New-onset Refractory Status Epilepticus (NORSE) in Paediatric Patients: Causes, Characteristics and Outcomes

Overview

Journal BMJ Neurol Open

Specialty Neurology

Date 2022 Dec 19

PMID 36530417

Authors

Ana Luiza Tainski de Azevedo

Cristian Tedesco Tonial

Gabriela Rupp Hanzen Andrades

Caroline Abud Drumond Costa

Francielly Crestani

Alessandra Rodrigues Lessa

Francisco Bruno

Paulo Carvalho

Guilherme Eckert

Jeferson Piva

Pedro Celiny Ramos Garcia

Affiliations

Soon will be listed here.

Abstract

Background: New-onset refractory status epilepticus (NORSE) refers to patients without a previous history of seizures who have refractory status epilepticus for at least 72 hours without an identified aetiology. Despite the severe neurological sequelae of NORSE, little is known about this condition in paediatric patients.

Objective: To describe the profile of paediatric patients with NORSE, the profile of seizures, possible causes attributed to this condition, treatments offered to patients and the outcomes at discharge from the paediatric intensive care unit (PICU).

Methods: This retrospective, multicentre, descriptive study (case series) was conducted in the PICUs of three tertiary hospitals. We reviewed the medical records of all patients aged 0-16 years admitted to the participating PICUs between December 2013 and December 2017 with refractory status epilepticus, without a previous history of seizures or neurological disease.

Results: Fifteen patients (2.4%) had NORSE. The median age of patients was 62.3 (IQR 26.2-75.4) months. All patients experienced prodromes before progressing to refractory status epilepticus. Twelve patients (80%) had fever up to 24 hours before seizures. NORSE was classified as cryptogenic in 66% of patients. Twelve patients were treated with complementary therapies, in addition to anticonvulsants. There was no standardisation in the treatment of patients. The overall mortality rate was 20%.

Conclusions: NORSE is associated with high morbidity and mortality, without an identified aetiology in most cases and with a wide range of proposed therapies.

References

Khawaja A, DeWolfe J, Miller D, Szaflarski J . New-onset refractory status epilepticus (NORSE)--The potential role for immunotherapy. Epilepsy Behav. 2015; 47:17-23. DOI: 10.1016/j.yebeh.2015.04.054. View

Sauro K, Wiebe S, Dunkley C, Janszky J, Kumlien E, Moshe S . The current state of epilepsy guidelines: A systematic review. Epilepsia. 2015; 57(1):13-23. DOI: 10.1111/epi.13273. View

Grover E, Nazzal Y, Hirsch L . Treatment of Convulsive Status Epilepticus. Curr Treat Options Neurol. 2016; 18(3):11. DOI: 10.1007/s11940-016-0394-5. View

Serino D, Santarone M, Caputo D, Fusco L . Febrile infection-related epilepsy syndrome (FIRES): prevalence, impact and management strategies. Neuropsychiatr Dis Treat. 2019; 15:1897-1903. PMC: 6635824. DOI: 10.2147/NDT.S177803. View

Li J, Saldivar C, Maganti R . Plasma exchange in cryptogenic new onset refractory status epilepticus. Seizure. 2012; 22(1):70-3. DOI: 10.1016/j.seizure.2012.09.011. View

Gaspard N, Hirsch L, Sculier C, Loddenkemper T, Baalen A, Lancrenon J . New-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES): State of the art and perspectives. Epilepsia. 2018; 59(4):745-752. DOI: 10.1111/epi.14022. View

Slater A, Shann F, Pearson G . PIM2: a revised version of the Paediatric Index of Mortality. Intensive Care Med. 2003; 29(2):278-85. DOI: 10.1007/s00134-002-1601-2. View

Baalen A, Hausler M, Boor R, Rohr A, Sperner J, Kurlemann G . Febrile infection-related epilepsy syndrome (FIRES): a nonencephalitic encephalopathy in childhood. Epilepsia. 2010; 51(7):1323-8. DOI: 10.1111/j.1528-1167.2010.02535.x. View

Hirsch L, Gaspard N, Baalen A, Nabbout R, Demeret S, Loddenkemper T . Proposed consensus definitions for new-onset refractory status epilepticus (NORSE), febrile infection-related epilepsy syndrome (FIRES), and related conditions. Epilepsia. 2018; 59(4):739-744. DOI: 10.1111/epi.14016. View

10.

Perulli M, Cicala G, Turrini I, Musto E, Quintiliani M, Gambardella M . Fighting autoinflammation in FIRES: The role of interleukins and early immunomodulation. Epilepsy Behav Rep. 2022; 18:100531. PMC: 8958320. DOI: 10.1016/j.ebr.2022.100531. View

11.

Spatola M, Dalmau J . Seizures and risk of epilepsy in autoimmune and other inflammatory encephalitis. Curr Opin Neurol. 2017; 30(3):345-353. PMC: 5831325. DOI: 10.1097/WCO.0000000000000449. View

12.

Jafarpour S, Hodgeman R, De Marchi Capeletto C, de Lima M, Kapur K, Tasker R . New-Onset Status Epilepticus in Pediatric Patients: Causes, Characteristics, and Outcomes. Pediatr Neurol. 2018; 80:61-69. DOI: 10.1016/j.pediatrneurol.2017.11.016. View

13.

Wilder-Smith E, Lim E, Teoh H, Sharma V, Tan J, Chan B . The NORSE (new-onset refractory status epilepticus) syndrome: defining a disease entity. Ann Acad Med Singap. 2005; 34(7):417-20. View

14.

Ismail F, Kossoff E . AERRPS, DESC, NORSE, FIRES: multi-labeling or distinct epileptic entities?. Epilepsia. 2011; 52(11):e185-9. DOI: 10.1111/j.1528-1167.2011.03293.x. View

15.

Husari K, Labiner K, Huang R, Said R . New-Onset Refractory Status Epilepticus in Children: Etiologies, Treatments, and Outcomes. Pediatr Crit Care Med. 2019; 21(1):59-66. DOI: 10.1097/PCC.0000000000002108. View

16.

Iizuka T, Kanazawa N, Kaneko J, Tominaga N, Nonoda Y, Hara A . Cryptogenic NORSE: Its distinctive clinical features and response to immunotherapy. Neurol Neuroimmunol Neuroinflamm. 2017; 4(6):e396. PMC: 5614728. DOI: 10.1212/NXI.0000000000000396. View

17.

Dubey D, Alqallaf A, Hays R, Freeman M, Chen K, Ding K . Neurological Autoantibody Prevalence in Epilepsy of Unknown Etiology. JAMA Neurol. 2017; 74(4):397-402. DOI: 10.1001/jamaneurol.2016.5429. View

18.

Gall C, Jumma O, Mohanraj R . Five cases of new onset refractory status epilepticus (NORSE) syndrome: outcomes with early immunotherapy. Seizure. 2013; 22(3):217-20. DOI: 10.1016/j.seizure.2012.12.016. View

19.

Gofton T, Gaspard N, Hocker S, Loddenkemper T, Hirsch L . New onset refractory status epilepticus research: What is on the horizon?. Neurology. 2019; 92(17):802-810. DOI: 10.1212/WNL.0000000000007322. View

20.

Gaspard N, Foreman B, Alvarez V, Cabrera Kang C, Probasco J, Jongeling A . New-onset refractory status epilepticus: Etiology, clinical features, and outcome. Neurology. 2015; 85(18):1604-13. PMC: 4642147. DOI: 10.1212/WNL.0000000000001940. View