Lambert-Eaton syndrome (LEMS) disrupts the communication between nerves and muscle fibers due to autoimmune activity. Typically associated with, occurring alongside, or developing after specific cancers, particularly small-cell lung cancer in men,
In LEMS, antibodies target voltage-gated calcium channels at the neuromuscular junction, hindering the release of acetylcholine, which is responsible for transmitting nerve signals. This results in gradual and escalating muscle weakness over weeks or months.
Symptoms
The immune system acts as a protective shield, warding off bacteria, viruses, toxins, and cancer cells. In response to detecting harmful substances, it generates antibodies, specialized proteins that eradicate these threats. Yet, in cases of autoimmune diseases, the immune system erroneously identifies its own cells as foreign entities, leading to an attack on the body’s own tissues.
Individuals with LEMS face a greater than 50% likelihood of developing small-cell lung cancer, the predominant cancer type associated with this syndrome. This connection is often attributed to a shared gene alteration linked to autoimmune conditions.
Regardless of their history with cancer, it is advised for everyone who exhibits symptoms of LEMS to get a thorough cancer test. Blood tests, assessments of muscle function (such electromyography and nerve conduction studies), physical examinations, and X-rays of the lungs are all examples of diagnostic techniques. Given the connection to cancer, further tests like CT or MRI scans could be used to look for any potential malignancies. To treat this disorder’s symptoms, doctors may also recommend drugs that increase acetylcholine release.
Diagnosis
The immune system protects the body against bacteria, viruses, toxins, and cancer cells. When it detects harmful substances, it produces proteins called antibodies that destroy them. But sometimes, the immune system mistakes its cells for these foreign substances and attacks them. This is what happens in people with autoimmune diseases.
Understanding Lambert-Eaton syndrome occurs when the body’s immune system attacks the connections between nerves and muscles. It most often occurs in people with small-cell lung cancer but can also happen in people without cancer. Symptoms include weak muscles, trouble walking, tingling sensations, and fatigue.
In 1956, American neurologists Edward H. Lambert and Lee M. Eaton described six patients with a neuromuscular disorder similar to myasthenia gravis, although there were some differences. The patients had a characteristic electrophysiological pattern on repetitive nerve stimulation (RNS) tests and were found to have serum P/Q-type voltage-gated calcium channel (VGCC) antibodies.
These antibodies are believed to target the presynaptic VGCC in the muscle terminal, which prevents the release of the chemical acetylcholine and thus causes the weakness seen in LEMS. Half of people with this autoimmune disease have associated small-cell lung cancer (SCLC), which also expresses functional VGCC.
Doctors can diagnose this condition by reviewing symptoms and doing a physical exam. They may also order X-rays or CT scans of the lungs to look for any cancerous growths. A blood test can also confirm that you have the antibodies.
Treatment
In Lambert-Eaton syndrome, your immune system attacks the neuromuscular junctions, where nerves and muscles connect. This makes it hard for them to send the signals that control muscle movement. The weakness develops slowly, typically in the hip and thigh muscles, then spreads to the shoulders, arms, and legs. Eventually, even the muscles that connect the head, face, eyes, nose and ears to the brain (cranial nerves) can weaken. You may have trouble getting up from a chair or climbing stairs, and your muscles often cramp and tire easily.
In more than half of the cases of LEMS, it is associated with cancer such as small-cell lung cancer. This is called paraneoplastic LEMS (P-LEMS). The tumor may cause P-LEMS symptoms by blocking certain cell calcium channels. In the remaining cases, there is no clear relationship to cancer.
The first step in diagnosing a neuromuscular junction disorder such as LEMS is doing a physical exam and recording your symptoms. Your doctor will also check your medical history.
Several tests can help diagnose this condition, including electrophysiology and blood tests for anti-P/Q-type voltage-gated calcium channel antibodies. These are released by nerve endings when they release the chemical acetylcholine to start nerve-muscle communication. Other testing includes a test for areflexia and autonomic dysfunction, which are typical in this condition.
Prevention
The autoimmune disease Lambert-Eaton syndrome impairs the communication between nerve cells and muscles. It usually precedes, occurs with, or develops after certain types of cancer, especially small-cell lung cancer (SCLC) in men. It may also happen without cancer as part of a paraneoplastic syndrome. Symptoms of this rare disease include muscle weakness, fatigue, and dry mouth.
In LEMS, autoantibodies attack the part of your motor nerve called the neuromuscular junction. This damage prevents the release of a chemical called acetylcholine, which transmits nerve signals to muscles. This results in the weakness you see with LEMS.
Weakness in LEMS usually starts in the proximal muscles of your legs or arms. It then spreads to other forces, such as those in your shoulders and hands, and the powers that help you speak and swallow. The weakness gets worse over time, and you may have trouble breathing.
The cause of LEMS isn’t clear, but it seems to happen when your immune system mistakes the calcium channels on the nerve endings for a cancer cell and releases antibodies that destroy the media. This leads to the onset of the classic clinical triad of proximal muscle weakness, autonomic dysfunction, and absent deep tendon reflexes. Usually, the cancer-associated LEMS (CA-LEMS) type occurs in people with SCLC. Other cases of CA-LEMS occur in people with non-small-cell lung cancer, such as adenocarcinoma and non-squamous NSCLC.