Lambert-Eaton myasthenic syndrome
Lambert-Eaton myasthenic syndrome is an autoimmune presynaptic neuromuscular junction disorder caused by antibodies to P/Q-type voltage-gated calcium channels, producing proximal leg-predominant weakness that improves with repeated effort, depressed reflexes, and autonomic symptoms. About half of cases are paraneoplastic, usually from small cell lung cancer. Diagnosis rests on the voltage-gated calcium channel antibody and an incremental response to high-rate repetitive nerve stimulation, followed by a search for the tumor; treating the cancer comes first, with amifampridine, pyridostigmine, IVIG, plasma exchange, or immunosuppression for symptoms.
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What this article covers
- Overview
Definition: Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of the presynaptic neuromuscular junction in which antibodies against P/Q-type voltage-gated calcium channels (VGCC)…
- Epidemiology
Uncommon: LEMS is far less frequent than myasthenia gravis, which is the most common neuromuscular junction disorder.
- Risk factors
Small cell lung cancer: the dominant association and the cause of most paraneoplastic cases.
- Pathophysiology
Tumor-driven autoimmunity: SCLC cells express antigens that provoke a vigorous immune response; the resulting antibodies cross-react with VGCC on presynaptic nerve terminals.
- Clinical features
Hallmark, proximal weakness that improves with use: slowly progressive weakness of the hip and shoulder girdle, legs more than arms (difficulty rising from a chair, climbing stairs, combing hair)…
- Differential diagnosis
Myasthenia gravis: fatigable weakness that worsens with use, ocular and bulbar predominance, preserved reflexes, no autonomic symptoms, acetylcholine receptor antibodies, and a decremental response to repetitive stimulation.
- Diagnosis
The diagnosis is established by the clinical triad (proximal weakness, hyporeflexia, autonomic dysfunction) plus a positive anti-P/Q-type VGCC antibody and/or the characteristic electrodiagnostic…
- Management
First, if a tumor is found, treat the cancer, which is the primary therapy and often improves the weakness: limited-stage SCLC: cisplatin 60 mg/m2 IV day 1 plus etoposide 120 mg/m2 IV days 1-3, every…
- Complications
Respiratory failure: diaphragmatic weakness, worsened by infection, anesthesia, or precipitating drugs, can require ventilatory support.
- Prognosis
Cancer status determines survival: in paraneoplastic LEMS, survival is driven by SCLC, which carries the poorest prognosis of the lung cancers.
- Prevention
Screen for lung cancer in eligible smokers: annual low-dose CT for adults aged 50-80 years with a 20 pack-year smoking history who currently smoke or quit within the past 15 years.
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