Abstracts

Rationale: A clinical dilemma is when to treat immunologically drug resistant epilepsy (DRE) patients who have some signs of autoimmune etiology but negative neural antibody tests (-AB). This situation is encountered frequently by epileptologists. Diagnoses and treatment decisions for this group of patients present considerable clinical challenges. Although a firm diagnosis would be highly recommended before initiating immunotherapy, biomarkers must be taken into consideration, which aren't always accurate. Considering these challenges, this study sought to determine whether immunotherapy trials (IMT) could be effective in treating patients with DRE with some features suggesting possible autoimmune etiology either on clinical presentation, cognition, psychiatric comorbidities, electroencephalography , or cerebrospinal fluid. The value of IMT in such patients, however, remains unclear. Therefore, we reviewed immunotherapy responses of these seronegative epilepsy patients at our center.

Methods: Retrospective review of DRE patients admitted to the Western University Epilepsy Monitoring Unit between 2018 and 2021 who received IMT. All had -AB or irrelevant results on neural antibody (AB) testing and received immunotherapy (methylprednisolone (IVMP) or immune globulin (IVIg) or plasma exchange (PLEX) or rituximab). Responders were those with ≥ 50% reduction in seizures after treatment.

Results: A total of 36 patients received IMT. Twelve were excluded because another etiology was found. AB were detected in eight patients. Patients with DRE, autoimmune epilepsy (AE) characteristics and negative -AB were identified in fifteen. Among these -AB, three excluded due to partial panel AB testing and twelve had full panel and were included for final analysis. Of them, 50% (n=7) were female, with a median age 43.5 years (IQR= 28.8-63.3). All were refractory to ≥ 2 anti-seizure medications (ASM). Median age of epilepsy onset 39.5 years (IQR=23.8-60.3). Median time from epilepsy diagnosis until received immunotherapy was 15.5 months (IQR=12.8 -21.8). Patients received either IVIG and IVMP (50%, n=6) or IVIG alone (33.3%, n=4) or IVIG, IVMP and PLEX (8.3%, n=1) or IVIG, IVMP and rituximab (8.3%, n=1). Median follow-up was 25 months (IQR=24-31.3). Majority of patients (n=8/12) had non-sustained immunotherapy responses at 3 months. However, sustained response to immunotherapy at last follow-up was only observed in 16.6% (n=2/12). All responders had factors confounding immunotherapy efficacy determination (e.g., changes in ASM, lack of correlation between immunotherapy administration and seizure reduction)

Conclusions: Our study shows that IMT in DRE patients who had -AB were largely unsuccessful, even if some features of autoimmune-associated epilepsy (AAE) were present. This may suggest that immunomodulatory treatment was insufficient or that non-immune mechanisms may be responsible. Critical evaluations of IMT in patients with suspected AAE with -AB are needed.

Funding: None