Trends in management of patients with new-onset refractory status epilepticus (NORSE) from 2016 to 2023: An interim analysis

Aurelie Hanin; Anthony D. Jimenez; Margaret Gopaul; Hannah Asbell; Seyhmus Aydemir; Maysaa Merhi Basha; Ayush Batra; Charlotte Damien; Gregory S. Day; Onome Eka; Krista Eschbach; Safoora Fatima; Madeline C. Fields; Brandon Foreman; Elizabeth E. Gerard; Teneille E. Gofton; Hiba A. Haider; Stephen T. Hantus; Sara Hocker; Amy Jongeling; Mariel Kalkach Aparicio; Padmaja Kandula; Peter Kang; Karnig Kazazian; Marissa A. Kellogg; Minjee Kim; Jong Woo Lee; Lara V. Marcuse; Christopher M. McGraw; Wazim Mohamed; Janet Orozco; Cederic M. Pimentel; Vineet Punia; Alexandra M. Ramirez; Claude Steriade; Aaron F. Struck; Olga Taraschenko; Andrew K. Treister; Mark Wainwright; Ji Yeoun Yoo; Sahar Zafar; Daniel J. Zhou; Deepti Zutshi; Nicolas Gaspard; Lawrence J. Hirsch

doi:10.1111/epi.18014

Trends in management of patients with new-onset refractory status epilepticus (NORSE) from 2016 to 2023: An interim analysis

Aurelie Hanin^*, Anthony D. Jimenez, Margaret Gopaul, Hannah Asbell, Seyhmus Aydemir, Maysaa Merhi Basha, Ayush Batra, Charlotte Damien, Gregory S. Day, Onome Eka, Krista Eschbach, Safoora Fatima, Madeline C. Fields, Brandon Foreman, Elizabeth E. Gerard, Teneille E. Gofton, Hiba A. Haider, Stephen T. Hantus, Sara Hocker, Amy JongelingMariel Kalkach Aparicio, Padmaja Kandula, Peter Kang, Karnig Kazazian, Marissa A. Kellogg, Minjee Kim, Jong Woo Lee, Lara V. Marcuse, Christopher M. McGraw, Wazim Mohamed, Janet Orozco, Cederic M. Pimentel, Vineet Punia, Alexandra M. Ramirez, Claude Steriade, Aaron F. Struck, Olga Taraschenko, Andrew K. Treister, Mark Wainwright, Ji Yeoun Yoo, Sahar Zafar, Daniel J. Zhou, Deepti Zutshi, Nicolas Gaspard, Lawrence J. Hirsch

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

In response to the evolving treatment landscape for new-onset refractory status epilepticus (NORSE) and the publication of consensus recommendations in 2022, we conducted a comparative analysis of NORSE management over time. Seventy-seven patients were enrolled by 32 centers, from July 2016 to August 2023, in the NORSE/FIRES biorepository at Yale. Immunotherapy was administered to 88% of patients after a median of 3 days, with 52% receiving second-line immunotherapy after a median of 12 days (anakinra 29%, rituximab 25%, and tocilizumab 19%). There was an increase in the use of second-line immunotherapies (odds ratio [OR] = 1.4, 95% CI = 1.1–1.8) and ketogenic diet (OR = 1.8, 95% CI = 1.3–2.6) over time. Specifically, patients from 2022 to 2023 more frequently received second-line immunotherapy (69% vs 40%; OR = 3.3; 95% CI = 1.3–8.9)—particularly anakinra (50% vs 13%; OR = 6.5; 95% CI = 2.3–21.0), and the ketogenic diet (OR = 6.8; 95% CI = 2.5–20.1)—than those before 2022. Among the 27 patients who received anakinra and/or tocilizumab, earlier administration after status epilepticus onset correlated with a shorter duration of status epilepticus (ρ =.519, p =.005). Our findings indicate an evolution in NORSE management, emphasizing the increasing use of second-line immunotherapies and the ketogenic diet. Future research will clarify the impact of these treatments and their timing on patient outcomes.

