myasthenia gravis-like syndrome
Introduction
Introduction to myasthenia gravis syndrome Various factors lead to dysfunction of the acetylcholine receptor (AchR) function in the synaptic membrane of the neuromuscular junction (NMJ), which can be similar to myasthenia gravis (MG)-like clinical manifestations. After skeletal muscle activity, muscle weakness is aggravated, after rest Alleviated, this group of diseases is collectively referred to as myasthenia gravis syndrome. basic knowledge The proportion of illness: 0.003% Susceptible people: no specific population Mode of infection: non-infectious Complications: Urinary tract infection
Cause
Causes of myasthenia gravis syndrome
Genetic factors (20%):
Neonatal myasthenia gravis MG mother serum AchR-Ab enters the fetal blood circulation through the blood-placental barrier, NMJ postsynaptic membrane AchR function disorder, leading to neonatal muscle weakness. Genetic and environmental factors of congenital myasthenia gravis play a role in the pathogenesis of this disease.
Drugs (25%):
Drug-induced myasthenia gravis drugs and toxins cause disorders in the AchR function of the NMJ postsynaptic membrane, and similar clinical manifestations of MG appear. After long-term application of penicillamine in large doses, many patients have clinical manifestations of myasthenia gravis.
Congenital endplate Ach esterase deficiency (20%):
NMJ can release Ach with a small amount of unit release, and the amount of AchR is normal or reduced.
Slow channel syndrome (15%):
It is a rare autosomal dominant disease.
Pathogenesis
1. Neonatal myasthenia gravis NMJ post-synaptic membrane AchR function disorder, leading to neonatal muscle weakness, although AchR-Ab positive mother will pass this antibody to the fetus during pregnancy, not all fetuses are affected, neonatal muscle weakness Compared with the severity of maternal disease, the level of maternal serum AchR-Ab is not related, and the newborn may also have muscle weakness when the mother is in remission.
2. Congenital myasthenia gravis syndrome has been established since the MG autoimmune theory in the 1970s and 1980s. After determining the morphological and physiological characteristics of the disease, the disease is differentiated from the familial infantile myasthenia gravis. According to electrophysiology and super Microstructural features, six clear and rare congenital myasthenia gravis syndromes have been elucidated to date, and some describe many other types of features. All types of congenital muscle weakness are unique to the synapse itself, presynaptic or postsynaptic. Defects are characterized by presynaptic Defect Ach resynthesis or packaging disorders, synaptic vesicle deficiencies, synaptic endplate Ach esterase reduction, post-synaptic AchR channel kinetic abnormalities with or without AchR deficiency, familial The cause of infantile myasthenia gravis may be Ach synthesis and presynaptic membrane dysfunction in the packaging site. No abnormal AchR was observed by light microscopy and electron microscopy. Electrophysiological findings were similar to experimental hemicholine poisoning. However, Engel systematically defined and classified this group of diseases through more than 100 patients with congenital myasthenia gravis, pointing out that about 3/4 of the cases were post-synaptic defects, 13% were synaptic defects, and 8% were synapses. Caused by defects.
3. In vitro electrophysiological studies of congenital endplate Ach esterase deficiency show that endplate potential and microendplate potential are prolonged. Endplate potential can produce repetitive muscle action potential during single electrical stimulation, and amplitude is reduced during repeated stimulation. Moderately strong stimulation The performance of the first facilitation and post-depletion; the amplitude and amplitude of the motor unit potential changes during random exercise, the proportion of multi-phase action potential increases, pathological changes: electron microscopy studies show that motor nerve endings become smaller, may be compensatory features of cholinesterase deficiency , the number of AchR is normal or reduced.
