Lambert-Eaton Myasthenic Syndrome
Introduction[edit | edit source]
Lambert-Eaton Myasthenic Syndrome (LEMS) is a rare autoimmune disorder of presynaptic neuromuscular transmission with impaired release of acetylcholine (ACh). Clinically, it is often mistaken for myasthenia gravis (MG), by the untrained eye.
Etiology[edit | edit source]
There is a strong association with small-cell lung carcinoma, although other auto-immune disorders have also been associated with LEMS.
Pathophysiology[edit | edit source]
Calcium plays an important role in the release of ACh from its vesicles within the presynaptic membrane of the neuromuscular junction. In LEMS, antibodies are created against the voltage-gated calcium channels. This blocks the normal flow of calcium, thereby preventing the release of ACh from its vesicles. There is little to no ACh being released into the synaptic cleft. Therefore, there will be minimal to no muscle contraction.
In contrast to myasthenia gravis, continuous or repeated contractions result in improvement of strength. This occurs due to an increased influx of calcium in the presynaptic membrane, by repetitive muscle contractions. This calcium buildup facilitates the release of ACh by binding with multiple vesicles. In time, the excess calcium is cleared off by mitochondria. Thus, this effect is short-lived.
Clinical Features[edit | edit source]
The patient will usually be an adult over the age of 40, presenting with either of the following:
- Weakness (proximal > distal, lower limb > upper limb), usually associated with a high level of disability
- Lambert's Sign, wherein the grip becomes more powerful on repeated evaluation of strength
- Hyporeflexia
- Autonomic dysfunction
- Bulbar involvement (very rare)
- Respiratory failure (very rare, occurs late)
Diagnosis[edit | edit source]
Electrophysiological testing is able to reliably confirm the diagnosis of LEMS. On nerve conduction studies, the latencies and conduction velocities are normal while the CMAP is reduced. On repetitive nerve stimulation (RNS), there will be an initial decrement in the CMAP which is similar to myasthenia gravis. On brief exercise, there will be a steady rise in the CMAP. This will be seen for up to 30 seconds. A single-fiber examination will show increased jitters, signifying a pathology at the neuromuscular junction.
In EMG-confirmed cases of LEMS, most patients will demonstrate antibodies to voltage-gated calcium channels on serological testing. Secondary laboratory tests (such as creatine kinase, thyroid function test) may assist in reaffirming the diagnosis.
On confirmed diagnosis of LEMS, the clinician may suggest a CT or MRI scan to screen for tumours (especially lung carcinoma).
