Myasthenia gravis is a neuromuscular junction in skeletal muscle dysfunction, the main transmission of disease, for the performance of involvement in skeletal muscle weakness and fatigue easily, the symptoms of late-morning light, after the rest can be reduced, the application of anti-cholinesterase Drugs (such as the new Andean Ming) can quickly ease the symptoms. The disease incidence rate of 0.5 to 5 / 10 million, China Southern higher than the incidence of the North. Female incidence rate significantly higher than male, male to female ratio was 1:2 to 1:5, but in the older age groups in the incidence of male than female high. The age of onset of the disease in more than 20 to 40-year-old female多见. However, 60 to 70-year-old age for another peak, with male多见. And more incentives pathogenesis for upper respiratory tract infection, trauma, Guodupilao, menstruation, childbirth, surgery, and so on. These factors may also condition deteriorated even evoked myasthenia crisis.
Cause since the mid-20th century after a series of studies prove that the disease is a kind of auto-immune disease. As the body produce its own antibodies ─ ─ acetylcholine receptor (AchR) antibody, and destroyed the neuromuscular junction of the postsynaptic membrane AchR, the synaptic transmission occurred obstacles, not the full cause muscle contraction, Lead to myasthenia gravis. The vast majority of patients with serum can be measured in the anti-AchR...
Myasthenia gravis is a neuromuscular junction in skeletal muscle dysfunction, the main transmission of disease, for the performance of involvement in skeletal muscle weakness and fatigue easily, the symptoms of late-morning light, after the rest can be reduced, the application of anti-cholinesterase Drugs (such as the new Andean Ming) can quickly ease the symptoms. The disease incidence rate of 0.5 to 5 / 10 million, China Southern higher than the incidence of the North. Female incidence rate significantly higher than male, male to female ratio was 1:2 to 1:5, but in the older age groups in the incidence of male than female high. The age of onset of the disease in more than 20 to 40-year-old female多见. However, 60 to 70-year-old age for another peak, with male多见. And more incentives pathogenesis for upper respiratory tract infection, trauma, Guodupilao, menstruation, childbirth, surgery, and so on. These factors may also condition deteriorated even evoked myasthenia crisis.
Cause since the mid-20th century after a series of studies prove that the disease is a kind of auto-immune disease. As the body produce its own antibodies ─ ─ acetylcholine receptor (AchR) antibody, and destroyed the neuromuscular junction of the postsynaptic membrane AchR, the synaptic transmission occurred obstacles, not the full cause muscle contraction, Lead to myasthenia gravis. The vast majority of patients with serum antibodies can be detected AchR, while in other patients with myasthenia gravis in general difficult to detect, so the detection of antibodies to the diagnosis of the disease are very helpful. About 80 percent of patients with MG thymus mast, about 10 percent of the merger thymoma. Thymus central organ for immunization, which also further clarify the incidence of this disease and immune mechanism. Histological examination found that the thymus MG patients in a residual "muscle cells" (the cells should have been born in the normal degradation), also cross striations and AchR, so to speculate in the thymus lymphocytes may be due to long-term This "muscle cells" to stimulate and produce antibodies, causing the muscle AchR's own immune response. In addition, according to statistics a considerable number of patients with MG while other autoimmune diseases combined, such as hyperthyroidism, thyroiditis, systemic lupus erythematosus, rheumatoid arthritis, pemphigus, and so on. The study found that the incidence of this disease and certain human leukocyte antigen (HLA) type, so MG and genetic factors may be relevant.
Pathological pathological changes occurred mainly in skeletal muscle, thymus and the neuromuscular junction. Changes in skeletal muscle itself is not serious, only see muscle fibers focal necrosis, or muscle fibers surrounding the small blood vessels that sometimes infiltrating lymphocytes, called "lymphatic overflow." Myocardial can also see a similar change. Thymus is visible mast, lymphoid follicles proliferated, even thymoma. The most prominent pathological changes in the neuromuscular junction, electron microscopy showed synaptic gap widened, postsynaptic membrane fold reduction, it is relatively flat, and little change in synaptic membranes, reducing the number of synaptic vesicles .
