ArticleFrontiers in medicine2026
Ocular involvement, fever, and holocranial headache predict intracranial infection in immunocompetent patients with cranial herpes zoster: a multicenter propensity score-matched study.
Article in Frontiers in medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: 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. Objectives: 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). Study design: In this multicenter retrospective cohort study (January 2023-December 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 >1.5) and neuroimaging. Propensity score matching (PSM) balanced baseline characteristics. A multivariate logistic regression-derived scoring model was developed to quantify risk. Results: After PSM, 134 cases and 127 controls were analyzed. Five independent clinical triggers were identified: keratitis/conjunctivitis (aOR 2.50, 95% CI 1.45-4.31); elevated intraocular pressure/glaucoma (aOR 8.15, 95% CI 1.92-34.58); peak body temperature (aOR 2.80 per category, 95% CI 1.95-4.02); fever duration (aOR 1.25 per day, 95% CI 1.12-1.40); and holocranial headache (aOR 12.05, 95% CI 2.65-54.85). The integrated risk-stratification model demonstrated excellent discrimination with an AUC of 0.87 (95% CI 0.83-0.91). 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. Conclusions: 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.
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