A rare autoimmune disorder of the neuromuscular junction.
Lambert-Eaton myasthenic syndrome (LEMS) occurs either as a paraneoplastic disorder in association with an underlying cancer (CA-LEMS), or without cancer and as part of a more general autoimmune state (NCA-LEMS).
Symptoms include insidious and gradual onset of fatigue, weakness, and a dry mouth.
Clinical findings include proximal muscle weakness in hip girdle and thigh muscles; absent or reduced tendon reflexes that may facilitate after brief exercise; and dilated, poorly reactive pupils.
Serum P/Q-type voltage-gated calcium-channel antibodies are usually present. Electrophysiological studies usually demonstrate decremental responses to low-frequency repetitive nerve stimulation, and may also exhibit postactivation facilitation of >100%.
Over 40% of LEMS patients have underlying cancer, usually small cell lung cancer. Effective treatment of underlying cancer frequently improves symptoms.
Effective symptomatic and long-term treatment options include agents that augment neuromuscular transmission and immunomodulators. However, many patients have long-term disability due to weakness.
Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of the neuromuscular junction. It may occur as a paraneoplastic disorder in association with cancer (CA-LEMS), usually a small cell carcinoma of the lung, or may also occur without cancer, as part of a more general autoimmune state (NCA-LEMS). In both types, LEMS is characterised by the presence of circulating antibodies against voltage-gated calcium channels; these impair neuromuscular transmission by inhibiting inward calcium current and subsequently the release of acetylcholine into the synaptic cleft.
History and exam
Key diagnostic factors
- presence of risk factors
- limb weakness
- dry mouth
Other diagnostic factors
- orthostatic hypotension
- pupillary dilation
- cerebellar ataxia
- underlying small cell lung cancer or other malignancy
- co-existing autoimmune disorder
- cigarette smoking
- family history of autoimmune disease
1st investigations to order
- nerve conduction studies
- low-frequency repetitive nerve stimulation
- anti-P/Q voltage-gated calcium-channel serology
- chest CT scan
- anti-acetylcholine receptor (AChR) serology
Investigations to consider
- serial PFTs
- total-body fluoro-2-deoxyglucose positron emission tomography (FDG-PET) scan
- high-frequency or tetanic repetitive nerve stimulation (RNS)
- single-fibre electromyography
- HLA haplotyping
- thyroid-stimulating hormone (TSH)
- antinuclear antibodies (ANA)
- rheumatoid factor (RF)
- antineutrophil cytoplasmic autoantibodies (ANCA)
- B12 and methylmalonic acid (MMA)
- alpha-1A P/Q voltage-gated calcium-channel subunit antibodies
- anti-SOX1 antibodies
severe respiratory or bulbar weakness
without severe respiratory or bulbar weakness
- Myasthenia gravis
- Evidence-based guideline: intravenous immunoglobulin in the treatment of neuromuscular disorders
- Clinical guidelines for immunoglobulin use (second edition update)
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