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Lambert-Eaton Myasthenic Syndrome

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Overview

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease of the neuromuscular junction and is much rarer than myasthenia gravis. It is due to antibodies to the voltage-gated calcium ion channels in neuromuscular junctions reducing the number of calcium ions entering the presynaptic nerve and hence, reducing the amount of acetylcholine (ACh) which is needed for muscle contraction.

It is strongly associated with small cell lung cancer, therefore patients with LEMS should have thorough investigations for underlying cancer.

Epidemiology

  • Associated with small cell lung cancer
  • Men are affected more than women

Risk Factors

  • Small cell lung cancer
  • Co-existing autoimmune disease
  • Family history of autoimmune disease

Presentation

Unlike myasthenia gravis, repeated muscle contractions lead to increased muscle strength. This is because repeated exercise eventually leads to enough calcium ions being released for sufficient ACh release and muscle contraction.

Features may be:

  • Limb weakness – usually the lower limbs and hips are affected first
  • Hyporeflexia – may be absent/reduced but can appear after muscle contraction
  • Dysphagia
  • Autonomic dysfunction – the autonomic system also involves calcium ions and ACh release
  • Diplopia/ptosis usually appears later in the disease, unlike MG, where it is seen earlier

Differential Diagnoses

Myasthenia gravis (MG)

  • Muscle weakness is worse with activity and at the end of the day
  • Diplopia/ptosis appears earlier in MG compared to LEMS
  • Tendon reflexes are normal
  • Pupils are normal

Investigations

  • Anti-P/Q voltage-gated calcium channel antibodies:
    • Positive in LEMS
  • Acetylcholine receptor antibody (anti-AChR):
    • Negative in LEMS
  • EMG:
    • Repetitive nerve stimulation shows increasing responses
  • CT chest:
    • May show underlying small-cell lung cancer

Management

  • 1st-line: investigate for/treat the underlying cancer
  • Consider 3,4-diaminopyridine (amifampridine) for symptomatic relief
  • Consider immunosuppression in severe cases – prednisolone/azathioprine/ methotrexate/ciclosporin
  • Patients should be closely followed up and screened for any underlying cancer

Complications and Prognosis

Complications

Prognosis

  • The prognosis depends on the presence and severity of underlying malignancy or associated autoimmune disease
  • LEMS often leads to the early detection of small cell lung cancer, allowing for the prognosis of both to be improved

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