Original language	English (US)
Pages (from-to)	e148-e155
Journal	Epilepsia
Volume	65
Issue number	8
DOIs	https://doi.org/10.1111/epi.18014
State	Published - Aug 2024

Funding

Dr. Batra: Athersys Inc. (clinical trial, site principal investigator), GE Neuro SA (research funding), Wolters Kluwer (royalties). Dr. Foreman: UCB Pharma (honorarium, speakers bureau), SAGE Therapeutics, Inc. (scientific advisory board), Marinus Pharmaceuticals (scientific advisory board, honorarium), Natus, Inc. (honorarium), Neurocritical Care Society Curing Coma Campaign (scientific advisory committee, unpaid), Research funding from National Institutes of Health (NIH), Department of Defense, and Marinus Pharmaceuticals. Dr. Gerard has served as site principal investigator for clinical trials supported by Xenon and Eisai/Stanford University. She has received salary support from NIH/NINDS grants unrelated to the submitted work. She has received travel reimbursement from The One Eight Foundation, and her university has received funds from The One Eight Foundation for research coordinator time. Dr. Haider received salary support from an NIH\u2010funded UG3 grant (1UG3TR004501\u201001A1) unrelated to the submitted work, and author royalties from Springer Publishing and UpToDate Inc. Dr. Taraschenko received support from the NIH P20GM130447 Cognitive Neuroscience and Development of Aging (CONDA) Award and the DHHS LB606 Nebraska Stem Cell Grant. Dr. Gaspard has received unrelated grants from Innoviris and Fonds Erasme pour la Recherche M\u00E9dicale, honoraria from UCB, and Ligue Francophone Belge contre l'Epilepsie. Dr. Hirsch has received consultation fees for advising from Ceribell, Eisai, Gilead, Marinus, Neurelis, Neuropace, Rafa Laboratories, UCB, and Vial Health; royalties from Wolters\u2010Kluwer for authoring chapters for UpToDate\u2010neurology and from Wiley for co\u2010authoring the book \u201CAtlas of EEG in Critical Care,\u201D 1st and 2nd editions; and honoraria for speaking from Neuropace, Natus, and UCB. Dr Steriade reports salary support from The Epilepsy Study Consortium Consulting given to NYU for work provided to the following entities: Alterity, Baergic, Biogen, BioXcel, Cerebral, Cerevel, Eliem, Equilibre, Janssen, Longboard, Lundbeck, Marinus, NeuCyte, Neurocrine, Neuroelectrics, Ono, SK Life Science, and UCB. Dr Steriade also receives grants from NINDS, NORD, UCB, and the Parekh Centre for Interdisciplinary Neurology outside the submitted work. Dr. Day is supported by grants from NIH (K23AG064029, U01AG057195, U01NS120901, U19AG032438) and the Chan Zuckerberg Initiative. He is a consultant for Parabon Nanolabs Inc and a Topic Editor (Dementia) for DynaMed (EBSCO). He is the co\u2010project principal investigator for a clinical trial in anti\u2010NMDAR encephalitis, which receives support from Amgen Pharmaceuticals, and a consultant for Arilays Therapeutics. He has developed educational materials for PeerView Media, Inc. and Continuing Education, Inc. He owns stock in ANI Pharmaceuticals. Dr. Day's institution has received support from Eli Lilly for the development and participation in an educational event promoting early diagnosis of symptomatic Alzheimer's disease and in\u2010kind contributions of radiotracer precursors for tau\u2010PET neuroimaging in studies of memory and aging (via Avid Radiopharmaceuticals, a wholly owned subsidiary of Eli Lilly). Dr. Gofton has research funding from the Canadian Institutes for Health Research, the New Frontiers in Research Fund, the Academic Medical Organization of Southwestern Ontario, and the Lawson Health Research Institute Internal Research Fund. Dr. Lee received research funding from NIH R43NS120394, Marinus, and UCB; a consultation fee from SK Biopharmaceuticals; and performs contract work for Teladoc, all of which are unrelated to the submitted work. Dr. Yoo receives salary support from NIH 1UH3NS109557\u201001A and royalty from Elsevier for co\u2010authoring a book, Rowan's Primer of EEG. Dr. Wainwright is a member of the Neurology Clinical Advisory Board for Sage Therapeutics. Dr. Marcuse is a speaker for Neuropace, which is unrelated to this submitted work. Dr. Struck received a grant from Ceribell for an unrelated study. Dr. Basha: Advisory Board, Ovid Therapeutics. Dr. Zafar received funding from NIH and speaking honoraria from Marinus. Dr Damien received funding from Innoviris and Fonds Erasme pour la Recherche M\u00E9dicale. Dr. McGraw received funding from NIH (K08NS118107\u201301; R21NS127345) and the Orphan Disease Center (CDKL5\u201021\u2010105\u201001; CDKL5\u201023\u2010D\u2010103\u201001), which is not related to this work. Other authors have no disclosures to report. Dr. Hirsch received support for investigator\u2010initiated studies from The Daniel Raymond Wong Neurology Research Fund and the NORSE/FIRES Research Fund at Yale. Dr. Hanin received postdoctoral grants from the Paratonnerre Association, the Swebilius Foundation, the Servier Institute, and the Philippe Foundation for NORSE\u2010related research. Dr. Eschbach, Dr. Haider, Dr. Hocker, Dr. Gofton, Dr. Kellogg, Dr. Taraschenko, Dr. Gaspard, and Dr. Hirsch are members of the Medical and Scientific Advisory Board of the NORSE Institute. Dr. Eschbach received funding from the friends and family of Finn Mussetter for NORSE and FIRES research. Dr Haider received in 2020\u20132022 philanthropic funding from the Neal Nichols Foundation for Status Epilepticus/NORSE Research. The NORSE/FIRES biorepository is supported by the NORSE/FIRES Research Fund at Yale and the NORSE Institute (for more information, see https://www.norseinstitute.org/ or email [email protected] ).

