Weakness during physical activity (pathologic muscle weakness)

Muscle fatigue may be caused not only by damage to the neuromuscular synapse (immune-dependent myasthenia and myasthenic syndromes), but also by general internal diseases without direct damage to the neuromuscular apparatus, such as chronic infections, tuberculosis, sepsis, Addison's disease or malignant diseases. Weakness is usually combined with specific symptoms of the underlying disease; general clinical and physical examination in these cases is most important for diagnosis.

The main causes of muscle fatigue during physical activity:

1. Myasthenia gravis.
2. Lambert-Eaton syndrome.
3. Hereditary (congenital) myasthenic syndromes.
4. Polymyositis.
5. Multiple sclerosis (early stages).
6. AGDP (Guillain-Barre syndrome).
7. Endocrinopathies.
8. Botulism.
9. Glycogenosis (McArdle disease).
10. Disorders of potassium metabolism.
11. Disorders of calcium metabolism.
12. Mental disorders (asthenia and depression).
13. Chronic fatigue syndrome.
14. Caudogenic intermittent claudication.
15. Iatrogenic myasthenic-like syndrome (drug-induced).

Myasthenia

It is well known that weakness during physical exertion (pathological muscle fatigue) is the main complaint of patients suffering from immune-dependent myasthenia (myasthenia gravis). At the onset of the disease, weakness is completely absent in the morning hours after a night's rest, patients experience a decrease in muscle strength during various types of activity - depending on the muscles or muscle groups involved in these types of activity: reading, speaking, walking, stereotypical hand work, stereotypical foot movements (e.g. typing on a typewriter, pressing the pedal of a machine). Rest allows (at least partially) to restore muscle strength. Weakness is most pronounced in the evening.

If myasthenia is suspected, a simple clinical test should be performed to detect pathological muscle fatigue - the patient is asked to perform the affected movements 30-40 times (or less) in a row. For example, closing and opening the eyes (in the ocular form of myasthenia), counting loudly, raising the head while lying on the back, clenching the fingers into a fist, etc. (in generalized limb-girdle myasthenia). The indicator muscle when performing tests for myasthenia is m. triceps. If a decrease in muscle strength (or fading of the voice) is noted during this test, then pharmacological tests should be performed. Intramuscular injections of anticholinesterase drugs (for example, prozerin) restore muscle strength in 30 sec - 2 min for a period of several minutes to half an hour. The longer the recovery period, the less typical it is for myasthenia, and should be the basis for continuing the diagnostic search. It is necessary to keep in mind the possibility of the patient developing severe side effects of the anticholinesterase drug and to be prepared to administer an injection of atropine.

To exclude the psychogenic nature of muscle weakness, it is recommended to give an intramuscular injection of saline solution.

Electrical stimulation of a peripheral nerve results in attenuation of action potentials in the corresponding muscle; this effect is reversed by the action of an anticholinesterase drug or substances acting on the postsynaptic membrane.

When diagnosing myasthenia, further investigation is necessary. Blood should be examined for antibodies to acetylcholine receptors and skeletal muscles. Studies are also necessary to determine whether there is a thymoma or persistent functioning of the thymus that has not undergone timely involution. Myasthenic weakness can also develop in hyperthyroidism, systemic lupus erythematosus, Sjogren's disease, polymyositis, rheumatoid arthritis, and in the debut stage of multiple sclerosis.

Lambert-Eaton syndrome

Lambert-Eaton syndrome is a paraneoplastic syndrome in which abnormal muscle fatigability may resemble myasthenic fatigability. However, the observed muscle fatigability has distinctive features that allow differentiation between myasthenia and Lambert-Eaton myasthenic syndrome. Weakness does not begin in the extraocular or facial muscles, as is the case with myasthenia; moreover, these muscles are often intact in Lambert-Eaton syndrome. The muscles most often involved are those of the pelvic or shoulder girdle. Although patients complain of weakness during physical exertion, clinical examination reveals that with repeated contractions of the involved muscles, their strength initially increases and decreases only after a minute or more. This phenomenon is also noted in EMG studies: the amplitude of the action potential first increases and then decreases. Pharmacological tests give a minimal effect or are negative. The syndrome is more common in men. In 70% of cases, the disease is caused by lung carcinoma.

