciculation potentials. Formed contractures, equinovarus deformity of the feet. Already in infancy, children are observed curvature of the spine, deformities of the chest, dysplasia of the hip joints.

Diagnostics.The concentration of CPK is normal. The results of genetic analysis and EMG data are the same as in the acute infantile form.

Juvenile spinal amyotrophy (Kugelberg-Welander disease, or type III SMA) occurs in the general population with a frequency of 1.2 per 100,000. Motor activity in the intrauterine period is sufficient; the baby is healthy at birth. The onset of symptoms occurs between the 2nd and 15th year of life. Children begin to walk unsteadily due to increasing proximal muscle weakness in the legs. Pseudohypertrophy of the gastrocnemius muscles develops, which often leads to misdiagnosis of Duchenne muscular dystrophy. The disease flows benignly, progresses very slowly. The brushes are affected later. The facial muscles may be weakened, but the movements of the eyeballs are always full. Bulbar disturbances are uncharacteristic. Approximately half of the patients may develop bone deformities, occasionally - tendon retractions and contractures in the joints. Tendon reflexes from weakened muscles are absent or significantly depressed. Often recorded fascicular tremor of the hands.

Diagnostics.Of paramount importance is the identification of a genetic mutation. The concentration of CPK can exceed the upper limit of the norm by 2-4 times. Half of the patients with EMG recorded spontaneous activity (fasciculations, fibrillations and positive sharp waves). With muscle tension, an increase in amplitude and polyphasia, an increase in duration and a decrease in the number of potentials of motor units are noted. Conduction along the sensitive fibers of the nerves is always normal. The speed of conduction along the motor fibers with a long course of the disease may decrease. Type III SMA is differentiated from limb-girdle myodystrophy.

Kennedy bulbospinal amyotrophy - a rare X-linked recessive form of SMA, debuting in the 4th decade of life; occasionally there are cases of debut of symptoms at 12-15 years. The gene is mapped on the long arm of the X chromosome. The mutation affects the androgen receptor gene, including spinal motor neurons, which makes these

receptors insensitive to the effects of male sex hormones (androgens). The core of the clinical picture is weakness, atrophy and fasciculations in the proximal muscle groups of the limbs, tendon areflexia, facial weakness, atrophy and fasciculations in the tongue, perioral fasciculations, dysarthria and dysphagia, tremor and painful muscle spasms (cramps). Rarely, axonal neuropathy develops. Bulbar disorders usually occur 10 years after the onset of the disease. Endocrine disorders are characteristic: gynecomastia, testicular atrophy, decreased potency and libido, diabetes mellitus, infertility due to azoospermia. The prognosis of the disease is generally favorable: the ability to walk and the possibility of self-care are preserved. Life expectancy does not decrease, but the risk of malignant neoplasms due to hormonal imbalances (including breast cancer) is increased.

Diagnostics.Currently, it is possible to conduct direct DNA diagnostics, establish heterozygous carriage, and perform prenatal diagnostics. EMG reveals signs of denervation. CPK levels may be normal. The disease must be distinguished from amyotrophic lateral sclerosis.

6.4. Multiple congenital arthrogryposis

Multiple congenital arthrogryposis is a syndrome, the main manifestation of which is the restriction of mobility in the joints in combination with their deformities. Distal joints (ankle, wrist) are usually affected, less often - knee and elbow joints. Muscle weakness in arthrogryposis can be both neurogenic and myogenic in nature. The vast majority of cases are sporadic, the remaining cases are inherited in an autosomal recessive or X-linked manner. With neurogenic arthrogryposis, the most active phase of the disease is observed in the prenatal period, and already in the neonatal period, breathing and swallowing are disturbed; some children die from aspiration. In milder cases, survival is better, and muscle weakness progresses very slowly or does not progress at all. Respiratory disorders and feeding problems subsequently disappear. Contractures are present in both proximal and distal joints. Some newborns have associated micrognathia, high palate, facial abnormalities, as in

Edwards syndrome (trisomy 18). Some children with neurogenic arthrogryposis have anomalies in the development of the forebrain. There are combinations with meningomyelocele, microcephaly and mental retardation. The syndrome of myogenic arthrogryposis can be observed in myopathy with a disproportion of fiber types, congenital myodystrophy, myotonic dystrophy, myasthenic syndromes, phosphofructokinase deficiency.

Diagnostics.Histological examination of the muscles reveals characteristic signs of denervation and reinnervation. Also, manifestations of myopathy are revealed: an increase in the proportion of collagen fibers and adipose tissue, the chaotic arrangement of medium-sized fibers, fibrosis of muscle spindle capsules.

6.5. Inflammatory myopathies

Dermatomyositis is a systemic immune-dependent angiopathy in which vascular occlusions and infarcts are observed, leading to the development of all characteristic pathological changes in muscles, connective tissue, skin, gastrointestinal tract and nerve fibers. Pathogenesis is associated with the formation of antibodies and immune complexes and activation of the complement system. The composition of the perivascular infiltrate includes T-lymphocytes, which in the vast majority are T-helpers, B-lymphocytes and plasma cells.

clinical picture. The peak incidence occurs at the age of 5-10 years, but cases of an earlier onset (up to 4 months of age) have been described. Symptoms come on gradually or at lightning speed. The latent onset is characterized by fever, malaise, and loss of appetite (anorexia). Muscle weakness at this time may be absent. These non-specific symptoms persist for weeks to months, suggesting a persistent infection. In most children, dermatitis appears before myositis. The rash is initially localized on the upper eyelids and looks like

erythema with foci of impaired pigmentation and edema. It then spreads around the eyes and into the cheek area. Erythema and edema on the extensor surfaces of the interphalangeal, elbow, and knee joints develop later. Over time, the skin becomes atrophic and flaky. Myopathic changes include proximal weakness, muscle stiffness, and pain. Weakness increases, flexion contractures and joint deformities develop rapidly. Tendon reflexes decrease and then disappear. In 60% of patients, calcifications are found in the subcutaneous tissue, especially under those areas of the skin where pigmentation is impaired. Multiple calcifications create an "armor" effect on x-rays. In some children, the leading initial symptom is muscle rigidity, and skin and myopathic symptoms are less pronounced. Gastrointestinal tract infarcts in the terminal stages of the disease in the past led to death. Mortality in dermatomyositis has now decreased and is less than 5%, which is associated with the improvement of treatment methods. More than 30% of adults with dermatomyositis are later diagnosed with malignancy.

Diagnostics.The combination of fever, rash, myalgia, and weakness supports the diagnosis of dermatomyositis. At the onset of the disease, the level of CPK is usually elevated. During active dermatomyositis, resting EMG reveals fibrillations and positive sharp waves; with muscle tension, shortened low-amplitude polyphasic potentials are recorded. Muscle biopsy reveals myofibril atrophy. Capillary necrosis first occurs along the periphery of the muscle bundle and causes ischemia of the adjacent myofibrils. The most pronounced atrophy is in the bundles that are in contact with large fascial cases. Fibers I and II types (tonic and phasic) are equally affected.

