LEMS: Unraveling the Rare Neurological Connection

By Christophe Rude Jul 14, 2023 #LEMS
LEMS Unraveling the Rare Neurological ConnectionLEMS Unraveling the Rare Neurological Connection

Researchers are unraveling the rare neuromuscular disorder Lambert-Eaton Syndrome. The condition causes a lack of a chemical called acetylcholine, which transmits impulses between nerves and muscles. The disease is similar to myasthenia gravis (MG) but differs because the transmission defect is presynaptic rather than postsynaptic. MG also has different autoantibodies from LEMS.

What is Lambert-Eaton Syndrome?

Lambert-Eaton syndrome (LEMS) is an autoimmune disorder affecting the acetylcholine receptors in nerve and muscle cells. During LEMS, autoantibodies attack presynaptic voltage-gated calcium channels, interfering with the regular presynaptic calcium influx required for acetylcholine release and resulting in weakness. In some cases, LEMS coexists with MG, and this combination is called myasthenia gravis Lambert-Eaton overlap syndrome. The symptoms of LEMS can appear in different ways in each person. Most often, they start in the leg muscles (upper legs) and then progress to the arms and shoulders, fingers and toes, or the muscles that help with speaking and swallowing.

In the early stages of the disease, patients may also experience trouble breathing. It is not uncommon for patients with LEMS to have a malignancy, so a medical team, including an oncologist, surgeon, hematologist, neurologist, and ophthalmologist, must evaluate them. If the diagnosis is nonparaneoplastic Lambert-Eeaton syndrome (NT-LEMS), a patient’s survival rates are similar to those of the general population, and long-term function and health-related quality of life are not significantly affected. If cancer is identified, however, it has been shown that the prognosis for the patient with LEMS is much worse. This is because the underlying tumor can cause further damage to the nervous system and increase weakness or other symptoms.

How is Lambert-Eaton Syndrome Diagnosed?

Lambert-Eaton syndrome is a rare neuromuscular disorder. It happens when your immune system makes antibodies that attack the contact point between motor nerves and muscles — called the neuromuscular junction. This disrupts signals to your muscles, causing weakness. In more than half of cases, the antibody attacks P/Q-type voltage-gated calcium channels on presynaptic nerve terminals. This reduces the acetylcholine released from these nerve cells, leading to muscle weakness.

Most people with LEMS also have fatigue and autonomic dysfunction. Your healthcare provider will review your symptoms and do a physical exam. They may order a blood test to check for antibodies that cause Lambert-Eaton syndrome. You’ll also have an electromyography, which measures how well your muscles are working. Your healthcare provider can also look for signs of this condition by testing your muscle action potential size after repetitive nerve stimulation, during exercise, or after a drug called pyridostigmine. The size of this potential should get larger after you contract your muscles, a sign that the nerves are sending signals to your muscles to contract.

What are the Symptoms of Lambert-Eaton Syndrome?

Lambert-Eaton syndrome is a rare disorder that causes your body’s immune system to attack the contact point between nerves and muscles — the neuromuscular junction. This damage impairs the transmission of signals to muscles, causing weakness. This weakness usually begins in the legs but can spread to other muscle groups and your lungs. The condition may also be accompanied by other signs of cancer or autoimmune diseases such as vitiligo, which causes loss of skin pigmentation. There are two types of conditions: Those associated with cancer (CA-LEMS) and those that do not (NCA-LEMS). People with CA-LEMS have anti-P/Q voltage-gated calcium channel and synaptotagmin antibodies in their bodies. This type of LEMS is considered a paraneoplastic syndrome because it is associated with small-cell lung cancer. When a person develops CA-LEMS, looking for the cancer that caused it is essential because early detection and treatment can improve the outcome.

How is Lambert-Eaton Syndrome Treated?

Lambert-Eaton syndrome is an autoimmune disorder in which the immune system attacks the contact points where nerves and muscles connect. These are called neuromuscular junctions. When they are damaged, the nerve cells cannot send enough signals to muscle fibers, and the muscles weaken. Lambert-Eaton syndrome develops most often in people with small-cell lung cancer and can also occur in people without cancer. The underlying cancer is found and treated in over half of all cases. This helps to improve symptoms of the condition. But sometimes, the weakness caused by this condition persists even after the cancer is treated. This is sometimes referred to as paraneoplastic Lambert-Eaton syndrome, and it can improve with medicines that help increase communication between nerves and muscle fibers.

The most common medications used to treat paraneoplastic Lambert-Eaton Syndrome are anticholinesterase agents. It reduces the breakdown of acetylcholine, a chemical that transmits nerve impulses to the muscles. Another medication is 3,4-aminopyridine, which prolongs the opening of voltage-gated calcium channels, releasing more acetylcholine at the synaptic junction. People with a non-tumor Lambert-Eaton Syndrome can benefit from cancer screening. It includes a CT or MRI scan and a PET scan of the chest. Doctors should consider the possibility of a malignant tumor if they find that someone has weak muscles, especially if they are over 60 and have no family history of lung cancer.

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