Hereditary (congenital) myasthenic syndromes

Descriptions of benign congenital myopathy periodically appear in the literature, in which myasthenic manifestations can be observed in the neonatal period or in the immediate subsequent period. These are non-progressive forms of myopathy; their manifestations remain stable throughout life; sometimes they progress slightly, in other cases they even have a regressive course (central core disease, nemaline myopathy, tubular myopathy, etc.). It is almost impossible to differentiate these diseases based on the clinical picture (usually the diagnosis is "floppy baby"). An electron microscopic picture characteristic of one form or another is revealed.

On the other hand, true congenital myasthenic syndromes have been described, each of which is distinguished by a unique defect in the cholinergic synapse (features of the structure of presynaptic terminals, postsynaptic receptors, disturbances in the kinetics of acetylcholine, etc.). Already in newborns, symptoms such as increasing ptosis, bulbar and respiratory disturbances during crying are noted. Later, fluctuating paralysis of the oculomotor muscles and fatigue during movements join these symptoms. In some cases, myasthenic symptoms become clinically noticeable only in the second or third decade of life (slow-channel syndrome). All congenital myasthenic syndromes are inherited in an autosomal recessive manner.

Polymyositis

Polymyositis is manifested by the gradual development of symmetrical proximal muscle weakness, myalgic syndrome, and early swallowing disorder. Usually, there is an increase in serum CPK, changes in EMG (fibrillation potentials, positive waves, decreased duration of motor unit potentials), and increased ESR. In addition to muscle weakness, fatigue may occur during physical exertion.

Multiple sclerosis

In the early stages of multiple sclerosis, complaints of fatigue during physical exertion are possible. The cause of fatigue remains unknown. The revealed symptoms in the form of characteristic paresthesia, visual, pyramidal and cerebellar symptoms indicating multifocal damage to the central nervous system leave no doubt for the diagnosis.

AIDP (Guillain-Barre syndrome)

In the early stages of acute inflammatory demyelinating polyneuropathy of Guillain-Barré, increased fatigue during physical activity may be observed with mild or subclinical manifestations of polyneuropathy. The development of a typical clinical picture of polyneuropathy removes diagnostic questions.

Endocrinopathies

Some endocrinopathies may include myasthenic-like manifestations in their clinical manifestations: hypothyroidism (characterized by cold, pale, dry skin, lack of desire, constipation, thickening of the tongue, hoarse voice, bradycardia, muscle swelling, slowing of the Achilles reflexes, etc.; rarely accompanied by other neurological symptoms such as paresthesia, ataxia, carpal tunnel syndrome, cramps); hyperthyroidism (characterized by proximal muscle weakness with difficulty rising from a squatting position, sweating, tachycardia, tremor, hot skin, heat intolerance, diarrhea, etc.; neurological symptoms such as pyramidal signs are rarely noted); hypoparathyroidism (muscle weakness and cramps, tetany, headaches, fatigue, ataxia, seizures, rarely hallucinations and choreoathetoid symptoms are noted); hyperparathyroidism (characterized by true myopathy with muscle atrophy, depression, emotional lability, irritability, confusion, constipation); Cushing's disease, hypopituitarism, diabetes mellitus. All these diseases are characterized by complaints of fatigue, which sometimes reaches a noticeable severity. In Addison's disease and Simonds' disease, fatigue becomes one of the main manifestations.

Botulism

Botulism is a severe intoxication resulting from the ingestion of foods containing toxins from the bacterium Clostridium botulinum. Botulinum toxin is a potent poison that blocks the release of acetylcholine from presynaptic endings. Progressive muscle fatigue and weakness are characteristic, often beginning with the oculomotor (incomplete or complete external and internal ophthalmoplegia) and pharyngeal muscles, followed by generalization (diplopia, ptosis, dysarthria, dysphagia, symmetrical weakness of the muscles of the extremities and respiratory muscles). Dilation of the pupils and absence of pupillary reactions are usually observed, but consciousness is not impaired. In severe cases, involvement of the respiratory muscles is observed. Symptoms of generalized cholinergic transmission disorder may be observed: poorly reacting pupils, dry mouth, intestinal paresis ("paralytic ileus") and, sometimes, bradycardia.

