Myopathic syndrome: causes, symptoms, diagnosis

The term myopathy in the broad sense is understood as a disease of skeletal muscles. According to one of the modern classifications, myopathies are divided into muscular dystrophies, congenital myopathies, membrane myopathies, inflammatory myopathies and metabolic myopathies. Clinicians also use the term "myopathic syndrome" as a purely clinical concept, which refers to a specific reduction or loss of the ability to perform certain motor functions due to the weakness of certain muscles.

"Muscular dystrophy"

Membrane myopathies

Inflammatory myopathies

Metabolic myopathies

Toxic myopathies

Alcohol Myopathy

Paraneoplastic myopathy

Diagnosis of myopathies

The basic forms of myopathy:

• I. Hereditary progressive muscular dystrophies: Duchenne-strongecker muscular dystrophy, Emery-Dreifuss dystrophy, fasio-skapulo-humeral, skapuloperoneal, limb-distal, distal, oculopharyngeal, progressive external ophthalmoplegia. Congenital muscular dystrophy.
• II. Myopathies with myotonic syndrome (membranous myopathies).
• III. Inflammatory myopathies: polymyositis, AIDS, collagenoses, etc.
• IV. Metabolic myopathies (including endocrine and mitochondrial myopathies, myoglobulinemia, etc.).
• V. Iatrogenic and toxic myopathies.
• VI. Alcoholic myopathy.
• VII. Paraneoplastic myopathy.

[1], [2], [3]

"Muscular dystrophy"

Muscular dystrophy is a term used to refer to hereditary forms of myopathy, accompanied by degeneration of muscles. This - a whole group of diseases, most of which begins in childhood or adolescence, has a steadily progressing course and sooner or later leads to severe disability. Several detailed classifications of muscular dystrophies based on different principles (genetic, biochemical, clinical) have been proposed, but there is no unified classification.

Dystrophin-deficient dystrophies combine basically two forms: Duchenn's muscular dystrophy (Duchenn) and Becker's muscular dystrophy (strongecker).

Duchenne muscular dystrophy, or Duchenne's pseudo-hypertrophic muscular dystrophy is the most malignant and most common form of X-linked myodystrophy. Enzyme (CK) is detected already in the neonatal period, but clinical symptoms appear at the age of 2-4 years. These children start walking late, they find it difficult or impossible to run and jump, they often fall down (especially when they try to escape), they hardly walk up the steps or along an inclined floor (weakness of the proximal muscles) and walk on their thumbs (toe-walking) for contractures of the tendons of the foot. Perhaps a decrease in intelligence. Characterized by pseudohypertrophy of gastrocnemius muscles. Gradually the process takes the ascending direction. Hyperlordosis and kyphoscoliosis are formed. By 8-10 years, the gait is grossly violated. The patient rises from the floor with the help of characteristic "myopathic" techniques. By the age of 14-15, the patients are usually completely immobilized and die by the age of 15-17 from the weakness of the respiratory muscles of the chest. The ECG detects abnormalities in almost 90% of cases (cardiomyopathy). The level of CPK is sharply increased. On EMG - muscle damage level. In the biopsy of muscles, nonspecific, although characteristic histopathological disorders.

Becker's muscular dystrophy is the second most frequent, but benign form of pseudohypertrophic myodystrophy. The onset of the disease is between 5 and 15 years. The pattern of muscle involvement is the same as in the Duchenne form. The weakness of the muscles of the pelvic girdle and the proximal parts of the legs is characteristic. The gait changes, difficulties arise when getting up from a low stool, while climbing the stairs. The expressed pseudohypertrophy of gastrocnemius muscles develops; the process slowly spreads upward to the muscles of the shoulder girdle and the proximal parts of the hands. The level of CK is elevated

The course of the disease is more favorable and slow with a later disability.

