Diagnosing Lambert-Eaton myasthenic syndrome (LEMS) as early as possible is key for effectively managing the disease, according to a review study, which also highlights the need to test for small cell lung cancer in these patients.
The review, “Lambert-Eaton Myasthenic syndrome: early diagnosis is key,” was published in the journal Degenerative Neurological and Neuromuscular Disease.
LEMS is an autoimmune neuromuscular disorder caused by autoantibodies that attack the neuromuscular junction— the site where nerve cells and muscle connect — causing the cells to stop communicating.
Approximately 90% of LEMS patients have autoantibodies that specifically attack voltage-gated calcium channels (VGCCs). Nerve impulses normally open these channels (which are located at the membrane of nerve cell terminals) allowing the release of the neurotransmitter acetylcholine. Neurotransmitters are molecules released by nerve cells to communicate with other cells, such as muscles. In LEMS, lower levels of acetylcholine are released from the nerve terminal, resulting in muscle weakness.
LEMS is often under-diagnosed or misdiagnosed. A 2004 Dutch study indicated that 58% of patients were incorrectly diagnosed before LEMS was confirmed. Awareness and clinical suspicion are essential in ensuring the disease is diagnosed early. LEMS should be considered in patients who show proximal muscle weakness, dry mouth, constipation, or oculobulbar weakness, involving the eyes and the muscles innervated by cranial nerves.
Multiple diagnostic tests are required to confirm whether a patient has LEMS, as some symptoms are often similar to myasthenia gravis, another autoimmune disease. An established set of steps should be used in diagnosing LEMS to help avoid underdiagnosis of the disease, the authors suggest.
Electromyography (EMG), which records electrical signals coming from the muscle in response to a nerve signal and can help detect neuromuscular abnormalities, is often the first test used. The initial response recorded by the EMG, known as the compound motor action potential (CMAP), is lower in LEMS patients. Following short exercise, the CMAP increases by more than 60% in people with LEMS. An increase of more than 100% is especially indicative of LEMS. On low frequency repetitive nerve stimulation, the CMAP normally decreases. A more than 10% reduction is considered to be abnormal.
When the EMG results are conclusive, a blood test should be performed to detect the presence of autoantibodies against a protein called voltage-gated calcium channel (VGCC). If the EMG results are suggestive but not conclusive, then the test should be repeated and the detection of antibodies carried out to increase the probability of a correct diagnosis.
“A diagnosis of a rare disorder supposes a complex process in which knowledge, awareness and a high degree of suspicion are critical factors for an early diagnosis. In clinically suspected LEMS, diagnosis is straightforward and should be assured given that highly specific diagnostic tools are easily available,” the researchers wrote.
“Clinical and electrodiagnostic criteria for LEMS are currently the mainstay in the diagnosis of LEMS,” including an increase in anti-VGCC levels. However, these “are helpful when a strong clinical suspicion is present but need to be interpreted carefully when they are positive without clinical correlations,” they added.
Approximately 60% of LEMS cases are associated with small cell lung cancer. Following a LEMS diagnosis, tests to detect cancer should therefore be started immediately.
A screening program previously showed that small cell lung cancer was identified in 91% of cases within three months, and in 96% of cases within one year. Some studies have also suggested that patients with LEMS associated with small cell lung cancer have higher survival rates than patients with only small cell lung cancer.
“Early recognition and the prompt initiation of the screening program are the priorities in the management of LEMS,” the researchers concluded.