We describe a rare case of GAD65-associated musicogenic epilepsy and characterize response to antiseizure medication (ASM) and immunotherapy.

Antibodies against GAD65 are associated with a number of neurologic syndromes, including antibody-associated epilepsy. Musicogenic epilepsy is consistently localized to the temporal lobes, and an established association exists between musicogenic seizures and high-titer GAD65 antibodies.

A 50-year-old right-handed female with type 1 diabetes presented with a 5-year history of drug-resistant epilepsy with two seizure types: nocturnal bilateral tonic-clonic seizures and focal seizures with rising epigastric aura, right hand and oral automatisms, and ictal aphasia. Seizures were specifically triggered by Zac Brown Band music. Initial seizure frequency was once monthly. The patient failed multiple ASMs including lamotrigine, topiramate, zonisamide, oxcarbazepine, levetiracetam, clobazam, and perampanel. MRI demonstrated a small left anterior temporal encephalocele. Video-EEG captured musicogenic focal seizures with left temporal onset, PET showed left superior temporal hypometabolism, MEG demonstrated left lateral temporal epileptiform dipoles, and fMRI confirmed left language dominance. Further surgical workup was deferred pending CSF studies, given atypical features concerning for autoimmune epilepsy. Serum anti-GAD65 was 23.6 nmol/L (Mayo), and CSF anti-GAD65 was 2.31 nmol/L. She was initiated on IVIG with partial response, then rituximab, and ultimately transitioned to ublituximab after infusion reaction. Though her overall seizure burden was reduced by >50%, she had several breakthrough seizures in the setting of missed IVIG doses and insurance-related delays in obtaining second-line anti-CD20 therapy, compounded by significant psychosocial stressors. Current regimen of IVIG, ublituximab, cenobamate, and brivaracetam has resulted in 10 months of seizure freedom.

This case highlights the importance of recognizing musicogenic seizures as a feature of GAD65 autoimmune epilepsy, which should prompt early autoimmune investigation. Seizure freedom was achieved with multimodal immunotherapy and ASM optimization in this patient.