Lambert-Eaton Myasthenic Syndrome
Lambert-Eaton Myasthenic Syndrome
Lambert-Eaton Myasthenic Syndrome (LEMS) is a rare autoimmune disease which affects the neuromuscular junction and interrupts the connection between nerve cells and the muscles.(1) Less than one in every one million people are diagnosed with this disease every year. (5) It was first described in 1953 by Anderson, who examined a 47 year-old man with oat cell lung cancer. In 1966, Lambert, Eaton, and Rooke did an initial study of the disease, and thus it is named after them. (2) LEMS primarily affects middle-aged adults, but cases in children have been found. Cancer is a factor in about 50% of all cases of LEMS; small-cell lung cancer tends to be present in the majority of them. (2) Some researchers suspect that the cancerous cells cause an excess release of a certain protein in nerve cells, which then causes the formation of anti-bodies to this protein. (1) However, one of the most striking aspects of LEMS is that for patients without cancer, the cause of the disease in unknown.
In order for nerve cells to effectively relay signals to muscles so
they can contract,they must emit a neurotransmitter called
acetylcholine. The emission of acetylcholine from a nerve cell is
dependent on a protein called P/Q type voltage-gated calcium channel
(VGCC). VGCC allows admission of calcium into nerve cells and therefore
the emission of acetylcholine. About 85-90 percent of people with LEMS
have been shown to have antibodies for VGCC, therefore preventing the
emission of acetylcholine, and associated weakness of muscles. (1)
Symptoms of LEMS are similar to Myasthenia Gravis. They include weakness of upper leg and arm muscles, problems walking, weakness of the facial muscles, problems talking, swallowing or chewing. Other symptoms include dryness of the mouth, eyes, or skin, and droopy eyelids. (3) The progression of symptoms resulting from LEMS tends to move slowly and can often be mistaken for another disease called Myasthenia Gravis. Like Myasthenia Gravis, LEMS primarily affects adults, and is distinguished by weakness of the muscles. However, with Myasthenia Gravis, the body makes antibodies for
acetylcholine receptors, instead of the protein which allows for the emission of the transmitter. Also unlike Myasthenia Gravis, the weakness associated with LEMS tends to improve after exercise. Some doctors think that the repetitive action causes an increase of calcium in the nerve cells, which then increases the amount of acetylcholine released. (1)
The initial diagnosis of LEMS can be made through a physical examination which will demonstrate the patient's muscle weakness. However, in order to distinguish LEMS from Myasthenia Gravis, a blood test is needed to identify the specific autoimmune antibodies that are being produced. In addition, a test can be given, in which a patient is injected with the edrophonium chloride (Tensilon), and if muscles strengthen as a result, the diagnosis is Myasthenia Gravis. (3) The presence of cancer in a patient is also a sign that LEMS is the diagnosis, as opposed to Myasthenia Gravis.
As I mentioned earlier, about 50% of all LEMS cases are associated with some form of cancer. (2) However, Small-Cell Lung Carcinoma (SCLC) is by far the most common. About 60% of people who have LEMS also have SCLC. (6) Research shows that the connection between the two is most likely due to the antigenetic characteristic of SCLC which triggers body's autoimmune response to the cancer and in turn, the production of antibodies to VGCC. (6) Since this process occurs during the very early stages of the tumor, LEMS is usually detected before the cancer. In some cases, the symptoms of LEMS can appear anywhere from 2-5 years before the symptoms of the cancer. (6) However, when symptoms of LEMS are discovered and the disease is diagnosed, the patient should immediately be tested for cancer, SCLC in particular.
For patients with LEMS and cancer, treatment normally centers on
treatments to eliminate the cancerous tumors. However for patients
without cancer, a process called Plasmapheresis, in which blood plasma
is removed from the patient and replaced by
fluid, tends to ameliorate symptoms. (4) One drug, called Pyridostigmine (or Mestinon), is commonly used for patients with Myasthenia Gravis, and may help increase the release of acetylcholine. However, a commonly recommended drug in cases of LEMS is 3,4-Diaminopyridine, which, like Pyridostigmine, increases the emission of acetylcholine from nerve terminals. (6) For patients with more severe or persistent symptoms, immunosuppressant drugs such as Prednisone, Imuran, and Neoral can also help decrease the formation of antibodies.
So why is LEMS so fascinating? Primarily because (in cases where cancer is not a factor) the cause is unknown. It is an autoimmune disease so we know that the body starts creating antibodies to something it would not normally try to suppress. But why? A research study performed in 2001 by the Dr. Andrew Caton at Wistar Institute in Philadelphia showed that the existence of T cells in the body plays a large role in preventing autoimmune responses. T cells are white blood cells that recognize the body's natural proteins, or the 'self'. (7) Dr. Caton explains that in the case of autoimmune diseases, these T cells are altered so that, instead of working towards the destruction of infected cells, they inhibit the usual immune response. He says, "What's interesting about these regulatory T cells is that, although their purpose is to prevent autoimmunity, they themselves react against the 'self'." (7)
Most of the time, we are trying to figure out how the idea of the
"self" fits into the nervous system. We never think of the nervous
system as an actual "self" because we usually think that our life
battles consist of the nervous system (physical) versus
the "self" (mental). However, if part of the nervous system revolts against its normal routine (as with autoimmune diseases like LEMS), does that not mean that we should entertain the idea that a "self" exists within the nervous system? Perhaps if we stop
viewing the nervous system as one entity that always works perfectly, we might be able to better appreciate its partition and complexity.
1) Muscular Dystrophy Association, Facts about LEMS
2) eMedicine, Very technical, but in depth article about LEMS by Paul Kleinschmidt, MD
3) Rare Diseases.com, facts about LEMS
4) ADAM encyclopedia on About.com, Health Encyclopedia- Treatment for LEMS
5) Cleveland Clinical Health System, Basic overview of LEMS
6) DLD Diagnostika GMBH, Great article that thoroughly discusses and presents visual images of the voltage-gated calcium channels involved in LEMS.7) Autoimmune Related Diseases Association, Research study abstract
Dr. Donald B. Sanders at Duke is, I think, the leading authority on LEMS in this country. He did the DAP trials. If you know of any other doctor in this country that is well versed in this disease, please let me know. I am at the end of the road. My local doctor only tells me that I should (already) be dead, I am living on "borrowed time", and that I will die soon. I can't find any information on anyone who has lived with this autoimmune variety as long as me ... Charlotte Kiffer, 6 April 2006