Clinical presentation of new onset refractory status epilepticus in children (the pSERG cohort)

pSERG

doi:10.1111/epi.16950

Clinical presentation of new onset refractory status epilepticus in children (the pSERG cohort)

pSERG

Pediatrics

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

27 Scopus citations

Abstract

Objective: We aimed to characterize the clinical profile and outcomes of new onset refractory status epilepticus (NORSE) in children, and investigated the relationship between fever onset and status epilepticus (SE). Methods: Patients with refractory SE (RSE) between June 1, 2011 and October 1, 2016 were prospectively enrolled in the pSERG (Pediatric Status Epilepticus Research Group) cohort. Cases meeting the definition of NORSE were classified as "NORSE of known etiology" or "NORSE of unknown etiology." Subgroup analysis of NORSE of unknown etiology was completed based on the presence and time of fever occurrence relative to RSE onset: fever at onset (≤24 h), previous fever (2 weeks–24 h), and without fever. Results: Of 279 patients with RSE, 46 patients met the criteria for NORSE. The median age was 2.4 years, and 25 (54%) were female. Forty (87%) patients had NORSE of unknown etiology. Nineteen (48%) presented with fever at SE onset, 16 (40%) had a previous fever, and five (12%) had no fever. The patients with preceding fever had more prolonged SE and worse outcomes, and 25% recovered baseline neurological function. The patients with fever at onset were younger and had shorter SE episodes, and 89% recovered baseline function. Significance: Among pediatric patients with RSE, 16% met diagnostic criteria for NORSE, including the subcategory of febrile infection-related epilepsy syndrome (FIRES). Pediatric NORSE cases may also overlap with refractory febrile SE (FSE). FIRES occurs more frequently in older children, the course is usually prolonged, and outcomes are worse, as compared to refractory FSE. Fever occurring more than 24 h before the onset of seizures differentiates a subgroup of NORSE patients with distinctive clinical characteristics and worse outcomes.

Original language	English (US)
Pages (from-to)	1629-1642
Number of pages	14
Journal	Epilepsia
Volume	62
Issue number	7
DOIs	https://doi.org/10.1111/epi.16950
State	Published - Jul 2021

Funding

C.S. is funded by the International Federation of Clinical Neurophysiology. C.B.A. is funded by the Fundación Alfonso Martín Escudero. I.S.F. is funded by the Epilepsy Research Fund and was funded by the Fundación Alfonso Martín Escudero and the HHV6 Foundation. M.A.‐G. was funded by the Fundación Alfonso Martín Escudero. J.N.B. is funded by National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke 1K23NS116225. He also served as a consultant for Novartis. W.D.G. is an editor for and . T.A.G. is funded by NIH grants 2U01‐NS045911, U10‐NS077311, R01‐NS053998, R01‐NS062756, R01‐NS043209, R01‐LM011124, R01‐NS065840, U24 NS107200, and 1U01TR002623. He has received consulting fees from Supernus, Sunovion, Eisai, and UCB. He also serves as an expert consultant for the US Department of Justice and has received compensation for work as an expert on medicolegal cases. He receives royalties from a patent license. D.T. has received research funding from Children's Miracle Network Hospitals and Duke Forge. He has also received consultation fees from Gerson Lehrman Group, Guidepoint, IQVIA, and bioStrategies Group. M.S.W. serves as a scientific consultant and on the clinical advisory board for Sage Pharmaceuticals. A.A.W. receives research funding from Novartis, Eisai, Pfizer, UCB, Acorda, Lundbeck, GW Pharma, Upsher‐Smith, and Zogenix and receives publication royalties from UpToDate. T.L. serves on the board of the NORSE Institute, on the council (and as past president) of the American Clinical Neurophysiology Society, as committee chair at the American Epilepsy Society (Investigator Workshop Committee), as founder and consortium principal investigator of the pediatric status epilepticus research group, as an associate editor for 6th and 7th editions. He is part of pending patent applications to detect, treat, and predict seizures and to diagnose epilepsy. He receives research support from the NIH, Patient‐Centered Outcomes Research Institute, Epilepsy Research Fund, Epilepsy Foundation of America, Epilepsy Therapy Project, and Pediatric Epilepsy Research Foundation, and has received research grants from Lundbeck, Eisai, Upsher‐Smith, Mallinckrodt, Sage, and Pfizer. He has served in the past as a consultant for Zogenix, UCB, Engage, Amzell, Upsher‐Smith, Eisai, and Sunovion. He performs video‐electroencephalographic long‐term and ICU monitoring, electroencephalograms, and other electrophysiological studies at Boston Children's Hospital and affiliated hospitals and bills for these procedures, and he evaluates pediatric neurology patients and bills for clinical care. He has received speaker honorariums from national societies including the American Academy of Neurology, American Epilepsy Society, and American Clinical Neurophysiology Society, and for grand rounds at various academic centers. T.L. is a coinventor of the TriVoxHealth technology. In the future, this technology may be sold commercially. If this were to occur, T.L. and Boston Children's Hospital might receive financial benefits in the form of compensation. As in all research studies, the hospital has taken steps designed to ensure that this potential for financial gain does not endanger research subjects or undercut the validity and integrity of the information learned by this research. His wife, Dr. Karen Stannard, is a pediatric neurologist, and she performs video‐electroencephalographic long‐term and ICU monitoring, electroencephalograms, and other electrophysiological studies and bills for these procedures and she evaluates pediatric neurology patients and bills for clinical care. None of the other authors has any conflict of interest to disclose. Epilepsia Epilepsy Research Wyllie's Treatment of Epilepsy This study and consortium were funded by the Epilepsy Research Fund, the Epilepsy Foundation of America (EF‐213583, Targeted Initiative for Health Outcomes), the American Epilepsy Society/Epilepsy Foundation of America Infrastructure Award, and the Pediatric Epilepsy Research Foundation.

