{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T06:05:36Z","timestamp":1784786736070,"version":"3.55.0"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"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 and objective<\/jats:title>\n                    <jats:p>Age-specific clinical characteristics and prognostic predictors of pediatric herpes simplex virus encephalitis (HSE) remain incompletely characterized. This study aimed to characterize age-dependent manifestations and identify factors independently associated with poor long-term outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A longitudinal cohort study included 56 pediatric patients with confirmed HSE who were admitted to the Children\u2019s Hospital Affiliated to Zhengzhou University from January 2018 to June 2023. Patients were stratified into three age groups: infant\/toddler group (0\u20133\u202fyears), preschool group (3\u20136\u202fyears), and school-age and older group (6\u201318\u202fyears). Clinical, laboratory, and cranial magnetic resonance imaging (MRI) data were collected. Neurological outcomes were assessed using the pediatric modified Rankin Scale (mRS). Multivariate logistic regression analysis was performed to identify independent associated factors of poor prognosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The median age of onset was 2.09\u202fyears, and 60.7% of patients were aged under 3\u202fyears. Unilateral facial and\/or perioral twitching occurred in 33.9% of patients, all of whom under 5\u202fyears of age, with the highest incidence in the preschool group (70.0%,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.001). This sign was associated with higher rates of frontal\/insular lobe involvement and severe long-term language impairment (89.5% vs. 51.4%,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.005). The median follow-up duration was 62.5\u202fmonths. Overall, 73.2% of patients had a poor outcome. The incidence of post-encephalitic epilepsy (PE) was 53.6%, of which 63.3% were drug-refractory. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis developed in 17.9% of patients, and its incidence increased significantly with age (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.002). Multivariate logistic regression analysis identified a lower acute Glasgow Coma Scale (GCS) score (OR\u202f=\u202f0.577, 95% CI: 0.376\u20130.885,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.012) and prolonged total seizure duration (OR\u202f=\u202f1.635, 95% CI: 1.126\u20132.374,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.010) as factors independently associated with poor prognosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Pediatric HSE exhibits notable age-associated heterogeneity. A low acute GCS score and prolonged seizure duration were identified as independent associated factors for poor prognosis in this exploratory analysis, whereas early facial\/perioral twitching was associated with subsequent language sequelae. The risk of anti-NMDAR encephalitis increases with age, necessitating long-term surveillance. These age-stratified findings are descriptive and hypothesis-generating and require confirmation in larger prospective cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1882046","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T05:37:54Z","timestamp":1784785074000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Age-stratified clinical characteristics and long-term neurological outcomes of pediatric herpes simplex virus encephalitis: a longitudinal cohort study of 56 children"],"prefix":"10.3389","volume":"17","author":[{"given":"Ying","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, China"]},{"name":"Department of Neurology, Children\u2019s Hospital Affiliated to Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanli","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Neurology, Children\u2019s Hospital Affiliated to Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Children\u2019s Hospital Affiliated to Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixiao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Children\u2019s Hospital Affiliated to Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Children\u2019s Hospital Affiliated to Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunge","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging, Children\u2019s Hospital Affiliated to Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijie","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging, Children\u2019s Hospital Affiliated to Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Centre for Children\u2019s Health, Beijing Children\u2019s Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufeng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1016\/S1474-4422(18)30244-8","article-title":"Frequency, symptoms, risk factors, and outcomes of autoimmune encephalitis after herpes simplex encephalitis: a prospective observational study and retrospective analysis","volume":"17","author":"Armangue","year":"2018","journal-title":"Lancet Neurol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1053\/j.spid.2004.09.007","article-title":"Herpes simplex encephalitis: children and adolescents","volume":"16","author":"Whitley","year":"2005","journal-title":"Semin Pediatr Infect Dis"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1111\/epi.12879","article-title":"Postencephalitic epilepsy: clinical characteristics and predictors","volume":"56","author":"Singh","year":"2015","journal-title":"Epilepsia"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.seizure.2018.05.012","article-title":"Pediatric refractory and super-refractory status epilepticus","volume":"68","author":"Vasquez","year":"2019","journal-title":"Seizure"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"e399","DOI":"10.1542\/peds.2006-1494","article-title":"A 12-year prospective study of childhood herpes simplex encephalitis: is there a broader spectrum of disease?","volume":"119","author":"Elbers","year":"2007","journal-title":"Pediatrics"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1007\/s13311-016-0433-7","article-title":"Herpes simplex Virus-1 encephalitis in adults: pathophysiology, diagnosis, and 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