BackgroundEpilepsy is one of the most common and chronic neurological diseases. About one-third of epilepsy patients do not achieve seizure freedom despite adequate therapy with antiseizure medications (ASMs) and develop drug-resistant epilepsy (DRE). Autoimmunity is increasingly being recognized as a cause of epilepsy in those patients. Some cases are associated with antibodies against several target antigens, including neuronal extracellular proteins as well as intracellular structures. In such patients, immunotherapy may be highly effective. This study aimed to investigate the presence of NMDA-R, AMPA1-R, AMPA2-R, CASPR2, LGI1, GABAB-R, and GAD65 autoantibodies in a sample of Egyptian patients with new-onset DRE; also, to assess the clinical, cerebrospinal fluid (CSF), electroencephalogram (EEG), and radiological characteristics of those patients. Twenty-five patients with recent onset DRE were recruited from the department of Neurology at Ain Shams University (ASU) hospitals. All patients underwent serum and CSF antibody testing using cell-based assay (CBA) at the Immunology unit of the Clinical pathology laboratory at ASU hospitals. This is beside routine CSF analysis, EEG and MRI brain with contrast.ResultsOut of 25 patients with recent onset DRE, one (4%) patient tested positive to anti-NMDA-R antibodies and another one (4%) tested positive to anti-GAD 65 in both serum and CSF. Although the remaining 23 patients tested negative for the 7 autoantibodies, yet 92% of them achieved either seizure freedom or more than 50% reduction in the frequency of seizure and 84% had marked improvement in seizure-associated symptoms after receiving immunotherapy trial. Also, evidence of neuroinflammation was detected in the CSF and MRI brain of the majority of those patients.ConclusionsAutoimmunity should be considered as a possible etiology of new-onset DRE. It is essential to provide insight into the clinical phenotypes and other associated features of those patients, as there are probably numerous patients who are not positive for one of the available antibodies via clinical laboratory testing. In addition to early diagnosis, early treatment and empirical immunotherapy trial based on the clinical judgment is crucial and is likely to improve outcomes with near-complete seizure freedom.