🎯 Pathology

• autoimmune disorder of the neuromuscular junction (NMJ) disorder caused by the depletion of voltage-gated calcium channels (VGCC) due to the development of autoantibodies against these channels

• the consequence is reduced release of acetylcholine from the pre-synaptic neuron

 

🧪 Normal mechanism of acetylcholine release

• acetylcholine is synthesised and stored in vesicles at the axon terminal of the pre-synaptic motor neuron

• the action potential travels triggers the influx of calcium ions through the pre-synaptic VGCC

• this release of acetylcholine into the synaptic cleft

• in Lambert-Eaton myasthenic syndrome, calcium cannot enter the neuron due to the destruction of VGCCs, limiting the secretion of acetylcholine into the synaptic cleft

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💡 Risk factors

• malignancy as a paraneoplastic syndrome

  • small cell lung cancer (most common)

  • lymphoproliferative disorders

  • prostate cancer

• non-paraneoplastic

  • associated autoimmune disease

  • cigarette smoking

  • HLA-B8-DR3

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🩺 Clinical features

• muscle weakness

  • improves with activity (key differentiating factor from myasthenia gravis)

  • typically affects the proximal muscles of the leg —> difficulties with standing up from a seated position

• reduced/absent deep tendon reflexes

• ocular and bulbar muscles are spared (in contrast to myasthenia gravis)

• autonomic dysfunction

  • dry mouth (most commonly)

  • erectile dysfunction

  • decreased sweating

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🕵️‍♂️ Investigations

• serology

  • antibodies against VGCCs

• repetitive nerve stimulation

  • incremental response

• imaging

  • chest CT to exclude lung malignancy

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💆‍♂️ Management

• treat the underlying malignancy

• symptomatic management to elevate levels of acetylcholine

  • 3,4-diaminopyridine: enhances the release of acetylcholine into the synaptic cleft

  • pyridostigmine: inhibits the degradation of acetylcholine in the synaptic cleft

• treatment for refractory cases

  • immunosuppression with prednisolone or azathioprine

  • if severe, plasma exchange or intravenous immunoglobulin (IVIG) is considered

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🧲 High-yield tips

• repetitive nerve stimulation shows classic decremental response in myasthenia gravis while an incremental response is seen in Lambert-Eaton myasthenic syndrome

• lung mass + muscle weakness = Lambert-Eaton myasthenic  syndrome in a patient with small cell lung cancer

• anterior mediastinal mass + clinical weakness = myasthenia gravis in a patient with thymoma