New onset refractory status epilepticus (NORSE)

Abstract

To summarize the clinical features, suggested work-up, treatment and prognosis of new-onset refractory status epilepticus (NORSE), a condition recently defined as the occurrence of refractory status epilepticus (RSE) in a patient without active epilepsy, and without a clear acute or active structural, toxic or metabolic cause; and of the related syndrome of febrile infection-related epilepsy syndrome (FIRES), also recently defined as a subgroup of NORSE preceded by a febrile illness between 2 weeks and 24 h prior to the onset of RSE. Method: Narrative review of the medical literature about NORSE and FIRES. Results: NORSE and FIRES mainly affect school-age children and young adults. A prodromal phase with flu-like symptoms precedes the SE onset in two third of NORSE cases, and by definition in all FIRES. Status epilepticus usually starts with repeated focal seizures with secondary bilateralization. Most cases evolve to super RSE (SRSE) and have unfavorable outcome, with short-term mortality of 12-27%, long-term disability and epilepsy. No specific imaging or laboratory abnormalities have been identified so far that allows an early diagnosis and half of adult cases remain of unknown etiology. A standardized diagnostic algorithm is provided and. Autoimmune encephalitis is the most frequent identified cause. In the absence of specific diagnosis, immunotherapy could be tried in addition to antiepileptic treatment. Conclusions: This review presents the rare but devastating syndrome of NORSE, including the subcategory of FIRES. Early recognition with complete work-up is primordial to identify the underlying cause and promptly start appropriate treatment.

Seizure specificities in patients with antibody‐mediated autoimmune encephalitis

“…A particular clinical scenario in which antibody testing needs to be considered, regardless of the APE score, is new‐onset refractory status epilepticus (NORSE). This applies to previously healthy individuals who develop refractory status epilepticus of unknown etiology, despite a comprehensive 72‐hour workup . The operative definitions of NORSE, as well as that of its main subgroup, which is characterized by a preceding febrile illness (FIRES), were recently discussed in a consensus proposal .…”

“…Nevertheless, even in the case of antibody‐negative testing, immunotherapy can be effective in terminating seizures. Finally, AE can also present as NORSE, and the absence of GABA A R testing probably accounts for a proportion of reportedly antibody‐negative cases …”

“…This applies to previously healthy individuals who develop refractory status epilepticus of unknown etiology, despite a comprehensive 72-hour workup. [94][95][96] The operative definitions of NORSE, as well as that of its main subgroup, which is characterized by a preceding febrile illness (FIRES), were recently discussed in a consensus proposal. 94 Several important differences exist between these conditions and the AE syndromes previously described.…”

“…Finally, AE can also present as NORSE, and the absence of GABA A R testing probably accounts for a proportion of reportedly antibody-negative cases. 94,96,97…”

Functional deficiency in endogenous interleukin‐1 receptor antagonist in patients with febrile infection‐related epilepsy syndrome

“…Febrile infection‐related epilepsy syndrome (FIRES), a subtype of new onset refractory status epilepticus (SE), is a rare seizure disorder defined by the occurrence of refractory SE that lacks a structural, toxic, or metabolic cause starting between 2 weeks and 24 hours after febrile illness, with or without fever at the onset of SE . Most FIRES patients are treated with antiseizure drugs, ketogenic diet, immunomodulatory therapies, and/or medically induced coma, with low overall therapeutic efficacy rates .…”