Introduction:
Myasthenia gravis is a chronic neuromuscular autoimmune disease in which autoantibodies are formed against the cholinergic receptors in the neuromuscular junction. Myasthenia gravis is of Greek and Latin origin, which means ‘grave, serious, muscle weakness.’ It is more common in females than males. The younger females have abnormalities in the thymus, like thymus hyperplasia. It causes fatigue in the muscles that are under voluntary control. In addition, it weakens the skeletal muscles. The symptoms are intermittent, not, which is worse for some time and improve after some rest. The powers responsible for breathing and some body parts are involved in moving, like the arms and legs. Eighty-five percent of the patients with myasthenia gravis have autoantibodies directed against nicotinic receptors of the muscle. As a result, people experience symptoms such as drooping of the eye muscles, blurred or double vision, impaired speech (dysarthria), difficulty swallowing, a change in facial expression, and weakness in the hands, arms, legs, neck, and fingers.
What Are the Causes of Myasthenia Gravis?
It is due to the problem of transmitting impulses from the nerves to the muscles. It happens when communication is interrupted between the muscle and the nerves. The neurons use neurotransmitters like acetylcholine to communicate information in the brain. When the impulses travel down a motor nerve, the neurotransmitters are released from the nerve endings that bind to the acetylcholine receptors in the muscle. This activates the muscle for muscle contraction. In myasthenia gravis, autoimmune antibodies destroy the receptors for acetylcholine and prevent muscle contraction. Antibodies to other proteins, such as muscle-specific kinase protein, also impair the transmission at the neuromuscular junction.
How Does Thymus Gland Cause Myasthenia Gravis?
The thymus gland plays a significant role in developing the immune system because it produces T-lymphocytes that protect the body against infections. After puberty, the thymus gland becomes small and is replaced by fat. People with this condition have clusters of immune cells in the thymus gland that develop into thymus gland tumors. They can be cancerous in the future. In myasthenia gravis, the thymus gland may give incorrect information to the growing immune cells, producing autoimmune antibodies (acetylcholine receptor antibodies) that act against their acetylcholine receptors in the muscle.
What Is Neonatal Transient Myasthenia Gravis?
Neonatal myasthenia gravis affects neonates born to mothers with autoimmune myasthenia gravis. The transmission occurs through the transplacental passage of antibodies directed against the neuromuscular junction. The antibodies are directed against the antigens like the nicotinic acetylcholine receptor (AChr) and specific receptor tyrosine kinase (MuSKR). In this disorder, there is the transplacental transmission of maternal antibodies. The circulating maternal antibodies are transmitted to the baby through the placenta, which destroys the acetylcholine receptors in the developing fetus. Seventy-five percent of the mothers have acetylcholine receptor antibodies. These antibodies degrade the nicotinic acetylcholine receptor that blocks the acetylcholine binding to the muscles. It is not very clear why the antibodies are transferred to the fetus. It is believed that it is due to the specific autoantibody characteristics that differ between individuals. Infants with this condition may be born to mothers who are not displaying only a few or no symptoms of myasthenia gravis. Women who surgically removed their thymus glands also have significantly less chance of transmitting the disease to the baby.
What Are the Signs and Symptoms of Neonatal Transient Myasthenia Gravis?
Most infants exhibit symptoms 3 to 72 hours after birth. The signs and symptoms include:
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They lack facial expressions (facial diplegia).
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Breathing.
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Cry weakly.
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Poor sucking.
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Respiratory distress.
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Generalized hypotonia with a weak cry.
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Swallowing difficulties.
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Ptosis (the upper eyelid droops over the eye) may be unilateral, bilateral, or asymmetric.
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Multiple joint fractures (arthrogryposis multiplex congenital).
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Frog leg position suggestive of diffuse hypotonia.
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Open mouth.
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Flabby muscles and prominent head lags.
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Deep tendon reflexes are intact.
What Is Arthrogryposis Multiplex Congenita?
