How do Myasthenia Gravis (MG) and Lambert-Eaton Myasthenic Syndrome (LEMS) differ in response to exercise?

From the Guidelines

Myasthenia Gravis (MG) and Lambert-Eaton Myasthenic Syndrome (LEMS) exhibit distinct responses to exercise, with MG symptoms worsening due to fatiguability and LEMS demonstrating temporary improvement with brief exercise or repeated muscle contraction, known as post-exercise facilitation. In MG, symptoms typically worsen with continued exercise, as autoantibodies block or destroy acetylcholine receptors, reducing the muscle's ability to respond to repeated nerve stimulation 1. This is in contrast to LEMS, which involves autoantibodies against voltage-gated calcium channels at the presynaptic nerve terminal, initially reducing acetylcholine release, but with repeated stimulation or exercise, calcium accumulation in the nerve terminal temporarily overcomes this defect, improving neuromuscular transmission 1. Some key points to consider when differentiating between MG and LEMS include:

• The effect of exercise on muscle strength, with MG showing decreased strength and LEMS showing temporary improvement
• The underlying pathophysiology, with MG involving autoantibodies against acetylcholine receptors and LEMS involving autoantibodies against voltage-gated calcium channels
• The importance of individual assessment of neuromuscular function in patients with MG, as sensitivity to non-depolarizing neuromuscular blocking agents (NMBAs) can vary greatly 1. The distinctive exercise response pattern is valuable for clinical differentiation and can guide appropriate diagnostic testing, such as repetitive nerve stimulation studies or specific antibody tests.

From the Research

Differences in Response to Exercise

• Myasthenia Gravis (MG) and Lambert-Eaton Myasthenic Syndrome (LEMS) are two autoimmune disorders that affect the neuromuscular junction, but they differ in their response to exercise 2.
• In MG, patients typically experience fatigable weakness, which worsens with repeated use of the affected muscles and improves with rest 3.
• In contrast, LEMS patients often exhibit a characteristic pattern of postexercise facilitation, where muscle strength increases after brief, maximal voluntary contraction or with high-rate stimulation 2.
• The repetitive nerve stimulation (RNS) test can help distinguish between MG and LEMS, with LEMS patients showing a significant increment in compound muscle action potential amplitude after exercise or high-rate stimulation, whereas MG patients exhibit a decrement at low-rate stimulation 2.

Diagnostic Features

• The RNS test is abnormal in all patients with LEMS and in approximately 54% of patients with MG, highlighting the importance of this test in diagnosing and distinguishing between these two conditions 2.
• The diagnostic hallmark of LEMS is a ≥60% increment at high-rate stimulation or postexercise facilitation, which is present in approximately 97% of patients, whereas the diagnostic hallmark of MG is a decrement at low-rate stimulation, present in approximately 46% of patients 2.

Treatment Implications

• Understanding the differences in response to exercise between MG and LEMS is crucial for developing effective treatment strategies, as patients with LEMS may require different approaches to manage their symptoms and improve muscle strength 4, 5.
• Treatment options for MG and LEMS include immunosuppressive drugs, corticosteroids, and intravenous immunoglobulins, which can help improve symptoms and quality of life for patients with these conditions 4, 5, 6.