This case report describes a novel adverse effect of pembrolizumab causing autoimmune epilepsy due to GAD65 autoantibodies. 

While encephalitis secondary to immunocheckpoint inhibitors has been previously reported, this is the first case report of an autoimmune epilepsy due to GAD65 autoantibodies that persisted after pembrolizumab administration.

The patient was a 34-year-old, right-handed female with a past medical history of type 1 diabetes mellitus, hypogammaglobulinemia, systemic lupus erythematosus and triple-negative breast cancer due to the BRAC1 mutation who underwent a clinical trial with a neoadjuvant regimen of pembrolizumab plus carboplatin and docetaxel.  A few weeks after therapy, she developed drug-resistant, musicogenic, multifocal seizures.  Her seizures occurred daily and resulted in impaired consciousness.  A comorbid reflex epilepsy was present as listening to certain songs could trigger her seizures.  Both serum and CSF studies confirmed the presence of GAD65 autoantibodies.  Phase I EEG monitoring revealed multifocal seizures with independent onsets at the right fronto-temporal, right posterior-occipital, right parieto-occipital, bilateral temporal-parietal and bilateral posterior-temporal head regions. The brain MRI and PET scan were both non-lesional.  The magnetoencephalogram showed frequent-to-abundant multifocal epileptiform discharges that were maximal in the right occipital head region.  Stereo-EEG confirmed multifocal seizures independently arising from the bilateral temporal and occipital head regions.  She ultimately underwent surgical treatment with responsive neurostimulation using the left anterior and left pulvinar thalamic nuclei as stimulation targets.  She was maintained on intravenous immunoglobulin, hydroxychloroquine and mycophenolic acid for immunotherapy and clobazam, lamotrigine, levetiracetam, lorazepam and cenobamate for antiseizure medications.  Despite these treatments, the patient continued to have daily seizures with impaired consciousness and is undergoing a repeat evaluation for alternative neuromodulation therapies.

This case report describes a phenotypic evolution of GAD65 disease from adult-onset, type 1 diabetes mellitus to multifocal, musicogenic, drug-resistant autoimmune epilepsy after pembrolizumab use.