Limb-lumbar muscular dystrophy (Erba-Rota) is a hereditary disease with an autosomal dominant type of inheritance. The onset of the disease falls on the age of 14-16 years. There is muscle weakness and then atrophy of the muscles of the pelvic girdle and proximal legs, less often the muscles of the shoulder girdle also suffer less. Muscle hypotension, "looseness" of the joints is revealed. As a rule, the muscles of the back and abdomen are involved ("duck" gait, difficulty rising from the lying position, pronounced lordosis in the lumbar region and protrusion of the abdomen forward, "pterygoid scapula"). The patient begins to apply special techniques in the process of self-service. In far-reaching cases it is possible to detect terminal atrophies, retractions of muscles and tendons and even contractures. In most cases, the muscles of the face do not suffer. Pseudohypertrophies of gastrocnemius muscles also develop here. The level of CK in the blood is increased. On EMG - muscle damage level.

Fazio-skapulo-humeral muscular dystrophy (face-scapular-brachial myodystrophy of the Landusi-Dezherin) is a relatively benign autosomal dominant form that begins to appear at the age of 20-25 with symptoms of muscle weakness and atrophy in the face ("myopathic face"), , the shoulder girdle, back and proximal parts of the hands. The defeat of only the upper half of the trunk can last up to 10-15 years. Then there is a tendency to a downward spread of atrophy. Tendon reflexes remain intact for a long time. The asymmetry of symptoms is characteristic. The level of enzymes in the blood is normal or increased slightly.

Oculopharyngeal muscular dystrophy is characterized by a late onset (at 4-6 days of life) and is manifested by the defeat of the oculomotor muscles, as well as the pharyngeal muscles with swallowing disorders. There is also a form with an isolated lesion of only the oculomotor muscles, which, gradually progressing, eventually leads to total external ophthalmoplegia. The latter usually proceeds without doubling (ocular myopathy, or progressive external ophthalmoplegia Gref). The diagnosis is confirmed by EMG-study. The level of CPK rises rarely (if the process extends to other striated muscles).

Scapuloperoneal (scapular-peroneal) amiogrophy of Davidenkov is characterized by progressive atrophy and weakness in peroneal muscle groups, and then in the muscles of the shoulder girdle. Some researchers believe that the syndrome of scapula-peroneal atrophy is a variant of the development of the myodystrophy of the Landusi-Dezherin.

Distal muscular dystrophy is an exception to the whole group of myodystrophies, since it affects the distal musculature at first the shins and feet, then the arms. Tendon reflexes fall out in the same sequence Rarely the process extends to the proximal musculature. For the diagnosis it is necessary to preserve the sensitivity and the normal speed of excitation on the nerves. The level of CK is normal or slightly elevated. EMG confirms the muscular level of lesion.

There are variants of distal muscular dystrophy with onset in infancy, in childhood, with late onset (type Welander), with accumulation of desmine inclusions.

Emery-Dreyfus muscular dystrophy has an X-linked type of inheritance, begins at 4-5 years of age with a characteristic shoulder-peroneal distribution of atrophy and weakness (distal sections remain intact even in far-reaching cases). Typically, the early formation of contractures in the elbows, neck and in the field of Achilles tendons. Another typical feature is the absence of pseudohypertrophies. Characterization of heart rhythm disturbances, conduction defects (sometimes complete blockade with sudden death of the patient). The level of CK in the serum remains for a long time normal. EMG shows both neurogenic and muscular lesion levels.

A special group - congenital myopathies unites several diseases that are usually detected from birth or early childhood and are characterized by a benign course: they often remain stable throughout their life; sometimes they even begin to regress; If there is a progression in some cases, then it is very insignificant.

It is almost impossible to recognize these diseases according to the clinical picture. For this, histochemical, electron microscopic and fine biochemical studies are used. Usually this is a picture of a "floppy baby" with generalized or proximal muscle weakness, atrophy and hypotension, a decrease or absence of tendon reflexes, and sometimes contractures develop.

