What Is Lambert Eaton Myasthenic Syndrome?

Overview

Lambert-Eaton myasthenic syndrome (LEMS), also referred to as myasthenic syndrome or Eaton-Lambert syndrome, is a rare autoimmune disease - a disease where the immune system overreacts and attacks your body’s tissues. This attack happens at the neuromuscular junction (the connection between the nerve and muscle) and inhibits the function of the nerve cells to transmit signals to the muscle cells. As a result, people with this autoimmune disorder experience difficulty performing certain movements or tasks that require muscle strength. Although more than half of LEMS cases are commonly diagnosed in middle-aged or older people with lung cancer, there is a significant proportion of cases that are not linked to cancer and can happen at any age. 

In this article, we will delve into the causes, symptoms, diagnosis, and management of this rare autoimmune disorder to provide a comprehensive understanding of it.

Causes of LEMS

In this condition, your body’s immune system produces a type of antibody called an autoantibody, which attacks and destroys a specific type of calcium channel found on nerve endings that functions by releasing an important chemical called acetylcholine, which is important for muscle function. If there are fewer calcium channels, this means less acetylcholine is released by your nerve endings. In people with this autoimmune disorder, the decreased amount of acetylcholine leads to muscle weakness mainly in the upper arms, shoulders, legs and hips, as well as problems in your body’s automatic functions and reflexes. ¹

Studies have found that approximately 50–60% of patients with LEMS have lung cancer, specifically small-cell lung cancer (SCLC), although a few cases of non-small-cell lung cancer (NSCLC) and other types of lung cancer are linked to LEMS.² In these cases, it is believed that where the immune system is trying to fight the calcium channels in the cancer cells, it also unintentionally affects the calcium channels in the nerve cells, leading to the development of LEMS. 

It is also important to note that LEMS can occur in people who don’t have an underlying malignancy; in such cases, it is considered to be of unknown cause (idiopathic). 

Signs and symptoms of LEMS

LEMS is a rare autoimmune disorder that is typically characterised by the following symptoms: ³

• Proximal muscle weakness and fatigue in the hips and shoulders 
• Problems in tasks requiring muscle strength such as walking, climbing the stairs, lifting objects, raising the arms above your head and standing up from a seated position 
• Muscle pain and stiffness 
• Issues with automatic bodily functions, which include dry mouth, dry eyes, impotence (sexual dysfunction), constipation, difficulties with bladder and bowel control, reduced sweating, fixed and dilated pupils, lightheadedness when standing, and poor movement of the oesophagus (food tube) and intestines.
• Poor or absent reflexes, including the knee-jerk reflex

In severe cases, people may develop the following symptoms:

• Problems with cranial nerves include double vision, drooping eyelids, slurred speech, difficulty chewing and swallowing, a weaker voice, and your head leaning forward. 
• Respiratory muscle weakness, which causes difficulty in breathing 

Diagnosis

To diagnose LEMS, your healthcare provider will perform a thorough evaluation by first checking your medical history and current symptoms, taking a physical examination, and testing how well your reflexes are.

In the majority of cases, your healthcare provider may refer you to a medical specialist, such as a neurologist, who will perform further detailed tests to accurately diagnose and distinguish LEMS based on the symptoms present. 

These tests include:⁴

• A blood test is carried out to detect the presence of calcium channel antibodies in your bloodstream based on your immune system's attack on your nerve cells.
• Electrophysiological testing to check the electrical signals in your muscles. It involves placing small sensors on your skin and recording the muscle responses. In LEMS, the test usually reveals small electrical signals (action potentials).
• Imaging tests such as a chest X-ray, CT or MRI scan to identify whether the individual has small-cell lung cancer.

Management and treatment for LEMS

The goal of managing and treating LEMS is to alleviate symptoms and improve muscle strength. 

Cancer treatment

As people with LEMS tend to have small-cell lung cancer, treating the cancer can improve the symptoms of LEMS. Cancer treatment options may include surgery, chemotherapy, radiotherapy, or even a combination of these approaches, depending on the type and stage of cancer examined by your healthcare provider. 

