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

German Network for Research on Autoimmune Encephalitis (GENERATE), Marie Madlener, Christine Strippel, Franziska S Thaler, Kathrin Doppler, Klaus P Wandinger, Jan Lewerenz, Marius Ringelstein, Rosa Roessling, Til Menge, Jonathan Wickel, Christoph Kellingshaus, Sigrid Mues, Andrea Kraft, Andreas Linsa, Simone C Tauber, Florian Then Berg, Stefan T Gerner, Asterios Paliantonis, Alexander FinkeJosef Priller, Ingo Schirotzek, Marie Süße, Kurt W Sühs, Christian Urbanek, Makbule Senel, Claudia Sommer, Tania Kuempfel, Harald Pruess, Gereon R Fink, Frank Leypoldt, Nico Melzer, Michael P Malter

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Pages (from-to)120540
JournalJournal of the Neurological Sciences
Volume445
DOIs
Publication statusPublished - 15 Feb 2023

Keywords / Materials (for Non-textual outputs)

  • Humans
  • Cerebellar Ataxia/drug therapy
  • Glutamate Decarboxylase
  • Autoantibodies
  • Oligoclonal Bands
  • Limbic Encephalitis/therapy
  • Stiff-Person Syndrome/therapy

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