Table of ContentsView AllTable of ContentsSymptomsCausesDiagnosisTreatmentTumor SurveillancePrognosis
Table of ContentsView All
View All
Table of Contents
Symptoms
Causes
Diagnosis
Treatment
Tumor Surveillance
Prognosis
Verywell / Katie Kerpel
The symptoms of LEMS don’t come on rapidly, as they might if one were having a stroke. Instead, they generally begin slowly and gradually worsen with time.
Fatigue and muscle weakness are key symptoms of LEMS. The fatigue may be intense and worse after exercise.
The muscle weakness usually first affects the muscles of the upper legs. This leads to problems with climbing stairs or getting oneself up out of a deep chair. Weakness of the upper arms usually comes next. Eventually, the weakness may spread to the lower arms and legs and eventually to the hands and feet.
People with LEMS also often develop symptoms due to problems with theautonomic nervous system, the part of your nervous system that unconsciously regulates many body functions.
These might include:
Some people with LEMS also have symptoms related to their eyes. These might includedrooping eyelidsor double vision.
LEMS also sometimes causes difficulty swallowing or speaking. However, these symptoms tend to be mild and temporary, if present.
In people who have LEMS from underlying small-cell lung cancer, symptoms of LEMS usually occur before any symptoms from the lung cancer.
LEMS occurs because of problems at an area called the neuromuscular junction. This is a part of the body where a neuron, traveling from the spinal cord, meets up with a muscle.
Normally, a signal from the brain sends a message through this neuron to move the muscle. To send this signal, the neuron receives a nerve signal that causes some calcium channels to open. This causes some calcium ions to rush inside the neuron.
In LEMS, antibodies to these calcium channels are produced. Because of this, fewer of these channels can work properly. That means that less neurotransmitter signal to the muscle can be released. Sometimes antibodies to the other parts of the neuromuscular junction are present as well.
Because of all this, the involved muscle doesn’t contract as well. That leads to the symptoms of LEMS.
LEMS From Cancer
In around 50% to 60% of people with LEMS, these antibodies form as a part of an individual’s immune response to a cancer. This can happen from a type of lung cancer known as small-cell lung cancer. It has been very rarely found in cancers such as non-small cell lung cancer, thymoma, and prostate cancer.
No one knows for sure why some people with small-cell lung cancer develop such antibodies and why some don’t. Sometimes LEMS that is associated with cancer is called T-LEMS.
Idiopathic LEMS
Some people get LEMS, even though they don’t have an underlying cancer. It’s thought that antibodies to these calcium channels are also present, as they are for people with T-LEMS. These individuals are said to have “idiopathic” LEMS.
Although it’s not clear what is going on with idiopathic LEMS, dysregulation of the immune system seems to play a role. People with idiopathic LEMS commonly have variations of certain immune system genes (HLA genes) that increase one’s risk of different autoimmune diseases.
Such individuals also have an increased risk of autoimmune diseases, such astype 1 diabetes, compared to people in the general population.
Idiopathic LEMS vs. T-LEMS
On average, symptoms may progress more rapidly when someone has LEMS from small-cell lung cancer compared to idiopathic LEMS.
People with T-LEMS are more likely to be men than women. Diagnosis happens around an average age of 60. Most people with idiopathic LEMS, in contrast, are women, and the most common age of onset is in the mid-30s.
Unfortunately, a correct diagnosis of LEMS doesn’t always happen right away. Because it is such a rare disease, it’s important that clinicians think of it as a possibility.
Neurologists can bring special expertise to the diagnostic process. They must consider not only diseases that can affect the nervous system but also causes that affect the musculoskeletal system.
Medical History and Clinical Exam
Medical history and clinical exam are critical parts of diagnosis. Through these alone, a clinician might suspect LEMS.
Your clinician should ask about all your current symptoms as well as your other medical conditions. It’s especially important to ask about autonomic symptoms. Such symptoms are often not as concerning to patients compared to their intense fatigue and muscle weakness, so they might not think to bring them up.
The medical exam itself, especially a completeneurological exam, also gives important clues. In a person with muscle weakness of the upper legs, decreased reflexes, and autonomic-type symptoms (e.g., sweating, constipation, dry mouth), LEMS is a strong possibility.
It’s also important to investigate medical symptoms or exam findings that might make lung cancer more likely. For example, your healthcare provider should ask about whether you’ve ever smoked and whether you have a cough.
Healthcare providers need to distinguish LEMS from other possibilities that might cause some similar symptoms. For example, a condition calledmyasthenia gravishas some similar symptoms, and it is much more common than LEMS. However, it is more likely to cause eye symptoms than LEMS.
