Eaton-Lambert Syndrome

Overview

• Eaton-Lambert Syndrome (ELS) is a rare presynaptic disorder of the neuromuscular junction (NMJ), characterised by decreased acetylcholine (ACh) release due to defective voltage-gated calcium (Ca²⁺) channels.

• Considered the "opposite" of myasthenia gravis (MG) in pathophysiology (ELS is presynaptic, MG is postsynaptic).

Key Features

• Weakness Improves with Repeated Use

  • Incremental improvement in muscle strength with repeated stimulation or exercise, unlike MG.

• Proximal Muscle Weakness

  • Primarily affects proximal limbs (difficulty climbing stairs, lifting objects, rising from chairs).

  • Lower limbs typically more affected than upper limbs.

• Strong Association with Small Cell Lung Cancer (SCLC)

  • 50–60% of cases are paraneoplastic, commonly linked to SCLC.

  • Increased suspicion in older patients with smoking history.

• Autonomic Dysfunction

  • Dry mouth (reduced salivary secretion)

  • Erectile dysfunction (in males)

  • Possible constipation, orthostatic hypotension, blurred vision

• Opposite of Myasthenia Gravis

  • ELS: Presynaptic (↓ Ca²⁺ channel function → ↓ ACh release)

  • MG: Postsynaptic (antibodies against ACh receptors → ↓ ACh binding)

Diagnosis

• Clinical Suspicion

  • Proximal muscle weakness improving with repeated use

  • Autonomic symptoms (dry mouth, impotence)

  • Heavy smoking history or suspicion of malignancy

• Electrophysiological Testing

  • Nerve conduction studies (NCS), repetitive nerve stimulation (RNS)

  • Initially low-amplitude muscle action potentials

  • Incremental response (>100%) after high-frequency stimulation (20–50 Hz) or sustained exercise

• Imaging & Malignancy Workup

  • Chest CT to confirm/exclude SCLC

  • PET scan if indicated

• Autoantibody Tests

  • Anti-VGCC (P/Q type calcium channels) antibodies (supports diagnosis but not always readily available)

Management

• Treat Underlying Malignancy

  • Oncological treatments (chemotherapy, radiotherapy, surgery) significantly improve symptoms

  • Smoking cessation support

• Symptomatic Therapies

  • 3,4-Diaminopyridine (3,4-DAP): First-line treatment; improves ACh release (TGA authority required)

  • IV Immunoglobulin (IVIg): Severe cases or if 3,4-DAP unavailable/contraindicated

  • Pyridostigmine (adjunctive, less effective compared to MG)

• Supportive Care

  • Physiotherapy (maintain strength/function)

  • Occupational therapy (daily living support)

  • Regular respiratory function monitoring

  • Carer support and psychosocial resources

• Follow-up & Monitoring

  • Surveillance for tumour recurrence/progression

  • Regular reassessment of muscle strength, function, autonomic symptoms

Prognosis

• Paraneoplastic ELS: Dependent on successful malignancy treatment

• Non-Paraneoplastic ELS: Generally more responsive to symptomatic treatment

• Smoking cessation and regular follow-up essential for managing malignancy risk

Key Points

• Eaton-Lambert Syndrome is presynaptic, reducing ACh release at NMJ.

• Hallmark: proximal muscle weakness improving with repeated muscle use.

• Strong association with SCLC (50–60% cases).

• Diagnosis: Electrophysiology (incremental response on repetitive stimulation), malignancy screening.

• Management: Treat underlying malignancy, symptomatic relief with 3,4-DAP, supportive care.