Anti-Glutamic Acid Decarboxylase 65 (Anti-GAD65) Autoimmune Encephalopathy: A Case of Diagnostic and Treatment Challenge

Anti-glutamic acid decarboxylase 65 (anti-GAD65) autoimmune encephalopathy is an uncommon but increasingly recognized cause of cognitive impairment and refractory seizures. We report a 69-year-old woman with a background of insulin-treated diabetes mellitus, hypertension, hypercholesterolemia, and prior hyperthyroidism, who presented with acute altered consciousness and cognitive dysfunction. Initial investigations excluded metabolic, infectious, vascular, and paraneoplastic causes. Cerebrospinal fluid (CSF) analysis showed mildly elevated protein without pleocytosis, and MRI brain demonstrated nonspecific periventricular T2/FLAIR hyperintensities. Thyroid antibodies were markedly elevated, raising suspicion for Hashimoto’s encephalopathy; however, an extended autoimmune panel revealed strongly positive anti-GAD65 antibodies (50.9 nmol/L; reference <0.02). She was treated with intravenous immunoglobulin and pulsed methylprednisolone, with partial improvement but persistent slow mentation. Rituximab was planned, but follow-up was lost. This case highlights the diagnostic overlap between anti-GAD65 encephalitis and Hashimoto’s encephalitis, underscores the importance of comprehensive antibody testing in unexplained encephalopathy, and illustrates the incomplete response to first-line immunotherapy.