Lambert–Eaton myasthenic syndrome

Lambert–Eaton myasthenic syndrome
SynonymsLambert–Eaton syndrome, Eaton–Lambert syndrome
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Neuromuscular junction. Lambert–Eaton myasthenic syndrome is caused by autoantibodies to the presynaptic membrane. Myasthenia gravis is caused by autoantibodies to the postsynaptic acetylcholine receptors.
Classification and external resources

Lambert–Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder characterized by muscle weakness of the limbs. It is the result of an autoimmune reaction in which antibodies are formed against presynaptic voltage-gated calcium channels, and likely other nerve terminal proteins, in the neuromuscular junction (the connection between nerves and the muscle that they supply).[1] The prevalence is 3.4 cases per million.[2] Around 60% of those with LEMS have an underlying malignancy, most commonly small-cell lung cancer; it is therefore regarded as a paraneoplastic syndrome (a condition that arises as a result of cancer elsewhere in the body).[3]

LEMS usually occurs in people over 40 years of age, but may occur at any age. The diagnosis is usually confirmed with electromyography and blood tests; these also distinguish it from myasthenia gravis, a related autoimmune neuromuscular disease.[1]

If the disease is associated with cancer, direct treatment of the cancer often relieves the symptoms of LEMS. Other treatments often used are steroids, azathioprine, which suppress the immune system, intravenous immunoglobulin, which outcompetes autoreactive antibody for Fc receptors, and pyridostigmine and 3,4-diaminopyridine, which enhance the neuromuscular transmission. Occasionally, plasma exchange is required to remove the antibodies.[1]

Signs and symptoms

The weakness from LEMS typically involves the muscles of the proximal arms and legs (the muscles closer to the trunk). In contrast to myasthenia gravis, the weakness affects the legs more than the arms. This leads to difficulties climbing stairs and rising from a sitting position. Weakness is often relieved temporarily after exertion or physical exercise. High temperatures can worsen the symptoms. Weakness of the bulbar muscles (muscles of the mouth and throat) is occasionally encountered.[1] Weakness of the eye muscles is uncommon. Some may have double vision, drooping of the eyelids and difficulty swallowing,[1] but generally only together with leg weakness; this too distinguishes LEMS from myasthenia gravis, in which eye signs are much more common.[3] In the advanced stages of the disease, weakness of the respiratory muscles may occur.[1] Some may also experience problems with coordination (ataxia).[4]

Three-quarters of people with LEMS also have disruption of the autonomic nervous system. This may be experienced as a dry mouth, constipation, blurred vision, impaired sweating, and orthostatic hypotension (falls in blood pressure on standing, potentially leading to blackouts). Some report a metallic taste in the mouth.[1]

On neurological examination, the weakness demonstrated with normal testing of power is often less severe than would be expected on the basis of the symptoms. Strength improves further with repeated testing, e.g. improvement of power on repeated hand grip (a phenomenon known as " Lambert's sign"). At rest, reflexes are typically reduced; with muscle use, reflex strength increases. This is a characteristic feature of LEMS. The pupillary light reflex may be sluggish.[1]

In LEMS associated with lung cancer, most have no suggestive symptoms of cancer at the time, such as cough, coughing blood, and unintentional weight loss.[3] LEMS associated with lung cancer may be more severe.[4]