Normally, for muscles to move, a nerve signal is sent from the brain and travels along the nerve fibers. This is an electrical signal that is transformed into a chemical signal at the neuromuscular junction — the point at which the nerve cell meets the muscle cell. The chemical messenger that relays the nervous signal at the neuromuscular junction is called acetylcholine. Acetylcholine binds to receptors found on the surface of muscle cells, initiating muscle contraction. In order for the muscle to relax, an enzyme called cholinesterase digests the acetylcholine, removing it from the junction and “resetting” the system for the next nervous signal.
In LEMS, the immune system attacks the nerve cell endings, reducing the amount of acetylcholine that is released. Without acetylcholine, muscles are unable to contract strongly and weaken over time.
There is currently no cure for LEMS, but there are treatments to manage symptoms and improve patients’ quality of life.
Roughly half of all LEMS patients also have small-cell lung cancer. In these cases, treating the cancer is the priority, and often also relieves the symptoms of LEMS.
Cholinesterase inhibitors block the enzyme that breaks down acetylcholine, meaning that a stronger, longer-lasting nervous signal is sent to the muscles. Mestinon (pyridostigmine) is the most commonly used cholinesterase inhibitor.
This type of treatment usually is only mildly effective in treating LEMS, but for some patients, it is sufficient to manage the symptoms.
Potassium channel blockers
Potassium channel blockers change the way electrical signals are sent from the nerve cells to the muscles, meaning that they continue longer, which increases the amount of acetylcholine that is released by the nerve cell. In a sense, that increases the signal from the nerve cell to the muscle. Firdapse (amifampridine) is a potassium channel blocker that is approved by the U.S. Food and Drug Administration (FDA) for the relief of LEMS symptoms. Firdapse also is available in the European Union.
Guanidine is another potassium channel blocker that may be used to treat LEMS, and is sometimes used in combination with Mestinon. However, this treatment is less common because of its potential toxic effect on kidneys and bone marrow.
Treatments that block or suppress the immune system can be used to reduce the autoimmune attacks that damage the nerve endings. One such treatment is prednisone (a corticosteroid) that mimics an immune-suppressing hormone that is normally produced by the body.
Azathioprine and mycophenolate are other immune suppressant treatments that may be used to treat LEMS. Once ingested, azathioprine is metabolized into a small molecule that blocks the synthesis of DNA. This is most important in rapidly-dividing cells such as immune cells. By inhibiting DNA synthesis, the immune system is weakened, reducing the autoimmune attack on the nerve endings.
Intravenous immunoglobulin (IVIG) is a treatment that can be used to block the binding of antibodies to their target. Immunoglobulin is a type of antibody isolated from human blood. By increasing the amount of non-specific antibody in the blood, the immune system is distracted from attacking the nerve endings.
Plasmapheresis is a treatment in which blood is removed from the body, filtered of antibodies and immune cells, and then returned to the body, reducing the number of immune cells available to attack the nerve endings.
For patients who do not respond to other immune suppressants, rituximab may be prescribed. Rituximab contains an antibody that binds to immune cells that produce antibodies, causing them to self-destruct.
Any immune suppressant therapy can make patients more susceptible to infection and possibly cancer, so careful monitoring is necessary after these treatments are prescribed.
Physical therapy helps patients with strengthening exercises to ensure they maintain mobility, flexibility, and range of motion for as long as possible. Physical therapists can design routines so patients can exercise safely.
Speech therapy, using exercises to strengthen the muscles involved, may help patients who have difficulty chewing, swallowing, or speaking.
Last updated: July 18, 2019
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