{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T11:58:57Z","timestamp":1785239937703,"version":"3.55.0"},"reference-count":17,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Varicella-zoster virus (VZV) reactivation in the head and facial region can cause severe intracranial complications. Early identification of central nervous system (CNS) involvement is critical, yet specific bedside predictors to guide prompt antiviral escalation are lacking, frequently leading to diagnostic delays and poor neurological prognosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To develop and internally validate a clinical risk-stratification scoring system based on ocular involvement, systemic inflammation, and headache patterns to identify intracranial infection in head and facial herpes zoster (HZ).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study design<\/jats:title>\n                    <jats:p>In this multicenter retrospective cohort study (January 2023\u2013December 2025), 302 patients from four tertiary hospitals were enrolled. Intracranial infection (meningitis, encephalitis, or vasculitis) was confirmed via rigorous cerebrospinal fluid (CSF) analysis (VZV PCR targeting ORF 62 or intrathecal antibody index &amp;gt;1.5) and neuroimaging. Propensity score matching (PSM) balanced baseline characteristics. A multivariate logistic regression-derived scoring model was developed to quantify risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>After PSM, 134 cases and 127 controls were analyzed. Five independent clinical triggers were identified: keratitis\/conjunctivitis (aOR 2.50, 95% CI 1.45\u20134.31); elevated intraocular pressure\/glaucoma (aOR 8.15, 95% CI 1.92\u201334.58); peak body temperature (aOR 2.80 per category, 95% CI 1.95\u20134.02); fever duration (aOR 1.25 per day, 95% CI 1.12\u20131.40); and holocranial headache (aOR 12.05, 95% CI 2.65\u201354.85). The integrated risk-stratification model demonstrated excellent discrimination with an AUC of 0.87 (95% CI 0.83\u20130.91). At the optimal cutoff, the model achieved a sensitivity of 84.3%, specificity of 81.9%, and a positive predictive value of 84.1%, indicating high clinical utility for ruling in CNS involvement.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A clinical triad of sight-threatening ocular involvement, high-grade\/prolonged fever, and holocranial headache serves as a highly accurate early warning system for VZV-related intracranial infection (sensitivity 84.3%, specificity 81.9%, PPV 84.1%). This readily applicable scoring tool supports prioritized CSF analysis and immediate intravenous acyclovir initiation, addressing a major unmet need in the clinical triage of head and facial HZ.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1901262","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T11:10:16Z","timestamp":1785237016000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Ocular involvement, fever, and holocranial headache predict intracranial infection in immunocompetent patients with cranial herpes zoster: a multicenter propensity score-matched study"],"prefix":"10.3389","volume":"13","author":[{"given":"Xiaoyu","family":"Yin","sequence":"first","affiliation":[{"name":"Cerebrovascular Disease Department, Hangzhou Third People's Hospital","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changyang","family":"Zhong","sequence":"additional","affiliation":[{"name":"Cerebrovascular Disease Department, Hangzhou Third People's Hospital","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lv","sequence":"additional","affiliation":[{"name":"Emergency Department, Hangzhou Third People's Hospital","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Wu","sequence":"additional","affiliation":[{"name":"The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou","place":["Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianghao","family":"Zhou","sequence":"additional","affiliation":[{"name":"The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou","place":["Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"192","DOI":"10.3390\/v14020192","article-title":"Herpes zoster: a review of clinical manifestations and management","volume":"14","author":"Patil","year":"2022","journal-title":"Viruses."},{"key":"B2","doi-asserted-by":"publisher","first-page":"e70166","DOI":"10.1002\/jmv.70166","article-title":"Incidence and risk factors for varicella-zoster virus-associated central nervous system infections: a nationwide Swedish retrospective case-control study","volume":"97","author":"Tyrberg","year":"2025","journal-title":"J Med Virol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2463","DOI":"10.1097\/SCS.0000000000008631","article-title":"Herpes zoster opthalmicus-related ophthalmoplegia: anatomical, pathogenetic, and therapeutic perspectives","volume":"33","author":"Pupic-Bakra\u010d","year":"2022","journal-title":"J Craniofac Surg."},{"key":"B4","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1111\/acem.12984","article-title":"Spontaneous subarachnoid hemorrhage: a systematic review and meta-analysis describing the diagnostic accuracy of history, physical examination, imaging, and lumbar puncture with an exploration of test thresholds","volume":"23","author":"Carpenter","year":"2016","journal-title":"Acad Emerg Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e13622","DOI":"10.1111\/ctr.13622","article-title":"AST Infectious Diseases Community of Practice. 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