{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T07:06:40Z","timestamp":1774940800066,"version":"3.50.1"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"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. Pediatr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This single-center retrospective study aims to analyze the clinical characteristics, treatment strategies, and outcome at discharge of neonatal-onset herpes simplex virus encephalitis (NHSE).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a single-center retrospective case review of infants diagnosed with NHSE at the Children's Hospital of Fudan University between February 1, 2016, and February 1, 2024. Clinical data, including demographics, clinical symptoms, laboratory findings, neuroimaging results, treatment regimens, and outcomes at discharge, were collected and analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 14 infants with NHSE (7 males, 7 females) were identified at our center, with a median age at diagnosis of 26 days (range: 7\u201351 days). Initial symptoms predominantly included fever and seizures, with neurological involvement (e.g., seizures, lethargy, irritability or altered mental states) in 13 cases. Physical examinations, such as bulging anterior fontanel, were noted. Herpes simplex virus (HSV)-DNA was detected in 13 cases (6 HSV-1, 7 HSV-2) through cerebrospinal fluid (CSF) polymerase chain reaction (PCR) or metagenomic testing. Among these, 9 cases were identified via CSF-PCR, with 7 testing positive on the initial examination and 2 on repeated testing. Notably, 6 cases were diagnosed using metagenomic next-generation sequencing (mNGS), all of which yielded positive results on the first test. Ten out of the 12 children often exhibited temporal lobe spikes on video electroencephalograms (VEEGs). Early magnetic resonance imaging (MRI) revealed cytotoxic edema, progressing to multicystic encephalomalacia. All received acyclovir antiviral treatment. Seven discontinued treatments, one was referred for ocular lesions, and six improved and were discharged.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this single-center cohort, NHSE often presents with nonspecific fever and seizures, with late onset and absent indicative rashes, complicating early diagnosis. For newborns suspected of having NHSE, early CSF HSV-DNA testing and prompt antiviral treatment are essential to improve outcomes. Metagenomic sequencing is especially valuable for accurate, rapid diagnosis when conventional methods fail.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2026.1740937","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T05:34:40Z","timestamp":1774935280000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Neonatal herpes simplex virus encephalitis: a single-center retrospective study of 14 cases"],"prefix":"10.3389","volume":"14","author":[{"given":"Lu","family":"Liu","sequence":"first","affiliation":[{"name":"Pediatrics Department of Shanghai Fifth People\u2019s Hospital, Fudan University Affiliated","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Le","family":"Wang","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, NICU, Xi'an Children\u2019s Hospital","place":["Xi'an, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Neonatal Disease, Ministry of Health, Children\u2019s Hospital of Fudan University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingyu","family":"Gan","sequence":"additional","affiliation":[{"name":"Clinical Genetic Center, Children\u2019s Hospital of Fudan University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruixuan","family":"Liujiang","sequence":"additional","affiliation":[{"name":"Department of Neonatology, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guoqiang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Neonates, Children\u2019s Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengmeng","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Neonates, Children\u2019s Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1053\/j.semperi.2018.02.004","article-title":"Neonatal herpes simplex virus infections","volume":"42","author":"Pinninti","year":"2018","journal-title":"Semin Perinatol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1093\/jpids\/piab105","article-title":"Neonatal herpes simplex virus infection: epidemiology and outcomes in the modern era","volume":"11","author":"Melvin","year":"2022","journal-title":"J Pediatric Infect Dis Soc"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1766","DOI":"10.1002\/jmv.23999","article-title":"Comparison of clinical manifestations, outcomes and cerebrospinal fluid findings between herpes simplex type 1 and type 2 central nervous system infections in adults","volume":"86","author":"Moon","year":"2014","journal-title":"J Med Virol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.clp.2014.10.005","article-title":"Neonatal herpes simplex virus infection: epidemiology and treatment","volume":"42","author":"James","year":"2015","journal-title":"Clin