Lambert–Eaton myasthenic syndrome

Disease class: Autoimmune diseases of the nervous system
Disease class: Nervous system paraneoplastic syndromes
Disease class: Neuromuscular junction diseases 

Also known as LEMS.

This is an example of a paraneoplastic syndrome.

 

Pathophysiology

1. A neoplasm over-expresses a voltage gated calcium channel (VGCC). Usually small cell lung cancer.
2. There is production of autoantibodies in response to this channel.
3. These autoantibodies bind to VGCCs in the pre-synaptic membranes at the neuromuscular junctions of skeletal muscles.
4. The blockade of the calcium channels prevents the influx of calcium ions.
5. This prevents the activation of the cellular machinery responsible for acetylcholine release. 
6. There is reduced acetylcholine signalling. 
7. There is a decrease in skeletal muscle contractility and autonomic function (e.g. gland secretions). 

There are other known mechanisms of autoantibody disruption of acetylcholine release in LEMS.

 

Symptoms and signs

• Proximal muscle weakness, which is usually relieved after exertion or exercise.
• The muscles of the legs and trunk are usually the worst affected.
• The muscles of the eyes are rarely affected.
• Dysfunction of the autonomic nervous system
• Dry mouth
• Constipation
• Blurred vision  

 

Investigations

• Nerve conduction study (NCS) 
• Electromyography (EMG)
• Voltage gated Ca2+ Antibodies

 

Management

• Medical therapy
• Treatment of underlying malignancy. 
• Acetylcholinesterase inhibitors
• Immunosuppression (therapeutic)
• Airway management
• Tracheal intubation
• Mechanical ventilation

 

Compare with 

• Botulism
• Guillain–Barré syndrome
• Myasthenia gravis
• Organophosphate poisoning