Introduction

Lambert-Eaton Myasthenic Syndrome, or LEMS for short, is a rare condition that disrupts the communication between your nerves and muscles.¹ This connection is essential for your muscles to contract and function properly. When it’s disrupted, it can lead to muscle weakness, fatigue, and difficulty with everyday movements like walking or climbing stairs.

For most people with LEMS, medications can help manage the symptoms effectively. But in some cases, these medicines don't work well enough. This is called refractory LEMS, which simply means the condition is hard to treat with standard therapies. When this happens, doctors may use advanced treatments like plasmapheresis or intravenous immunoglobulin (IVIg) to better control the disease.

In this article, we will explore what LEMS is and how it affects your body, what refractory LEMS is, what plasmapheresis and IVIg are, and how they help in the management of refractory LEMS.

What is Lambert-Eaton Myasthenic Syndrome (LEMS)?

Lambert-Eaton myasthenic syndrome, also known as Eaton-Lambert syndrome, is an autoimmune disorder in which your immune system attacks your own healthy cells, specifically the nerve cells. In LEMS, your immune cells produce autoantibodies (which are usually produced and act against infections), bind to and block the calcium channels present at your nerve endings.^1,3 This is the point where your nerve and muscle cells meet, and is known as the neuromuscular junction.

These calcium channels are really important because they allow the release of a chemical substance (neurotransmitter) called acetylcholine, which signals your muscles to move. When the calcium channels are blocked, your nerves cannot release enough acetylcholine, leading to a breakdown in the communication between your nerves and muscles. This leads to a characteristic set of symptoms of LEMS, which are given below.²

Symptoms of LEMS

The first and most common symptom you might notice in LEMS is muscle weakness. This weakness typically begins in the muscles of your upper legs and gradually spreads to involve the muscles of your hands, feet, mouth, and throat.¹ Along with muscle weakness, you may experience several other symptoms such as:^1,2,3

• Dry mouth (xerostomia)
• Dry eyes
• Constipation
• Fluctuations in blood pressure
• Reduced or absent muscle reflexes

Causes of LEMS

LEMS most commonly occurs in people who have an underlying malignancy, where it is referred to as paraneoplastic LEMS.^1,3 In this condition, your immune system mistakenly attacks the healthy cells of your body while trying to fight off the cancer cells. According to studies, 40 to 62% of individuals with LEMS have an underlying small cell lung cancer (SCLC).² However, in many cases, the symptoms of LEMS develop even before the cancer is diagnosed. LEMS has also been seen in people with prostate cancer and thymoma, although such cases are much less common.

In other cases, LEMS occurs on its own without any associated malignancy. The exact reason why this occurs is still not fully understood. However, it is believed that environmental and genetic factors may play a role in causing the immune system to go wrong.

How is LEMS usually treated?

The main goals of LEMS treatment are to:

Improve muscle strength

Medications such as amifampridine and pyridostigmine are commonly prescribed to help improve muscle function.^1,2,3 These drugs work by increasing the amount of acetylcholine at your neuromuscular junction. This, in turn, boosts the communication between your nerves and muscles, thus relieving your symptoms.

Control the immune system

When symptomatic treatment is inadequate in managing the condition, immunomodulator drugs such as prednisolone and azathioprine may be used.^1,2 They control the attack of your immune system on the healthy cells of your body.

Treat any underlying cancer, if present

In cases where LEMS is linked to an underlying cancer, treating the cancer itself often leads to significant improvement in symptoms.²

What is refractory LEMS?

When you have refractory LEMS, your condition does not get better even after trying standard treatments described above. You may continue to feel weak, tired, or have trouble with daily activities despite taking medications for several weeks or months. In such cases, doctors consider more advanced treatments, including plasmapheresis and intravenous immunoglobulin (IVIg).²

Intravenous immunoglobulin: IVIG

Doctors usually recommend IVIg as the primary treatment option for people who have refractory patterns of weakness, in other words, for those who do not respond to usual treatment.³

What is IVIG?

IVIG is a treatment made from antibodies collected from the blood of thousands of healthy donors. These antibodies are purified and administered via a vein (i.e., intravenously) to help calm down your overactive immune system, which mistakenly attacks your body's nerve-muscle communication.

How does IVIG work?

Although the exact mechanism through which it works is still not fully understood, scientists believe that it works by following mechanisms:³ 

Reduction in the levels of autoantibodies

As LEMS is caused by the production of autoantibodies that block the calcium channels present at your nerve endings, IVIg reduces the number of these autoantibodies in your bloodstream. It also blocks their binding with calcium channels, thus restoring the nerve-muscle communication, which in turn improves your muscle strength.

