In Lambert-Eaton myasthenic syndrome (LEMS), antibodies against presynaptic 
voltage-gated calcium channels reduce the quantal release of acetylcholine, 
causing muscle weakness and autonomic dysfunction. More than half of the 
affected patients have associated small cell lung cancer, and thorough screening 
for an underlying malignancy is crucial. The mainstay of treatment for LEMS is 
symptomatic but immunotherapy is needed in more severely affected patients. 
Symptomatic therapies aim at increasing the concentration of acetylcholine at 
the muscle endplate. While acetylcholinesterase inhibitors were the first drugs 
to be used for the amelioration of symptoms, 3,4-diaminopyridine (3,4-DAP, 
amifampridine) has been shown to be more effective. 3,4-DAP blocks presynaptic 
potassium channels, thereby prolonging the action potential and increasing 
presynaptic calcium concentrations. This then results in increased quantal 
release of acetylcholine. The efficacy of 3,4-DAP for increasing muscle strength 
and resting compound muscle action potentials has been demonstrated by four 
placebo-controlled trials. Side effects are usually mild, and the most 
frequently reported are paresthesias. The most common serious adverse events are 
epileptic seizures. 3,4-DAP is currently the treatment of choice in patients 
with Lambert-Eaton myasthenic syndrome.