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

Claudine Sculier; Cristina Barcia Aguilar; Nicolas Gaspard; Marina Gaínza-Lein; Iván Sánchez Fernández; Marta Amengual-Gual; Anne Anderson; Ravindra Arya; Brian T Burrows; James N Brenton; Jessica L Carpenter; Kevin E Chapman; Justice Clark; William D Gaillard; Tracy A Glauser; Joshua L Goldstein; Howard P Goodkin; Mark Gorman; Yi-Chen Lai; Tiffani L McDonough; Mohamad A Mikati; Anuranjita Nayak; Katrina Peariso; James Riviello; Allison Rusie; Katherine Sperberg; Coral M Stredny; Robert C Tasker; Dmitry Tchapyjnikov; Alejandra Vasquez; Mark S Wainwright; Angus A Wilfong; Korwyn Williams; Tobias Loddenkemper; pSERG

doi:10.1111/epi.16950

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

Epilepsia. 2021 Jul;62(7):1629-1642. doi: 10.1111/epi.16950. Epub 2021 Jun 6.

Authors

Claudine Sculier^{1

2}, Cristina Barcia Aguilar^{1

3}, Nicolas Gaspard^{2

4}, Marina Gaínza-Lein^{1

5

6}, Iván Sánchez Fernández^{1

7}, Marta Amengual-Gual^{1

8}, Anne Anderson⁹, Ravindra Arya¹⁰, Brian T Burrows^{11

12}, James N Brenton¹³, Jessica L Carpenter¹⁴, Kevin E Chapman¹⁵, Justice Clark¹, William D Gaillard¹⁴, Tracy A Glauser¹⁰, Joshua L Goldstein¹⁶, Howard P Goodkin¹³, Mark Gorman¹, Yi-Chen Lai⁹, Tiffani L McDonough¹⁷, Mohamad A Mikati¹⁸, Anuranjita Nayak⁹, Katrina Peariso¹⁰, James Riviello⁹, Allison Rusie¹⁶, Katherine Sperberg¹⁴, Coral M Stredny¹, Robert C Tasker¹⁹, Dmitry Tchapyjnikov¹⁷, Alejandra Vasquez^{1

20}, Mark S Wainwright²¹, Angus A Wilfong²², Korwyn Williams²², Tobias Loddenkemper¹; pSERG

Affiliations

¹ Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
² Department of Neurology, Erasmus Hospital, Free University of Brussels, Brussels, Belgium.
³ Department of Child Neurology, La Paz University Hospital, Autonomous University of Madrid, Madrid, Spain.
⁴ Neurology Department, Comprehensive Epilepsy Center, Yale University School of Medicine, New Haven, CT, USA.
⁵ Faculty of Medicine, Institute of Pediatrics, Austral University of Chile, Valdivia, Chile.
⁶ Children's Neuropsychiatry Service, San Borja Arriarán Clinical Hospital, University of Chile, Santiago, Chile.
⁷ Department of Child Neurology, SJD Barcelona Children's Hospital, University of Barcelona, Barcelona, Spain.
⁸ Pediatric Neurology Unit, Department of Pediatrics, Son Espases University Hospital, University of the Balearic Islands, Palma, Spain.
⁹ Section of Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
¹⁰ Division of Pediatric Neurology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
¹¹ Department of Pediatrics, Barrows Neurological Institute, Phoenix Children's Hospital, University of Arizona School of Medicine, Phoenix, AZ, USA.
¹² Department of Neurology, Mayo Clinic, Scottsdale, AZ, USA.
¹³ Department of Neurology and Pediatrics, University of Virginia Health System, Charlottesville, Virginia, USA.
¹⁴ Center for Neuroscience, Children's National Hospital, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
¹⁵ Departments of Pediatrics and Neurology, Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO, USA.
¹⁶ Ruth D. & Ken M. Davee Pediatric Neurocritical Care Program, Northwestern University Feinberg, School of Medicine, Chicago, IL, USA.
¹⁷ Division of Neurology and Epilepsy, Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹⁸ Division of Pediatric Neurology, Duke University Medical Center, Duke University, Durham, NC, USA.
¹⁹ Department of Neurology, Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
²⁰ Division of Child and Adolescent Neurology, Mayo Clinic, Mayo Clinic School of Medicine, Rochester, MN, USA.
²¹ Division of Pediatric Neurology, Department of Neurology, University of Washington, Seattle, WA, USA.
²² Division of Pediatric Neurology, Department of Child Health, Phoenix Children's Hospital, University of Arizona College of Medicine, Phoenix, AZ, USA.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Child
Child, Preschool
Cohort Studies
Databases, Factual
Drug Resistant Epilepsy / diagnosis*
Electroencephalography
Female
Fever / complications
Humans
Infant
Male
Prospective Studies
Seizures, Febrile / cerebrospinal fluid
Seizures, Febrile / diagnosis*
Status Epilepticus / cerebrospinal fluid
Status Epilepticus / diagnosis*
Treatment Outcome