This group includes diseases such as central core disease, multicore disease, nemaline myopathy, centrally nucleated myopathy, congenital fiber type disproportion, myopathy with congenital disproportion of types of fibers, reduction body myopathy, myopathy with fingerprint body myopathy, myopathy with cytoplasmic body myopathy, myopathy with tubular aggregates (myopathy with tubular aggregates), myopathy with predominance muscular x fibers of the first type (type I myofiber predominance).

EMG reveals nonspecific myopathic changes in these forms. Muscle enzymes in the blood either normal or slightly elevated. The diagnosis is made on the basis of electron-microscopic examination.

Membrane myopathies

The so-called membrane myopathies, which include myotonic syndromes.

Inflammatory myopathies

The group of inflammatory myopathies includes such diseases as poliomyositis and dermatomyositis; Myositis and myopathy with inclusion bodies; myositis in connective tissue diseases; sarcoid myopathy; myositis in infectious diseases.

Poliomyositis

It occurs at any age, but most often in adults, women are more likely to get sick than men. The disease begins gradually and progresses over several weeks or months. There are spontaneous remissions and relapses. Weakness refers to the main clinical manifestations and most of all it is noticeable in the proximal parts of the arms and flexors of the neck (the symptom of the "combs", the "bus" symptom and other similar manifestations). The affected muscles are often painful and pasty. The absence of myalgia is considered a rare exception. Dysphagia is another typical symptom that reflects the involvement of the muscles of the pharynx and esophagus. The heart muscle is also often involved, as evidenced by ECG data. Respiratory dysfunction can be the result of a combination of damage to the respiratory muscles and lung parenchyma (in 10% of patients). The level of CK in the blood is elevated, sometimes significantly. But approximately in 1% of patients the level of CK remains normal. Myoglobulinuria can be observed in both polymyositis and dermatomyositis. ESR is enhanced, but does not directly correlate with the activity of the process. EMG reveals fibrillation and short polyphase potentials of small amplitude. A biopsy shows the variable number of necrotic fibroblasts and inflammatory changes.

The presence of skin changes (erythema, malformation of pigmentation, telangiectasia) is the main difference between dermatomyositis and polymyositis. Poliomyositis can be primary and secondary (with malignant neoplasm).

"Myositis with inclusion bodies"

It affects more often middle-aged or elderly patients (predominate men) and manifests itself slowly progressive symmetrical weakness in the extremities. Unlike other inflammatory myopathies, both proximal and distal pronounced muscle weakness are present here, involving the extensors of the foot and flexors of the fingers. Pain is not typical. Sometimes myositis with inclusion bodies is combined with connective tissue diseases or immune disorders (Sjogren's disease, thrombocytopenia). The level of CK is moderately elevated. EMG reveals mixed neurogenic and myopathic changes in the nature of bioelectrical activity. A biopsy of the muscles reveals small vacuoles with inclusion granules.

Myositis associated with connective tissue diseases

This combination is especially characteristic for cases of mixed connective tissue disease. It is characterized by high titers of antiribonucleoprotein antibodies; lupus-like rashes on the skin; changes in connective tissue resembling scleroderma; arthritis and inflammatory myopathy. Clinically, myopathy is manifested by the weakness of the flexors of the neck and muscles of the proximal parts of the extremities. Histologically, this inflammatory myopathy resembles dermatomyositis.

Inflammatory myopathy can be observed with scleroderma, rheumatoid polyarthritis, systemic lupus erythematosus, Sjogren's syndrome.

Sarcoid myopathy

It can be observed in sarcoidosis (multisystem granulomatous disorder of unknown etiology). Granulomatous changes are found in the brain envelopes, brain, pituitary, spinal cord and peripheral nerves (as well as in the tissues of the eye, in the skin, lungs, bones, lymph nodes and salivary glands). Diagnosis is placed on the grounds of multisystem lesion detection and muscle biopsy.

