Hocker, Sara E.

Abstract Febrile infection–related epilepsy syndrome (FIRES) is a rare clinical presentation of refractory status epilepticus following a febrile infection. This study analyzes data from the NORSE/FIRES Family Registry, an international web‐based registry available in six languages with data entered by patients, families, and clinicians to explore clinical presentations, survivorship, and long‐term outcomes in adult and pediatric FIRES patients. We characterize and examine differences in demographics, prodromal symptoms, seizure frequency, anti‐seizure medications (ASMs), quality of life, cognition, mood, and anxiety in adults vs pediatric populations with FIRES. Eighty‐six participants were included in the study. Pediatric patients ( n = 54) were predominantly male (77.8%) and experienced a significantly higher post‐FIRES seizure burden than adult survivors (67.7% ≥12 seizures/month in pediatrics vs 11.8% in adults, p <.001). Adults ( n = 32) were more likely to be female (59.4%) and have flu‐like prodromal symptoms (90.6%). At ≥6 months post‐FIRES, both groups exhibited high ASM use, with the majority (87.5%) taking three or more medications. Pediatric patients reported worse mood and anxiety outcomes compared to adults ( p <.005). Self‐reported quality of life and cognition were rated as moderate across in adults (5.2/10) and pediatric (4.7/10) patients, although pediatric patients indicated poorer cognition. Our findings highlight the challenges in managing post‐FIRES outcomes across different age groups, particularly in pediatric patients who face a higher seizure burden and report worse cognitive outcomes.

AbstractIn response to the evolving treatment landscape for new‐onset refractory status epilepticus (NORSE) and the publication of consensus recommendations in 2022, we conducted a comparative analysis of NORSE management over time. Seventy‐seven patients were enrolled by 32 centers, from July 2016 to August 2023, in the NORSE/FIRES biorepository at Yale. Immunotherapy was administered to 88% of patients after a median of 3 days, with 52% receiving second‐line immunotherapy after a median of 12 days (anakinra 29%, rituximab 25%, and tocilizumab 19%). There was an increase in the use of second‐line immunotherapies (odds ratio [OR] = 1.4, 95% CI = 1.1–1.8) and ketogenic diet (OR = 1.8, 95% CI = 1.3–2.6) over time. Specifically, patients from 2022 to 2023 more frequently received second‐line immunotherapy (69% vs 40%; OR = 3.3; 95% CI = 1.3–8.9)—particularly anakinra (50% vs 13%; OR = 6.5; 95% CI = 2.3–21.0), and the ketogenic diet (OR = 6.8; 95% CI = 2.5–20.1)—than those before 2022. Among the 27 patients who received anakinra and/or tocilizumab, earlier administration after status epilepticus onset correlated with a shorter duration of status epilepticus (ρ = .519, p = .005). Our findings indicate an evolution in NORSE management, emphasizing the increasing use of second‐line immunotherapies and the ketogenic diet. Future research will clarify the impact of these treatments and their timing on patient outcomes.

Abstract Febrile infection‐related epilepsy syndrome (FIRES) is a subset of new onset refractory status epilepticus (NORSE) that involves a febrile infection prior to the onset of the refractory status epilepticus. It is unclear whether FIRES and non‐FIRES NORSE are distinct conditions. Here, we compare 34 patients with FIRES to 30 patients with non‐FIRES NORSE for demographics, clinical features, neuroimaging, and outcomes. Because patients with FIRES were younger than patients with non‐FIRES NORSE (median = 28 vs. 48 years old, p = .048) and more likely cryptogenic (odds ratio = 6.89), we next ran a regression analysis using age or etiology as a covariate. Respiratory and gastrointestinal prodromes occurred more frequently in FIRES patients, but no difference was found for non‐infection‐related prodromes. Status epilepticus subtype, cerebrospinal fluid (CSF) and magnetic resonance imaging findings, and outcomes were similar. However, FIRES cases were more frequently cryptogenic; had higher CSF interleukin 6, CSF macrophage inflammatory protein‐1 alpha (MIP‐1a), and serum chemokine ligand 2 (CCL2) levels; and received more antiseizure medications and immunotherapy. After controlling for age or etiology, no differences were observed in presenting symptoms and signs or inflammatory biomarkers, suggesting that FIRES and non‐FIRES NORSE are very similar conditions.