Keywords

age
etiology
immunotherapy
new-onset refractory status epilepticus
outcome

ASJC Scopus subject areas

Neurology
Clinical Neurology

Access to Document

10.1111/epi.18014

Cite this

Hanin, A., Jimenez, A. D., Gopaul, M., Asbell, H., Aydemir, S., Basha, M. M., Batra, A., Damien, C., Day, G. S., Eka, O., Eschbach, K., Fatima, S., Fields, M. C., Foreman, B., Gerard, E. E., Gofton, T. E., Haider, H. A., Hantus, S. T., Hocker, S., ... Hirsch, L. J. (2024). Trends in management of patients with new-onset refractory status epilepticus (NORSE) from 2016 to 2023: An interim analysis. Epilepsia, 65(8), e148-e155. https://doi.org/10.1111/epi.18014

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title = "Trends in management of patients with new-onset refractory status epilepticus (NORSE) from 2016 to 2023: An interim analysis",

abstract = "In response to the evolving treatment landscape for new-onset refractory status epilepticus (NORSE) and the publication of consensus recommendations in 2022, we conducted a comparative analysis of NORSE management over time. Seventy-seven patients were enrolled by 32 centers, from July 2016 to August 2023, in the NORSE/FIRES biorepository at Yale. Immunotherapy was administered to 88% of patients after a median of 3 days, with 52% receiving second-line immunotherapy after a median of 12 days (anakinra 29%, rituximab 25%, and tocilizumab 19%). There was an increase in the use of second-line immunotherapies (odds ratio [OR] = 1.4, 95% CI = 1.1–1.8) and ketogenic diet (OR = 1.8, 95% CI = 1.3–2.6) over time. Specifically, patients from 2022 to 2023 more frequently received second-line immunotherapy (69% vs 40%; OR = 3.3; 95% CI = 1.3–8.9)—particularly anakinra (50% vs 13%; OR = 6.5; 95% CI = 2.3–21.0), and the ketogenic diet (OR = 6.8; 95% CI = 2.5–20.1)—than those before 2022. Among the 27 patients who received anakinra and/or tocilizumab, earlier administration after status epilepticus onset correlated with a shorter duration of status epilepticus (ρ =.519, p =.005). Our findings indicate an evolution in NORSE management, emphasizing the increasing use of second-line immunotherapies and the ketogenic diet. Future research will clarify the impact of these treatments and their timing on patient outcomes.",