Treatment.The inflammatory process is active for 2 years. Corticosteroids reduce its activity, helping to reduce symptoms. The best results are achieved when corticosteroids are given early in the disease, at high doses and for a long time. Prednisolone is the drug of choice. Its initial dose is given at the rate of 2 mg / kg per day, but not higher than 100 mg / day. Body temperature often returns to normal within the first 48 hours from the start of therapy. Sometimes CPK levels come back

to normal on the 2nd week of treatment in parallel with a noticeable increase in the strength of muscle contraction. In this case, further administration of prednisolone can be carried out according to the scheme every other day and at a dose that will reduce the severity side effects steroid therapy. Therapy with prednisolone is equally effective when taking the drug daily or on a schedule every other day, but only in cases where treatment is not interrupted. When muscle strength increases, the initial dose of prednisolone taken every other day can be reduced by 10% per month for 5 months. Further reduction in the dose of prednisolone is permissible only by 5% per month. When deciding whether to reduce the dose of corticosteroids, it is unacceptable to focus only on a decrease in CPK activity, since a noticeable increase in muscle strength occurs only 1-2 months after a decrease in the level of the enzyme, i.e. The leading criterion for reducing the dose of corticosteroids is the positive clinical dynamics. In most patients, the maintenance dose of prednisolone taken according to the regimen every other day, which is necessary to normalize the strength of muscle contraction and CPK concentration, is 25% of the starting dose.

When treated with prednisone, the rash completely disappears in some patients, but the majority remain cicatricial changes in the skin. Long-term steroid therapy requires monitoring of gastrointestinal function. To protect the gastric mucosa, preparations of potassium chloride and H2-receptor blockers are prescribed. A serious complication of long-term therapy is the development of steroid myopathy, which can be regarded as an exacerbation of the underlying disease. It is quite difficult to distinguish developing steroid myopathy from exacerbation of dermatomyositis by clinical criteria. With steroid myopathy, as a rule, the proximal extremities suffer, pronounced atrophies develop, and CPK activity does not increase. In most children with dermatomyositis, treatment improves after 3 months, but prednisolone therapy should be continued for 2 years. If treatment is interrupted prematurely, relapses are inevitable, calcification and contractures develop. Drug treatment is supplemented with physical rehabilitation, breathing exercises are necessary. Massage in the active phase is contraindicated. With proper treatment, a favorable outcome is observed in 80% of children with dermatomyositis. With resistance or intolerance to prednisone

oral administration of cytostatics is indicated: methotrexate at a dose of 10 to 20 mg / m 2 of body surface 2 times a week or azathioprine at a dose of 50-150 mg / day. During therapy, regular monitoring of liver function and blood cell composition is necessary. The combination of corticosteroids and cytostatics avoids long-term therapy with high doses of prednisolone. In cases where the use of corticosteroids is limited by their side effects, plasmapheresis or a course of intravenous infusions of immunoglobulin are used. In the inactive stage, exacerbations usually do not occur.

Polymyositis. The etiology in most cases remains unknown. It is assumed that cellular and humoral mechanisms play a role in pathogenesis, which is confirmed by the frequent development of the disease against the background of autoimmune processes (systemic lupus erythematosus, periarteritis nodosa, rheumatoid arthritis, scleroderma), as well as the good effect of the use of corticosteroids and immunosuppressants. The pathogenesis is associated with a cell-mediated cytotoxic reaction implemented by T-lymphocytes sensitized to the surface antigens of muscle fibers.

clinical picture. Polymyositis usually occurs in adulthood (45-55 years), is rare in children and adolescents and is not associated with malignant neoplasms. Gradually, gradually, symmetrical proximal muscle weakness increases, fever and myalgia are atypical. Weakness of the neck flexors ("drooping head") often develops. The disease is characterized by dysphagia and asthma attacks. Gradually, weakness spreads to the distal extremities. The severity of paresis varies, and in severe cases, tetraplegia develops. Occasionally, weakness is limited to distal muscle groups, muscles of the eye or face. The patient may experience periods of stabilization and even remission, which can lead to an erroneous diagnosis of limb-girdle myodystrophy. In the chronic course of the disease, muscle atrophy gradually increases; possible formation of contractures. Tendon reflexes are elicited early in the disease and decrease as muscle mass decreases, but never completely disappears. This most important differential diagnostic feature makes it possible to exclude polyneuropathy. Sometimes the disease begins acutely with a general malaise; sharp muscle weakness develops within a few days, pain in the muscles of the shoulder girdle appears. Muscle atrophy is very mild

or absent. Muscles often show calcifications on x-rays. In adults, cardiopulmonary complications are typical, uncharacteristic of the childhood form of the disease.

Diagnostics.Changes in CPK are rare. An EMG study almost always reveals typical signs of both myopathic and neurogenic processes. Muscle biopsy reveals various pathological abnormalities. Histologically, perivascular inflammatory infiltration is not always observed, so the absence of cellular infiltrates in biopsy specimens does not exclude the diagnosis of polymyositis.

For the treatment of polymyositis, the same scheme is used as for dermatomyositis. Patients who are resistant to corticosteroids are shown cytostatics (methotrexate). Plasmapheresis and intravenous immunoglobulin are viable alternative therapies where conventional therapy is not effective.

Acute infectious myositis occurs after the flu or other respiratory viral infection. Symptoms of a viral infection persist from 1 to 7 days, and then intense symmetrical pain and weakness in the muscles appear. In severe cases, the patient becomes immobilized within 1 day. Against the background of general weakness, the proximal muscle groups are more severely affected than the distal ones. Painful palpation of the muscles. Tendon reflexes are preserved. The level of CPK is usually more than 10 times the upper limit of normal. Almost immediately after the development of myositis, its spontaneous reverse development is observed. In the worst case, for the disappearance of the pain syndrome, it takes from 2 to 7 days of bed rest, after which the patient recovers completely.

Myotonia.The phenomenon of myotonia is a delayed reaction of relaxation (relaxation) of the muscle after its contraction. Allocate action myotonia, percussion or mechanical myotonia and electromyographic myotonia.

In the pathogenesis of myotonia, the instability of the muscle fiber membrane plays a role, which leads to repeated contractions of the muscle in response to a single stimulus. Repeated myotonic impulses do not occur spontaneously, but always with external influence or as a result of voluntary contraction. Myotonia of action can be observed in a patient after intense muscle contraction. The patient is asked, for example, to strongly squeeze the brush in

Rice. 6.14.Myotonic phenomena in a child with Thomsen's myotonia:

a- pseudohypertrophy of muscles; b- muscle roller with myatonic

reactions; in- inability to relax the hands during repeated movements

Rice. 6.15.

