What is primarily impaired in Eaton-Lambert syndrome?

In Eaton-Lambert syndrome, the primary impairment involves the release of acetylcholine (ACh) at the neuromuscular junction (NMJ). This condition is characterized by an autoimmune attack on presynaptic voltage-gated calcium channels, leading to reduced calcium influx when an action potential arrives at the nerve terminal. Since calcium is crucial for the release of ACh, its decreased availability results in insufficient ACh being released into the synaptic cleft. Consequently, this reduced neurotransmitter availability leads to muscle weakness, particularly after sustained activity, as the muscles do not receive the necessary signals to contract effectively.

The clinical manifestation often includes weakness that improves with repetitive nerve stimulation, highlighting the relation to the impaired ACh release. This phenomenon is in contrast to other conditions affecting the NMJ, where the problem may lie in the muscle's response to ACh or other factors unrelated to its release.