Neuromuscular junction diseases, particularly myasthenia gravis, are high yield for neurology examinations because they command a deep understanding of pathology, diagnostic testing, and therapeutics. Test your knowledge with questions after completing this chapter packed with high-yield facts.
Author: Brian Hanrahan MD
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Table of Contents
Myasthenia Gravis (MG)
- MG is a postsynaptic autoimmune disease with antibodies directed toward acetylcholine receptors or receptor-associated proteins.
- Patients usually present with weakness, diplopia, dysarthria, and/or dysphagia. Symptoms worsen with sustained or repetitive activity and improve with rest.
- 15% of patients have only ocular deficits referred to as ocular myasthenia gravis.
- Rarely associated with CTLA4 gene single-nucleotide polymorphisms (SNPs) or exposure to ipilimumab.
- Clinical testing
- The ice pack test (placing a bag of ice on a closed lid for one minute) can be performed to look for improved ptosis/diplopia as colder temperatures mediate neuromuscular transmission.
- The Tensilon (edrophonium) test can also be done but is rarely performed anymore in clinical practice.
- EMG testing:
- Single fiber electromyography is the most sensitive test for MG (but not specific). If pathologic it will show variable depolarization of a single action potential described as “jitter”.
- Repetitive nerve stimulation at 2 to 3 Hz would show a decrement in compound muscle action potentials (CMAPs) due to the progressive failure of neuromuscular transmission.
- Antibody testing:
- ~80% of cases have anti-Acetylcholine receptor (AChR) antibodies.
- 40% of seronegative patients for anti-AChR (i.e. about 5-10% of all MG patients) have anti-muscle-specific receptor tyrosine kinase (MuSK) antibodies.
- MuSK mediates the clustering of Ach receptors in the neuromuscular junction.
- Anti-MuSK MG patients may have atypical presentations with prominent facial, bulbar, and neck involvement with sparing of ocular muscles.
- LRP4 is involved in MuSK activation, and antibodies to LRP4 have more recently been implicated in MG. Approximately 50% of double-negative (i.e. MuSK and AChR negative) MG patients will have positive anti-LRP4.
- CXR vs. CT chest to evaluate for thymoma.
- Patients with myasthenia plus thymoma often have circulating serum striational antibodies (anti-titin, anti-ryanodine receptor (RyR), and anti-Kv1.4) in addition to anti-AChR antibodies.