Juvenile myasthenia gravis

The symptoms of myasthenia gravis (MG), an autoimmune neuromuscular disease that causes muscle weakness and fatigue, can emerge at any age. When the rare disorder affects children and teens, it is called juvenile myasthenia gravis.

Like other types of MG, juvenile MG occurs when the immune system mistakenly disrupts communication between muscles and nerves, leading to weakness in various muscle groups that worsens with activity and improves with rest.

In the U.S., MG in children accounts for approximately 10% to 15% of all MG cases. This proportion is much higher in other regions, particularly in Asia, where as many as half of cases may affect children younger than 18. Girls are generally more likely to develop juvenile MG than boys.

Early diagnosis and appropriate pediatric MG treatments can help manage symptoms and improve quality of life for children and young adults living with MG.

Causes

Juvenile MG occurs when the body produces antibodies that target proteins involved in nerve-muscle communication. That, in turn, causes muscle weakness and fatigue.

Most children with juvenile MG have antibodies that target the acetylcholine receptor (AChR) protein, which enables muscle cells to receive signals from nerve cells. As with adult MG, other types of antibodies can also less commonly cause the disease, including those targeting a protein called muscle-specific kinase (MuSK). Some children may also be seronegative, meaning they test negative for common disease-causing antibodies.

Some children and teenagers with MG may have abnormalities in the thymus gland, an immune organ in the chest. These abnormalities may trigger the production of antibodies that target AChR. The most common thymus problem in juvenile MG is an enlarged gland, called thymic hyperplasia.

Juvenile MG is different from transient neonatal MG, a form of the disease that temporarily affects infants in the weeks after birth. Babies with transient neonatal MG are responding to antibodies transferred from their mothers during pregnancy, not producing their own disease-causing antibodies.

Symptoms

The most common juvenile MG symptoms are similar to those seen in adults. The disease can cause weakness in several muscle groups, including:

• eye (ocular) muscles: droopy eyelids, known as ptosis, and double vision, called diplopia
• head and neck (bulbar) muscles: difficulty chewing, swallowing, or speaking, and changes in facial expression
• limb muscles: movement problems and changes in posture
• respiratory muscles: shortness of breath or difficulty breathing

Ocular and generalized weakness

Ocular MG is a form of the disease in which only the muscles of the eyes and eyelids are affected. Purely ocular juvenile MG is common, particularly among younger children. Diagnosis may be more challenging in these cases, as diplopia and ptosis in children can be subtle.

Some children may have more widespread symptoms early on, including bulbar weakness or limb problems. Called generalized MG, this disease type is more common in adolescents who begin experiencing symptoms after puberty.

Some children and teens may initially experience only eye symptoms, then later develop generalized MG. This generalization usually occurs within two years of developing the disease, and is less common in children than in adult populations.

Recognizing a myasthenic crisis

Children with generalized MG or those with more recently diagnosed ocular MG who may still experience disease generalization are at risk of myasthenic crisis, a medical emergency that occurs when respiratory muscles become too weak to support normal breathing. Caregivers should monitor children for myasthenic crisis symptoms and have an emergency plan in place.

Warning signs of myasthenic crisis can include:

• worsening of bulbar symptoms, such as severe chewing and swallowing problems or choking
• severe generalized weakness
• shortness of breath
• lethargy or severe drowsiness

About 10% of people with juvenile MG experience myasthenic crisis, which is similar to the percentage of adults with this symptom. However, myasthenic crisis is less likely to be fatal in pediatric populations.

Diagnosis

Because juvenile MG is a rare condition, and its symptoms can overlap with those of other diseases, it may take doctors time to accurately diagnose the disorder. The process involves ruling out other possible causes of symptoms, including other pediatric neuromuscular disorders such as muscular dystrophy, and congenital myasthenic syndromes (CMS).

The first step toward a juvenile MG diagnosis involves clinical examinations, often done by pediatric neurologists and ophthalmologists. Doctors will first look for characteristic signs of muscle weakness and fatigue. Other diagnostic tests may include:

• the ice pack test: to evaluate if ptosis may be related to MG
• blood tests: to identify disease-causing antibodies
• repetitive nerve stimulation and single fiber electromyography: to measure muscle activity
• imaging scans: to visualize thymus abnormalities

Ice pack test

The ice pack test is an easy bedside exam in which doctors place an ice pack over a closed eye, then measure the degree of droopiness. With MG, but not other causes of ptosis, the eyelid droopiness often eases after icing. Ice pack test results can support an MG diagnosis, but are not sufficient to confirm the diagnosis alone.