keywords = "age, etiology, immunotherapy, new-onset refractory status epilepticus, outcome",

author = "Aurelie Hanin and Jimenez, {Anthony D.} and Margaret Gopaul and Hannah Asbell and Seyhmus Aydemir and Basha, {Maysaa Merhi} and Ayush Batra and Charlotte Damien and Day, {Gregory S.} and Onome Eka and Krista Eschbach and Safoora Fatima and Fields, {Madeline C.} and Brandon Foreman and Gerard, {Elizabeth E.} and Gofton, {Teneille E.} and Haider, {Hiba A.} and Hantus, {Stephen T.} and Sara Hocker and Amy Jongeling and Mariel Kalkach Aparicio and Padmaja Kandula and Peter Kang and Karnig Kazazian and Kellogg, {Marissa A.} and Minjee Kim and Lee, {Jong Woo} and Marcuse, {Lara V.} and McGraw, {Christopher M.} and Wazim Mohamed and Janet Orozco and Pimentel, {Cederic M.} and Vineet Punia and Ramirez, {Alexandra M.} and Claude Steriade and Struck, {Aaron F.} and Olga Taraschenko and Treister, {Andrew K.} and Mark Wainwright and Yoo, {Ji Yeoun} and Sahar Zafar and Zhou, {Daniel J.} and Deepti Zutshi and Nicolas Gaspard and Hirsch, {Lawrence J.}",

note = "Publisher Copyright: {\textcopyright} 2024 International League Against Epilepsy.",

year = "2024",

month = aug,

doi = "10.1111/epi.18014",

language = "English (US)",

volume = "65",

pages = "e148--e155",

journal = "Epilepsia",

issn = "0013-9580",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "8",

}

Hanin, A, Jimenez, AD, Gopaul, M, Asbell, H, Aydemir, S, Basha, MM, Batra, A, Damien, C, Day, GS, Eka, O, Eschbach, K, Fatima, S, Fields, MC, Foreman, B, Gerard, EE, Gofton, TE, Haider, HA, Hantus, ST, Hocker, S, Jongeling, A, Kalkach Aparicio, M, Kandula, P, Kang, P, Kazazian, K, Kellogg, MA, Kim, M, Lee, JW, Marcuse, LV, McGraw, CM, Mohamed, W, Orozco, J, Pimentel, CM, Punia, V, Ramirez, AM, Steriade, C, Struck, AF, Taraschenko, O, Treister, AK, Wainwright, M, Yoo, JY, Zafar, S, Zhou, DJ, Zutshi, D, Gaspard, N & Hirsch, LJ 2024, 'Trends in management of patients with new-onset refractory status epilepticus (NORSE) from 2016 to 2023: An interim analysis', Epilepsia, vol. 65, no. 8, pp. e148-e155. https://doi.org/10.1111/epi.18014

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T1 - Trends in management of patients with new-onset refractory status epilepticus (NORSE) from 2016 to 2023

T2 - An interim analysis

AU - Hanin, Aurelie

AU - Jimenez, Anthony D.

AU - Gopaul, Margaret

AU - Asbell, Hannah

AU - Aydemir, Seyhmus

AU - Basha, Maysaa Merhi

AU - Batra, Ayush

AU - Damien, Charlotte

AU - Day, Gregory S.

AU - Eka, Onome

AU - Eschbach, Krista

AU - Fatima, Safoora

AU - Fields, Madeline C.

AU - Foreman, Brandon

AU - Gerard, Elizabeth E.

AU - Gofton, Teneille E.

AU - Haider, Hiba A.

AU - Hantus, Stephen T.

AU - Hocker, Sara

AU - Jongeling, Amy

AU - Kalkach Aparicio, Mariel

AU - Kandula, Padmaja

AU - Kang, Peter

AU - Kazazian, Karnig

AU - Kellogg, Marissa A.

