Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder of the neuromuscular junction, marked by proximal weakness, autonomic dysfunction, and reduced reflexes. It is often paraneoplastic — most commonly linked to small-cell lung cancer — so malignancy screening is essential in every newly diagnosed adult, and may need to be repeated over time.
Amifampridine: first-line symptomatic therapy
Amifampridine (3,4-diaminopyridine, marketed as Firdapse) blocks presynaptic potassium channels, prolonging the action potential and enhancing calcium-dependent acetylcholine release at the neuromuscular junction. Across multiple randomized trials it has produced significant, sustained improvements in muscle strength and autonomic symptoms (on the order of a two-point gain in Quantitative Myasthenia Gravis score versus placebo) and remains the only disease-directed symptomatic therapy approved for LEMS. It is approved for adults and children, and in 2024 the FDA raised the maximum daily dose to 100 mg for greater flexibility; an extended-release formulation intended to reduce dosing frequency was filed for review in 2025. The main adverse effects are paresthesias and gastrointestinal upset, with a dose-related seizure risk at higher doses.
Immunotherapy and acute management
When symptomatic therapy is insufficient — particularly in paraneoplastic disease or more severe presentations — immunosuppression with corticosteroids, azathioprine, or mycophenolate mofetil can induce remission and allow symptomatic drugs to be tapered, though these take time to work. For severe, rapidly progressive, or refractory disease, or before surgery, plasmapheresis and intravenous immunoglobulin provide rapid but transient benefit, serving as a bridge until slower-acting immunotherapy takes effect. In paraneoplastic LEMS, treating the underlying cancer is itself often the most effective intervention.
| Therapy | Role | Notes |
|---|---|---|
| Amifampridine (Firdapse) | First-line symptomatic | Only approved disease-directed therapy; max dose now 100 mg; extended-release in review |
| Immunosuppressants | Steroid-sparing / remission | Steroids, azathioprine, mycophenolate |
| Plasmapheresis / IVIg | Acute / refractory | Rapid but temporary; bridging therapy |
| Cancer treatment | Paraneoplastic LEMS | Screen all adults for SCLC |
Further reading: reviews of amifampridine in LEMS (Neuromuscular Junction Disorders, Oh 2021; Verschuuren et al., Lancet Neurology 2022); Firdapse dosing update (2024).