Central Nervous System Infection Is Common in Multiple Strains of Herpesvirus

Some herpesviruses impact the central nervous system (CNS) more than others, and messenger ribonucleic acid (RNA)-based vaccines are being studied to vaccinate against herpes— especially following their success in preventing COVID-19, according to the authors of a study published in the National Library of Medicine. Currently, the authors explained that a polymerase chain reaction (PCR) test may be able to determine what strain of herpes an individual has contracted.

“Herpesviruses are the most frequently diagnosed cause of infectious encephalitis worldwide and make up a significant portion of meningitis cases as well. Despite the many potential infectious etiologies of meningoencephalitis in tropical regions, HSV1 and HSV2 should remain high on the differential given their high incidence,” wrote the study authors.

The herpesviruses can be a leading cause of acute encephalitis, or brain inflammation. CNS infection like encephalitis often occurs during viral reactivation, and the herpesvirus becomes reactivated in most patients.

Herpes simplex virus 1 (HSV1) is the leading cause of sporadic infectious encephalitis, and it has also surpassed the herpes simplex virus 2 (HSV2) as a leading cause of neonatal encephalitis.

The HSV2 virus shares 50% of genetic material with HSV1; however, although HSV2 typically causes genital infections and viral meningitis, it can also sometimes lead to encephalitis.

Varicella zoster virus (VZV) is human herpesvirus (HHV3), which can cause CNS, especially acute cerebellitis, during reactivation. Many complications that are associated with CNS VZV can relate to VZV vasculopathy, which has been associated with arterial dissection, aneurysm and subarachnoid hemorrhage, ischemic cranial neuropathies, ischemic myelopathy, venous sinus thrombosis, and temporal arteritis.

Additionally, the study authors explained that although the herpesvirus vaccine can decrease reactivation of the HHV3 strain, reactivation and latent infection have still been found to occur.

“While zoster vaccination may lead to a reduction in VZV CNS infection, VZV remains a critical pathogen and should not be overlooked. Other herpes viruses should also be considered in the correct clinical context, especially in cases of immunosuppression,” study authors wrote in the report.

Additionally, PCR tests revealed that CNS symptoms like meningitis and encephalitis from VZV are quite common—1 study even found that 30% of all meningitis or encephalitis cases were caused by VZV.

To combat the VZV form of herpes, the FDA approved a live attenuated herpes zoster vaccine in 2006. It reduced incidences of VZV reactivation by 60%. In 2017, the FDA approved a second vaccine in the form of a recombinant subunit inactivated shingles vaccine—this reduced VZV reactivation by more than 95%.

A fourth herpesvirus is called the Epstein-Barr virus (EBV), which usually infects young children and adolescents. Reactivation of EBV does not usually cause CNS infection, but those at a greater risk are organ transplant recipients.

The cytomegalovirus virus is a variant that has infected 100% of the developing world, according to researchers. “Like EBV, it is rarely associated with neurologic manifestations in the immunocompetent host,” study authors wrote in the report.

Other herpesviruses, such as HHV6, HHV7, and HHV8, usually do not cause neurological issues when they are reactivated in the body.

“When available, PCR-based CSF testing is critical to establish these diagnoses,” study authors wrote. “Empiric treatment should not be delayed or stopped if the clinical suspicion is high. Research is ongoing into prevention, diagnostics, and optimal treatment of herpes virus encephalitides and the newly described post-infectious autoimmune encephalitis.”

Reference

Matthews E, Beckham D, Piquet A, et al. Herpesvirus-Associated Encephalitis: an Update. Curr Trop Med Rep. 2022; 9(3): 92–100. Published online 2022 Sep 23. doi:10.1007/s40475-022-00255-8