Lambert-Eaton myasthenic syndrome (LEMS)

Learning objectives

Lambert-Eaton myasthenic syndrome (LEMS) is a very rare condition in which the immune system attacks the neuromuscular junctions thereby interfering with the ability of nerve cells to send signals to muscle cells
A miscommunication between the nerve cell and the muscles that leads to the gradual onset of muscle weakness and autonomic nervous system dysfunction
More specifically, voltage-gated calcium channels in the presynaptic neuronal cell membrane are attacked by antibodies, and with fewer calcium channels, acetylcholine release from the presynaptic nerve terminals is reduced
Two types of LEMS:
- Paraneoplastic LEMS is often associated (50-60%) with small-cell lung cancer
  - Treat underlying cancer as this may improve symptoms from this condition
  - Characterized by an older age of onset (average 60 years)
  - Caused by an accidental attack by the immune system as it attempts to fight the cancer
- LEMS may also be associated with:
  - Endocrine diseases such as hypothyroidism or diabetes mellitus type 1
  - It may have a genetic component linked to autoimmunity
  - Younger age of onset (on average 35 years)
Myasthenia gravis has very similar symptoms to Lambert-Eaton syndrome
In contrast to myasthenia gravis, the weakness in Eaton–Lambert syndrome usually improves with exercise

Primary clinical manifestation: muscle weakness and muscle fatigue
Trouble walking
Muscle pain or stiffness
Tingling sensation in your hands or feet
Droopy eyelids (ptosis)
Double vision (diplopia)
Dry mouth and dry eyes
Constipation
Decreased sweating
Weight loss
Difficulty peeing
Erectile dysfunction
Dysarthria and dysphagia are late-stage symptoms
Dyspnea and respiratory failure
Lambert-Eaton myasthenic syndrome typically affects upper leg muscle strength first, followed by shoulder muscles, muscles of the hands and feet, muscles affecting speech and swallowing, and eye muscles
Symptoms develop gradually over weeks or months

Treatment for underlying malignancy: surgery, radiation, or chemotherapy
Improve muscle strength: amifampridine, guanidine
Acetylcholinesterase inhibitors: pyridostigmine (30-120 mg every 3-6 hours) or 3,4-diaminopyridine
Intravenous immune globulin
Immunosuppression: prednisolone, azathioprine, methotrexate, cyclosporine
Plasmapheresis
Rituximab