Evidence map›Paper›PMID 40651295›Full record

ArticleJournal of neuroimmunology2025

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

Friederike A Arlt, Masoud Majed, Jack Wu, Anastasia Zekeridou, Shahar Shelly, Vanda A Lennon, Sean J Pittock, Andrew McKeon, Christopher J Klein, Divyanshu Dubey and 1 more

Abstract read
In one paragraph

Article in Journal of neuroimmunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Friederike A ArltDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States of America.
Masoud MajedDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States of America; Department of Neurology, Mayo Clinic, Rochester, MN, United States of America.
Jack WuDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States of America.
Anastasia ZekeridouDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States of America; Department of Neurology, Mayo Clinic, Rochester, MN, United States of America.
Shahar ShellyDepartment of Neurology, Mayo Clinic, Rochester, MN, United States of America.
Vanda A LennonDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States of America; Department of Neurology, Mayo Clinic, Rochester, MN, United States of America; Department of Immunology, Mayo Clinic, Rochester, MN, United States of America.
Sean J PittockDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States of America; Department of Neurology, Mayo Clinic, Rochester, MN, United States of America.
Andrew McKeonDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States of America; Department of Neurology, Mayo Clinic, Rochester, MN, United States of America.
Christopher J KleinDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States of America; Department of Neurology, Mayo Clinic, Rochester, MN, United States of America.
Divyanshu DubeyDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States of America; Department of Neurology, Mayo Clinic, Rochester, MN, United States of America.
John R MillsDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States of America. Electronic address: mills.john2@mayo.edu.

Funding

A Phase-2b, Double-Blind, Randomized Controlled Trial to Evaluate the Activity and Safety of Inebilizumab in Anti-N-methyl-D-aspartate receptor (NMDAR) Encephalitis and Assess Markers of DiseaseU01NS120901 · NINDS · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Stacey Lynn Clardy · 2021 to 2026
$19.6M
Seronegative Autoimmune Encephalopathies: Biomarker Discovery, Validation & Deep PhenotypingR01NS126227 · NINDS · MAYO CLINIC ROCHESTER · PI Andrew McKeon · 2022 to 2026
$1.9M
NINDS NIH HHS R01 NS126227NINDS NIH HHS U01 NS120901
6 · The paper itself

Abstract

INTRODUCTION/

aimsDiagnostic 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.

methodsA 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.

resultsAmong 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. DISCUSSION: 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.

Indexed as

AutoantibodiesCalcium Channels, N-TypeLambert-Eaton Myasthenic SyndromeAdolescentAdultAgedBiomarkersChildCross-Sectional StudiesFemaleHumansMaleMiddle AgedRetrospective StudiesYoung AdultAutoantibodiesBiomarkersCalcium Channels, N-TypeLambert-Eaton myasthenic syndromeN-type voltage-gated calcium channel antibodyP/Q-type voltage-gated calcium channel antibodySOX1-IgGVoltage-gated calcium channel antibody

Identifiers

PMID40651295
PMCPMC12477647

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.