What is Neonatal Myasthenia Gravis?
Myasthenia gravis (MG) is a health condition that weakens the body’s voluntary muscles, which are the muscles you control, such as those in the eyes, mouth, throat, arms, and legs. Although this condition most commonly affects adults, it may also occur in children. A specific type known as Neonatal MG is temporary and can affect babies born to mothers who have MG. This happens when the mother’s antibodies cross over to the baby, but the symptoms usually go away after a few weeks or months as the body naturally replaces these antibodies. Importantly, this does not mean the baby has a higher risk of having MG later in life.
This condition is different from congenital MG, an extremely rare type of MG, that starts from birth due to rare genetic disorders, causing lifelong symptoms. Neonatal MG is also different from juvenile MG, which is the most common type of MG in children that behaves the same way as adult MG. However, juvenile MG does not occur in new-born babies and usually begins late infancy.
What Causes Neonatal Myasthenia Gravis?
This condition is a type of autoimmune disorder that typically affects newborn babies born to mothers who have a similar autoimmune disorder known as MG. Autoimmune disorders are when your body’s immune system attacks your own cells. This happens in neonatal MG as a result of certain antibodies moving from the mother to the baby while still in the womb. These are antibodies that target certain materials at neuromuscular junctions, which are the places where the nerves meet the muscles.
The most frequently targeted material in this condition is called nicotinic acetylcholine receptor (AChR). Another key material that the antibodies can affect is known as muscle-specific receptor tyrosine kinase (MuSKR). Both of these materials are within the neuromuscular junction and help the muscles to function properly. But when they are attacked by these antibodies, it leads to problems in the muscle, manifesting as neonatal MG.
Risk Factors and Frequency for Neonatal Myasthenia Gravis
Myasthenia Gravis (MG) is a condition that affects a varying number of people. The condition affects between 1.7 and 30 people per million each year with around 77.7 people per million having the condition at any given time. Research also suggests that juvenile MG happens to between 1 and 5 people per million every year.
- Around 10 to 15% of all people with MG are young people, according to a study in Virginia.
- Asian populations have a higher rate of juvenile MG compared to white populations, accounting for half of all cases of MG.
- Data for newborn MG is scanty due to difficulty in detection and likely underreporting.
- Neonatal MG is generally considered a rare condition, but affects about 10 to 15% of newborns born to mothers with MG.
- There’s a higher risk of neonatal MG in siblings born in later pregnancies.
- No preference for race or gender has been reported.
- No direct link has been found between the severity of a mother’s condition and how it affects her newborn.
Signs and Symptoms of Neonatal Myasthenia Gravis
Newborn babies begin to show symptoms 3 to 72 hours after birth. These symptoms can include poor sucking reflexes, difficulty breathing, generalized muscle weakness, a feeble cry, and weakness in facial muscles. In severe cases, these babies may require methods like tube feeding for swallowing difficulties or ventilator support for help with breathing. Ptosis (drooping of the eyelid) and ophthalmoplegia (weakness or loss of control in the eye muscles) are less common in newborns with MG. A severe and untypical presentation of this condition in newborns can result in multiple joint contractures, known as arthrogryposis multiplex congenita.
However, most infants fully recover before they reach four months. Moreover, over 90% recover before the age of two months. This improvement aligns with the disappearance of the mother’s antibodies from their system.
It’s worth noting that pure ocular MG, which only affects the eye muscles, doesn’t occur in newborns with MG, and is more common in children than adults. It is more often seen in children who haven’t gone through puberty. In contrast, generalized MG, which affects muscles throughout the body, is more common in teenagers who’ve gone through puberty.
During a physical exam, newborns with MG can exhibit a frog-leg position, suggestive of generalized muscle weakness. Other indications would include an open mouth and apparent ptosis. Flabby muscles, noticeable head lags are pretty standard. Though deep tendon reflexes are generally intact, other simple reflexes might be challenging to prompt or might be absent.