Arthrogryposis multiplex congenita is congenital contracture tightening the muscles, tendons, skin, and nearby tissues. The situation occurs alone or is associated with multiple developmental defects and is a part of many syndromes. The disease is characterized by fluctuating pathological painless muscle weakness with remission and exacerbations involving one or several skeletal muscles. In addition, the continuous flow of acetylcholine receptor antibodies during pregnancy can lead to severe fetal movement, leading to arthrogryposis multiplex congenita.
What Are the Diagnosis Test Done for the Neonates?
The infants often recover soon after the condition like, within a few weeks or months, because the maternal antibodies disappear independently. Most neonates completely recover before four months, and more than 90 percent before two months. Neonatal myasthenia gravis is the ultimate clinical diagnosis. A strong history with a mother with known autoimmune myasthenia gravis and a physical examination is sufficient to make the diagnosis. However, in rare cases, the clinical presentation is not classic, and the mother is asymptomatic for myasthenia gravis. Getting positive results on one or more standard diagnostic tests.
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Electromyogram or Nerve Conduction Study (EMG or NCS) - The test measures the electrical activity of muscles. A single-fiber EMG test is done, which is a more sensitive test. Traditional single-fiber electromyography is impractical for children, as it cannot be performed under sedation or general anesthesia. A variant of single-fiber electromyography, stimulated single-fiber electromyography, is beneficial in children and adolescents.
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Intramuscular Neostigmine Test - Intramuscular neostigmine (acetylcholinesterase inhibitors) can be administered to evaluate the response of ptosis, dysphagia, and head lag. Suppose there are negative results, a second dose is given after 4 hours. It is best if this testing is performed in a monitored setting where advanced cardiorespiratory support is available in case of any rare heart signs during the testing, primarily when higher doses are used. The adverse effects are abdominal cramps, sudden diarrhea, and cardiac arrhythmia (abnormality in heart rhythm). Therefore, intravenous neostigmine is contraindicated in babies before two years of age due to the risk of cardiac arrhythmia (abnormal heartbeats).
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Antibody Testing for Anti-acetylcholine Receptor - Antibody testing is done in myasthenia gravis. Positive antibody titers confirm the diagnosis, and further testing is needed if the clinical presentation is atypical. Antibody testing only involves serum testing and is relatively inexpensive, especially for acetylcholine receptor antibodies.
What Is the Treatment for Neonatal Transient Myasthenia Gravis?
Neonatal myasthenia gravis is treated by the following methods:
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The treatment for neonatal myasthenia gravis involves drug treatment to increase the availability of acetylcholine neurotransmitters.
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In addition, immunomodulation and immunosuppression are more robust approaches to medical therapy.
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However, immunomodulation and immunosuppression are typically more invasive and have significant side effects. Immunosuppression improves the clinical situation because the antibodies released from the immune cells are decreased.
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The pediatric patients are counseled regarding medications that may exacerbate myasthenia gravis. If mildly symptomatic, small and frequent feeding is necessary with proper surveillance for aspiration and dysphagia (difficulty in swallowing).
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In severe cases, oral or intramuscular neostigmine is required with gavage feeding (a small tube is placed through the mouth or nose).
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Administration of Neostigmine 30 minutes before feeding can help with dysphagia. Pyridostigmine (a slightly longer-acting agent) can be used alternatively.
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Fortunately, plasmapheresis (a method of removing blood plasma from the body separating into plasma and cells), intravenous immunoglobulins, and corticosteroids are all efficient in treating myasthenia gravis in older children and adults but rarely are needed and only necessary for managing severely affected neonates for rapid removal of circulating antibodies.
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Infants born to mothers who have taken corticosteroids during pregnancy should be monitored for adrenal inefficiencies during the newborn period.
Conclusion:
The results of the classical form of neonatal myasthenia gravis are excellent, provided the respiratory and nutritional support is good. Long-term complications in neonates with myasthenia gravis are found in severe and rare disease variants. However, most patients experience spontaneous remission after a period of weeks to months.
