Human Herpesvirus 6 Encephalitis in Immunocompetent and Immunocompromised Hosts

Abstract

Objective: The aim of this study was to analyze the clinical, radiologic, and biological features associated with human herpesvirus 6 (HHV-6) encephalitis in immunocompetent and immunocompromised hosts to establish which clinical settings should prompt HHV-6 testing.

Methods: We performed a retrospective research in the virology database of Fondazione IRCCS Policlinico San Matteo (Pavia, Italy) for all patients who tested positive for HHV-6 DNA in the CSF and/or in blood from January 2008 to September 2018 and separately assessed the number of patients meeting the criteria for HHV-6 encephalitis in the group of immunocompetent and immunocompromised hosts.

Results: Of the 926 patients tested for HHV-6 during the period of interest, 45 met the study criteria. Among immunocompetent hosts (n = 17), HHV-6 encephalitis was diagnosed to 4 infants or children presenting with seizures or mild encephalopathy during primary HHV-6 infection (CSF/blood replication ratio <<1 in all cases). Among immunocompromised hosts (n = 28), HHV-6 encephalitis was diagnosed to 7 adolescents/adults with hematologic conditions presenting with altered mental status (7/7), seizures (3/7), vigilance impairment (3/7), behavioral changes (2/7), hyponatremia (2/7), and anterograde amnesia (1/7). Initial brain MRI was altered only in 2 patients, but 6 of the 7 had a CSF/blood replication ratio >1.

Conclusions: The detection of a CSF/blood replication ratio >1 represented a specific feature of immunocompromised patients with HHV-6 encephalitis and could be of special help to establish a diagnosis of HHV-6 encephalitis in hematopoietic stem cell transplant recipients lacking radiologic evidence of limbic involvement.

Figure 1. Flowchart Diagram Illustrating Final Diagnoses Depending on the Immunologic Status of the Host and the Compartment(s) of Viral Replication

ciHHV-6 = chromosomally integrated human herpesvirus 6.

Figure 2. MRI Findings in 2 HSCT Transplant Recipients Developing HHV-6 Encephalitis

Panels A–F (patient 1 in table 4): on initial brain MRI, performed 3 days after symptom onset, no abnormal findings were detected on axial FLAIR (panels A and B) and coronal T2-weighted (panel C) images, though in the presence of motion artifacts. At control MRI, performed 16 days after symptom onset, a quite marked hyperintensity was evident at the level of the left temporo-mesial region, with swelling of the amygdala and the ipsilateral insular cortex on axial FLAIR (panels D and E) and coronal T2-weighted (panel F) images. No diffusivity restriction or gadolinium enhancement was evident (not shown). Panels G–I (patient 7 in table 4): brain MRI performed 4 days after neurologic symptom onset showed bilateral hyperintensity of temporo-mesial structures, prevalent on the right side, on axial FLAIR images (panel G), with a correspondent b1000 hypersignal (panel H) and some areas of true low ADC signal (panel I) but predominant T2 shine through effect. FLAIR = fluid-attenuated inversion recovery; HHV-6 = human herpesvirus 6; HSCT = hematopoietic stem cell transplantation.