Myopathic syndrome: causes, symptoms, diagnosis

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

"Muscular dystrophies"

Membrane myopathies

Inflammatory myopathies

Metabolic myopathies

Toxic myopathies

Alcoholic myopathy

Paraneoplastic myopathy

Diagnosis of myopathies

The main forms of myopathy:

• I. Hereditary progressive muscular dystrophies: Duchenne and Becker muscular dystrophy, Emery-Dreifuss dystrophy, facio-scapulohumeral, scapuloperoneal, limb-girdle, distal form, oculopharyngeal, progressive external ophthalmoplegia. Congenital muscular dystrophy.
• II. Myopathies with myotonic syndrome (membrane 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.

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"Muscular dystrophies"

Muscular dystrophies are a term used to describe hereditary forms of myopathy accompanied by muscle degeneration. This is a whole group of diseases, most of which begin in childhood or adolescence, have a steadily progressive course and sooner or later lead to severe disability. Several detailed classifications of muscular dystrophies have been proposed, based on different principles (genetic, biochemical, clinical), but there is no unified classification.

Dystrophin-deficiency dystrophies mainly include two forms: Duchenne muscular dystrophy and Becker muscular dystrophy.

Duchenne muscular dystrophy, or pseudohypertrophic Duchenne muscular dystrophy, is the most malignant and most common form of X-linked muscular dystrophy. CPK enzymemia is detected already in the neonatal period, but clinical symptoms appear at the age of 2-4 years. These children start walking late, it is difficult or impossible for them to run and jump, they often fall (especially when trying to run), have difficulty climbing stairs or on an inclined floor (weakness of the proximal muscles) and walk on their big toes (toe-walking) due to contracture of the tendons of the foot. A decrease in intelligence is possible. Pseudohypertrophy of the gastrocnemius muscles is characteristic. Gradually, the process takes an ascending direction. Hyperlordosis and kyphoscoliosis are formed. By the age of 8-10 years, gait is severely impaired. The patient gets up from the floor with the help of characteristic "myopathic" techniques. By the age of 14-15, patients are usually completely immobilized and die by the age of 15-17 from weakness of the respiratory muscles of the chest. ECG reveals abnormalities in almost 90% of cases (cardiomyopathy). The CPK level is sharply increased. EMG shows a muscular level of damage. Muscle biopsy reveals nonspecific, although characteristic, histopathological abnormalities.

Becker muscular dystrophy is the second most common but benign form of pseudohypertrophic myodystrophy. Onset of the disease is between 5 and 15 years. The pattern of muscle involvement is the same as in the Duchenne form. Weakness of the pelvic girdle and proximal leg muscles is characteristic. Gait changes, difficulties arise when getting up from a low chair, when climbing stairs. Severe pseudohypertrophy of the calf muscles develops; the process slowly spreads upward to the muscles of the shoulder girdle and proximal arms. The level of CPK is elevated

The course of the disease is more favorable and slower with a later impairment of working capacity.

Limb-girdle muscular dystrophy (Erb-Roth) is a hereditary disease with an autosomal dominant type of inheritance. The onset of the disease occurs at the age of 14-16 years. Muscle weakness appears, followed by atrophy of the muscles of the pelvic girdle and proximal parts of the legs, less often the muscles of the shoulder girdle are also affected. Muscle hypotonia and "looseness" of the joints are revealed. As a rule, the muscles of the back and abdomen are involved ("duck" gait, difficulty getting up from a lying position, pronounced lordosis in the lumbar region and protrusion of the abdomen forward, "winged shoulder blades"). The patient begins to use special techniques in the process of self-care. In advanced cases, terminal atrophy, muscle and tendon retractions, and even contractures can be detected. In most cases, the facial muscles are not affected. Pseudohypertrophy of the calf muscles also develops here. The CPK level in the blood is elevated. The EMG shows a muscular level of damage.

