Lambert-Eaton myasthenic syndrome (LEMS)
Lambert-Eaton myasthenic syndrome (LEMS) is a rare disorder caused by a problem with the transmission of nerve signals to the muscles.
It results in muscle weakness and sometimes dryness of the mouth, constipation and impotence.
The immune system mistakenly attacks the nerve endings, which weakens the nerve impulses from the nerves to the muscles and prevents the muscles contracting (tightening) properly.
In about 50% of people with LEMS, the disease is triggered by an underlying lung cancer (the type associated with smoking). These people usually develop the disease in middle age or later.
There is no obvious trigger in the other 50% of patients with LEMS who don't have cancer. This form of the disease may start at any age.
LEMS is estimated to affect between 1 in 250,000 and 1 in 333,000 people worldwide. It is also known as myasthenic syndrome or Eaton-Lambert syndrome.
What are the symptoms?
LEMS causes weakness and sometimes aching in the arm and leg muscles. This can make it difficult to climb stairs, get up from sitting, and lift objects or raise the arms.
Very characteristically, people with LEMS have difficulty walking. They may describe this as "like walking through treacle".
Strength may improve initially when exercising, only to lessen as exercise continues.
The neck muscles can also be affected, making swallowing, chewing, speaking and even breathing difficult. Some people may struggle to keep their neck upright.
A few people will have weakness of the eye muscles, resulting in drooping eyelids.
Problems with the autonomic nervous system
The autonomic nervous system is the nervous system in charge of automatic body functions we don't need to think about, such as breathing, sexual arousal and swallowing.
When the nerves in the autonomic nervous system are affected, it may cause a wide range of symptoms, including a dry mouth, impotence, blurry vision, constipation and dizziness upon standing.
In about 50% of patients, LEMS is associated with small cell lung cancer, an aggressive type of cancer that spreads quickly.
Very rarely, it may be associated with other forms of cancer.
What is the cause?
LEMS is caused by a problem with the immune system. The body releases antibodies to attack the nerve endings as if they were invading germs.
Normally, nerve signals travel down the nerves and stimulate the nerve endings to release a chemical called acetylcholine. Acetylcholine comes into contact with the nearby muscle receptors, activating the receptors and causing the muscles to contract.
When antibodies attack the nerve endings in LEMS, it decreases the amount of acetylcholine that is released. The nerve impulse from the nerve to the muscle isn't strong enough, so the muscle cannot properly contract and becomes weak.
When someone with LEMS also has problems such as a dry mouth and blurred vision, it's because the nerves in the autonomic nervous system have been affected, too.
LEMS is not inherited.
How is it diagnosed?
If you have any of the above symptoms, see your GP.
They should look at your medical history and your symptoms, carry out a physical examination, and test your reflexes.
The symptoms of LEMS are common in a number of different conditions. For example, it's very similar to another autoimmune condition called myasthenia gravis. This means you'll need to be referred to a neurologist (a specialist in nervous system disorders), who will carry out some tests.
A special type of blood test can be used to detect the antibodies (proteins) that damage the nerve endings. These antibodies are not detectable in people without LEMS.
Nerve conduction tests
Electromyography is a procedure that can be used to identify communication problems between the nerves and muscles. It involves inserting a needle electrode through the skin into the muscle.
This produces an electrical recording of the muscle activity. If you have LEMS, your muscles will not respond very well to the electrical stimulation.
A nerve stimulation test is also used, and can show whether the transmission of signals between the nerve and muscle is poor.
How is it treated?
Anyone who has been diagnosed with LEMS must first be investigated for possible underlying cancer. If cancer is present, this needs to be treated. Removal of the cancer can significantly improve symptoms.
LEMS cannot be cured, but the symptoms can be managed through a variety of approaches:
by stimulating greater release of acetylcholine – through the use of 3,4-diaminopyridine
by prolonging the activity of the acetylcholine that is released– with a drug called pyridostigmine
by reducing the levels of the antibodies causing the condition– with steroids or immunosuppressant drugs
You can also use intravenous immunoglobulin or plasma exchange to temporarily improve your condition while waiting for immunosuppressant drug therapy to become effective.
These treatment options are covered below.
3,4-diaminopyridine (DAP) tablets increase the release of acetylcholine from nerve cells. DAP is usually well tolerated and effective. It may be used in combination with pyridostigmine.
Pyridostigmine tablets slow down the breakdown of acetylcholine. They can sometimes cause side effects, such as stomach cramps, muscle twitching, diarrhoea and nausea. Your doctor will be able to prescribe additional medication for you if you experience these.
These medicines tend to work best in cases of mild LEMS. They can improve muscle contractions and strength in the affected muscles. They are always used as the first line of treatment.
If these simple treatments are not effective in controlling symptoms, you may be tried on steroid tablets (prednisolone). Initially, a high dose is required to bring the condition under control, which may take many months.
Such high doses can cause side effects (weight gain, high blood pressure, diabetes, cataracts, and osteoporosis).
Doctors may prescribe an additional medication that suppresses the immune system, such as azathioprine or methotrexate. These are slow to act, but in the long term may allow you to reduce the dose of steroids and therefore reduce the risk of side effects.
Regular blood monitoring is required for all people taking these immunosuppressants. All of these medications have associated side effects that your doctors will discuss with you.
Plasmapheresis and immunoglobulin therapy
Plasmapheresis or intravenous immunoglobulin therapy may be needed in very severe cases of LEMS, where a person has such severe muscle weakness that it is causing life-threatening breathing or swallowing problems.
Plasmapheresis involves redirecting your blood through a machine, which removes the plasma that contains the harmful antibodies.
Intravenous immunoglobulin therapy means you're given an injection of normal antibodies from donated blood. This temporarily changes the way your immune system operates.
Both treatments can produce a rapid improvement in the symptoms of LEMS, but the benefits usually only last a few weeks. They are therefore not suitable as long-term treatments, and are usually only used to treat people who are seriously ill while they are waiting for other treatments to become effective.
What's the outlook?
Some people respond well to medication and are able to stop using all steroids when their symptoms stop (in remission), while continuing to take secondary immunosuppressant medication.
In time – usually years – it may be possible for some patients to stop all immunosuppressant medication if they remain well.
Others respond less well to medication and find the disease affects their everyday activities and quality of life.
If there is no cancer, LEMS does not shorten life. But people with small cell lung cancer will have a shorter life expectancy because of the aggressive nature of the cancer. They can develop complications such as difficulty breathing, difficulty swallowing and pneumonia.