Human herpesvirus-6 encephalitis after allogeneic hematopoietic cell transplantation: what we do and do not know

Human herpesvirus-6 (HHV-6) encephalitis following allogeneic hematopoietic cell transplantation is a serious and often fatal complication accompanying reactivation of HHV-6B. Incidence varies among studies, but is reportedly 0-11.6% after bone marrow or PBSC transplantation and 4.9-21.4% after umbilical cord blood transplantation, typically around 2-6 weeks post transplant. Symptoms are characterized by memory loss, loss of consciousness and seizures. Magnetic resonance imaging (MRI) typically shows bilateral signal abnormalities in the limbic system. This complication is considered to represent acute encephalitis caused by direct virally induced damage to the central nervous system, but our understanding of the etiologies and pathogenesis is still limited. The mortality rate attributable to this pathology remains high, and survivors are often left with serious sequelae such as impaired memory and epilepsy. Despite the poor prognosis, no validated treatments or preventative measures have been established. Establishment of preventative strategies represents an important challenge. This article reviews the current knowledge of the clinical features, incidence, pathogenesis and treatment of HHV-6 encephalitis, and discusses issues needing clarification in the future to overcome this serious complication.