Facio-scapulohumeral muscular dystrophy (Landouzy-Dejerine facioscapulohumeral muscular dystrophy) is a relatively benign autosomal dominant form that begins to manifest itself at the age of 20-25 years with symptoms of muscle weakness and atrophy in the face ("myopathic face"), shoulder girdle, back and proximal parts of the arms. The lesion of only the upper half of the body can continue for up to 10-15 years. Then there is a tendency for a downward spread of atrophy. Tendon reflexes remain intact for a long time. Asymmetry of symptoms is characteristic. The level of enzymes in the blood is normal or slightly elevated.

Oculopharyngeal muscular dystrophy is characterized by a late onset (in the 4th-6th decade of life) and manifests itself in damage to the extraocular muscles, as well as the muscles of the pharynx with swallowing disorders. There is also a form with isolated damage to only the extraocular muscles, which, gradually progressing, eventually leads to complete external ophthalmoplegia. The latter usually occurs without double vision (ocular myopathy, or Graefe's progressive external ophthalmoplegia). The diagnosis is confirmed by EMG examination. The CPK level rarely rises (if the process spreads to other striated muscles).

Scapuloperoneal (scapuloperoneal) amyotrophy of Davidenkov is characterized by progressive atrophy and weakness in the peroneal muscle groups, and then in the muscles of the shoulder girdle. Some researchers believe that scapuloperoneal atrophy syndrome is a variant of the development of Landouzy-Dejerine muscular dystrophy.

Distal muscular dystrophy is an exception from the whole group of myodystrophies, as it affects the distal muscles first of the shins and feet, then the arms. Tendon reflexes are lost in the same sequence. Rarely, the process spreads to the proximal muscles. For diagnosis, it is necessary to preserve sensitivity and normal speed of excitation conduction along the nerves. The CPK level is normal or slightly elevated. EMG confirms the muscular level of the lesion.

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

Emery-Dreifuss muscular dystrophy has an X-linked type of inheritance, begins at the age of 4-5 years with a characteristic shoulder-peroneal distribution of atrophy and weakness (the distal sections remain intact even in advanced cases). Early formation of contractures in the elbow joints, neck and Achilles tendons is typical. Another typical feature is the absence of pseudohypertrophy. Heart rhythm disturbances, conduction defects (sometimes complete block with sudden death of the patient) are characteristic. The serum CPK level remains normal for a long time. EMG shows both neurogenic and muscular levels of damage.

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

It is almost impossible to recognize these diseases by their clinical picture. Histochemical, electron microscopic and fine biochemical studies are used for this purpose. Usually this is a picture of a "floppy baby" (@Floppy baby") with generalized or proximal muscle weakness, atrophy and hypotonia, decreased or absent tendon reflexes. Sometimes contractures develop.

This group includes such diseases as central core disease, multicore disease, nemaline myopathy, centronuclear myopathy, congenital fiber type disproportion myopathy, reducing body myopathy, fingerprint body myopathy, cytoplasmic body myopathy, myopathy with tubular aggregates, type I myofiber predominance.

EMG reveals non-specific myopathic changes in these forms. Muscle enzymes in the blood are either normal or slightly elevated. The diagnosis is based on 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 diseases of connective tissue; sarcoid myopathy; myositis in infectious diseases.

Polymyositis

It occurs at any age, but most often in adults. Women are affected more often than men. The disease begins gradually and progresses over several weeks or months. Spontaneous remissions and relapses are possible. Weakness is one of the main clinical manifestations and is most noticeable in the proximal parts of the arms and flexors of the neck (the "comb" symptom, 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, which reflects the involvement of the muscles of the pharynx and esophagus. The heart muscle is also often involved, which is confirmed by ECG data. Respiratory dysfunction can result from a combination of damage to the respiratory muscles and lung parenchyma (in 10% of patients). The level of CPK in the blood is elevated, sometimes significantly. But in about 1% of patients, the level of CPK remains normal. Myoglobulinuria may be observed in both polymyositis and dermatomyositis. ESR is elevated but does not directly correlate with the activity of the process. EMG reveals fibrillations and short polyphasic potentials of small amplitude. Biopsy shows a variable number of necrotic myofibrils and inflammatory changes.