The diagnosis is confirmed if, when a laboratory mouse is given the patient's serum or contaminated food, it shows signs of the disease.

Glycogenosis

All types of glycogenoses, especially McArdle's disease (insufficiency of muscle phosphorylase), may be accompanied by muscle fatigue during physical exertion. A characteristic sign of insufficiency of muscle phosphorylase is pain and tension in the muscles that occur in young people during physical work. After exertion, the lactate content in the blood does not increase. Contractures with electromyographic silence in the affected muscles may develop. Muscle biopsy reveals an increase in glycogen content.

Potassium Metabolism Disorders

These disorders may manifest, in addition to muscle fatigue, as three paroxysmal muscle weakness syndromes: familial hypokalemic periodic paralysis, hyperkalemic periodic paralysis, and normokalemic periodic paralysis.

Periodic hypokalemic paralysis (paroxysmal myoplegia)

Disruption of potassium metabolism in muscle tissue causes paroxysmal hypokalemic paralysis. The leading symptom is periodic paralysis of the trunk and limb muscles, lasting for hours. As a rule, the facial muscles and diaphragm remain uninvolved. Most attacks occur at night without any specific cause. Physical exertion may be a provoking factor. Attacks may also be provoked by eating foods rich in carbohydrates.

During an attack, there is a dramatic decrease in plasma potassium concentration, which sometimes reaches 2-1.7 mmol/l, and a "silent" EMG may be recorded, i.e. there is no spontaneous activity or action potentials on the EMG. In less intense attacks, the amplitude of the action potentials is low and their duration is reduced.

If the diagnosis is uncertain, an attack can be induced for diagnostic purposes by giving the patient a high dose of glucose orally in combination with 20 units of insulin subcutaneously.

A normokalemic variant of periodic paralysis has also been described.

Severe hypokalemia (less than 2.5 mmol/l) may lead not only to fatigue but also to marked flaccid tetraplegia. The main causes are: Conn's syndrome (aldosterone-secreting tumor of the adrenal gland), renal failure, enteritis and severe diarrhea, excessive diuretic therapy, alcoholism, lithium intoxication, mineralocorticoid effect, thyrotoxicosis.

Severe hyperkalemia (>7 mmol/L) may result in severe tetraplegia with an ascending course, resembling Guillain-Barré syndrome. The most common causes are: renal failure, adrenal insufficiency, rhabdomyolysis, excessive intravenous potassium administration, administration of aldosterone antagonists.

Disorders of calcium metabolism

Chronic hypocalcemia (primary or secondary hypoparathyroidism, kidney disease), in addition to muscle fatigue, can cause attacks of tetany and noticeable muscle weakness. In infants, hypocalcemia can even lead to seizures, edema of the fundus, and calcification of the basal ganglia. In young people, the presence of cataracts should serve as a reason to exclude hypocalcemia. These symptoms, in the presence of complaints of muscle fatigue and weakness, should help in the diagnosis of hypocalcemia.

Acutely developed hypercalcemia (hyperparathyroidism in parathyroid adenoma) can cause complaints of fatigue (as well as acute psychosis or severe cerebral dysfunction).

Mental disorders

Asthenic syndrome in the picture of psychogenic disorders is recognized by characteristic accompanying manifestations: irritability, anxiety, tension headaches, insomnia disorders, vegetative dystonia syndrome.

Depression, in addition to low mood, can manifest itself as general weakness, fatigue, decreased motivation and drive, sleep disorders (early awakening is especially characteristic). In latent depression, complaints of weakness, fatigue, various pain syndromes, vegetative and somatic complaints dominate in the absence of objectively confirmed visceral diseases. Antidepressants cause the reverse development of somatic symptoms of latent depression.

Chronic fatigue syndrome

The syndrome is most often observed in women aged 20-40 years. Many of them have a history of some viral infection ("postviral fatigue syndrome"), most often in the form of infectious mononucleosis or Epstein-Barr syndrome (virus). Some of these patients have symptoms of latent immunodeficiency or a history of mild traumatic brain injury. The diagnosis of chronic fatigue syndrome requires persistent (at least 6 months) fatigue and the presence of constant or recurrent characteristic symptoms, such as low-grade fever, cervical or axillary lymphadenopathy, myalgic syndrome, headaches, migratory arthralgia, difficulty concentrating, irritability, sleep disorders. These patients often complain of muscle weakness. Neurological status is normal. Most patients show some degree of depression or neurotic disorders. The nature of chronic fatigue syndrome is not fully understood.

