Human herpesvirus 6 encephalitis

Human herpesvirus 6 (HHV-6) encephalitis, also known as human herpesvirus 6 (HHV-6) encephalopathy, is a rare CNS infection caused by human herpesvirus 6 reactivation. It is typically seen in immunosuppressed individuals, particularly in those following an allogeneic hematopoietic stem cell transplant, who develop a characteristic limbic encephalitis syndrome with MRI abnormalities confined to the mesial temporal lobes ¹.

Notably, HHV-6 false positivity on multiplex polymerase chain reaction (PCR) panels of cerebrospinal fluid (CSF) is well-described, and thus, interpretation of a positive result should be made in the context of the patient demographics, clinical presentation, radiographic features, and quantitative viral load studies ⁵.

Clinical presentation

The clinical presentation is somewhat non-specific, resembling a limbic encephalitis ³. Common clinical features include confusion and altered conscious state, headache, fever, nausea and vomiting, seizures, and focal neurological deficits ³.

Radiographic features

CT

CT brain is usually normal ².

MRI

Changes are most commonly confined to the mesial temporal lobes ². Extratemporal involvement is considered rare ^2,6, but when present is typically in structures adjacent to the mesial temporal lobe ⁶.

Signal characteristics of affected regions include ^2,4:

• T2/FLAIR: high signal

• DWI/ADC: restricted diffusion

• SWI: blooming artefact indicating hemorrhage is usually absent

Treatment and prognosis

Management is primarily with antiviral medications such as ganciclovir or foscarnet ³. Notably, acyclovir, which is commonly commenced empirically for suspected viral encephalitis, is not effective ³. Other symptomatic management may include initiation of antiseizure medications.

Differential diagnosis

• herpes simplex encephalitis ^2,4

  • more likely to have an abnormal CT brain than HHV-6 encephalitis

  • also involves the mesial temporal lobes in essentially all cases

  • more likely to involve extratemporal regions than HHV-6 encephalitis

  • more likely to have parenchymal swelling than HHV-6 encephalitis

  • more likely to have hemorrhage than HHV-6 encephalitis

  • both commonly demonstrate high DWI signal

• other causes of encephalitis (viral, autoimmune/paraneoplastic, etc.)