>Background: This study was designed to investigate the difference in the prevalence of neuronal autoantibodies in patients diagnosed with established temporal lobe epilepsy (TLE) of unknown cause with mesial temporal sclerosis (MTS) and patients with TLE without MTS. >Methods: In an observational cohort study design, we included thirty-three consecutive adult patients and divided them into two groups with and without MTS. We evaluated anti-neuronal and nuclear antibodies with immunofluorescence (IF) and enzyme-linked immunosorbent assay (ELISA), respectively. >Results: From the thirty-three consecutive patients with epilepsy 17 (51.1%) had MTS of which 12 had unilateral and 5 had bilateral MTS. No significant difference was detected between seropositive and seronegative patients in MTS versus non-MTS groups. The studied autoantibodies were present in 16 patients, including gamma-aminobutyric acid receptor (GABA-R) antibodies being the most common in 11 (33.3%), followed by N-methyl-D-aspartate receptor (NMDA-R) in 2 (6.1%), glutamic acid decarboxylase receptor (GAD-R) in 1 (3.0%), anti-phospholipid (APL) antibody in 1 (3.0%), CV2 in 1 (3.0%), Tr in 1 (3.0%), recoverin in 1 (3.0%), and double-stranded deoxyribonucleic acid (dsDNA) antibody in 1 (3.0%) of our patients with focal epilepsy. In both MTS and non-MTS groups, eight patients were positive for antibodies; four patients were positive for GABA in the MTS group and seven for GABA in the non-MTS group. >Conclusion: Neuronal antibodies were presented in half of patients with focal epilepsy, GABA antibody being the leading one. No specific magnetic resonance imaging (MRI) findings were found in the seropositive group. Our results suggest that screening for relevant antibodies may enable us to offer a possible treatment to this group of patients.
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