Low-Titer Anti-GAD Cerebellar Ataxia: Evidence That Diagnosis Should Extend Beyond Serum Antibody Levels - A Case Report and Systematic Review.

BACKGROUND

Anti-glutamic acid decarboxylase (anti-GAD) antibodies are associated with cerebellar ataxia. Although high antibody titers are considered a key diagnostic feature, the significance of low titers remains uncertain. We describe a patient with low-titer anti-GAD cerebellar ataxia and systematically review the literature.

METHODS

We report the case of a 38-year-old woman with autoimmune cerebellar ataxia associated with low-titer anti-GAD antibodies. A systematic review of PubMed/MEDLINE and SciELO identified published cases of cerebellar ataxia associated with low anti-GAD antibody titers.

RESULTS

The patient developed progressive cerebellar ataxia over six years. Brain magnetic resonance imaging demonstrated cerebellar atrophy, cerebrospinal fluid analysis revealed type 2 oligoclonal bands, and serum anti-GAD antibodies were detected at a low titer (435 IU/mL), consistent with the recently proposed low-titer anti-GAD cerebellar ataxia (LACA) classification. Partial improvement followed intravenous immunoglobulin and corticosteroids, with sustained improvement after rituximab. The systematic review identified 10 studies including 17 previously reported patients, supporting the diagnostic relevance of low anti-GAD antibody titers in the appropriate clinical context.

CONCLUSIONS

Low anti-GAD antibody titers do not exclude autoimmune cerebellar ataxia. Diagnosis should integrate clinical presentation, neuroimaging, cerebrospinal fluid findings, and therapeutic response rather than rely solely on serum antibody levels, facilitating earlier diagnosis and timely immunotherapy.