Lambert-Eaton Myasthenic Syndrome

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Biology 202, Spring 2005
Second Web Papers
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Lambert-Eaton Myasthenic Syndrome

Flicka Michaels


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.

References

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

 

 

Comments made prior to 2007
I want to praise Flicka Michaels for her very comprehensive and readable paper on LEMS. I've had the autoimmne variety for 26 years and I added this article to my favorites before I noted that it was written by a student. It took two years for a diagnosis in my case, and then Predisone for 11 years allowed me to live a virtually normal life. That is a nasty drug especially long term. I have been on disability retirement since July 2002. I'm now 62 years old and my doctors won't do anything for me, except to schedule IVIG infusions, which do help. I take the DAP and Mestinon every 3 or 4 hours just to keep going.

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

Comments

Donald Semi 's picture

Waiting on VA

Pursuing diagnosis with VA so it takes time. Did you folks have strength loss in legs and arms over a period of a year or so? What led you to seek help? (Symptoms)

Deborah Gaultney's picture

Lambert Eaton and taking Diaminopyridine 3.4

I am taking taking the above medication for two weeks now. I am wondering what are the side effects of people who are currently taking it.
Since it is a orhpan drug no one really knows what the side effects are. I currently have numbness in my lips for about an hour after I take it. It is helping my leg muscles pretty good. I do have small cell lung cancer along with it and am taking chemo.
Really interested in side effects of this med from people who are now taking it.

marty's picture

causes for LEMS

I am a 62 yr old male diagnosed with Lambert-Eaton Myasthenic Syndorme. I do not have cancer. I was in the gulf coast region post Huricane Katrina for a pediod of ten weeks. Is it possible to have contracted this disease from contact with any contaminated air, water or food?

Anonymous's picture

LEMS

Nonsmoking LEMS patients under the age of 50 only rarely have a tumor! Take it one day at a time. You are going to die old of something else.

Jean's picture

LEMS - newly dx

I am scared. I have just be dx a week ago. My Neurologist is sending me to Mayo in MN in a couple of weeks. I am only 48 with young sons who need their mom. In the past week - I feel like my whole body has been CT-scanned. So far no cancer. What does a LEMS patient do - just wait for a cancer to develope? i feel like my whole world has stopped. I have never smoked and have lived a healthy lifestyle. This is not fair.

Anonymous's picture

11 years and counting

I was diagnosed with LEMS 11 years ago. No cancer.
I take the mestinon and DAP daily and I am now 87 years old. Before I was diagnosed I went through many tests and examinations by my doctor, who prescribed several different treatments and I even knocked over a big pile of cans in the grocery store because I couldn't control my legs. Life for me improved after going on the DAP pills. At first I walked around then I needed a cane and now use a walker, but I am 87. I have never been diagnosed with cancer and have never smoked. You can live with LEMS and be cancer free.

Anonymous's picture

Your story sounds like mine.

Your story sounds like mine. Im 46 with two young children. How have you faired since your post? And, may I ask, by what type of MD were you initially diagnosed and what was the final test that confirmed the LEMS?I ask b/c my reg MD did the diagnosis and I am to see the Neurologist in a few weeks. Mayo in Scottsdale has accepted my case, however, I am on a wait list to see them.

Deborah Gaultney's picture

LEMS

My symptoms were heavy legs and heavy droopy eylelids. Thats how they knew it was mysesthenia gravis. Then they did a blood test specific to Lambert Eaton Syndrome which told them to look for cancer. I was then diagnosed with Small Cell Lung Cancer and am taking chemo. I am on my last chemo set next week. I will have had 6 sets (1 1/2 hours first day and 1 hour the next two. Two weeks ago they told me I am cancer free. Just because you have Lambert Eaton it doesn't mean you have cancer but best to check it out. The other test ran was EMG test for muscle strength which also told them it was Lambert Eaton. I saw a Neurologist who diagnosed this.
I hope you get to the bottom of this and don't have the cancer
with it. Good Luck.
Debbie

barbara morhet's picture

i have had LEMS for 3 years

i have had LEMS for 3 years now . i take predisone and mestinone, but still have days when i have trouble moving. i too, wounder how long i will live. i have small cell lung cancer, but the origin has not been found yet. i had the cancer removed from my lymph node and chemo and radiation. i hope there will always be help for people with LEMS

ty jenkins's picture

i am a 33 year old man who

i am a 33 year old man who suffers from lems. i was dx in 2005 and i am currently on dap AND MESTINON.i have good days and bad days.there has never been cancer found but i keep going for the sake of my 5 children,so i say the same to you all,just keep your head up and continue to let God lead you.

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