If a clinician is concerned about LEMS, some other diagnostic tests can be helpful.
Antibody Tests
Antibody tests are very helpful in confirming a diagnosis. Most people with LEMS will have antibodies to one or more of the types of calcium channels at the neuromuscular junction. (You might see these written as P/Q type VGCCs.)
A blood test which shows high amounts of these antibodies means that LEMS is likely to be the cause of symptoms.
However, these tests are not perfect. A minority of people with small-cell lung cancer have high amounts of these antibodies even though they don’t have symptoms of LEMS. Also, a small percentage of people with LEMS do not have high amounts of these antibodies.
On the other hand, some types of antibody tests can help to eliminate other possible causes. Your healthcare provider might also order antibody tests for acetylcholine receptors. These would be expected to be high in a person with myasthenia gravis but low in a person with LEMS.
Electrophysiology Tests
Sometimeselectrophysiology testscan help confirm a diagnosis as well. A test like electromyography (EMG) can provide some helpful information. Repetitive nerve stimulation studies (RNS) are even more helpful and can usually be used to confirm a diagnosis.
These tests provide information about how signaling is working at the neuromuscular junction when the nerve is active and resting. In both, an electrode is inserted into your muscle and the electrical activity is monitored. These two types of tests are usually performed during the same visit.
Cancer Diagnosis
It’s also critical to investigate whether a cancer, particularly small-cell lung cancer, might be present. For this reason, it’s usually recommended that people diagnosed with LEMS receive a computed tomography (CT) scan of the chest.
If that doesn’t show anything, you might still need other imaging tests, like a positron emission tomography scan (PET scan).These tests can help detect a lung cancer, if present, unless the cancer is still very small.
If you do have a small-cell lung cancer, you might needadditional testingto find out more about your disease and see if it has spread. For example, you may need a biopsy of the cancerous area.
Medications
Unfortunately, we don’t have good ways to cure LEMS for people with idiopathic disease. However, we do have some therapies that can help reduce symptoms. This may be helpful both for people with idiopathic LEMS and people with LEMS from cancer.
The most recommended treatment is Firdapse.(The generic name is amifampridine or 3,4-DAP). The version of the medication that has been FDA approved for children is sold under the name Ruzurgi.
This drug allows more of the calcium channels to open when the nerve signals, decreasing symptoms. Unfortunately, this treatment can cause some side effects, especially as the dose increases. This may limit the amount you can take. Some of these include:
Paradoxically, at higher doses this medication can also lead to fatigue and poor muscle strength—the very issues it is trying to treat. Because of these side effects, many people who take Firdapse alone don’t experience enough relief from their symptoms to return to their normal activities.
If this is the case, your clinician may want to try additional medications or therapies. Another potential agent is Mestinon (pyridostigmine), which may increase the signal from the nerve to the muscle.
Other options are therapies that tone down a person’s immune response. For example, you might take a steroid such asprednisolone. Another immunosuppressive agent, like azathioprine, might be taken in addition to the steroid.
Other possible treatment options are intravenous immunoglobulin and plasma exchange therapy. However, none of these other choices are as well-established as Firdapse.
Cancer Treatment
In people who have LEMS from small-cell lung cancer, addressing the cancer itself is the priority. With successful cancer treatment, the symptoms of LEMS often go away.
Depending on the situation, treatments to address a small-cell lung cancer might include:
However, even if you’ve been treated for cancer, you might still experience symptoms from LEMS, especially if not all of the cancer could be removed. If so, you might benefit from the same medications used for idiopathic LEMS.
Tumor surveillance is another key part of treatment. Even if your imaging tests didn’t show any signs of cancer, it’s possible that you might have a very small cancer that just didn’t show up on the test.
For this reason, it’s recommended that most people with LEMS get repeatimaging testsdone of their chests, at least for a while. This can ensure that a potential cancer is detected and treated as soon as possible.
The frequency of screening is based on the likelihood that you have LEMS from a cancer compared to idiopathic LEMS. People with a lot of factors that increase the risk of cancer should be screened more frequently and for a longer period. Factors that increase risk include history of smoking, age of 50 or older, and recent weight loss.
People at high risk might need to be screened every six months over a period of two years. People without risk factors might need only one repeat imaging test.
People with LEMS from a small-cell lung cancer tend to live longer than people with small-cell lung cancer who don’t have LEMS. This might be because people with LEMS tend to get diagnosed with cancer at an earlier cancer stage, when treatment can work more effectively.
Or it might be that having LEMS is a sign of a strong immune response to a cancer, which might make it more likely that you will beat the cancer.
