Introduction 

Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disease.

It means your body produces antibodies that attack its own tissues.

In LEMS, this immune attack targets your neuromuscular junction- the point where your nerves communicate with one another or with muscle to initiate movement.¹

These autoimmune cells affect communication between your nerves and muscles. As a result, your muscles do not receive enough signals, leading to weakness. 

This weakness makes it difficult to initiate movement. The weakness usually starts in the upper parts of your legs. You can also feel weakness in your arms and face.

Who does LEMS affect?

Two groups of people get Lambert-Eaton myasthenic syndrome (LEMS).

• Paraneoplastic LEMS (50–60% of cases):¹

This form usually occurs in people with underlying cancer, especially small-cell lung cancer (SCLC). It begins around age 58²

• Non-paraneoplastic LEMS: Occurs in younger and older adults.

Happens around age 35 and again at about age 60. It's usually because of other autoimmune conditions¹

The condition is more common in males. 

In this article, we‘ll explore Lambert-Eaton Myasthenic Syndrome in the elderly, including diagnostic challenges and considerations. We are taking this approach because it often begins later in life and 

Age-related changes and comorbidities can affect diagnosis.

Common causes of lambert-eaton myasthenic syndrome in the elderly 

The majority of the cases are associated with small-cell lung carcinoma (SCLC). Others may result from unknown autoimmune conditions.

Some predisposing risk factors are: 

• History of smoking 
• Age-related immune changes
• Malignancy incidence in older adults
• Being male 

What happens in LEMS?

In normal neuromuscular transmission:

• Nerve impulse reaches the presynaptic terminal of a motor neuron.
• Voltage-gated calcium channels (VGCCs) open.
• Calcium enters the neuron, causing the release of acetylcholine (ACh).
• ACh crosses the synapse and binds to receptors on the muscle, causing it to contract.

In LEMS:

• Your immune system produces autoantibodies, primarily against P/Q-type voltage-gated calcium channels
• These antibodies block or destroy the calcium channels
• Less calcium enters the nerve terminal, so less ACh is released
• Your muscle receives less stimulation, leading to weakness, especially in the proximal muscles (e.g., hips, shoulders)

What are the symptoms of lambert-eaton myasthenic syndrome in the elderly?

• Muscle weakness, especially in the upper parts of your legs
• Difficulty moving or standing from a chair
• Double vision and drooping of the upper eyelid 
• Misalignment of the eyes and pupillary dysfunction 
• Slurred speech 
• Dry mouth 
• Erectile dysfunction 
• Constipation 
• Dizziness on standing or orthostatic dysfunction
• Changes in sweating patterns 
• Difficulty swallowing. Occurs in advanced stages
• Respiratory failure is in the late stage of disease, but usually rare

Atypical symptoms in the elderly 

• Weakness can be mistaken for Parkinson’s or diabetic neuropathy. 
• Common signs like fatigue or slow gait can be overlooked as part of normal aging. 
• Symptoms like dry mouth, constipation and erectile dysfunction can often be dismissed as age-related or side effects of medication.
• Polypharmacy and cognitive decline can mask or confuse a diagnosis.

Diagnosis of lambert-eaton myasthenic syndrome

Clinical examination 

 Your provider will take a thorough history and perform a physical examination.

Blood test

Shows if voltage-gated calcium channel antibodies are present. 

Electromyography

Measures how your muscles respond to nerve signals. EMG detects if muscle movement improves after activity, which is a unique feature of LEMS

Imaging (CT or MRI of the chest)

Used to detect underlying small-cell lung cancer.

Diagnostic challenges in the elderly 

Overlap of symptoms

LEMS usually present with symptoms similar to other neuromuscular disorders like 

myasthenia gravis, age-related sarcopenia, parkinson’s disease and peripheral neuropathies.⁴ The symptoms can be mistaken for symptoms of these conditions, leading to misdiagnosis.

Age-related symptoms

Common ageing health problems like dry eyes, weakness, or erectile dysfunction may mask LEMS. This can delay diagnosis.

Polypharmacy

The elderly are prone to taking multiple medications at the same time. 

Side effects of medication can appear as symptoms and complicate diagnosis.

