About eaton-lambert syndrome
What is eaton-lambert syndrome?
Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder characterized by the gradual onset of muscle weakness, especially of the pelvic and thigh muscles. Approximately 60 percent of LEMS cases are associated with a small cell lung cancer (SCLC), and the onset of LEMS symptoms often precedes the detection of the cancer. The LEMS patients with cancer tend to be older and nearly always have a long history of smoking. In cases in which there is no associated cancer, disease onset can be at any age.
What are the symptoms for eaton-lambert syndrome?
LEMS is characterized by Weakness and Fatigue especially of the muscles in the legs and arms. The disease may affect the patient’s ability to engage in strenuous exercise and may make such activities as climbing stairs or walking up a steep walkway difficult. Onset is gradual, typically taking place over several weeks to many months. There is often a progression of symptoms whereby the shoulder muscles, muscles of the feet & hands, speech & swallowing muscles and eye muscles are affected in a stepwise fashion. The symptoms progress more quickly when LEMS is associated with cancer. Most LEMS patients also exhibit the following symptoms (sometimes called autonomic symptoms): dry mouth, dry eyes, constipation, impotence, and decreased sweating. LEMS patients with or without cancer may also undergo significant weight loss. The tendon reflexes are diminished or absent on examination. Hence, in summary, LEMS is often described as a clinical “triad” of proximal muscle weakness, autonomic symptoms and reduced tendon reflexes.
What are the causes for eaton-lambert syndrome?
LEMS is an autoimmune disorder. Autoimmune disorders are caused when the body’s natural defenses against “foreign” or invading organisms (e.g., antibodies) begin to attack healthy tissue for unknown reasons. LEMS occurs because autoantibodies damage the “voltage-gated calcium channels (VGCC)” on the motor nerve membrane at the neuromuscular junction. These channels normally conduct calcium into the nerve resulting in release of a chemical known as acetylcholine. Acetylcholine helps in the communication between nerve cells and muscles and is one of a group of chemicals known as neurotransmitters, which help to transmit nerve impulses. The autoantibodies attack the VGCC resulting in less acetylcholine release.
In patients who have LEMS associated with cancer, the immune mediated response is initiated because VGCC are present on the surface of cancer cells and the immune system triggers the production of antibodies to fight off cancer cells. The idea is that autoantibodies created against the VGCC on the small cell lung cancer mistakenly attack the VGCC on the nerve membrane instead. One of the major risk factors for SCLC is smoking, and in patients who have LEMS associated with cancer, a long history of smoking is also a major contributing factor.
In people who have LEMS not associated with cancer, genetic associations have been made with human leukocyte antigen (HLA) genotypes. HLA are proteins also present on the cell surface, and their function is to regulate the human immune system. However, it is unknown what causes these proteins to go awry array and trigger autoantibody production.
What are the treatments for eaton-lambert syndrome?
Treatment of LEMS may vary depending upon the presence of associated cancer. If cancer is present, treatment first involves treatment directed at the cancer, this alone may result in relief of LEMS symptoms.
There is no cure for LEMS and treatment usually involves improving quality of life. Therefore, symptomatic treatment is the focus in the management of LEMS. The FDA recently approved a new drug for the symptomatic relief of symptoms associated with muscle weakness called Firdapse (amifampridine). It is a potassium channel blocker that works by increasing the release of acytelcholine. At this time, it is the only drug approved for the indication of LEMS. The medication has shown to have significant benefits such as improving muscle strength and CMAP. In addition, it is a well-tolerated medication.
If Firdapse alone does not improve symptoms, there are additional options that can be added in case of symptom progression. Mestinon is indicated for the treatment of MG, but is often used in combination with Firdapse to treat symptoms of autonomic dysfunction (dry mouth, dry eyes, constipation, impotence and, decreased sweating). In MG, Menstinon improves muscle strength, but in LEMS, it has only shown to improve symptoms of autonomic dysfunction.
In 2019, Ruzurgi (amifampridine) was approved to treat LEMS in patients 6 to less than 17 years of age. This is the first FDA approved treatment specifically for pediatric patients with LEMS.
Drugs that suppress the activity of the immune system (immunosuppressive drugs) are used in LEMS patients with more severe symptoms, e.g. prednisone (alone or in conjunction with azathioprine or cyclosporin). In some patients, a course of high dose immunoglobulins may prevent further disease progression.
What are the risk factors for eaton-lambert syndrome?
The estimated worldwide prevalence of LEMS is about 2.8 per million, making it a rare disease. There are approximately 400 known cases of LEMS in the United States. When LEMS is associated with SCLC, the patients tend to be older and are more likely to be men than women. The average age of onset of SCLC is around 60 years of age. Approximately 3% of SCLC patients develop LEMS, but clinical symptoms of LEMS usually precede the SCLC diagnosis (sometimes by many years). When LEMS is not related to cancer, the syndrome may occur at any age, and the typical onset is about 35 years of age. LEMS is extremely rare in the pediatric population, and there have only been 11 affected children reported in literature.