Myasthenia Gravis
Introduction and Facts
Myasthenia gravis is an autoimmune disorder characterized by an abnormal and progressive weakness in skeletal muscles that is used continuously and is accompanied by fatigue during activity. This disease arises due to interference with synaptic transmission or at the neuromuscular junction. Where when the patient rests, then not long afterward muscle strength will recover.
Myasthenia gravis is a rare disease. The incidence is 20 in 100,000 population. Usually this disease is more often seen at the age of over 50 years. Women suffer from this disease more often than men and it can occur at any age. In women, this disease appears at a younger age, which is around 28 years, while in men, this disease often occurs at the age of 60 years.
Pathophysiology
Clinical observations that support this include the emergence of autoimmune disorders associated with patients suffering from myasthenia gravis, such as autoimmune thyroiditis, systemic lupus erythematosus, rheumatoid arthritis, and others. Thus, immunogenic mechanisms play a very important role in the pathophysiology of myasthenia gravis.
This is what plays an important role in the weakening of the muscles of patients with myatenia gravis. Since the 1960s, it has been demonstrated how autoantibodies in the serum of patients with myasthenia gravis directly oppose constituents in muscle. There is no doubt that antibodies to nicotinic acetylcholine receptors are a major cause of muscle weakness in patients with myasthenia gravis. Autoantibodies to acetylcholine receptors (anti-AChRs), have been detected in the serum of 90% of patients with generalized acquired myasthenia gravis.
Myasthenia gravis can be said to be a “B cell-associated disease”, in which antibodies which are products of B cells actually fight against acetylcholine receptors. The role of T cells in the pathogenesis of myasthenia gravis is becoming increasingly prominent. Although the exact mechanism of loss of immunologic tolerance to acetylcholine receptors in patients with myasthenia gravis is not fully understood. The thymus is a central organ of T cell-associated immunity, whereas abnormalities in the thymus, such as thymic hyperplasia or thymoma, usually appear earlier in patients with myasthenic symptoms.
The alpha subunit is also the binding site of acetylcholine. Thus, in myasthenia gravis patients, IgG antibodies are composed of a number of different subclasses, where one antibody directly opposes the major immunogenic area of the alpha subunit. The binding of acetylcholine receptor antibodies to acetylcholine receptors will result in obstruction of neuromuscular transmission in several ways, including: cross-linking of acetylcholine receptors to anti-acetylcholine receptor antibodies and reducing the number of acetylcholine receptors at the neuromuscular junction by destroying the binding junctions on the postsynaptic membrane, thereby reducing the area of the acetylcholine receptor. surface that can be used for the insertion of newly synthesized acetylcholine receptors
Clinical Symptoms and Complications
Myasthenia gravis is characterized by fluctuating weakness in the skeletal muscles and this weakness increases with activity. Patients will feel very weak muscles during the day and this weakness will decrease when the patient rests. Clinical symptoms of myasthenia gravis include weakness in the extraocular muscles or ptosis. Ptosis which is one of the symptoms is often the main complaint of patients with myasthenia gravis, this is caused by paralysis of the oculomotor nerve. Although in myasthenia gravis the levator palpebral muscles are clearly paralyzed, there are times when the ocular muscles still move normally. But in the advanced stages of paralysis of the ocular muscles on both sides will complete ptosis myasthenia gravis. From time to time there can also be weakness of the masseter muscle so that the patient's mouth is difficult to close. Weakness of the bulbar muscles is also common, followed by weakness in flexion and extension of the head. In addition, difficulty swallowing and speaking can also arise due to weakness of the pharyngeal, tongue, soft palate, and larynx muscles, resulting in paresis of the soft palate which will cause a nasal sound. In addition, if the patient drinks water, the water may come out of his nose
Diagnosis
A careful physical examination should be performed to establish the diagnosis of a myasthenia gravis. Muscle weakness can appear in the proximal part of the body and is symmetrical in both the right and left limbs. Although in varying degrees, usually tendon reflexes are still within normal limits. Bilateral facial muscle weakness will cause a myasthenic sneer with ptosis and a horizontal smile and myasthenia gravis is usually always accompanied by weakness in the facial muscles. On physical examination, there is weakness of the palate muscles, which causes the patient's voice to feel like being in the nose (nasal twang to the voice) and regurgitation of food, especially liquid into the patient's nose. In addition, people with myasthenia gravis will have difficulty chewing and swallowing food, so that fluid aspiration can occur which causes sufferers to cough and choke when drinking. Bulbar muscle weakness is also common in patients with myasthenia gravis. Characterized by weakness of the jaw muscles in myasthenia gravis which makes it difficult for the patient to close his mouth, so the patient's chin must be supported by the hand. The neck muscles also experience weakness, resulting in disturbances in flexion and extension of the neck. Weakness of the lateral and medial rectus muscles will cause pseudointernuclear ophthalmoplegia, which is characterized by limited adduction ability of one eye accompanied by nystagmus in the abducting eye.
Tensilon Test (edrophonium chloride)
For the tensilon test, 2 mg of tensilon is injected intravenously, if there is no reaction then 8 mg of tensilon is injected intravenously. Immediately after tensilon is injected we should pay attention to weak muscles such as the eyelids that show the presence of ptosis. If the weakness is really caused by myasthenia gravis, then the ptosis will soon disappear. In this test weak eyelids must be observed very carefully, because the effectiveness of tensilon is very short.