Generally, the following symptoms can be present:
- Poor sucking reflexes
- Difficulty breathing
- Generalized muscle weakness
- Weak cry
- Facial diplegia (facial muscle weakness)
- Frog-leg position
- Apparent ptosis (drooping of the eyelid)
- Flabby muscles
- Prominent head lag
Testing for Neonatal Myasthenia Gravis
Neonatal Myasthenia Gravis (MG), a muscle weakness disease like the adult form, is usually diagnosed through examining the baby’s symptoms and medical history. If the baby’s mother is known to have autoimmune MG, that makes it even more likely. However, in rare cases where the baby’s symptoms aren’t typical, or the mother shows no signs of MG, it’s often helpful to conduct some tests.
The first test is usually looking for antibodies in the blood that are characteristic of the MG condition. Antibody testing is pretty simple and not too expensive. They specifically look for antibodies against the acetylcholine receptor – proteins that help send signals from nerves to muscles. If these antibodies are present and the infant’s symptoms match, this test could confirm the MG diagnosis, and further tests might only be required if the symptoms are not typical.
Intramuscular neostigmine, a type of medicine, could also be used to assess the response if the infant has symptoms like drooping eyelids (ptosis), difficulty swallowing (dysphagia), and lagging head control. If the first medicine dose doesn’t show clear results, another dose might be given after 4 hours. It is important to note that this test is best performed in a closely watched medical environment, as there can be rare side effects like slow heart rate or even stoppage, particularly when higher dosages are used. Side effects can also include stomach cramps, sudden diarrhea, irregular heart rhythm, and excess lung secretions like phlegm. Using this medicine through the vein (intravenous) is not advised for children under the age of 2 due to the risk of heart rhythm problems.
Also, an Electromyogram/Nerve Conduction Study (EMG/NCS) might be used. This test measures the electrical activity of the muscles. In some situations, a more sensitive version of this test, called a single-fiber EMG, might be done. However, it’s not generally suitable or practical for children, as it can’t be done under sedation or anesthesia. A variant of this test, known as stimulated single-fiber electromyography, is usually more helpful in diagnosing MG in children and teenagers. Although useful, this test is not generally performed on neonates (newborn babies) in most medical facilities.
Treatment Options for Neonatal Myasthenia Gravis
When it comes to dealing with myasthenia gravis (MG) in newborns, the approach differs from treatment in older children. Medical treatments usually involve drugs to increase the availability of acetylcholine neurotransmitters, which help pass signals in the nerves. Other treatments also include immunomodulatory and immunosuppressive drugs. Immunomodulatory drugs help regulate the immune system and immunosuppressive drugs help reduce the body’s immune response.
However, it’s important to note that these treatments are powerful and typically carry more side effects, or health issues caused by medicines. They are also usually more invasive, meaning they require procedures that enter the body.
Similar to adults with MG, children and their families should be educated about certain medications that might make MG worse. For newborns, particularly important is the use of a type of drug called aminoglycoside, as it might intensify MG symptoms. Thankfully, treatment for neonatal MG often lasts only a few days to a few months.
If a baby has mild symptoms, small and frequent feedings are necessary. Care should be taken to watch for symptoms such as trouble swallowing (dysphagia) or food or drink entering the airway (aspiration). In more severe cases, other treatments, such as the drug neostigmine or tube feeding, might be necessary. Giving the baby neostigmine about 30 minutes before feeding can help with difficulty in swallowing. Alternatively, pyridostigmine, a similar drug with a slightly longer effect, can be used.
Luckily, treatments such as plasmapheresis (a process to filter the blood), intravenous (IV) immunoglobulins (proteins that help the immune system), and corticosteroids (medications to reduce inflammation) are all useful in treating MG in older children and adults. However, they’re rarely needed for newborns, and are used only in severe cases for the quick removal of circulating antibodies (substances that fight off diseases).
