ANTIVIRAL THERAPY AND MANAGEMENT OF COMPLICATIONS IN THE TREATMENT OF HERPETIC ENCEPHALITIS

Abstract

The management of Herpes Simplex Encephalitis (HSE) requires advancing beyond the mere eradication of viral load. Although intravenous acyclovir remains the unquestionable cornerstone of treatment, its effectiveness is intrinsically limited by the timing of administration—ideally within the first 24 to 48 hours—and by its inability to prevent biological damage independent of viral replication. The persistence of sequelae in up to 70% of survivors highlights that virological control does not guarantee neurological preservation. The pathogenesis involves sustained activation of the TNF/NF-κB inflammatory pathway and the identification of ferroptosis (iron-dependent cell death driven by lipid peroxidation) as a key event, suggesting new adjuvant therapeutic targets such as ferroptosis inhibitors. Long-term complications, such as post-herpetic autoimmune encephalitis, occur in approximately 25% to 27% of patients and require rapid intervention with aggressive immunotherapy. The discovery that around 10% of sporadic pediatric HSE cases originate from inborn errors of immunity (defects in the TLR3 pathway and type I interferon signaling) underscores the need for genomic surveillance to support precision medicine strategies. In summary, the future of HSE treatment lies in the implementation of multimodal protocols that integrate genetic and immunological diagnostics with early virological control, combining antivirals with neuroprotective and immunomodulatory agents.