Lambert-Eaton Syndrome and Small-Cell Lung Cancer

Medically Reviewed by Sabrina Felson, MD on July 24, 2022
6 min read

Lambert-Eaton syndrome, or Lambert-Eaton myasthenic syndrome, is a rare autoimmune disease that affects some people with small-cell lung cancer (SCLC). A problem with the immune system disrupts the nerve signals that tell your muscles to move, which causes weakness of the legs, arms, and sometimes the face.

It's possible to have symptoms of Lambert-Eaton syndrome up to 6 years before SCLC is discovered. Muscle weakness could be the tip-off that leads your doctor to a lung cancer diagnosis.

Though there's no cure for Lambert-Eaton syndrome, treating your cancer should help bring your symptoms under control. If you notice any muscle weakness, especially in your arms or legs, it's important to see your doctor to find the cause.

Lambert-Eaton syndrome is an autoimmune disease. Normally, your immune system protects you against germs and other harmful substances. In Lambert-Eaton syndrome, it mistakenly attacks the neuromuscular junction – the place where your nerves and muscles connect.

To make your muscles work, electrical impulses travel down motor nerves. When these impulses get to the nerve ending, they open little gates called calcium channels to release the chemical messenger acetylcholine into the neuromuscular junction. Acetylcholine makes your muscles contract.

Lambert-Eaton syndrome damages the part of your nerve endings that release acetylcholine. Less of this chemical is released, which weakens the signal that reaches your muscle cells. That's why your muscles can't contract as strongly and you feel weak.

This condition is very rare, even in people with small-cell lung cancer. It affects around 3% of people with SCLC. Only about 400 people in the United States have Lambert-Eaton syndrome.

More than half of people diagnosed with Lambert-Eaton syndrome either have or will eventually get small-cell lung cancer. The connection between the two diseases is thought to be your immune system and the calcium channels present on your nerve endings and in small-cell lung cancer cells.

Your immune system releases proteins called antibodies against cancer. Because small-cell lung cancer cells contain the same calcium channels as nerve endings, the immune system sometimes mistakes the nerve endings for a threat. It releases antibodies that damage some of the calcium channels.

Lambert-Eaton syndrome is very rare, even in people with small-cell lung cancer. You're more likely to get this condition if you:

  • Are over 60 years old
  • Smoked cigarettes for a long time
  • Were assigned male at birth

A small percentage of people with Lambert-Eaton syndrome don't have cancer. Many of them have a gene change that's linked to autoimmune diseases.

The main symptom is weakness as motor nerves become damaged. Lambert-Eaton syndrome affects both voluntary muscles – the ones you control – and muscles of your autonomic nervous system that you don't control.

Weakness often starts in the upper legs, hips, arms, and shoulders. Your legs and arms might feel heavy, making it hard to walk, climb stairs, or lift your arms. The weakness should improve when you exercise. You might also feel an aching or tingling in your muscles.

Less often, Lambert-Eaton syndrome affects muscles of the face and causes symptoms like:

  • Eyelid drooping
  • Double vision or blurred vision
  • Problems chewing, swallowing, and speaking

Damage to your autonomic nerves can cause symptoms like these:

  • Dry mouth
  • Dry eyes
  • Constipation
  • Trouble controlling erections in men, called erectile dysfunction
  • Reduced sweating
  • Dizziness when you stand up

Lambert-Eaton syndrome also affects nerve signals to muscles that control breathing and blood pressure. If the condition gets severe enough, it may be hard to breathe.

Symptoms slowly get worse over a period of weeks or months as the nerve signals are interrupted. When you have cancer, your symptoms may come on faster.

It is very difficult to diagnose this condition.

Weakness, nerves tingling, and other symptoms are reasons to visit your primary care doctor, who will ask about your symptoms and do an exam. If your doctor thinks you have a problem with your nerves or muscles, they will send you to a neurologist for more tests.

A blood test checks for the antibodies that are attacking your nerves. Up to 90% of people with Lambert-Eaton syndrome have antibodies against calcium channels in their blood.

Electromyography (EMG) is a test that places a thin needle into your skin and muscle to test the speed of signals from your nerves to your muscles. A monitor shows the electrical activity in your muscles when you move and when you're at rest.

Slower than normal nerve signals are a sign of Lambert-Eaton syndrome. EMG can also rule out myasthenia gravis, a more common autoimmune disease that also affects the muscles.

Because Lambert-Eaton syndrome has such a strong link to small-cell lung cancer, your doctor should test you for cancer if you haven't been diagnosed already. Tests to diagnose lung cancer include:

If these tests don't show cancer, your doctor will likely check you again every few months.

There is no cure for Lambert-Eaton syndrome, but a few treatments can help you manage the symptoms. The first step is to treat your cancer with chemotherapy, surgery, radiation, and other therapies. These treatments should improve Lambert-Eaton syndrome symptoms, too.

Amifampridine (Firdapse) is the only medicine approved to treat muscle weakness from Lambert-Eaton syndrome. Firdapse is a potassium channel blocker. It makes your body release more acetylcholine to strengthen the nerve signals to your muscles.

Ruzurgi is a version of amifampridine that's approved for children, although Lambert-Eaton syndrome is rare in children. Both medicines have a small risk of causing seizures.

If Firdapse doesn't improve your symptoms enough, there are a few other treatments you might try:

Pyridostigmine (Mestinon) is a medicine that increases acetylcholine release to improve signals between your nerves and muscle cells. Mestinon helps with weakness and autonomic symptoms like dry mouth, dry eyes, and constipation. You have to take it a few times a day for it to work.

Immune-suppressing medicines like steroids (prednisone), azathioprine (Azasan, Imuran), and methotrexate (Rheumatrex, Trexall) calm your immune system to stop it from damaging your nerves.

Immunoglobulin therapy is a treatment where you get antibodies from a healthy donor to stop your immune system from attacking your nerves.

Plasmapheresis filters the harmful antibodies out of the liquid part of your blood (plasma). This treatment can also help with muscle weakness.

There are other things you can do, besides taking medicine, to control your symptoms. Lambert-Eaton syndrome tends to flare up with stress, heat, and lack of sleep.

Try relaxation techniques like meditation and deep breathing to manage stress. Take lukewarm showers instead of hot ones and keep the air conditioning on in warm weather. Let your doctor know if you get an infection that causes a fever.

Get enough sleep by going to bed at the same time each night and waking up at the same time each morning. Exercise as often as you can to preserve your muscle strength.

The effects of Lambert-Eaton syndrome are different in each person. Some people respond well to treatment and go into a long-term remission where they have no symptoms. Others have symptoms that come and go or get worse over time.

Severe symptoms like trouble breathing and swallowing are rare, and they usually happen after many years of living with the disease. Getting on a treatment plan can prevent Lambert-Eaton syndrome from causing you disability or affecting your daily life.

Lambert-Eaton syndrome isn't life-threatening. In fact, some people with this condition survive longer with small-cell lung cancer than those without it. This may be because your overactive immune system attacks the tumor.

Getting support can help you live better with Lambert-Easton syndrome. Your medical team is one good source of information and advice. You can also turn to an organization like the Muscular Dystrophy Association or the National Institute of Neurological Disorders and Stroke (NINDS).