Prostigmine (neostigmine) Test
In this test, 3 cc or 1.5 mg of prostigmine methylsulfate is injected intramuscularly (if necessary, atropine or mg is also given). If the weakness is really caused by myasthenia gravis then symptoms such as ptosis, strabismus or other weakness will soon disappear.
Quinine Test
Given 3 quinine tablets each 200 mg. 3 hours later given 3 more tablets (each 200 mg per tablet). For this test, prostigmine injection should also be prepared, so that myasthenic symptoms do not get worse. If the weakness is really caused by myasthenia gravis, then symptoms such as ptosis, strabismus, and others will get worse.
Laboratory
Antistriated muscle (anti-SM) antibodies. This test is positive in about 84% of patients with thymoma who are less than 40 years of age. So it is one of the important tests in patients with myasthenia gravis. In patients without thymoma, anti-SM antibodies may show positive results in patients older than 40 years,
Anti-muscle-specific kinase (MuSK) antibodies. Nearly 50% of patients with myasthenia gravis who show negative anti-AChR Ab results (seronegarive myasthenia gravis), test positive for anti-MuSK Ab.
Antistriational antibodies. These antibodies react with epitopes on the titin and ryanodine (RyR) protein receptors. These antibodies have always been associated with thymoma patients with myasthenia gravis at a young age. Detection of titin/RyR antibody is a strong suspicion of thymoma in a young patient with myasthenia gravis. This is due in serum Anti-Acetylcholine receptor antibodies.
Electrodiagnostics. Electrodiagnostic examination can reveal defects in neuromuscular transmission by 2 techniques. Single-fiber Electromyography (SFEMG) and Repetitive Nerve Stimulation (RNS)
Management and Care
Anticholinesterase (acetylcholinesterase inhibitors) and immunomodulatory therapy are the mainstay of treatment for myasthenia gravis. Anticholinesterases are usually used in mild myasthenia gravis. Meanwhile, in patients with generalized myasthenia gravis, routine immunomodulation therapy is necessary. The management of myasthenia gravis can be done with drugs, thymomectomy or with immunomodulation and immunosuppressive therapy which can provide a good prognosis in the recovery of myasthenia gravis.
Plasma Exchange (PE)
PE is most effective in situations where beneficial short-term therapy is a priority. The basis of therapy with PE is the effective removal of anti-acetylcholine. The response to this therapy is a decrease in antibody titers. Where patients who receive treatment in the form of hospitalization and intubation for a long time and tracheostomy, can be minimized because of the dramatic effect of PE.
Intravenous Immunoglobulin (IVIG)
The mechanism of action of IVIG is not known with certainty, but IVIG is thought to be able to modulate the immune response. Reduction of antibody titer cannot be demonstrated clinically, because in most patients there is no decrease in antibody titer. Certain products, which are 99% IgG, are complement-activating aggregates that are relatively safe to administer intravenously. The effects of IVIG therapy can appear about 3-4 days after starting therapy.
Intravenous Methylprednisolone (IVmp)
IVMP is given at a dose of 2 grams within 12 hours. If there is no response, then the administration can be repeated 5 days later. If the response is still not there, then the administration can be repeated 5 days later. About 10 of 15 patients showed a response to IVMP on the second treatment, while the other 2 patients showed a response to the third therapy. Maximum effect is achieved in about 1 week after therapy. The use of IVMp in a crisis situation will be considered if other therapies fail or cannot be used.
Corticosteroids
Corticosteroids are the longest used and least expensive therapy for the treatment of myasthenia gravis. Corticosteroids have complex effects on the immune system and the exact therapeutic effect on myasthenia gravis is unknown. The duration of action of corticosteroids can last up to 18 months, with an average of 3 months. Where the response to corticosteroid treatment will begin to appear within 2-3 weeks after the initiation of therapy.
Azathioprine
Azathioprine can be converted to mercaptopurine, an analogue of purines that has an effect on inhibiting nucleotide synthesis in DNA and RNA. Azathioprine is a drug that is relatively well tolerated by the body and generally has fewer side effects than other immunosuppressive drugs. Azathioprine is usually used in patients with myasthenia gravis who are relatively controlled but are taking high doses of corticosteroids.
Cyclosporine
Response to cyclosporine is faster than azathioprine. The initial dose of Cyclosporine is about 5 mg/kg/day divided into two or three doses. Cyclosporine affects the production and release of interleukin-2 from T-helper cells. Suppression of T-helper cell activation, has an effect on antibody production.
Cyclophosphamide (CPM)
In theory, CPM has a direct effect on antibody production compared to other drugs. CPM is an alkylating agent that has an effect on B cell proliferation, and can indirectly suppress immunoglobulin synthesis.
Thymectomy (Surgical Care)
There have been many studies on the relationship between the thymus gland and the incidence of myasthenia gravis. Germinal center hyperplasia of the thymus is considered as a possible cause responsible for the occurrence of myasthenia gravis. Many neurologists have convincing experience that thymectomy has an important role in the treatment of myasthenia gravis, although the benefits vary, are difficult to explain and still cannot be proven by rigorous standards.
Reference:
A.A Gde Agung Anom Arie W, Adnyana MO, Widyadharma IPE. DIAGNOSIS DAN TATA LAKSANA MIASTENIA GRAVIS. [Internet] [Cited 28/8/2021]. Available from: https://ojs.unud.ac.id › eum › article › download
