From the Guidelines
Human herpesvirus 6 (HHV-6) detected in cerebrospinal fluid (CSF) is clinically significant and warrants prompt antiviral treatment, typically with ganciclovir or foscarnet, especially in immunocompromised patients. This finding indicates potential central nervous system infection or reactivation, which can cause encephalitis, meningitis, or other neurological complications with symptoms including fever, altered mental status, seizures, and focal neurological deficits 1. The virus establishes latency after primary infection and can reactivate during periods of immunosuppression, particularly in transplant recipients, HIV patients, or those on immunosuppressive medications.
Key Considerations
- Diagnosis typically requires PCR testing of CSF, as the virus is difficult to culture 1.
- While some individuals may have chromosomally integrated HHV-6 that can appear in CSF without active infection, true HHV-6 CNS disease carries significant morbidity with potential for cognitive impairment, epilepsy, or other long-term neurological sequelae if not properly treated 1.
- The presence of HHV-6 DNA in CSF does not always indicate active infection, as it can also be detected in individuals with chromosomally integrated HHV-6 1.
Treatment Options
- Ganciclovir and foscarnet are recommended for treatment of HHV-6 encephalitis post-HSCT, with response rates of 83.8% and 71.4% with foscarnet monotherapy and ganciclovir monotherapy, respectively 1.
- Full-dose therapy with foscarnet (≥180 mg/kg) or ganciclovir (≥10 mg/kg) is associated with a better response rate than treatment with lower doses 1.
Prevention and Screening
- Routine screening of HHV-6 DNA in blood post-HSCT is not recommended, and anti-HHV-6 prophylactic or pre-emptive therapy is not recommended for the prevention of HHV-6B reactivation or encephalitis post-HSCT 1.
From the Research
Significance of Human Herpesvirus 6 (HHV-6) in Cerebrospinal Fluid (CSF)
- HHV-6 is an important cause of meningitis and meningoencephalitis, and its detection in CSF can lead to the discontinuation of empirical antiviral treatment and the initiation of appropriate therapy 2.
- The presence of HHV-6 in CSF can be predictive of true infections, and its detection can aid in the identification of disease etiology and the optimization of antimicrobial therapy 2.
- HHV-6 encephalitis is a significant cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant recipients, and the use of antiviral medications such as ganciclovir and foscarnet can be effective in treating this condition 3.
- The detection of HHV-6 in CSF can be achieved through polymerase chain reaction (PCR) testing, and this can be an important diagnostic tool in the management of suspected central nervous system infections 4, 5.
- The viral load of HHV-6 in CSF can be an important factor in determining the effectiveness of treatment, and monitoring of HHV-6 load in CSF can be necessary to ensure optimal treatment outcomes 6.
Clinical Presentation and Treatment
- HHV-6 meningitis and meningoencephalitis can present with a range of clinical symptoms, including pleocytosis and radiographic findings 2.
- Treatment of HHV-6 encephalitis can involve the use of antiviral medications such as ganciclovir and foscarnet, and combination therapy may be more effective than monotherapy in reducing sequelae 3.
- Intravenous immunoglobulin and valganciclovir can also be effective in treating HHV-6 meningoradiculitis 4.
- The management of HHV-6 encephalitis in children can involve the use of CSF HHV-6 PCR testing and the consideration of antiviral therapy 5.
Diagnostic Considerations
- The detection of HHV-6 in CSF can be an important diagnostic tool in the management of suspected central nervous system infections 2, 5.
- CSF parameters may not be generally predictive of HHV-6 positivity, and the presence of chromosomally integrated HHV-6 (ciHHV-6) DNA can be confirmed in some patients 2.
- The use of PCR testing can be an important factor in determining the effectiveness of treatment and monitoring of HHV-6 load in CSF 6.