People who have LEMS without an underlying cancer do not seem to have a shortened life span. However, you might still have some physical limitations, even after you’ve explored all your treatment options.
For example, one study of 63 people with LEMS found that 62% were initially able to fully perform self-care activities before treatment, and 85% could do so after one year of treatment. Though you might have some residual symptoms, these seem to plateau with treatment and time in most people.
A Word From Verywell
A diagnosis of LEMS is very serious, especially if you are someone at high risk of small-cell lung cancer. However, you may be relieved to receive the correct diagnosis for your symptoms so you can begin to do something about them. It may take some time to find the right treatment, but your medical team will help you navigate your plan.
10 SourcesVerywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Lorenzoni PJ, Kay CSK, Werneck LC, Scola RH.Lambert-Eaton myasthenic syndrome: the 60th anniversary of Eaton and Lambert’s pioneering article.Arq Neuropsiquiatr. 76(2):124-126. doi:10.1590/0004-282X20170194Tarr TB, Wipf P, Meriney SD.Synaptic pathophysiology and treatment of Lambert-Eaton myasthenic syndrome.Mol Neurobiol. 52(1):456-63. doi:10.1007/s12035-014-8887-2Anwar A, Saleem S, Ahmed MF, Ashraf S, Ashraf S.Recent advances and therapeutic options in Lambert-Eaton myasthenic syndrome.Cureus. 11(8):e5450. doi:10.7759/cureus.5450Ivanovski T, Miralles F.Lambert-Eaton myasthenic syndrome: early diagnosis is key.Degener Neurol Neuromuscul Dis. 9:27-37. doi:10.2147/DNND.S192588Briggs SE, Gozzard P, Talbot DC.The association between Lambert-Eaton myasthenic syndrome and small cell lung carcinoma.Immunotargets Ther. 2:31-37. doi:10.2147/ITT.S31971Kesner VG, Oh SJ, Dimachkie MM, Barohn RJ.Lambert-Eaton myasthenic syndrome.Neurol Clin. 36(2):379-394. doi:10.1016/j.ncl.2018.01.008Gonzalez-Perez P, Torre M, Helgager J, Amato AA.Proximal muscle weakness.Pract Neurol. 19(4):321-325. doi:10.1136/practneurol-2019-002204Keogh M, Sedehizadeh S, Maddison P.Treatment for Lambert-Eaton myasthenic syndrome.Cochrane Database Syst Rev. (2):CD003279. doi:10.1002/14651858National Institutes of Health. National Cancer Institute.Small cell lung cancer treatment—health professional version.Lipka AF, Boldingh MI, van Zwet EW, et al.Long-term follow-up, quality of life, and survival of patients with Lambert-Eaton myasthenic syndrome.Neurology. 2020 Feb 4;94(5):e511-e520. doi:10.1212/WNL.0000000000008747
10 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Lorenzoni PJ, Kay CSK, Werneck LC, Scola RH.Lambert-Eaton myasthenic syndrome: the 60th anniversary of Eaton and Lambert’s pioneering article.Arq Neuropsiquiatr. 76(2):124-126. doi:10.1590/0004-282X20170194Tarr TB, Wipf P, Meriney SD.Synaptic pathophysiology and treatment of Lambert-Eaton myasthenic syndrome.Mol Neurobiol. 52(1):456-63. doi:10.1007/s12035-014-8887-2Anwar A, Saleem S, Ahmed MF, Ashraf S, Ashraf S.Recent advances and therapeutic options in Lambert-Eaton myasthenic syndrome.Cureus. 11(8):e5450. doi:10.7759/cureus.5450Ivanovski T, Miralles F.Lambert-Eaton myasthenic syndrome: early diagnosis is key.Degener Neurol Neuromuscul Dis. 9:27-37. doi:10.2147/DNND.S192588Briggs SE, Gozzard P, Talbot DC.The association between Lambert-Eaton myasthenic syndrome and small cell lung carcinoma.Immunotargets Ther. 2:31-37. doi:10.2147/ITT.S31971Kesner VG, Oh SJ, Dimachkie MM, Barohn RJ.Lambert-Eaton myasthenic syndrome.Neurol Clin. 36(2):379-394. doi:10.1016/j.ncl.2018.01.008Gonzalez-Perez P, Torre M, Helgager J, Amato AA.Proximal muscle weakness.Pract Neurol. 19(4):321-325. doi:10.1136/practneurol-2019-002204Keogh M, Sedehizadeh S, Maddison P.Treatment for Lambert-Eaton myasthenic syndrome.Cochrane Database Syst Rev. (2):CD003279. doi:10.1002/14651858National Institutes of Health. National Cancer Institute.Small cell lung cancer treatment—health professional version.Lipka AF, Boldingh MI, van Zwet EW, et al.Long-term follow-up, quality of life, and survival of patients with Lambert-Eaton myasthenic syndrome.Neurology. 2020 Feb 4;94(5):e511-e520. doi:10.1212/WNL.0000000000008747
