Myasthenia gravis in pregnancy
Introduction
Introduction to pregnancy with myasthenia gravis Myasthenia gravis is an acquired autoimmune disease of neuromuscular transmission disorder. The clinical feature is that part or whole body skeletal muscle is prone to fatigue, usually aggravated after activity and relieved after rest. So far, there has been no significant progress in the treatment of myasthenia gravis. Pregnancy with MG, due to its own and treatment complications, seriously threatens the health and life safety of pregnant women and their babies. basic knowledge Sickness ratio: 0.05% Susceptible population: pregnant women Mode of infection: non-infectious Complications: sudden death
Cause
Pregnancy with myasthenia gravis
(1) Causes of the disease
The etiology and pathogenesis of myasthenia gravis is still not very clear. In the past, it was thought that the pathogenesis of this disease is related to too little acetylcholine or excessive cholinesterase at the neuromuscular junction. It is also believed that thymic changes can cause this disease. After the anti-skeletal muscle autoantibodies were found in the serum of patients with myasthenia gravis, the disease was classified as an autoimmune disease.
It has been confirmed that this disease is closely related to the acetylcholine receptor antibody in the body. The results support the myometrial weakness in the post-synaptic membrane, the increase of serum anti-acetylcholine receptor (AChR) antibody and the post-synaptic membrane. The reduction in the number of effective AChR caused by deposition on the surface is the main mechanism of the disease.
Abnormal thymus is also associated with the occurrence of this disease. 80% of MG patients have abnormal changes in thymus tissue. Thymectomy can improve a considerable number of patients, and thymocytes and skeletal muscle cells are known to have a common antigen. A special reticular cell (muscle-like cell) of thymic medulla is similar to skeletal muscle cells. It also has acetylcholine receptor. Acetylcholine receptor has good immunogenicity. AChR protein extracted from human skeletal muscle can stimulate Lymphocyte transformation and release of macrophage migration inhibitory factor in patients with muscle weakness, pre-excision of thymus in animals receiving AChR protein immunity can not produce experimental muscle weakness, so thymus-based cellular immune response abnormalities also play a role in the pathogenesis of MG .
In addition, MG patients are often associated with other immune diseases, such as thyroid dysfunction, polymyositis, systemic lupus erythematosus, etc., anti-thyroglobulin, anti-nuclear antibodies, rheumatoid factor are also often detected in the serum of MG patients. Wait.
(two) pathogenesis
1. The most characteristic electrophysiological changes of myasthenia gravis are the decrease of the amplitude of the small endplate potential (MEPP) and the gradual decay of the low frequency limit repeated electrical stimulation. MEPP refers to the spontaneous release of ACh from synaptic vesicles at rest. (Quantum release) The potential generated by post-synaptic membrane ion migration, the amplitude of which is related to the amount of ACh contained in each quantum release, the AChR density and sensitivity on the postsynaptic membrane, and therefore myasthenia gravis The amplitude of MEPP is weakened, or the synthesis of ACh in synaptic vesicles is decreased, the content is decreased, or the number of AChR in the postsynaptic membrane is decreased, and the sensitivity is decreased.
2. There is lymphocytic infiltration around the venules of the affected skeletal muscle fibers, which is called lymphatic leakage. In the acute phase, there are macrophage infiltration between the muscle fibers and the neuromuscular junction, scattered necrosis between the muscle fibers, and bones in the advanced disease. Muscle atrophy, intracellular fatty degeneration, thymus abnormalities are mostly tissue hyperplasia, thymus germinal center increases; thymoma may be lymphocytes mainly according to pathological morphology, epithelial cells are predominant or mixed type.
3. Interaction between pregnancy and MG
(1) The effect of pregnancy on MG: Pregnancy can cause great changes in the maternal immune system, but the effect on MG varies from person to person, and there is no consistent result. Plauche reports that about 31% of pregnant women have no condition during pregnancy and postpartum period. Changes, 28% at least some of the disease eased, and about 41% of the disease worsened, the literature reported that the maternal mortality rate is about 4%, the myasthenia gravis is exacerbated in postpartum conditions, often the condition is severely sudden, respiratory failure is common Phenomenon, maternal pregnancy often dying from the symptoms of muscle weakness or treatment complications, increased pregnancy may be related to progesterone increase during pregnancy and its effects on mineralocorticoids, in addition to early pregnancy nausea, vomiting, unable to take oral anti-biliary Alkaline esterase drugs also affect the MG process; physiological stress during pregnancy, uterine growth, diaphragmatic elevation also affects lung respiratory function, so that lung ventilation is insufficient, and the risk is increased when the respiratory muscles are weak.
