EARLY DIAGNOSIS AND TREATMENT PROTOCOLS FOR HERPES ENCEPHALITIS IN PUBLIC HEALTH

Abstract

Herpes simplex virus encephalitis (HSE) is one of the leading infectious causes of central nervous system disease, characterized by high morbidity and mortality and a significant risk of neurological sequelae despite standardized antiviral treatment. This narrative review aims to compile the main evidence related to early diagnosis, pathophysiology, immunobiology, and current therapeutic approaches to herpes simplex encephalitis, with an emphasis on the pathways of tissue damage and secondary immune-mediated manifestations. The literature search was conducted on the PubMed platform using the search terms “Herpes Simplex Encephalitis” and “Therapeutics,” combined with the Boolean operators “AND” and “OR.” We selected original studies, prospective cohort studies, translational research, and conceptual reviews published in the last five years in English and Portuguese, excluding duplicate publications, studies with methodological weaknesses, and works that fell outside the scope of this study. The evidence indicates that the clinical presentation of HSE can be nonspecific, requiring integration of clinical manifestations, neuroimaging, electroencephalography, and cerebrospinal fluid analysis, with particular emphasis on polymerase chain reaction (PCR) for the detection of HSV DNA. However, laboratory confirmation should never delay the empirical infusion of intravenous acyclovir based on clinical suspicion, since therapeutic latency is directly correlated with a worse functional prognosis. Furthermore, recent data demonstrate that residual morbidity is not exclusively related to viral replication but involves mechanisms of neuroinflammation, alterations in intrinsic cerebral immunity, ferroptosis, and post-herpetic autoimmunity. Translational models reinforce the finding that HSV-1 infection can disrupt neuroepithelial integrity, neuronal activity, and antioxidant mechanisms; in this context, adjunctive immunomodulatory approaches have been shown to provide preclinical neuroprotection. Additionally, the identification of innate defects in cerebral immunity and the recognition of post-herpetic autoimmune encephalitis have expanded our understanding of the clinical and immunological heterogeneity of the disease. Ultimately, the management of herpes simplex encephalitis prioritizes early recognition and immediate administration of acyclovir, while new immunomodulatory strategies remain under investigation. Given the complex host immune response, clinical studies are still needed to establish the safety and efficacy of combination therapies, as well as biomarkers capable of identifying patients at higher risk for neurological damage and autoimmune complications.