Which are the causes of Lambert-Eaton myasthenic syndrome?

Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder that affects the neuromuscular junction, causing muscle weakness and fatigue. The condition is characterized by a disruption in the communication between nerve cells and muscles, leading to impaired muscle contraction.

The exact cause of LEMS is not fully understood, but it is believed to be primarily associated with an autoimmune response. In autoimmune disorders, the immune system mistakenly attacks healthy tissues in the body, in this case, the neuromuscular junction. The immune system produces antibodies that target specific proteins involved in the transmission of nerve signals to the muscles.

One of the main causes of LEMS is the presence of autoantibodies against voltage-gated calcium channels (VGCCs). These channels are responsible for regulating the entry of calcium ions into nerve terminals, which is crucial for the release of neurotransmitters. In LEMS, autoantibodies bind to VGCCs and interfere with their normal function, reducing the release of neurotransmitters like acetylcholine. As a result, the communication between nerves and muscles is disrupted, leading to muscle weakness.

The exact trigger for the development of autoantibodies in LEMS is not well understood. However, it is believed that certain underlying conditions or factors may contribute to the development of the autoimmune response. Small cell lung cancer (SCLC) is strongly associated with LEMS, as approximately 60-70% of LEMS cases are found in individuals with SCLC. The tumor cells in SCLC produce proteins that are similar to the VGCCs found in the neuromuscular junction. This similarity may lead to the immune system mistakenly targeting both the tumor cells and the VGCCs, resulting in the development of LEMS.

In addition to SCLC, other malignancies such as breast, ovarian, and lymphoid cancers have also been associated with LEMS, although less frequently. It is believed that the presence of these tumors may trigger an immune response that leads to the production of autoantibodies against VGCCs.

Furthermore, genetic factors may play a role in the development of LEMS. Certain genetic variations have been identified in individuals with LEMS, suggesting a genetic predisposition to the condition. However, more research is needed to fully understand the genetic factors involved.

It is important to note that while the association between LEMS and cancer is significant, not all individuals with LEMS have an underlying malignancy. In some cases, LEMS may occur without any identifiable cause, referred to as idiopathic LEMS.

In conclusion, Lambert-Eaton myasthenic syndrome is primarily caused by an autoimmune response, with autoantibodies targeting voltage-gated calcium channels in the neuromuscular junction. The presence of certain malignancies, particularly small cell lung cancer, is strongly associated with LEMS. Genetic factors may also contribute to the development of the condition. However, further research is needed to fully understand the underlying causes of LEMS.