FIRES and NORSE are distinct entities

Abstract

To the Editors: Recently, a brief communication was published in Epilepsia (Ismail & Kossoff, 2011) concerning new-onset refractory status epilepticus (NORSE) and fever-induced refractory epileptic encephalopathy syndrome (FIRES). The authors of this article proposed that these syndromes are the same entities. In our view, these syndromes are distinct diseases with different underlying pathomechanisms. Certainly, a small population described by Glaser et al. (2008) in the California Encephalitis Project might present with overlapping features, such as devastating outcome, rare pathologic alterations on cerebral magnetic resonance imaging (cMRI), and only mild changes in the cerebrospinal fluid. However, FIRES appears in children 2–17 years of age (mainly between the age 4 and 9), and is characterized by a fever-induced refractory status epilepticus (rSE) (van Baalen et al., 2010). In contrast, NORSE has often been described as rSE in adulthood (18–53 years), but not always with preceding febrile illness. Furthermore, NORSE shows a clear preponderance (4:1) in women (at ages 20–32 years) (e.g., Costello et al., 2009 and our own unpublished data), whereas slightly more men (57%) are affected in FIRES (Kramer et al., 2011). Electroencephalography results in patients with FIRES show focal epileptic activity with predominance in the temporal or frontal lobe (Kramer et al., 2011), whereas in NORSE, multifocal activity has been reported without a focal preponderance, indicating a more unspecific origin (Costello et al., 2009). In both entities, the underlying cause is enigmatic. We propose that considering the young age of onset, a genetic coetiology might be worth pursuing in FIRES; in NORSE, such a genetic etiology is not very likely. Because these disorders appear to affect two distinct populations and present with different clinical symptoms, we believe that they should not be mixed up. The authors have no conflict of interest to disclose. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.