Insights into new-onset refractory status epilepticus (NORSE) from biorepository-based studies

New-onset refractory status epilepticus (NORSE) is a rare clinical condition characterized by the occurrence of refractory status epilepticus in previously healthy children or adults. When preceded by a febrile illness 1-14 days prior, it is known as Febrile Infection-Related Epilepsy Syndrome (FIRES). In most cases, no underlying etiology is identified despite extensive evaluation, and these patients are classified as having cryptogenic NORSE. The NORSE Institute was established to define the condition, increase awareness, and facilitate collaborative research, notably through the creation of a biorepository designed to collect biospecimens and clinical data from patients with NORSE. In recent years, extensive research has been conducted using these samples and datasets, as well as complementary resources from additional collaborating biorepositories. In this review, we summarize recent advances in the field, namely the development of guidelines for biospecimen collection and use, the characterization of immune dysfunction and its potential link to neuronal excitability and possibly to personalized treatments, the interaction between the microbiome and inflammatory pathways, and the characterization of clinical outcomes in patients with NORSE. Together, these advances are improving our understanding of NORSE mechanisms, helping to identify prognostic biomarkers and to support the development of personalized treatments.