Diagnosis of LEMS

The diagnosis of Lambert-Eaton myasthenic syndrome (LEMS) typically is a multi-step process that involves testing and a thorough assessment of a patient’s symptoms.

Multiple diagnostic tests are essential, as the symptoms of LEMS often overlap with those of another autoimmune disease called myasthenia gravis (MG).

Physical examination

The first step in the diagnosis of LEMS is a physical examination in which a clinician will look for signs of muscle weakness. One trait that can be helpful to identify in diagnosing LEMS is that patients sometimes have poor reflexes that tend to improve after repeated muscle contraction. A dry mouth also can be a sign of LEMS.


Electromyography (EMG) records electrical signals coming from muscles in response to nerve signals and can help detect anomalies in nerve-muscle communication. EMG typically is conducted in association with another test, called nerve conduction study (NCS), which evaluates the ability and speed at which nerve cells send signals.

Nerve responses are usually low in LEMS patients. To pick up the sudden increases in muscle strength that often happen in LEMS patients after repeated exercise, doctors may ask patients to exercise for about 10 seconds before performing these tests. An increase in response of 60% or more may be indicative of LEMS.

In some patients, EMG results may be inconclusive. In these cases, a more sensitive test called single-fiber electromyography (SFEMG) may be performed. This type of test is used to evaluate the electrical activity of a single muscle fiber.

Blood tests

If physical symptoms are accompanied by abnormal EMG results suggestive of LEMS, physicians may recommend that patients have specific blood tests done to look for antibodies against voltage-gated calcium channels (VGCCs) and a protein called SOX1. The SOX1 protein is found in a large number of patients with LEMS associated with small-cell lung cancer (SCLC).

Anti-VGCC antibodies

These self-reactive antibodies target and damage proteins that play a key role in nerve-muscle communication, and are considered the underlying cause of LEMS. Anti-VGCC antibodies can be detected in about 85% of LEMS patients, especially those in whom LEMS is associated with SCLC.

The presence of these antibodies confirms the diagnosis of LEMS, as they are highly specific to the condition. However, their absence does not necessarily rule out LEMS, as in about 10–15% of patients, autoantibodies against VGCC cannot be detected in blood tests.

Anti-SOX1 antibodies

The presence of anti-SOX1 antibodies in the blood in addition to anti-VGCC antibodies also can serve as a diagnostic measure to confirm LEMS in SCLC patients and distinguish LEMS associated with SCLC from non-SCLC LEMS.

Although these antibodies can be detected in a large percentage of patients with LEMS associated with SCLC, their absence does not mean the disease is not present — their levels may just be too low to be detected.

SCLC screening

Once the diagnosis of LEMS is confirmed, patients are usually screened for SCLC, a specific type of lung cancer often seen in patients with LEMS. This is done by having a chest CT scan. If negative, a PET-CT scan of the chest also may be performed. If there are no signs of SCLC, a follow-up screening is normally performed after three months and repeated every six months until two years as per the European Federation of Neurological Sciences (EFNS) guidelines.


Last updated: Oct. 22, 2021


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