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

"Inclusion body myositis"

It most often affects middle-aged or elderly patients (men predominate) and manifests itself as slowly progressing symmetrical weakness in the limbs. Unlike other inflammatory myopathies, it is characterized by both proximal and distal pronounced muscle weakness 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 CPK is moderately elevated. EMG reveals mixed neurogenic and myopathic changes in the nature of bioelectrical activity. Muscle biopsy reveals small vacuoles with inclusion granules.

Myositis associated with connective tissue disease

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

Inflammatory myopathy can be observed in scleroderma, rheumatoid arthritis, systemic lupus erythematosus, and Sjogren's syndrome.

Sarcoid myopathy

May be seen in sarcoidosis (multisystem granulomatous disorder of unknown etiology). Granulomatous changes are found in the meninges, brain, pituitary gland, spinal cord, and peripheral nerves (as well as in the tissues of the eye, skin, lungs, bones, lymph nodes, and salivary glands). Diagnosis is based on the detection of multisystem involvement 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 rare. Pseudohypertrophic myopathy has been described in cysticercosis. Viral myositis can manifest itself with varying degrees of severity from myalgia to rhabdomyolysis. A type of such inflammatory myopathy is characteristic of 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 called glycogen storage diseases. They are associated with a deficiency of certain enzymes. Deficiency of muscle phosphorylase (McArdle disease) and other enzymes, as well as lipid myopathies. Among these diseases, lysosomal glycogen storage disease (Pompe-Rotre disease) remains unmentioned, which manifests itself in the first months of life (rapidly progressing muscle weakness and massive cardiomegaly) and leads to death in the first year of life.

Kearns-Sayre syndrome is characterized by progressive external ophthalmoplegia. It is a sporadic disease (but there is also a familial variant of progressive external ophthalmoplegia) and is typically accompanied by the involvement of many organs and systems. The disease begins before the age of 20 and is characterized by pigmentary degeneration of the retina. Obligatory signs of this disease are: external ophthalmoplegia, cardiac conduction disorders and the aforementioned pigmentary degeneration of the retina. Other additional symptoms include ataxia, hearing loss, multiple endocrinopathy, increased protein content in the cerebrospinal fluid and other manifestations. With the familial variant of progressive external ophthalmoplegia, manifestations of weakness in the muscles of the neck and limbs are possible.

Endocrine myopathies occur in a wide variety of endocrine disorders. Myopathy is quite common in hyperthyroidism. Weakness is detected mainly in the proximal parts of the limbs (rarely in the distal and bulbar muscles) and is subject to regression during treatment of hyperthyroidism. The CPK level is usually not elevated. EMG and muscle biopsy show nonspecific myopathic changes.

However, cases of severe thyrotoxicosis occur, especially with its rapid progression, accompanied by rhabdomyolysis, myoglobinuria and renal failure. Weakness of the respiratory muscles requiring mechanical ventilation is rare.

Hypothyroidism is often accompanied by proximal muscle weakness, cramps, pain, and stiffness (although objective measurement of weakness is rarely conclusive). These symptoms resolve with successful treatment of hypothyroidism. Muscle hypertrophy is rare in hypothyroidism, but its presence in adults is called Hoffman syndrome.

Kocher-Debre-Semelaign syndrome is observed in children (hypothyroidism with generalized muscle tension and hypertrophy of the calf muscles). The CPK level is elevated in 90% of patients with hypothyroidism, although overt rhabdomyolysis is very rare. Myopathic changes on EMG vary from 8% to 70%. In muscle biopsy, there are weak signs of myopathy. Hypothyroidism worsens glycogenolysis in muscles and the oxidative capacity of mitochondria.

