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
Chapter Multimedia Content
Table of Contents
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.
Diagnostic tests
- 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.
Normal repetitive stimulation testing of the left facial muscles. Action potential amplitudes remain consistent with repeated stimulation.
Abnormal repetitive nerve stimulation of the right trapezius muscle. Note the decrement of the action potentials with repeated stimulations.
- 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.
Tip:
MuSK helps AChR cluster, and MuSK + myasthenic patients have prominent symptoms that cluster around the face and neck.
Additional workup
- 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.