Myositis in infectious diseases

Bacterial and fungal myositis are rare and are usually a component of a systemic disease. Parasitic myositis (toxoplasmosis, trichinosis, cysticercosis) is also infrequent. Cysticercosis describes pseudohypertrophic myopathy. Viral myositis can manifest itself in varying degrees of severity from myalgia to rhabdomyolysis. A variety of such inflammatory myopathies is typical for complications of HIV infection and is usually observed in the context of other neurological and somatic manifestations of AIDS.

Metabolic myopathies

Metabolic myopathies include carbohydrate myopathies, lipid myopathies, mitochondrial myopathies, endocrine myopathies, myalgic syndromes, myoglobulinuria, and toxic myopathies.

Carbohydrate myopathies are referred to as glycogen storage diseases. They are associated with the insufficiency of these or other enzymes. Insufficiency of muscle phosphorylase (Mc-Ardl's disease) and other enzymes, as well as lipid myopathies. Among these diseases, the lysosomal accumulation of glycogen (Pompe-Rotre disease) remains unreported, which manifests itself in the first months of life (rapidly progressing muscle weakness and massive cardiomegaly) and leading to death in the first year of life.

The syndrome of Kearns-Sayre is manifested by progressive external ophthalmoplegia. It refers to sporadic diseases (but there is also a family variant of progressive external ophthalmoplegia) and, that is typical, is accompanied by the involvement of many organs and systems. The disease begins before the age of 20 and is manifested by pigmentary degeneration of the retina. Obligatory signs of this disease: external ophthalmoplegia, conduction disorders of the heart and the mentioned pigmental degeneration of the retina. Other additional symptoms include ataxia, worsening of hearing, multiple endocrinopathy, an increase in protein content in the cerebrospinal fluid, and other manifestations. With a family version of progressive external ophthalmoplegia, weaknesses in the muscles of the neck and extremities are possible.

Endocrine myopathies occur in a wide variety of endocrine disorders. Quite often, myopathy is observed in hyperthyroidism. Weakness is revealed mainly in the proximal parts of the extremities (rarely in the distal and bulbar muscles) and is reversed in the treatment of hyperthyroidism. The level of CK is usually not elevated. On the EMG and in the muscle biopsy, nonspecific myopathic changes.

However, there are cases of severe thyrotoxicosis, especially with its rapid progression, accompanied by rhabdomyolysis, myoglobinuria and kidney deficiency. The weakness of the respiratory muscles, requiring mechanical ventilation, is rare.

Hypothyroidism is often accompanied by proximal muscle weakness, cramp, pain and a sense of stiffness of the muscles (although in an objective measurement, weakness is not often confirmed). These symptoms disappear with the successful treatment of hypothyroidism. Muscular hypertrophy is rare in hypothyroidism, but their presence in adults is called Hoffmann's syndrome.

Koher-Debre-Semeleigna syndrome is observed in children (hypothyroidism with generalized muscle tension and hypertrophy of gastrocnemius muscles). The level of CK is increased in 90% of patients with hypothyroidism, although obvious rhabdomyolysis is very rare. Myopathic changes in EMG vary from 8% to 70%. In the muscle biopsy, there are mild signs of myopathy. Hypothyroidism worsens glycogenolysis in muscles and the oxidative ability of mitochondria.

We do not discuss here the distearoid orbitopathy, also associated with the defeat of the muscular apparatus of the orbit.

Muscle weakness, fatigue and krampi very often accompany Addison's disease. Sometimes, weakness can be episodic. There may be periodic paralysis with quadriplegia and hyperkalemia.

Patients with hyperaldosteronism occasionally observe attacks of periodic paralysis with hypokalemia. 70% of these patients complain of weakness.

The muscle weakness is often complained of patients with Isenko-Cushing syndrome and patients receiving long-term treatment with glucocorticoids. Streoid myopathy often develops slowly with long-term treatment of, for example, diseases such as systemic lupus erythematosus, rheumatoid arthritis, bronchial asthma, polymyositis, and affects mainly proximally located muscles. The level of CK usually does not change; on EMG - minimal signs of myopathy.

