New onset refractory status epilepticus: Long-term outcomes beyond seizures

Poul H Espino¹, Krista Eschbach², Leah J Blank³, Mackenzie C Cervenka⁴, Eyal Muscal⁵, Raquel Farias-Moeller⁶, Emily J Gilmore⁷, Margaret T Gopaul⁷, Hiba A Haider⁸, Aurelie Hanin^{7

9}, Lawrence J Hirsch⁷, Marissa A Kellogg¹⁰, Gerhard Kluger^{11

12}, Soon-Tae Lee¹³, Alexandria E Melendez-Zaidi¹⁴, Vincent Navarro¹⁵, Audrey C Oliger¹⁰, Elena Pasini¹⁶, Gitta Reuner¹⁷, Cynthia M Sharpe¹⁸, Zubeda B Sheikh¹⁹, Leon Steigleder²⁰, Claude Steriade²¹, Coral M Stredny²², Adam Strzelczyk²³, Olga Taraschenko²⁴, Andreas van Baalen²⁵, Sarah A Vinette²⁶, Ronny Wickström²⁷, Nora W Wong²⁸, Jiyeoun Yoo³, Teneille E Gofton¹

Affiliations

¹ Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
² Section of Child Neurology, Department of Pediatrics, Children's Hospital Colorado, University of Colorado, Aurora, Colorado, USA.
³ Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁴ Department of Neurology, Johns Hopkins Hospital, Baltimore, Maryland, USA.
⁵ Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
⁶ Department of Neurology, Children's Hospital of Wisconsin, Milwaukee, Wisconsin, USA.
⁷ Department of Neurology, Comprehensive Epilepsy Center, Yale University School of Medicine, New Haven, Connecticut, USA.
⁸ Department of Neurology, Comprehensive Epilepsy Center, University of Chicago, Chicago, Illinois, USA.
⁹ Institut du Cerveau, Paris Brain Institute, ICM, INSERM, Assistance Publique Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Sorbonne Université, Paris, France.
¹⁰ Department of Neurology, Oregon Health & Science University, Portland, Oregon, USA.
¹¹ Research Institute for Rehabilitation, Transition, and Palliation, Paracelsus Medical University Salzburg, Salzburg, Austria.
¹² Clinic for Neuropediatrics, Epilepsy Center for Children and Adolescents, Schoen Clinic Vogtareuth, Vogtareuth, Germany.
¹³ Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
¹⁴ Division of Neurology, Department of Pediatrics, Texas Children's Hospital and Baylor College of Medicine, Houston, Texas, USA.
¹⁵ Epilepsy Unit, Paris Brain Institute, AP-HP, Pitié-Salpêtrière Hospital, ERN EpiCARE, Sorbonne Université, Paris, France.
¹⁶ Unit of Neurology, Istituto di Ricovero e Cura a Carattere Scientifico-Istituto delle Scienze Neurologiche di Bologna, Bellaria Hospital, Bologna, Italy.
¹⁷ Institute of Education Studies, Heidelberg University, Heidelberg, Germany.
¹⁸ University of Auckland, Auckland, New Zealand.
¹⁹ Department of Neurology, Virginia Commonwealth University, Richmond, Virginia, USA.
²⁰ University of Ulm, Ulm, Germany.
²¹ Department of Neurology, NYU Langone Medical Center, New York, New York, USA.
²² Department of Neurology, Boston Children's Hospital, Boston, Massachusetts, USA.
²³ Department of Neurology, Epilepsy Center Frankfurt Rhine-Main, University Medicine Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany.
²⁴ Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, Nebraska, USA.
²⁵ Department of Neuropediatrics, University Medical Center Schleswig-Holstein, Kiel University (CAU), Kiel, Germany.
²⁶ Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
²⁷ Neuropediatric Unit, Department of Women's and Children's Health, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden.
²⁸ NORSE Institute, Summit, New Jersey, USA.

PMID: 39825688
PMCID: PMC11997932
DOI: 10.1111/epi.18267

Review

New onset refractory status epilepticus: Long-term outcomes beyond seizures

Poul H Espino et al. Epilepsia. 2025 Apr.

. 2025 Apr;66(4):988-1005.

doi: 10.1111/epi.18267. Epub 2025 Jan 18.

