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. 2024 Jun 17;5(2):201-208.
doi: 10.3390/neurosci5020015. eCollection 2024 Jun.

Characterization of Anti-GAD65-Associated Neurological Syndromes: Clinical Features and Antibody Titers

João Moura  1 , Firmina Sambayeta  1 , Ana Paula Sousa  2 , Paula Carneiro  3 , Esmeralda Neves  3 , Raquel Samões  1   4   5 , Ana Martins Silva  1   4   5 , Ernestina Santos  1   4   5
Affiliations

Characterization of Anti-GAD65-Associated Neurological Syndromes: Clinical Features and Antibody Titers

João Moura et al. NeuroSci. .

Abstract

Introduction: Anti-GAD65 antibodies are associated with several neurological phenotypes. Antibody titers are increasingly recognized as useful in diagnosis and prognosis.

Objective: To describe a Portuguese cohort of patients with anti-GAD65-associated neurological syndromes.

Methods: Retrospective analysis of all patients with positive anti-GAD65 antibodies and associated neurological syndromes followed in a tertiary referral center.

Results: Nineteen anti-GAD65 antibody-positive neurological patients were identified, 62.3% female, with a mean age of onset of 56.0 (SD = 13.3) years. Comorbid autoimmune disorders were present in seven patients. Six patients had limbic encephalitis (31.6%), four had epilepsy (21.1%), four had cerebellar ataxia (21.1%), and three had stiff-person syndrome (15.8%). Two patients presented with isolated cognitive dysfunction (executive and mnesic) in the absence of other neurological symptoms. The mean follow-up time was 24.0 (14.0-42.0) months, at the end of which the mean modified Rankin Scale (mRS) value was 2.0 (1.0-4.0). Screening for malignancies was negative in all patients. Serum quantitative analysis was carried out in 18 patients, 10 of whom showed titers above previously defined cut-off points (>10,000 IU/L for ELISA and >20 mmol/L for RIA). Quantitative CSF analysis was performed in nine patients, with four showing above-threshold titers. There was no association between anti-GAD65 levels and clinical phenotype or the final mRS values. High-dose intravenous methylprednisolone and oral prednisolone were the most common acute and chronic treatment regimens, respectively.

Conclusion: Anti-GAD65 antibodies are associated with varied neurological syndromes, and antibody titers alone should not be used to exclude a disease.

Keywords: anti-GAD65; cerebellar ataxia; epilepsy; limbic encephalitis; stiff-person syndrome.

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Conflict of interest statement

Conflicts of InterestThe authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
T2-weighted brain MRI with fluid-attenuated inversion recovery (FLAIR) hyperintense lesions attributable to autoimmune encephalitis related to anti-GAD65. (A) A patient with a temporal lesion involving the white matter that clinically presented with limbic encephalitis. (B) Parietal and frontal tumefactive lesions in a patient presenting with epilepsy.
See this image and copyright information in PMC

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