We do not discuss here dysthyroid orbitopathy, which is also associated with damage to the orbital muscular apparatus.

Muscle weakness, fatigue, and cramps are very common in Addison's disease. Sometimes the weakness may be episodic. Periodic paralysis with quadriplegia and hyperkalemia may occur.

Patients with hyperaldosteronism sometimes experience attacks of periodic paralysis with hypokalemia. 70% of these patients complain of weakness.

Muscle weakness is often complained of by patients with Itsenko-Cushing syndrome and patients receiving long-term glucocorticoid treatment. Steroid myopathy often develops slowly during long-term treatment of diseases such as systemic lupus erythematosus, rheumatoid arthritis, bronchial asthma, polymyositis, and affects mainly proximal muscles. The CPK level usually does not change; EMG shows minimal signs of myopathy.

Acute steroid myopathy develops less frequently: often after a week of treatment with high doses of corticosteroids. Such myopathy may involve the respiratory muscles. Acute steroid myopathy may also occur when treating patients with myasthenia with corticosteroids.

Toxic myopathies

Toxic myopathies may be iatrogenic. Drugs can cause: myalgia, muscle stiffness, or cramps; myotonia (delayed relaxation of skeletal muscles after voluntary contraction) - painless proximal myopathy with muscle weakness; myositis or inflammatory myopathy; focal myopathy in the area of injury (injection); hypokalemic mimopathy with the introduction of drugs that cause hypokalemia; mitochondrial myopathy due to inhibition of mitochondrial DNA; rhabdomyolysis (acute muscle necrosis with myoglobinuria and systemic complications).

Necrotizing myopathy has been described with the use of lovastatin (cholesterol synthesis inhibitor), cyclosporine, aminocaproic acid, procainamide, and phencyclidine. Muscle weakness and pain (spontaneous and upon muscle palpation) develop; the CPK level increases; EMG shows myopathic changes. Intramuscular administration of the antibiotics doxorubicin, chlorpromazine, phenythion, lidocaine, and diazepam can cause local muscle necrosis and fibrous myopathy. Emetine causes progressive proximal myopathy. The same ability has been found in clozapine, D-penicillamine, growth hormone, interferon-alpha-2b, and vincristine.

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

Alcoholic myopathy

There are several variants. One type is characterized by painless, predominantly proximal muscle weakness that develops over several days or weeks of prolonged alcohol abuse, combined with severe hypokalemia. Liver and muscle enzyme levels are markedly elevated.

Another type of alcoholic myopathy develops acutely against the background of long-term alcohol consumption 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 high levels of CPK and aldolase, as well as myoglobinuria. This may be accompanied by other syndromes of alcoholism. Recovery is quite slow (weeks and months); relapses associated with alcoholism are typical.

There is a variant of acute alcoholic myopathy, accompanied by severe cramps and generalized weakness. Chronic alcoholic myopathy is possible, manifested by painless atrophy and weakness of the muscles of the proximal parts of the extremities, especially the legs, with minimally expressed signs of neuropathy.

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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 dystrophies are not presented here, such as Mabry muscular dystrophy, Rottauff-Mortier-Beyer muscular dystrophy, Leiden-Mobius muscular dystrophy, Bethlem muscular dystrophy, and distal Miyoshi muscular dystrophy.

Diagnosis of myopathies

Diagnostic studies for suspected myopathy include, in addition to clinical analysis, electromyography and electroneuromyography, blood analysis for enzymes (creatinine phosphokinase, aldolase, AST, ALT, LDH, etc.). CPK in the blood is the most sensitive and reliable indicator of the myodystrophic process. Urine is also tested for creatine and creatinine. Muscle biopsy is sometimes indispensable for identifying the nature of myopathy (for example, in congenital myopathies). Accurate diagnosis of the type of myopathy may require molecular genetic, immunobiochemical or immunohistochemical studies.

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