{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:15:21Z","timestamp":1789517721397,"version":"build-2803163510"},"reference-count":26,"publisher":"Korean Pediatric Society","issue":"1","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Capital\u2019s Funds for Health Improvement and Research of Beijing Nova Program","award":["20240484656"],"award-info":[{"award-number":["20240484656"]}]},{"DOI":"10.13039\/501100012425","name":"Beijing Children\u2019s Hospital, Capital Medical University","doi-asserted-by":"crossref","award":["2020-2-2094"],"award-info":[{"award-number":["2020-2-2094"]}],"id":[{"id":"10.13039\/501100012425","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["e-cep.org"],"crossmark-restriction":true},"short-container-title":["Clin Exp Pediatr"],"published-print":{"date-parts":[[2026,1,15]]},"abstract":"<jats:p>Background: Acute necrotizing encephalopathy (ANE) is a rare but devastating neurological disorder in children that is typically triggered by viral infections such as influenza, sudden acute respiratory syndrome coronavirus 2, and human herpesvirus-6. ANE is characterized by cytokine storm and associated with high mortality; however, optimal immunomodulatory strategies remain undefined.Purpose: To evaluate the effectiveness of multiple immunomodulatory strategies, including high-dose methylprednisolone (MP), plasma exchange (PLEX), and tocilizumab, at reducing short-term mortality among pediatric patients with ANE stratified by disease severity using the ANE severity score (ANE-SS).Methods: We retrospectively reviewed 65 pediatric patients (median age, 4.8 years; interquartile range, 2.8\u20137.7 years) diagnosed with ANE at Beijing Children\u2019s Hospital from 2016 to 2024. Patients were stratified by ANE-SS at admission into low- to medium-risk (ANE-SS&lt;5) and high-risk (ANE-SS\u22655) groups. Immunomodulatory treatments included different doses of MP, intravenous immunoglobulin, PLEX, and tocilizumab. The primary outcome was the 28-day postdischarge mortality. Multivariate logistic regression was used to identify the treatment strategies that were independently associated with improved survival.Results: The overall 28-day postdischarge mortality rate was 45.9%, significantly higher in patients with ANE-SS \u22655 (65.7%) than in those with ANE-SS&lt;5 (16.7%; P&lt;0.001). A notable decline in mortality has been observed since 2022, coinciding with the increased use of high-dose MP (20 and 30 mg\/kg\/day) and tocilizumab. The annual mortality rate will drop to 38.9% in 2022, 36.8% in 2023, and 16.7% in 2024. In low- to medium-risk patients (ANE-SS&lt;5), both 20-mg\/kg\/day and 30-mg\/kg\/day MP were associated with improved outcomes. In high-risk patients (ANE-SS\u22655), the combination of 30-mg\/kg\/day MP and tocilizumab provided the greatest survival benefit. Multivariable logistic regression analysis identified that this combined therapy was independently associated with reduced mortality (odds ratio, 0.04; 95% confidence interval, 0.01\u20130.18; P&lt;0.001). No significant survival benefit was observed following PLEX treatment.Conclusion: In low- to moderate-risk patients, the 20- and 30-mg\/kg\/day MP regimens were effective. In high-risk patients with ANE, high-dose MP (30 mg\/kg\/day), particularly when combined with tocilizumab, may improve survival and possibly long-term neurological recovery. These findings support the use of a severity-based immunotherapy strategy for pediatric patients with ANE.<\/jats:p>","DOI":"10.3345\/cep.2025.01431","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T06:33:47Z","timestamp":1761114827000},"page":"56-64","update-policy":"https:\/\/doi.org\/10.3345\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["High-dose methylprednisolone and tocilizumab improve survival of patients with high-risk pediatric acute necrotizing encephalopathy"],"prefix":"10.3345","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-0096-0996","authenticated-orcid":true,"given":"Chaonan","family":"Fan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4242-1280","authenticated-orcid":true,"given":"Fei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0843-3076","authenticated-orcid":true,"given":"Kechun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0613-1804","authenticated-orcid":true,"given":"Zheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3178-6570","authenticated-orcid":true,"given":"Yiyang","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1062-2156","authenticated-orcid":true,"given":"Lijuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5818-2551","authenticated-orcid":true,"given":"Gang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2944-1691","authenticated-orcid":true,"given":"Yingchao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5187-526X","authenticated-orcid":true,"given":"Quan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5974-8254","authenticated-orcid":true,"given":"Suyun","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1897","reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.16067"},{"key":"ref2","volume-title":""},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2011.07.012"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix412"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.12659\/msm.928374"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2020.08.001"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11195921"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2021.655074"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1002\/ped4.12280"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2024.07.009"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-024-12661-1"},{"key":"ref12","first-page":"868","volume-title":"Diagnostic 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encephalopathy","author":"Zhou","year":"2024"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.3906\/sag-2102-47"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-023-11915-8"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1080\/14740338.2024.2382227"}],"container-title":["Clinical and Experimental Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/e-cep.org\/upload\/pdf\/cep-2025-01431.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/e-cep.org\/journal\/view.php?doi=10.3345\/cep.2025.01431","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/e-cep.org\/upload\/pdf\/cep-2025-01431.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T08:34:38Z","timestamp":1768379678000},"score":1,"resource":{"primary":{"URL":"http:\/\/e-cep.org\/journal\/view.php?doi=10.3345\/cep.2025.01431"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,15]]},"references-count":26,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"URL":"https:\/\/doi.org\/10.3345\/cep.2025.01431","relation":{},"ISSN":["2713-4148"],"issn-type":[{"value":"2713-4148","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,15]]},"assertion":[{"value":"2025-06-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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