Clinical manifestations of this disease onset implicit attack, about 80 percent of cases the first symptom to eye, myasthenia gravis, expressed as ptosis, often from the side, then to the development of contralateral. Eyeball activities were limited and as a dual, but the pupil sphincter will not be affected. If the masticatory muscles and throat muscles involved, and Yanxia difficulty eating, drinking choking, and unable even to speak with nasal. Facial expression is the lack of involvement, Bimu weakness. Sternocleidomastoid and trapezius involvement is unable to Zhuantou and Song Jian. Limbs, muscle proximal involvement often heavier, can affect day-to-day activities, serious when forced to bed. These symptoms usually Chen Qi reduced symptoms of post-rapid increase, after the rest have varying degrees of recovery, this disease-the main clinical features. General feeling normal, tendon reflexes do not change, but after repeated Kouji tendon reflexes can be reduced. If violations of respiratory muscle lesions occurred breathing difficulties, this is known as myasthenia gravis crisis is often the main reason of death. Myocardial involvement, can cause sudden death. A small number of cases may be the natural response (in more than three years after onset). Fulminant individual cases were, in most cases deferred several years to several decades of relying on drugs, the condition often volatile. As a considerable number of cases of mergers or thymoma thymus mast, it should be for the patients chest X-ray tomography, or CT scan radiography.
Various different types. At present the majority's application of Osserman classification:
Ⅱ ocular lesions limited to the eye muscles, more stable condition, but the confrontation CHE drug sensitivity poor.
Ⅱ A mild body type, from the symptoms of eye muscles, gradually spread to the limbs and muscles of the throat, respiratory muscles do not invasion.
Ⅱ B-moderate systemic symptoms than Ⅱ A re-affected day-to-day activities, but was able activities of daily living.
Ⅲ radical type of severe, acute onset, and more within six months to the development of respiratory muscle paralysis, a myasthenic crisis. This type of high mortality.
Ⅳ delayed severe type, or from Ⅱ A Ⅱ B developed from 2 to 3 years after MG crisis, the prognosis is poor.
Ⅴ muscular atrophy type, a small number of patients with muscular atrophy.
Some women with pregnancy, the body's antibody AchR fetus through the placenta into the body so that the newborn delivered after symptoms appear myasthenia gravis, the weak performance to cry, breathing difficulty. Such as temporary neonatal myasthenia gravis, usually four to six weeks after the passive antibody in all of inactivation, symptoms also will disappear.
In addition to relying on the diagnosis of clinical features, can still carry out the following checks to help diagnosis.
Fatigue test (about Lee's trial) so that patients with repeated movement affected muscle symptoms are obvious increase. If so that patients turn to repeat, eyes closed eye movements are increasingly split; repeat chewing movement is not final, such as chewing.
Anti-CHE drug test with anti-CHE drugs alleviate symptoms.
① Teng-hi-long trial. Long-teng will use water for injection 10 mg to 10 ml diluted intravenous injection, Ban Fenzhong around quickly ease the symptoms for the positive reaction, 10 minutes later to restore muscle strength and status before treatment.
② of the new Sri Lanka Test. Dimethyl sulfate that the new Slovak 0.5 mg intramuscular injection, 20 minutes after the symptoms were alleviated for the positive, sustainable effectiveness of drugs around two hours. To prevent that from the new Slovak muscarinic kind of reaction (drooling, sweating, abdominal pain, diarrhea, vomiting, etc.), while intramuscular injection of atropine 0.5 mg.
EMG re-stimulate the check before the test should be suspended anti-drug CHE more than 17 hours, otherwise positive rate lower. Typical change for the repeated use of low frequency stimulation (1 ~ 3 Hz) after the muscle action potential volatility decline, the diagnosis of the disease. Single fiber EMG show the same dominance of the muscle fiber potential to extend the interval, it also shows that neuromuscular junction between the transmission barriers.
AchR antibody in the diagnosis of the disease are characteristic value. More than 80 percent of patients with MG AchR in significantly higher antibody titration, only ocular titer lower.
Differential diagnosis of typical cases it is not difficult, but the disease to be identified with the following:
Chronic hyperthyroidism myopathy limbs, but also for the proximal weakness, muscular atrophy obviously, that the new sensitivity of the Andean poor, AchR serum antibody negative. The timely investigation of iodine thyroid acid 3 (T3), four iodine thyroxine (T4) often can be confirmed. Early treatment the prognosis is good.