4. Slow channel syndrome This disease is the extension of AchR calcium channel opening time, leading to prolonged endplate potential, increased calcium ion influx of synaptic folds, and overload of calcium ions in wrinkles can produce influx currents in serosal serosal membrane And the myofiber area showed myopathy characteristics, post-synaptic defects with or without AchR deficiency, light microscopy showed that some cases of I-type fiber predominance, fiber atrophy, tubule agglomeration, NMJ area with small vacuoles, fiber size and Bifurcation, endometrial and fascia connective tissue increased, severely affected muscle AchR decreased, cholinesterase activity was normal, no immune complexes were seen, electron microscopy showed lesions involving synaptic folds and muscle sarcolemma, adjacent processes Degenerative changes in the palpable fold area, nerve endings shrink, and synaptic vesicle density increases.
5. The lack of AchR in the congenital acetylcholine receptor may reflect a decrease in synthesis, AchR insertion into cell membrane defects or accelerated AchR degradation.
6. Drug-induced myasthenia gravis
(1) In recent years, it has been found that high-dose penicillamine has a positive effect on rheumatoid arthritis (RA), but after long-term application of penicillamine in large doses, many patients have clinical manifestations of myasthenia gravis, consistent with NMJ postsynaptic membrane AchR. Characteristics of the disease, although the long-term use of penicillamine for a large number of cases, it rarely causes MG performance. So far, only 3 cases have been reported internationally. The etiology and pathogenesis of this disease are unclear. It may be penicillamine itself to NMJ. Post-synaptic membrane AchR-specific selective destruction or inhibition, some authors believe that penicillamine makes MG in patients with RA. It is likely that RA is originally an autoimmune disease. Penicillamine starts on the basis of the patient's original immune dysfunction. AchR abnormal immune response caused by post-synaptic membrane, Vincent et al detected AchR-Ab in the serum of patients with this disease, considered to be acquired autoimmune myasthenia gravis, not penicillamine on NMJ post-synaptic membrane AchR directly Destructive effect.
(2) More than 30 drugs (excluding anesthetics) in clinical applications today can interfere with neuromuscular transmission in normal people, the most important of which are aminoglycoside antibiotics. It has been reported that 18 antibiotics are related to muscle weakness. Especially neomycin, kanasig, colistin, streptomycin, polymyxin B and tetracycline; and gentamicin There are fewer (gentamicin) drugs that have been shown to interfere with transmitter release by interfering with calcium flux in nerve endings. The use of these drugs in patients with myasthenia gravis can have serious consequences and can be applied with respirator support if necessary.
Certain immunosuppressive drugs, such as adrenocorticotropic hormone (ACTH), prednisone, and azathioprine, can depolarize through nerve endings or reduce Ach release, resulting in a temporary increase in muscle weakness.
Other drugs, such as anticholinesterase drugs, especially insecticides and nerve gases, can cause sputum, which is blocked by cholinesterase, which hinders Ach degradation. The endplates are always depolarized, and the nerves are Stimulation does not result from a response.
Many of the neurotoxins present in the natural environment are known to act on neuromuscular junctions, causing muscle spasms like MG distribution. Natural neurotoxin-induced poisoning poses a serious threat to public health in many parts of the world, especially in the tropics.
Common animal toxins are: 1 botulinum: binds to cholinergic motor nerve endings, prevents the release of Ach minimal release units; 2 black widow spider venom: releases Ach in large quantities , causing muscle contraction, followed by Ach depletion leading to muscle paralysis, snake and venom venom is also a well-known animal toxin; 3 chloramphenicol (d-tubocurarine), succinylcholine (suxamethonium) and Decamethonium: can be combined with AchR, curare is extracted from plants; 4 organophosphate: irreversible binding with Ach esterase, malathion and sulfur Parathion also inhibits Ach esterase; 5 ciguatera and related toxins: fish from ingesting certain dinoflagellates; 6 clostridium, in addition to organophosphates Role, all other toxins are temporary.
(3) Myasthenia gravis caused by interferon-: treatment with interferon- (IFN-) may cause autoimmune myasthenia gravis.
