The Cases of Acute Necrotizing Encephalopathy Due to Human Herpes Virus-6

BACKGROUND: Human herpesvirus-6 (HHV-6) is a neurotropic virus that typically remains latent in immunocompetent individuals but may cause severe neurologic complications, including encephalitis, particularly in immunocompromised hosts. Rarely, HHV-6 encephalitis can also occur in immunocompetent children, often presenting with features of acute necrotizing encephalopathy. CASES: We report 2 cases of previously healthy toddlers who presented with fever, seizures and altered mental status. Neuroimaging revealed bilateral thalamic involvement consistent with acute necrotizing encephalopathy. HHV-6 DNA was detected in cerebrospinal fluid via polymerase chain reaction, confirming the diagnosis. Both patients received antiviral therapy with foscarnet, alongside immunomodulatory treatments including intravenous immunoglobulin, corticosteroids, plasmapheresis and, in 1 case, tocilizumab. Clinical outcomes varied, with 1 patient achieving full recovery and the other showing partial neurologic improvement. CONCLUSIONS: These cases highlight the potential for HHV-6 to cause severe encephalopathy in immunocompetent children. Early recognition, neuroimaging, and cerebrospinal fluid polymerase chain reaction testing are essential for diagnosis. Combined antiviral and immunomodulatory therapies may improve outcomes by addressing both viral replication and neuroinflammation.