Keywords

clinical neurology
epilepsy
febrile infection-related epilepsy syndrome
new onset refractory status epilepticus
pediatric
refractory status epilepticus
status epilepticus

ASJC Scopus subject areas

Neurology
Clinical Neurology

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10.1111/epi.16950

Cite this

@article{449f676af9994ce482eeccd75b2914f8,

title = "Clinical presentation of new onset refractory status epilepticus in children (the pSERG cohort)",

abstract = "Objective: We aimed to characterize the clinical profile and outcomes of new onset refractory status epilepticus (NORSE) in children, and investigated the relationship between fever onset and status epilepticus (SE). Methods: Patients with refractory SE (RSE) between June 1, 2011 and October 1, 2016 were prospectively enrolled in the pSERG (Pediatric Status Epilepticus Research Group) cohort. Cases meeting the definition of NORSE were classified as {"}NORSE of known etiology{"} or {"}NORSE of unknown etiology.{"} Subgroup analysis of NORSE of unknown etiology was completed based on the presence and time of fever occurrence relative to RSE onset: fever at onset (≤24 h), previous fever (2 weeks–24 h), and without fever. Results: Of 279 patients with RSE, 46 patients met the criteria for NORSE. The median age was 2.4 years, and 25 (54%) were female. Forty (87%) patients had NORSE of unknown etiology. Nineteen (48%) presented with fever at SE onset, 16 (40%) had a previous fever, and five (12%) had no fever. The patients with preceding fever had more prolonged SE and worse outcomes, and 25% recovered baseline neurological function. The patients with fever at onset were younger and had shorter SE episodes, and 89% recovered baseline function. Significance: Among pediatric patients with RSE, 16% met diagnostic criteria for NORSE, including the subcategory of febrile infection-related epilepsy syndrome (FIRES). Pediatric NORSE cases may also overlap with refractory febrile SE (FSE). FIRES occurs more frequently in older children, the course is usually prolonged, and outcomes are worse, as compared to refractory FSE. Fever occurring more than 24 h before the onset of seizures differentiates a subgroup of NORSE patients with distinctive clinical characteristics and worse outcomes.",

keywords = "clinical neurology, epilepsy, febrile infection-related epilepsy syndrome, new onset refractory status epilepticus, pediatric, refractory status epilepticus, status epilepticus",

author = "pSERG and Claudine Sculier and {Barcia Aguilar}, Cristina and Nicolas Gaspard and Marina Ga{\'i}nza-Lein and {S{\'a}nchez Fern{\'a}ndez}, Iv{\'a}n and Marta Amengual-Gual and Anne Anderson and Ravindra Arya and Burrows, {Brian T.} and Brenton, {James N.} and Carpenter, {Jessica L.} and Chapman, {Kevin E.} and Justice Clark and Gaillard, {William D.} and Glauser, {Tracy A.} and Goldstein, {Joshua L.} and Goodkin, {Howard P.} and Mark Gorman and Lai, {Yi Chen} and McDonough, {Tiffani L.} and Mikati, {Mohamad A.} and Anuranjita Nayak and Katrina Peariso and James Riviello and Allison Rusie and Katherine Sperberg and Stredny, {Coral M.} and Tasker, {Robert C.} and Dmitry Tchapyjnikov and Alejandra Vasquez and Wainwright, {Mark S.} and Wilfong, {Angus A.} and Korwyn Williams and Tobias Loddenkemper",