Prevention
Prevention of myasthenia gravis syndrome
There are no better preventive measures. Those with a family history of genetics should undergo genetic counseling, prenatal diagnosis and selective abortion. Different clinical types should pay attention to the fall of the bed caused by sputum, asphyxia, lung or urinary tract infection, such as drug Or caused by toxins, should still actively treat the primary disease, stop the relevant drugs.
Complication
Complications of myasthenia gravis syndrome Complications, urinary tract infections
may cause a bed crash, suffocation, lung or urinary tract infections, such as due to drugs or toxins, there are still primary manifestations.
Symptom
Symptoms of myasthenia gravis syndrome Common symptoms Myasthenia gravis crisis Muscle muscle weakness Facial muscle weakness Muscle tension Reduce fatigue Reflex crisis Difficulty cholinergic crisis
1. Neonatal myasthenia gravis
(1) It is estimated that only 12% to 20% of the live babies born to MG mothers have decreased muscle tone, small crying, weak suction and other muscle weakness; the remaining infant blood AchR-Ab can be increased, but not Express muscle weakness.
(2) About 78% of newborn MGs have muscle weakness and electrophysiological manifestations within a few hours to one day, and blood AchR-Ab can be increased. Since the sick child itself does not produce AchR-Ab, the muscle weakness gradually decreases until it disappears. After 18 days and rarely more than 2 months, the AchR-Ab in the blood gradually decreased and no longer relapsed.
(3) The phenomenon of intrauterine fetal movement reduction during MG mother's pregnancy is rare. If the fetal muscle weakness is severe, the fetus is inactive in the uterus for a long time, and the joint is bent after birth. This condition may also occur after the mother produces it.
2. Congenital muscle weakness syndrome
(1) The child has less fetal movement before birth, and occurs soon after birth or birth. The neonatal period shows intermittent or progressive aggravation of ptosis, medullary muscle weakness, facial muscle weakness, often affecting feeding, and weak sucking. The crying is weak, and the respiratory muscle weakness occurs when crying. It is an important clue to the congenital muscle weakness syndrome. There is no obvious progress in the course of the disease. The generalized muscle weakness is either with or without, generally not serious. It can start at 6 to 7 years old. Better, but not completely relieved.
(2) Most of the onset in infancy or childhood, continuous exercise can produce muscle weakness, fluctuating eye muscle paralysis and abnormal fatigue, etc. In some cases, until 10 years old or 20 years old, there is obvious muscle weakness and fatigue. Check the normal sputum reflex, no muscle atrophy, patients are prone to respiratory infections, often due to fever, excitement and vomiting, causing potentially fatal muscle weakness, respiratory muscle weakness can lead to decreased ventilation, dyspnea and hypoxia Sexual brain injury, with age, the crisis can be gradually reduced.
3. Congenital endplate Ach esterase deficiency This disease occurs in males. All skeletal muscle weakness and abnormal fatigue are present at birth, muscle biopsy is normal, and Ach esterase is absent by light and electron microscopy.
4. In slow-channel syndrome infants, children or adults with onset, progressive aggravation, may have several years of intermittent period, typical muscle weakness can affect the neck, shoulder and finger extensor muscles, may have mild to moderate ptosis, Excessive extraocular muscle activity, mandibular muscles, facial muscles, upper limb muscles, respiratory muscles and trunk muscles, and other degrees of muscle weakness, the lower limbs are relatively spared, the affected muscles can be seen muscle atrophy and fatigue, severely affected limbs tendon reflexes.
5. Congenital acetylcholine receptor deficiency often begins in infancy, clinical symptoms and electrophysiological characteristics are similar to myasthenia gravis. Muscle biopsy shows a decrease in AchR number, normal cholinesterase, negative serum AchR-Ab, and endplate area. See immune complexes.
