Миастения гравис: Аутоиммунды бұлшық әлсіздігінің сипаттамасы

Autoimmune disease resulting in skeletal muscle weakness

Myasthenia gravis is an autoimmune disease of the neuromuscular junction which results from antibodies that block or destroy nicotinic acetylcholine receptors (AChR) at the junction between the nerve and muscle. Rarely, an inherited genetic defect in the neuromuscular junction results in a similar condition known as congenital myasthenia. Babies of mothers with myasthenia may have symptoms during their first few months of life, known as neonatal myasthenia. MG affects 50 to 200 people per million. It is newly diagnosed in 3 to 30 people per million each year. MG most commonly occurs in women under the age of 40 and in men over the age of 60. It is uncommon in children.

The initial, main symptom in MG is painless weakness of specific muscles, not fatigue. The muscle weakness becomes progressively worse (fatigue) during periods of physical activity and improves after periods of rest. Typically, the weakness and fatigue are worse toward the end of the day. MG generally starts with ocular (eye) weakness; it might then progress to a more severe generalized form, characterized by weakness in the extremities or in muscles that govern basic life functions.

In about two thirds of individuals, the initial symptom of MG is related to the muscles around the eye. or food and liquids may regurgitate into the nose rather than go down the throat (velopharyngeal insufficiency). or have a nasal quality. In a myasthenic crisis, a paralysis of the respiratory muscles occurs, necessitating assisted ventilation to sustain life. Crises may be triggered by various biological stressors such as infection, fever, an adverse reaction to medication, or emotional stress. Other, less frequent antibodies are found against LRP4, agrin, and titin proteins. Human leukocyte antigen haplotypes are associated with increased susceptibility to myasthenia gravis and other autoimmune disorders. Relatives of people with myasthenia gravis have a higher percentage of other immune disorders. The thymus gland cells form part of the body's immune system. In those with myasthenia gravis, the thymus gland is large and abnormal. It sometimes contains clusters of immune cells that indicate lymphoid hyperplasia, and the thymus gland may give wrong instructions to immune cells.

For women who are pregnant and already have MG, in a third of cases, they have been known to experience an exacerbation of their symptoms, and in those cases, it usually occurs in the first trimester of pregnancy. Signs and symptoms in pregnant mothers tend to improve during the second and third trimesters. Complete remission can occur in some mothers. Immunosuppressive therapy should be maintained throughout pregnancy, as this reduces the chance of neonatal muscle weakness, and controls the mother's myasthenia. A child with TNM typically responds very well to acetylcholinesterase inhibitors, and the condition generally resolves over a period of three weeks, as the antibodies diminish, and generally does not result in any complications. Transient neonatal myasthenia occurs in 10 to 15% of babies born to mothers afflicted with the disorder, and disappears after a few weeks. Congenital myasthenia, the rarest form, occurs when genes are present from both parents. Juvenile myasthenia gravis is most common in females. Congenital myasthenias cause muscle weakness and fatigability similar to those of MG. The signs of congenital myasthenia usually are present in the first years of childhood, although they may not be recognized until adulthood.

During a physical examination to check for MG, a doctor might ask the person to perform repetitive movements. For instance, the doctor may ask one to look at a fixed point for 30 seconds and to relax the muscles of the forehead, because a person with MG and ptosis of the eyes might be involuntarily using the forehead muscles to compensate for the weakness in the eyelids. In specific situations, testing is performed for Lambert Eaton syndrome.

Muscle fibers of people with MG are easily fatigued, which the repetitive nerve stimulation test can help diagnose. In single fiber electromyography, which is considered to be the most sensitive (although not the most specific) test for MG,

Applying ice for 2–5 minutes to the muscles reportedly has a sensitivity and specificity of 76.9% and 98.3%, respectively, for the identification of MG. Acetylcholinesterase is thought to be inhibited at the lower temperature, which is the basis for this diagnostic test. This generally is performed on the eyelids when ptosis is present and is deemed positive if a ≥2 mm rise in the eyelid occurs after the ice is removed.

This test requires the intravenous administration of edrophonium chloride or neostigmine, drugs that block the breakdown of acetylcholine by cholinesterase (acetylcholinesterase inhibitors). This test is no longer typically performed, as its use can lead to life threatening bradycardia (slow heart rate) which requires immediate emergency attention. Production of edrophonium was discontinued in 2008. MRI of the cranium and orbits may also be performed to exclude compressive and inflammatory lesions of the cranial nerves and ocular muscles.

The forced vital capacity may be monitored at intervals to detect increasing muscular weakness. Acutely, negative inspiratory force may be used to determine adequacy of ventilation; it is performed on those individuals with MG.