Electromyography testing difficulties

• The test needs experienced neurologists and high-quality machines
• Elderly patients may struggle with the discomfort or length of the test
• Early-stage LEMS may not show electrical changes, making it hard to detect
• Muscle weakness makes it hard to get clear results

All these affect diagnosis 

Antibody blood tests limitations

•  P/Q-type voltage-gated calcium channels are not only found in LEMS conditions. They can also be seen in other neurological conditions²
• Not all people with LEMS test positive for VGCC antibodies (5–15% test negative)²
• There is currently no universally accepted antibody cut-off that distinguishes pathogenic VGCC antibodies from incidental VGCC antibodies
• A high voltage-gated calcium channel antibody level alone does not mean LEMS³

A study found that 58% of the patients with high VGCC antibodies didn't indicate LEMS or anything similar. In fact, only 6 patients (6%) had LEMS. This means that high voltage-gated calcium channel antibody levels are not found only in LEMS.

Cancer screening and timing

• LEMS often precedes the clinical detection of cancer. In fact, cancer signs sometimes take months and years before they show
• Early screening is critical but may initially yield false negatives

All these can lead to misdiagnosis

Best practices for diagnosis

1. Take a detailed history and do a proper physical examination. 
2. Look for unexplained muscle weakness in the upper parts of the legs with normal sensation. This is a hallmark symptom of LEMS.
3. Work with different specialists to treat LEMS, because older people often have other health problems that can affect their symptoms.
4. Elderly people may not tolerate long invasive procedures. Start with the important and non-invasive tests.

Management of Lambert-Eaton myasthenic syndrome

Treat according to symptoms

Symptomatic therapies improve symptoms at the neuromuscular transmission and relieve muscle weakness.

Eg:

• Amifampridine (3,4-Diaminopyridine)- improves muscle strength, mobility, and fatigue¹
• Pyridostigmine (Mestinon): helps especially in mild LEMS or in combination with amifampridine¹

Supportive care

Provide supportive care like physical and occupational therapy. 

Provide assistive devices and also prevent falls. 

Immunosuppressive therapies

This is when LEMS is not purely paraneoplastic.  Immunosuppressive treatments suppress the autoimmune response against voltage-gated calcium channels (VGCCs).⁵

• Oral Corticosteroids (Prednisone): Suppresses autoimmune response by stopping T-cell and B-cell activity
• Azathioprine or Mycophenolate Mofetil: Steroid-sparing agents that reduce antibody production

Manage other conditions 

Elderly patients with LEMS commonly have comorbidities like hypertension, diabetes, and cancer (especially small-cell lung cancer). Treat comorbid conditions that can worsen neuromuscular weakness.

Reduce polypharmacy

Reduce the use of medications that have neuromuscular side effects.  

Prioritise only important drugs and prescribe once-daily regimens whenever possible.

Treat Underlying Small-Cell Lung Cancer (SCLC)

If LEMS is paraneoplastic, it is associated with small-cell lung cancer (SCLC).

Treat the underlying cancer, as it may lead to significant improvement or even resolution of LEMS symptoms.

Prognosis 

The prognosis of Lambert-Eaton Myasthenic Syndrome (LEMS) varies based on its cause and response to treatment.

In paraneoplastic cases, especially those associated with small-cell lung cancer (SCLC), the outcome depends on the cancer's progression.

Treating the cancer may significantly improve neuromuscular symptoms. 

Non-paraneoplastic LEMS often respond well to symptomatic treatment and immunosuppressive treatment.

Supportive care, fall prevention, and managing comorbidities further improve quality of life. 

However, the chronic nature of the condition requires ongoing monitoring. 

With early diagnosis and comprehensive care, many individuals with LEMS can maintain a good long-term functional status.

Summary 

Lambert-Eaton Myasthenic Syndrome (LEMS) is a rare autoimmune disorder where your immune system attacks the neuromuscular junction.

This leads to muscle weakness, especially in the legs. It commonly affects older adults.

It is often linked to small-cell lung cancer (paraneoplastic LEMS), or may occur with other autoimmune diseases. 

Diagnosing LEMS in the elderly is challenging due to overlapping symptoms with ageing and other conditions, polypharmacy, and testing limitations. Management involves symptomatic treatments, immunosuppressants, treating underlying cancer, and supportive care. 

Early recognition, multidisciplinary care, and careful medication review improve outcomes and quality of life for elderly patients living with LEMS.