Rice. 6.16.Myotonic phenomena in a child with Thomsen's myotonia

fist and then quickly unclench it (Fig. 6.14-6.16). In this case, there is a certain time delay before the brush is fully opened. When performing the same task again, the myotonic phenomenon decreases each time and eventually disappears. In congenital paramyotonia, there is reverse phenomenon- increase in myotonia with repeated movements (paradoxical myotonia). Percussion myotonia is manifested by muscle contraction after mechanical stimulation (quick and vigorous blow of the hammer on the muscle). This phenomenon can be observed in any muscle, but it looks most impressive when hitting the thenar muscles: there is a rapid flexion and adduction of the thumb to the palm, which lasts for several seconds. With percussion of large muscles, symptoms of "roll" and "ditch" occur; with transverse percussion of the tongue, a "constriction" or "fossa" of the tongue is formed. Electromyographic myotonia is recorded when a needle is injected into the muscle

Rice. 6.17.EMG in myotonia, "dive bomber drone"

Rice. 6.18.Myotonia Thomsen in a child. "Herculean Muscles"

electrode. Active muscle tension or its percussion causes the appearance of high-frequency repetitive discharges, which initially increase in frequency (from 100 to 150 Hz) and amplitude, and then decrease. The total duration of such discharges is about 500 ms, and the sound equivalent resembles the rumble of a dive bomber (Fig. 6.17).

The phenomenon of myotonia is the most important symptom of several heterogeneous hereditary diseases (Fig. 6.18, 6.19).

Myotonic dystrophy, or Rossolimo-Kurshman-Steinert-Batten disease, is a multisystem disease that is inherited in an autosomal dominant manner with variable penetrance of the pathological gene. The etiology of the disease is associated with the instability of the DNA region of chromosome 19, which is expressed in its pathological amplification (repeatability). As a result, the number of copies of this gene increases from 50 to several thousand. Myotonic dystrophy can rightly be attributed to the class of so-called diseases of the expansion of nucleotide triplets. The number of repetitions increases in subsequent generations and correlates with a more severe course of the disease (anticipation phenomenon). The number of repetitions in a child

Rice. 6.19.Thomsen's myotonia in an adult patient

Rice. 6.20.Myotonia Rossolimo-Kurshman-Steinert-Batten. Typical patient appearance

when inheriting the disease from the mother, it increases to a much greater extent than when inheriting from the father. A mother with 100 trinucleotide repeats has a higher than 90% risk of having a baby with 400 repeats.

The disease is the most common type of muscular dystrophy that debuts in adults. The incidence of the disease is 3-5 cases per 100,000 population. Both sexes are affected with equal frequency. The first symptoms usually appear in teenagers. In advanced stages, myotonia, weakness of the facial muscles and distal extremities, cataracts, frontal alopecia, multiple endocrinopathy are noted. Atrophy of facial muscles is so stereotyped in appearance that all patients look similar: the face is elongated and thin due to weakness of the temporal and masticatory muscles; the neck is thin ("swan") due to atrophy of the sternocleidomastoid muscles; the eyelids and corners of the mouth are lowered, the lower half of the face sags, which makes the expression sad. Atrophy of the extremities is most pronounced in the distal sections: forearms and peroneal muscles (Fig. 6.20, 6.21). There is dysphagia due to damage to the muscles of the pharynx and smooth muscles of the esophagus. Tendon reflexes decrease and disappear.

In the later stages of the disease, atrophy of the small muscles of the hands develops. Patients complain of muscle tension, difficulty in movement due to stiffness. Myotonia increases with cold. In general, myotonic phenomena are not as pronounced as in congenital myotonia. A doctor can identify myotonic syndrome upon questioning and confirm upon examination. For example, when shaking hands, a patient with myotonic dystrophy fails to immediately unclench the hand. Extraneural symptoms of myotonic dystrophy - cataracts, frontal alopecia, or endocrine disorders - occur even before clinically significant symptoms of myotonia. ECG changes are often recorded. In later stages, severe cardiomyopathy with transverse block, Adams-Stokes-Morgagni attacks, and heart failure may develop. Intestinal peristalsis is disturbed, megacolon develops. Paresis of the diaphragm and intercostal muscles leads to hypoventilation and recurrent bronchopulmonary infections. Endocrine disorders include testicular atrophy, female infertility, hyperinsulinism, diabetes mellitus, adrenal atrophy, and impaired growth hormone secretion. Often develop hypersomnia and obstructive sleep apnea, mental disorders up to severe dementia.

Diagnosis is based on characteristic clinical manifestations and family history. EMG reveals myotonic phenomena, myopathic potentials, and slight signs of denervation. The activity of CPK most often corresponds to the norm. There is no need for a muscle biopsy to confirm the diagnosis. DNA analysis detects an increase in the number of trinucleotide repeats; it can be used to identify asymptomatic patients and perform prenatal diagnosis.

Treatment.The symptoms of myotonia weaken when prescribing drugs - membrane stabilizers: quinidine, novocainamide, phenytoin

Rice. 6.21.Myotonia Rossolimo-Kurshman-Steinert-Batten. "Swan" neck due to atrophy of the sternocleidomastoid muscle. Atrophy of the extensor muscles of the forearms, peroneal muscle groups, which leads to the appearance of a cock's gait

(difenin) and carbamazepine (finlepsin). It should be taken into account that myotonia in itself does not incapacitate the patient and does not require constant drug therapy. Unfortunately, the treatment of increasing muscle weakness is not yet effective. Patients often react negatively to treatment; do not tolerate anesthesia, which can be complicated by the development of malignant hyperthermia.

Congenital myotonic dystrophy. In a mother with myotonic dystrophy, the probability of having a child with a congenital form of the disease is 1:4, and if the father is sick - 1:12. The main signs of the pathology of the prenatal period in the congenital form are a decrease in the motor activity of the fetus and polyhydramnios. 50% of children are born prematurely. Labor can be protracted due to inadequate uterine contraction, and forceps are often required. In some newborns, the function of the diaphragm and intercostal muscles is so severely affected that they are not capable of independent breathing at all. In the absence of immediate intubation and mechanical ventilation, many of them die immediately. The most noticeable clinical symptoms in newborns are: facial diplegia, in which the mouth is unusually pointed and the shape of the upper lip resembles an inverted Latin letter "V"; generalized muscular hypotension; joint deformity, ranging from bilateral clubfoot to widespread arthrogryposis; dysfunction of the gastrointestinal tract in the form of paresis of the muscles of the stomach, impaired swallowing and aspiration. Weakness is most pronounced in the proximal limbs. Tendon reflexes are absent. Myotonic phenomena are not caused by muscle percussion and may not be detected by EMG. Neonatal mortality reaches 16% and is often due to cardiomyopathy. In surviving children, muscle strength, as a rule, increases, and the processes of feeding and breathing normalize within 1 month of life.

