Citations

Immune-mediated epilepsies represent an etiologically unique category defined by immune activation within the central nervous system that initiates a pathophysiological cascade resulting in seizures, encephalopathy, and sometimes epileptogenesis with long-term epilepsy. Once considered rare and largely confined to paraneoplastic or postinfectious syndromes, immune-mediated and inflammatory mechanisms are now recognized across a broad spectrum ranging from acute autoimmune encephalitis with reversible seizures, new-onset refractory status epilepticus, or febrile illness-related refractory status epilepticus, to chronic autoimmune-associated epilepsy and drug-refractory structural epilepsies. This review integrates historical perspectives, mechanistic insights from animal and human studies, and contemporary clinical frameworks. It synthesizes advances in neuroimmunology, clinical phenotyping, diagnostics, immunomodulatory and antiseizure therapies, neuromodulation, and patient and family centered outcomes, and outlines future directions focused on biomarker-driven precision medicine, disease-modifying strategies, and interdisciplinary care models.

Abstract Objective This study aims to better characterize the long‐term neurological quality of life (QOL) outcomes (using the Neuro‐QOL scale) in survivors of new onset refractory status epilepticus (NORSE), including its subtype febrile infection‐related epilepsy syndrome (FIRES), and provide guidance for psychological and social support strategies. Methods Utilizing data from a multicenter prospective study of NORSE/FIRES led by Yale University, we enrolled patients who completed the validated, patient‐reported Neuro‐QOL scale at least once at 3–6 months ( n = 37), 12 months ( n = 29), 24 months ( n = 23), or ≥36 months ( n = 9) following discharge. The Neuro‐QOL scale assesses physical, mental, and social health in patients with neurological disorders. QOL impairment (QOL‐I) scores were calculated, with higher scores indicating greater impairment. T ‐scores enabled comparisons with reference populations. Results In adults, median QOL‐I improved from 44.1% at 3–6 months to 37.6% at 36+ months. Paired analysis showed significant improvement in QOL‐I between 3–6 and 24 months ( p = .016), with specific improvements in communication, satisfaction with social roles, fatigue, and mobility. Greater improvement was also observed for participation in social roles (5.5‐point T ‐score gain) compared to the reference population, suggesting meaningful change. A gradual improvement in overall QOL‐I scores was also observed in pediatric participants, despite a modest sample size ( n = 5 with data at 3–6 and 12 months). Measures of fatigue and anxiety persisted in adults, and cognitive difficulties persisted in both adults and children. In adults, longer status epilepticus duration and intensive care unit stay were associated with poorer QOL. Additionally, a higher number of antiseizure medications was associated with more depression, cognitive impairments, and perceived stigma. Significance These findings highlight the potential for recovery following an acute episode of NORSE, although many patients continue to face challenges requiring ongoing support, and the clinical meaning of the reported QOL improvement remains unclear. Furthermore, the findings underscore the importance of strategic multidisciplinary support systems in the years following discharge.

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.