Lambert-Eaton Myasthenic Syndrome (LEMS)

What is Lambert-Eaton myasthenic syndrome (LEMS)?

Lambert-Eaton myasthenic syndrome (LEMS), also known as Eaton-Lambert syndrome and Myasthenic Syndrome of Lambert Eaton, is an autoimmune disorder. In this condition, your body’s own immune system attacks the contact point between motor nerves and muscles — the so-called neuromuscular junction. The damage at this contact point impairs signaling to your muscles, causing weakness. This weakness usually begins in your upper legs, but can come to involve other muscle groups in your arms, as well as muscles involved in breathing, swallowing and speech.

Who gets Lambert-Eaton myasthenic syndrome (LEMS)?

Two groups of people develop Lambert-Eaton myasthenic syndrome.

About 60% of cases happen in people who have an underlying malignancy. The most common is small-cell lung cancer. Symptoms of LEMS can begin many months or years before the cancer develops or is diagnosed. People tend to be older, with a diagnosis around the age of 60. It’s more commonly seen in people assigned male at birth (AMAB) and in people with a history of using tobacco products.

In about 40% of LEMS cases, no underlying cancer is identified. These people tend to be diagnosed at two peaks: around the age of 35 and a second peak occurring at the age of 60. Both sexes tend to be equally affected in this group.

LEMS is rare in children.

Is small-cell lung cancer the only cancer that happens in people with Lambert-Eaton myasthenic syndrome (LEMS)?

While small-cell lung cancer is the most common malignancy associated with LEMS, other cancers have also been associated with the development of LEMS, including prostate cancer, thymoma and lymphoproliferative disorders. Given that LEMS can develop before a person may show signs of cancer, your healthcare provider should ensure you undergo a thorough assessment for cancer if they make the diagnosis of LEMS.

Do genetic changes cause Lambert-Eaton myasthenic syndrome (LEMS)?

Scientists think there may be a genetic link to autoimmune diseases in general. Lambert-Eaton myasthenic syndrome is an autoimmune disease.

How common is Lambert-Eaton myasthenic syndrome (LEMS)?

Lambert-Eaton myasthenic syndrome is a rare disease. Worldwide, it affects about 2.8 million people. In the U.S., about 400 people have LEMS.

What are the symptoms of Lambert-Eaton myasthenic syndrome?

Lambert-Eaton myasthenic syndrome symptoms include:

• Muscle weakness and muscle fatigue.
• Trouble walking.
• Muscle pain or stiffness.
• Tingling sensation in your hands or feet.
• Droopy eyelids (ptosis).
• Double vision (diplopia).
• Dry mouth (xerostomia) and dry eyes.
• Constipation.
• Decreased sweating.
• Weight loss.
• Difficulty peeing.
• Erectile dysfunction.
• Trouble speaking (dysarthria) and trouble swallowing (dysphagia). These are late-stage symptoms.
• Trouble breathing (dyspnea) and respiratory failure. This is an uncommon, late-stage symptom.

How does Lambert-Eaton myasthenic syndrome typically appear and progress?

Lambert-Eaton myasthenic syndrome typically affects leg muscle strength (upper leg) first, followed by shoulder muscles, muscles of your hands and feet, muscles affecting your speech and swallowing, and eye muscles.

Early in the disorder, you may have trouble getting up from a chair, walking up stairs or a steep walkway, or doing anything strenuous with your legs.

Symptoms usually develop slowly over weeks to many months. Symptoms develop more quickly if you have cancer and LEMS.

What causes Lambert-Eaton myasthenic syndrome (LEMS)?

Lambert-Eaton myasthenic syndrome is an autoimmune disorder. This means your body’s natural defenders (antibodies) attack your own healthy tissue. In LEMS, your antibodies attack where nerve cells meet muscle fibers (neuromuscular junction); more specifically, at calcium channels that are critical in signaling at this contact point.

Like a lineup of dominoes, the attack causes a sequence of events:

1. Antibodies bind to and block calcium channels at the end of nerve cells.
2. Fewer calcium channels mean less of the neurotransmitter acetylcholine is released. Acetylcholine is critical to signal your muscles to activate.
3. As there isn’t enough acetylcholine released, not enough “messages” reach muscle fibers, and then your muscles can’t be fully activated. Your muscles won’t function as they normally should, which causes weakness.

LEMS happens in people who have small-cell lung cancer. In this case, your body’s antibodies recognize their “call to action” when there’s cancer in your body. However, instead of attacking the cancer cells (specifically, the calcium channel on cancer cells), it attacks the calcium channel at the end of nerve cells. And the sequence listed above happens. When this happens, your muscle cells can’t pick up the message to contract to make your muscle move.

Scientists think the cause of LEMS in people who don’t have lung cancer is an immune response that simply goes awry. It remains unclear why this happens.

How is Lambert-Eaton myasthenic syndrome (LEMS) diagnosed?

The first step in the diagnosis of LEMS is a thorough evaluation by your healthcare provider, in most cases a general neurologist or a neurologist who specializes in disorders of nerves and muscles. A detailed history of your symptoms, as well as a review of your medical and medication history, is part of this process. A detailed neurological examination is often done to look for patterns of weakness and signs consistent with a diagnosis of LEMS.

The next step in the evaluation is testing. Testing for LEMS includes:

• Blood test. A blood test can reveal if you have anti-calcium channel antibodies. About 85% of people with LEMS have these antibodies in their blood.
• Electromyography. This test shows how well your muscles and nerves are working together. LEMS produces very specific findings on electromyography that can help confirm a diagnosis.
• Lung X-ray or computed tomography (CT) scan or magnetic resonance imaging (MRI) of your chest. These imaging tests check for signs of lung cancer, as LEMS can happen in people who have small-cell lung cancer.

