{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T06:36:20Z","timestamp":1773815780516,"version":"3.50.1"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pediatric infection-triggered encephalopathy syndromes (ITES) cause severe neurologic and cognitive deficits, but reliable biomarkers for early diagnosis and improved outcomes are lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This retrospective study analyzed the clinical characteristics and laboratory data from 48 children with infection-triggered encephalopathy syndromes, using a case\u2013control design. Ultra-high-performance liquid chromatography\u2013tandem mass spectrometry, the Luminex xMAP\n                      <jats:sup>\u00ae<\/jats:sup>\n                      multiplex assay system, the Cobas\n                      <jats:sup>\u00ae<\/jats:sup>\n                      8,000 analyzer, and immunoturbidimetry were utilized to measure blood and urine metabolites, cerebrospinal fluid and plasma cytokines, and cerebrospinal fluid biomarkers and proteins.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Initial urinary metabolomic profiling identified 56 differentially abundant metabolites in the infection-triggered encephalopathy syndromes group (50 upregulated, 6 downregulated). Partial least-squares discriminant analysis highlighted 13 metabolites with variable importance in projection scores &amp;gt;1, 12 of which may serve as candidate biomarkers (area under the curve &amp;gt; 0.75; e.g., 3-hydroxybutyrate, fucose). Random Forest modeling prioritized five urinary metabolites: stearate, malate, glucose1, glucose2, and fucose. Similarly, five metabolites, such as C4OH, C14OH(CIL), C18:1OH, C10:2(CIL), and C5DC(CIL)\/C16, may serve as potential biomarkers (AUC\u202f&amp;gt;\u202f0.75). Cerebrospinal fluid analysis showed elevated interleukin-6 and interleukin-8 levels in the infection-triggered encephalopathy syndromes group (area under the curve &amp;gt; 0.75 each). Clinically, there were significant differences between the ITES group and the control group in terms of Modified Rankin Scale scores, infection status, fever, seizures, and altered consciousness (all\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>This study identifies a panel of urinary, plasma, and cerebrospinal fluid biomarkers, which provide a thorough molecular profile of infection-triggered encephalopathy syndromes in children. These findings provide a direction for future research on mechanistic studies, early identification, and risk classification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1730057","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T05:39:32Z","timestamp":1773812372000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pediatric infection-triggered encephalopathy syndromes: a multidimensional biomarker analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Caihui","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Neurology, Capital Center for Children's Health, Capital Medical University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuowen","family":"Wang","sequence":"additional","affiliation":[{"name":"Capital Center for Children\u2019s Health, Capital Medical University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhijie","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Capital Center for Children's Health, Capital Medical University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zijun","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Shijitan Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Capital Center for Children's Health, Capital Medical University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yizhi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Capital Center for Children's Health, Capital Medical University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuo","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Capital Center for Children's Health, Capital Medical University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Capital Center for Children's Health, Capital Medical University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianzhao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Capital Center for Children's Health, Capital Medical University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1111\/dmcn.16067","article-title":"International consensus definitions for infection-triggered encephalopathy syndromes","volume":"67","author":"Sakuma","year":"2025","journal-title":"Dev Med Child Neurol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.braindev.2011.07.012","article-title":"Epidemiology of acute encephalopathy in Japan, with emphasis on the association of viruses and syndromes","volume":"34","author":"Hoshino","year":"2012","journal-title":"Brain Dev"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1016\/j.braindev.2020.04.006","article-title":"Epidemiological changes of acute encephalopathy in Japan based on national surveillance for 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