Lambert Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder that affects your nerves and muscles. It affects about 400 people in the U.S.
“I’ve been doing this for about 31 years now and I have seen about two to three a year because of the nature of what I do,” says Nestor Galvez-Jimenez, MD, a neurologist and director of the autonomic neurology program at Baptist Health Miami Neuroscience Institute in Florida. “But for general neurology, they may not even see one for a few years.”
LEMS affects the signals that go from your nerves to your muscles — it’s a miscommunication of sorts. “I like to use a pitcher‑and‑catcher analogy,” Galvez-Jimenez says. “The nerve ending is like the pitcher, and the muscle is like the catcher with a glove. Normally, the pitcher (nerve) throws the ball (the chemical signal) and the catcher (muscle) uses its glove (receptor) to catch it so the muscle can contract. In Lambert Eaton myasthenic syndrome, antibodies interfere with the pitcher’s ability to throw the ball in the first place. The catcher is sitting there with the glove ready, but the ball never arrives, and that’s what leads to muscle weakness.”
Better diagnosis and treatment of LEMS means determining if that ball isn’t reaching the glove and if it’s not, helping it get there.
Refining Lambert-Eaton Diagnosis
Although LEMS is a rare disease, doctors believe there are many more people who have it but aren’t diagnosed. “I’ve wondered if it’s underdiagnosed because some of the symptoms are very general, like fatigue and weakness,” says Andrew D. Galbreath, DO, a neurologist with Sentara Neurology Specialists in Virginia Beach, Virginia. Studies back this up. An article published in 2025 says that there’s “marked underdiagnosis” of the syndrome among people who have small-cell lung cancer. But research has improved and refined this, so diagnosis may improve.
Lambert-Eaton Antibody Test
Advances in antibody testing have improved the speed of coming to diagnosis, Galbreath says. Testing for calcium channel antibodies, especially one called the P/Q-type voltage-gated calcium channel antibody, can now be done quickly in one specialized blood test. Over 90% of people with LEMS have this antibody.
Nerve and muscle testing
There have also been improvements in the nerve and muscle testing that can lead to a LEMS diagnosis. Standard tests for LEMS have been:
- Nerve conduction studies
- Repetitive stimulation
- Electromyography (measures the electrical activity in your muscle after it’s stimulated)
But the nerve-test patterns are more clearly defined now. Instead of doctors individually interpreting the results, they must look for a clearer pattern: very small muscle response while your muscle is relaxed and a much bigger signal right after your muscle contracts or after fast nerve stimulation. There are specific cut‑off values for how big the changes should be. “Now that we have the antibodies [to look for] and we recognize the patterns on diagnostic studies, LEMS becomes easier to diagnose,” Galvez-Jimenez says.
There is also an improved plan for cancer screening people in LEMS. This leads to better treatment of the syndrome for those who have both. Patients who aren’t at high risk of cancer should have a computed tomography (CT) scan or magnetic resonance imaging (MRI) of their chest. A positive emission tomography (PET) is recommended if the CT scan is negative (doesn’t show any signs of cancer). Patients should be screened every three to six months for at least two years after. Those who are at high risk for cancer should be screened with the Dutch-English LEMS Tumor Association Prediction (DELTA-P) score.
The scoring looks at:
- The patient’s age
- Smoking history
- Weight loss
- If weakness affects speech, swallowing, and facial movement (called bulbar involvement)
- Erectile dysfunction
- Ability to perform daily tasks (called the Karnofsky performance status)
If there’s no cancer, they should continue to be screened every three months.
Advances in LEMS Treatment
Treatment is improving for LEMS and similar diseases like myasthenia gravis. The goal is to control the disease and eliminate the symptoms by controlling the immune system. If that doesn’t work, then the goal changes to trying to keep the disease from getting worse.
“The main way the treatment has changed is with a medication called Firdapse,” Galbreath says. Firdapse (generic name amifampridine) is a potassium channel blocker. It was first approved by the FDA in 2018 for adults, with another approval, under the name Ruzurgi, in 2022 for children ages 6 and older.
“When I was a trainee, we had the same molecule but it was done through a compounding pharmacy. [There had to be] a specific protocol in place and there were a few centers who kept it, but it was not widely available. Now it’s FDA-approved and you can have easy accessibility to the medication, standard medication.”
Amifampridine is also called 3,4‑diaminopyridine, or 3,4‑DAP. The medication increases the chemical acetylcholine, which helps the nerves send the signals to the muscles. Studies are small (because the disease is rare), but they do show that the drug improves muscle strength. According to the guidelines, amifampridine must be used when someone is newly diagnosed.
The usual starting dosage for adults is one 5-milligram pill three times a day for a total of 15 milligrams, but the dose can go as high as 80 milligrams. For children, the dose is calculated based on their size. Children weighing less than 45 kilograms (100 pounds) start with 5 to 10 milligrams in two or three divided doses throughout the day. They can go as high as 40 milligrams per day. Those over 45 kilograms may start with 10 to 20 milligrams divided in two or three doses. They can go as high as 80 milligrams, and in some cases, 100 milligrams per day.
People who have cancer as well as LEMS must be treated for that particular cancer and take glucocorticosteroids, usually prednisone or methylprednisolone. This is to suppress the immune system. To keep steroid treatment as short as possible, the next step is azathioprine (AZA), which also suppresses the immune system. Other options, if needed, are cyclosporine A (CSA), mycophenolate mofetil (MMF), rituximab (RTX), and tacrolimus.
Takeaways
There are no new drugs for LEMS in the research pipeline. But with the diagnosis and treatment updates that are available, people with LEMS without cancer generally live a normal lifespan. The survival of those with cancer depends on what type of cancer it is, how far it’s progressed, and how well it responds to treatment. “If it's primary, not due to underlying [cancer], the prognosis is good because we have ways to treat the inflammatory process, control the immune process,” Galvez-Jimenez says. “We have ways to diagnose. We have ways to treat, so we are always hopeful.”
