eMedicine Specialties > Neurology > Neuromuscular Diseases
Lambert-Eaton Myasthenic Syndrome: Treatment & Medication
Updated: Jan 29, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
- Individually tailor therapy on the basis of severity of weakness, underlying disease(s), life expectancy, and response to previous treatment.
- When the Lambert-Eaton myasthenic syndrome (LEMS) diagnosis is confirmed, extensively search for an underlying malignancy with radiography and CT scanning of the chest, bronchoscopy, and possibly PET scanning.
- Initial treatment should be aimed at the neoplasm because weakness frequently improves with effective cancer therapy. No further LEMS treatment may be necessary in some patients.
- If no tumor is found, periodically search again for occult malignancy. Frequency of these evaluations is determined by the patient's risk of cancer.
- Patients younger than 50 years without history of long-term smoking have a low risk of associated malignancy, especially if evidence of coexisting autoimmune disease is present. Extensive surveillance for cancer may not be necessary for such patients.
- Patients older than 50 years with history of long-term smoking almost certainly have underlying small cell lung cancer (SCLC).
- In patients with cancer, LEMS is usually not the major therapeutic concern. The initial concern is the cancer.
- Immunotherapy of LEMS without effective treatment of the underlying cancer usually produces little or no improvement in strength. A theoretical concern is that the immunosuppression may reduce immunologic suppression of tumor growth.
- In patients with LEMS who do not have cancer, aggressive immunotherapy is justified more readily.
Consultations
Appropriate consultations include a neurologist and may include an oncologist and a physical medicine specialist.
Medication
The initial pharmacotherapy of LEMS is with agents that increase the transmission of ACh across the neuromuscular junction, either by increasing the release of ACh or by decreasing the action of acetylcholinesterase. Treatment of the associated cancer may also decrease the weakness and other symptoms.
If these treatments are not effective and the patient has relatively mild weakness, determine if aggressive immunotherapy is justified. When such therapy is warranted, PEX or high-dose IVIg may be used initially to induce rapid, albeit transitory, improvement. Immunosuppressants should be added for more sustained improvement, although a theoretical concern exists that immunologic suppression of tumor growth may thereby be reduced in paraneoplastic LEMS.
Prednisone and azathioprine, the most frequently used immunosuppressants, can be used alone or in combination. Cyclosporine may benefit patients with LEMS who are candidates for immunosuppression but cannot take or do not respond well to azathioprine. Improvement may be seen within 1-2 mo after beginning cyclosporine, while the maximum response is usually observed in 3-4 mo.
PEX produces improvement in many patients with LEMS. Improvement is temporary unless the patient is also receiving immunosuppression. Response to PEX in patients with LEMS is often more gradual than in those with MG. Maximal response may take several weeks. Repeated courses of PEX may be necessary to maintain improvement. PEX may be performed 4-6 times over 7-10 d, as described in standard protocols. Potential complications include autonomic instability, hypercalcemia, and bleeding due to depletion of clotting factors.
IVIg, given in a course of 2 g/kg over 2-5 d, also induces clinically significant temporary improvement in many patients. The frequency of improvement in response to repeated courses of treatment has not been determined.
Neuromuscular agents
These agents produce symptomatic improvement in strength, autonomic symptoms, or both in some patients with LEMS.
Pyridostigmine bromide (Mestinon)
Acetylcholinesterase inhibitors do not usually produce dramatic improvement in LEMS, but they may provide relief from weakness or dry mouth in some patients. Pyridostigmine is the preferred agent and should be administered for several days before assessing response.
Adult
30 or 60 mg PO q4-6h
Pediatric
Not established
Complements beneficial actions and adverse GI effects of 3,4-diaminopyridine; increases effects of depolarizing neuromuscular blockers; increases toxicity of edrophonium
Documented hypersensitivity; GI or GU obstruction
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
Individually determine dose for each patient; an excessively high dose may cause diarrhea, abdominal cramping, or increased weakness; beneficial and adverse actions of these medications complement those of 3,4-diaminopyridine
3,4-Diaminopyridine (DAP)
Aminopyridines improve neuromuscular transmission by facilitating release of ACh from the motor nerve terminal. They act by presynaptic potassium channel blockade, prolonging action potentials and extending activation of VGCC. For >20 y, has been used to improve strength and autonomic function in patients with LEMS. Effect begins about 20 min after a PO dose. Each dose lasts about 4 h, and maximum effect of a given dosage may not be observed for 2-3 d. Patients with or without underlying cancer benefit from DAP. In the authors' experience, >80% of patients with LEMS have significant clinical benefit; in over half of these, improvement is marked. Not approved for clinical use in the United States, but available on a compassionate-use basis for individual patients. In most patients, pyridostigmine enhances and prolongs duration of action, permitting lower doses.
