Lambert-Eaton Myasthenic Syndrome (LEMS)

Medical Management

There is currently no cure for Lambert-Eaton myasthenic syndrome (LEMS); treatment aims either to improve neuromuscular transmission (symptomatic therapy) or to reduce the autoimmune response (immune modulation).

Potassium channel blockers

Amifampridine (3,4-diaminopyridine, branded FIRDAPSE® in the U.S.) is the main FDA-approved symptomatic management for LEMS. It is a potassium channel blocker and works by allowing the electrical activity that passes through the neuromuscular junction to continue for a longer period, thereby increasing calcium influx into the nerve ending and release of acetylcholine.

Firdapse was approved by the FDA in November 2018 for the treatment of adults with LEMS, and the product label now also includes pediatric patients 6 years of age and older with LEMS.

Cholinesterase inhibitors

Cholinesterase inhibitors such as pyridostigmine (Mestinon) block the action of enzymes that break down acetylcholine (acetylcholinesterases), keeping acetylcholine available for longer at the neuromuscular junction and also in the autonomic nervous system (which controls involuntary bodily functions). Sometimes the therapies can cause diarrhea, abdominal cramps, and/or excessive saliva. At high doses, they can increase weakness. Imodium can be used to treat diarrhea caused by pyridostigmine.

Cholinesterase inhibitors are usually only mildly effective for LEMS, but in rare cases they prove sufficient for managing the disease.

Other symptomatic approaches

Guanidine, a potassium channel blocker, has historically been used in conjunction with pyridostigmine, but is now largely avoided because of significant toxicity (kidney effects and bone marrow suppression). If guanidine is used, low starting doses and close monitoring of side effects are required.

Immunotherapy/immune modulation

When immunosuppressive therapy is needed for severe, progressive, or refractory disease, clinicians generally use approaches similar to myasthenia gravis. Corticosteroids (e.g., prednisone) and steroid-sparing agents (e.g., azathioprine and mycophenolate mofetil) are commonly used.

Short-term immune modulation with intravenous immunoglobulin (IVIG) or plasma exchange is also an option. IVIG therapy can be used to decrease the production of antibodies and/or block the binding of antibodies to their targets (e.g., calcium channels), while plasma exchange removes antibodies from the blood. IVIG is usually preferred, with clinical improvements that become evident within two to four weeks, though the duration of benefits may vary. IVIG can also be given in combination with other immunotherapies.

It is important to note that therapies that suppress the immune system can have side effects and increase susceptibility to infections and, possibly, cancer. Close follow-up is essential given these risks.

Cancer-related LEMS

In LEMS with an underlying cancer, treating the cancer (most commonly small-cell lung cancer) is a key component of management and may improve neuromuscular symptoms when the cancer is controlled.

Additional reading

• Roden, D. M. Pharmacogenetics of potassium channel blockers. doi:10.1016/j.ccep.2016.02.003
• FIRDAPSE® (amifampridine) [Prescribing Information].Coral Gables, FL:Pharmaceuticals, Catalyst.
• MESTINON (pyridostigmine bromide) [prescribing information].Philadelphia, PA: ICN Pharmaceuticals.
• Keogh, M., Sedehizadeh, S. & Maddison, P. Treatment for Lambert-Eaton myasthenic syndrome. Cochrane Database Syst. Rev. (2011). doi:10.1002/14651858.cd003279.pub3
• Varon MC, Dimachkie MM. Diagnosis and treatment of Lambert-Eaton myasthenic syndrome. Practical Neurology (US). 2024;23(3):26-28,47.

Last revised December 2025.