Abstracts

Rationale: Autoantibodies to glutamic acid decarboxylase (GAD-ab) have been associated with numerous neurologic disorders particularly stiff person syndrome, cerebellar ataxia, encephalitis and epilepsy. Currently, GAD-ab are considered as markers of inflammation and whether these antibodies are pathogenic is still under investigation. We set to describe the clinical and immunologic spectrum of epilepsy associated with GAD-ab. Methods: Retrospective chart review of patients from comprehensive epilepsy clinic at tertiary care center over last 3 years was performed. Adult patients with age ≥ 18 years with epilepsy and positive serum GAD-ab titer were selected. We reviewed the chart for clinical presentation, immunologic profile, therapeutic interventions and response for these patients. Results: Total of 12 patients (5 men and 7 women) were included in the study. All the patients had localization related temporal lobe epilepsy. Mean age of onset was earlier for women as compared to men (25.6 ± 9.9 years vs 34.2 ± 23.4 years, p=0.049). Among women, one patient presented with new onset refractory status epilepticus, two with explosive onset of multiple seizures (one during pregnancy), and four with occasional seizures. Among men, one patient had a protracted course with seizures resulting in death; two presented with rare seizures, one with one multiple seizures and one with transient change in mental status with rapid resolution. The serum titers for GAD-ab ranged from 7.4 to > 250 and there was no clear association between antibody titer and severity of disease. 4 patients had associated Hashimoto's thyroiditis, 2 had diabetes and 1 had primary sclerosing cholangitis. CSF analysis for 8 patients was available and showed mild pleocytosis (WBC 0-2), normal protein to mildly increased protein (27-47 mg/dl except one with protein > 230 mg/dl), absent oligoclonal bands and IgG index < 0.7 in all the 5/8 samples. Most patients had bitemporal independent epileptiform discharges. 9 patients had pharmacoresistant epilepsy and 3 patients were well controlled with anti-epileptic drugs (AEDs) only. Of the 9 patients, 5 patients underwent surgery, of which only one patient responded well with significant reduction in seizures; 4 patients received immunotherapy with IVIG, 2 of which showed good response; 2 patients received cyclophosphamide one of which responded well to treatment. Conclusions: Our study is a retrospective descriptive study, which emphasizes that autoimmune epilepsy associated with GAD-ab is a spectrum of disease rather than a prototype autoimmune syndrome. Men and women are equally affected; women tend to have a younger age of onset as compared to men. The clinical presentation ranges from refractory status epilepticus, pharmacoresistant epilepsy to well-controlled seizures. Immunologic profile shows variable serum antibody titers, which does not correlate with disease severity, normal to mildly elevated CSF protein without any oligoclonal bands and normal IgG index. Response to treatment also varies from AEDs only to immunotherapy and resective surgery.