OBJECTIVES: There have been conflicting reports about the frequency of neural autoantibodies in epilepsy cohorts, which is confounded by the lack of clear distinction of epilepsy from acute symptomatic seizures due to encephalitis. The aim of this study was to determine the frequency of neural autoantibodies in a well characterised population of refractory focal epilepsy of known and unknown cause. METHODS: Cases were recruited from epilepsy outpatient clinics at the Princess Alexandra, Mater, Royal Brisbane and Women's and Cairns Base Hospitals from 2021 - 2023. Included cases were refractory to medical therapy, met the ILAE definition of focal epilepsy and were characterised using anatomo-electro-clinical correlation. Cases with prior encephalitis, inflammatory neurological disease or prior parenchymal brain insults were excluded. RESULTS: A total of 100 patients were recruited. No cases with clinically significant neural autoantibodies were discovered. One was positive for serum anti-NMDAR antibodies, however autoantibodies were absent from CSF. Cases were also screened using a predictive score (McGinty et al.). From this, 2 cases were identified as seronegative autoimmune associated epilepsy and demonstrated significant reduction in seizure frequency with administration of immunotherapy. These cases had common features including temporo-perisylvian semiology especially ictal piloerection and high seizure frequency. CONCLUSION: Clinically relevant neural autoantibodies are uncommon in well characterised chronic focal epilepsy populations. Despite this there are isolated cases that still demonstrate improved seizure control with the use of immunotherapy. Such cases highlight the need for further studies to understand the role of immunity in novel pathophysiological mechanisms in epilepsy.