Human Herpesvirus 6 (HHV-6) is a common virus that infects nearly all humans, typically during childhood. The primary infection, usually caused by the HHV-6B strain, often manifests as roseola infantum, a mild illness characterized by a high fever followed by a rash. Like other herpes viruses, HHV-6 establishes a lifelong, inactive presence (latency) in the body, primarily within blood cells. Encephalitis is a severe complication defined by inflammation of the brain tissue, which can rapidly lead to serious neurological dysfunction. Progression to HHV-6 encephalitis is a rare but devastating complication that occurs when the virus reactivates and spreads to the central nervous system.
How HHV-6 Progresses to Encephalitis
HHV-6 encephalitis is strongly tied to the virus emerging from its latent state. For most people, the immune system keeps the virus dormant after the initial childhood infection. Encephalitis most commonly results from viral reactivation, not a new infection, when a person’s immune defenses are severely weakened.
The most susceptible population consists of individuals who have undergone hematopoietic stem cell transplantation (HSCT). This procedure requires intense immunosuppression, creating a window for the latent HHV-6 to reactivate and multiply. Solid organ transplant recipients, those with advanced HIV infection, or hematologic malignancies are also at high risk for reactivation and subsequent neurological disease.
Once reactivated, the virus moves into the central nervous system, crossing the protective blood-brain barrier. HHV-6 exhibits an affinity for structures in the limbic system, such as the temporal lobes and the hippocampus. This is known as limbic encephalitis, where direct viral replication in the brain tissue causes severe inflammation and damage to these areas, driving the neurological symptoms seen in HHV-6 encephalitis.
Identifying the Clinical Symptoms
The onset of HHV-6 encephalitis is often rapid, with symptoms reflecting severe inflammation within the brain. Systemic signs like a high fever and general malaise are common, but the most concerning manifestations are neurological.
A defining feature is an altered mental status, which can range from confusion and lethargy to profound disorientation. Patients frequently experience seizures, which may be localized to specific brain regions or become generalized. Due to the virus’s tendency to attack the limbic system, specifically the hippocampus, memory impairment is a hallmark symptom.
Patients may suffer from anterograde amnesia, the inability to form new memories. This memory deficit, along with changes in personality and behavior, often presents as a distinct post-transplant acute limbic encephalitis syndrome in high-risk patients. Headaches, nausea, and vomiting can also be reported, but the combination of fever, confusion, and seizures suggests a severe central nervous system infection.
Confirming the Diagnosis
Diagnosing HHV-6 encephalitis requires a high degree of clinical suspicion, especially in at-risk patients, followed by definitive laboratory testing. The gold standard for confirmation is the detection of the virus’s genetic material within the cerebrospinal fluid (CSF).
A lumbar puncture is performed to collect CSF for analysis. The CSF sample is then tested using Polymerase Chain Reaction (PCR), which amplifies and detects the DNA of HHV-6. A positive PCR result for HHV-6 DNA in the CSF of a symptomatic patient confirms an active infection in the central nervous system.
Imaging studies, particularly Magnetic Resonance Imaging (MRI), provide visual evidence of inflammation. MRI scans often show characteristic signal abnormalities (hyperintensities), primarily localized to the mesial temporal lobes and hippocampus. While this pattern is suggestive, it is not always present early in the disease course, making the CSF PCR test the most reliable diagnostic tool. These tools are also used to distinguish HHV-6 encephalitis from other forms of viral encephalitis.
Antiviral Treatment and Patient Outcome
Treatment for HHV-6 encephalitis relies on specific antiviral medications that target the herpesvirus family, administered intravenously. The two primary drugs used are Ganciclovir and Foscarnet, and therapy should be initiated immediately upon strong suspicion, even before test results are finalized. Ganciclovir works by interfering with the virus’s ability to replicate its DNA, while Foscarnet directly inhibits viral DNA polymerase.
Treatment is typically continued for a minimum of three weeks and until HHV-6 DNA is no longer detectable in the CSF. The choice between Ganciclovir and Foscarnet, or combination therapy, depends on a patient’s underlying health conditions, such as kidney function or bone marrow status, as both drugs have side effects. Foscarnet is associated with a lower rate of neurological sequelae compared to Ganciclovir monotherapy, though it carries a risk of kidney toxicity.
Supportive care in an intensive care setting is administered to manage serious symptoms like seizures and elevated intracranial pressure. Despite prompt antiviral treatment, HHV-6 encephalitis carries a guarded prognosis, particularly in immunocompromised patients. Long-term neurological complications (sequelae) are common among survivors, with over half experiencing persistent deficits. These lasting effects include significant memory impairment, cognitive deficits, and the development of epilepsy, often correlating with severe atrophy of the hippocampal region.