(2) The effect of MG on pregnancy: patients with myasthenia gravis have abortion after pregnancy, premature delivery, stillbirth and perinatal mortality are significantly increased, the abortion rate is 12.2%, premature birth rate is 13% to 41.3% (the general population is 8.8%~ 24.8%), the perinatal mortality rate can reach 8.2%.
Pregnancy-induced hypertension may be a specific complication of pregnancy related to immunity, and myasthenia gravis is also an autoimmune disease. Therefore, the incidence of pregnancy-induced hypertension in pregnancy with MG is high, and other immune diseases are also common in such patients.
Physiological stress during childbirth also aggravates the condition of myasthenia gravis. The maternal is more prone to fatigue and weakness. Because the uterine smooth muscle is not based on the acetylcholine mechanism, the contractions are often unaffected. The main effect of myasthenia gravis on delivery is the second stage of labor. Because the maternal abdominal muscles and levator ani muscles are weak, the abdominal labor cannot be used to assist the fetal head rotation and the second stage of labor is prolonged, and surgery is often required.
(3) The effect of MG on fetal infants: Anti-AChR antibodies in pregnant women with myasthenia gravis can enter the fetal blood through the placenta, and the affected fetus can have reduced fetal movement; AChR antibody interferes with the function of acetylcholine receptors in neonatal skeletal muscles and makes nerves There is a disorder in the conduction function of the muscle joint. The neonatal myasthenia gravis (NMG) is born after birth, the incidence rate is 12% to 19%. Symptoms often appear within 24 hours after birth, but also appear as late as 3 days. NMG Newborns have weak sucking power, weak muscles, respiratory distress, crying weakness, facial muscle weakness, NMG mostly temporary muscle weakness, most babies return to normal after a few weeks, rarely more than 3 months, in a wide range Before the application of the neonatal intensive care unit, the child mortality rate can reach 11%.
The occurrence of NMG cannot be predicted by the process and severity of my mother's myasthenia gravis. In the maternal MG remission period, NMG can occur in neonates. The mechanism of NMG production is not fully understood, but NMG is generally considered to be due to maternal AChR antibody passive. Sexual transfer to its fetus, high maternal antibody titer, increase the risk of fetal and neonatal, but the titer is not an absolute indicator of neonatal myasthenia gravis (NMG), through the mother plasma exchange method, reduce maternal antibody drops Degree can reduce the risk of myasthenia gravis in neonates.
Prevention
Pregnancy with myasthenia gravis prevention
1. Pay attention to proper rest, do not master the combination of movement and static, rest well, is conducive to the recovery of the body; exercise can enhance physical strength and enhance disease resistance, and the combination of the two can better recover.
2. Continue taking the medicine and take care of it. 3. It is very important to maintain a good attitude, to maintain a good mood, to have an optimistic, open-minded spirit, and to be confident in the fight against disease. Don't be afraid, only in this way can you mobilize your subjective initiative and improve your body's immune function. 4. Appropriate nutrient supply, in today's living conditions, it is advisable to consume high-sugar, high-protein, high-vitamin and low-fat diets. However, the nutrition should be balanced, and the vegetarian diet should be accompanied by vegetables, fruits, meat, egg milk, etc. The intake is determined by the fatness of the person.Complication
Pregnancy with myasthenia gravis Complications
Due to the development of the disease, improper application of drugs, infection, childbirth, surgery and other factors, the dangerous state of respiratory muscle weakness and unable to maintain normal ventilation function is called MG crisis, which is the main cause of death, and the heart muscle can also be affected. sudden death.
Symptom
Pregnancy with myasthenia gravis symptoms common symptoms muscle atrophy limbs weakness paralysis ptosis sagging fatigue muscle weakness crisis smile face diplopia dyspnea cholinergic crisis
Whole body skeletal muscles, including extraocular muscles, facial expression muscles, throat muscles, neck muscles and limb muscles can be affected, but the muscles innervated by the brain (extraocular muscles, expression muscles, throat muscles) are more common, Regardless of the group of muscles involved, the weakness of the affected skeletal muscles always fluctuates, the morning light is heavy, the fatigue is aggravated, the disease often has spontaneous remission and recurrence in the early stage, and the advanced disease has severe dyskinesia, although the symptoms cannot be recovered after rest. Adult patients often start from a group of muscle weakness, gradually affect other muscle groups in 1 to several years, extraocular muscle involvement is the most common first symptom, manifested as ptosis, diplopia, as the disease progresses, gradually appearing articulation Difficulties, eating cough, facial lack of expression, insufficiency, unable to lift, weakness, limb weakness, etc., severely ill patients may suffer from breathing difficulties due to respiratory muscle involvement, for ease of observation and description, can be divided into the following clinical types.
