A 6-year-old male came to clinic for a cough and runny nose for 4 days. He initially had a low grade fever but this had resolved. He continued to cough more at night which was disturbing his sleep. He had no pain. The past medical history was positive for ocular myasthenia gravis that had been diagnosed at age 3. He took pyridostigmine. The review of systems was otherwise negative.
The pertinent physical exam showed a somewhat tired appearing male, wearing glasses and tilting his head backward. His vital signs were normal without a measured fever. His growth parameters were around the 50th percentile. He had bilateral ptosis, moderate clear rhinorrhea, with normal pharynx and ear examinations. He had coarse upper airway sounds but no wheezing or other adventitial breath sounds on lung examination. He had no rashes. His neurological examination showed no other obvious muscle weakness.
The diagnosis of an upper respiratory tract infection was made. The physician commented on the ptosis to the family. The mother said that it seemed to get worse with minor infections but then improved. “He always has some droopiness, so this is just part of being sick,” she noted. The physician discussed symptomatic treatment and reiterated signs of respiratory distress with the family. The mother indicated that she was always looking for respiratory distress and knew when to call neurology or go to the emergency room.
Myasthenia gravis (MG) is a problem of the neuromuscular junction which causes muscle weakness. It can occur in all ages and have a range of symptoms from mild localized disease to mortality-threatening respiratory failure. MG occurs in 1.7-30 cases/million, with a prevalence of 77.7 cases/million. Pediatric patients comprise 10-15% of all patients with MG. In various Asian populations, the juvenile MG can be up to 50% of all of the MG cases. Fluctuations in muscle weakness is a hallmark of the disease.
As a reminder, “[i]n normal synaptic transmission in the neuromuscular junction, the axon is depolarized and this depolarization travels to the axon terminal. Voltage-gated calcium channels open, leading to acetylcholine containing vesicles to fuse to the cell membrane. Acetylcholine is then released from synaptic vesicles into the synaptic cleft from the axon terminal. The acetylcholine travels across the synaptic cleft to the AChR [acetylcholine receptor] sites where binding causes sodium channels to open, depolarizing the motor end plate of the muscle fiber. Acetylcholinesterase degrades the acetylcholine, and the sodium channels close, allowing repolarization of the muscle fiber.”
The diagnosis of MG is made by history of fatiguable weakness, clinical examination trying to fatigue muscles such as continuous upward gaze (patients worsen with this activity), physiological testing such as the Tensilon test (which has improved symptoms when the drug is given), electrophysiological testing (worsening with repeated muscle stimulation) and serological testing for antibodies. Treatment varies from none, to acetylcholinesterase inhibitors, immunosuppressive medications, intravenous immunoglobulin and plasmapheresis. Surgical treatment by thymectomy is also used as there appears to be an association with thymomas. Prognosis depends on the type of MG and remissions do occur.
MG is worsened by “systemic illness, pregnancy, the menstrual cycle, drugs that affect neuromuscular transmission,…, increase temperature, hyperthyroidism or hypothyroidism and emotional upset.”
Patients are formally classified by disease severity, but MG has 2 basic forms based on clinical type:
- Ocular MG
- Muscles of the eye are preferentially affected in MG and if only ocular muscles are affected it is termed ocular MG (OMG)
- OMG patients can have ptosis, strabismus or diplopia. Because this is a fatigable muscle disease, patients may have improved symptoms in the morning and worsen throughout the day
- Patients may complain of difficulty walking not because of affected extremity weakness but because of difficulty seeing where they are walking, particularly with stairs
- OMG can be unilateral or bilateral
- Rates of progression to generalized MG are 8-49%. Preadolescents are less likely to progress than adolescents
- Spontaneous remission with OMG is common
- Generalized MG
- Any muscle can be affected
- Patients will relate various abnormalities in muscular endurance and exercise intolerance
- Weakness of the respiratory muscles can cause respiratory distress including respiratory failure
- Patients with bulbar weakness can have problems with chewing or swallowing, which may cause choking including having nasal regurgitation of food
- Speech can be affected including slurring, quieter voice or having a nasal voice as fatigue worsen even over a day
- Patients may also have issues with basic hygiene such as toileting, brushing their teeth or washing their hair
MG has 3 forms based on cause:
- Transient neonatal MG
- Cause: Maternal antibodies are transplacentally passed to the newborn
- Occurs in 5-30% of infants of mothers with MG
- Presents at or shortly after birth
- Ocular MG or more generalized weakness may occur – weak cry, poor suck, generalized weakness or respiratory distress
- Diagnosis is by detecting the antibodies
- Resolves when antibodies are gone
- Congenital MG
- Cause: Functional or structural abnormalities in the proteins involved in the neuromuscular junction
- Most commonly the AChR proteins and function are affected
- Mutation specific treatment is important as treatment for one type may worsen another
- It must be distinguished from myopathies or other neurological conditions
- Fatigable weakness usually at young age even infancy is the usual presentation
- Ocular MG or more generalized weakness may occur
- Juvenile MG
- Cause: Autoimmune disorder causing dysfunction of the AChR
- Auto antibodies targeted against various structural proteins, mainly the AChR but also muscle-specific kinase (MuSK)
- Patients with MuSK antibodies have more severe disease
Questions for Further Discussion
1. What causes ptosis? A review can be found here
2. What causes muscle weakness? A review can be found here
3. What causes hypotonia? A review can be found here
4. What causes peripheral neuropathy? A review can be found here
- Disease: Myasthenia Gravis
- Specialty: Neurology / Neurosurgery
- Age: School Ager
To Learn More
To view pediatric review articles on this topic from the past year check PubMed.
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.
Della Marina A, Trippe H, Lutz S, Schara U. Juvenile myasthenia gravis: recommendations for diagnostic approaches and treatment. Neuropediatrics. 2014;45(2):75-83. doi:10.1055/s-0033-1364181
Jastrzebska A, Jastrzebski M, Ryniewicz B, Kostera-Pruszczyk A. Treatment outcome in juvenile-onset myasthenia gravis. Muscle Nerve. 2019;59(5):549-554. doi:10.1002/mus.26445
Peragallo JH. Pediatric Myasthenia Gravis. Semin Pediatr Neurol. 2017;24(2):116-121. doi:10.1016/j.spen.2017.04.003
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa