A rare autoimmune disease which affects the peripheral nervous system, resulting in muscle weakness.
Pathophysiology
- Normally, when a nervous impulse reaches the nerve ending at the neuromuscular junction, it triggers the opening of voltage gated calcium channels, resulting in influx of calcium ions into the nerve terminal.
- This triggers the release of vesicles containing acetylcholine into the synaptic cleft, which bind to the post-synaptic membrane and cause depolarisation there, which triggers muscle contraction.
- In LEMS, however, there are antibodies against the voltage gated calcium channels on the presynaptic cell membrane of neurones which bind to, and block, these channels.
- If most calcium channels are blocked, there is insufficient calcium influx to trigger release of acetylcholine, meaning there is no muscle contraction.
- With repeated stimulation by the action potentials, enough calcium may eventually be present to trigger the release of acetylcholine into the synaptic cleft, and thus trigger muscle contraction. This is why in LEMS, patients tend to be able to move better with repeated muscle use.
OpenStax, CC BY 4.0 , via Wikimedia Commons
Neuromuscular Junction
Causes
LEMS is associated with small cell lung cancers as part of a paraneoplastic syndrome. This is because small cell lung cancers can have voltage gated calcium channels on their surface, which induces the production of antibodies which can then cross-react with self voltage gated calcium channels. The disease can also be associated with other autoimmune diseases.
Clinical Features
- Weakness:
- Tends to affect the legs more than the arms
- Tends to affect the proximal muscles first
- Weakness relieved by exertion or exercise
- Hyporeflexia or areflexia – reflexes return after a few minutes of exercise/muscle use
- Autonomic dysfunction: dry mouth, constipation, orthostatic hypotension
Investigations
Presence of antibodies to voltage gated calcium channels and electromyography can be used for diagnosis. Chest x-ray or CT of the thorax can be used to look for any underlying cancer i.e. small-cell lung cancer.
Management
Treatment of any underlying cancer is of course imperative in LEMS. Treatment is typically with one of the following:
- 3,4-diaminopyridine: This helps to prolong the action potential and keep voltage gated calcium channels open for longer periods of time
- Pyridostigmine: An acetylcholinesterase inhibitor
- Patients may alternatively be treated with immunosuppression using intravenous immunoglobulin or other agents such as azathioprine.
References
https://www.ncbi.nlm.nih.gov/books/NBK507891/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182560/
