Treatment Options for Epstein-Barr Virus-Related Disorders of the Central Nervous System

Abstract

Epstein-Barr virus (EBV), a causative agent for several types of lymphomas and mucosal cancers, is a human lymphotropic herpesvirus with the capacity to establish lifelong latent infection. More than 90% of the human population worldwide is infected. The primary infection is usually asymptomatic in childhood, whereas infectious mononucleosis (IM) is common when the infection occurs in adolescence. Primary EBV infection, with or without IM, or reactivation of latent infection in immunocompromised individuals have been associated with a wide range of neurologic conditions, such as encephalitis, meningitis, acute disseminated encephalomyelitis, and cerebellitis. EBV is also involved in malignant lymphomas in the brain. An increasing number of reports on EBV-related disorders of the central nervous system (CNS) including the convincing association with multiple sclerosis (MS) have put in focus EBV-related conditions beyond its established link to malignancies. In this review, we present the clinical manifestations of EBVrelated CNS-disorders, put them in the context of known EBV biology and focus on available treatment options and future therapeutic approaches.

Epstein-Barr Virus Encephalitis: A Review of Case Reports from the Last 25 Years

“…This work also highlights the lack of treatment and standardization of practices, despite the attempts of a recent review to summarize therapeutic options [112]. The only drug approved for the treatment of EBV infectious diseases is rituximab, an anti-CD-20 antibody more often used in EBV-associated lymphomas.…”

Metagenomic next-generation sequencing of cell-free DNA for the identification of viruses causing central nervous system infections

“…For example, EBV is a common virus in humans, and around 95% of people have asymptomatic EBV infection ( 33 ), but it was the cause of CNS symptoms (headache, fever, vomiting, neck stiffness, epileptic seizures, and altered mental status) in only 13 patients in our study. EBV can remain dormant in the CNS, and a positive CSF EBV result can occur in latent infection, active infection, EBV-related lymphoproliferative diseases, and EBV infection-associated neuroimmune disorders ( 34 ). The number of CSF EBV copies varies between conditions (e.g., higher in CNS EBV lymphoma than EBV encephalitis) and can increase non-specifically with other CNS infections ( 34 , 35 ).…”

“…EBV can remain dormant in the CNS, and a positive CSF EBV result can occur in latent infection, active infection, EBV-related lymphoproliferative diseases, and EBV infection-associated neuroimmune disorders ( 34 ). The number of CSF EBV copies varies between conditions (e.g., higher in CNS EBV lymphoma than EBV encephalitis) and can increase non-specifically with other CNS infections ( 34 , 35 ). Hence, the significance of CSF EBV depends on the clinical context and should be assessed in conjunction with the patient’s presentation, medical history, and immune status, and serial testing and monitoring may be warranted.…”

Mendelian randomization analysis suggests no associations of human herpes viruses with amyotrophic lateral sclerosis

“…In addition, VZV can cause neurological syndromes such as myelitis and segmental motor paralysis ( Gershon et al, 2015 ). EBV is most commonly associated with infectious mononucleosis, while primary or latent infections are mostly associated with neurological disorders, such as encephalomyelitis ( Andersen et al, 2023 ). CMV can exhibit tropism for neural stem cells and cause multiple spinal cord radiculitis ( Kleinschmidt-DeMasters and Gilden, 2001 ; Kamte et al, 2021 ).…”