Authors

Affiliations

¹ Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
² Section of Child Neurology, Department of Pediatrics, Children's Hospital Colorado, University of Colorado, Aurora, Colorado, USA.
³ Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁴ Department of Neurology, Johns Hopkins Hospital, Baltimore, Maryland, USA.
⁵ Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
⁶ Department of Neurology, Children's Hospital of Wisconsin, Milwaukee, Wisconsin, USA.
⁷ Department of Neurology, Comprehensive Epilepsy Center, Yale University School of Medicine, New Haven, Connecticut, USA.
⁸ Department of Neurology, Comprehensive Epilepsy Center, University of Chicago, Chicago, Illinois, USA.
⁹ Institut du Cerveau, Paris Brain Institute, ICM, INSERM, Assistance Publique Hôpitaux de Paris, Hôpital de la Pitié-Salpêtrière, Sorbonne Université, Paris, France.
¹⁰ Department of Neurology, Oregon Health & Science University, Portland, Oregon, USA.
¹¹ Research Institute for Rehabilitation, Transition, and Palliation, Paracelsus Medical University Salzburg, Salzburg, Austria.
¹² Clinic for Neuropediatrics, Epilepsy Center for Children and Adolescents, Schoen Clinic Vogtareuth, Vogtareuth, Germany.
¹³ Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
¹⁴ Division of Neurology, Department of Pediatrics, Texas Children's Hospital and Baylor College of Medicine, Houston, Texas, USA.
¹⁵ Epilepsy Unit, Paris Brain Institute, AP-HP, Pitié-Salpêtrière Hospital, ERN EpiCARE, Sorbonne Université, Paris, France.
¹⁶ Unit of Neurology, Istituto di Ricovero e Cura a Carattere Scientifico-Istituto delle Scienze Neurologiche di Bologna, Bellaria Hospital, Bologna, Italy.
¹⁷ Institute of Education Studies, Heidelberg University, Heidelberg, Germany.
¹⁸ University of Auckland, Auckland, New Zealand.
¹⁹ Department of Neurology, Virginia Commonwealth University, Richmond, Virginia, USA.
²⁰ University of Ulm, Ulm, Germany.
²¹ Department of Neurology, NYU Langone Medical Center, New York, New York, USA.
²² Department of Neurology, Boston Children's Hospital, Boston, Massachusetts, USA.
²³ Department of Neurology, Epilepsy Center Frankfurt Rhine-Main, University Medicine Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany.
²⁴ Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, Nebraska, USA.
²⁵ Department of Neuropediatrics, University Medical Center Schleswig-Holstein, Kiel University (CAU), Kiel, Germany.
²⁶ Division of Neurology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
²⁷ Neuropediatric Unit, Department of Women's and Children's Health, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden.
²⁸ NORSE Institute, Summit, New Jersey, USA.

PMID: 39825688
PMCID: PMC11997932
DOI: 10.1111/epi.18267

Abstract

We propose and prioritize important outcome domains that should be considered for future research investigating long-term outcomes (LTO) after new onset refractory status epilepticus (NORSE). The study was led by the international NORSE Institute LTO Working Group. First, literature describing the LTO of NORSE survivors was identified using a PubMed search and summarized to identify knowledge gaps. Subsequently, a consensus-building process was performed to prioritize and rank important LTO domains for further research. The prioritization of LTO domains was qualitative, enabling the expert panel to generate ideas, share opinions, and provide reasons for the rankings. A second round took place to allow expansion and agreement regarding specific details for each domain. Outcomes were classified into eight main domains: (1) Function: Neuropsychological, Neurological (other than seizures), and Psychiatric (mood and behavior); (2) Quality of Life; (3) Epilepsy; (4) Nonneurological (medical); (5) Social; (6) Caregiver Burden; (7) Long-Term Mortality; and (8) Health Care System Impact. In addition, the working group suggested obtaining outcome measures for each domain at 6 months and 1 year after discharge and annually thereafter until stability has been reached. There are no currently established time frames set for when LTO in NORSE begin or plateau, and previously there existed no consensus regarding which LTO should be considered. This consensus process identifies and recommends NORSE LTO domains that should be considered in future research studies to provide more consistent results that can be compared between studies. Survivors of NORSE should be evaluated serially and at fixed points over time to maximize our understanding of the recovery trajectory for all LTO domains. Establishing reliable and standardized data describing LTO (beyond seizures) after NORSE will support discussions with families during the acute stages, prognostication, the development of targeted management strategies for survivors, and future comparative research globally helping to identify biomarkers that may predict LTO.

Keywords: FIRES; NORSE; epilepsy; neuropsychological; psychiatric; quality of life.

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Conflict of interest statement

T.E.G. has received support from the Robert N. Kohn NORSE Family Registry Memorial Research Fund and from the Canadian Institutes of Health Research, Lawson Internal Research Fund, and Academic Medical Organization of Southwestern Ontario for unrelated research. M.C.C. has received support from the Johns Hopkins Center for Refractory Status Epilepticus and Neuroinflammation; has served as a paid consultant for Nutricia/Danone, Vitaflo/Nestle Health Science; and has received honoraria from Nutricia/Danone, Vitaflo/Nestle Health Science and royalties from Demos Health/Springer Publishing Company during the period of the research activity and generation of the current report. A.H. has received support from the Paratonnerre Association, the Swebilius Foundation, the Servier Institute, the Philippe Foundation, and the NORSE Institute for NORSE‐Related Research. H.A.H. has received support from the NORSE Institute Medical as an advisory board member, Springer Publishing, and UpToDate (research funding: NINDS R21NS137117 and NCATS UG3TR004501‐01A1). S.‐T.L. has received support from Roche/Genentech (steering committee), Advanced Neural Technologies (advisory board), GC Pharma, and Celltrion, outside the submitted work. A.S. has received support from Angelini Pharma, Biocodex, Desitin Arzneimittel, Eisai, Jazz Pharmaceuticals, Takeda, UCB Pharma, and UNEEG medical. C.M.Sh. has received support from the Pediatric Epilepsy Research Foundation. C.S. has received support from the Epilepsy Study Consortium for work provided to Alterity, Baergic, Biogen, BioXcel, Cerebral, Cerevel, Eliem, Equilibre, Janssen, Longboard, Lundbeck, Marinus, NeuCyte, Neurocrine, Neuroelectrics, Ono, SK Life Science, and UCB; grants from NINDS, AES, UCB, and Parekh Centre for Interdisciplinary Neurology outside the submitted work; speakers bureau fees on behalf of SK Life Sciences and Neurelis; and fees for editorial work for Dynamed. The remaining authors have no conflict of interest. No funding was received to directly support this article. 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.

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New onset refractory status epilepticus: Long-term outcomes beyond seizures

Affiliations

New onset refractory status epilepticus: Long-term outcomes beyond seizures

Authors

Affiliations

Abstract

Conflict of interest statement

References

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LinkOut - more resources

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