Lambert-Eaton myasthenic syndrome: The lack of short-term in vitro effects of serum factors on neuromuscular transmission

Abstract

Serum was obtained from 7 patients with the Lambert-Eaton myasthenic syndrome (LES), 3 patients with small-cell carcinoma of the lung (SCCL), and 9 healthy control subjects. Serum samples were applied in vitro to the rat neuromuscular junction (for 1–3 h for control LES sera; 4 h for SCCL sera), following which the pre- and postjunctional physiological effects of serum factors were studied in the presence of 10 mM [Mg 2+] o. All sera produced a marked reduction in the frequency of spontaneous miniature end-plate potentials (MEPPs), while causing slight to moderate changes in MEPP amplitude. There were no consistent changes in the quantum content of the impulse-evoked end-plate potentials, though the serum from one LES patient significantly and reversibly inhibited the evoked quantal release. No significant effect was found when a human intercostal muscle was exposed to serum from another LES patient for 2 h. Therefore, when applied in vitro on a short-term basis, the putative LES autoantibodies do not consistently react with voltage-dependent calcium channels in the motor nerve terminal and thus fail to reproduce the physiologic abnormality of the syndrome. We suggest that the pathogenic IgG molecules may require more than 3 h of incubation in order to gain access to, and inhibit the function of, the prejunctional Ca 2+ channels.