note = "Funding Information: C.S. is funded by the International Federation of Clinical Neurophysiology. C.B.A. is funded by the Fundaci{\'o}n Alfonso Mart{\'i}n Escudero. I.S.F. is funded by the Epilepsy Research Fund and was funded by the Fundaci{\'o}n Alfonso Mart{\'i}n Escudero and the HHV6 Foundation. M.A.‐G. was funded by the Fundaci{\'o}n Alfonso Mart{\'i}n Escudero. J.N.B. is funded by National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke 1K23NS116225. He also served as a consultant for Novartis. W.D.G. is an editor for and . T.A.G. is funded by NIH grants 2U01‐NS045911, U10‐NS077311, R01‐NS053998, R01‐NS062756, R01‐NS043209, R01‐LM011124, R01‐NS065840, U24 NS107200, and 1U01TR002623. He has received consulting fees from Supernus, Sunovion, Eisai, and UCB. He also serves as an expert consultant for the US Department of Justice and has received compensation for work as an expert on medicolegal cases. He receives royalties from a patent license. D.T. has received research funding from Children's Miracle Network Hospitals and Duke Forge. He has also received consultation fees from Gerson Lehrman Group, Guidepoint, IQVIA, and bioStrategies Group. M.S.W. serves as a scientific consultant and on the clinical advisory board for Sage Pharmaceuticals. A.A.W. receives research funding from Novartis, Eisai, Pfizer, UCB, Acorda, Lundbeck, GW Pharma, Upsher‐Smith, and Zogenix and receives publication royalties from UpToDate. T.L. serves on the board of the NORSE Institute, on the council (and as past president) of the American Clinical Neurophysiology Society, as committee chair at the American Epilepsy Society (Investigator Workshop Committee), as founder and consortium principal investigator of the pediatric status epilepticus research group, as an associate editor for 6th and 7th editions. He is part of pending patent applications to detect, treat, and predict seizures and to diagnose epilepsy. He receives research support from the NIH, Patient‐Centered Outcomes Research Institute, Epilepsy Research Fund, Epilepsy Foundation of America, Epilepsy Therapy Project, and Pediatric Epilepsy Research Foundation, and has received research grants from Lundbeck, Eisai, Upsher‐Smith, Mallinckrodt, Sage, and Pfizer. He has served in the past as a consultant for Zogenix, UCB, Engage, Amzell, Upsher‐Smith, Eisai, and Sunovion. He performs video‐electroencephalographic long‐term and ICU monitoring, electroencephalograms, and other electrophysiological studies at Boston Children's Hospital and affiliated hospitals and bills for these procedures, and he evaluates pediatric neurology patients and bills for clinical care. He has received speaker honorariums from national societies including the American Academy of Neurology, American Epilepsy Society, and American Clinical Neurophysiology Society, and for grand rounds at various academic centers. T.L. is a coinventor of the TriVoxHealth technology. In the future, this technology may be sold commercially. If this were to occur, T.L. and Boston Children's Hospital might receive financial benefits in the form of compensation. As in all research studies, the hospital has taken steps designed to ensure that this potential for financial gain does not endanger research subjects or undercut the validity and integrity of the information learned by this research. His wife, Dr. Karen Stannard, is a pediatric neurologist, and she performs video‐electroencephalographic long‐term and ICU monitoring, electroencephalograms, and other electrophysiological studies and bills for these procedures and she evaluates pediatric neurology patients and bills for clinical care. None of the other authors has any conflict of interest to disclose. Epilepsia Epilepsy Research Wyllie's Treatment of Epilepsy Funding Information: This study and consortium were funded by the Epilepsy Research Fund, the Epilepsy Foundation of America (EF‐213583, Targeted Initiative for Health Outcomes), the American Epilepsy Society/Epilepsy Foundation of America Infrastructure Award, and the Pediatric Epilepsy Research Foundation. Publisher Copyright: {\textcopyright} 2021 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.",

year = "2021",

month = jul,

doi = "10.1111/epi.16950",

language = "English (US)",

volume = "62",

pages = "1629--1642",

journal = "Epilepsia",

issn = "0013-9580",

publisher = "Wiley-Blackwell",

number = "7",

}

TY - JOUR

T1 - Clinical presentation of new onset refractory status epilepticus in children (the pSERG cohort)

AU - pSERG

AU - Sculier, Claudine

AU - Barcia Aguilar, Cristina

AU - Gaspard, Nicolas

AU - Gaínza-Lein, Marina

AU - Sánchez Fernández, Iván

AU - Amengual-Gual, Marta

AU - Anderson, Anne

AU - Arya, Ravindra

AU - Burrows, Brian T.