Class of myasthenia gravis syndrome (Lambert - Eaton II's syndrome) more common in small cell lung cancer (oat cell carcinoma) patients. Neuromuscular junction is also the shortcomings, but the main lesions in the synaptic membrane. As in a film for presynaptic calcium channel or vesicles release (with activities) autoantibodies, resulting in acetylcholine (Ach) to reduce the release, resulting in myasthenia gravis. Clinical symptoms and MG similar, but more for the general muscle weakness, ocular, masticatory muscles, and other less involvement. Cholinesterase drug reaction as the MG-sensitive. AchR and serum antibody negative. EMG for re-inspection frequency to stimulate use high-frequency stimulation (15 Hz or more) when the muscle action potential volatility increased, the characteristics of the disease-oriented performance. Oral GuHCl can promote acetylcholine secretion, can ease the symptoms. If found to be malignant tumor removed. But sometimes tumor removed after the symptoms of myasthenia gravis are not necessarily followed ease. In some cases symptoms of myasthenia gravis in a few years after the cancer occurred. Therefore, the clinical syndrome that type of myasthenia gravis should be closely followed up the early detection of potentially malignant lesions and to be radical.
Treatment includes the following aspects:
Anti-drug therapy generally preferred for cholinesterase drugs.
① anti-cholinesterase drugs, will cholinergic nerve endings release of acetylcholine is not the accumulation of damage. Are commonly used for the bromide that the new Sri Lanka, pyridostigmine, the suppression of Nanjing, oral administration. If the symptoms of myasthenia gravis mainly to chew, the impact of eating, you can take half an hour before meals. If there muscarinic-like reaction can be added to atropine. In addition, the fair plus potassium chloride and ephedrine as a supplementary drug to enhance the effect.
② corticosteroids and immunosuppressive agents. Corticosteroid can inhibit the autoimmune response. High-dose therapy may surprise, gradually reduced to maintain the volume. But at the beginning of 1 or 2 times after a temporary increase myasthenia gravis, the need for tracheotomy and ventilator emergency preparations. 3 to 4 times after symptoms begin easing. Can also be used to maintain long-term low-dose, several months after the symptoms can be alleviated. Other immunosuppressive drugs such as azathioprine, cyclophosphamide, also optional.
Where impact of the neuromuscular junction drug delivery (such as Jiandu, quinidine, propranolol, streptomycin, neomycin, kanamycin, polymyxin, etc.) must be anti.
Surgical treatment of young, short duration, disease progress faster without major complications, to early thymus removed, the better operation of the long-term effect. Thymomas are less effective merger, but the operation should also be removed.
Radiotherapy older, heart and kidney complications rather than surgical treatment can be carried out deep X-ray treatment, X-ray damage thymus, but also achieve a satisfactory effect.
Plasma replacement therapy for patients with severe attack or myasthenia crisis, each taken from the patient plasma 1000 ~ 2000 ml, while the importation of fresh plasma, or the equivalent of plasma, 1 to 2 times per week, can quickly remove the AchR antibodies in the blood, Relieve symptoms. However, this method can only temporarily relieve symptoms and can not be used as conventional therapy.
Crisis should be treated in a timely manner, if a respiratory muscle paralysis, respiratory should first maintain patent and, if necessary, a tracheotomy, the application of artificial respirator, at any time suction to remove respiratory secretions. At the same time the nature of the crisis should be based on a different treatment.
① myasthenia crisis. For the most common crisis, often by the anti-cholinesterase drugs arising from inadequate consumption, may, by intravenous injection Teng-hi-identification. First intravenous injection Teng-hi-2 mg, if the symptoms improve, then the remaining 8 mg injection, quickly alleviate symptoms of myasthenia crisis. Anti-cholinesterase drugs should increase the amount of dimethyl sulfate could be the new Sri Lanka that the 0.5 mg or pyridostigmine from 1 mg intravenous infusion of small pots, each 2 to 3 hours, 1, until after the crisis eased Adjusted dosage, or switch to corticosteroid therapy.
② cholinergic crisis. Because of anti-cholinesterase drug overdose caused. Apart from clinical respiratory muscle paralysis, can still see the muscle bundle fibrillation, sweating, drooling, abdominal pain, diarrhea and other muscarinic-like response. Lung-teng-test for the intravenous injection of 2 mg symptoms of myasthenia gravis, but heavier. At this point should disable all anti-cholinesterase drugs, use of artificial respiration, or to switch to corticosteroid treatment until the crisis eased, for further adjustment of treatment.
