PT  - JOURNAL ARTICLE
AU  - Muñoz-Lopetegi, Amaia
AU  - de Bruijn, Marienke A.A.M.
AU  - Boukhrissi, Sanae
AU  - Bastiaansen, Anna E.M.
AU  - Nagtzaam, Mariska M.P.
AU  - Hulsenboom, Esther S.P.
AU  - Boon, Agnita J.W.
AU  - Neuteboom, Rinze F.
AU  - de Vries, Juna M.
AU  - Sillevis Smitt, Peter A.E.
AU  - Schreurs, Marco W.J.
AU  - Titulaer, Maarten J.
TI  - Neurologic syndromes related to anti-GAD65
AID  - 10.1212/NXI.0000000000000696
DP  - 2020 May 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e696
VI  - 7
IP  - 3
4099  - http://nn.neurology.org/content/7/3/e696.short
4100  - http://nn.neurology.org/content/7/3/e696.full
SO  - Neurol Neuroimmunol Neuroinflamm2020 May 01; 7
AB  - Objective Antibodies against glutamic acid decarboxylase 65 (anti-GAD65) are associated with a number of neurologic syndromes. However, their pathogenic role is controversial. Our objective was to describe clinical and paraclinical characteristics of anti-GAD65 patients and analyze their response to immunotherapy.Methods Retrospectively, we studied patients (n = 56) with positive anti-GAD65 and any neurologic symptom. We tested serum and CSF with ELISA, immunohistochemistry, and cell-based assay. Accordingly, we set a cutoff value of 10,000 IU/mL in serum by ELISA to group patients into high-concentration (n = 36) and low-concentration (n = 20) groups. We compared clinical and immunologic features and analyzed response to immunotherapy.Results Classical anti–GAD65-associated syndromes were seen in 34/36 patients with high concentration (94%): stiff-person syndrome (7), cerebellar ataxia (3), chronic epilepsy (9), limbic encephalitis (9), or an overlap of 2 or more of the former (6). Patients with low concentrations had a broad, heterogeneous symptom spectrum. Immunotherapy was effective in 19/27 treated patients (70%), although none of them completely recovered. Antibody concentration reduction occurred in 15/17 patients with available pre- and post-treatment samples (median reduction 69%; range 27%–99%), of which 14 improved clinically. The 2 patients with unchanged concentrations showed no clinical improvement. No differences in treatment responses were observed between specific syndromes.Conclusion Most patients with high anti-GAD65 concentrations (>10,000 IU/mL) showed some improvement after immunotherapy, unfortunately without complete recovery. Serum antibody concentrations' course might be useful to monitor response. In patients with low anti-GAD65 concentrations, especially in those without typical clinical phenotypes, diagnostic alternatives are more likely.CA=cerebellar ataxia; CBA=cell-based assay; Ep=epilepsy; GAD=glutamic acid decarboxylase; IHC=immunohistochemistry; IVIg=IV immunoglobulin; LE=limbic encephalitis; mRS=modified Rankin Scale; SARA=Scale for the Assessment and Rating of Ataxia; SPS=stiff-person syndrome