The long-term prognosis is unfavorable: mental retardation and pronounced clinical symptoms of myotonic dystrophy are found in all children. Diagnosis requires a diagnosis of myotonic dystrophy in the mother, who usually has multiple clinical signs of the disease and myotonic EMG phenomena.

The diagnosis of the mother and child can be clarified after the amplification of a DNA segment of chromosome 19. Family members are at risk and subsequently undergo genetic testing to establish carriage.

Emergency care for the newborn consists of immediate intubation and mechanical ventilation. The function of the gastrointestinal tract is normalized with the appointment of cerucal (metoclopramide). Joint stiffness is reduced with the use of physical therapies and immobilization.

congenital myotonia - a hereditary disease characterized by stiffness and true muscle hypertrophy. In 19% of families, autosomal dominant inheritance (Thomsen's disease) is traced, less often - autosomal recessive inheritance (Becker's disease). Most cases are sporadic. In general, in patients with an autosomal recessive form, the disease begins later and proceeds with more severe myotonic disorders than with an autosomal dominant form. However, the symptoms of both forms are the same, so it is impossible to draw a conclusion about the type of inheritance solely on clinical criteria (see Fig. 6.18, 6.19).

The pathological gene for both dominant and recessive forms of myotonia congenita is mapped on the long arm of chromosome 7, where the chloride ion channel gene is located.

The autosomal dominant form usually debuts in infancy with a change in voice with crying; the child begins to choke, and after crying, the face relaxes very slowly. The disease is mild. In adulthood, myotonia can lead to generalized muscle hypertrophy (athleticism), but even in childhood, the muscles have the appearance of "Herculean muscles". Sometimes the muscles of the tongue, face, and masticatory muscles are involved. Muscle stiffness is not accompanied by pain; it increases when the patient stays in the cold. Percussion myotonic symptoms are revealed. Muscle mass, contraction strength and tendon reflexes are normal. Immediately after rest, the muscles remain constrained, and movements are difficult. However, after activation, the stiffness disappears, the normal range of motion is restored.

Diagnostics.The diagnosis is confirmed by an EMG study. The frequency of repeated muscle oscillations varies from 20 to 80 cycles per second from the moment of initial insertion of the needle into the muscle until the onset of voluntary contraction. The amplitude and frequency of the potentials rise and fall, which is accompanied by a characteristic sound - "the rumble of a dive bomber." There are no signs of muscular dystrophy. The level of CPK is normal. Muscle biopsy specimens show muscle fiber hypertrophy.

Treatment.Myotonia does not always require treatment, and drugs are not effective enough. Stiffness can sometimes be relieved with phenytoin (Diphenin) or carbamazepine (Finlepsin) preparations given at moderate anticonvulsant doses. Novocainamide is prescribed at an initial dose of 200 mg 2 times a day, and then it is gradually increased to 400 mg 3 times a day. The drug reduces muscle stiffness in children with the recessive form of the disease. Diacarb (acetazolamide) is effective for some patients. In severe cases, a short course of corticosteroids is indicated. Useful calcium antagonists (nifedipine 10-20 mg 3 times a day), as well as disopyramide 100-200 mg 3 times a day. It must be taken into account that succinylcholine, veroshpiron, potassium, antihyperlipidemic agents and β-blockers can exacerbate myotonic syndrome.

Relapsing myotonia (myotonia aggravated by excess potassium) is an autosomal dominant syndrome associated with a mutation in the sodium channel gene. The gene is mapped on chromosome 17. Clinical manifestations are similar to myotonia congenita. The onset of muscle stiffness usually occurs after 10 years of age and may be triggered by general anesthesia. Myotonic phenomena are generalized, involving the trunk, limbs, and oculomotor muscles. The severity of myotonia varies from day to day and decreases with warming. The condition may worsen after intense exercise or ingestion of large amounts of potassium in the diet.

Diagnostics.EMG study reveals myotonic phenomena. There is no pathology in muscle biopsy specimens. Possible DNA analysis of the mutant gene encoding the α-subunit of the sodium channel.

Treatment.Stiffness in relapsing myotonia can be prevented by mexiletine, a drug similar in structure to lidocaine; as with other channelopathies, diacarb (acetazolamide) may be effective.

6.6. Periodic paralysis

Periodic paralysis, or paroxysmal myoplegia, is an umbrella term for a group of channelopathies, rare hereditary diseases characterized by bouts of flaccid skeletal muscle paralysis due to ion channel pathology. Paralysis is divided depending on the level of potassium in the blood: hyperkalemic (Gamstorp disease), hypokalemic and normokalemic. In addition, periodic paralysis can

be primary (genetically determined) or secondary. Secondary hypokalemic periodic paralysis is caused by the loss of potassium in the urine or its excess excretion from the gastrointestinal tract. "Urinary" potassium losses are associated with primary hyperaldosteronism, licorice (licorice) intoxication, amphotericin B therapy, and some renal tubular defects. "Gastrointestinal" potassium losses are most commonly observed in severe chronic diarrhea, prolonged tube feeding, and gastrofistula. Potassium is lost in adolescents with anorexia nervosa who abuse diuretics or self-vomit to “lose weight.” Hypokalemic periodic paralysis complicates thyrotoxicosis. Secondary hyperkalemic periodic paralysis may be due to renal or adrenal insufficiency.

Familial hyperkalemic paralysis inherited in an autosomal dominant manner with high penetrance. The mutation is located in the sodium channel gene.

clinical picture. The onset of attacks of muscle weakness refers to early childhood and even infancy. Attacks of weakness occur after intense physical exertion. Before an attack, there are sensitive disorders - paresthesia in the face, upper and lower extremities, a feeling of heaviness in the back. Occasionally, the patient can slow down the development of paralysis by walking or moving from place to place. In infants and young children, attacks are expressed by a sudden loss of muscle tone: they fall and cannot move. Older children and adults may experience both moderate attacks (lasting less than an hour and not leading to deep paralysis) and severe attacks (up to several hours). After several severe attacks, some residual muscle weakness may remain. Symptoms of myotonia in patients with hyperkalemic paralysis are moderate and may increase with cooling. Characterized by myotonia of the eyelids, tongue, muscles of the forearm and thumb.

Diagnostics.During an attack, the potassium content in the blood usually exceeds 5 mmol / l. Oral intake of potassium chloride immediately after exercise immediately provokes an attack of weakness, during which the muscles do not respond to electrical stimuli.

