Paraneoplastic manifestation of small-cell bronchial carcinoma due to defective acetylcholine release at the neuromuscular junction

Aetiology

• Strong association with underlying small cell carcinoma
• A smaller proportion of cases are autoimmune without underlying malignancy

Pathophysiology

• Antibodies against voltage activated Ca2+ channels in the motor neuron terminal result in reduced Ca2+ entry in response to depolarisation → reduced ACh release

Clinical features

• Proximal limb muscle weakness, sometimes with ocular/bulbar muscles, some absent tendon reflexes
• Weakness tends to improve after a few minutes of muscular contraction (exertion), and absent reflexes return

Investigations

• Repetitive nerve stimulation
• Detection of underlying malignancy - imaging

Management

Medical

• Potassium channel blockers (e.g. 3,4-diaminopyridine aka amifampridine) increase the release of ACh by prolonging the action potential in the motoneurone terminal
• Immunosuppression recommended for severe cases - prednisolone and a steroid-sparing agent e.g. azathioprine

Surgical

• Depends on the nature of any malignancy discovered