The muscle weakness that worsens with activity (abnormal muscle fatigue) in myasthenia gravis is a symptom shared by other neuromuscular diseases. Most of the metabolic myopathies, such as McArdle disease (GSD V), have abnormal muscle fatigue rather than fixed muscle weakness. Also, like myasthenia gravis, A small minority of patients with McArdle disease also have the comorbidity of ptosis (drooping upper eyelid). Late onset GSD II (Pompe disease) and GSD XV also have muscle weakness or fatigue with comorbidities of ptosis and ophthalmoplegia; as do many of the mitochondrial myopathies. Other diseases that involve abnormal muscle fatigue (which may be described as exercise induced muscle weakness, reversible muscle weakness, or muscle weakness that improves with rest) include: endocrine myopathies (such as Hoffman syndrome), Tubular aggregate myopathy (TAM), ischemia (such as intermittent claudication, popliteal artery entrapment syndrome, and chronic venous insufficiency), and poor diet or malabsorption diseases that lead to vitamin D deficiency (osteomalic myopathy). Although limb girdle muscular dystrophies (LGMDs) involve fixed muscle weakness, LGMDR8 also involves muscle fatigue; as do some limb girdle muscular dystrophy dystroglycanopathies such as MDDGC3 (a. k. a. LGMDR15 and LGMD2O). Myofibrillar myopathy 10, dimethylglycine dehydrogenase deficiency, erythrocyte lactate transporter defect, and myopathy with myalgia, increased serum creatine kinase, with or without episodic rhabdomyolysis (MMCKR) also include muscle fatigue. X linked episodic muscle weakness (EMWX) includes general muscle weakness, ptosis, and fluctuations in strength. In some individuals, fatiguability was demonstrable, the phenotype having features comparable to congenital myasthenic syndromes and channelopathies. Signs and symptoms of myasthenia presenting from infancy or childhood may be one of the congenital myasthenic syndromes, which can be inherited in either an autosomal dominant or recessive manner. There are currently over two dozen types of congenital myasthenic syndromes. Limb–girdle myasthenia gravis is a distinct condition from myasthenia gravis. It is an adult onset, autoimmune condition affecting the neuromuscular junction. However, it lacks eye abnormalities and is associated with autoimmune conditions such as systemic lupus erythematosus, Hashimoto's thyroiditis, and thymoma. Lambert–Eaton myasthenic syndrome (LEMS) is an autoimmune condition that attacks the neuromuscular junction, either as a paraneoplastic syndrome (typically older patients) or associated with a non cancerous primary autoimmune condition (typically younger patients). It usually involves lower limb weakness and exercise induced fatiguability, although the upper limbs and eyes may also be involved. Lambert's sign is the unusual improvement of grip strength that follows after squeezing the hand at maximum intensity for 2 3 seconds.

Treatment is by medication and/or surgery. Medication consists mainly of acetylcholinesterase inhibitors to directly improve muscle function and immunosuppressant drugs to reduce the autoimmune process. Thymectomy is a surgical method to treat MG.

Worsening may occur with medication such as fluoroquinolones, aminoglycosides, and magnesium. About 10% of people with generalized MG are considered treatment refractory. Autologous hematopoietic stem cell transplantation (HSCT) is sometimes used in severe, treatment refractory MG. Available data provide preliminary evidence that HSCT can be an effective therapeutic option in carefully selected cases. Efgartigimod alfa (Vyvgart) was approved for medical use in the United States in December 2021. Efgartigimod alfa/hyaluronidase (Vyvgart Hytrulo) was approved for medical use in the United States in June 2023. Rozanolixizumab (Rystiggo) was approved for medical use in the United States in June 2023.

Acetylcholinesterase inhibitors can provide symptomatic benefit and may not fully remove a person's weakness from MG. While they might not fully remove all symptoms of MG, they still may allow a person the ability to perform normal daily activities. Pyridostigmine is a relatively long acting drug (when compared to other cholinergic agonists), with a half life around four hours with relatively few side effects. Generally, it is discontinued in those who are being mechanically ventilated, as it is known to increase the amount of salivary secretions. or azathioprine.

As thymomas are seen in 10% of all people with the MG, they are often given a chest X ray and CT scan to evaluate their need for surgical removal of their thymus glands and any cancerous tissue that may be present. A 2016 randomized, controlled trial, however, found some benefits.

People with MG should be educated regarding the fluctuating nature of their symptoms, including weakness and exercise induced fatigue. Exercise participation should be encouraged with frequent rest.

In people with myasthenia gravis, older forms of iodinated contrast used for medical imaging have caused an increased risk of exacerbation of the disease, but modern forms have no immediate increased risk.

The prognosis of people with MG is generally good, as is quality of life, when given very good treatment. Monitoring of a person with MG is very important, as at least 20% of people diagnosed with it will experience a myasthenic crisis within two years of their diagnosis, requiring rapid medical intervention. In the United Kingdom, an estimated 15 cases of MG occur per 100,000 people. The term "myasthenia gravis pseudo paralytica" was proposed in 1895 by Jolly, a German physician. Some research recently has been on anti c5 inhibitors for treatment research as they are safe and used in the treatment of other diseases. In the laboratory, MG is mostly studied in model organisms, such as rodents. In addition, in 2015, scientists developed an in vitro functional, all human, neuromuscular junction assay from human embryonic stem cells and somatic muscle stem cells. After the addition of pathogenic antibodies against the acetylcholine receptor and activation of the complement system, the neuromuscular co culture shows symptoms such as weaker muscle contractions.