Acute steroid myopathy develops less often: often a week after the start of treatment with high doses of corticosteroids. Such a myopathy can involve respiratory muscles. Acute steroid myopathy can also occur with corticosteroid treatment in myasthenia patients.

Toxic myopathies

Toxic myopathies can be of iatrogenic nature. Drugs are able to cause: myalgia, muscle tension (stiffness), or krampi; myotonia (delayed relaxation of skeletal muscles after an arbitrary contraction) - painless proximal myopathy with muscle weakness; myositis or inflammatory myopathy; focal myopathy in the area of injury (injection); hypokalemic mildness with the administration of drugs that cause hypokalemia; mitochondrial myopathy in connection with inhibition of mitochondrial DNA; rhabdomyolysis (acute muscular necrosis with myoglobinuria and systemic complications).

Necrotizing myopathy is described when using lovastatin (a cholesterol synthesis inhibitor), cyclosporine, aminocaproic acid, procainamide, phencyclidine. Muscle weakness, pain (spontaneous and palpation of muscles) develops; the level of CK is increased; on EMG - a picture of myopathic changes. Intramuscular administration of botulinum, chlorpromazine, fenionion, lidocaine and diazepam antibiotic antibiotics may be the cause of local muscle necrosis and fibrotic myopathy. Emetin causes progressive proximal myopathy. The same ability was found in clozapine, D-penicillamine, growth hormone, interferon-alpha-2b, vincristine.

Myalgia and muscle cramps can cause: angiotensin-converting factor inhibitors, anticholinesterase, beta-adrenergic agonists, calcium antagonists, corticosteroid cancellations, cytotoxic drugs, dexamethasone, diuretics, D-penicillamine, levamisole, lithium, L-tryptophan, nifedipine, pindolol, procainamide , rifampicin, salbutamol. Drug-induced myalgia without muscle weakness usually passes quickly after drug withdrawal.

Alcohol Myopathy

It occurs in several variants. One type is characterized by a painless, predominantly proximal muscle weakness that develops over several days or weeks of prolonged alcohol abuse, which is associated with severe hypokalemia. The level of hepatic and muscle enzymes is markedly increased.

Another type of alcoholic myopathy develops sharply against the background of prolonged use of alcohol and is manifested by severe pain and swelling of the muscles of the limbs and trunk, which is accompanied by symptoms of renal failure and hyperkalemia. Myonecrosis (rhabdomyolysis) is reflected in a high level of CK and aldolase, as well as myoglobinuria. This may be accompanied by other alcoholism syndromes. Recovery is quite slow (weeks and months); relapses associated with alcoholism are typical.

There is a variant of acute alcoholic myopathy, accompanied by severe krampi and generalized weakness. Possible chronic alcoholic myopathy, manifested by painless atrophy and weakness of the muscles of the proximal parts of the extremities, especially the legs, with minimal signs of neuropathy.

[4], [5], [6]

Paraneoplastic myopathy

A separate position should be occupied by myopathy with osteodystrophy and osteomalacia, which is described among other paraneoplastic syndromes.

Some rare forms of muscular dystrophy, such as Mabry's myodystrophy, Rottauf-Mortier-Beyer's myodystrophy, Leiden-Moebius pelvic myodystrophy, Betlem's muscular dystrophy, and Mioshi's distal miodystrophy are not represented here.

Diagnosis of myopathies

Diagnostic studies with suspicion of myopathy include, in addition to clinical analysis, an electromigraphic and electroneuromyographic study, a blood test for enzymes (CK, aldolase, ACT, ALT, LDH, etc.). CK in the blood is the most sensitive and reliable indicator of the myodystrophic process. Also examine urine for creatine and creatinine. Muscle biopsy is sometimes indispensable for revealing the nature of myopathy (for example, in congenital myopathies). Exact diagnosis of the type of myopathy may require carrying out molecular genetic, immunobiochemical or immunohistochemical studies.

[7], [8]