Treatment.Acute attacks rarely require treatment because they are short-lived. With a deployed attack can help intravenous

infusion of 40% glucose solution (up to 40 ml) or 10% calcium gluconate solution (up to 20 ml). Daily intake of diacarb (acetazolamide) prevents recurrent attacks, the mechanism of the preventive action of this drug in hyperkalemic and hypokalemic paralysis is unknown. You should avoid eating foods rich in potassium, increase the amount of carbohydrates and salt in the daily diet.

Familial hypokalemic paralysis inherited in an autosomal dominant manner. The penetrance of the gene in women is reduced. The mutation is located on the long arm of chromosome 7, in the calcium channel gene. In 60% of patients, symptoms occur before the age of 16, in the rest - up to 20 years of life. At first, attacks of weakness are infrequent, but then there are up to several times a week. Attacks provoke: rest after physical activity (often attacks are observed in the early morning), abundant intake of carbohydrate foods, excess salt in the diet, emotional stress, alcohol intake, hypothermia; in women - menstruation. Before and during an attack, the patient may experience thirst and oliguria, pain in the proximal muscle groups, then general weakness develops. Sometimes there is total paralysis, in which the patient is not even able to raise his head. Weakness of the facial muscles is rare, eye movements are always preserved. Respiratory failure does not develop. Most attacks last from 6 to 12 hours, and some - throughout the day (so-called myoplegic status). Muscle strength is quickly restored, but after several severe attacks, fatigue, weight loss, especially of the proximal limbs, and suppression of tendon reflexes may be noted. Autonomic disorders are typical: skin flushing, hyperhidrosis, lability of the pulse and blood pressure. Outside of attacks of muscle weakness, patients have no symptoms of neuromuscular pathology.

Diagnostics.During an attack, the level of potassium in the blood may drop to 1.5 mmol / l, which corresponds to ECG changes: bradycardia, flattening of the wave T, increasing intervals P-Q and Q-T. Muscles do not contract in response to electrical stimuli. For diagnostic purposes, an attack can be provoked by taking glucose at a dose of 2 g / kg and simultaneous subcutaneous administration of 10-20 units of insulin: an attack of paralysis develops after 2-3 hours.

Treatment.Acute attacks in patients with adequate renal function are treated with repeated doses of potassium at a dose of 5 to 10 g.

The same dose taken daily is recommended to prevent their occurrence. In younger children, the dose is lower. Daily intake of diacarb (acetazolamide) has been shown to be beneficial in preventing seizures in many cases. It has low toxicity and is generally well tolerated even with long-term use. You should reduce the caloric content of the daily diet due to carbohydrates and reduce the amount of salt. At the same time, foods rich in potassium are shown: dried fruits, dried apricots, prunes, dairy products, potatoes.

Familial normokalemichesky paralysis. In some families, there are cases of autosomal dominant periodic paralysis with normal levels of potassium in the blood. This is a variant of hyperkalemic periodic paralysis with a violation of the influx of potassium into the blood, when it is impossible to assess its true content in the tissues. Myoplegia lasts from several days to 2-3 weeks. The rate of increase and decrease in muscle weakness is usually slow. Tendon reflexes during attacks disappear. In some patients, hypertrophy of individual muscle groups is observed. Attacks are provoked by rest after intense physical activity, alcohol intake, cooling. Taking potassium chloride can provoke an attack of paralysis, while the use of 8-10 g of table salt daily avoids them.

6.7. myasthenia gravis

myasthenia gravis(myasthenia gravis)- an autoimmune neuromuscular disease, clinically characterized by pathological weakness and fatigue of voluntary muscles and associated with damage to the acetylcholine receptors (ACh-R) of the postsynaptic membrane of striated muscles by specific complement-fixing antibodies (AT).

The prevalence of myasthenia gravis is 0.5-5 cases per 100,000 population in all populations. Children and adolescents under 17 years of age account for 9-15% of the number of patients with myasthenia gravis. Average age onset of the disease - 7.2 years. The debut of myasthenia gravis is possible at any age. Congenital forms are described. Women get sick 3 times more often than men.

Etiology.A multifactorial disease in which hereditary predisposition due to an immunological defect and associated with anti-

B8 histocompatibility genes of the HLA system. The cause of myasthenia may be a viral lesion of the thymus gland, as a result of which it begins to produce T-lymphocytes with altered membrane structures; thymus tumor; in rare cases, a primary brain lesion of various etiologies.

The basis of the pathogenesis of myasthenia gravis is an autoimmune reaction to acetylcholinesterase receptors (ACh-R) of skeletal muscles. The level of antibodies to ACh-R in the blood of patients correlates with the severity of the disease. Antibodies to ACh-R block neuromuscular conduction, because they destroy ACh, reduce the rate of its recovery, irreversibly changing the receptors of the postsynaptic membrane.

Pathological anatomy. Dystrophic changes in axon terminals, synaptic clefts and postsynaptic structures occur, immunoglobulins and complement are deposited in them. Moderate degenerative atrophy is observed in the muscles, less often fiber necrosis in combination with mild lymphoid infiltration and plasmorrhagia. In 70-90% of patients, pathology of the thymus gland is detected (hyperplasia of germinal follicles, lymphoepithelial thymomas). In rare cases, myocarditis, thyroiditis, focal accumulations of lymphocytes in various organs are noted.

Clinical classification of myasthenia gravis (according to B.M. Gekht).

1. The degree of generalization of movement disorders:

1) generalized;

2) local:

a) eye

b) bulbar,

c) skeletal.

2. Severity of movement disorders:

1) light;

2) average;

3) heavy.

3. The course of the myasthenic process:

1) relapsing (myasthenic episodes);

2) non-progressive (myasthenic condition);

3) progressive;

4) malignant.

4. The degree of compensation of movement disorders under the influence of anticholinesterase drugs:

1) full (up to restoration of working capacity);

2) incomplete (the ability to self-service is restored);

3) bad (patients need outside care). clinical picture. Myasthenia gravis is characterized by pathological

fatigue and weakness of striated muscles. It is difficult for patients to climb stairs, walk, stay in one position for a long time, carry weights.

The most commonly affected are the oculomotor, facial, chewing muscles, as well as the muscles of the pharynx, larynx, and tongue. Damage to the external muscles of the eye during the first examination is detected in 40-50% of patients, and as the disease develops - in 90-95%. Ptosis can be unilateral, and occurs on one side or the other. In the morning and after rest, ptosis is less, increases with general or visual stress, towards evening. On examination, it is possible to provoke an increase in ptosis by asking the patient to close his eyes or sit down several times. Oculomotor disturbances are asymmetric, changeable under load and do not correspond to the innervation zones of the oculomotor nerves. Due to muscle weakness, nystagmus occurs in the extreme leads. Diplopia increases with visual and physical activity, bright light, in the afternoon (especially when watching TV), is more pronounced when looking into the distance, decreases after resting with eyes closed and in the morning (Fig. 6.22).

