{"doi":"10.1002/ana.26627","title":"Cytokines in<scp>New‐Onset</scp>Refractory Status Epilepticus Predict Outcomes","abstract":"OBJECTIVE: The 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. METHODS: Patients 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. RESULTS: A 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. INTERPRETATION: We 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.","journal":"Annals of Neurology","year":2023,"id":316117,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":115,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7999,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1019347,"name":"Jorge Cespedes","orcid":"0000-0001-9826-7077","position":1,"is_corresponding":false},{"id":104144,"name":"Karim Dorgham","orcid":"0000-0001-9539-3203","position":2,"is_corresponding":false},{"id":1019348,"name":"Yashwanth Pulluru","orcid":"0009-0009-2336-5209","position":3,"is_corresponding":false},{"id":1019349,"name":"Margaret Gopaul","orcid":"0000-0002-1329-3258","position":4,"is_corresponding":false},{"id":104228,"name":"Guy Gorochov","orcid":"0000-0003-2097-9677","position":5,"is_corresponding":false},{"id":37332,"name":"David A. Hafler","orcid":"0000-0003-4664-535X","position":6,"is_corresponding":false},{"id":567062,"name":"Virginie Lambrecq","orcid":"0000-0001-9442-0302","position":7,"is_corresponding":false},{"id":614732,"name":"Nicolas Gaspard","orcid":"0000-0003-1148-6723","position":8,"is_corresponding":false},{"id":227172,"name":"Lawrence J. Hirsch","orcid":"0000-0002-6333-832X","position":9,"is_corresponding":false},{"id":1019346,"name":"Aurélie Hanin","orcid":"0000-0002-5912-9998","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-19T01:06:38.213358Z","pmid":"36871188","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}