(I) Treatment
1.Drug treatment
(1) Anticholinesterase drugs: they are the most important drugs for the treatment of this disease. These drugs can inhibit acetylcholinesterase, reduce the destruction of acetylcholine, increase the combination of acetylcholine and AChR, thus increasing the excitability of neuromuscular, to improve the symptoms of the purpose. There are three commonly used drugs: neostigmine, pyridostigmine and mytelase. The general dosage of neostigmine tablets is 15~45mg, 3~4 times/d, with a short duration of action. Excessive dosage is prone to muscarinic-like side effects such as abdominal pain and diarrhea, which can be alleviated by taking appropriate amount of atropine. This drug is mainly used for the initial mild cases and acute exacerbation cases, and can be combined with other anticholinesterase drugs. This drug has a longer duration of action and milder side effects. It is effective for ptosis medullary muscle paralysis and has a wide range of safety. It is also used for generalized myasthenia gravis at a dose of 5-10 mg 3 times/d. After the above drugs have been used until the disease is stabilized, the dose can be reduced or discontinued completely as appropriate.
In addition, 0.5% and 1% bisoprolide bromide can be used as eye drops, which is the drug of choice for the treatment of ptosis in this disease. To increase the effect of anticholinesterase drugs or to reduce the dosage of anticholinesterase drugs, ephedrine, guanidine, spironolactone, etc. can be used in combination, which have the effect of increasing free acetylcholine in the nerve endings but have a weaker effect compared to anticholinesterase drugs. Calcium agents maintain intracellular calcium ion concentrations and work best in combination. Another large class of drugs, including synaptic receptor competitive agents, myofilament inhibitors and whistle inhibitors, such as central nervous system inhibitors, antiarrhythmics and some antibiotics (especially the streptomycin family) drugs, have similar arrow-like effects or magnesium, which can inhibit acetylcholine and should be disabled when applying anticholinesterase drugs.
(2) corticosteroids: currently widely used in the treatment of myasthenia gravis of generalized and oculomotor type. In China, some people applied prednisone high-dose therapy to treat 8 cases of oculomotor type myasthenia gravis, and 6 cases were cured and 2 cases were effective. The ptosis began to improve 6 to 18 days after treatment, and the oculomotor disorder disappeared 18 to 26 days after treatment. Ptosis generally improved 5 to 14 days after treatment, and oculomotor disorders improved or disappeared in 2 to 5 weeks. Cui Guoyi reported 43 cases, 35 cases (81.4%) were cured and basically cured, and 8 cases (22.9%) were relapsed. The mechanisms of corticosteroid treatment for myasthenia gravis are: (1) correcting the abnormalities of thymic immune function; (2) inhibiting the formation of thymic germinal centers; (3) improving the immune function of lymphocytes regulated by thymus; (4) inhibiting the production of motor endplate antibodies in serum; and (5) promoting the release of acetylcholine at the neuromuscular junction, thus improving the neuromuscular conduction function. Experiments have confirmed that glucocorticoids can cause nuclear fixation, deep staining and nuclear cleavage in thymocytes. Through the action of glucocorticoid receptor (CGP), it affects the synthesis of thymus cell cycle-related proteins, which in turn induces apoptosis of immune cells and thymus atrophy, resulting in immune suppression.
Corticosteroids are used in two ways.
Tapered method: It is indicated for outpatients. The method is to take 10-20 mg of prednisone orally every day, and increase the dose once a week, and the dose can be increased to 70-100 mg for about 1 month, and then changed to every other day dose.
Decreasing method: Start with 100-200mg of prednisone or 10-15mg of dexamethasone, and take it once a day or every other day in the morning. Gradually reduce the dose after the effect is seen. Children under 15 years of age should take 2-3mg/kg every other day for 15-20 times, and the dose should be gradually reduced to stop after the symptoms improve. Adrenocorticotropic hormone can also be used, and 50-200 U can be injected intramuscularly or intravenously every day for 10-15 days, and then changed to once a week to consolidate the efficacy.
