N-type voltage-gated calcium channel antibody testing lacks diagnostic value in Lambert-Eaton myasthenic syndrome

Diagnostic evaluation for Lambert-Eaton myasthenic syndrome (LEMS) includes serological testing for voltage-gated calcium channel antibodies (VGCC-P/Q-type [VGCC-PQ] and VGCC-N-type [VGCC-N]). While VGCC-PQ antibodies are well-established biomarkers in LEMS, the clinical utility of VGCC-N antibody testing remains obscure. We aimed to determine the diagnostic value of VGCC-N antibody testing.

A retrospective cross-sectional study was performed. The Mayo Clinic electronic medical record from 1995 to 2021 was reviewed for inclusion of patients fitting clinical electrodiagnostic criteria for LEMS, who were evaluated for serum VGCC antibodies (n = 123). Available sera were additionally tested for SOX1 antibodies (n = 68). Healthy adults were tested for VGCC-PQ and VGCC-N antibodies (n = 122). Clinical performance of each antibody test was evaluated statistically.

Among adult LEMS cases, 84.6 % (n = 99/117) tested positive for VGCC-PQ antibody while none of the healthy controls did. In contrast, 20.5 % (n = 24/117) were VGCC-N antibody positive, of which 95.8 % (n = 23/24) co-occurred with VGCC-PQ antibodies. The frequency of isolated VGCC-N antibody positivity was higher in controls than in LEMS (2.5 % [n = 3/122] vs. 0.9 % [n = 1/117]), and pediatric patients had no VGCC-N antibody reactivity. Neither VGCC-N antibody positivity nor titer was predictive of an associated small-cell lung cancer (SCLC-LEMS). By contrast, SOX1-IgG seropositivity associated significantly with SCLC-LEMS.

Inclusion of VGCC-N antibody testing does not improve diagnostic accuracy for LEMS, nor does it serve as a predictor of LEMS-associated cancers in contrast to SOX1-IgG testing. We recommend the exclusion of VGCC-N antibody testing given its non-specific disease associations and poor positive predictive value in LEMS screening.