Blood tests and EMG studies

Blood tests can identify antibodies that target AChR and other proteins involved in nerve-muscle communication. While a positive antibody test is a strong sign of MG, some children with MG test negative for these antibodies, so the test is not always definitive.

Electromyography (EMG) studies that may be used are repetitive nerve stimulation (RNS) and single fiber EMG. Both involve measuring how muscles respond to nerve input.

In MG, the muscles typically become less responsive to repeated stimulation, as captured by RNS. Single-fiber EMG is a more sensitive test that can detect subtle signal changes in individual muscle fibers. It’s often helpful for detecting the disease when symptoms are mild or restricted to the eyes.

Thymus gland assessment

MRI or CT scans of the chest can help doctors identify any abnormalities in the thymus gland, such as thymic hyperplasia. A type of thymus tumor called a thymoma can also cause MG, but this is very rare in juvenile cases, occurring in about 2% of cases.

Treatment options

Treatment for juvenile MG depends on factors like the severity of symptoms and a child’s overall health needs. It may involve:

• acetylcholinesterase inhibitors, like Mestinon (pyridostigmine bromide)
• corticosteroids or other immune-suppressing medications
• Imaavy (nipocalimab-aahu)
• Soliris (eculizumab)
• intravenous immunoglobulin, or IVIG
• plasma exchange, known as plasmapheresis
• surgical removal of the thymus gland, called a thymectomy

Acetylcholinesterase inhibitors are often the first-line treatment for children with MG. These treatments work by increasing the levels of acetylcholine, the molecule that helps trigger muscle contractions.

Corticosteroids and immunosuppressants work to suppress immune system activity in order to ease MG symptoms.

Soliris and Imaavy are targeted therapies that can be used for certain children with generalized MG. Soliris works to inhibit the complement cascade, a part of the immune system that may contribute to disease processes in MG, and can be used in children ages 6 and older with anti-AChR antibodies. Imaavy helps to accelerate the breakdown of disease-causing antibodies and can be used for patients ages 12 and older with anti-AChR or anti-MuSK antibodies.

IVIG and plasmapheresis are procedures to help reduce the levels of disease-causing antibodies. IVIG involves intravenous, or into-the-vein, infusions of healthy donor antibodies, while plasmapheresis involves removal of harmful antibodies from a patient’s blood.

Thymectomy in children with MG remains controversial, because limited data are available. However, the procedure may help some juvenile MG patients and could potentially reduce the risk of complications.

Ongoing trials are also evaluating certain approved adult MG therapies for pediatric populations.

Home care

Home care for juvenile MG may involve:

• following a healthy diet and lifestyle
• regularly exercising
• receiving vaccinations on time
• regularly monitoring symptoms
• therapy to help prevent or cope with depression and fatigue

These strategies may help support overall health and quality of life for children with MG.

Juvenile MG vs. adult MG

While many features of MG are similar in pediatric and adult populations, there are some notable differences. Generally, juvenile MG is less severe and is more likely to remain restricted to the eyes, corresponding with better long-term outcomes.

Juvenile MG vs. congenital myasthenic syndromes

CMS is a group of genetic conditions that affect nerve-muscle communication and can cause symptoms similar to those of MG.  The two conditions are distinct, and differentiating between them is important because treatment approaches differ. CMS typically appears earlier in life, and the ensuing muscle weakness is more often generalized than in juvenile MG.

Long-term outlook

The long-term outlook is generally positive for children with juvenile MG, who typically have a normal life expectancy with the right treatment. Children are also more likely than adults to enter remission, or a state of low to no disease activity. In one study, the juvenile MG remission rate was about 25%.

Factors that may be associated with better outcomes in juvenile MG include:

• developing symptoms before puberty
• having less severe symptoms
• having only ocular symptoms
• receiving proper treatment

Juvenile MG is typically a lifelong condition and requires a multidisciplinary care team to support quality of life. This includes emotional and psychological support to help children cope with the challenges of living with a chronic condition.