Abstracts

Rationale: Autoantibodies against glutamic acid decarboxylase 65 (GAD-65) have been identified in 1.8%-12.5% of patients with unexplained adult onset focal epilepsy, predominantly drug-resistant temporal lobe epilepsy. These rates of GAD-65 antibodies were obtained using ELISA assays that may be prone to false positive results. The objective of our study is to determine the prevalence of GAD-65 antibodies in patients with epilepsy of unknown etiology using a more specific cell based assay. Methods: Serum samples of patients with epilepsy were obtained from the Penn Medicine Biobank. Patients were excluded if they had acute symptomatic seizures, brain tumors (primary or metastatic), known autoimmune encephalitis, psychogenic non-epileptic spells without confirmation of epilepsy, and if serum samples were insufficient. Medical records were reviewed to confirm eligibility and collect phenotypic data. Control samples were matched for age, gender, and race controls without Type I DM and epilepsy. Serum samples were tested for GAD-65 antibodies using a cell based assay, with dilution titers performed on positive samples. Positive samples were confirmed by measuring reactivity to rat brain sections in the characteristic distribution of GAD-65 with immunohistochemistry (IHC). Results: A total of 270 epilepsy cases and 100 matched controls were included. 53% our subjects were women with a median age of 47 years and a median duration of epilepsy of 16 years. 87 % had focal epilepsy, 12% had generalized epilepsy and the remaining had epileptic encephalopathy. Of those with focal epilepsy, 20% had temporal lobe epilepsy; 27 % had an epileptogenic lesion on MRI, covering a range of different lesion types; and 45% had drug-resistant epilepsy, as defined by ILAE. GAD-65 was positive in 2 epilepsy cases (0.7%, 95% CI [0.2, 2.6]) and 0 controls. These positive cases had titers of 1:204,800 and 1:12,800. Moreover, the samples demonstrated the typical GAD-65 antibody pattern of brain reactivity on IHC. Case 1 is a 34-year-old woman with history of encephalitis in childhood who developed new onset left frontal epilepsy. MRI showed left frontal developmental venous anomaly (DVA) and EEG showed left frontal seizures. She is seizure free on lamotrigine monotherapy. Case 2 is a 54-year-old man with history of severe traumatic brain injury and drug resistant left temporal-lobe epilepsy beginning at age 48. His MRI is normal; EEG showed left temporal seizures and he underwent a left hippocampal laser ablation. His seizures are controlled on clobazam and lamotrigine. Conclusions: GAD-65 antibodies, measured with our specific cell-based assays, were very rare in epilepsy patients without autoimmune encephalitis. Prior brain injury may be a risk factor for GAD-65 antibody associated epilepsy. This small group of GAD-65 positive epilepsy patients merit further investigation. Funding: Drs. Ellis and Tizazu do not have any disclosures. Dr. Lancaster has the following disclosures: consulting for Grifols Inc., Merck Inc., Janssen Inc., and Novartis.