It’s important to monitor newborns who were exposed to corticosteroids during their mothers’ pregnancies for adrenal inefficiencies. Adrenal glands produce hormones, and if they don’t work well, the newborn may experience health problems.
Lastly, a thymectomy, which is the removal of the thymus gland, is not necessary for newborns with MG. However, previous studies suggest that it might be beneficial for older children with MG.
What else can Neonatal Myasthenia Gravis be?
The following conditions can often be mistaken for neonatal Myasthenia Gravis (MG):
- Spinal muscular atrophy
- Congenital MG
- Specific types of congenital myopathies like central core disease, nemaline myopathy, and myotubular myopathy
- Congenital muscular dystrophies
- Limb-girdle or facioscapulohumeral muscular dystrophy
- Infantile myotonic dystrophy
- Mitochondrial myopathy
- Brainstem anomaly
- Mobius syndrome
- Congenital fibrosis of extraocular muscles
- Infantile botulism
- Seropositive and seronegative forms of autoimmune MG
What to expect with Neonatal Myasthenia Gravis
The outcome for the standard type of newborn Myasthenia Gravis (MG), a rare condition that may cause muscle weakness, is generally very good, as long as correct breathing and dietary support is provided. However, more severe and uncommon forms of this disease can lead to long-term complications in babies born with MG.
Most patients tend to naturally recover after a few weeks to months. This is known as spontaneous remission, essentially meaning the disease goes away on its own after some time.
Possible Complications When Diagnosed with Neonatal Myasthenia Gravis
Generally, neonatal Myasthenia Gravis (MG) has been seen as a pretty harmless disease in new-born babies, with no long-lasting effects if treated correctly. Despite that, some more serious types of this condition, which can have long-term health implications, have been documented, e.g., the fetal acetylcholine receptor inactivation syndrome. For this reason, when a child presents unexplained muscle weakness along with other specific symptoms related to these types of neonatal MG, these variants should be included as possible diagnoses.
Common Symptoms of Neonatal MG to Consider:
- Unexplained muscle weakness in a child
- Specific symptoms related to severe variants of neonatal MG
- Signs of fetal acetylcholine receptor inactivation syndrome
Preventing Neonatal Myasthenia Gravis
Myasthenia Gravis (MG) is a condition that can appear in children, either from birth (neonatal MG) or during the teenage years (juvenile MG). It’s important to note that if a mother has a newborn with transient MG, her future children are more likely to also have transient MG. MG in infants and teenagers can vary a lot in how it shows up. However, things like the severity and length of the mother’s MG don’t give any clues about whether or not her baby will have the condition. This is why all births should take place at a special kind of hospital called a tertiary birth center.
The symptoms of MG can range from mild eye-related signs, such as tired, drooping eyelids, to more serious conditions like myasthenic crises that affect the muscles responsible for breathing and require a breathing machine for support. Although diagnosing MG can be tricky, if there’s a reason to think a patient might have MG, especially if they show signs of fatigue, doctors should conduct certain tests to see if the suspect is correct.
Treatment for MG should be based on the type and severity of the disease, and it’s important to remember that the same treatment can affect different patients in different ways. One tricky thing is that children with MG can’t tolerate certain muscle-relaxing drugs used in surgeries, like succinylcholine and pancuronium, because these could leave them paralyzed for weeks after just one dose. This is why if an MG patient needs surgery, the doctor who puts the patient to sleep during surgery (an anesthesiologist) needs to review their medical background carefully. These patients should only be given anesthesia by doctors who have a lot of experience with this.
Additionally, some antibiotics can worsen MG and should be avoided. These include aminoglycosides, beta-blocking agents, procainamide, chloroquine, and fluoroquinolones. Lastly, if a child with MG has symptoms involving the eyes, they should see a pediatric ophthalmologist regularly. This type of eye doctor can keep an eye out for any eye-related complications linked to juvenile MG.
