Lambert-Eaton myasthenic syndrome
Classification and external resources
Detailed view of a neuromuscular junction: 1. Presynaptic terminal 2. Sarcolemma 3. Synaptic vesicle 4. Nicotinic acetylcholine receptor 5. Mitochondrion
ICD-10	G73.1
ICD-9	358.1
DiseasesDB	4030
MedlinePlus	000710
eMedicine	neuro/181 emerg/292
MeSH	D015624

Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder that affects voltage-gated calcium channels on the pre-synaptic membrane of the nerve-muscle (neuromuscular) junction. The inhibition of the voltage-gated calcium channels prevents acetylcholine from being released from the presynaptic terminal and the subsequent stimulation of the post-synaptic terminal which would lead to muscle contraction.^[1] The etiology of LEMS may resemble myasthenia gravis, but there are substantial differences between the clinical presentation and pathogenetic features of the two disorders.

The disease is usually observed in middle aged and older individuals, although children and young adults may also be affected. The incidence of the disease is difficult to determine due to its low frequency.

Contents 1 History 2 Causes 3 Clinical findings 4 Diagnosis 5 Treatment 6 References

[edit] History

Anderson was the first person to mention a case with possible clinical findings of LEMS in 1953, but Lambert, Eaton and Rooke were the first physicians to substantially describe the clinical and electrophysiological findings of the disease in 1966.^[2][3]

It is usually associated with auto-immune self antibodies against the pre-synaptic voltage gated calcium channels,^[4] which leads to neuromuscular block.

[edit] Causes

While LEMS may be found as a solitary disease, 50% of cases have an associated small-cell lung cancer. Other malignancies associated with LEMS are extremely rare. The myasthenic syndrome associated with thymoma is actually true myasthenia gravis, where weakness worsens with repeated activity (as opposed to LEMS, where weakness improves with repeated activity).^[5]

Whether solitary or cancer-associated, the disease is believed to be of autoimmune origin. In 1989, the previously anticipated antibodies were demonstrated to be directed against presynaptic calcium channels, which are located in the neuromuscular junction (see synapse) and are responsible for the presynaptic release of acetylcholine. The calcium channel antibodies prevent the opening of calcium channels and thus prevent the release of acetylcholine.

There are some patients that do not carry these antibodies in their serum samples and the exact cause of disease in these cases still remains to be determined.^{[citation needed]} In cases with both LEMS and lung cancer (usually small cell type), the antibodies are suggested to be aimed at cancer cells and to bind and affect the antigens in neuromuscular junction accidentally.

[edit] Clinical findings

The major clinical finding is progressive weakness that does not usually involve the respiratory muscles and the muscles of face. In patients with affected ocular and respiratory muscles, the involvement is not as severe as myasthenia gravis. Also, in contrast to MG, symptoms of LEMS tend to be worse in the morning and improve with exercise and nerve stimulation. The proximal parts of the legs and arms are predominantly affected. Many patients have autonomic symptoms like dry mouth or impotence. Reflexes are usually reduced or absent.

[edit] Diagnosis

The diagnosis is established by clinical and laboratory findings (chest x-ray for a possible lung malignancy, antibodies to calcium channels, incremental response in repetitive nerve stimulation). Incremental response is an increased response of muscle fibers to very high frequencies of electrical stimulation. Observed increase in the response of muscle fibers proves that there is a difficulty with the release of acetylcholine and this difficulty can be overwhelmed by intensive stimulation.

[edit] Treatment

Corticosteroids, azathioprine and 3,4-diaminopyridine are used in treatment of LEMS with limited success. In some cases with a progressive and intractable course, plasma exchange or intravenous immunoglobulin can be tried.

3,4 diaminopyridine works by blocking K⁺ channel efflux in nerve terminals so that action potential duration is increased. Ca²⁺ channels thus remain open for a longer period of time, which allows greater acetylcholine release to stimulate the muscle at the end plate.

[edit] References

v • d • e Diseases of myoneural junction and muscle / neuromuscular disease (G70-G73, 358-359) Neuromuscular- junction disease autoimmune (Myasthenia gravis, Lambert-Eaton myasthenic syndrome) Myopathy/ congenital myopathy Muscular dystrophy (DAPC) AD Limb-girdle muscular dystrophy 1 · Oculopharyngeal · Facioscapulohumeral · Myotonic · Distal (most) AR Limb-girdle muscular dystrophy 2 · Congenital (Fukuyama, Ullrich) XR dystrophin (Becker's, Duchenne) · Emerin Emery-Dreifuss Other structural collagen disease (Bethlem myopathy) · PTP disease (X-linked MTM) · adaptor protein disease (BIN1-linked centronuclear myopathy) · cytoskeleton disease (Nemaline myopathy, Zaspopathy) Channelopathy Myotonia Myotonia congenita · Thomsen disease · Neuromyotonia/Isaacs syndrome · Paramyotonia congenita Periodic paralysis Hypokalemic · Hyperkalemic Other Central core disease Mitochondrial myopathy MELAS · MERRF · KSS · PEO Other Inflammatory myopathy muscle, DF+DRCT navs: anat/hist/physio, acquired myopathy/congenital myopathy/neoplasia, symptoms+signs/eponymous, proc

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