LEMS can appear from months to up to six years before the cancer does. The typical lung cancer screening schedule is every three to six months for at least two years after your diagnosis. Your healthcare provider will recommend a screening schedule that’s appropriate for you.

How is Lambert-Eaton myasthenic syndrome (LEMS) treated?

Lambert-Eaton myasthenic syndrome (LEMS) treatments include:

• Treatment of the underlying cancer. If LEMS is associated with a cancer like small-cell lung cancer, treating the cancer can help treat LEMS. Cancer treatment may include chemotherapy, radiation therapy and/or surgery based on the type of cancer and the recommendations of your healthcare providers.
• Treatments for LEMS include symptomatic treatment (medicines designed to alleviate some of the symptoms of the disorder) and immune-modulating treatments, which help to control your immune system’s attack on your body.

Symptom treatment

• Amifampridine (Firdapse®), Guanidine. These medications improve muscle strength. They increase the release of the neurotransmitter acetylcholine at the neuromuscular junction, improving the signaling of your muscles.
• Pyridostigmine (Mestinon®). Pyridostigmine helps prevent the breakdown of acetylcholine at the neuromuscular junction. This helps increase the signaling of acetylcholine to improve muscle strength. Pyridostigmine is sometimes taken with amifampridine to improve muscle function and treat dry mouth, dry eyes, constipation, impotence and decreased sweating that occurs with LEMS. Using pyridostigmine to treat LEMS is an off-label use. This means it’s not approved by the U.S. Food and Drug Administration (FDA) for this condition.

Immune-modulating treatment

• Immunosuppressants. These medications help hold back your immune system’s “defensive” action. Your healthcare provider may prescribe these medications if others aren’t managing your symptoms. An example of an immunosuppressant is prednisone, given with or without azathioprine or cyclosporine.
• Plasma exchange. In this procedure, a machine separates the liquid part of your blood (plasma) from blood cells. Your antibodies are in your plasma. After separation, your blood is returned to your body. Your healthcare provider may consider this treatment if you have severe symptoms that need immediate attention.
• Immunoglobulins. In some individuals, high-dose immunoglobulin therapy may help keep the disease from getting worse.

Can Lambert-Eaton myasthenic syndrome (LEMS) be prevented?

The exact cause of Lambert-Eaton myasthenic syndrome isn’t completely understood. So it’s not entirely known if there’s any way to prevent the disorder.

However, because LEMS can occur in people who have lung cancer, you can help prevent lung cancer by:

• Not smoking. If you’re a user of tobacco products, ask your healthcare provider about quitting tips.
• Avoiding second-hand smoke.
• Getting your home checked for radon. Exposure to radon for a long time can increase your risk of lung cancer.

You can also take steps to maintain a healthy lifestyle, including:

• Eat more fruits and vegetables. Follow the Mediterranean or DASH diet.
• Maintain a healthy weight.
• Exercise as advised by your healthcare provider.
• Get adequate sleep — usually seven to nine hours.
• Reduce your stress level. Stress can make your symptoms worse.
• Avoid hot showers or baths. Heat can make the symptoms of Lambert-Eaton myasthenic syndrome worse.
• See your healthcare provider regularly, and any time your health changes or you develop symptoms.

Is there a cure for Lambert-Eaton myasthenic syndrome?

There isn’t a cure for Lambert-Eaton myasthenic syndrome. Treatment for an underlying cancer associated with LEMS has been shown to improve LEMS-related symptoms. Immunosuppressive drugs can help control the autoimmune attack, as well as control symptoms along with symptomatic treatments that improve muscle strength by increasing the amount of acetylcholine at the nerve endings

If you have LEMS without cancer, you can expect a near-normal length of life. If you have LEMS and a cancer that was found early and managed, your symptoms may improve over time (but not to full recovery).

Your quality of life largely depends on the severity of your symptoms.

When should I contact my doctor if I have Lambert-Eaton myasthenic syndrome (LEMS)?

Contact your healthcare provider any time your health changes or your symptoms worsen.

What’s the difference between Lambert-Eaton myasthenic syndrome (LEMS) and myasthenia gravis (MG)?

Lambert-Eaton myasthenic syndrome and myasthenia gravis share some similar symptoms. They both cause muscle weakness and rapid muscle fatigue.

Myasthenia gravis commonly affects the muscles around your eyes and muscles used for swallowing first. Then, it can affect muscles more generally, including breathing muscles and muscles of your arms and legs.

LEMS usually begins with weakness in your upper legs and later involves your arms. LEMS can cause weakness of eye muscles, but this is usually mild compared to myasthenia gravis.

Severe respiratory muscle weakness (muscles that help you breathe) can be fatal in MG. This is rare in LEMS.

People with MG don’t often show signs of autonomic dysfunction such as dry eyes, dry mouth, constipation, decreased sweating and impotence. In contrast, people with LEMS more commonly have these complaints and can sometimes help in differentiating between the two conditions.

A note from Cleveland Clinic

Lambert-Eaton myasthenic syndrome (LEMS) is a disease caused by an immune system that has gone awry. Your nerve cells aren’t sending enough “messages” telling your muscle fibers to contract. The result is muscle weakness and other symptoms. Small cell lung cancer is present in about 60% of people with LEMS. If you have LEMS, but don’t have cancer, make sure you and your provider are scheduling cancer screenings every few months for at least two years after your diagnosis. Treatments include treating cancer (if it’s present) and taking medications that help increase nerve cell-muscle fiber communication. Increasing communication improves muscle strength and other symptoms.