Weakness of the masticatory and temporal muscles leads to fatigue when chewing, sometimes to the sagging of the lower jaw, patients support the jaw while eating and help themselves when chewing with their hands. An important symptom is weakness of the facial muscles. It is more pronounced in the upper half of the face (in the circular muscles of the eyes), increases with repeated squinting and general physical activity. It is difficult for the patient to inflate his cheeks, a “transverse” smile occurs due to weakness of the circular muscle of the mouth. Weakness of masticatory and temporal muscles is also noted.

Rice. 6.22.Weakness of the eye muscles in myasthenia gravis

Damage to the bulbar muscles (soft palate, pharynx, and upper esophageal muscles), leading to dysphagia and dysarthria, develops in 40% of patients. It increases with speech, general physical activity, during meals and decreases after rest. Swallowing is disturbed (the patient chokes when eating, liquid food enters the nasal passages). Speech becomes nasal, hoarseness of voice or modulation disturbances similar to stuttering may be noted. In severe dysarthria, the patient cannot swallow or speak.

Weakness of the muscles of the neck and trunk is more typical for elderly patients. Weakness of the back muscles is manifested by a violation of posture. Due to the weakness of the back muscle group of the neck, it becomes difficult to raise the head in a supine position or when extending the neck in a vertical position. If myasthenia gravis debuts with weakness of the muscles of the trunk, bulbar and respiratory disorders develop in the future.

Complaints of shortness of breath when inhaling are due to weakness of the diaphragm or intercostal muscles. The weakening of the cough shock leads to the accumulation of thick sputum, viscous saliva, which cannot be spit out or swallowed.

The muscles of the extremities, especially the proximal, neck, and trunk are weakened. On examination, muscle atrophy, decreased muscle tone, lability of tendon and periosteal reflexes are revealed. Weakness of the muscles of the extremities can be isolated (without other symptoms of myasthenia gravis) or combined with weakness of other muscle groups. Weakness of the proximal extensor muscles is typical. The deltoid muscle, the triceps muscle of the shoulder, and the iliac muscle are most often affected.

In addition to motor disorders, myasthenia gravis is accompanied by various autonomic and endocrine disorders (hypo- and hyperthyroidism, hypocorticism, etc.). Myasthenia gravis is characterized by the dynamism of muscle weakness during the day, its intensification after exercise, reversibility or decrease in weakness after rest. Deterioration is provoked by physical activity, negative emotions, menstruation, infections, fever environment, and improve - night sleep, rest. The decrease in fatigue after the administration of anticholinesterase drugs (ACP) is pathognomonic.

The course of the disease is most often progressive, with remissions or progressive without remissions. In a malignant course, bulbar and respiratory disorders develop during the first weeks of the disease. Myasthenia often debuts after SARS or

stress, one symptom (transient ptosis, bulbar paresis, etc.). The condition of patients with myasthenia may be complicated by myasthenic crises or cholinergic crises.

myasthenic crisis develops due to decompensation of myasthenia gravis or insufficient dosage of ACP; may be caused by a bronchopulmonary infection. In this case, there is a sharp deterioration in the state with a violation of vital functions. Myasthenic crisis can be differentiated from other severe conditions accompanied by respiratory disorders by the presence of asymmetric external ophthalmoparesis, ptosis, bulbar syndrome, hypomia, limb and neck muscle weakness, which decreases in response to the administration of AChE drugs (Table 10).

Cholinergic crisis develops with an excessive dose of AChE drugs.

Table 10Differential diagnosis of myasthenic and cholinergic crises

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

The prognosis depends on the clinical form and treatment. Practical recovery is possible (in about 1/3 of patients), significant improvement, disability, deaths, especially with thymoma. The main symptoms that threaten the life of the patient are weakness of the muscles of the larynx and respiratory muscles. Causes of death in myasthenia: respiratory failure, aspiration pneumonia, side effects of corticosteroids and cytotoxic drugs.

Diagnosis includes history taking, clinical examination, test with AChE preparations (prozerin, tensilon, kalimin), electromyography, immunological examination, thymus examination, morphological examination of muscle biopsy, dynamic observation.

The clinical examination includes a study of the general neurological status and an assessment of the strength of the voluntary muscles of the face, neck, trunk and limbs before and after exercise. Muscle strength is assessed from 0 to 5 points, where 0 is no strength, 5 is normal strength, taking into account age and gender. Also, a syndrome of pathological muscle fatigue (increase in symptoms after exercise) is detected in the absence of symptoms of damage to the central nervous system.

Diagnostic criteria

1. Ptosis (unilateral, bilateral, asymmetric, symmetrical): the appearance or intensification of ptosis after looking up for a long time or after rapidly opening or closing the eyes repeatedly.

2. Weakness of chewing muscles:

Insufficient resistance to forced closing of the lower jaw;

Palpation of the temporal muscles during chewing reveals their weak contraction;

Patients are unable to tightly close the eyelids or to resist the passive opening of the eyes;

Patients cannot inflate their cheeks when pressing on them.

3. Weakness of the muscles of the larynx and palate is detected if:

The palate is inactive, the gag reflex is reduced or absent;

Difficulty swallowing liquid food.

4. Weakness of the muscles of the tongue is detected when the tongue is pressed on the doctor's finger through the cheek.

5. With severe weakness of the neck muscles, the “head hangs down”.

6. A proserin test with an assessment of muscle strength and fatigue is carried out before the subcutaneous injection of a 0.05% solution of proserin in a single age dosage and 30-40 minutes after it. The test is considered positive if muscle strength increases. Distinguish:

A sharply positive test, when all myasthenic symptoms disappear;

Positive test - only individual symptoms remain;

A weakly positive test, in which the severity of myasthenic symptoms decreases;

Doubtful proserin test - the severity of manifestations of myasthenia gravis changes slightly;

Negative prozerin test - clinical symptoms do not change after the introduction of prozerin.

Confirmation of the diagnosis of myasthenia gravis is the presence of one of the first three variants of the prozerin test.

An EMG of the most weakened muscles is performed to identify the features of neuromuscular transmission disorders (the muscle that removes the little finger in the digastric muscle of the floor of the mouth). The study is carried out against the background of the abolition of AHEP during the day, immediately after exercise and 2 minutes after exercise. Of great importance is the reversibility of EMG phenomena against the background of ACEP - an increase in the amplitude of the M-response. Electromyography shows a decrease in the amplitude of the second muscle action potential (normally both potentials are equal) in response to nerve stimulation with paired impulses with an interval of 0.1-0.7 s. In myasthenia, a decrease in the amplitude of potentials with constant stimulation of the nerve is replaced by a plateau phase or an increase in amplitude, while in other diseases there is a steady decrease in the amplitude of the response. When registering the activity of individual muscle fibers, characteristic signs of damage to neuromuscular synapses are often revealed. In 95% of cases, EMG reveals pathognomonic changes.

