The diagnosis of Lambert-Eaton myasthenic syndrome (LEMS) is a multi-step approach that involves a thorough assessment of the symptoms. Multiple diagnostic tests are essential, as the symptoms of LEMS often overlap with that of another autoimmune disease, myasthenia gravis (MG).

Physical examination

The first step in the diagnosis of LEMS is a physical examination where the neurologist will look for signs of weakness in the arms and legs. One trait that can be helpful in diagnosing LEMS is that patients sometimes have a late improvement in reflexes after a muscle is activated. A dry mouth can also be an indication of LEMS.


Electromyography (EMG) records electrical signals coming from the muscle in response to a nerve signal and can help detect neuromuscular abnormalities. The initial response recorded by the EMG, called the compound motor action potential (CMAP), is low, but increases by more than 60 percent when stimulated after a short exercise. This is called an increment. An increment greater than 100 percent indicates LEMS.

Blood tests

If the observed physical symptoms match the EMG results, the neurologist recommends a blood test to detect specific antibodies in the blood called anti-VGCC antibodies. These are antibodies directed against voltage-gated calcium channels (VGCC) at the neuromuscular junction, the point where a nerve cell meets muscle, and their presence is a characteristic of LEMS.

Anti-VGCC antibodies can be detected in about 85 percent of LEMS patients, especially those where LEMS is associated with small-cell lung cancer (SCLC). The presence of these antibodies confirms LEMS as they are highly specific to VGCCs. However, their absence does not rule out LEMS.

Recently, it has been postulated that the presence of anti-SOX1 antibodies in the blood in addition to anti-VGCC antibodies can also serve as a diagnostic measure to confirm LEMS in SCLC patients. This test helps differentiate LEMS associated with SCLC from non-SCLC LEMS.

SCLC screening

Once the diagnosis of LEMS is confirmed, screening for SCLC is done by performing a CT or a PET-CT scan of the chest. If there are no signs of SCLC in the initial screen, a follow-up screening should be performed after three months and repeated every six months until two years as per the European Federation of Neurological Sciences (EFNS) guidelines.


Last updated: July 23. 2019


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