{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T20:08:34Z","timestamp":1793909314118,"version":"4.8.0"},"reference-count":67,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Cryptogenic new onset refractory status epilepticus (cNORSE) carries high risks of long\u2010term disability and post\u2010NORSE epilepsy, but mechanisms remain unclear. We aimed to assess the predictive value of inflammatory and brain injury biomarkers and determine whether immune disturbances persist in the chronic phase.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We enrolled 93 cNORSE patients from the Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital and the Yale NORSE\/FIRES biorepository (2013\u20132025). Serum and cerebrospinal fluid (CSF) samples were collected during status epilepticus (SE), with outcomes assessed 6\u201312\u2009months after resolution. To investigate post\u2010cNORSE epilepsy, we compared 39 post\u2010cNORSE patients (25 with paired acute samples) to 40 patients with temporal lobe epilepsy due to hippocampal sclerosis (TLE\u2010HS) and 20 with chronic immune\u2010mediated encephalitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      During cNORSE, elevated innate cytokines (serum CXCL8, CCL2; CSF IL\u20106, CXCL8, CCL2, MIP\u20101\u03b1, G\u2010CSF) and brain injury biomarkers (serum and CSF neurofilament light chain [NfL], CSF neuron\u2010specific enolase) correlated with worse functional outcomes. Multivariate models demonstrated that adding serum NfL to cytokines improved poor outcome prediction (area under the curve\u2009=\u2009.75). In contrast, no acute biomarker predicted post\u2010cNORSE epilepsy, which was instead associated with prolonged SE, magnetic resonance imaging abnormalities, and the need for more intensive treatment. In paired analyses, most serum cytokines normalized during the chronic phase, particularly IL\u20106, IL\u201010, and IL\u20101\u03b2, although new adaptive immune disturbances (IL\u201017A, IL\u201012p70, TNF\u03b1) appeared in 20% of patients. No chronic elevations of innate cytokines were observed in post\u2010cNORSE patients. Conversely, elevated age\u2010adjusted NfL levels were more frequent in post\u2010cNORSE epilepsy (64%) than encephalitis (45%) and TLE\u2010HS (20%), (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.001), with elevated NfL levels correlating with poor functional outcomes (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.019).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Innate immune activation is a hallmark of acute cNORSE but largely resolves in the chronic phase, arguing against persistent innate inflammation as the driver of post\u2010cNORSE epilepsy. In contrast, persistently elevated NfL levels suggest ongoing axonal injury, potentially contributing to poor outcomes. Integrating inflammatory and neuroaxonal injury biomarkers may improve risk stratification and guide long\u2010term management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70146","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T20:11:21Z","timestamp":1771272681000},"page":"2326-2346","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Exploring pathways leading to drug\u2010resistant epilepsy for patients with cryptogenic new onset refractory status epilepticu\n                    <scp>s<\/scp>"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5912-9998","authenticated-orcid":false,"given":"Aur\u00e9lie","family":"Hanin","sequence":"first","affiliation":[{"name":"Sorbonne Universit\u00e9, Institut du Cerveau\u2013Paris Brain Institute\u2013ICM, Institut National de de la Sant\u00e9 et de Recherche M\u00e9dicale (INSERM) Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche en Informatique et en Automatique (INRIA), Assistance Publique H\u00f4pitaux de Paris (AP\u2010HP), H\u00f4pital de la Piti\u00e9 Salp\u00eatri\u00e8re  Paris France"},{"name":"Department of Metabolic Biochemistry, DMU BioGeMH, Assistance Publique H\u00f4pitaux de Paris (AP\u2010HP) Sorbonne Universit\u00e9, Piti\u00e9\u2010Salp\u00eatri\u00e8re\u2013Charles Foix University Hospital  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3266-0623","authenticated-orcid":false,"given":"Cl\u00e9mence","family":"Marois","sequence":"additional","affiliation":[{"name":"Assistance Publique H\u00f4pitaux de Paris (AP\u2010HP) Sorbonne Universit\u00e9, H\u00f4pital de la Piti\u00e9\u2010Salp\u00eatri\u00e8re, Neuro\u2010Intensive Care Unit  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2523-8712","authenticated-orcid":false,"given":"Martin","family":"Guillemaud","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Institut du Cerveau\u2013Paris Brain Institute\u2013ICM, Institut National de de la Sant\u00e9 et de Recherche M\u00e9dicale (INSERM) Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche en Informatique et en Automatique (INRIA), Assistance Publique H\u00f4pitaux de Paris (AP\u2010HP), H\u00f4pital de la Piti\u00e9 Salp\u00eatri\u00e8re  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0390-4833","authenticated-orcid":false,"given":"Mario","family":"Chavez","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Institut du Cerveau\u2013Paris Brain Institute\u2013ICM, Institut National de de la Sant\u00e9 et de Recherche M\u00e9dicale (INSERM) Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche en Informatique et en Automatique (INRIA), Assistance Publique H\u00f4pitaux de Paris (AP\u2010HP), H\u00f4pital de la Piti\u00e9 Salp\u00eatri\u00e8re  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0625-0348","authenticated-orcid":false,"given":"L\u00e9a","family":"Cosme","sequence":"additional","affiliation":[{"name":"Assistance Publique H\u00f4pitaux de Paris (AP\u2010HP), H\u00f4pital de la Piti\u00e9\u2010Salp\u00eatri\u00e8re, Sorbonne Universit\u00e9 Epilepsy Unit and Department of Clinical Neurophysiology, European Reference Network EpiCARE  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4696-8703","authenticated-orcid":false,"given":"Zineb","family":"Hayatou","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Institut du Cerveau\u2013Paris Brain Institute\u2013ICM, Institut National de de la Sant\u00e9 et de Recherche M\u00e9dicale (INSERM) Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche en Informatique et en Automatique (INRIA), Assistance Publique H\u00f4pitaux de Paris (AP\u2010HP), H\u00f4pital de la Piti\u00e9 Salp\u00eatri\u00e8re  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurore","family":"Besnard","sequence":"additional","affiliation":[{"name":"Assistance Publique H\u00f4pitaux de Paris (AP\u2010HP), H\u00f4pital de la Piti\u00e9\u2010Salp\u00eatri\u00e8re, Sorbonne Universit\u00e9 Epilepsy Unit and Department of Clinical Neurophysiology, European Reference Network EpiCARE  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwen","family":"Goudard","sequence":"additional","affiliation":[{"name":"Assistance Publique H\u00f4pitaux de Paris (AP\u2010HP), H\u00f4pital de la 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Institut National de la Recherche en Informatique et en Automatique (INRIA), Assistance Publique H\u00f4pitaux de Paris (AP\u2010HP), H\u00f4pital de la Piti\u00e9 Salp\u00eatri\u00e8re  Paris France"},{"name":"Assistance Publique H\u00f4pitaux de Paris (AP\u2010HP), H\u00f4pital de la Piti\u00e9\u2010Salp\u00eatri\u00e8re, Sorbonne Universit\u00e9 Epilepsy Unit and Department of Clinical Neurophysiology, European Reference Network EpiCARE  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9488-4868","authenticated-orcid":false,"given":"Margaux","family":"Cheval","sequence":"additional","affiliation":[{"name":"Assistance Publique H\u00f4pitaux de Paris (AP\u2010HP), H\u00f4pital de la Piti\u00e9\u2010Salp\u00eatri\u00e8re, Sorbonne Universit\u00e9 Epilepsy Unit and Department of Clinical Neurophysiology, European Reference Network EpiCARE  Paris 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