③ counter-argue crisis. Since confrontation is not sensitive cholinesterase drugs, anti-cholinesterase drugs after a little of cholinergic crisis and therefore need to disable anti-cholinesterase drugs, used to maintain artificial respiration. May ease the crisis after anti-cholinesterase drug trial, or to switch to corticosteroid therapy.
Cause since the mid-20th century after a series of studies prove that the disease is a kind of auto-immune disease. As the body produce its own antibodies ─ ─ acetylcholine receptor (AchR) antibody, and destroyed the neuromuscular junction of the postsynaptic membrane AchR, the synaptic transmission occurred obstacles, not the full cause muscle contraction, Lead to myasthenia gravis. The vast majority of patients with serum can be measured in the anti-AchR...
Myasthenia gravis is a neuromuscular junction in skeletal muscle dysfunction, the main transmission of disease, for the performance of involvement in skeletal muscle weakness and fatigue easily, the symptoms of late-morning light, after the rest can be reduced, the application of anti-cholinesterase Drugs (such as the new Andean Ming) can quickly ease the symptoms. The disease incidence rate of 0.5 to 5 / 10 million, China Southern higher than the incidence of the North. Female incidence rate significantly higher than male, male to female ratio was 1:2 to 1:5, but in the older age groups in the incidence of male than female high. The age of onset of the disease in more than 20 to 40-year-old female多见. However, 60 to 70-year-old age for another peak, with male多见. And more incentives pathogenesis for upper respiratory tract infection, trauma, Guodupilao, menstruation, childbirth, surgery, and so on. These factors may also condition deteriorated even evoked myasthenia crisis.
Cause since the mid-20th century after a series of studies prove that the disease is a kind of auto-immune disease. As the body produce its own antibodies ─ ─ acetylcholine receptor (AchR) antibody, and destroyed the neuromuscular junction of the postsynaptic membrane AchR, the synaptic transmission occurred obstacles, not the full cause muscle contraction, Lead to myasthenia gravis. The vast majority of patients with serum antibodies can be detected AchR, while in other patients with myasthenia gravis in general difficult to detect, so the detection of antibodies to the diagnosis of the disease are very helpful. About 80 percent of patients with MG thymus mast, about 10 percent of the merger thymoma. Thymus central organ for immunization, which also further clarify the incidence of this disease and immune mechanism. Histological examination found that the thymus MG patients in a residual "muscle cells" (the cells should have been born in the normal degradation), also cross striations and AchR, so to speculate in the thymus lymphocytes may be due to long-term This "muscle cells" to stimulate and produce antibodies, causing the muscle AchR's own immune response. In addition, according to statistics a considerable number of patients with MG while other autoimmune diseases combined, such as hyperthyroidism, thyroiditis, systemic lupus erythematosus, rheumatoid arthritis, pemphigus, and so on. The study found that the incidence of this disease and certain human leukocyte antigen (HLA) type, so MG and genetic factors may be relevant.
Pathological pathological changes occurred mainly in skeletal muscle, thymus and the neuromuscular junction. Changes in skeletal muscle itself is not serious, only see muscle fibers focal necrosis, or muscle fibers surrounding the small blood vessels that sometimes infiltrating lymphocytes, called "lymphatic overflow." Myocardial can also see a similar change. Thymus is visible mast, lymphoid follicles proliferated, even thymoma. The most prominent pathological changes in the neuromuscular junction, electron microscopy showed synaptic gap widened, postsynaptic membrane fold reduction, it is relatively flat, and little change in synaptic membranes, reducing the number of synaptic vesicles .