Perinatol"},{"key":"B5","first-page":"A9634","article-title":"Neonatal herpes simplex infection","volume":"160","author":"van Ham-Borawitz","year":"2016","journal-title":"Ned Tijdschr Geneeskd"},{"key":"B6","doi-asserted-by":"publisher","first-page":"105526","DOI":"10.1016\/j.jcv.2023.105526","article-title":"Characteristics of neonatal herpes simplex central nervous system disease in Australia (1997\u20132020)","volume":"165","author":"Teutsch","year":"2023","journal-title":"J Clin Virol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.jpeds.2016.02.015","article-title":"Initial presentation of neonatal herpes simplex virus infection","volume":"172","author":"Curfman","year":"2016","journal-title":"J Pediatr"},{"key":"B8","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1016\/j.jpeds.2014.11.011","article-title":"Plasma and cerebrospinal fluid herpes simplex virus levels at diagnosis and outcome of neonatal infection","volume":"166","author":"Melvin","year":"2015","journal-title":"J Pediatr"},{"key":"B9","doi-asserted-by":"publisher","first-page":"e14216","DOI":"10.2196\/14216","article-title":"Tools for the diagnosis of herpes simplex virus 1\/2: systematic review of studies published between 2012 and 2018","volume":"5","author":"Arshad","year":"2019","journal-title":"JMIR Public Health Surveill"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1016\/j.cmi.2022.06.004","article-title":"Diagnostic accuracy of rapid one-step PCR assays for detection of herpes simplex virus-1 and -2 in cerebrospinal fluid: a systematic review and meta-analysis","volume":"28","author":"Vaugon","year":"2022","journal-title":"Clin Microbiol Infect"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1104858","DOI":"10.3389\/fcimb.2023.1104858","article-title":"Metagenomic next-generation sequencing and proteomics analysis in pediatric viral encephalitis and meningitis","volume":"13","author":"Wang","year":"2023","journal-title":"Front Cell Infect Microbiol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"16961","DOI":"10.1038\/s41598-024-68034-1","article-title":"Clinical application and evaluation of metagenomic next-generation sequencing in pathogen detection for suspected central nervous system infections","volume":"14","author":"Yuan","year":"2024","journal-title":"Sci Rep"},{"key":"B13","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/s41390-022-02393-1","article-title":"Neuromonitoring in neonatal critical care part I: neonatal encephalopathy and neonates with possible seizures","volume":"94","author":"El-Dib","year":"2023","journal-title":"Pediatr Res"},{"key":"B14","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.pediatrneurol.2022.09.001","article-title":"Seizure burden, EEG, and outcome in neonates with acute intracranial infections: a prospective multicenter cohort study","volume":"137","author":"Mehta","year":"2022","journal-title":"Pediatr Neurol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1016\/j.jpeds.2014.04.046","article-title":"Clinical and neuroimaging findings in neonatal herpes simplex virus infection","volume":"165","author":"Bajaj","year":"2014","journal-title":"J Pediatr"},{"key":"B16","doi-asserted-by":"publisher","first-page":"447","DOI":"10.11251\/ojjscn.46.447","article-title":"A case of neonatal herpes simplex virus encephalitis with characteristic MRI features in the early period","volume":"46","author":"Sakai","year":"2014","journal-title":"No To Hattatsu"},{"key":"B17","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.neurad.2022.05.003","article-title":"Contribution of diffusion-weighted imaging to distinguish herpetic encephalitis from auto-immune encephalitis at an early stage","volume":"50","author":"Bani-Sadr","year":"2023","journal-title":"J Neuroradiol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"e20220004","DOI":"10.1002\/SMMD.20220004","article-title":"Current landscape in antiviral drug development against herpes simplex virus infections","volume":"1","author":"Frejborg","year":"2022","journal-title":"Smart Med"},{"key":"B19","doi-asserted-by":"publisher","first-page":"72","DOI":"10.5863\/1551-6776-19.2.72","article-title":"Safety of alternative antiviral agents for neonatal herpes simplex virus encephalitis and disseminated infection","volume":"19","author":"Wang","year":"2014","journal-title":"J Pediatr Pharmacol Ther"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e41580","DOI":"10.7759\/cureus.41580","article-title":"The many faces of neurological neonatal herpes simplex virus infection","volume":"15","author":"Shahoud","year":"2023","journal-title":"Cureus"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1740937\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T05:34:41Z","timestamp":1774935281000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1740937\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,31]]},"references-count":20,"alternative-id":["10.3389\/fped.2026.1740937"],"URL":"https:\/\/doi.org\/10.3389\/fped.2026.1740937","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,31]]},"article-number":"1740937"}}