Glutamic acid decarboxylase antibody-associated neurological syndromes: Clinical and antibody characteristics and therapy response

Madlener M, Strippel C, Thaler FS, Doppler K, Wandinger KP, Lewerenz J, Ringelstein M, Roessling R, Menge T, Wickel J, Kellingshaus C, Mues S, Kraft A, Linsa A, Tauber SC, Berg FT, Gerner S, Paliantonis A, Finke A, Priller J, Schirotzek I, Süße M, Sühs KW, Urbanek C, Senel M, Sommer C, Kuempfel T, Pruess H, Fink GR, Leypoldt F, Melzer N, Malter MP (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Book Volume: 445

Article Number: 120540

DOI: 10.1016/j.jns.2022.120540

Abstract

Background: Antibodies against glutamic acid decarboxylase (GAD-abs) at high serum levels are associated with diverse autoimmune neurological syndromes (AINS), including cerebellar ataxia, epilepsy, limbic encephalitis and stiff-person syndrome. The impact of low serum GAD-ab levels in patients with suspected AINS remains controversial. Specific intrathecal GAD-ab synthesis may serve as a marker for GAD-ab-associated nervous system autoimmunity. We present characteristics of a multicentric patient cohort with suspected AINS associated with GAD antibodies (SAINS-GAD+) and explore the relevance of serum GAD-ab levels and intrathecal GAD-ab synthesis. Methods: All patients with SAINS-GAD+ included in the registry of the German Network for Research on Autoimmune Encephalitis (GENERATE) from 2011 to 2019 were analyzed. High serum GAD-ab levels were defined as RIA>2000 U/mL, ELISA>1000 U/mL, or as a positive staining pattern on cell-based assays. Results: One-hundred-one patients were analyzed. In descending order they presented with epilepsy/limbic encephalitis (39%), cerebellar ataxia (28%), stiff person syndrome (22%), and overlap syndrome (12%). Immunotherapy was administered in 89% of cases with improvements in 46%. 35% of SAINS-GAD+ patients had low GAD-ab serum levels. Notably, unmatched oligoclonal bands in CSF but not in serum were more frequent in patients with low GAD-ab serum levels. GAD-ab-levels (high/low) and intrathecal GAD-ab synthesis (present or not) did not impact clinical characteristics and outcome. Conclusions: Overall, immunotherapy in SAINS-GAD+ was moderately effective. Serum GAD-ab levels and the absence or presence of intrathecal GAD-ab synthesis did not predict clinical characteristics or outcomes in SAINS-GAD+. The detection of unmatched oligoclonal bands might outweigh low GAD-ab serum levels.

Authors with CRIS profile

Involved external institutions

Universitätsklinikum Münster Germany (DE) Klinikum der Universität München Germany (DE) Julius-Maximilians-Universität Würzburg Germany (DE) Universitätsklinikum Schleswig-Holstein (UKSH) Germany (DE) Universitätsklinikum Ulm Germany (DE) Heinrich-Heine-Universität Düsseldorf Germany (DE) Charité - Universitätsmedizin Berlin Germany (DE) Universitätsklinikum Jena Germany (DE) Klinikum Osnabrück Germany (DE) Universitätsklinikum Carl Gustav Carus Dresden Germany (DE) Carl-Thiem-Klinikum Germany (DE) Universitätsklinikum Köln Germany (DE) Universitätsklinikum Aachen (UKA) Germany (DE) Universität Leipzig Germany (DE) Alfried Krupp Krankenhaus Germany (DE) Städtisches Klinikum Lüneburg Germany (DE) Universitätsklinikum Gießen und Marburg (UKGM) Germany (DE) Universitätsmedizin Greifswald / Universitätsklinikum Greifswald Germany (DE) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Klinikum der Stadt Ludwigshafen am Rhein gGmbH Germany (DE) Christian-Albrechts-Universität zu Kiel Germany (DE)

How to cite

APA:

Madlener, M., Strippel, C., Thaler, F.S., Doppler, K., Wandinger, K.P., Lewerenz, J.,... Malter, M.P. (2023). Glutamic acid decarboxylase antibody-associated neurological syndromes: Clinical and antibody characteristics and therapy response. Journal of the Neurological Sciences, 445. https://dx.doi.org/10.1016/j.jns.2022.120540

MLA:

Madlener, Marie, et al. "Glutamic acid decarboxylase antibody-associated neurological syndromes: Clinical and antibody characteristics and therapy response." Journal of the Neurological Sciences 445 (2023).

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