Lambert-Eaton Myasthenic Syndrome: Difference between revisions
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== Introduction == | == Introduction == | ||
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. | Lambert-Eaton Myasthenic Syndrome (LEMS) is a rare autoimmune disorder of presynaptic neuromuscular transmission with impaired release of acetylcholine (ACh).<ref name=":0">Titulaer MJ, Lang B, Verschuuren JJ. Lambert-Eaton myasthenic syndrome: from clinical characteristics to therapeutic strategies. Lancet Neurol. 2011;10(12):1098–107.</ref><ref name=":1">Mareska M, Gutmann L. Lambert-Eaton myasthenic syndrome. ''Semin Neurol''. 2004;24(2):149–53.</ref> Clinically, it is often mistaken for myasthenia gravis (MG), by the untrained eye.<ref name=":1" /> | ||
== Etiology == | == Etiology == | ||
There is a strong association with small-cell lung carcinoma, although other auto-immune disorders have also been associated with LEMS. | There is a strong association with small-cell lung carcinoma<ref name=":0" /><ref name=":1" />, although other auto-immune disorders have also been associated with LEMS.<ref name=":1" /> | ||
== Pathophysiology == | == Pathophysiology == | ||
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. | 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.<ref name=":0" /><ref name=":1" /> | ||
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. | 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.<ref name=":1" /> | ||
== Clinical Features == | == Clinical Features == | ||
The patient will usually be an adult over the age of | The patient will usually be an adult male over the age of 50, presenting with either of the following<ref name=":0" /><ref name=":1" />: | ||
* Weakness (proximal > distal, lower limb > upper limb), usually associated with a high level of disability | * 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 | * Lambert's Sign, wherein the grip becomes more powerful on repeated evaluation of strength | ||
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== Diagnosis == | == Diagnosis == | ||
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. | Electrophysiological testing is able to reliably confirm the diagnosis of LEMS.<ref name=":0" /><ref name=":1" /> On nerve conduction studies, the latencies and conduction velocities are normal while the CMAP is reduced. Repetitive nerve stimulation (RNS) is the study of choice to detect LEMS.<ref name=":0" /> There will be an initial decrement in the CMAP which is similar to myasthenia gravis. However on brief exercise, there will be a steady rise in the CMAP. This will be seen for up to 30 seconds.<ref name=":1" /> Although the single-fiber EMG examination is more sensitive, it requires exceptional technical prowess.<ref name=":0" /> It will exhibit an increased jitter, signifying a pathology at the neuromuscular junction.<ref name=":1" /> Unfortunately, it is unable to differentiate between MG and LEMS.<ref name=":0" /> | ||
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. | 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.<ref name=":1" /> | ||
On confirmed diagnosis of LEMS, the clinician may suggest a CT or MRI scan to screen for | On confirmed diagnosis of LEMS, the clinician may suggest a CT or MRI scan to screen for tumors (especially lung carcinoma).<ref name=":1" /> | ||
== Medical Management == | == Medical Management == | ||
== Physiotherapy Management == | == Physiotherapy Management == | ||
== References == | |||
<references /> | |||
Revision as of 19:17, 21 April 2020
Introduction[edit | edit source]
Lambert-Eaton Myasthenic Syndrome (LEMS) is a rare autoimmune disorder of presynaptic neuromuscular transmission with impaired release of acetylcholine (ACh).[1][2] Clinically, it is often mistaken for myasthenia gravis (MG), by the untrained eye.[2]
Etiology[edit | edit source]
There is a strong association with small-cell lung carcinoma[1][2], although other auto-immune disorders have also been associated with LEMS.[2]
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.[1][2]
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.[2]
Clinical Features[edit | edit source]
The patient will usually be an adult male over the age of 50, presenting with either of the following[1][2]:
- 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.[1][2] On nerve conduction studies, the latencies and conduction velocities are normal while the CMAP is reduced. Repetitive nerve stimulation (RNS) is the study of choice to detect LEMS.[1] There will be an initial decrement in the CMAP which is similar to myasthenia gravis. However on brief exercise, there will be a steady rise in the CMAP. This will be seen for up to 30 seconds.[2] Although the single-fiber EMG examination is more sensitive, it requires exceptional technical prowess.[1] It will exhibit an increased jitter, signifying a pathology at the neuromuscular junction.[2] Unfortunately, it is unable to differentiate between MG and LEMS.[1]
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.[2]
On confirmed diagnosis of LEMS, the clinician may suggest a CT or MRI scan to screen for tumors (especially lung carcinoma).[2]
Medical Management[edit | edit source]
Physiotherapy Management[edit | edit source]
References[edit | edit source]
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 Titulaer MJ, Lang B, Verschuuren JJ. Lambert-Eaton myasthenic syndrome: from clinical characteristics to therapeutic strategies. Lancet Neurol. 2011;10(12):1098–107.
- ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 Mareska M, Gutmann L. Lambert-Eaton myasthenic syndrome. Semin Neurol. 2004;24(2):149–53.