6. Drug-induced myasthenia gravis
(1) Drugs and toxins cause acute onset of myasthenia gravis syndrome, symptoms lasting for several hours to several days, patients can completely recover without respiratory failure, eye muscles, facial muscles, bulbar muscles and limb muscles can be affected, medication History, history of toxic exposure and history of poisoning can provide an important basis for clinical diagnosis.
(2) Chronic graft ver sus host disease may occur in long-term (2 to 3 years) survivors after allogeneic bone marrow transplantation. Typical myasthenia gravis is a local manifestation.
(3) Myasthenia gravis caused by interferon-: Batocchi et al (1995) reported autoimmune myasthenia gravis during treatment of interferon- (IFN-) in 2 patients with malignant tumors; Piccolo et al. (1996) reported One patient with chronic hepatitis C developed MG after treatment with IFN-; Mase et al (1996) reported that a patient with hepatitis C who was susceptible to MG genetic quality developed severe MG during IFN-2a treatment.
Examine
Examination of myasthenia gravis syndrome
1. Neonatal myasthenia gravis
AchR-Ab can be increased from a few hours to one day after birth. Since the diseased child does not produce AchR-Ab itself, the blood AchR-Ab gradually decreases, lasting for 18 days on average, rarely exceeding 2 months.
2. Congenital muscle weakness syndrome
(1) Tengxilong test: usually negative, but some types of hereditary muscle weakness can be positive.
(2) AchR-Ab measurement: AchR-Ab is negative in patients with hereditary myasthenia. For example, an increase in serum antibody can rule out the diagnosis of congenital myasthenia gravis syndrome.
3. Congenital endplate Ach esterase deficiency Ach esterase deficiency.
4. The slow channel syndrome serum AchR-Ab is absent.
5. Congenital acetylcholine receptor deficiency cholinesterase normal; serum AchR-Ab negative.
6. Drug-induced myasthenia susceptibility drug and toxin detection.
7. Neonatal myasthenia gravis develops muscle weakness and electrophysiological manifestations within hours to 1 day. Since the sick child does not produce AchR-Ab itself, the muscle weakness gradually decreases until it disappears.
8. Electromyography of congenital myasthenia gravis syndrome, EMG examination of intercostal muscle showed that the amplitude of the endplate potential of the resting state was normal, and the amplitude of the microplate endplate decreased after 10 min of stimulation of the nerve at 10 Hz, which could lead to the endplate potential and muscle complex action. The potential amplitude is reduced, and the low-frequency (<10Hz) repeated electrical stimulation shows that the amplitude is progressively decreasing. After the super-stimulation, the facilitation period becomes inconspicuous, and the depletion period gradually increases. The needle-electrode EMG shows the motion unit waveform and the amplitude variable, and the single-fiber muscle. The electrogram shows twitch broadening and blocking.
9. Congenital endplate Ach esterase deficiency muscle biopsy is normal, light and electron microscopic cytochemical examination found that Ach esterase is absent.
10. The electromyogram of the slow channel syndrome shows that the endplate potential and the microendplate potential are prolonged by about 3 times, and the anticholinergic enzyme is used to prolong more, but not all muscle microendplate potential amplitudes are reduced, and the endplate potential is released. The unit volume is normal, 2Hz repeated electrical stimulation, muscle weakness, muscle complex action potential amplitude reduction, in the voluntary contraction reaction, the motion unit potential waveform or amplitude is variable.
11. The electrophysiological characteristics of congenital acetylcholine receptors are similar to those of myasthenia gravis; muscle biopsy shows a decrease in the number of AchR.
12. Drug-induced myasthenia gravis electrophysiological characteristics are similar to myasthenia gravis.
Diagnosis
Diagnosis and differentiation of myasthenia gravis syndrome
Diagnosis can be made based on the clinical manifestations of different clinical types and related laboratories and other auxiliary examinations. See clinical manifestations and related laboratory tests, and auxiliary examinations.
Mainly differentiated from myasthenia gravis (MG), Lambert-Eaton syndrome, and other types of myopathy.