AU - Kim, Minjee

AU - Lee, Jong Woo

AU - Marcuse, Lara V.

AU - McGraw, Christopher M.

AU - Mohamed, Wazim

AU - Orozco, Janet

AU - Pimentel, Cederic M.

AU - Punia, Vineet

AU - Ramirez, Alexandra M.

AU - Steriade, Claude

AU - Struck, Aaron F.

AU - Taraschenko, Olga

AU - Treister, Andrew K.

AU - Wainwright, Mark

AU - Yoo, Ji Yeoun

AU - Zafar, Sahar

AU - Zhou, Daniel J.

AU - Zutshi, Deepti

AU - Gaspard, Nicolas

AU - Hirsch, Lawrence J.

PY - 2024/8

Y1 - 2024/8

N2 - In response to the evolving treatment landscape for new-onset refractory status epilepticus (NORSE) and the publication of consensus recommendations in 2022, we conducted a comparative analysis of NORSE management over time. Seventy-seven patients were enrolled by 32 centers, from July 2016 to August 2023, in the NORSE/FIRES biorepository at Yale. Immunotherapy was administered to 88% of patients after a median of 3 days, with 52% receiving second-line immunotherapy after a median of 12 days (anakinra 29%, rituximab 25%, and tocilizumab 19%). There was an increase in the use of second-line immunotherapies (odds ratio [OR] = 1.4, 95% CI = 1.1–1.8) and ketogenic diet (OR = 1.8, 95% CI = 1.3–2.6) over time. Specifically, patients from 2022 to 2023 more frequently received second-line immunotherapy (69% vs 40%; OR = 3.3; 95% CI = 1.3–8.9)—particularly anakinra (50% vs 13%; OR = 6.5; 95% CI = 2.3–21.0), and the ketogenic diet (OR = 6.8; 95% CI = 2.5–20.1)—than those before 2022. Among the 27 patients who received anakinra and/or tocilizumab, earlier administration after status epilepticus onset correlated with a shorter duration of status epilepticus (ρ =.519, p =.005). Our findings indicate an evolution in NORSE management, emphasizing the increasing use of second-line immunotherapies and the ketogenic diet. Future research will clarify the impact of these treatments and their timing on patient outcomes.

AB - In response to the evolving treatment landscape for new-onset refractory status epilepticus (NORSE) and the publication of consensus recommendations in 2022, we conducted a comparative analysis of NORSE management over time. Seventy-seven patients were enrolled by 32 centers, from July 2016 to August 2023, in the NORSE/FIRES biorepository at Yale. Immunotherapy was administered to 88% of patients after a median of 3 days, with 52% receiving second-line immunotherapy after a median of 12 days (anakinra 29%, rituximab 25%, and tocilizumab 19%). There was an increase in the use of second-line immunotherapies (odds ratio [OR] = 1.4, 95% CI = 1.1–1.8) and ketogenic diet (OR = 1.8, 95% CI = 1.3–2.6) over time. Specifically, patients from 2022 to 2023 more frequently received second-line immunotherapy (69% vs 40%; OR = 3.3; 95% CI = 1.3–8.9)—particularly anakinra (50% vs 13%; OR = 6.5; 95% CI = 2.3–21.0), and the ketogenic diet (OR = 6.8; 95% CI = 2.5–20.1)—than those before 2022. Among the 27 patients who received anakinra and/or tocilizumab, earlier administration after status epilepticus onset correlated with a shorter duration of status epilepticus (ρ =.519, p =.005). Our findings indicate an evolution in NORSE management, emphasizing the increasing use of second-line immunotherapies and the ketogenic diet. Future research will clarify the impact of these treatments and their timing on patient outcomes.

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KW - etiology

KW - immunotherapy

KW - new-onset refractory status epilepticus

KW - outcome

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Trends in management of patients with new-onset refractory status epilepticus (NORSE) from 2016 to 2023: An interim analysis

Abstract

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