Myasthenic Syndromes

Key Features

Essentials of Diagnosis

• Asymmetric, variable weakness, usually coming on or increasing with use (fatigue)

• Involves extraocular, bulbar, and respiratory muscles

• Positive response to neostigmine and edrophonium

General Considerations

• Characterized by easy fatigability of muscles, particularly the extraocular, bulbar, and respiratory muscles

• In the neonatal period or in early infancy, the weakness may be so constant and general that an affected infant may present nonspecifically as a "floppy infant"

• Three general categories are recognized

  • Neonatal (transient) myasthenia

  • Autoimmune myasthenia gravis

  • Congenital myasthenia

Clinical Findings

Symptoms and Signs

• Neonatal (transient) myasthenia

  • Bulbar weakness, difficulty feeding, weak cry, and hypotonia present before the third day of life

  • Occurs in 12–19% of infants born to myasthenic mothers as a result of passive transfer of maternal acetylcholine receptor antibody across the placenta

• Autoimmune myasthenia gravis

  • Characterized by fatigable and asymmetric weakness

• Tends to recur and remit

• Can be precipitated by illness or medications such as aminoglycoside antibiotics

  • Typical signs include difficulty chewing foods like meat, dysphagia, nasal voice, ptosis, ophthalmoplegia, and proximal limb weakness.

  • Other autoimmune disorders such as rheumatoid arthritis and thyroid disease may be associated findings

  • Systemic or bulbar symptoms develop within 2 years in 50% of children and in 75% within 4 years

• Congenital myasthenic syndromes

  • These syndromes are a heterogenous group of hereditary, nonimmune disorders of presynaptic, synaptic, or postsynaptic neuromuscular transmission

  • Symptom onset is before the age of 2 years and can vary from mild motor delay to dramatic episodic apnea

Diagnosis

Laboratory Findings

• Neostigmine test

  • May be preferable to the edrophonium (Tensilon) test in newborns and very young infants because the longer duration of its response permits better observation, especially of sucking and swallowing movements

  • There is a delay of about 10 minutes before the effect may be manifest

  • Clinician should be prepared to suction secretions, and administer atropine if necessary

• Edrophonium testing

  • Used in older children who are capable of cooperating in certain tasks and who exhibit easily observable clinical signs, such as ptosis, ophthalmoplegia, or dysarthria

  • Maximum improvement occurs within 2 minutes

• Serum acetylcholine receptor binding, blocking, and modulating antibodies typically, though not always, are found in autoimmune myasthenia gravis

• Commercially available genetic testing is limited for patients with congenital myasthenic syndromes

Imaging

• Chest radiograph and CT scanning in older children may show thymic hyperplasia

• Thymomas are rare

Diagnostic Procedures

• Electrophysiologic studies

  • May be helpful when myasthenic syndromes are considered

  • Repetitive stimulation of a motor nerve at slow rates of 2–3 Hz with recording over an appropriately chosen muscle reveals a progressive fall in compound muscle action potentials by the fourth to fifth repetition in myasthenic patients

  • At higher rates of stimulation ...