SCLC cells originate from neuroectoderm, share a number of antigens with peripheral nervous system tissue, and contain high concentrations of VGCCs. Calcium influx into these cells is inhibited by LEMS IgG. Antibodies to VGCCs are found in the serum of most LEMS patients. These observations suggest that VGCC antibodies downregulate VGCCs in LEMS.
In patients with LEMS who have SCLC or other cancer, cancer cells presumably contain antigens that mimic VGCCs and induce production of VGCC antibodies. In patients with LEMS but no cancer, VGCC antibodies are probably produced as part of a more general autoimmune state. In patients who have LEMS without cancer, an antibody response to domain IV of the 1A subunit of P/Q-type VGCCs is more common than in patients who have LEMS with cancer.
VGCC antibody levels do not correlate with disease severity among patients with LEMS. However, antibody levels do fall in individual patients if the disease improves after cancer therapy or immunosuppression.
All patients with LEMS who have associated SCLC have a history of long-term smoking. Only half of patients with autoimmune LEMS are long-term smokers.
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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.