Regulation of autoreactive immune cells

Autoreactive cells are those that produce antibodies against own tissues. IVIg also helps regulate the function of these immune cells (specifically B cells) and slows down the production of harmful antibodies, easing the autoimmune response.

How is IVIG given?

IVIg is usually given in a hospital or clinic, through a slow drip into your vein (IV infusion). The full dose is typically given over 2 to 5 days, depending on your needs. Some people may need repeated infusions every few weeks as part of maintenance treatment.³

During this process, the medical team will monitor your blood pressure, pulse, and temperature regularly to make sure your body is handling the treatment well.

Is IVIG effective?

Yes, IVIg has been shown to be effective in improving symptoms of refractory LEMS. However, the effects may not be immediate, and it often takes two to four weeks before any noticeable improvement begins. In some people, the benefits may wear off over time, and additional infusions are needed to maintain progress.^3,4

A clinical trial published in the journal Neurology found that people with LEMS who received IVIg had stronger muscles and lower levels of the harmful antibodies in their blood.⁴

Are there any side effects?

Most people tolerate IVIg well. However, some may experience some mild side effects, such as:^3,5

• Headache
• Fever or chills
• Nausea 
• Tiredness

Some people may also have serious side effects, but they are rare. These include:

• Blood clots
• Kidney problems (especially in older adults or those with kidney disease)

Plasmapheresis

Plasmapheresis, also known as plasma exchange, is a medical procedure that replaces your plasma (the liquid portion of your blood) with the aim of removing the harmful substances present in it. In the case of LEMS, the goal is to eliminate the autoantibodies that interfere with communication between your nerves and muscles. 

How is it done?

Plasmapheresis is typically performed in a hospital setting. 

Your blood is composed of cells (red blood cells, white blood cells, and platelets) and plasma. Plasma is the liquid portion of your blood and contains electrolytes, proteins, and clotting factors in addition to the autoantibodies responsible for LEMS. The first step in plasmapheresis involves separating plasma from the rest of your blood. This can be done using one of two techniques.⁶

Centrifugation

In this method, your blood is collected into tubes and placed inside a machine called a centrifuge, which spins it at high speed. This causes the blood components to separate based on their weight. It is the most commonly used method in many European countries.⁷

Membrane Filtration

This technique involves passing your blood through a special porous membrane. The membrane has tiny pores that allow plasma to pass through while blocking the larger blood cells.

After separation, plasma is removed, and the blood cells are combined with healthy donor plasma, which is then returned to your body.

When is it recommended?

Doctors usually recommend plasmapheresis in severe cases of LEMS, when the initial treatments do not work or when immediate relief is required.

Plasmapheresis is often used in combination with other treatment options, including immunosuppressants, to achieve a more comprehensive approach to managing LEMS.

Does it work?

Plasmapheresis can provide short-term relief during periods of severe muscle weakness, but it does not stop your immune system from producing autoantibodies responsible for the disease. This makes it necessary to combine plasmapheresis with other long-term therapies to help maintain improvement over time.

In a study published in the journal Neurology, nine people received several plasmapheresis sessions along with immune-suppressing medications like prednisone and azathioprine. Most of the people showed noticeable improvement. The best results, however, were seen about 10 to 15 days after treatment, and some people kept improving with continued medication.⁸

Are there any side effects?

Plasmapheresis is generally a safe procedure, when performed under proper medical care. However, it can lead to some side effects, the most common of which is hypotension or low blood pressure. You may feel lightheaded due to a decrease in your plasma volume. You may also have an increased risk of bleeding or infections after undergoing the procedure.⁹

Summary

Lambert-Eaton Myasthenic Syndrome (LEMS) is an autoimmune condition that can lead to muscle weakness by interrupting the communication between your nerves and muscles. It becomes refractory LEMS when standard medications are not enough to treat the condition. In these cases, doctors might consider advanced options like intravenous immunoglobulin (IVIg) and plasmapheresis. IVIg helps by regulating your immune system and reducing the harmful antibodies that disrupt nerve-muscle communication. This, in turn, leads to gradual improvements in your muscle strength. On the other hand, plasmapheresis acts more quickly by replacing your plasma (containing harmful antibodies) with healthy donor plasma. Thus, it provides short-term relief during severe symptoms. Both treatments are generally safe, although they might come with mild side effects. They are often used alongside other medications for long-term benefits.