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This chapter provides a practical approach, to the evaluation
and treatment of the most common pediatric-acquired neuromuscular transmission
disorder, myasthenia gravis.
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Thomas Willis is credited with the 17th century description of
myasthenia gravis (MG).1-3 In 1879 Erb elaborated
on the characteristic MG clinical syndrome.3Jolly
followed in 1895, reporting a 14-year-old boy with varying ptosis,
oropharyngeal, and generalized muscle weakness suggested the term myasthenia
gravis pseudoparalytica.4 Important investigations
in the 1930s included physostigmine’s symptomatic efficacy5 and
the chemical basis of neuromuscular transmission.6 Specific
EMG features of MG were reported in 1941.7
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An association of 2 previously recognized autoimmune disorders, namely
thyroiditis and pernicious anemia, sometimes occurring concomitantly
in MG patients, provided the basis for the proposed autoimmune basis
of MG.8 Acetylcholine was next identified as the
primary neuromuscular junction neurotransmitter.9 In
1973 an experimental allergic myasthenia gravis with clinical, pharmacologic,
and EMG equivalence to human MG was discovered.10 Subsequently,
acetylcholine receptor antibodies were identified in human MG.11 (See eFigs. 571.1, 571.2.)
Positive therapeutic responses to plasmapheresis supported myasthenia
gravis’s autoimmune nature.12 Testing
for acetylcholine antibodies is the most valuable current means
to diagnose the disease.13-15
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Most (85%) MG patients have antibodies against the nicotinic
acetylcholine receptors (AChR) at skeletal muscle end plates. Another
antibody-specific tyrosine kinase (muscle-specific kinase) is found
in 50% of MG patients who are AChR antibody negative.16,17 These
various antibodies damage and reduce the number of AChRs. Thymic
hyperplasia occurs in many adult MG patients; a benign thymoma is
present in 10% of adults. In contrast, this is an extremely
uncommon occurrence in children.
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Myasthenia gravis (MG) is the most common neuromuscular transmission
disorder in children and adults. Young children typically present
with ocular MG manifested by ptosis and or diplopia.18Generalized
MG presents with varied combinations of ocular, bulbar, neck, and
limb weakness, and, rarely, respiratory distress, and is more common
in adolescents.17Neonatal myasthenia gravis occurs
in 15% of babies born to mothers with autoimmune MG.19 Congenital
myasthenia gravis syndromes are a group of widely differing, much
less-common neuromuscular transmission disorder, each characterized
by compromised neuromuscular transmission safety margin.20 These
genetically determined myasthenic disorders generally
present during the first years of life with a more subtle ptosis
and extraocular weakness. In contrast, other variants may have a
very acute presentation, with the baby in extremis with a sudden
life-threatening respiratory distress that ...