Human herpes 6 virus encephalitis complicating allogeneic hematopoietic stem cell transplantation

Neurology. 2013 Apr 16;80(16):1494-500. doi: 10.1212/WNL.0b013e31828cf8a2. Epub 2013 Mar 20.


Objective: To describe the presentation and management of encephalitis due to human herpes 6 virus (HHV-6) in patients who underwent allogeneic hematopoietic stem cell transplant (alloHSCT), via retrospective chart review.

Methods: Of the 243 patients who underwent alloHSCT at the NIH Clinical Center during 2009 to 2011, we retrospectively analyzed 9 diagnosed with HHV-6 encephalitis post-alloHSCT.

Results: Eight men and 1 woman (aged 19-60 years) met diagnostic criteria for study inclusion. The median time from HSCT to initial symptoms was 21 days. All patients presented with altered mental status and headaches. Seven patients had amnesia and 2 presented with fever of unknown etiology. Four patients had clinical seizures during the disease course. Brain MRI within 7 days was normal in all patients. Repeat MRI after 7 days showed hyperintensity in the limbic area in 3 patients. On initial testing, CSF analysis indicated acellularity and normal or minimally elevated protein; presence of HHV-6 was detected by PCR. After 7 days, mildly elevated protein and minimal pleocytosis were noted. Ganciclovir, foscarnet, or valganciclovir alone or in combination was initiated with subsequent improvement. Four patients remained alive at 1 year posttransplant; 2 had persistent memory deficits. Presence of encephalitis was associated with higher mortality post-alloHSCT.

Conclusion: High clinical suspicion and CSF PCR testing are important for early diagnosis of HHV-6 encephalitis post-HSCT. Abnormalities on brain MRI or CSF testing may be minimal and delayed. Diagnosis and management of HHV-6 encephalitis is challenging, and a larger prospective study is needed for further research.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / therapeutic use
  • Brain / pathology
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Headache / etiology
  • Hematologic Neoplasms / complications
  • Hematologic Neoplasms / therapy
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods*
  • Hematopoietic Stem Cell Transplantation / mortality
  • Herpesvirus 6, Human*
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neuroimaging
  • Prognosis
  • Retrospective Studies
  • Roseolovirus Infections / complications*
  • Roseolovirus Infections / drug therapy
  • Roseolovirus Infections / virology
  • Seizures / etiology
  • Survival
  • Viral Load
  • Young Adult


  • Antiviral Agents