Symptomatic treatment

This includes medications to improve the symptoms of the LEMS, such as muscle weakness and fatigue. The following medications include ⁵

• Amifampridine Phosphate (Firdapse), Guanidine:⁶ These medications help the nerves release acetylcholine to the muscles at the neuromuscular junction to alleviate muscle weakness and fatigue. Guanidine is usually avoided as it can potentially harm the kidneys and bone marrow. 
• Pyridostigmine: This medication works by blocking an enzyme called cholinesterase, which breaks down acetylcholine at the neuromuscular junction. This then increases the amount of acetylcholine needed to send signals at the neuromuscular junction to improve muscle function. This medication is often prescribed along with guanidine for moderate to severe muscle weakness. The side effects of pyridostigmine are usually mild, such as nausea, abdominal cramping, and diarrhoea.

Immune therapy

This therapy works by boosting the immune system and helps manage the symptoms of LEMS, improving muscle function. The available options for immune therapy include

• Intravenous immunoglobulin (IVIG):  Intravenous immunoglobulin (IVIG) is a first-line treatment for the stubborn weakness seen in LEMS patients. It works by neutralising harmful autoantibodies and regulating specific immune cells that are overactive. The treatment involves injecting a total dose of IVIG over two to five days, with additional infusions over several weeks if needed. Improvement in weakness may take a few weeks, and occasional recurrent weakness can occur. 
• Immunosuppressants: These medications are used to control your body’s overactive immune system. They work by reducing the activity of specific immune cells that may be causing damage to your immune system. Examples of immunosuppressants include prednisone, azathioprine, mycophenolate and cyclosporine. Your healthcare provider may prescribe rituximab when other immunosuppressive drugs aren’t managing your symptoms effectively. 
• Plasma exchange: This is a medical procedure that removes harmful antibodies and other immune system components that attack your nerve cells from your bloodstream. It works by using a machine to separate the liquid part of your blood (plasma), which contains your antibodies and other immune system components, and then putting the cleaned blood cells back into your body. This treatment is only recommended by your healthcare provider if you have become severely affected by LEMS and require immediate attention.

FAQs

How can I prevent LEMS?

Preventing Lambert-Eaton myasthenic syndrome (LEMS) is challenging since its root cause is not fully understood. 

However, as LEMS has been found to occur in people with lung cancer, you can lower your risk of developing lung cancer by

• Quitting smoking
• Avoid second-hand smoke
• Doing a radon check
• Following a healthy lifestyle
• Getting enough sleep

• Managing stress
• Avoiding heat exposure
• Getting regular checkups

How common is LEMS?

LEMS affects around 2.8 people per million worldwide, and more than half of LEMS cases are commonly diagnosed in middle-aged or older people with lung cancer. However, if LEMS is not associated with lung cancer, it can occur at any age. The condition is extremely rare in children, with only 11 cases reported in the literature.

Who is at risk of LEMS?

LEMS can be associated with certain risk factors, which may increase the likelihood of developing the condition. These risk factors include:

• Underlying malignancy (cancer)
• Co-existing autoimmune conditions: These may include rheumatoid arthritis, multiple sclerosis, lupus, type 1 diabetes and various other autoimmune conditions.
• Smoking
• Family history

When should I see a doctor?

If you notice unusual signs like muscle weakness that makes walking a challenge, double vision or drooping eyelids, slurred speech, difficulty swallowing, or any unexplained neurological symptoms, please consult your doctor. It's especially important to seek medical attention if you have a history of cancer or autoimmune disorders or if you're a smoker or exposed to secondhand smoke. Remember, your health is invaluable, and early detection and treatment can make a world of difference.

Summary

Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder that weakens the connection between your nerve and muscle cells, leading to muscle fatigue. It can occur on its own or be associated with small-cell lung cancer or other autoimmune diseases. Common symptoms include proximal muscle weakness, double vision, and difficulty swallowing. The exact cause is not fully understood, and there's no known way to prevent LEMS. However, treatments like medications to improve nerve-muscle communication, immunosuppressive therapy, and plasma exchange can help manage symptoms and improve quality of life. If you experience any concerning symptoms, seek medical attention promptly for an early diagnosis and appropriate care.