Testing for N-type Voltage Gated Calcium Channel Antibody has Limited Utility in Evaluating Patients With Suspected Lambert-Eaton Myasthenic Syndrome

Abstract

Objective To determine if testing for N-type voltage-gated calcium channel antibody improves diagnostic performance of serological testing for Lambert-Eaton Myasthenic Syndrome. Background Patients with suspected autoimmune neuromuscular junction transmission disorders are commonly tested for both P/Q-type (VGCC-P/Q) and N-type (VGCC-N) voltage-gated calcium channel antibodies to aid the diagnosis of Lambert-Eaton Myasthenic Syndrome (LEMS). Design/Methods This retrospective cross-sectional study included 93 patients diagnosed at Mayo Clinic with LEMS based on electrodiagnostic findings, clinical presentation and positive serology for VGCC-P/Q and/or VGCC-N. Results Forty-five patients (48.4%) were female, of median age 61 years (range 11- 99). Twenty-five (26.9%) were positive for both VGCC antibody types (reference interval <0.04 nmol/L [VGCC-N] and <0.03 nmol/L [VGCC-P/Q]); 67 (72.0%) were positive for VGCC-P/Q only and one (1.1%) was positive for VGCC-N only. The single VGCC-N positive only result [VGCC-N = 0.10 nmol/L; VGCC-PQ = 0.02 nmol/L] was from a patient with classic LEMS presentation and no evidence of malignancy by Chest CT. The prevalence of VGCC-N only positivity was lower than in the healthy population or other disease control populations. VGCC-P/Q antibody titers were higher in patients who had detectable co-existing VGCC-N antibody (median titer 1.58 versus 0.39 nmol/L, P = 0.02) and there was a positive correlation (r = 0.762, P < 0.001) between VGCC-N and VGCC-P/Q titers in double positive cases. Dual positivity did not significantly increase the likelihood of an underlying cancer (40.9% versus 30.1%, P = 0.33). Conclusions Testing for VGCC-P/Q antibodies alone is sufficient in the serological evaluation of suspected LEMS cases. Inclusion of VGCC-N antibody testing does not improve diagnostic performance. A positive VGCC-N antibody did not significantly increase the risk of paraneoplastic LEMS.