1. Adult myasthenia gravis
(1) simple eye muscle type: manifested as one side or both sides, or left and right alternately appearing ptosis, morning eye cracks are large, in the afternoon or evening when the ptosis is obvious, there may be diplopia, strabismus, late The eyeball is fixed and some patients can evolve into other types.
(2) medullary muscle type: manifested as chewing, difficulty in swallowing, unclear articulation, multi-nasal voice, continuous sound after continuous speech, in addition, closed eyes when the eyelids are closed or the eyes are not tight, drumsticks, Blowing, toothless, facial expression, smile, face, this group of patients can be associated with cervical muscle weakness, severe cases can not eat at all, need nasal feeding, this type of muscle weakness patients can often aggravate symptoms after infection, it is easy to breathe Difficult and life-threatening.
(3) generalized muscle weakness: from simple eye muscle type, medullary muscle type as the first symptom gradually affects the whole body skeletal muscle, can also develop from the first hair to the whole body muscle weakness, this type of disease is expressed as extraocular muscle, bulbar muscle The expression muscles, the neck muscles and the muscles of the limbs are weak. The muscle weakness of the muscles starting from other muscle weakness often progresses rapidly within weeks to months after the first symptoms, and respiratory crisis occurs.
(4) Spinal muscle weakness: only the muscles in the spinal nerve dominating area are weak, showing uplifting, stiff neck, often head sag, difficulty in lifting arms and walking easily, especially when going up and down stairs, most of this type of disease Insidious disease, easily misdiagnosed as limb-type muscular dystrophy or functional disease, more common in adolescents, some can develop into systemic muscle weakness, and most patients have a good prognosis.
(5) Muscular atrophy: all types of muscle weakness can be associated with muscle atrophy, but rare, muscle atrophy of the diaphragm, perioral, neck, limb and calf muscles are more common.
2. Children with myasthenia gravis Our children with myasthenia gravis account for 15% to 25% of the total. Except for a few cases, the vast majority of cases only show extraocular muscle paralysis, such as ptosis, diplopia, etc., upper respiratory tract infection, fever Such as predisposing factors, about 1/4 of the children can spontaneously relieve, but often relapse.
3. Neonatal myasthenia gravis is difficult to feed, low crying, weak sucking, reduced movement, etc., often anti-AchR antibodies in the serum of sick mothers are induced by placenta in the fetus, with a family history of congenital MG It is called familial MG and is associated with AchR deficiency.
Examine
Pregnancy with myasthenia gravis
65% to 85% of patients with myasthenia gravis have anti-AchR antibody positive in serum, and some can detect pre-synaptic membrane receptor (PsmR) antibody. MuSK antibody can be detected in antibody-negative patients, and anti-nuclear can be detected in serum of some patients. Antibodies, anti-thyroid antibodies, thymoma patients can be measured Titin, Ryanodine antibodies, combined with hyperthyroidism can have T3, T4 increased.
1. The neostigmine test was given intramuscularly with 0.5 to 1 mg of neostigmine methyl sulfate. After 20 minutes, the symptoms were significantly reduced.
2. The nerve repetition frequency stimulation test is typically changed to low frequency (2 ~ 3Hz) and high frequency (10Hz or more) to repeatedly stimulate the ulnar nerve, facial nerve and phrenic nerve, and the amplitude of the muscle action potential may decrease, and the decreasing amplitude is more than 10%.
3. X-ray chest X-ray, CT and MRI can be found in thymic hypertrophy or thymoma.
Diagnosis
Diagnosis and differentiation of pregnancy complicated with myasthenia gravis
According to the fatigue of the affected muscle group, the condition fluctuates, the situation is light and heavy, and the nervous system examination has no abnormal findings. The general diagnosis is not difficult. The suspicious patient can be fatigue tested, that is, the patient can repeat or continue the affected skeletal muscle. Contraction (such as repeated eye closure, blinking, chewing, lifting arms, fists, two arms flat, etc.) dozens of times can appear temporary examination of muscle spasm, if still can not be diagnosed can be combined with EMG repeat electrical stimulation and Single fiber electromyography test to confirm the diagnosis.
Simple ocular muscle type MG should be differentiated from ocular muscular dystrophy, congenital ptosis, Honer syndrome and eyelid. The medullary muscle weakness should be associated with Guillain-Barré syndrome, progressive bulbar palsy. The difference, if the onset of MG after the age of 50, if the clinical manifestations of dry mouth, less tears, morning heavy night light, or after the activity, the symptoms are reduced, the affected limbs are heavy, regardless of whether accompanied by the lungs or other parts Tumors should consider the possibility of Lambert-Eaton syndrome and must be further examined for identification.
