Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

The Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease in which autoantibodies are directed against voltage-gated calcium channels (VGCCs) at presynaptic nerve terminals. We first demonstrated the presence of P/Q-type and N-type VGCCs in digitonin extracts prepared from human and rabbit cerebellum using the specific ligands 125I-omega-conotoxin MVIIC (125I-omega-CmTx) and 125I-omega-conotoxin GVIA (125I-omega-CgTx), respectively. We then tested sera from 72 LEMS patients' 25 with proven small cell lung cancer (SCLC) and 66 healthy or other neurological, SCLC or autoimmune disease controls in an immunoprecipitation assay using 125I-omega-CmTx-labelled (P/Q-type) VGCCs in human cerebellar extract. Sixty-six of 72 LEMS serum samples (91.7%) were positive for the presence of VGCC antibodies, as defined as a titre greater than 3 standard deviations above the mean for the healthy controls (n = 22). Rabbit cerebellar extract as antigen gave similar results (r = 0.94, P < 0.001, n = 30). By contrast, only 24/72 (33%) LEMS sera were positive in the assay for anti-N-type VGCC antibodies using 125I-omega-CgTx. All these 24 were also positive in the 125I-omega-CmTx assay. All healthy and disease control sera were negative in both assays. The anti-P/Q-type VGCC antibody titres did not correlate with an electrophysiological index of disease severity across individuals; however, longitudinal studies in a LEMS patient with SCLC receiving chemotherapy, and in a non-SCLC LEMS patient receiving immunosuppressive therapy showed an inverse relation between antibody titre and disease severity. These results support the view that anti-P/Q-type VGCC antibodies are implicated in the motor disorder in LEMS, and show that the omega-CmTx radioimmunoassay is a highly specific and sensitive means of detecting them.


Journal article


J Neurol Sci

Publication Date





35 - 42


Adolescent, Adult, Aged, Aged, 80 and over, Animals, Autoantibodies, Binding Sites, Calcium Channel Blockers, Calcium Channels, Carcinoma, Small Cell, Case-Control Studies, Cerebellum, Female, Humans, Lambert-Eaton Myasthenic Syndrome, Lung Neoplasms, Male, Middle Aged, Mollusk Venoms, Peptides, Rabbits, Radioligand Assay, omega-Conotoxins