Lambert-Eaton Myasthenic Syndrome
Lambert-Eaton myasthenic syndrome
Lambert-Eaton myasthenic syndrome is an autoimmune disease that causes muscle weakness and easy fatigability, particularly in the pelvic muscles and thighs.
In order to understand Lambert-Eaton myasthenic syndrome, it's important to have some understanding of the basics of nerve transmission and stimulation of muscle movement. Nerve impulses in the body are electrical and chemical currents that travel down a nerve fiber. When they reach the end of that nerve fiber, they trigger the release of the neurotransmitter chemical acetylcholine. Acetycholine must cross a tiny gap called the synapse in order to stimulate the muscle to contract. The nerves leading to the synapse or synaptic junction are called the presynaptic nerves.
In the case of Lambert-Eaton myasthenic syndrome, the body's immune system accidentally treats specialized areas (called calcium channels) along the presynaptic nerve as if they were foreign. These calcium channels are vital to the presynaptic nerve's ability to release acetylcholine into the synaptic junction. The immune cells attack the calcium channels as they would attack an invader such as a virus or bacteria. When the calcium channels are damaged, the release of acetylcholine into the synapse is compromised, resulting in less acetycholine being available to stimulate the muscle.
Lambert-Eaton myasthenic syndrome has a very strong association with cancer, particularly small-cell lung cancer. The symptoms of Lambert-Eaton myasthenic syndrome often occur prior to diagnosis with lung cancer. In fact, about two-thirds of all people with Lambert-Eaton myasthenic syndrome will be diagnosed with some type of cancer, usually small-cell lung cancer, within two to three years of the onset of their initial symptoms of Lambert-Eaton myasthenic syndrome. Other types of cancer associated with Lambert-Eaton myasthenic syndrome include non-small-cell lung cancer; lymphosarcoma; malignant thymoma; and carcinoma of the breast, stomach, colon, prostate, bladder, kidney, or gallbladder.
Because of the strong connection between Lambert-Eaton myasthenic syndrome and cancer, it is sometimes considered to be a paraneoplastic syndrome (a syndrome in which substances produced by cancer cells prompt abnormalities in the body at a distance from the actual site of the malignancy). In the case of Lambert-Eaton myasthenic syndrome, it is thought that the immune system produces immune cells in response to the presence of early cancer cells. These immune cells cross-react with the calcium channels on nerve cells, resulting in the symptoms of Lambert-Eaton myasthenic syndrome.
Lambert-Eaton myasthenic syndrome is very rare, only striking about five people per every one million annually. At any one time, there are thought to be about 400 people in the United States suffering from Lambert-Eaton myasthenic syndrome. Twice as many men than women are affected, and the average age at diagnosis is about 60 years of age. Family history of Lambert-Eaton myasthenic syndrome is a known risk factor for development of the disease, as is a personal history of smoking.
Causes and symptoms
In Lambert-Eaton myasthenic syndrome, the immune system accidentally attacks the calcium channels of the presynaptic nerve cells, preventing normal release of the neurotransmitter acetylcholine into the synaptic junction, and compromising the flow of nervous information between the presynaptic and postsynaptic nerves.
Symptoms of Lambert-Eaton myasthenic syndrome begin with weakness and some achiness and tenderness in the thigh and pelvic muscles. The upper arms may also exhibit some weakness. Due to the weak thigh and upper arm muscles, the patient's walk may have a waddling appearance, and it may be difficult for the patient to lift his or her arms above the head. Exercise may initially improve the weakness, but the weakness may become more pronounced as exercise continues. Eyelids may droop (ptosis). Many patients notice uncomfortably dry eyes, mouth, and skin. Patients may develop difficulty chewing, swallowing, and/or speaking, as well as constipation, sudden drops in blood pressure when rising from lying down to sitting or standing, abnormalities of sweating, and erectile problems in men.
Lambert-Eaton myasthenic syndrome may be diagnosed by demonstrating the presence of specific antibodies in the blood that are directed against aspects of the presynaptic nerve, such as the calcium channels. Studies of nerve conduction and muscle function will reveal a variety of abnormalities. When Lambert-Eaton myasthenic syndrome is diagnosed, a search should also be done for the presence of a previously undiagnosed cancer, especially small-cell lung cancer.
Patients with Lambert-Eaton myasthenic syndrome should be examined and then treated by both a neurologist and an appropriate cancer specialist (oncologist).
When a cancer is identified, the first concern should be the appropriate treatment of that malignancy. Secondarily, treatment of Lambert-Eaton myasthenic syndrome may include medications to improve transmission of nerve impulses across the synaptic junction (such as pyridostigmine bromide) as well as immunosuppressant agents (such as corticosteroids, azathioprine, cyclosporine, or intra-venous immungoglobulin) to decrease the immune system's ability to further damage the presynaptic nerves. A treatment called plasmapheresis may help remove damaging immune cells from the blood.
The prognosis of individuals with Lambert-Eaton myasthenic syndrome varies widely. In fact, the most important element of prognosis involves the prognosis associated with any existing cancer.
Patients who develop Lambert-Eaton myasthenic syndrome should be thoroughly screened for the presence of a previously undetected cancer. If none is found, the patient should undergo regularly scheduled surveillance to monitor for the subsequent development of a malignancy.
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Lambert-Eaton Myasthenic Syndrome Fact Sheet. National Institute of Neurological Disorders and Stroke (NINDS). Bethesda, MD: NINDS, 2003.
Rosalyn Carson-DeWitt, MD