i Lambert-Eaton myasthenic syndrome (LEMS) is a uncommon, but debilitating, neuromuscular disorder that is estimated to affect 2.32 people per million in Europe 1 with a prevalence of up to 3,000 cases in the US. 2 The disease has an autoimmune etiology in which autoantibodies bind to P/Q-type voltage-gated calcium channels (VGCCs) and decrease the release of acetylcholine at the synapses affecting peripheral cholinergic neurotransmission. 3 The impaired function of the VGCCs decreases the secretion of acetylcholine and disrupts synaptic transmission at neuromuscular junctions and certain autonomic nerve terminals leading to muscular weakness and symptoms of autonomic dysfunction.2,4-6More than half the patients with LEMS, particularly male smokers aged over 50 years, present with an underlying malignancy, usually small cell lung cancer (SCLC). 7,8 However, there are also case reports on a wide variety of lung and non-lung malignancies observed in LEMS patients. The peak age of onset of non-tumor LEMS is 35 years with a second peak at 60 years, whereas paraneoplastic LEMS occurs primarily in middleaged and older adults, with a median age of onset of 58 years. 9 Nonparaneoplastic LEMS can be associated with other organic-specific autoimmune disorders. 10 Paraneoplastic cerebellar degeneration can also occur in cancer-associated LEMS cases.
11The diagnosis of LEMS can be challenging since the clinical presentation of sub-acute progressive fatigue and weakness is unspecific. As a result, diagnosis is often delayed from many months up to even decades. and appears to be as efficacious as the base in relieving the symptoms of LEMS. The product has also received orphan drug status in the US and is currently being evaluated in a multicenter, double-blind, placebo-controlled phase III trial to support New Drug Application (NDA) approval in the US. A recent safety trial in healthy volunteers using doses at and above normal levels has shown no effect on QT intervals, heart rate, or cardiac depolarization. Based on available clinical trial data, amifampridine phosphate was recently given Breakthrough Therapy designation by the FDA, which may enable fast-track NDA approval, thus increasing the potential for more patients with LEMS to receive an effective therapy.