AU - Brenton, James N.

AU - Carpenter, Jessica L.

AU - Chapman, Kevin E.

AU - Clark, Justice

AU - Gaillard, William D.

AU - Glauser, Tracy A.

AU - Goldstein, Joshua L.

AU - Goodkin, Howard P.

AU - Gorman, Mark

AU - Lai, Yi Chen

AU - McDonough, Tiffani L.

AU - Mikati, Mohamad A.

AU - Nayak, Anuranjita

AU - Peariso, Katrina

AU - Riviello, James

AU - Rusie, Allison

AU - Sperberg, Katherine

AU - Stredny, Coral M.

AU - Tasker, Robert C.

AU - Tchapyjnikov, Dmitry

AU - Vasquez, Alejandra

AU - Wainwright, Mark S.

AU - Wilfong, Angus A.

AU - Williams, Korwyn

AU - Loddenkemper, Tobias

N1 - Funding Information: C.S. is funded by the International Federation of Clinical Neurophysiology. C.B.A. is funded by the Fundación Alfonso Martín Escudero. I.S.F. is funded by the Epilepsy Research Fund and was funded by the Fundación Alfonso Martín Escudero and the HHV6 Foundation. M.A.‐G. was funded by the Fundación Alfonso Martín Escudero. J.N.B. is funded by National Institutes of Health (NIH) National Institute of Neurological Disorders and Stroke 1K23NS116225. He also served as a consultant for Novartis. W.D.G. is an editor for and . T.A.G. is funded by NIH grants 2U01‐NS045911, U10‐NS077311, R01‐NS053998, R01‐NS062756, R01‐NS043209, R01‐LM011124, R01‐NS065840, U24 NS107200, and 1U01TR002623. He has received consulting fees from Supernus, Sunovion, Eisai, and UCB. He also serves as an expert consultant for the US Department of Justice and has received compensation for work as an expert on medicolegal cases. He receives royalties from a patent license. D.T. has received research funding from Children's Miracle Network Hospitals and Duke Forge. He has also received consultation fees from Gerson Lehrman Group, Guidepoint, IQVIA, and bioStrategies Group. M.S.W. serves as a scientific consultant and on the clinical advisory board for Sage Pharmaceuticals. A.A.W. receives research funding from Novartis, Eisai, Pfizer, UCB, Acorda, Lundbeck, GW Pharma, Upsher‐Smith, and Zogenix and receives publication royalties from UpToDate. T.L. serves on the board of the NORSE Institute, on the council (and as past president) of the American Clinical Neurophysiology Society, as committee chair at the American Epilepsy Society (Investigator Workshop Committee), as founder and consortium principal investigator of the pediatric status epilepticus research group, as an associate editor for 6th and 7th editions. He is part of pending patent applications to detect, treat, and predict seizures and to diagnose epilepsy. He receives research support from the NIH, Patient‐Centered Outcomes Research Institute, Epilepsy Research Fund, Epilepsy Foundation of America, Epilepsy Therapy Project, and Pediatric Epilepsy Research Foundation, and has received research grants from Lundbeck, Eisai, Upsher‐Smith, Mallinckrodt, Sage, and Pfizer. He has served in the past as a consultant for Zogenix, UCB, Engage, Amzell, Upsher‐Smith, Eisai, and Sunovion. He performs video‐electroencephalographic long‐term and ICU monitoring, electroencephalograms, and other electrophysiological studies at Boston Children's Hospital and affiliated hospitals and bills for these procedures, and he evaluates pediatric neurology patients and bills for clinical care. He has received speaker honorariums from national societies including the American Academy of Neurology, American Epilepsy Society, and American Clinical Neurophysiology Society, and for grand rounds at various academic centers. T.L. is a coinventor of the TriVoxHealth technology. In the future, this technology may be sold commercially. If this were to occur, T.L. and Boston Children's Hospital might receive financial benefits in the form of compensation. As in all research studies, the hospital has taken steps designed to ensure that this potential for financial gain does not endanger research subjects or undercut the validity and integrity of the information learned by this research. His wife, Dr. Karen Stannard, is a pediatric neurologist, and she performs video‐electroencephalographic long‐term and ICU monitoring, electroencephalograms, and other electrophysiological studies and bills for these procedures and she evaluates pediatric neurology patients and bills for clinical care. None of the other authors has any conflict of interest to disclose. Epilepsia Epilepsy Research Wyllie's Treatment of Epilepsy Funding Information: This study and consortium were funded by the Epilepsy Research Fund, the Epilepsy Foundation of America (EF‐213583, Targeted Initiative for Health Outcomes), the American Epilepsy Society/Epilepsy Foundation of America Infrastructure Award, and the Pediatric Epilepsy Research Foundation. Publisher Copyright: © 2021 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.