Clinical manifestations of this disease onset implicit attack, about 80 percent of cases the first symptom to eye, myasthenia gravis, expressed as ptosis, often from the side, then to the development of contralateral. Eyeball activities were limited and as a dual, but the pupil sphincter will not be affected. If the masticatory muscles and throat muscles involved, and Yanxia difficulty eating, drinking choking, and unable even to speak with nasal. Facial expression is the lack of involvement, Bimu weakness. Sternocleidomastoid and trapezius involvement is unable to Zhuantou and Song Jian. Limbs, muscle proximal involvement often heavier, can affect day-to-day activities, serious when forced to bed. These symptoms usually Chen Qi reduced symptoms of post-rapid increase, after the rest have varying degrees of recovery, this disease-the main clinical features. General feeling normal, tendon reflexes do not change, but after repeated Kouji tendon reflexes can be reduced. If violations of respiratory muscle lesions occurred breathing difficulties, this is known as myasthenia gravis crisis is often the main reason of death. Myocardial involvement, can cause sudden death. A small number of cases may be the natural response (in more than three years after onset). Fulminant individual cases were, in most cases deferred several years to several decades of relying on drugs, the condition often volatile. As a considerable number of cases of mergers or thymoma thymus mast, it should be for the patients chest X-ray tomography, or CT scan radiography.
Various different types. At present the majority's application of Osserman classification:
Ⅱ ocular lesions limited to the eye muscles, more stable condition, but the confrontation CHE drug sensitivity poor.
Ⅱ A mild body type, from the symptoms of eye muscles, gradually spread to the limbs and muscles of the throat, respiratory muscles do not invasion.
Ⅱ B-moderate systemic symptoms than Ⅱ A re-affected day-to-day activities, but was able activities of daily living.
Ⅲ radical type of severe, acute onset, and more within six months to the development of respiratory muscle paralysis, a myasthenic crisis. This type of high mortality.
Ⅳ delayed severe type, or from Ⅱ A Ⅱ B developed from 2 to 3 years after MG crisis, the prognosis is poor.
Ⅴ muscular atrophy type, a small number of patients with muscular atrophy.
Some women with pregnancy, the body's antibody AchR fetus through the placenta into the body so that the newborn delivered after symptoms appear myasthenia gravis, the weak performance to cry, breathing difficulty. Such as temporary neonatal myasthenia gravis, usually four to six weeks after the passive antibody in all of inactivation, symptoms also will disappear.
In addition to relying on the diagnosis of clinical features, can still carry out the following checks to help diagnosis.
Fatigue test (about Lee's trial) so that patients with repeated movement affected muscle symptoms are obvious increase. If so that patients turn to repeat, eyes closed eye movements are increasingly split; repeat chewing movement is not final, such as chewing.
Anti-CHE drug test with anti-CHE drugs alleviate symptoms.
① Teng-hi-long trial. Long-teng will use water for injection 10 mg to 10 ml diluted intravenous injection, Ban Fenzhong around quickly ease the symptoms for the positive reaction, 10 minutes later to restore muscle strength and status before treatment.
② of the new Sri Lanka Test. Dimethyl sulfate that the new Slovak 0.5 mg intramuscular injection, 20 minutes after the symptoms were alleviated for the positive, sustainable effectiveness of drugs around two hours. To prevent that from the new Slovak muscarinic kind of reaction (drooling, sweating, abdominal pain, diarrhea, vomiting, etc.), while intramuscular injection of atropine 0.5 mg.
EMG re-stimulate the check before the test should be suspended anti-drug CHE more than 17 hours, otherwise positive rate lower. Typical change for the repeated use of low frequency stimulation (1 ~ 3 Hz) after the muscle action potential volatility decline, the diagnosis of the disease. Single fiber EMG show the same dominance of the muscle fiber potential to extend the interval, it also shows that neuromuscular junction between the transmission barriers.
AchR antibody in the diagnosis of the disease are characteristic value. More than 80 percent of patients with MG AchR in significantly higher antibody titration, only ocular titer lower.
Differential diagnosis of typical cases it is not difficult, but the disease to be identified with the following:
Chronic hyperthyroidism myopathy limbs, but also for the proximal weakness, muscular atrophy obviously, that the new sensitivity of the Andean poor, AchR serum antibody negative. The timely investigation of iodine thyroid acid 3 (T3), four iodine thyroxine (T4) often can be confirmed. Early treatment the prognosis is good.
