Tissue-based assay-confirmed, antibody-negative autoimmune encephalitis responsive to low-dose rituximab in an elderly patient.

Abstract

Antibody-negative Autoimmune encephalitis (AE) presents a diagnostic challenge, requiring a high index of clinical suspicion and comprehensive evaluation. We report a 66-year-old man presenting with a seizure accompanied by progressive cognitive decline over several days. Despite the presence of hallmark symptoms and suggestive imaging, the patient was initially misdiagnosed, delaying timely immunotherapy. The diagnosis of antibody-negative AE was made based on clinical criteria, including consistent serological and cerebrospinal fluid (CSF) analyses (negative for known autoimmune and paraneoplastic antibodies), alongside a positive tissue-based assay (TBA), cranial MRI findings, and peripheral blood B-cell profiling. The patient responded well to immunotherapy with a low-dose sequential rituximab regimen, demonstrating clinical improvement and halting disease progression. This case highlights the importance of adhering to diagnostic criteria for AE and integrating TBA into the diagnostic workflow for antibody-negative AE.