{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T10:57:22Z","timestamp":1789469842156,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T00:00:00Z","timestamp":1687219200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1193648"],"award-info":[{"award-number":["APP1193648"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Infection\u2010triggered encephalopathy syndromes (ITES) are potentially devastating neuroinflammatory conditions. Although some ITES syndromes have recognisable MRI neuroimaging phenotypes, there are otherwise few biomarkers of disease. Early detection to enable immune modulatory treatments could improve outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We measured CSF neopterin, quinolinic acid, kynurenine and kynurenine\/tryptophan ratio using a liquid chromatography coupled to tandem mass spectrometry (LC\u2013MS\/MS) system. The CSF of 18 children with ITES were compared with acute encephalitis (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200920), and three control groups, namely epilepsy (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200920), status epilepticus (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200918) and neurogenetic controls (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200920).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The main ITES phenotypes in 18 patients were acute encephalopathy with biphasic seizures and late restricted diffusion (AESD,\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20094), febrile infection\u2010related epilepsy syndrome (FIRES\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20094) and other ITES phenotypes. Influenza A was the most common infectious trigger (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20095), and 50% of patients had a preceding notable neurodevelopmental or family history. CSF neopterin, quinolinic acid and kynurenine were elevated in ITES group compared to the three control groups (all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0002). The ROC (area under curve) for CSF neopterin (99.3%, CI 98.1\u2013100) was significantly better than CSF pleocytosis (87.3% CI 76.4\u201398.2) (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.028). Elevated CSF neopterin could discriminate ITES from other causes of seizures, status epilepticus and febrile status epilepticus (all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0002). The elevated CSF metabolites normalised during longitudinal testing in two patients with FIRES.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>CSF neopterin and quinolinic acid are neuroinflammatory and excitotoxic metabolites. This CSF metabolomic inflammatory panel can discriminate ITES from other causes of new onset seizures or status epilepticus, and rapid results (4\u2009h) may facilitate early immune modulatory therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.51832","type":"journal-article","created":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T02:35:19Z","timestamp":1687314919000},"page":"1417-1432","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["<scp>CSF<\/scp>\n                    neopterin and quinolinic acid are biomarkers of neuroinflammation and neurotoxicity in\n                    <scp>FIRES<\/scp>\n                    and other infection\u2010triggered encephalopathy syndromes"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2495-1826","authenticated-orcid":false,"given":"Russell C.","family":"Dale","sequence":"first","affiliation":[{"name":"Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health University of Sydney  Westmead New South Wales Australia"},{"name":"Clinical School, The Children's Hospital at Westmead, Faculty of Medicine and Health University of Sydney  Westmead New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terrence","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Neurology Service KK Women's and Children's Hospital  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shrujna","family":"Patel","sequence":"additional","affiliation":[{"name":"Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health University of Sydney  Westmead New South Wales Australia"},{"name":"Clinical School, The Children's Hospital at Westmead, Faculty of Medicine and Health University of Sydney  Westmead New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Velda X.","family":"Han","sequence":"additional","affiliation":[{"name":"Khoo Teck Puat\u2010National University Children's Medical Institute National University Health System  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavitha","family":"Kothur","sequence":"additional","affiliation":[{"name":"Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health University of Sydney  Westmead New South Wales Australia"},{"name":"Clinical School, The Children's Hospital at Westmead, Faculty of Medicine and Health University of Sydney  Westmead New South Wales Australia"},{"name":"TY Nelson Department of Neurology and Neurosurgery, The Children's Hospital at Westmead The University of Sydney  Westmead New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Troedson","sequence":"additional","affiliation":[{"name":"TY Nelson Department of Neurology and Neurosurgery, The Children's Hospital at Westmead The University of Sydney  Westmead New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachin","family":"Gupta","sequence":"additional","affiliation":[{"name":"TY Nelson Department of Neurology and Neurosurgery, The Children's Hospital at Westmead The University of Sydney  Westmead New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak","family":"Gill","sequence":"additional","affiliation":[{"name":"Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health University of Sydney  Westmead New South Wales Australia"},{"name":"TY Nelson Department of Neurology and Neurosurgery, The Children's Hospital at Westmead The University of Sydney  Westmead New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Malone","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Queensland Children's Hospital  South Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Waak","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Queensland Children's Hospital  South Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Calvert","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Queensland Children's Hospital  South Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gopinath","family":"Subramanian","sequence":"additional","affiliation":[{"name":"Department of Paediatrics John Hunter Children's Hospital  Newcastle New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. 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