To exclude a tumor or hyperplasia of the thymus gland, which develops in 75% of patients with myasthenia gravis, computed tomography of the mediastinum, radionuclide scanning is performed.

An immunological study reveals the presence of antibodies to cholinergic receptors in 50% of patients with the ocular form of myasthenia gravis and in 80-90% of patients with a generalized form. With thymoma, antigens to skeletal muscles are also detected.

Immunological study (ELISA, RIA) is a quantitative method for determining antibodies to AChR in the blood serum of patients with myasthenia gravis, which allows confirming the diagnosis with a probability of up to 80%.

Differential diagnosis is carried out with conditions, the leading symptom of which is muscle weakness:

Myasthenic syndromes (botulism, poisoning with antibiotics from the aminoglycoside group, Itsenko-Cushing's disease, Addison's disease, hypo- and hyperthyroidism, poliomyositis);

Multiple sclerosis, neuroinfections (encephalitis, polyneuropathy,is): in patients, ophthalmoparesis is accompanied by hyporeflexia, ataxia, impaired sensitivity, changes in CSF;

Amyotrophic lateral sclerosis: constant weakness, atrophy, fasciculations, increased tendon reflexes, Babinsky's symptom;

Ocular form of myopathy: ptosis and symmetrical restriction of eyeball movements are characteristic; slight weakness of the muscles of the pharynx, neck, limbs and face;

Mitochondrial myopathies;

neuroendocrine syndromes;

Other diseases of the central nervous system (tumors, vascular diseases of the brain and spinal cord): reflex disturbances, conduction disorders are characteristic;

Asthenoneurotic reactions, chronic fatigue syndrome, etc.

Treatment. General principles:

1. With a generalized form, the patient is hospitalized and physical activity is limited until anticholinesterase therapy is selected.

2. Means blocking neuromuscular transmission, as well as having a depressing effect on the central nervous system, are contraindicated,

and especially on the respiratory center (quinine, quinidine, propranolol, lidocaine, aminoglycosides, polymyxin, morphine, barbiturates, tranquilizers). 3. The objectives of treatment depend on the severity of the disease. Anticholinesterase drugs (ACEPs)- drugs of choice for myasthenia gravis, inhibit the destruction of acetylcholine and contribute to its accumulation in the synaptic cleft, acting on cholinergic synapses, do not penetrate the BBB (Table 11). Side effects are due to the simultaneous effect on autonomic cholinergic synapses and depend on the dose and tone of the ANS. They can be reduced if AChE inhibitors are taken more often, but in smaller doses and with meals, which slows down absorption. In some situations (menstruation, infections, remission), the sensitivity to AHEP increases, and their dose is reduced. Patients are taught to adjust the dose on their own. Relative contraindications to the use of AHEP are bronchial asthma, severe atherosclerosis, coronary artery disease, epilepsy.

Table 11Anticholinergic drugs

Complementary Therapy: potassium preparations (prolong the action of AHEP); a diet rich in potassium (baked potatoes, dried apricots, bananas, etc.); potassium-sparing drugs (veroshpiron); potassium chloride 3.0 g/day in solutions, powders, tablets to prevent an overdose of AHEP; calcium preparations; tonic (extracts of eleutherococcus, rhodiola, leuzea, pantocrine); multivitamins, aminophylline (a phosphodiesterase blocker that increases the content of cAMP in the presynaptic membrane), anabolics (riboxin, retabolil).

Pathogenetic therapy - thymectomy. Efficiency - 70-90%, remissions are possible. Indications for surgical treatment are:

a) malignant forms of myasthenia gravis;

b) progressive form of myasthenia gravis;

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

Contraindications for thymectomy:

a) severe decompensated somatic diseases;

b) old age.

Preoperative preparation includes restorative therapy, plasmapheresis, according to indications - glucocorticoids, radiation therapy (contraindicated in children and adolescents).

Glucocorticoids (prednisolone, dexamethasone) shown when other methods are ineffective. They are prescribed daily or every other day, 60-150 mg / day (1-1.5 mg / kg / day) in the morning, immediately after breakfast, every other day; with a pronounced exacerbation, daily (until compensation of vital disorders), after 5-7 days (until the therapeutic effect) they switch to the scheme every other day. Maintenance dose - every other day 20-30 mg per day, taken for several months. Approximately 75% of patients corticosteroid therapy leads to significant improvement. After stable improvement, the dose of corticosteroids is slowly (over several months) reduced to maintenance (5-15 mg daily or 10-30 mg every other day). Sometimes it is possible to completely cancel corticosteroids. To avoid initial deterioration, treatment can be started at low doses (25 mg prednisolone every other day) with a gradual increase in dose of 12.5 mg every third dose until the daily dose reaches 100 mg or a good effect is obtained. Improvement is noted after 6-7 weeks of treatment. The dose in these cases begins to be reduced no earlier than 3 months after the first dose.

Plasmapheresisprescribed for exacerbations, myasthenic crises, preoperative preparation, ineffectiveness of corticosteroid therapy. 3-5 sessions are carried out every other day, then 2-3 times a week. Plasmapheresis is performed with plasma exchange or the use of protein substitutes. Hemosorption and enterosorption are carried out in patients with a generalized form of myasthenia gravis in order to remove antibodies, and in case of mixed crises and the ineffectiveness of massive drug therapy - in order to detoxify.

Cytostatics (azathioprine, cyclophosphamide and cyclosporine) prescribed under the control of blood tests. Immunoglobulin G preparations (in / in 0.4 g / kg / day daily for 5 days; or 3-5 g per course) are effective in intercurrent infections, during myasthenic or mixed crisis.

Crisis treatmentIt is aimed at compensation of vital disorders, relief of exacerbation and elimination of metabolic disorders. In the treatment of myasthenic crisis, AHEP is administered parenterally (kalimin-forte 1-1.5 ml IV or IM every 4-5 hours or prozerin 1.5-2 ml every 3 hours). ALV with the complete abolition of AHEP, the appointment of immunosuppressive therapy against the background of antibacterial drugs is carried out in order to prevent intercurrent infections. Disconnection from the apparatus is carried out only after 30 minutes of spontaneous breathing, with compensation for respiratory disorders and against the background of kalimina-forte for 5-6 hours. Large doses of glucocorticoids are prescribed according to an alternating scheme (pulse therapy - 1000-2000 mg IV drip every other day) with subsequent transfer to oral approx. They also stabilize cardiopulmonary activity. Plasmapheresis, intravenous infusions of normal human immunoglobulin are carried out. Cholinergic crisis is stopped by atropine, cholinesterase reactivators (dipiroxime); use detoxification.

There is a huge amount various diseases that occur in children regardless of circumstances or environmental influences. This is the category of hereditary diseases. Now we will talk about such a problem as Duchenne muscular dystrophy: what kind of illness is this, what are its symptoms and whether it can be dealt with.

