{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T10:30:43Z","timestamp":1787135443342,"version":"build-2736575974"},"reference-count":30,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"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":["Develop Med Child Neuro"],"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To evaluate the timing and safety of tocilizumab in acute necrotizing encephalopathy (ANE).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>This was a multicentre retrospective study evaluating outcomes (modified Rankin Scale [mRS]) in children with ANE treated with tocilizumab.\u00a0A logistic regression model determined a cut\u2010off for outcomes (binary good [mRS 0\u20132] vs poor [mRS 3\u20135]) according to day of tocilizumab administration, enabling a dichotomy of \u2018early\u2019 and \u2018late\u2019 treatment groups. Expected outcomes according to ANE severity score (ANE\u2010SS) in early\u2010treatment and late\u2010treatment groups were compared against reference data (conventional therapy, no tocilizumab) for outcomes according to risk category (medium risk: ANE\u2010SS score 2\u20134; high risk:\u00a0ANE\u2010SS score\u2009\u22655).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      From 2018 to 2023, 63 children (mean age 6\u2009years 0\u2009months [range: 8\u2009months\u201315\u2009years 4\u2009months]; 33 males, 30 females) were treated with tocilizumab, alongside corticosteroids in all and intravenous immunoglobulin in 33 (52.4%). Logistic regression defined an optimal treatment window of\u2009\u22643.3\u2009days. Compared to the reference data, early tocilizumab (\u2264\u200972\u2009hours after onset,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a049) was associated with good outcomes in both high\u2010risk (OR\u00a0=\u00a011.43, 95% confidence interval [CI]\u00a0=\u00a01.64\u2013127.4,\n                      <jats:italic>p\u2009=<\/jats:italic>\n                      \u00a00.01) and medium\u2010risk (OR\u00a0=\u00a012.80, 95% CI\u00a0=\u00a02.15\u201367.8;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.006) ANE\u2010SS categories. No tocilizumab\u2010related adverse events were reported.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Early tocilizumab treatment was associated with improved outcomes in severe ANE, with no adverse events, compared to conventional therapy alone.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dmcn.70454","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T10:15:06Z","timestamp":1787134506000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Early tocilizumab and outcomes in acute necrotizing encephalopathy"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4633-4316","authenticated-orcid":false,"given":"Velda X","family":"Han","sequence":"first","affiliation":[{"name":"Khoo\u2010Teck Puat\u2010National Children's Medical Institute National University Health System  Singapore Singapore"},{"name":"Department of Paediatrics, Yong Loo Lin School of Medicine National University of Singapore  Singapore"},{"name":"The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Healthy University of Sydney  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0385-5060","authenticated-orcid":false,"given":"Prithuja","family":"Poudyal","sequence":"additional","affiliation":[{"name":"Dhulikhel Hospital Kathmandu University Hospital  Dhulikhel Nepal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3988-204X","authenticated-orcid":false,"given":"Vanessa","family":"Lee","sequence":"additional","affiliation":[{"name":"Children's Neurosciences Evelina London Children's Hospital at Guy's and St Thomas' NHS Foundation Trust  London 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Research  Chandigarh India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3838-923X","authenticated-orcid":false,"given":"Ahmad Rithauddin","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit Hospital Tunku Azizah Kuala Lumpur  Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5643-2601","authenticated-orcid":false,"given":"Lokesh","family":"Lingappa","sequence":"additional","affiliation":[{"name":"Department of Neurology Rainbow Children's Hospital  Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6522-0704","authenticated-orcid":false,"given":"Hiroshi","family":"Sakuma","sequence":"additional","affiliation":[{"name":"Tokyo Metropolitan Institute of Medical Science  Tokyo 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