Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Aug 11;63(11):2827-2839.
doi: 10.1111/epi.17391. Online ahead of print.

International consensus recommendations for management of New Onset Refractory Status Epilepticus (NORSE) including Febrile Infection-Related Epilepsy Syndrome (FIRES): Summary and Clinical Tools

Ronny Wickstrom  1 , Olga Taraschenko  2 , Robertino Dilena  3 , Eric T Payne  4 , Nicola Specchio  5 , Rima Nabbout  6 , Sookyong Koh  7 , Nicolas Gaspard  8 , Lawrence J Hirsch  9 ; International NORSE Consensus Group
Collaborators, Affiliations

International consensus recommendations for management of New Onset Refractory Status Epilepticus (NORSE) including Febrile Infection-Related Epilepsy Syndrome (FIRES): Summary and Clinical Tools

Ronny Wickstrom et al. Epilepsia. .

Abstract

Objective: To develop consensus-based recommendations for the management of adult and pediatric patients with NORSE/FIRES based on best available evidence and expert opinion.

Methods: The Delphi methodology was followed. A facilitator group of 9 experts was established, who defined the scope, users and suggestions for recommendations. Following a review of the current literature, recommendation statements concerning diagnosis, treatment and research directions were generated which were then voted on a scale of 1 (strongly disagree) to 9 (strongly agree) by a panel of 48 experts in the field. Consensus that a statement was appropriate was reached if the median score was greater than or equal to 7, and inappropriate if the median score was less than or equal to 3.

Results: Overall, 85 recommendation statements achieved consensus. The recommendations are divided into five sections: 1) disease characteristics, 2) diagnostic testing and sampling, 3) acute treatment, 4) treatment in the post-acute phase, and 5) research, registries and future directions in NORSE/FIRES. These are summarized in this article along with two practical clinical flowsheets: one for diagnosis and evaluation and one for acute treatment. A corresponding evidence-based analysis of all 85 recommendations alongside responses by the Delphi panel is presented in a companion article.

Significance: The recommendations generated by this consensus can be used as a guide for the diagnosis, evaluation, and management of patients with NORSE/FIRES, and for planning of future research.

Keywords: Adult; Anti-seizure medication; Delphi; Epilepsy; Immunotherapy; Ketogenic diet; Pediatric; Refractory status epilepticus; Status epilepticus.

PubMed Disclaimer

Conflict of interest statement

RW has served on scientific advisory boards for GW Pharma and Octapharma and has received speaker honoraria from Eisai and Sanofi. OT was supported by research grant from the National Institutes of Health (NIH) (P20GM130447). RD has received speaker honorarium fee from Sobi. ETP has received a speaker honorarium from Eisai. RN has no disclosures for this study. SK has served on scientific advisory boards for Zogenix and Neurelis. NG has no disclosures for this study. LJH has received consultation fees for advising from Accure, Aquestive, Ceribell, Eisai, Marinus, Medtronic, Neurelis, Neuropace, and UCB; royalties from Wolters‐Kluwer for authoring chapters for UpToDate‐Neurology and from Wiley for co‐authoring the book “Atlas of EEG in Critical Care,” by Hirsch and Brenner; and honoraria for speaking from Neuropace, Natus, and UCB. NS has served on scientific advisory boards for GW Pharma, BioMarin, Arvelle, Marinus, and Takeda; has received speaker honoraria from Eisai, Biomarin, Livanova, and Sanofi; and has served as an investigator for Zogenix, Marinus, Biomarin, UCB, and Roche. RW, OT, RN, SK, NG, and LJH are members of the Scientific Board of the NORSE Institute. The present study is not industry sponsored. 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.

Figures

FIGURE 1
FIGURE 1
Algorithm for diagnostic workup in NORSE including FIRES. Adapted from NORSE Institute website (https://www.norseinstitute.org/) and Sculier et al. Ag, antigen; ANA, anti‐nuclear antibodies, ANCA, anti‐neutrophil cytoplasmic antibodies; B. henselae, Bartonella henselae; BUN, blood urea nitrogen; C. burnetii, Coxiella burnetii; C. pneumoniae, Chlamydia pneumoniae; C. psittaci, Chlamydia psittaci; CBC, complete blood count; cEEG, continuous EEG; CGH, comparative genomic hybridization; CMV, cytomegalovirus; CNS, central nervous system; CRP, C‐reactive protein; CSF, cerebrospinal fluid; DNA, deoxyribonucleic acid; EBV, Epstein–Barr virus; EEEV, eastern equine encephalitis virus; EEG, electroencephalography; ESR, erythrocyte sedimentation rate; GAD, glutamic acid decarboxylase; HHV, human herpesvirus; HIV, human immunodeficiency virus; HSV, herpes simplex virus; ID, infectious disease; IgG, immunoglobulin G; JC, John Cunningham; LDH, lactate dehydrogenase; LFT, liver function test; M. pneumoniae, Mycoplasma pneumoniae; MOG, myelin oligodendrocyte glycoprotein; MRA, magnetic resonance angiography; MRI, magnetic resonance imaging; MRV, magnetic resonance venography; PCR, polymerase chain reaction; PET‐CT, positron emission tomography–computed tomography; SARS‐CoV2, severe acute respiratory syndrome coronavirus 2; SLE, systemic lupus erythematosus; UA, urine analysis; US; ultrasound; VLCFA, very long chain fatty acid; VDRL, Venereal Disease Research Laboratory; VZV, varicella‐zoster virus; WNV, West Nile virus.
FIGURE 2
FIGURE 2
Suggested treatment algorithm for NORSE including FIRES (expert opinion). Adapted from Gaspard et al. van Baalen et al. and Sculier et al. AE, autoimmune encephalitis; ASM, anti‐seizure medication; IV, intravenous; IVIG, intravenous immunoglobulins; RSE, refractory status epilepticus; SE, status epilepticus.
See this image and copyright information in PMC

References

    1. Hirsch LJ, Gaspard N, van Baalen A, Nabbout R, Demeret S, Loddenkemper T, et al. Proposed consensus definitions for new‐onset refractory status epilepticus (NORSE), febrile infection‐related epilepsy syndrome (FIRES), and related conditions. Epilepsia. 2018;59:739–44. - PubMed
    1. Kortvelyessy P, Lerche H, Weber Y. FIRES and NORSE are distinct entities. Epilepsia. 2012;53:1276. - PubMed
    1. Gaspard N, Hirsch LJ, Sculier C, Loddenkemper T, van Baalen A, Lancrenon J, et al. New‐onset refractory status epilepticus (NORSE) and febrile infection‐related epilepsy syndrome (FIRES): state of the art and perspectives. Epilepsia. 2018;59:745–52. - PubMed
    1. Sculier C, Gaspard N. New onset refractory status epilepticus (NORSE). Seizure. 2019;68:72–8. - PubMed
    1. Sakuma H, Horino A, Kuki I. Neurocritical care and target immunotherapy for febrile infection‐related epilepsy syndrome. Biom J. 2020;43:205–10. - PMC - PubMed