Lambert-Eaton Myasthenic Syndrome (LEMS)

What happens in LEMS

When a nerve signal reaches a muscle, calcium enters the nerve ending through voltage-gated calcium channels (VGCC) and triggers the release of acetylcholine, which makes the muscle contract. In LEMS, antibodies block these channels, especially the P/Q type, so less acetylcholine is released. Muscles respond weakly.

Brief exercise temporarily increases calcium build-up in the nerve ending, which is why strength and reflexes can improve for a few seconds after effort, a hallmark of LEMS.

Two forms

• Paraneoplastic LEMS: triggered by a cancer, most often small cell lung cancer, whose cells carry the same calcium channels. Usually in older smokers. Weakness often progresses over weeks to months.
• Non-paraneoplastic (autoimmune) LEMS: no cancer; often in younger people, sometimes with other autoimmune conditions. It progresses more slowly.

Symptoms

• weakness of the hips and thighs: difficulty climbing stairs, getting up from a chair, walking
• shoulder and arm weakness later
• fatigue
• autonomic symptoms: dry mouth, constipation, erectile dysfunction, reduced sweating, dizziness on standing (orthostatic hypotension)
• reduced or absent reflexes
• mild drooping eyelids or double vision
• aching muscles
• rarely, breathing or swallowing difficulty

LEMS vs myasthenia gravis

Diagnosis

1. Examination: proximal weakness, reduced reflexes that increase after 10 seconds of muscle contraction.
2. Blood test: P/Q-type VGCC antibodies are present in about 85% to 90% of people with LEMS. SOX1 antibodies suggest an associated lung cancer.
3. Nerve conduction studies and EMG: small muscle responses that more than double after 10 seconds of exercise or with rapid repetitive nerve stimulation.
4. Cancer screening: CT of the chest and often PET-CT at diagnosis. If negative, screening is usually repeated every 3 to 6 months for about 2 years, especially in smokers, because the cancer may appear later.

Treatment

Treat the cancer

If small cell lung cancer is found, treating it with chemotherapy and radiotherapy often improves LEMS symptoms.

Symptom treatment

• Amifampridine (3,4-diaminopyridine): blocks potassium channels in the nerve ending, prolonging the signal so more acetylcholine is released. It is the first-line symptomatic treatment.
• Pyridostigmine: sometimes added, though less effective alone in LEMS.

Immune treatment

For persistent or severe weakness:

• corticosteroids, often combined with azathioprine or other immunosuppressants
• intravenous immunoglobulin (IVIG)
• plasma exchange for severe exacerbations
• rituximab in resistant cases

Medicines to use with caution

Some medicines can worsen weakness, including certain antibiotics (aminoglycosides, fluoroquinolones, macrolides), magnesium, some heart medicines, and muscle relaxants used in anesthesia. Always tell doctors and anesthetists that you have LEMS.

Outlook

The outlook depends largely on whether there is an associated cancer. People with LEMS and small cell lung cancer may survive longer than those with the cancer alone, possibly because the immune response also targets the tumor and the cancer is found earlier. Non-cancer LEMS is a long-term condition, but most people improve and remain independent with treatment.

Frequently asked questions

What are the symptoms of Lambert-Eaton syndrome?

The main symptoms are weakness of the hips and thighs, making stairs and rising from a chair difficult, plus fatigue, dry mouth, constipation, erectile dysfunction and reduced reflexes. Some people have mild drooping eyelids or double vision.

Is Lambert-Eaton syndrome a type of cancer?

No, but about half of cases are triggered by small cell lung cancer, which may not yet be detectable when LEMS starts. That is why people with LEMS have chest CT or PET scans at diagnosis and regular screening afterward.

How is LEMS different from myasthenia gravis?

LEMS usually starts with leg weakness, causes dry mouth and reduced reflexes, and strength briefly improves with exercise. Myasthenia gravis usually starts with drooping eyelids and double vision, and weakness worsens with repeated use. Different antibodies cause each condition.

What is the treatment for Lambert-Eaton myasthenic syndrome?

Treatment includes amifampridine to improve nerve signaling, immune therapies such as steroids, IVIG or plasma exchange, and treatment of any associated cancer, which can improve LEMS symptoms.

Can Lambert-Eaton syndrome be cured?

If LEMS is caused by cancer and the cancer is successfully treated, symptoms can improve substantially. Non-cancer LEMS is usually long-term, but most people achieve good control of symptoms with medication.