Lambert-Eaton Myasthenic Syndrome
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Direct answer
Lambert-Eaton myasthenic syndrome is a presynaptic neuromuscular junction disorder in which antibodies against P/Q-type voltage-gated calcium channels reduce acetylcholine release. It causes proximal limb weakness that improves briefly with exercise, dry mouth and autonomic upset, and an incremental response on high-frequency nerve stimulation. Much of it is paraneoplastic and linked to small cell lung cancer, so a chest search is always needed.
What you must remember
- Mechanism: antibodies against P/Q-type voltage-gated calcium channels at the motor nerve terminal, reducing acetylcholine release.
- Clinical triad: proximal leg weakness, areflexia that improves after brief maximal effort, and autonomic features such as dry mouth, constipation and erectile dysfunction.
- Repetitive stimulation: an incremental response of more than 100 per cent on high-frequency stimulation, around 20 to 50 Hz, with a decrement at low frequency.
- Malignancy link: small cell lung carcinoma is the commonest association, and the tumour may appear after the neurological symptoms.
- Amifampridine: a potassium channel blocker that prolongs presynaptic depolarisation, the first-line symptomatic drug where available.
- Immunotherapy: prednisolone, azathioprine, intravenous immunoglobulin or plasma exchange, with treatment of the tumour central to care.
- Versus myasthenia gravis: myasthenia is postsynaptic with acetylcholine receptor antibodies and improves with anticholinesterases, while this syndrome responds poorly to pyridostigmine.
From proximal weakness in a smoker to a diagnosis
A 63-year-old man who smokes reports four months of difficulty climbing stairs, dry mouth and erectile dysfunction. Examination shows proximal weakness of the hips and shoulders, with absent ankle reflexes that reappear briefly after a ten-second maximal contraction.
- Spot the facilitation: This post-exercise facilitation is the key clinical clue.
- Confirm on nerve studies: Nerve conduction studies show a low compound muscle action potential at rest, and high-frequency repetitive stimulation shows an increment of more than 100 per cent.
- Send the antibodies: Antibodies against P/Q-type calcium channels are then sent.
- Search for the cancer: Because the syndrome is paraneoplastic, a CT of the chest is the first imaging step. PET-CT follows if the CT is unrevealing, bronchoscopy is a further option, and repeat imaging is done if the search stays negative.
- Start symptomatic treatment: Treatment starts with amifampridine where available, to improve strength, and immunosuppression is added if needed.
- Treat the tumour in parallel: Definitive control depends on finding and treating the cancer, so the cancer search runs alongside symptomatic therapy. Repeat nerve studies after treatment show whether the incremental response and the strength are improving.
Where the examiner separates it from myasthenia
Four separators recur in examiner questions.
- Trap: calling any decrement myasthenia gravis Correct: both syndromes show a decrement at low-frequency stimulation, but the high-frequency response is incremental in Lambert-Eaton and absent in myasthenia.
- Trap: reading the phenotype the same way for both Correct: proximal leg weakness, dry mouth and reflexes that improve with effort point to Lambert-Eaton, while fatiguing ptosis and diplopia point to myasthenia.
- Trap: expecting anticholinesterases to work in both Correct: they help myasthenia but are poorly effective in Lambert-Eaton, so pharmacology is a further test.
- Trap: forgetting botulism as a mimic Correct: botulism is also presynaptic and can show an incremental response, but it causes cranial nerve palsies, dilated pupils and a descending paralysis, which are not typical of the syndrome.
Frequently asked questions
Which antibodies cause Lambert-Eaton myasthenic syndrome?
Lambert-Eaton myasthenic syndrome is caused by antibodies against P/Q-type voltage-gated calcium channels on the presynaptic motor nerve terminal. Their detection supports the diagnosis and directs the search for an underlying cancer.
Why does exercise improve strength in Lambert-Eaton syndrome?
Exercise improves strength in Lambert-Eaton syndrome because a brief maximal contraction increases calcium entry at the presynaptic terminal, which temporarily releases more acetylcholine. This post-exercise facilitation is why reflexes can reappear briefly after a short contraction.
What distinguishes Lambert-Eaton syndrome from myasthenia gravis on nerve testing?
Lambert-Eaton syndrome shows an incremental response of more than 100 per cent on high-frequency stimulation, whereas myasthenia gravis does not. Both show a decrement at low frequency, so the high-frequency pattern and the antibody type decide the diagnosis.
Which cancer should be sought in Lambert-Eaton myasthenic syndrome?
Small cell lung carcinoma is the cancer most commonly associated with Lambert-Eaton myasthenic syndrome, and it may appear after the neurological symptoms begin. Chest CT is the first step, followed by PET-CT, bronchoscopy where indicated and repeat imaging if the initial search is negative.