Acute Encephalitis in HHV-6 Infection: Is There More to It?

Background: Human Herpes Virus 6 (HHV-6) is an important member of the Herpesviridae family, frequently acquired by early age and transmitted postnatally via saliva from mother to infant. In children under the age of 3, it can cause several neurological manifestations, such as encephalitis and febrile seizures. In the immunocompetent child, it is usually a benign, self-resolving infection that, generally, does not warrant further treatment. Case presentation: A previously healthy 3-year-old girl presented to the local emergency department for acute onset drowsiness, fever (up to 39°C intrarectal), and one witnessed convulsion that lasted for approximately 2 minutes, followed by left-sided hemiplegia. Patient history revealed no recent travel or ill contacts, as well as incomplete immunization; family history is significant for epilepsy in the maternal grandfather. Upon clinical examination, no signs of meningeal irritation could be identified, and the arterial blood gas and inflammatory markers revealed no abnormal findings; however, as she manifested two generalized tonic-clonic seizures during the inspection, a native head CT scan was performed, showing no significant changes. The patient was started on phenobarbital in the local pediatric ward, but because the seizures were refractory to the administered medication, she was transferred to the emergency department in Cluj-Napoca. On arrival, she exhibited altered mental status with preserved motricity; moreover, a quick antigen test was positive for Influenza B (later confirmed by Multiplex PCR respiratory panel) and a further chest Rx indicated pneumonia. Infectious Diseases and Neurologic consultations were solicited, raising suspicion of acute encephalitis of unknown etiology, and the recommendations made were to initiate empirical antibiotic therapy (Ceftriaxone, Vancomycin), antiviral therapy (Acyclovir, Oseltamivir), as well as anticonvulsant therapy. After ensuring the patient manifested no other episodes of convulsing, she was brought to the Clinic of Infectious Diseases, where a diagnostic lumbar puncture was performed. The results of the Multiplex PCR panel uncovered an HHV-6 infection, allowing for discontinuation of the intravenous Vancomycin and Acyclovir. Under supportive hospital treatment, the patient’s condition improved gradually, and she was discharged after 10 days with normal mental status and without motor deficits. The patient was scheduled for a follow-up consultation as an outpatient in the Infantile Neurology Clinic, but we later learned that the family was non-compliant. Learning points discussion: In the case of encephalitis, prompt identification of the etiology is of significance, as this dictates the management and prognosis of the disease, limiting the use of resources and unnecessary therapy. It is known that the virus can remain dormant in mononuclear cells and may be reactivated in the event of significant immunosuppression. It is possible that the Influenza infection reactivated the HHV-6 virus, causing more drastic manifestations - though several studies suggest this pathogenesis to be unlikely. Another thing to consider is the positive family history for epilepsy, as there are studies that link HHV-6 and mesial temporal lobe epilepsy. The pathogenetic role of HHV-6 in different neurological diseases presents many unknowns and remains a topic to be studied further.