Abstracts

Rationale: GAD65-associated autoimmune epilepsy is rare and often overlooked in the work-up for adult-onset seizures of unknown etiology. Often seizures are the only presenting symptom without other manifestations, further adding to the complexity of this diagnosis. This is a challenging epilepsy to treat as patients are often refractory to antiepileptic drugs (AED) and may only show partial response to immunotherapy.  Methods: Retrospective chart review of 12 patients diagnosed with GAD65 antibody associated autoimmune epilepsy from two Tertiary Epilepsy Centers.  Results: Twelve patients with seizures associated with GAD65 Ab positivity were identified from Yale University and University of Miami Comprehensive Epilepsy Centers. Mean age was 45 years (range 25-60), with 100% females. Mean age at seizure onset was 29.6 years (range 13-58). The mean time to diagnosis was 13 years (range 0 to 45). Average duration of epilepsy is 15.4 years (range 2 to 45). Seizure risk factors (traumatic brain injury, family history) were identified in 8% (1). Mean concentration of GAD65 Ab in the serum was of 932 nmol/L (range 1.55 to 3117). CSF was sent in 58% (7) with mean GAD Ab. titers at 51.2 nmol/L (range 2.7 to 216). Other serum autoimmune antibodies were sent in 9 patients and identified in 22% (2) of those sent (P/Q Calcium Ab, and ANA). Ten patients (83%) experienced an aura: visual (1), olfactory (1) and sensory (8). Ten (83%) patients had focal with impaired awareness with subsequent bilateral tonic/clonic seizures. One patient had exclusively focal seizures with preserved awareness, and one patient had focal seizures with impaired awareness without secondary generalization. In terms of ictal EEG localization, 42% (5) had unilateral temporal onset, 42% (5) had bilateral temporal onset, and 17% (2) had extratemporal lobe onset. A quarter of our patients (4) had a history of status epilepticus. The median number of AEDs used was 5.5 (range 3-16). None of our patients had known malignancy. History of other autoimmune disease was identified in 50% (6) of our patients (Diabetes Mellitus Type 1, Stiff Person Syndrome, Graves Disease, Autoimmune Hepatitis). Immunotherapy was given to 92% (11) of patients. While 25% (3) had partial response, none of our patients had sustained seizure freedom (1 year seizure-free). Five forms of immunotherapy were used: high dose corticosteroids in 83% (10), rituximab in 75% (9), intravenous immunoglobulin in 50% (6), mycophenolate in 17% (2), and azathioprine in 8% (1). We found psychiatric changes in 58% (7) and cognitive changes in 75% (9) with 89% (8/9) reporting memory impairment. MRI was completed for all patients: 42% (5) had no changes, 33% (4) had unilateral temporal, 8% (1) had bilateral temporal, and 17% (2) had extratemporal changes.  Conclusions: This descriptive case series provides insight into the clinical and electrographic features, diagnosis, and treatment in 12 women of child-bearing age who developed refractory epilepsy in the absence of known etiology. Specifically, we noticed a significant delay in time to diagnosis in many of these patients, averaging 13 years and in one patient, 45 years. While our case series is retrospective and limited by number of patients, we posit that GAD-associated epilepsy is under-diagnosed and that earlier identification, diagnosis, and treatment of at-risk patients could lead to a higher response rate to therapy and better outcomes.  Funding: No funding