Cytokines in <scp>New‐Onset</scp> Refractory Status Epilepticus Predict Outcomes-Reference-Cited by-同舟云学术

Cytokines in New‐Onset Refractory Status Epilepticus Predict Outcomes

Published:2023-03-17 Issue:1 Volume:94 Page:75-90
ISSN:0364-5134
Container-title:Annals of Neurology
language:en
Short-container-title:Annals of Neurology

Author:

Hanin Aurélie¹²³^ORCID,Cespedes Jorge⁴⁵^ORCID,Dorgham Karim⁶^ORCID,Pulluru Yashwanth⁴⁷,Gopaul Margaret⁴,Gorochov Guy⁶,Hafler David A.¹,Navarro Vincent²³⁸^ORCID,Gaspard Nicolas⁴⁹^ORCID,Hirsch Lawrence J.⁴^ORCID

Affiliation:

1. Department of Neurology and Immunobiology Yale University School of Medicine New Haven CT United States

2. Sorbonne Université, Institut du Cerveau, Paris Brain Institute, ICM, Inserm, CNRS, AP‐HP, Hôpital de la Pitié‐Salpêtrière Paris France

3. Department of Clinical Neurophysiology, Epilepsy Unit, DMU Neurosciences 6 AP‐HP, Hôpital de la Pitié‐Salpêtrière Paris France

4. Comprehensive Epilepsy Center, Department of Neurology Yale University School of Medicine New Haven CT United States

5. Universidad Autonoma de Centro America, School of Medicine San Jose Costa Rica

6. Department of Immunology Sorbonne Université, Inserm, Centre d'Immunologie et des Maladies Infectieuses, AP‐HP, Hôpital de la Pitié‐Salpêtrière Paris France

7. Division of Epilepsy Nebraska Medical Center Omaha NE United States

8. Center of Reference for Rare Epilepsies AP‐HP, Hôpital de la Pitié‐Salpêtrière Paris France

9. Department of Neurology Université Libre de Bruxelles, Hôpital Erasme Brussels Belgium

Abstract

ObjectiveThe objective of this study was to investigate inflammation using cerebrospinal fluid (CSF) and serum cytokines/chemokines in patients with new‐onset refractory status epilepticus (NORSE) to better understand the pathophysiology of NORSE and its consequences.MethodsPatients with NORSE (n = 61, including n = 51 cryptogenic), including its subtype with prior fever known as febrile infection‐related epilepsy syndrome (FIRES), were compared with patients with other refractory status epilepticus (RSE; n = 37), and control patients without SE (n = 52). We measured 12 cytokines/chemokines in serum or CSF samples using multiplexed fluorescent bead‐based immunoassay detection. Cytokine levels were compared between patients with and without SE, and between the 51 patients with cryptogenic NORSE (cNORSE) and the 47 patients with a known‐etiology RSE (NORSE n = 10, other RSE n = 37), and correlated with outcomes.ResultsA significant increase of IL‐6, TNF‐α, CXCL8/IL‐8, CCL2, MIP‐1α, and IL‐12p70 pro‐inflammatory cytokines/chemokines was observed in patients with SE compared with patients without SE, in serum and CSF. Serum innate immunity pro‐inflammatory cytokines/chemokines (CXCL8, CCL2, and MIP‐1α) were significantly higher in patients with cNORSE compared to non‐cryptogenic RSE. Patients with NORSE with elevated innate immunity serum and CSF cytokine/chemokine levels had worse outcomes at discharge and at several months after the SE ended.InterpretationWe identified significant differences in innate immunity serum and CSF cytokine/chemokine profiles between patients with cNORSE and non‐cryptogenic RSE. The elevation of innate immunity pro‐inflammatory cytokines in patients with NORSE correlated with worse short‐ and long‐term outcomes. These findings highlight the involvement of innate immunity‐related inflammation, including peripherally, and possibly of neutrophil‐related immunity in cNORSE pathogenesis and suggest the importance of utilizing specific anti‐inflammatory interventions. ANN NEUROL 2023;94:75–90

Funder

Philippe Foundation

Institut Servier

Publisher

Wiley

Subject

Neurology (clinical),Neurology

Link

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ana.26627

Reference55 articles.

1. Proposed consensus definitions for new-onset refractory status epilepticus (NORSE), febrile infection-related epilepsy syndrome (FIRES), and related conditions

2. Febrile infection-related epilepsy syndrome (FIRES): Pathogenesis, treatment, and outcome