Evidence map›Paper›PMID 39985693›Full record

ArticleJournal of neurology2025

GAD antibodies in neurological disease: a critical evaluation of the utility and treatment implications of GAD antibodies in clinical practice.

Rachel L Brown, Gilbert Thomas-Black, Hector Garcia-Moreno, Michael Chou, Zofia Fleszar, Michael S Zandi, Miles Chapman, Andrew J Church, Melanie Hart, Paola Giunti and 2 more

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Article in Journal of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Review
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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

12 authors.

Rachel L BrownNational Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, WC1N 3BG, UK.ORCID http://orcid.org/0000-0002-9932-0228
Gilbert Thomas-BlackAtaxia Centre, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK.
Hector Garcia-MorenoAtaxia Centre, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK.
Michael ChouNational Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, WC1N 3BG, UK.
Zofia FleszarAtaxia Centre, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK.
Michael S ZandiNational Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, WC1N 3BG, UK.
Miles ChapmanNational Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, WC1N 3BG, UK.
Andrew J ChurchNational Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, WC1N 3BG, UK.
Melanie HartNational Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, WC1N 3BG, UK.
Paola GiuntiAtaxia Centre, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, WC1N 3BG, UK.
Angela VincentNuffield Department of Clinical Neurosciences, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK.
Michael P LunnNational Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust, London, WC1N 3BG, UK. michaellunn@nhs.net.

Funding

Medical Research Council MR/T001313/1
6 · The paper itself

Abstract

backgroundThe interpretation of antibodies to glutamic acid decarboxylase 65 (GAD-Abs) in neurological practice is challenging. GAD-Abs are not considered directly pathogenic and immunotherapy guidelines are lacking.

methodsWe undertook a single-center retrospective service evaluation of GAD-Abs, documenting clinical features, immunotherapy responses, and outcomes of 335 patients with positive GAD-Abs measured by indirect ELISA between 2012 and 2020. The serum:CSF ratio of GAD-Ab values was used as a surrogate for intrathecal synthesis.

results168 (50%) patients had diagnosed neurological disorders (GAD-ND). Ninety-six had neurological disorders often or sometimes associated with GAD-Abs, i.e., stiff person syndrome spectrum disorders (SPS-SD, n = 26), cerebellar ataxia (n = 21), epilepsy (n = 19), encephalitis (n = 18), or any combination of these ("mixed", n = 12). Seventy-two had other neurological disorders (ONDs) not typically associated with GAD-Abs. We defined a cut-off of 10,000 IU/mL a priori and a posteriori for GAD-Ab associated NDs, but identified values > 10,000 IU/mL in 21% and 11% of patients with ONDs or diabetes respectively, and < 10,000 IU/mL in 39% patients with classical GAD-Ab syndromes, indicating low assay specificity and sensitivity. Low serum: CSF GAD-Ab ratios were consistent with intrathecal synthesis in 12/19 tested; 25/54 patients had oligoclonal bands. 30/50 patients given adequate immunotherapies had partial (n = 17) or good (n = 13) responses, particularly those with SPS-SD or limbic encephalitis. Within the limitations of small subgroups and routine laboratory titrations, patients with GAD-Ab values > 10,000 IU/mL, intrathecal synthesis of GAD-Abs, or oligoclonal bands, were not more likely to improve with immunotherapies than those with GAD-Ab values < 10,000 IU/mL and a non-inflammatory CSF. Rather, treatment response correlated with disease group, principally SPS-SD and encephalitis.

conclusionsThese results suggest caution in over-interpreting GAD-Abs values. Better biomarkers for identifying patients with immunotherapy responsive GAD-Ab disease are needed.

Indexed as

AutoantibodiesGlutamate DecarboxylaseNervous System DiseasesAdolescentAdultAgedAged, 80 and overFemaleHumansImmunotherapyMaleMiddle AgedRetrospective StudiesYoung AdultAutoantibodiesGlutamate DecarboxylaseAntibodyCerebellar ataxiaEpilepsyGlutamic acid decarboxylaseLimbic encephalitisStiff person syndrome

Identifiers

PMID39985693
PMCPMC11846749

What OpenQuestion holds

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Registered trials

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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.