Clinical Information

Myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) are acquired autoimmune disorders of neuromuscular transmission. MG is caused by pathogenic autoantibodies binding and potentially removing (modulation) the muscle's nicotinic acetylcholine receptor (AChR) from the surface of the neuromuscular junction. Serologically, the detection of AChR binding antibody provides the best diagnostic sensitivity. However, the presence of both AChR binding and modulating activity improves diagnostic accuracy. A subset of patients who are AChR seronegative will have muscle-specific kinase (MuSK) antibodies.

LEMS is caused by autoantibodies binding to motor nerve terminal's voltage-gated P/Q-type calcium channel. Synaptic transmission fails when autoantibodies cause a critical loss of junctional cation channel proteins that activate the muscle action potential.

Both MG and LEMS can affect children as well as adults, although LEMS is very rare in children. In adults MG is 10 times more frequent than LEMS, but it is sometimes difficult to distinguish the two disorders clinically. Electrophysiological testing is extremely helpful in distinguishing these 2 disorders. MG patients have decrements of compound muscle action potential (CMAP) amplitudes on repetitive stimulation whereas LEMS has immediate and dramatic post exercise facilitation (elevation) of CMAP amplitudes. Neoplasms associated with LEMS or MG are an endogenous source of the antigens driving production of the autoantibodies that characterize each disorder. In adults with MG, there is at least a 20% occurrence of thymoma and, very rarely (<1%), extrathymic cancers. LEMS is frequently associated (80%) with small-cell lung carcinoma (SCLC). Thus far, MuSK antibody associated MG has not been associated with any neoplasm.

The diagnostic sensitivity of these tests depends on the disease severity and duration of symptoms. AChR binding antibodies may be undetectable for 6 to 12 months after MG symptom onset and similarly P/Q-type calcium channel antibody may be undetectable for 6 to 12 months after LEMS onset. Only about 5% of adult patients with generalized MG who are not immunosuppressed remain seronegative for muscle AChR beyond 12 months. Although immunotherapy is universally beneficial for MG, in LEMS resection of the identified SCLC and initiation of 3,4-diaminopyridine, which facilitates acetylcholine release by increasing presynaptic calcium concentration, is most beneficial.

Note: Single antibody tests may be requested in the follow-up of patients with positive results previously documented in this laboratory.