The ongoing dilemma of immunotherapy in antibody-negative suspected autoimmune encephalitis-associated epilepsy: A...

This study evaluates immunotherapy in drug-resistant epilepsy (DRE) patients with concern for autoimmune encephalitis-associated epilepsy (AEAE) but negative neural antibody testing (-Ab).

A retrospective cohort study, focusing on patients treated at our Epilepsy Monitoring Unit (EMU) from January 2018 to May 2022. Of 39 patients with DRE who received immunotherapy, 27 had clinical concern for AEAE. After excluding patients with absent or incomplete neural antibody testing (n = 7) or positive neural antibodies (n = 8), 12 antibody-negative patients constituted the final study cohort.

Among the final 12 patients, 41.7% were female (median age 43.5 years, IQR = 28.8-63.3). The median age of epilepsy onset was 39.5 years (IQR = 23.8-60.3), and patients began immunomodulatory treatment (IMT) at a median of 15.5 months after seizure onset (IQR = 12.8-21.8). Distribution of treatments was 41.6% both intravenous immunoglobulin (IVIg) and methylprednisolone (IVMP), 33.3% IVIG alone, 16.6% IVIG, IVMP, and plasma exchanges (PLEX), and 8.3% IVIG, IVMP, and rituximab. After a median follow-up of 25 months (IQR = 24-31.3), the majority (10/12) had non-sustained responses beyond 6 months, with only 2/12 showing sustained (>50% reduction in seizures) responses. Confounding factors (e.g., concomitant ASM addition/change, lack of temporal relationship to immunotherapy) were identified in both cases.

The study reveals IMT has limited success in patients with DRE and concern for AEAE but Ab-. Critical evaluation of IMT is essential in suspected AEAE cases with Ab- to avoid unnecessary administration of potentially hazardous immunotherapy in patients who are unlikely to benefit.