Weathering the Storm: Early Intervention for GAD65 Antibody-Mediated Encephalitis with Drug-Resistant Autoimmune Epilepsy

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Background/Purpose: Glutamate decarboxylase 1 (GAD65) catalyzes the conversion from glutamate to gamma-aminobutyric acid (GABA). Autoantibodies targeting GAD65 are associated with autoimmune diseases, such as type 1 diabetes and autoimmune thyroiditis. In addition, high anti-GAD65 titers in symptomatic patients should prompt a cerebrospinal fluid (CSF) analysis for intrathecal synthesis, as anti-GAD65 autoantibodies are also linked to a few neurological disorders, including autoimmune encephalitis, stiff-person syndrome, cerebellar ataxia, and drug resistant epilepsy (DRE). Methods: We present a case of a 12-year-old previously healthy boy who was admitted to our hospital after experiencing generalized and focal onset motor seizures which were refractory to treatment with valproic acid, clobazam, and lamotrigine. Results: The patient's EEG showed focal epileptic discharges. MRI of the brain demonstrated a voluminous and signal-altered right hippocampus. CSF analysis identified pleocytosis, elevated protein levels, and type 2 oligoclonal bands. Immunofluorescence analyses by tissue-based assay revealed a neuropil signal and by using cell-based assay we detected GAD65 antibodies of high titers in CSF and serum. We diagnosed a GAD65 antibody-mediated encephalitis with DRE. Immunotherapy with intravenous methylprednisolone resolved both seizures and EEG abnormalities. Within weeks, seizures reoccurred and were associated with episodes of confusion and amnesia. After further methylprednisolone pulses and due to persisting GAD65 antibodies, we intensified treatment by immunoadsorption and the novel GABA receptor modulator cenobamate, resulting in sustained resolution of symptoms. Conclusion: This case (1) illustrates the role of antineuronal autoantibodies in the etiology of drug-resistant epilepsies; it (2) emphasizes the importance of prompt and aggressive immunotherapy in GAD65-mediated neurological disorders; and (3) indicates the promising treatment option of cenobamate in GAD65-associated autoimmune epilepsy. Publication History Article published online: 13 November 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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