The application of high-dose corticosteroids, especially in the initial cases, may aggravate the condition, and requires preparation for tracheotomy and artificial whistling, and attention to sodium restriction and potassium supplementation, the addition of aluminum hydroxide gel, the administration of a high-protein diet and other measures to prevent the induction of myasthenia crisis and gastric bleeding and other serious complications.
(3) Other immunosuppressive drugs: such as cyclophosphamide 200mg/day intravenously or orally; azathioprine 50-150mg/d orally; 6-thiopurine 100-200mg/d, 2-3 times/d. Application of such drugs should pay attention to changes in white blood cell count, platelet count and clotting time.
(4) Combination of drugs: bromipyridamole, prednisone and cyclophosphamide are used in half of the above oral dose and reduced by decreasing method to six months discontinuation. Combination of drugs has the following advantages: ① reduce the dose of drugs; ② avoid the complications of obesity, hirsutism, decreased resistance and leukopenia and secondary infection caused by long-term application of corticosteroids, and avoid the occurrence of myasthenia gravis; ③ have obvious anti-relapse effect.
(5) Treatment of hyperthyroidism drugs: Because often after controlling the complication of hyperthyroidism, myasthenia gravis can be improved. Therefore, antithyroid drugs, thioureas and imidazoles, such as methionine, plus mercaptan imidazole, are commonly used.
2, de-plasma therapy Because the AChR antibody in the blood circulation plays an important role in myasthenia gravis, de-plasma therapy can remove the antibody to achieve the purpose of treatment. It is found that this method is also temporary, and the antibody potency rises immediately after plasma removal therapy, so it is now used sparingly.
3.Radiation therapy is applied to the whole body in small doses to destroy the surrounding lymphocytes to achieve the purpose of treatment, mainly for cases that are not suitable for thymectomy, 2Gy per day, once every other day, the total dose of 3-5Gy.
4.Surgical treatment
(1) Thymectomy: Patients under 40 years of age, with a disease duration of less than 5 years, and those who do not have significant effect of anticholinesterase drug treatment, can have thymectomy. In addition, thymectomy is an absolute indication for thymoma, and the earlier the better. Most patients with this disease without thymoma also have thymic hyperplasia, so thymectomy can be considered for anyone who has poor results with drug therapy. Some people advocate thymectomy as a routine treatment for patients other than oculomotor type, because drugs are difficult to cure and have many side effects, so it is better to perform surgery when the disease has not developed to a serious level. The condition may worsen in the near future after surgery and may even induce myasthenia gravis, so attention should be paid to emergency care.
(2) Correction of ptosis and strabismus: The following conditions should be present for surgical treatment of oculomotor myasthenia gravis.
(i) No response to anticholinesterase drugs and corticosteroid medication.
② non-response to Tensilon.
③Stable symptoms of ptosis and paralytic strabismus for more than six months.
④those who are at risk of amblyopia or have significant diplopia. As for the surgical method, ptosis is feasible with anterior migration of the levator muscle or frontalis suspension, and shortening is prudent; strabismus is feasible with anterior migration of the paralytic muscle and posterior migration of the antagonist muscle.
5. Treatment of amblyopia Children under 5 years of age with myasthenia gravis are prone to amblyopia. The cause of amblyopia is related to ptosis (especially monocular) and strabismus, and amblyopia should be actively treated along with medication for myasthenia gravis.
(ii) Prognosis
Treatment is limited. Early attention should be paid to the prevention of form deprivation amblyopia. In 1987, Grob et al. found that 50% of patients had ocular symptoms, 11% had abnormal ball function, 10% had lower extremity muscle weakness, and 9% had generalized muscle weakness. 40% of patients had ocular symptoms only and 40% had generalized muscle weakness within 1 month. Only 14% of patients had long-term ocular symptoms. The incidence of progression to generalized myasthenia gravis varied, with 87% of patients continuing to progress within 1 year and only 10% of patients able to spontaneously remit. In the absence of intensive care and mechanical ventilation treatment, the morbidity and mortality rate is between 30% and 60%. the discovery and use of cholinesterase inhibitors in 1934 led to a decrease in the morbidity and mortality rate; after 1939, thymectomy treatment was added and the morbidity and mortality rate of myasthenia gravis was further reduced.