Lambert-Eaton myasthenic syndrome
Autoimmune disorder of the neuromuscular junction (presynaptic) where antibodies target voltage-gated calcium channels, reducing acetylcholine release. Often a paraneoplastic syndrome (≈60% associated with small-cell lung carcinoma).
- Though rare, recognizing LEMS can lead to early diagnosis of an occult small cell lung cancer (LEMS symptoms often precede cancer detection by months). It's also a classic exam topic contrasting LEMS vs myasthenia gravis, highlighting LEMS's unique features (e.g. strength improves with use, autonomic involvement).
- Insidious onset of proximal leg weakness (difficulty rising from chairs, climbing stairs) that may transiently improve with exertion (facilitation).
- Marked hyporeflexia or absent deep tendon reflexes at rest, which temporarily return after brief exercise (post-exercise facilitation).
- Autonomic symptoms are common – notably dry mouth (often early), plus others like impotence, constipation, and orthostatic lightheadedness.
- Minimal ocular or bulbar involvement (ptosis or diplopia in <30%, much milder than in MG); respiratory muscle weakness is rare.
- Confirm diagnosis with electrodiagnostics: repetitive nerve stimulation shows a >100% increase in compound muscle action potential (CMAP) amplitude after exercise or high-frequency stimulation (incremental response).
- Detect anti–P/Q voltage-gated calcium channel antibodies in serum (present in ~85–90% of cases) to support the diagnosis.
- Always screen for malignancy: perform chest imaging (CT scan) to check for small cell lung carcinoma; if initial scan is negative, repeat every 6 months for 2 years.
- Differentiate from myasthenia gravis: LEMS has absent reflexes and autonomic dysfunction, and strength improves with use (MG typically has normal reflexes, purely motor fatigue, and worsens with use).
| Condition | Distinguishing Feature |
|---|---|
| myasthenia-gravis | postsynaptic ACh receptor issue; fatigable weakness worsens with use, more ocular findings, normal reflexes |
| botulism | acute toxin-mediated presynaptic block; descending paralysis with early cranial nerve involvement, autonomic signs (dry mouth, dilated pupils) |
| Polymyositis | proximal muscle weakness but a muscle fiber disease (high CK, no NMJ facilitation, normal reflexes, no autonomic symptoms) |
- If an underlying tumor is present, treat the cancer (e.g. chemo ± radiation for SCLC) – LEMS symptoms often improve after successful cancer therapy.
- Symptomatic therapy: 3,4-diaminopyridine (amifampridine) – a K⁺ channel blocker that prolongs nerve terminal depolarization and boosts ACh release. Pyridostigmine (acetylcholinesterase inhibitor) is often added for additional improvement.
- Immunosuppression can help in non-paraneoplastic or refractory LEMS: corticosteroids (e.g. prednisone) and/or azathioprine; also IVIG or plasmapheresis for short-term benefit, though LEMS responds less to these than MG.
- Mnemonic: LEMS – Legs (starts in proximal legs), Enhanced by Exercise (strength temporarily improves), Malignancy (paraneoplastic, often small cell lung CA), Spares eyes (ocular signs are mild).
- Facilitation phenomenon: brief exercise makes reflexes and strength transiently better – a hallmark of LEMS (contrast with MG).
- LEMS onset in a >50-year-old smoker → assume paraneoplastic until proven otherwise. Aggressively search for small cell lung carcinoma (initial and repeat scans).
- Prolonged paralysis after surgery (excessive response to neuromuscular blockers) can be an early clue to undiagnosed LEMS.
- Proximal muscle weakness + autonomic signs (dry mouth, etc.) → suspect LEMS.
- Electrodiagnosis: perform repetitive nerve stimulation EMG (look for high-frequency facilitation) and test for anti-VGCC antibodies to confirm LEMS.
- If LEMS confirmed → screen for SCLC with chest CT (repeat every 6 mos for 2 years if initial scan is normal).
- Manage: treat underlying malignancy if present; give 3,4-DAP ± pyridostigmine for symptoms; add immunosuppressive therapy or IVIG if needed.
- Older male smoker with chronic cough develops progressive proximal weakness that improves after exercise, accompanied by dry mouth and absent reflexes → Lambert-Eaton myasthenic syndrome (paraneoplastic; suspect small cell lung cancer).
- Patient treated for "myasthenia" shows hyporeflexia and autonomic symptoms (e.g. dry mouth) – minimal improvement with edrophonium – workup reveals a lung mass → LEMS misdiagnosed as MG (LEMS has autonomic involvement and poor response to Tensilon).
A 58‑year‑old man with a 40-pack‑year smoking history has had increasing difficulty climbing stairs over 8 months. He reports a chronically dry mouth. On exam, he has proximal leg weakness (4/5 strength) that **temporarily improves** after exercise, mild ptosis, and absent reflexes (which return after a brief effort). Chest imaging reveals a left hilar mass.
A 45‑year‑old woman is evaluated for fatigable muscle weakness. She notes it takes a few attempts to rise from a squat, after which her legs feel slightly stronger. She also has dry mouth and occasional lightheadedness. She has no ptosis or double vision. On exam, proximal muscle strength is 4/5 with **absent reflexes** that partially return after brief exercise. Workup for myasthenia gravis is negative (ACh receptor antibody not detected). CT chest is normal.
Diagram of a neuromuscular junction. In LEMS, autoantibodies target presynaptic calcium channels at the nerve ending, preventing acetylcholine release into the synapse.
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