Patient Presentation
The residents were discussing a 7-year-old female who was currently in the pediatric intensive care unit with muscle weakness. The resident taking care of her said, “The neurologists think she may have myasthenia gravis, but her autoantibodies are negative. Apparently this happens more with young kids. They are going to do a Tensilon® test this afternoon so I get to watch them do that. She’s having a lot of problems controlling her secretions so we’re monitoring her respiratory status closely.” One of the other residents asked about how she presented. “We’ll initially we thought this was Guillian-Barre, but once we got more history it didn’t seem to be an ascending paralysis, but was more generalized weakness, plus there was a history of her eyes being droopy when she would get sick. Plus this time when she got an ear infection and a bad cold, she had a lot of problems swallowing and parents thought she was really tired. Turns out she was really weak,” he recounted. The attending said that she had seen a Tensilon test performed when she was a resident, “I don’t remember if the patient had myasthenia or not, but I remember the neurology fellow trying to push the child’s eyes open to determine if weakness was improving with the Tensilon. I know there is a specific protocol for doing the test, plus I think there’s another specific test for monitoring patients. It’s been a long time since I looked up myasthenia though.”

Discussion
Myasthenia gravis (MG) is a rare disease in the pediatric population. The incidence depends on the population studied but is estimated at 1-9/1 million/year. It was first described by William Heinrich Erb in 1879. The cause is autoantibodies against components of the post-synaptic membrane of the neuromuscular junction, usually against the acetylcholine binding receptor (AChR).

It can occur at any age but is more common in the adult population. Juvenile patients (0-19 years) are divided into prepubertal (12 years) who have disease presentations similar to the adult population. In adults there are 5 grades: ocular symptoms, mild, moderate, severe and very severe.

MG symptoms include:

• Ocular symptoms are common
  • Ptosis – uni- or bilateral, children may tilt head to see
  • Ophthalmoplegic facial weakness – lid twitch, strabismus
• Facial/bulbar weakness
  • Masked facies
  • Chewing and swallowing problems
  • Speech problems
  • Coughing and coughing insufficiency
• Respiratory symptoms
  • Respiratory insufficiency
• Peripheral symptoms (proximal symmetrical weakness)
  • Exercise intolerance
  • Fatigability
  • Difficulty with climbing stairs, rising from seated position, personal hygiene
• Worsening of symptoms with
  • Exercise
  • Fever or infection
  • Elevated temperature
  • Medication

Symptoms often improve with rest such as sleeping with improved symptoms at night or early in the day. Prepubertal children usually present with ocular symptoms (which can wax/wane) such as ptosis, blurred or double vision. Generalized muscle weakness is rare. Ocular symptoms are common and may precede the other generalized symptoms by 2-3 years or they may not develop.

MG can be confused with other entities such as Guillain-Barre or brain stem encephalitis. Evaluation includes a strong history and physical examination (note that the physical examination may be falsely normal as patients may be resting more before the appointment). Autoantibodies to AChR, muscle-specific kinase and Titin are often positive in adults but frequently negative in children particularly younger children. Nerve stimulation testing can also be helpful. Intravenous edrophonium or Tensilon testing is also used. Edrophonium inhibits acetylcholine esterase and therefore the acetylcholine is in contact with the AChR for longer. Therefore patient symptoms improve with the administration of the drug. This is only carried out in an intensive care setting as side effects include hypotension and bradycardia. Edrophonium testing can improve MG symptoms but can also be positive in a number of other conditions.

Treatment in children usually begins with pyridostigmine which is an acetylcholine esterase inhibitor. Immunomodulators and immunosuppressive medications are also sometimes used especially if pyridostigmine is not effective. Sometimes plasma exchange or intravenous immunoglobulin is used. Thymectomy improves many patient symptoms and potentially patient remissions. There is a higher remission rate using thymectomy within 1 year after symptom onset. Spontaneous remission is common in prepubertal children with ocular symptoms only.

A review of causes of ptosis can be found here.
A review of hypotonia in infants can be found here.
A review of muscle weakness can be found here.

Learning Point
Drs. Besinger, Toyka, Homberg, Heininger, Hohlfeld, and Fateh-Moghadam first proposed a score for clinical severity for MG patients in 1983. Since that time the scoring system has been further developed and validated and is called the Quantitative Myasthenia Gravis (QMG) test that can be reviewed here. Components currently include:

• Ocular symptoms – double vision, ptosis
• Facial/bulbar symptoms – eyelid closure, swallowing, speech
• Muscle weakness – head lift, hand grip, arm lift, leg lift
• Respiratory weakness – forced vital capacity

The Myasthenia Gravis Foundation of American also has other instruments such as activities of daily living and quality of life available here.

Questions for Further Discussion
1. What is the difference between hypotonia and muscle weakness?
2. What are indications for treating a patient in the intensive care setting?
3. What are transient neonatal myasthenia gravis and congenital myasthenic syndromes?

Related Cases

Disease: Myasthenia Gravis

Symptom/Presentation: Weakness

Specialty: Critical Care | Medical History | Neurology / Neurosurgery

Age: School Ager

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Myasthenia Gravis

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Besinger UA, Toyka KV, Homberg M, Heininger K, Hohlfeld R, Fateh-Moghadam A. Myasthenia gravis: long-term correlation of binding and bungarotoxin blocking antibodies against acetylcholine receptors with changes in disease severity. Neurology. 1983 Oct;33(10):1316-21.

Barnett C, Katzberg H, Nabavi M, Bril V. The quantitative myasthenia gravis score: comparison with clinical, electrophysiological, and laboratory markers. J Clin Neuromuscul Dis. 2012 Jun;13(4):201-5.

Liew WK, Kang PB. Update on juvenile myasthenia gravis. Curr Opin Pediatr. 2013 Dec;25(6):694-700.

Della Marina A, Trippe H, Lutz S, Schara U. Juvenile myasthenia gravis: recommendations for diagnostic approaches and treatment. Neuropediatrics. 2014 Apr;45(2):75-83.

Sanders DB, Wolfe GI, Benatar M, et.al. International consensus guidance for management of myasthenia gravis: Executive summary. Neurology. 2016 Jul 26;87(4):419-25.

Myasthenia Gravis Foundation of America. Clinical Overview of MG. Available from the Internet at: http://myasthenia.org/HealthProfessionals/ClinicalOverviewofMG.aspx(cited 12/12/17)

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa