Introduction

Imagine finding it difficult to stand after sitting on a chair, climbing up stairs or feeling so tired despite getting plenty of rest. This could easily be dismissed as ageing or having a busy week, but what if they could be signs of a rare condition called Lambert-Eaton Myasthenic Syndrome (LEMS)?

LEMS is a type of disease in which the body’s own immune system targets its own cells, specifically a type of cell involved in the transmission of signals from nerves to muscles. This results in progressive neurological symptoms. The main signs of LEMS are muscle weakness and fatigue.¹

This autoimmune disease is relatively rare and is often underdiagnosed. Symptoms can be vague, and the disease may be missed or there can be overlap with other conditions, creating a diagnostic challenge. Early recognition is important, as once diagnosed, treatment can start earlier, improving quality of life and potentially earlier diagnosis of other underlying issues such as cancer.^1,2

What is Lambert-Eaton Myasthenic syndrome?

LEMS is an autoimmune disease that interferes with the signalling between nerves and muscles. Impairing their ability to function normally. In LEMS, the body makes specific proteins called antibodies, which are a part of the immune system and target a part of the nerve, particularly the nerve endings. This results in the signal not reaching the muscle properly, and this causes the muscle weakness seen in LEMS.^3,4

More than half of patients with LEMS have an associated underlying cancer, and most of these patients have a type of lung cancer called small-cell lung cancer (SCLC).³ The most common risk factor for SCLC is smoking. It is important that patients diagnosed with LEMS are screened for cancer to avoid missing these diagnoses.^3,5

Why early detection matters

LEMS can vary from person to person; however, there are key features to be aware of for recognising this disease. It is important that it is recognised as early as possible, as it is a disease that progressively worsens and significantly impacts the quality of life of patients. 

Starting treatment earlier improves patient outcomes in terms of physical and mental health. Also, the earlier we recognise LEMS, the earlier potential associated cancers can be diagnosed. This is very important as early treatment of these cancers improves patient survival.^4,6 The first step towards recognising this disease is understanding the main signs and symptoms.

Recognising early signs and symptoms

LEMS is a slow, progressive disease that can often be misunderstood and unrecognised. It can develop over weeks to months. When associated with cancer, LEMS may progress more quickly.⁴ 

The classic triad of symptoms is:

• Muscle weakness
• Reduced reflexes
• Dysfunction in the autonomic nervous system

Identifying these early signs in primary care can make a life-changing difference.⁵

Muscle weakness

Muscle weakness usually starts in the upper legs. This can manifest as difficulty standing after sitting, climbing stairs and walking. The weakness is symmetrical and can progress to other muscle groups further away from the centre of the body and from the lower body up towards the head. Patients can also experience dull aching and stiffness in muscles.^3,4

Fatigue

Patients also often experience severe tiredness that does not get better after rest.⁴

Reduced deep tendon reflexes

On examination, when a doctor uses a rubber hammer to tap over a tendon, which is the tissue attaching muscle to bone, there is a stretch reflex that normally causes involuntary muscle contraction. 

A classic example is tapping over the tendon of the knee, causing the lower leg to kick forward involuntarily. In LEMS, these reflexes are reduced or absent.⁷

Autonomic dysfunction

The autonomic nervous system is constantly working to control the involuntary functions of the body, such as digestion and breathing. In LEMS, there is dysfunction in this system. 

This most commonly causes signs like dry mouth, dry eyes, constipation, erectile dysfunction and reduced sweating. 

Signs like dry mouth and dry eyes can be more subtle and may not be as easily recognised.

Post-exercise facilitation

Another characteristic feature of LEMS is a brief improvement in muscle strength and reflexes after exercise. This can be a distinguishing feature of the disease.^4,8 

Oculobulbar weakness

Less commonly, later in the progression of the disease, there can be involvement of 12 pairs of nerves supplying specific parts of the head, neck and torso that originate directly from the brain. 

These nerves are called the cranial nerves. Weakness in the muscles supplied by these nerves can cause symptoms such as: drooping of the eyelids, double vision, difficulty swallowing and speech difficulty. 

These symptoms often present if the disease is more prolonged and severe.^4,8

When to see a doctor

If you start to have new onset muscle weakness, fatigue, or notice issues with your normal activities of daily living, it is important that you see a doctor. 

Trust your instincts if you feel that something is not right. It is important that in primary care, GPs are able to recognise the early signs of LEMS and decide when further investigations and specialist referrals are needed.

What to expect when seeing a doctor

A patient having symptoms suspicious for LEMS will have a physical examination to assess the functioning of the nervous system, including muscle strength and reflexes. 

Further investigations after this, if there are signs of LEMS, may include:^4,8

• Blood tests looking for specific antibodies
• Electromyography, which checks for problems with nerves and muscles
• Cancer screening investigations

LEMS can affect patients’ quality of life; however, there are treatments that can help reduce the symptoms.⁶ Treatments include targeted medications that act on nerves to improve the transmission of signals between the nerve and the muscle.^4,7,8 

There are also immunotherapies, for example, treatment aimed at removing the harmful antibodies, reducing the attack of the immune system on the nerves.⁷

FAQs

What is LEMS?

LEMS is an autoimmune disease where the immune system targets nerve endings that interfere with signalling related to muscle contraction.²

Who gets LEMS?

LEMS can occur at any age, and it is seen equally in both men and women. It is more common in people with small-cell lung cancer.¹

What are the main symptoms of LEMS?

• Muscle weakness – usually starts in the hips and thighs
• Fatigue
• Dry mouth
• Difficulty swallowing
• Speech difficulty
• Temporary decrease in muscle strength after exercise

Why is it important that LEMS is recognised early?

More than half of cases are associated with cancer, so recognition can lead to earlier cancer diagnosis and treatment. This can lead to better outcomes and increased survival.^4,5

Is it treatable?

There is no cure for LEMS; however, there are treatments, such as immunotherapies, that can significantly help with controlling symptoms. Additionally, if there is an underlying cancer, treating this can improve LEMS symptoms.⁷

Summary

LEMS is an autoimmune disease that can have a huge physical and mental impact on patients, and waiting for a diagnosis can be very difficult. Key early signs to look out for are muscle weakness, fatigue and autonomic symptoms such as dry mouth. 

There are investigations, such as EMG and tests for antibodies, that can be used in the diagnosis of the disease. It is important to be well-informed and know that there are treatment options available, including immunotherapies for controlling symptoms. There are also support groups and resources available for patients and their families.

It is important that we are able to recognise this disease early to ensure better outcomes. If you notice symptoms of LEMS such as muscle weakness and persistent fatigue, do not hesitate to see a doctor. It is also important to remember that LEMS diagnosis can be associated with a cancer diagnosis.