Sex-related molecular phenotypes in anxiety-depressive disorders: a machine learning analysis of routine blood biomarkers.

Herpes simplex virus encephalitis (HSE) is the most common and severe form of sporadic viral encephalitis, with an annual incidence of approximately 1/250,000–1/500,000 (, ). About one-third of cases occur in children (). Although acyclovir has significantly reduced acute mortality of HSE (), a considerable proportion of survivors suffer from long-term neurological sequelae (, ), imposing a heavy burden on families and society. A French multicenter study reported that 76% of pediatric HSE survivors had neurological deficits, including epilepsy (57%), intellectual disability (51%), and language impairment (47%) (). Current knowledge regarding the clinical features of HSE is derived mainly from adult studies or mixed-age cohorts. However, the pediatric central nervous system is dynamically developing, with large differences in immune maturity, myelination, and neuroplasticity across age groups. Systematic comparisons of age-specific clinical phenotypes of pediatric HSE are lacking in the literature. Specifically, the following questions remain unanswered: (1) Do clinical manifestations differ significantly between infants, preschool children, and school-aged children? (2) Which neuroimaging features independently predict long-term neurological outcomes? (3) Are there distinctive clinical signs that could improve early diagnosis in young children? To address these gaps, we analyzed 56 pediatric HSE cases. Through age stratification, we systematically describe the clinical, imaging, and long-term outcome characteristics of different age groups, aiming to improve early recognition and provide evidence for individualized treatment and long-term management.