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
Lorenzoni PJ, Kay CSK, Werneck LC, Scola RH.Lambert-Eaton myasthenic syndrome: the 60th anniversary of Eaton and Lambert’s pioneering article.Arq Neuropsiquiatr. 76(2):124-126. doi:10.1590/0004-282X20170194Tarr TB, Wipf P, Meriney SD.Synaptic pathophysiology and treatment of Lambert-Eaton myasthenic syndrome.Mol Neurobiol. 52(1):456-63. doi:10.1007/s12035-014-8887-2Anwar A, Saleem S, Ahmed MF, Ashraf S, Ashraf S.Recent advances and therapeutic options in Lambert-Eaton myasthenic syndrome.Cureus. 11(8):e5450. doi:10.7759/cureus.5450Ivanovski T, Miralles F.Lambert-Eaton myasthenic syndrome: early diagnosis is key.Degener Neurol Neuromuscul Dis. 9:27-37. doi:10.2147/DNND.S192588Briggs SE, Gozzard P, Talbot DC.The association between Lambert-Eaton myasthenic syndrome and small cell lung carcinoma.Immunotargets Ther. 2:31-37. doi:10.2147/ITT.S31971Kesner VG, Oh SJ, Dimachkie MM, Barohn RJ.Lambert-Eaton myasthenic syndrome.Neurol Clin. 36(2):379-394. doi:10.1016/j.ncl.2018.01.008Gonzalez-Perez P, Torre M, Helgager J, Amato AA.Proximal muscle weakness.Pract Neurol. 19(4):321-325. doi:10.1136/practneurol-2019-002204Keogh M, Sedehizadeh S, Maddison P.Treatment for Lambert-Eaton myasthenic syndrome.Cochrane Database Syst Rev. (2):CD003279. doi:10.1002/14651858National Institutes of Health. National Cancer Institute.Small cell lung cancer treatment—health professional version.Lipka AF, Boldingh MI, van Zwet EW, et al.Long-term follow-up, quality of life, and survival of patients with Lambert-Eaton myasthenic syndrome.Neurology. 2020 Feb 4;94(5):e511-e520. doi:10.1212/WNL.0000000000008747
Lorenzoni PJ, Kay CSK, Werneck LC, Scola RH.Lambert-Eaton myasthenic syndrome: the 60th anniversary of Eaton and Lambert’s pioneering article.Arq Neuropsiquiatr. 76(2):124-126. doi:10.1590/0004-282X20170194
Tarr TB, Wipf P, Meriney SD.Synaptic pathophysiology and treatment of Lambert-Eaton myasthenic syndrome.Mol Neurobiol. 52(1):456-63. doi:10.1007/s12035-014-8887-2
Anwar A, Saleem S, Ahmed MF, Ashraf S, Ashraf S.Recent advances and therapeutic options in Lambert-Eaton myasthenic syndrome.Cureus. 11(8):e5450. doi:10.7759/cureus.5450
Ivanovski T, Miralles F.Lambert-Eaton myasthenic syndrome: early diagnosis is key.Degener Neurol Neuromuscul Dis. 9:27-37. doi:10.2147/DNND.S192588
Briggs SE, Gozzard P, Talbot DC.The association between Lambert-Eaton myasthenic syndrome and small cell lung carcinoma.Immunotargets Ther. 2:31-37. doi:10.2147/ITT.S31971
Kesner VG, Oh SJ, Dimachkie MM, Barohn RJ.Lambert-Eaton myasthenic syndrome.Neurol Clin. 36(2):379-394. doi:10.1016/j.ncl.2018.01.008
Gonzalez-Perez P, Torre M, Helgager J, Amato AA.Proximal muscle weakness.Pract Neurol. 19(4):321-325. doi:10.1136/practneurol-2019-002204
Keogh M, Sedehizadeh S, Maddison P.Treatment for Lambert-Eaton myasthenic syndrome.Cochrane Database Syst Rev. (2):CD003279. doi:10.1002/14651858
National Institutes of Health. National Cancer Institute.Small cell lung cancer treatment—health professional version.
Lipka AF, Boldingh MI, van Zwet EW, et al.Long-term follow-up, quality of life, and survival of patients with Lambert-Eaton myasthenic syndrome.Neurology. 2020 Feb 4;94(5):e511-e520. doi:10.1212/WNL.0000000000008747
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