Terminology

Initially, you need to find out what So is, these are diseases that arise as a result of defects in the apparatus of hereditary cells. That is, these are certain failures that occur at the genetic level.

Duchenne muscular dystrophy is a hereditary disease. It manifests itself very quickly, the main symptom in this case is a rapidly progressive weakness in the muscles. It should be noted: like all other muscular Duchenne also leads to impaired motor skills and, of course, disability. In adolescence, children with this diagnosis are no longer able to move independently and cannot do without outside help.

What happens at the genetic level

As already noted, Duchenne muscular dystrophy is So, a mutation occurs in the gene that is responsible for the production of a special dystrophin protein. It is he who is necessary for the normal functioning of muscle fibers. It is important to note that this genetic mutation can either be inherited or occur spontaneously.

It is also important to note that the gene is localized on the X chromosome. But women cannot get sick with this disease, being only a transmitter of the mutation from generation to generation. That is, if a mother passes the mutation on to her son, he will get sick with a 50% chance. If the girl, she simply will be the carrier of the gene, she will not have clinical manifestations of the disease.

Symptoms: groups

Basically, the disease actively manifests itself at about 5-6 years of age. However, the first symptoms may occur in a baby who has not yet reached the age of three. It should be noted that all pathological disorders of the medical system are conditionally divided into several large groups:

1. Muscle damage.
2. Damage to the heart muscle.
3. Deformation of the child's skeleton.
4. Various endocrine disorders.
5. Violations of normal mental activity.

The most common manifestations of the disease

Be sure to also talk about how Duchenne syndrome manifests itself. The symptoms are as follows:

• Weakness. Which gradually grows and develops.
• It starts progressing precisely from the upper limbs, then the legs are affected, and only then - all other parts of the body and organs.
• The child loses the ability to move independently. By about 12 years of age, such children are already completely dependent on a wheelchair.
• There are also disorders of the respiratory system.
• And, of course, there are violations in the work of the cardiological system. Later, irreversible changes occur in the myocardium.

About skeletal muscle damage

It is muscle tissue damage that is the most common symptom when it comes to such a problem as Duchenne syndrome. It should be noted that children are born without any special deviations in development. At a young age, children are less active and mobile than their peers. But most often this is associated with the temperament and character of the child. Therefore, deviations are very rarely noticed. More significant signs appear already while the baby is walking. Such children can move on their toes without standing on a full foot. They also fall frequently.

When the boy can already speak, he constantly complains of weakness, pain in the limbs, fatigue. Such crumbs do not like to run, jump. They do not like any physical activity, and they try to avoid it. "Say" that the baby has Duchenne muscular dystrophy, maybe even gait. She becomes like a duck. The boys seem to be shifting from foot to foot.

A special indicator is also the symptom of Gowers. That is, the child, in order to get up from the floor, actively uses his hands, as if climbing on himself.

It should also be noted that with such a problem as Duchenne syndrome, the child's muscles gradually atrophy. But it often happens that in the crumbs outwardly the muscles seem to be very developed. The boy, even at the first vskidka, turns out to be pumped up, as it were. But this is just an optical illusion. The thing is that in the process of illness, muscle fibers gradually disintegrate, and adipose tissue takes their place. Hence, such an impressive appearance.

A little about the deformation of the skeleton

If a child has progressive Duchenne muscular dystrophy, then the shape of the skeleton will gradually change in the boy. First, the pathology will affect the lumbar region, then scoliosis will occur, that is, the curvature of the thoracic spine will occur. Later, stoop will appear and, of course, the normal shape of the foot will change. All these symptoms will be accompanied by a deterioration in the baby's motor activity to an even greater extent.

About the heart muscle

A mandatory symptom in this disease is also damage to the heart muscle. There is a violation of the rhythm of the heart, there are regular drops in blood pressure. In this case, the heart increases in size. But its functionality, on the contrary, is reduced. And as a result, heart failure gradually develops. If this problem is still combined with respiratory failure, then there is a high probability of death.

Mental Disorders

It should be noted that Duchenne-Becker muscular dystrophy is not always manifested by such a symptom, as this may be due to a deficiency of a substance such as apodystrophin, which is necessary for the brain to function. Intellectual disabilities can be very different - from mild mental retardation to idiocy. The aggravation of these cognitive disorders is also facilitated by the inability to attend kindergartens, schools, clubs and other places where children gather. The result is social maladjustment.

Disorders of the endocrine system

Various endocrine disorders occur in no more than 30-50% of all patients. Most often it is overweight, obesity. At the same time, children also have a lower growth than their peers.

Outcome of the disease

What is the clinical and epidemiological characteristics of Duchenne muscular dystrophy? Thus, the incidence of the disease is 3.3 patients per 100,000 healthy people. It should be noted that muscle atrophy gradually progresses, and by the age of 15 the boy can no longer do without the help of others, being completely immobilized. In addition, there is also a frequent attachment of various bacterial infections (most often it is the genitourinary and respiratory systems), with improper care of the child, bedsores occur. If problems with respiratory system combined with heart failure, it is fatal. Generally speaking, such patients almost never live more than 30 years.

Diagnosis of the disease

What procedures can help diagnose Duchenne muscular dystrophy?

1. Genetic testing, that is, DNA analysis.
2. Electromyography, when the primary muscle change is confirmed.
3. A muscle biopsy, when the presence of dystrophin protein in the muscle is determined.
4. Blood test to determine the level of creatine kinase. It should be noted that it is this enzyme that indicates the death of muscle fibers.

Treatment

It is impossible to completely recover from this disease. You can only alleviate the manifestation of symptoms, which will make the life of the patient a little easier and more convenient. So, after the patient is diagnosed with such a diagnosis, most often he is prescribed therapy with glucocorticosteroids, which are designed to slow down the development of the disease. Other procedures that can also be used for this problem:

• Additional ventilation of the lungs.
• Therapy with medicines, which is aimed at normalizing the work of the heart muscle.
• The use of various devices that increase the mobility of the patient.

It is also important to note that the latest techniques are being developed today, which are based on stem cell transplantation as well.

Other muscle diseases

There are also other muscular congenital diseases of children. Such diseases include, in addition to Duchenne dystrophy:

• Becker's dystrophy. This disease is very similar to Duchenne syndrome.
• Dreyfus muscular dystrophy. It is a slowly progressive disease in which intelligence is preserved.
• Erb-Roth progressive muscular dystrophy. Manifested in adolescence, progression is rapid, disability occurs early.
• The humeroscapular-facial form of Landouzy-Dejerine, when muscle weakness is localized in the face, shoulders.

It should be noted that none of these diseases manifests muscle weakness in newborns. All symptoms occur mainly in adolescence. The life expectancy of patients most often does not exceed 30 years.