Lambert-Eaton myasthenic syndrome (LEMS)
Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder that affects the neuromuscular junction, leading to progressive muscle weakness and decreased reflexes. One of the initial symptoms often experienced is a dry mouth, reflecting its impact on the autonomic nervous system. LEMS is primarily linked to small-cell lung cancer (SCLC) and can also be associated with other malignancies such as non-Hodgkin lymphoma and thymoma. The condition arises when antibodies disrupt the release of acetylcholine, a neurotransmitter essential for muscle contraction. Most commonly, symptoms such as weakness in the limbs and issues with mobility develop gradually over months or years. Diagnosis typically involves clinical evaluations and specific antibody testing, as no standard screening tests exist for LEMS. Treatment often focuses on addressing any underlying cancer, and supportive therapies like immunosuppressants or medications that enhance acetylcholine release may provide symptom relief. The prognosis for LEMS largely depends on the associated malignancy, with successful cancer treatment often leading to improvements in the syndrome itself.
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Lambert-Eaton myasthenic syndrome (LEMS)
ALSO KNOWN AS: Lambert-Eaton syndrome, Eaton-Lambert syndrome, Myasthenic Syndrome of Lambert Eaton
RELATED CONDITIONS: Small-cell lung cancer (SCLC), non-Hodgkin lymphoma, thymoma, carcinoma of the breast and colon, autoimmune disorders
DEFINITION: Lambert-Eaton myasthenic syndrome (LEMS) is a rare disorder of the neuromuscular junction, the point where nerve endings meet muscle fibers. LEMS affects muscles and nerves, causing progressive muscle weakness and decreased reflexes. Commonly, the first symptom an individual with LEMS notices is a parched mouth, which stems from the disorder’s effect on the autonomic nervous system. LEMS is frequently an early indication of cancer, allowing for early detection and treatment. It is usually associated with small-cell lung cancer (SCLC) and has been linked to non-Hodgkin lymphoma, thymoma, and carcinoma of the breast and colon.
Risk factors: People with various types of cancer, especially small-cell lung cancer, are at increased risk for developing Lambert-Eaton myasthenic syndrome. Additional risk factors include advanced age and smoking.
Etiology and the disease process: Lambert-Eaton myasthenic syndrome is an autoimmune disease caused by antibodies acting at the neuromuscular junction. These antibodies target the area of the nerve fiber responsible for releasing acetylcholine, a chemical needed to stimulate normal muscle contraction. The antibodies cause too little acetylcholine to be released, and muscle contractions are weakened. In patients who have cancer (about 60 percent of LEMS cases), antibodies are thought to be released in response to cancer-cell growth, affecting the muscles and as secondary reactions. In patients who do not have cancer, what triggers the release is unknown.
Typically, patients seek care well before the cancer is diagnosed because antibody release occurs at a very early stage in a tumor’s development. Symptoms of LEMS may begin two or more years before tumor detection. Because LEMS is a progressive disease, increasing weakness usually limits patients’ ability to perform routine daily activities. Although LEMS can cause respiratory difficulties, usually, the cancer is either successfully treated or leads to death before the syndrome itself progresses to a life-threatening stage.
Incidence: Lambert-Eaton myasthenic syndrome is uncommon. In the United States, around four hundred people have LEMS, and the disease impacts around 2.8 million people worldwide. The highest incidence occurs in people sixty or older, but it has also occurred in children. Between 50 and 70 percent of cases of LEMS are associated with small-cell lung cancer, but only about 3 percent of people with small-cell lung cancer develop LEMS. Almost all patients with both LEMS and small-cell lung cancer have a long-term history of smoking.
Symptoms: The symptoms of Lambert-Eaton myasthenic syndrome usually begin slowly, developing over months or years. The most common symptom is progressive weakness of the arms and legs, typically in the muscles closest to the body, with the thighs and hips being the most frequently affected. Reflexes in the affected extremities are usually absent or reduced. People with LEMS often have trouble walking, climbing stairs, or getting up from a seated or reclining position. As the disorder affects the autonomic nervous system, patients may complain of dry mouth, dizziness after standing up, and impotence. Additional symptoms of LEMS include double vision, constipation, excessive sweating, and difficulty talking, chewing, and swallowing.
Screening and diagnosis: There are no screening tests for Lambert-Eaton myasthenic syndrome. The disorder is typically diagnosed by clinical history, physical examination, and laboratory testing. If it is advanced and related to a malignancy, symptoms of the underlying cancer may be present. However, LEMS is usually diagnosed before the cancer produces discernible symptoms. Diagnostic tests include basic blood tests, such as complete blood count and chemistry; testing for voltage-gated calcium channel (VGCC) antibodies, which are present in about 85 percent of patients with LEMS; chest X-rays and computed tomography (CT) scan if malignancy is suspected; electromyography and nerve conduction studies; bronchoscopy; and positron emission tomography (PET) scanning. A Tensilon (edrophonium chloride) test, commonly used to differentiate LEMS from myasthenia gravis, may produce a noticeable short-term increase in strength. The associated cancer would determine staging.
Treatment and therapy: When Lambert-Eaton myasthenic syndrome has been diagnosed with underlying cancer, successful treatment of the cancer usually results in an improvement of LEMS. When no cancer is diagnosed, continued monitoring and testing are recommended because the typical time interval between the onset of LEMS and cancer diagnosis can be prolonged.
Immunosuppression therapy with corticosteroids or gamma globulin has proven to provide short-term relief. Still, it should only be used if symptoms do not resolve after effective treatment of an underlying cancer or if no cancer is present, as it may reduce immunologic suppression of tumor growth. Several drugs, including Amifampridine (Firdapse), Guanidine, and 3,4-diaminopyridine, increase the release of acetylcholine and have been shown to decrease symptoms significantly. Pyridostigmine (Mestinon) helps prevent the breakdown of acetylcholine in the junction.
Physical therapy and regular exercise can help patients maintain muscle tone and strength.
Prognosis, prevention, and outcomes: The prognosis of Lambert-Eaton myasthenic syndrome varies and is dependent on the prognosis for the associated cancer. There is no known prevention for LEMS, although smokers can reduce their risk by quitting. Patients should be aware that certain medications, such as neuromuscular blocking agents, aminoglycosides, magnesium, and calcium channel blockers, can worsen their condition. Additionally, exposure to hot environments and fever during illness can increase weakness in extremities.
Bibliography
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