Lambert-Eaton myasthenic syndrome (LEMS) is the most common paraneoplastic syndrome. Paraneoplastic refers to the disease’s association with cancer. In paraneoplastic syndromes, the condition is triggered by immune changes occurring in cancer. Paraneoplastic syndromes are not caused by the tumor, its metastasis, infection, or metabolic disruptions. In LEMS, cancers cause the production of antigens resembling voltage-gated calcium channels on presynaptic motor nerve terminals, inducing autoantibodies directing against these antigens.
Paraneoplastic Neurological Syndromes
The most common paraneoplastic neurological syndromes are LEMS, subacute cerbellar ataxia, limbic encephalitis, opsoclonus-myoclonus, retinopathies and melanoma-associated retinopathy, Stiff-Person syndrome, chronic gastrointestinal pseuodobstruction, sensory neuronopathy, encephalomyelitis, and dermatomyositis. In these disorders, the autoimmune process is triggered by the cancer and directed against antigens common to both the cancer and the nervous system, which are called onconeural antigens. Identifying onconeural proteins in the patient’s serum is the best way of determining that a neurological disorder is paraneoplastic.
Symptoms of Lambert-Eaton Myasthenic Syndrome
Symptoms of LEMS typically occur in late adulthood although children may rarely be affected. Symptoms usually arise insidiously, with muscle weakness being the major symptom. Proximal muscles (those closer to the trunk) are affected more than distal muscles. Usually a gradually worsening condition of proximal leg weakness is the chief complaint.
Muscles in LEMS are occasionally tender and may ache. Muscles of the eyes, nose, and throat may also be affected, although respiratory muscles are spared. Dry mouth is a common early symptom. Patients may also notice a metallic taste and have symptoms of autonomic dysfunction, such as impotence in males and postural hypotension. LEMS may also cause prolonged paralysis following the use of neuromuscular blocking agents in surgery.
Muscle weakness can cause a waddling gait and difficulty elevating the arms. Eyelid ptosis or double vision occurs in about 25 percent of patients. Patients may also have difficulty chewing or swallowing.
Risk Factors
Smoking is highly associated with cancer in patients with LEMS. Duration of smoking and of symptoms are also risk factors. If tumors are not found within two years of the onset of symptoms, cancer is unlikely. Patients with small cell lung cancer, the most common associated cancer, have a history of long-term smoking, whereas overall only half of patients with autoimmune LEMS are long-term smokers. About 50-70 percent of patients with LEMS are reported to have an underlying tumor that is usually diagnosed within 2 years of the LEMS diagnosis. Tumors associated with LEMS include small cell lung cancer, non-small cell lung cancer, lymphosarcoma, breast cancer, and cancers of the stomach, colon, prostate, bladder, kidney, or gallbladder.
Diagnosis
LEMS is often confused with other conditions, which it must first be differentiated from, including acute and chronic inflammatory dymeylinating polyradiculoneuropathy, dermatomysositis, polymyositis, inclusion body myositis, myasthenia gravis, and spinal muscular atrophy.
Voltage-gated calcium channel antibodies have been reported in 75-100% of patients with LEMS who have small cell lung cancer and in 50-90 percent of patients without underlying cancers. These antibodies are also seen in 5 percent of patients with myasthenia gravis and in some patients with systemic lupus erythematosus and rheumatoid arthritis. Acetylcholine receptor antibodies are occasionally found in low titers in patients with LEMS.
Repetitive nerve stimulation studies are used to confirm LEMS. These tests measure compound muscle action potentials. Needle electromyography tests show unstable motor unit action potentials. Single-fiber electromyography shows an increase in jitter and blocking in most muscles.
Treatment
When a diagnosis of LEMS is made, it’s important to look for underlying malignancies with radiography, CT scanning of the chest, and bronchoscopy. Initial therapies are directed at any underlying malignancies. In the absence of tumors, repeat testing for tumors should be performed at regular intervals. In patients with cancer, the primary therapy is aimed at the cancer, whereas when cancer is not found, immunotherapy is used.
Treatment is also used to increase the transmission of acetylcholine across the neuromuscular junction by increasing its release or decreasing the action of the enzyme acetylcholinesterase. Immunosuppressants such as plasma exchange or high-dose intravenous immunoglobulins are often used to induce rapid improvement. Sustained therapy with prednisone and azathioprine or cyclosporine is also used to reduce symptoms. Other therapies may be used to reduce specific symptoms.
Sources:
J. Honnorat, J.C. Antoine, Paraneoplastic Neurological Syndromes, Orphanet J Rare Diseases, May 2007:22.
L. Edminston, Lambert Eaton Myasthenic Syndrome (LEMS): An Autoimmune Syndrome Causing Muscle Weakness, Associated Content, April 22, 2009.
David Stickler and Donald Sanders, Lambert-Eaton Myasthenic Syndrome, http://emedicine.medscape.com/article/1170810, Jan 29, 2009.
 |
