From the Guidelines
Lambert-Eaton myasthenic syndrome (LEMS) worsens with the edrophonium (Tensilon) test because it increases acetylcholine levels without addressing the underlying deficiency of calcium channels in the presynaptic nerve terminal. The edrophonium test is used to diagnose neuromuscular disorders, but its effects can vary depending on the specific condition. In LEMS, autoantibodies target voltage-gated calcium channels (VGCCs), specifically the P/Q type, which are crucial for acetylcholine release at the neuromuscular junction 1. This results in decreased synaptic transmission due to reduced calcium influx into the presynaptic nerve terminal, leading to muscle weakness. When edrophonium is administered, it inhibits acetylcholinesterase, increasing acetylcholine levels at the neuromuscular junction. However, this increase does not compensate for the severely reduced acetylcholine release caused by the autoantibody-mediated blockade of VGCCs. Instead, the increased acetylcholine can cause desensitization of postsynaptic receptors, further exacerbating muscle weakness. Key characteristics of LEMS include:
- Craniocaudally progressive proximal muscle weakness, predominantly at the hip girdle
- Presence of anti-VGCC antibodies
- Diagnosis through clinical characteristics, electromyography, and anti-VGCC antibody testing
- Potential treatment with IVIg, as proposed in guidelines for LEMS management 1. The worsening of symptoms with edrophonium can serve as a diagnostic clue to differentiate LEMS from myasthenia gravis, where edrophonium typically improves symptoms by increasing acetylcholine availability.
From the Research
Lambert-Eaton Myasthenic Syndrome (LEMS) and Edrophonium Test
- LEMS is a rare autoimmune disorder characterized by muscle weakness, autonomic dysfunction, and areflexia 2.
- The edrophonium test is used to diagnose myasthenia gravis, but it can also be positive in LEMS patients 3.
- A positive edrophonium response has been reported in some cases of LEMS, but it is not necessarily diagnostic of myasthenia gravis 3.
Pathophysiology of LEMS
- LEMS is caused by autoantibodies against presynaptic membrane P/Q-type voltage-gated calcium channels (VGCC), leading to reduced acetylcholine release and muscle weakness 2, 4.
- The underlying cause of LEMS in some patients is small cell lung cancer, and cancer therapy is the priority for these patients 4.
Treatment of LEMS
- Symptomatic treatment options for LEMS include 3,4-diaminopyridine (3,4-DAP), which can improve muscle strength and reduce symptoms 5, 6, 4.
- However, 3,4-DAP can have significant dose-limiting side effects, and additional treatment approaches are needed 4.
- Recent studies have introduced a novel Ca(2+) channel agonist (GV-58) as a potential therapeutic alternative for LEMS, which can interact with 3,4-DAP to restore neurotransmitter release at the NMJ 4.
Edrophonium Test in LEMS
- The edrophonium test can worsen LEMS symptoms because it can further reduce acetylcholine release at the NMJ, exacerbating muscle weakness 3.
- The test should be used with caution in LEMS patients, and the diagnosis should be based on clinical features, edrophonium-responsiveness, and other laboratory findings 3.