Obtain application process information from
Jacobus Pharmaceutical Co., Inc.
Princeton, NJ
Fax # 609-799-1176
Adult
Optimal dose varies considerably among patients, so tailor dose and dosing schedule for each patient as follows:
10 mg PO tid/qid initial dose; observe response for 2 wk, increase dose in 5-mg increments at 2-wk intervals until maximum benefit obtained; not to exceed 80 mg/d; add pyridostigmine, 30 or 60 mg tid, and note effect on maximum response and on duration of action of each DAP dose; reduce DAP dose in 5-mg decrements until lowest effective dose determined
Optimal dose of DAP may change, so periodically reassess response to medication by slowly reducing dose to redetermine minimum dose that produces maximum response; repeat this procedure at least q12mo
Pediatric
In most patients, pyridostigmine enhances and prolongs the duration of action of DAP and permits lower doses; DAP may increase adverse GI effects of pyridostigmine; if this occurs, reduce dose of pyridostigmine
Documented hypersensitivity; history of seizures; cardiac arrhythmia
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Adverse effects minimal, usually limited to brief perioral and digital paresthesias, if dose is >10 mg; GI hyperactivity with cramps and diarrhea may occur when DAP is taken with pyridostigmine; minimize this effect by reducing pyridostigmine dose; seizures may occur at doses >100 mg/d; asthma attacks have been induced in patients with preexisting asthma; theoretically, DAP could cause cardiac arrhythmia, although no such effects have been reported; no known organ toxicity even in patients with LEMS who have taken aminopyridines for >10 y; because clinical experience with these agents is limited, periodically perform blood tests of liver, kidney, and hematologic functions to detect adverse effects; liver function tests, BUN and creatinine, and CBC should be performed q3mo for first year, then q6-12mo
Guanidine HCl
Increases ACh release and temporarily improves strength in many patients with LEMS.
Maximal effect may take 2-3 d.
Adult
5-10 mg/kg/d PO divided throughout waking hours as initial dose; may increase prn, but not more often than q3d; not to exceed 30 mg/kg/d depending on clinical response; adverse effects may be severe at doses > 1 g/d
Pediatric
Pyridostigmine enhances therapeutic response to guanidine and permits lower dose
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Use guanidine with extreme caution because of frequent adverse effects, including bone marrow suppression, renal tubular acidosis, chronic interstitial nephritis, cardiac arrhythmia, hepatic toxicity, pancreatic dysfunction, peripheral paresthesias, ataxia, confusion, and mood alterations; perform frequent blood tests of hematologic, hepatic, and renal functions
Blood products
Intravenous immunoglobulin can be an effective treatment for LEMS.
Intravenous immunoglobulin (IVIg)
Features that may be relevant to efficacy include neutralization of circulating antibodies through anti-idiotypic antibodies; down-regulation of proinflammatory cytokines, including IFN-gamma; blockade of Fc receptors on macrophages; suppression of inducer T and B cells and augmentation of suppressor T cells; and blockade of complement cascade.
Adult
2 g/kg IV over 2-5 d
Pediatric
Administer as in adults
None reported
Documented hypersensitivity; IgA deficiency; anti-IgE/IgG antibodies
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Consider checking serum IgA before IVIg and using IgA-depleted IVIg (G-Gard-SD), if indicated
May increase serum viscosity and thromboembolic events; adverse effects may include migraine attacks; 10% increased risk of aseptic meningitis; increased risk of urticaria, pruritus, or petechiae 2-5 d after infusion (possibly lasting up to 1 mo); increased risk of renal tubular necrosis in older patients and patients with diabetes mellitus, volume depletion, or preexisting kidney disease
Can lead to changes in laboratory values, eg, elevated antiviral or antibacterial antibody titers for 1 mo, 6-fold increased ESR for 2-3 wk, apparent hyponatremia
More on Lambert-Eaton Myasthenic Syndrome |
| Overview: Lambert-Eaton Myasthenic Syndrome |
| Differential Diagnoses & Workup: Lambert-Eaton Myasthenic Syndrome |
 Treatment & Medication: Lambert-Eaton Myasthenic Syndrome |
| Follow-up: Lambert-Eaton Myasthenic Syndrome |
| Multimedia: Lambert-Eaton Myasthenic Syndrome |
| References |
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References
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Further Reading
Keywords
Lambert-Eaton myasthenic syndrome, LEMS, acetylcholine release, ACh release, neuromuscular transmission, small cell lung cancer, SCLC, non-SCLC lung cancer, non–small cell lung cancer, lymphosarcoma, malignant thymoma, carcinoma of the breast, carcinoma of the stomach, carcinoma of the colon, carcinoma of the prostate, carcinoma of the bladder, carcinoma of the kidney, carcinoma of the gallbladder