PY - 2021/7

Y1 - 2021/7

N2 - Objective: We aimed to characterize the clinical profile and outcomes of new onset refractory status epilepticus (NORSE) in children, and investigated the relationship between fever onset and status epilepticus (SE). Methods: Patients with refractory SE (RSE) between June 1, 2011 and October 1, 2016 were prospectively enrolled in the pSERG (Pediatric Status Epilepticus Research Group) cohort. Cases meeting the definition of NORSE were classified as "NORSE of known etiology" or "NORSE of unknown etiology." Subgroup analysis of NORSE of unknown etiology was completed based on the presence and time of fever occurrence relative to RSE onset: fever at onset (≤24 h), previous fever (2 weeks–24 h), and without fever. Results: Of 279 patients with RSE, 46 patients met the criteria for NORSE. The median age was 2.4 years, and 25 (54%) were female. Forty (87%) patients had NORSE of unknown etiology. Nineteen (48%) presented with fever at SE onset, 16 (40%) had a previous fever, and five (12%) had no fever. The patients with preceding fever had more prolonged SE and worse outcomes, and 25% recovered baseline neurological function. The patients with fever at onset were younger and had shorter SE episodes, and 89% recovered baseline function. Significance: Among pediatric patients with RSE, 16% met diagnostic criteria for NORSE, including the subcategory of febrile infection-related epilepsy syndrome (FIRES). Pediatric NORSE cases may also overlap with refractory febrile SE (FSE). FIRES occurs more frequently in older children, the course is usually prolonged, and outcomes are worse, as compared to refractory FSE. Fever occurring more than 24 h before the onset of seizures differentiates a subgroup of NORSE patients with distinctive clinical characteristics and worse outcomes.

AB - Objective: We aimed to characterize the clinical profile and outcomes of new onset refractory status epilepticus (NORSE) in children, and investigated the relationship between fever onset and status epilepticus (SE). Methods: Patients with refractory SE (RSE) between June 1, 2011 and October 1, 2016 were prospectively enrolled in the pSERG (Pediatric Status Epilepticus Research Group) cohort. Cases meeting the definition of NORSE were classified as "NORSE of known etiology" or "NORSE of unknown etiology." Subgroup analysis of NORSE of unknown etiology was completed based on the presence and time of fever occurrence relative to RSE onset: fever at onset (≤24 h), previous fever (2 weeks–24 h), and without fever. Results: Of 279 patients with RSE, 46 patients met the criteria for NORSE. The median age was 2.4 years, and 25 (54%) were female. Forty (87%) patients had NORSE of unknown etiology. Nineteen (48%) presented with fever at SE onset, 16 (40%) had a previous fever, and five (12%) had no fever. The patients with preceding fever had more prolonged SE and worse outcomes, and 25% recovered baseline neurological function. The patients with fever at onset were younger and had shorter SE episodes, and 89% recovered baseline function. Significance: Among pediatric patients with RSE, 16% met diagnostic criteria for NORSE, including the subcategory of febrile infection-related epilepsy syndrome (FIRES). Pediatric NORSE cases may also overlap with refractory febrile SE (FSE). FIRES occurs more frequently in older children, the course is usually prolonged, and outcomes are worse, as compared to refractory FSE. Fever occurring more than 24 h before the onset of seizures differentiates a subgroup of NORSE patients with distinctive clinical characteristics and worse outcomes.

KW - clinical neurology

KW - epilepsy

KW - febrile infection-related epilepsy syndrome

KW - new onset refractory status epilepticus

KW - pediatric

KW - refractory status epilepticus

KW - status epilepticus

UR - http://www.scopus.com/inward/record.url?scp=85107392990&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85107392990&partnerID=8YFLogxK

U2 - 10.1111/epi.16950

DO - 10.1111/epi.16950

M3 - Article

C2 - 34091885

AN - SCOPUS:85107392990

SN - 0013-9580

VL - 62

SP - 1629

EP - 1642

JO - Epilepsia

JF - Epilepsia

IS - 7

ER -

Clinical presentation of new onset refractory status epilepticus in children (the pSERG cohort)

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