Class of myasthenia gravis syndrome (Lambert - Eaton II's syndrome) more common in small cell lung cancer (oat cell carcinoma) patients. Neuromuscular junction is also the shortcomings, but the main lesions in the synaptic membrane. As in a film for presynaptic calcium channel or vesicles release (with activities) autoantibodies, resulting in acetylcholine (Ach) to reduce the release, resulting in myasthenia gravis. Clinical symptoms and MG similar, but more for the general muscle weakness, ocular, masticatory muscles, and other less involvement. Cholinesterase drug reaction as the MG-sensitive. AchR and serum antibody negative. EMG for re-inspection frequency to stimulate use high-frequency stimulation (15 Hz or more) when the muscle action potential volatility increased, the characteristics of the disease-oriented performance. Oral GuHCl can promote acetylcholine secretion, can ease the symptoms. If found to be malignant tumor removed. But sometimes tumor removed after the symptoms of myasthenia gravis are not necessarily followed ease. In some cases symptoms of myasthenia gravis in a few years after the cancer occurred. Therefore, the clinical syndrome that type of myasthenia gravis should be closely followed up the early detection of potentially malignant lesions and to be radical.
Treatment includes the following aspects:
Anti-drug therapy generally preferred for cholinesterase drugs.
① anti-cholinesterase drugs, will cholinergic nerve endings release of acetylcholine is not the accumulation of damage. Are commonly used for the bromide that the new Sri Lanka, pyridostigmine, the suppression of Nanjing, oral administration. If the symptoms of myasthenia gravis mainly to chew, the impact of eating, you can take half an hour before meals. If there muscarinic-like reaction can be added to atropine. In addition, the fair plus potassium chloride and ephedrine as a supplementary drug to enhance the effect.
② corticosteroids and immunosuppressive agents. Corticosteroid can inhibit the autoimmune response. High-dose therapy may surprise, gradually reduced to maintain the volume. But at the beginning of 1 or 2 times after a temporary increase myasthenia gravis, the need for tracheotomy and ventilator emergency preparations. 3 to 4 times after symptoms begin easing. Can also be used to maintain long-term low-dose, several months after the symptoms can be alleviated. Other immunosuppressive drugs such as azathioprine, cyclophosphamide, also optional.
Where impact of the neuromuscular junction drug delivery (such as Jiandu, quinidine, propranolol, streptomycin, neomycin, kanamycin, polymyxin, etc.) must be anti.
Surgical treatment of young, short duration, disease progress faster without major complications, to early thymus removed, the better operation of the long-term effect. Thymomas are less effective merger, but the operation should also be removed.
Radiotherapy older, heart and kidney complications rather than surgical treatment can be carried out deep X-ray treatment, X-ray damage thymus, but also achieve a satisfactory effect.
Plasma replacement therapy for patients with severe attack or myasthenia crisis, each taken from the patient plasma 1000 ~ 2000 ml, while the importation of fresh plasma, or the equivalent of plasma, 1 to 2 times per week, can quickly remove the AchR antibodies in the blood, Relieve symptoms. However, this method can only temporarily relieve symptoms and can not be used as conventional therapy.
Crisis should be treated in a timely manner, if a respiratory muscle paralysis, respiratory should first maintain patent and, if necessary, a tracheotomy, the application of artificial respirator, at any time suction to remove respiratory secretions. At the same time the nature of the crisis should be based on a different treatment.
① myasthenia crisis. For the most common crisis, often by the anti-cholinesterase drugs arising from inadequate consumption, may, by intravenous injection Teng-hi-identification. First intravenous injection Teng-hi-2 mg, if the symptoms improve, then the remaining 8 mg injection, quickly alleviate symptoms of myasthenia crisis. Anti-cholinesterase drugs should increase the amount of dimethyl sulfate could be the new Sri Lanka that the 0.5 mg or pyridostigmine from 1 mg intravenous infusion of small pots, each 2 to 3 hours, 1, until after the crisis eased Adjusted dosage, or switch to corticosteroid therapy.
② cholinergic crisis. Because of anti-cholinesterase drug overdose caused. Apart from clinical respiratory muscle paralysis, can still see the muscle bundle fibrillation, sweating, drooling, abdominal pain, diarrhea and other muscarinic-like response. Lung-teng-test for the intravenous injection of 2 mg symptoms of myasthenia gravis, but heavier. At this point should disable all anti-cholinesterase drugs, use of artificial respiration, or to switch to corticosteroid treatment until the crisis eased, for further adjustment of treatment.
③ counter-argue crisis. Since confrontation is not sensitive cholinesterase drugs, anti-cholinesterase drugs after a little of cholinergic crisis and therefore need to disable anti-cholinesterase drugs, used to maintain artificial respiration. May ease the crisis after anti-cholinesterase drug trial, or to switch to corticosteroid therapy.
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