Pediatric Myasthenia Gravis Consortium

This is a rare form of MG that occurs in 10-15 percent of infants born to mothers with autoimmune MG. Maternal antibodies that cross the placenta in late pregnancy cause transient neonatal myasthenia. Symptoms include a weak cry or suck and generalized weakness at birth. Symptoms are usually displaued within the first 24 hours after birth. As the maternal antibodies degrade in infant’s body, symptoms gradually disappear, within a few weeks. Infants with transient neonatal myasthenia gravis do not have an increased risk for long-term or future MG.

The congenital myasthenic syndromes (CMS) are a diverse group of disorders that have an underlying defect in the transmission of signals from nerve cells to muscles. These disorders are characterized by muscle weakness, which is worsened upon exertion. The age of onset, severity of presenting symptoms, and distribution of muscle weakness can vary from one patient to another. Genetic diagnosis of these disorders is important because of the different types and different treatment options. For example, therapy that benefits one type CMS can worsen another type.

Juvenile Myasthenia Gravis (JMG) is defined as myasthenia gravis in children younger than 18 years of age. JMG is an autoimmune disorder in which antibodies interfere with nerve to muscle communication causing muscle weakness. Symptoms of weakness develop after exertion and tend to increase as the day progresses. The variability in symptoms can lead to the diagnosis of JMG often after weeks or months of symptoms. Drooping eyelids and/or incomplete movement of the eyes (causing crossing of the eyes and double vision) are frequently the earliest symptoms. However, any skeletal muscle can be involved so other symptoms may include problems chewing, swallowing and speaking clearly, shortness of breath or limb muscle weakness. Every person with JMG doesn’t have all of these symptoms, and the symptoms can change over time.

Supportive management should be initiated early in the disease course, both to manage the impact of the disease itself on physical and mental health but also to mitigate the potential medication side-effects, particularly of corticosteroids.

*Families need to be provided with a list of medications that affect the neuromuscular junction, with potential to worsen the condition, and should therefore be avoided. See list here.

• Adequate sleep and scheduled rest: Assuring adequate sleep and planning each day to allow for rest periods between more vigorous levels of activity is an important factor in minimizing symptoms of MG. Planning for quiet rest periods throughout a busy day or week is very helpful for individuals with myasthenia gravis. 
• Optimum nutrition and physical activity: Optimum nutrition and level of aerobic conditioning also help individuals with myasthenia function at their best. Both children and adults need to be cautious to avoid excessive weight gain in the context of reduced physical activity and advised with regard to healthy snacks and increased fruit and vegetable intake. The benefits of physical activity need to be highlighted, usually in the form of a graded exercise program, being mindful to avoid excessive fatigable weakness.
• Close communication with schools: Educational care plans may need to implemented to ensure that these children do not become unduly disadvantaged in accessing the educational curriculum. Informal discussions with the school, a Modification Plan under Section 504 of the 1973 Rehabilitation Act or an Individualized Education Plan under Federal Law 108-446 are ways that a child’s daily school schedule can be altered in response to medical needs. Many things can be done, as needed, to support the education of children with myasthenia gravis. These include: altering PE requirements (modified PE or temporary or long term exclusion), late starts, use of elevators between floors, transportation to school, allowing additional time between classes, providing a second set of books to be kept at home to prevent heavy backpacks, changing the number of repetitions of math problems, allowing computer access for classroom work or testing, changing nutrition/lunch times, and providing OT/PT/Speech Therapy as necessary. All, or none, of these modifications may be appropriate, depending on your child’s individual needs.
• Benefits for people with disabilities: Individuals with a disability might be eligible for Federal assistance benefits such as Social Security Disability Insurance (SSDI) or Supplemental Security Income (SSI), and Medicare. Learn more here.
• MG Support groups: Find both online and in-person support groups here.

Surgical removal of the thymus gland. A thymectomy with or without an existing thymoma (tumor, usually benign) has been believed to improve clinical status in adults with MG. Early removal of the thymus in a child with generalized, antibody positive juvenile MG (i.e., within two years from diagnosis) has been associated with better long-term outcomes. The clinical benefit of thymectomy appears over time (long-term). Therefore, thymectomy surgery should not be done on an urgent basis in a clinically ill or weak child as the risks of anesthesia and surgery outweigh the long-term benefit.

This is an cholinesterase inhibitor (ChE-I) usually used first-line as treatment for juvenile MG. It allows the body's neuromuscular transmitter acetylcholine to remain at the neuromuscular junction for a longer period, which in turn allows activation of more receptor sites, resulting in increased conductivity and muscle engagement.

• Corticosteroids, such as prednisolone, suppress the body’s production of antibodies that may be blocking or binding onto the body’s acetylcholine receptors. There are concerns about use of high dose, daily corticosteroids in children. They can lead to side-effects such as weight gain, slowing growth, bone loss, facial changes, mood changes, high blood sugar, high blood pressure and susceptibility to infection.
• Other medications can be used to avoid long-term use of corticosteroids. The medication which has been used most extensively is azathioprine. Careful monitoring of children on these medications is required as side effects can develop.

IV infusions of pooled human antibodies (IVIG) are effective at decreasing the clinical symptoms in many individuals with MG. The clinical improvement is frequently noted within several days to a week and lasts for variable intervals (generally not longer than 4-6 weeks).There is no consensus on the best dosing schedule for using IVIg to treat children with MG. Possible side effects are headache and nausea or less likely aseptic meningitis or rarely renal failure. IVIG therapy is expensive and usually requires preauthorization with third party payers.

Therapeutic Plasma Exchange, or Plasmapheresis – Also known as Plasma exchange or PLEX. This is a filtration procedure whereby abnormal antibodies are removed from blood plasma. This procedure requires two intravenous (IV) lines or a port placed before undergoing PLEX.  Repeated PLEX treatments may be required.