FFinalistSouthampton · 2027
Neurology
AKT · Neurology/Demyelinating & NMJ

Lambert-Eaton myasthenic syndrome

Autoantibodies to presynaptic voltage-gated calcium channels (VGCC)

Overview

An autoimmune disorder of the neuromuscular junction in which antibodies against presynaptic voltage-gated CALCIUM channels reduce acetylcholine release. The mirror image of myasthenia gravis: PROXIMAL weakness that IMPROVES with repeated use, with autonomic features, and a strong association with SMALL-CELL LUNG CANCER (paraneoplastic).

Recognise

  • Proximal lower-limb weakness and a waddling gait that IMPROVES transiently with repeated/sustained activity (post-exercise facilitation) — opposite to myasthenia's fatigability
  • Autonomic features: dry mouth, constipation, erectile dysfunction; reduced/absent reflexes that RETURN after exercise
  • Ocular/bulbar involvement is less prominent than in myasthenia; ~50% have an underlying small-cell lung cancer

Red flags

  • Underlying small-cell lung cancer — investigate (CT chest, and re-screen if initially negative); respiratory/bulbar involvement

Differentials & how to tell them apart

Myasthenia gravisweakness WORSENS with use (fatigability), prominent ocular/bulbar signs, anti-AChR antibodies, DECREMENTAL response — Lambert-Eaton improves with use and has autonomic features
Inflammatory myopathyproximal weakness with raised CK, no facilitation or autonomic features
Guillain-Barréascending areflexic weakness, acute, post-infective

Investigations

Anti-VGCC antibodies; nerve conduction studies (INCREMENTAL response on high-frequency/post-exercise stimulation — opposite to the decrement in myasthenia); CT chest ± PET to hunt for small-cell lung cancer.

Management

Investigate/treat small-cell lung cancer + amifampridine (3,4-DAP) for symptoms

  1. 1Confirm (anti-VGCC, incremental NCS) and HUNT FOR a small-cell lung cancer (CT chest ± PET). Symptomatic treatment with 3,4-diaminopyridine (amifampridine).Gate: Weakness that IMPROVES with repeated use (+ autonomic features + absent reflexes that return after exercise) is Lambert-Eaton, NOT myasthenia — and it mandates a search for small-cell lung cancer (paraneoplastic), which myasthenia does not
  2. 2Treat any underlying malignancy (often improves the syndrome); immunotherapy (IVIG/steroids/immunosuppression) for persistent weakness; re-screen for cancer if the initial work-up is negative.
Treat the underlying cancer — managing a small-cell lung cancer often improves the syndrome
3,4-diaminopyridine (amifampridine) — first-line symptomatic treatment — increases ACh release
Immunotherapy (IVIG, steroids, immunosuppressants) — for significant weakness

Key points

Improves with use + dry mouth + absent reflexes + smoker = Lambert-Eaton → look for small-cell lung cancer. It is the paraneoplastic mirror-image of myasthenia (which worsens with use).

Monitor & prognosis

Strength, cancer surveillance, respiratory function.

Depends on the underlying cancer; symptomatic treatment helps the weakness.

Source: NICE CKS; ABN guidance