Caudogenic intermittent claudication

The manifestations of caudogenic intermittent claudication can sometimes resemble pathological muscle fatigue in the legs.

In this disease, the patient experiences transient weakness in the legs while standing. The disease is more common in old age. The weakness increases significantly when walking, sometimes to such an extent that the patient is forced to sit down, otherwise a fall will occur. The first symptom is always pain in the calves, followed by numbness in the feet, which can rise to the upper legs. Pulsation in the peripheral vessels is preserved, which allows us to distinguish this condition from intermittent claudication of vascular origin. Unlike intermittent claudication of vascular origin, with caudogenic intermittent claudication, deep reflexes may be reduced: at first only during attacks of weakness, but then they are reduced steadily or disappear. Similarly, in the initial stages of the disease, nerve conduction may be slowed during an attack, later, a study of conduction velocities and EMG data indicate chronic pathology of the equine tail.

Radiography, in particular neuroimaging of the lumbar spine, usually reveals narrowing of the spinal canal. As a rule, the cause is a combination of severe degenerative pathology of the spine with arthrosis of the intervertebral joints and some protrusion of one or more intervertebral discs. One should always be careful and not extrapolate radiographic data to the clinical picture: not in every case is narrowing of the spinal canal the cause of the development of typical symptoms. The presence of such symptoms in itself should be a reason for myelography. Myelography should be performed both in lordotic curvature of the spine and in kyphosis. The images reveal a violation of the passage of contrast, at least in lordosis. The mechanism of the disease is complex: direct compression of the roots of the equine tail and impaired blood circulation in the radicular arteries.

Iatrogenic myasthenic-like syndrome

Increased muscle fatigue can be caused by such drugs as D-penicillamine, antihypertensive agents, especially beta-blockers; calcium channel blockers, some antibiotics (neomycin, gentamicin, kanamycin, streptomycin, colistin, polymyxin), glucocorticoids, some analgesics, muscle relaxants, anticonvulsants; anxiolytics; antidepressants and neuroleptics. Beta-interferon in the treatment of multiple sclerosis sometimes leads to increased fatigue.

Myasthenic-like symptoms are sometimes observed in patients with ALS; many animal venoms (cobra, rattlesnake, black widow spider, scorpion venom) contain neurotoxins that block neuromuscular transmission (the picture of intoxication may resemble a myasthenic crisis).

Diagnostic studies for pathological muscle fatigue

1. General and biochemical blood analysis;
2. Urine analysis and culture;
3. Wasserman reaction;
4. ECG (for patients over 40 years old);
5. Chest X-ray and abdominal X-ray;
6. Electrolytes;
7. CO2;
8. 36-hour fast (hypoglycemia);
9. Thyroid function test;
10. Daily urine for 17-ketosteroids and 17-oxycorticosteroids;
11. Daily urine aldosterone test;
12. Renin in blood plasma;
13. Liver function tests;
14. Calcium, phosphorus and alkaline phosphatase;
15. Skull and tubular bones (metastatic cancer);
16. Lymph node biopsy;
17. Arterial blood gases;
18. CT scan of abdominal organs;
19. CT scan of the spine;
20. CT or MRI of the brain;
21. EMG;
22. Muscle biopsy;
23. Psychometric assessment of depression, personality traits;
24. Consultation with a therapist, endocrinologist, psychiatrist.

To confirm the diagnosis of myasthenia, a proserin test is performed; 2 ml of a 0.05% proserin solution is injected subcutaneously, after first causing weakness with muscle load, and the effect of the injection is observed for 40 minutes. To exclude the placebo effect, a preliminary subcutaneous injection of a saline solution is recommended.

A study of antibodies to acetylcholine receptors and striated muscles, CT of the mediastinum (to exclude thymoma) is indicated.

[ 1 ], [ 2 ], [ 3 ], [ 4 ]