History
Symptoms of Lambert-Eaton myasthenic syndrome (LEMS) usually begin insidiously and progress slowly. Many patients have symptoms for months or years before the diagnosis is made. Weakness is the major symptom. Weak muscles may ache and are occasionally tender. Proximal muscles are more affected than distal muscles; lower extremity muscles are affected predominantly. Patients typically have difficulty rising from a chair, climbing stairs, and walking.
Increased temperatures from fever or the environment may worsen the weakness. Patients may experience transient worsening after hot baths and showers or during systemic illnesses.
The oropharyngeal and ocular muscles [4] are mildly affected in about one quarter of cases of LEMS, with symptoms that may include ptosis, diplopia, and dysarthria, but they are usually not affected to the same extent or severity as in myasthenia gravis (MG). Differentiation between the 2 diseases may be difficult.
A study examining the localization of the initial muscle weakness and at the time of maximum severity in MG and LEMS patients found that patients with MG had initial muscle weakness involving the extraocular muscles (59%) and bulbar muscles (29%). [5] Conversely, LEMS patients never presented initially with ocular weakness; 5% presented with bulbar weakness, and 95% presented with limb weakness. In fact, almost all LEMS patients with oculobulbar or proximal upper extremity weakness also have proximal lower extremity weakness.
In contrast, a significant portion of patients with MG never progress past weakness in the extraocular muscles. At the point of maximum weakness, 25% of patients with MG had purely ocular involvement, and there were no patients with LEMS who had only ocular involvement. [5]
Respiratory muscles are not usually affected. When respiratory muscle function often is involved, the involvement is usually not as severe as with MG. However, rare cases of severe respiratory compromise or respiratory failure have been reported in patients with LEMS. Acute respiratory compromise is the most significant complication of LEMS and the only one that is relevant in the emergency setting. It is usually of iatrogenic origin.
Most patients have a dry mouth, which frequently precedes other symptoms of LEMS. (Many do not mention this unless specifically questioned.) Many patients report an unpleasant metallic taste. Some patients have other manifestations of autonomic dysfunction, including impotence in males and postural hypotension.
LEMS may be discovered first when prolonged paralysis follows the use of neuromuscular blocking agents during surgery.
Exacerbation of weakness has been described after administration of aminoglycoside or fluoroquinolone antibiotics, magnesium, calcium channel blockers, and iodinated intravenous contrast agents.
Cancer and LEMS
Cancer is present or subsequently discovered in 50-70% of patients with LEMS. In the case of lung cancer, the clinical symptoms of LEMS may precede detection of the underlying disease. Symptoms of the underlying cancer, as well as the “B” symptoms of cancer, may be present.
Smoking and age at onset are major risk factors for cancer in patients with LEMS. Duration of symptoms is also a factor. If a tumor is not found within the first 2 years after symptom onset, cancer is unlikely. For example, a patient younger than 50 years at onset who does not have a tumor discovered after 2 years of close follow-up is unlikely to have an underlying cancer. On the other hand, a long-term smoker with LEMS onset after age 50 years probably has underlying lung cancer.
Physical Examination
Strength is usually reduced in proximal muscles of the legs and arms, producing a waddling gait and difficulty elevating the arms. The degree of weakness is usually mild, compared with that reported by the patient. Sensory examination is normal unless a coincident peripheral neuropathy is present, which is not uncommon in patients with underlying cancer.
Some degree of eyelid ptosis or diplopia, usually mild, is found in 25% of patients. Occasionally, difficulty chewing, dysphagia, or dysarthria is present. Most patients have a dry mouth, eyes, or skin. Constipation, urinary retention, pupillary constriction, sweating, postural hypotension, or respiratory muscle weakness may be present. Clinical manifestations of underlying malignancy (eg, cachexia) may be present. Fasciculations, common in diseases of the anterior horn cell, such as amyotrophic lateral sclerosis (ALS), are absent.
In some patients, strength may improve after exercise and then weaken as activity is sustained. This phenomenon is demonstrable in approximately half of all patients with LEMS. It can also occur in the proximal muscles of patients with MG; however, repeated testing of many separate muscle groups may differentiate the 2 diseases.
Reflexes usually are reduced or absent in LEMS. They can frequently be provoked or increased by having the patient actively contract the muscle group in question for 10 seconds prior to reflex testing or by repeatedly tapping the muscles. An increase in reflex activity after contraction is a hallmark of LEMS.
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Characteristic responses to repetitive nerve stimulation in patient with Lambert-Eaton myasthenic syndrome. (A) Responses elicited from hand muscle by stimulation of nerve at 3 Hz. Amplitude of initial response is less than normal, and response is decremental. (B) Responses as in A, immediately after voluntary activation of muscle for 10 seconds. Amplitude has increased. (C) Responses in hand muscle elicited by 20-Hz stimulation of nerve for 10 seconds. Response amplitude is less than normal initially, falls further during first few stimuli, then increases and ultimately becomes more than twice initial value.
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Compound muscle action potentials elicited from hand muscle before and immediately after maximal voluntary activation of muscle for 10 seconds. Amplitude is small initially, increasing almost 10 times after activation.
