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INTRODUCTION

The neuromuscular junction (NMJ) is an exquisitely organized and highly specialized synaptic interface between the motor nerve terminal and muscle fiber (Fig. 562-1). The NMJ transmits action potentials from the motor neuron to the muscle fiber (Fig. 562-2). The motor nerve terminal stores numerous presynaptic vesicles containing acetylcholine (ACh), and when it is activated, ACh is released by exocytosis across the NMJ synapse. It subsequently binds and activates the acetylcholine receptors on the postsynaptic muscle membrane, and this generates a postsynaptic action potential that translates into depolarization of the muscle fiber, which in turn leads to a contractile response. Diseases that lead to disruption of any of the structural components or function of the NMJ can impair transmission of the action potential and manifest as fatigue and muscle weakness.

Figure 562-1

Before it terminates in a skeletal muscle, each motor axon bundled in the nerve forms many branches, each of which forms a synapse with a muscle fiber. Silver staining can reveal the nerve bundle (NB), the terminal axonal twigs, and the motor end plates (MEPs; also called neuromuscular junctions [NMJs]) on striated muscle fibers (S) (×1200). (Reproduced with permission from Mescher AL: Junqueira’s Basic Histology, 14th ed. New York: McGraw-Hill; 2016.)

Figure 562-2

A: A scanning electron microscope (SEM) shows the branching ends of a motor axon, each covered by an extension of the last Schwann cell and expanded terminally as an motor end plate (MEP) embedded in a groove in the external lamina of the muscle fiber. B: Diagram of enclosed portion of the SEM indicating key features of a typical MEP: synaptic vesicles of acetylcholine (ACh), a synaptic cleft, and a postsynaptic membrane. This membrane, the sarcolemma, is highly folded to increase the number of ACh receptors at the MEP. Receptor binding initiates muscle fiber depolarization, which is carried to the deeper myofibrils by the T-tubules. (Reproduced with permission from Mescher AL: Junqueira’s Basic Histology, 14th ed. New York: McGraw-Hill; 2016.)

The most common disease of the NMJ is myasthenia gravis (MG). In children, there are 3 principal myasthenic disorders including autoimmune juvenile MG, neonatal MG, and congenital MG. All 3 have distinct pathophysiology with important consequences for diagnosis and treatment. Other diseases of the NMJ include paraneoplastic autoimmune myasthenia (Lambert-Eaton syndrome), toxins, and botulism. The NMJ diseases can be organized based on whether they affect presynaptic or postsynaptic function. This is a neurophysiologic characteristic that can aid in diagnosis.

AUTOIMMUNE JUVENILE MYASTHENIA GRAVIS

Pediatric patients with acquired autoimmune MG from birth to 19 years of age are typically defined as having juvenile MG (JMG), which is a postsynaptic NMJ disorder.

EPIDEMIOLOGY

Recent estimates suggest an ...

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