What is the pathophysiological cause of Lambert-Eaton Myasthenic Syndrome?

Lambert-Eaton Myasthenic Syndrome (LEMS) is primarily characterized by the body producing antibodies against the pre-synaptic voltage-gated calcium channels at the neuromuscular junction. This interference with calcium channel function results in a decreased release of acetylcholine (ACh) from the nerve terminals in response to nerve impulses. Consequently, muscle activation is impaired due to insufficient ACh binding to the postsynaptic receptors despite those receptors being intact.

In contrast to other neuromuscular disorders, which may involve direct targeting of the postsynaptic receptors or reduced neurotransmitter production, LEMS specifically involves an autoimmune attack targeting the pre-synaptic mechanism critical for ACh release. Thus, the specificity of antibody action in LEMS focuses on the calcium channels, which are essential for the docking and fusion of ACh-containing vesicles to the presynaptic membrane.